The MedSurg Handbook PDF

The MedSurg Handbook
Notes on medicine and surgery
Written by Garry KJ Pettet

Copyright Garry KJ Pettet 2005 - 2009
www.garrypettet.com
ANAESTHETICS ..................................................................................8
ACUTE PAIN AND THE ANAESTHETIST ..............................................................9

INTERMITTENT POSITIVE PRESSURE VENTILATION (IPPV) .....................................13
PREOPERATIVE GRADING ...........................................................................16
LOCAL AND REGIONAL ANAESTHESIA .............................................................17
BREAST SURGERY ............................................................................19
BENIGN BREAST PAIN ..............................................................................20

BREAST LUMPINESS AND LUMPS ...................................................................22
CYSTS ................................................................................................23
DUCT PAPILLOMA ...................................................................................24
FIBROADENOMA .....................................................................................25
FIBROADENOSIS ....................................................................................26
INFECTION OF THE BREAST ........................................................................28
MAMMARY DUCT ECTASIA ..........................................................................30
NIPPLE DISCHARGE .................................................................................31
TRAUMA TO THE BREAST ...........................................................................32
CANCER MEDICINE ..........................................................................33
ACUTE LYMPHOBLASTIC LEUKAEMIA (ALL) ......................................................36

ACUTE MYELOGENOUS LEUKAEMIA (AML) .......................................................37
ACUTE PROMYELOCYTIC LEUKAEMIA (APML) ....................................................39
BREAST CANCER ....................................................................................40
CANCER GENETICS ..................................................................................48
PALLIATIVE CARE IN CANCER PATIENTS ..........................................................50
CARCINOMA OF THE BRONCHUS ...................................................................52
CARCINOMA OF THE PROSTATE ....................................................................57
CHEMOTHERAPY .....................................................................................60
CHRONIC LYMPHOCYTIC LEUKAEMIA (CLL) ......................................................62
CHRONIC MYELOID LEUKAEMIA (CML) ...........................................................64
HAIRY CELL LEUKAEMIA (HCL) ....................................................................66
HODGKIN’S DISEASE (HD) ........................................................................67
MYELOABLATIVE THERAPY WITH HAEMOPOIETIC PROGENITOR CELL SUPPORT (HPCS) .....69
MYELOMA ............................................................................................72
NON-HODGKIN’S LYMPHOMA (NHL) .............................................................75
PAIN CONTROL IN CANCER PATIENTS .............................................................77
STAGING OF CANCER ...............................................................................80
CARDIOLOGY ...................................................................................82
ANGINA PECTORIS ..................................................................................83

AORTIC REGURGITATION (AR) ....................................................................87
AORTIC STENOSIS (AS) ...........................................................................89
ATRIAL TACHYCARDIAS .............................................................................91
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BUNDLE BRANCH BLOCK ...........................................................................93

CARDIOGENIC SHOCK (ACUTE HEART FAILURE) .................................................94
CHRONIC HEART FAILURE ..........................................................................96
INFECTIVE ENDOCARDITIS (IE) .................................................................101
MITRAL REGURGITATION (MR) ..................................................................104
MITRAL STENOSIS (MS) .........................................................................106
MYOCARDIAL INFARCTION (MI) .................................................................108
PULMONARY OEDEMA .............................................................................113
UNSTABLE ANGINA ................................................................................115
VENTRICULAR TACHYARRHYTHMIAS .............................................................116
WOLFF-PARKINSON-WHITE (WPW) SYNDROME .............................................119
DERMATOLOGY...............................................................................120
BULLOUS DISEASE ................................................................................121

ECZEMA (A.K.A. DERMATITIS) ...................................................................124
DERMATOLOGY TERMINOLOGY ...................................................................129
LICHEN PLANUS ...................................................................................130
MALIGNANT CUTANEOUS TUMOURS .............................................................131
PITYRIASIS ROSEA ................................................................................134
POTENTIALLY PRE-MALIGNANT CUTANEOUS TUMOURS ........................................135
PSORIASIS .........................................................................................137
WHEN SKIN STRUCTURE OR FUNCTION FAILS ..................................................140
ENDOCRINOLOGY ..........................................................................143
ACROMEGALY ......................................................................................144
ADDISON’S DISEASE ..............................................................................146
CUSHING’S SYNDROME ...........................................................................149
DIABETES ..........................................................................................153
NON-KETOTIC HYPEROSMOLAR STATE ..........................................................173
GOITRE ............................................................................................174
GOUT AND HYPERURICAEMIA ....................................................................177
HYPERCALCAEMIA .................................................................................180
HYPERPROLACTINAEMIA ..........................................................................184
HYPERTHYROIDISM ...............................................................................186
HYPOCALCAEMIA ..................................................................................192
HYPOPITUITARISM ................................................................................194
HYPOTHYROIDISM ................................................................................196
MYXOEDEMA COMA ...............................................................................199
OSTEOPOROSIS ...................................................................................200
PAGET’S DISEASE .................................................................................204
PITUITARY SPACE-OCCUPYING LESIONS AND TUMOURS ......................................206
REGULATION OF CALCIUM METABOLISM ........................................................208
GASTROENTEROLOGY ....................................................................210
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ACUTE GASTRITIS .................................................................................211

ACUTE HEPATITIS .................................................................................212
ACUTE HEPATITIS B VIRUS (HBV) ..............................................................213
ACUTE HEPATITIS C VIRUS (HCV) ..............................................................215
ACUTE HEPATITIS D VIRUS (HDV OR DELTA VIRUS) .........................................216
ACUTE PANCREATITIS .............................................................................217
ASCITES ............................................................................................220
AUTOIMMUNE HEPATITIS .........................................................................222
BACTERIAL OVERGROWTH ........................................................................224
CHOLESTATIC JAUNDICE .........................................................................225
CHRONIC GASTRITIS ..............................................................................226
CHRONIC HEPATITIS ..............................................................................227
CHRONIC HEPATITIS B INFECTION ..............................................................229
CHRONIC HEPATITIS C INFECTION ..............................................................231
CHRONIC HEPATITIS D INFECTION ..............................................................232
CHRONIC PANCREATITIS .........................................................................233
CIRRHOSIS ........................................................................................235
COELIAC DISEASE .................................................................................238
CONJUGATED CONGENITAL HYPERBILIRUBINAEMIAS ..........................................240
CONSTIPATION ....................................................................................241
DERMATITIS HERPETIFORMIS ....................................................................243
DIARRHOEA .......................................................................................244
DYSPHAGIA ........................................................................................247
FULMINANT HEPATIC FAILURE (FHF) ...........................................................248
GASTRO-OESOPHAGEAL REFLUX DISEASE ......................................................250
HEPATITIS A VIRUS (HAV) ......................................................................253
INTESTINAL RESECTION ..........................................................................255
JAUNDICE ..........................................................................................257
MALABSORPTION ..................................................................................261
MALIGNANT LIVER TUMOURS ....................................................................262
PEPTIC ULCER DISEASE ...........................................................................264
PORTAL HYPERTENSION ..........................................................................267
RADIATION ENTERITIS ............................................................................269
TROPICAL SPRUE ..................................................................................270
VOMITING ..........................................................................................271
WHIPPLE’S DISEASE ..............................................................................273
GENERAL MEDICINE ......................................................................274
ACUTE LUMBAR DISC PROLAPSE .................................................................275

ACUTE RENAL FAILURE (ARF) ...................................................................276
ALCOHOL ABUSE ..................................................................................281
ANAEMIA OF CHRONIC DISEASE .................................................................285
ANXIETY DISORDER ...............................................................................286
CAUSES OF SPINAL PAIN .........................................................................289
CEREBRAL INFARCTION ...........................................................................290
CEREBROVASCULAR DISEASE AND STROKE ....................................................295
CHRONIC RENAL FAILURE (CRF) ................................................................297
CLUSTER HEADACHE ..............................................................................303
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DELIRIUM ..........................................................................................304
DEMENTIA .........................................................................................306
DEPRESSION ......................................................................................309
FOLATE DEFICIENCY ..............................................................................313
GIANT CELL ARTERITIS ...........................................................................314
HAEMODIALYSIS ..................................................................................317
HAEMOFILTRATION ................................................................................318
HYPERTENSION ....................................................................................319
INTRACEREBRAL HAEMORRHAGE ................................................................323
IRON-DEFICIENCY ANAEMIA .....................................................................324
MENINGITIS .......................................................................................326
METABOLIC NEUROPATHIES ......................................................................328
MIGRAINE ..........................................................................................329
MONONEURITIS MULTIPLEX ......................................................................331
MONONEUROPATHIES .............................................................................332
OSTEOARTHRITIS .................................................................................334
MECHANISMS OF DAMAGE TO PERIPHERAL NERVES ...........................................338
PERIPHERAL OEDEMA .............................................................................339
PERITONEAL DIALYSIS ............................................................................341
POLYNEUROPATHIES ..............................................................................342
RENAL TRANSPLANTATION .......................................................................343
RHEUMATOID ARTHRITIS (RA) ..................................................................345
SEPTIC ARTHRITIS ................................................................................350
SUBARACHNOID HAEMORRHAGE (SAH) ........................................................352
TENSION HEADACHE ..............................................................................355
THIAMIN (VITAMIN B1) DEFICIENCY ...........................................................356
TRANSIENT ISCHAEMIC ATTACKS (TIAS) .......................................................357
CLINICAL PATTERNS OF UMN DISORDERS .....................................................359
VENOUS THROMBOEMBOLIC DISEASE ...........................................................361
VITAMIN B12 DEFICIENCY AND PERNICIOUS ANAEMIA .......................................363
GENERAL SURGERY ........................................................................366
ADULT UMBILICAL HERNIA .......................................................................367

ANTI-EMETIC DRUGS .............................................................................370
PROPHYLACTIC ANTIBIOTICS IN GUT SURGERY ................................................372
BLOOD GROUPS ...................................................................................373
BLOOD, BLOOD COMPONENTS AND BLOOD PRODUCTS ........................................374
COMPLICATIONS OF BLOOD TRANSFUSION .....................................................375
BURNS .............................................................................................377
PRINCIPLES OF FLUID AND ELECTROLYTE BALANCE ............................................379
HERNIA ............................................................................................382
INDICATIONS FOR REFERRAL TO ITU ...........................................................391
PAIN AND ITS RELIEF .............................................................................392
POSTOPERATIVE CHEST INFECTIONS ............................................................394
POSTOPERATIVE CIRCULATORY COLLAPSE ......................................................396
POSTOPERATIVE MONITORING ...................................................................398
PRESSURE SORES .................................................................................400
PROCEDURE FOR BLOOD TRANSFUSION ........................................................402
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SCROTAL SWELLINGS .............................................................................403

WOUND HEALING .................................................................................409
WOUND MANAGEMENT ...........................................................................411
GI SURGERY ...................................................................................414
ACUTE APPENDICITIS .............................................................................415

ACUTE CHOLANGITIS .............................................................................417
ACUTE CHOLECYSTITIS ...........................................................................419
ACUTE PERITONITIS ..............................................................................421
LARGE BOWEL NEOPLASMS .......................................................................423
BILIARY COLIC ....................................................................................428
CANCER OF THE OESOPHAGUS ...................................................................429
CARCINOMA OF THE PANCREAS ..................................................................432
CARCINOMA OF THE STOMACH ...................................................................436
CHRONIC CHOLECYSTITIS ........................................................................439
COMMON BILE DUCT STONES ....................................................................440
INFLAMMATORY BOWEL DISEASE ................................................................441
DIVERTICULAR DISEASE ..........................................................................448
FAMILIAL ADENOMATOUS POLYPOSIS (FAP) ...................................................450
GALLSTONE ILEUS ................................................................................451
GALLSTONES ......................................................................................452
INTESTINAL OBSTRUCTION .......................................................................454
OBSTRUCTIVE JAUNDICE .........................................................................456
SMALL BOWEL NEOPLASMS .......................................................................457
UPPER GI BLEEDS ................................................................................459
RESPIRATORY MEDICINE ...............................................................462
ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) .........................................463

ASTHMA ............................................................................................466
BRONCHIAL CARCINOMA .........................................................................469
COR PULMONALE ..................................................................................473
CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) ......................................478
HOW TO USE AN INHALER ........................................................................482
PLEURAL EFFUSION ...............................................................................483
PNEUMONIA .......................................................................................484
PNEUMOTHORAX ..................................................................................487
RESPIRATORY FAILURE ...........................................................................489
SARCOIDOSIS .....................................................................................492
TUBERCULOSIS (TB) .............................................................................495
VASCULAR SURGERY ......................................................................499
ABDOMINAL AORTIC ANEURYSM (AAA) ........................................................500

ARTERIOVENOUS MALFORMATION (AVM) ......................................................502
CAROTID ARTERY DISEASE .......................................................................504
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CRITICAL LIMB ISCHAEMIA (CLI) ...............................................................506

INTERMITTENT CLAUDICATION (IC) .............................................................509
RAYNAUD’S PHENOMENON .......................................................................512
THE DIABETIC FOOT ..............................................................................515
TRAUMATIC ARTERIOVENOUS FISTULA ..........................................................516
VARICOSE VEINS ..................................................................................517
VASCULAR TRAUMA ...............................................................................521
VENOUS LEG ULCERATION .......................................................................523
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Anaesthetics
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Acute pain and the anaesthetist
Postoperative pain:
• This is best dealt with by preventing it happening in the first
place
• The patient who wakes up in severe pain following surgery can
be a difficult problem and the mainstay of dealing with this sort
of occurrence is the IV administration of opioid drugs (e.g.
morphine), larger doses of which may be necessary
Trauma pain:
• Anaesthetists are most likely to encounter a trauma patient in
pain when in the process of resuscitation or in preparation for
theatre
• It is important that analgesia in these circumstances does not
interfere with the resuscitation process or mask important
diagnostic signs in the patient
• For example, the use of IV morphine to treat a man with a
fractured femur, shock and head injury may lower his BP further,
depress his level of consciousness, interfere with neurological
observations and increase the risk of regurgitation and aspiration
of gastric contents
• It is still important to treat pain in these circumstances,
however, and a nerve block with local anaesthetics is often the
technique of choice
Labour pain:
• The pain of childbirth is, at its worst, one of the most severe
pains that can be experienced, and very few mothers are lucky
enough to go through labour without the need for some form of
analgesia
• Several features distinguish the pain of labour from the other
forms of pain:
o It gets worse, not better, with time
o It is non-pathological
o Is associated with a happy outcome
o Its relief must not result in compromise to the baby
o Its relief should not interfere with the ability of the mother
to share in the birth experience
• This means that the ideal pain relief in labour must be very
potent, very safe and not have any depressant effect upon the
CNS
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• This is where regional block, in the form of epidural or spinal

anaesthesia, comes into its own
Simple analgesic drugs:

• E.g. aspirin and paracetamol
• Are of little use when dealing with severe pain
• They are not strong enough and they can usually only be
administered orally, a route which is certainly not practical
following major surgery
• However, it is important not to forget these drugs in the
postoperative period; while recovery from painful surgery, most
patients need a ‘halfway’ drug to tide them over the period
between opioid usage and total freedom from pain
Non-steroidal anti-inflammatory drugs (NSAIDs):

• This wide-ranging group of drugs (used for many years to treat
arthritis and other musculoskeletal disorders) is now finding a
role in the management of postoperative pain
• Recent additions to the range (e.g. diclofenac and ketorolac)
have more powerful analgesic properties than their ancestors
• Can be administered by a variety of routes, including:
o IV
o IM
o Rectal
• Have well recognised side-effects, the most notorious being GI
irritation and haemorrhage
• They also interfere with platelet function and may exacerbate
asthma and renal failure
Opioids:
• Of the drugs available, morphine is the most commonly
prescribed in the UK. It has a duration of action of ~3-4 hours
following a single IM dose
• Diamorphine (heroin) is a powerful analgesic with some
advantages over morphine. However, its association with
addiction and abuse have, probably unfairly, somewhat
restricted its use
• Pethidine, used especially in labour, is slightly shorter-acting and
has atropine-like properties:
o Bronchodilation
o Tachycardia
o Reduction in secretions
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• Pethidine derivatives (e.g. fentanyl and alfentanil) are very

potent, short-acting opioids that tend to be used
intraoperatively, although they can be used postoperatively via
the epidural/spinal route
• Opioid drugs may be administered via a variety of routes:
o IM:
• Painful
• Lag time of ~20 minutes
• Only effective if the muscle is well perfused
o IV:
• No lag time
• Can be painlessly via an indwelling cannula
• The dose can be accurately titrated
• No reliance on adequate tissue perfusion
o Infusions:
• Designed to maintain a constant blood level of
analgesia
o Patient-controlled analgesia (PCA):
• A syringe is filled with a large quantity of morphine
and connected to the patient via an indwelling
cannula
• The patient is given a button which, when pressed,
delivers a fixed small dose of morphine
• The machine ‘locks out’ for a short period of time to
give the dose a chance to achieve its effect (usually
5 minutes), and then the patient may take another
dose if needed
• A typical prescription would allow 1mg of morphine
to be taken every 5 minutes, thus allowing the
patient up to 12mg/hour
o Epidural/spinal:
• Receptors for opioids are found in high
concentrations in the spinal cord, and small doses of
these drugs can have profound analgesic effects
when administered into the epidural or intrathecal
(spinal) regions
• A dose of morphine as small as 0.2mg (1/50th of the
IM dose) can produce highly effective pain relief for
24 hours following lower abdominal surgery
Side-effects of opioids:
• Sedation
• Respiratory depression
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• Nausea and vomiting

• Itching
• Urinary retention
• Histamine release
• Miosis
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Intermittent positive pressure ventilation (IPPV)
Overview:
• This is achieved by intermittently inflating the lungs with a
positive pressure delivered by a ventilator and applied via an
endotracheal tube or a tracheostomy
• A number of refinements and modifications of IPPV have been
introduced with:
o Positive end-expiratory pressure (PEEP)
o Intermittent mandatory ventilation (IMV)
o High-frequency jet ventilation (HFJV)
• The rational use of IPPV depends on a clear understanding of its
potential beneficial effects as well as its dangers
Beneficial effects of IPPV:

• Improved CO2 elimination
• Relief from exhaustion:
o Artificial ventilation removes the work of breathing and
relieves the extreme exhaustion that may be present in
patients with respiratory failure
• Effects on oxygenation:
o In those with severe pulmonary parenchymal disease, the
lungs may be very stiff and the work of breathing is
therefore greatly increased
o Under these circumstances, the institution of IPPV may
significantly reduce total body O2 consumption
Indications for IPPV:

• Acute respiratory failure
• Acute ventilatory failure
• Other indications:
o Prophylactic postoperative ventilation
o Head injury – to avoid hypoxia and hypercarbia which
increase ICP. Hyperventilation reduces ICP
o Trauma – chest injury and lung contusion
o Severe LVF with pulmonary oedema
o Coma with breathing difficulties (e.g. following drug
overdose)
Institution of IPPV:
• Requires endotracheal intubation
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• Intubating patients in severe respiratory failure is an extremely

hazardous undertaking and should only be performed by
experienced staff
• It extreme emergencies, it may be preferable to ventilate the
patient by hand using and oropharyngeal airway, a face mask
and a self-inflating bag until experienced help arrives
• The patient is usually hypoxic and hypercarbic, with increased
sympathetic activity:
o The stimulus of laryngoscopy and intubation can
precipitate dangerous arrhythmias and even cardiac arrest
o ECG and O2 saturation should be monitored
o Patient should be preoxygenated with 100% O2 before
intubation
o In some deeply comatose patients, no sedation will be
required but in the majority of patients, a short-acting IV
anaesthetic agent followed by muscle relaxation will be
necessary
• Endotracheal tubes can now be left safely in place for several
weeks and tracheostomy is, therefore, less often performed
• Tracheostomy may be required for the long-term control of
excessive bronchial secretions and/or to maintain an airway and
protect the lungs in those with impaired pharyngeal and
laryngeal reflexes
• Tracheostomy can be performed surgically, the trachea being
opened through the second, third and fourth tracheal rings via a
small transverse skin incision, or percutaneously using a
guidewire and a series of dilators
• Tracheostomy has a mortality rate of up to 3%
• A life-threatening obstruction of the upper airway that cannot be
bypassed with an endotracheal tube should have a
cricothyroidotomy
Dangers of IPPV:
• Airway complications
• Disconnection, failure of gas or power supply, mechanical faults
• CVS complications:
o The intermittent application of positive pressure impedes
venous return and distends alveoli, thereby ‘stretching’ the
pulmonary capillaries and causing a rise in pulmonary
vascular resistance
o This produces a fall in cardiac output
• Respiratory complications:
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o V/Q mismatching
o Collapse of peripheral alveoli
o Secondary pulmonary infection
• Barotrauma:
o Pneumothorax
o Pneumomediastinum
o Pneumoperitoneum
o Subcutaneous emphysema
• GI complications:
o Abdominal distension associated with an ileus
o Unknown cause
• Salt and water retention:
o Increases secretion of ADH
o Decreases secretion of ANP
o The fluid retention is often particularly noticeable in the
lungs
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Preoperative grading
A commonly used grading system is that described by the American

Society of Anaesthesiologists (ASA), in which patients are allocated to
one of five categories
The scoring system allows easier communication between

anaesthetists and is a useful research tool
However, it gives only limited prognostic information about the

chances of an individual surviving an operation
Significant factors (including the type of procedure, a history of

difficult intubation and of obesity) are not included in the classification
Preoperative grading system of the ASA:

ASA I Healthy patient
ASA II Mild systemic disease, no functional disability
ASA III Moderate systemic disease, functional disability
ASA IV Severe systemic disease, constantly life-threatening
ASA V Moribund patient, unlikely to survive 24 hours with or
without an operation
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Local and regional anaesthesia
Definitions:
• Local anaesthesia:
o The use of a drug to produce anaesthesia by topical
application, infiltration or ring block
• Regional anaesthesia:
o Is a term reserved to describe major nerve blocks or
spinal/epidural techniques
o However, the terms are often used interchangeably
Regional versus general anaesthesia:
Advantages Disadvantages
Avoids adverse effects of general Toxicity of local anaesthetic drugs
anaesthetic agents:
• Respiratory depression
• CVS depression
• Nausea/vomiting
• ‘Hangover’
Avoids potential hazards of Often difficult techniques:
unconsciousness: • More risk of failure or partial
• Loss of airway success
• Aspiration • More discomfort while
• Damage to joints through performing block
malpositioning • May take longer to establish
Minimises endocrine stress Greater co-operation needed from
response to surgery patient
Decreased postoperative pain Sets time limit for surgery
Earlier discharge from hospital Restricts flexibility of surgeon if
operation needs to be more
extensive
Hazards of local anaesthetic agents:

• Local administration:
o Inadvertent IV injection - rapid onset of toxic effects
o Inadvertent intraneuronal injection - nerve damage
o Incorrect use of adrenaline –containing solution - tissue
necrosis
o Vasodilatation - increased bleeding
o Tachyphylaxis - reduced effectiveness of repeated doses
o Spread of infection - if injected into infected area
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• Regional anaesthesia:
o Marked vasodilatation – fall in BP
o Major nerve compression – haematoma or abscess
formation
o Large doses may be needed – risk of overdosage
• Effects of overdose:
o CVS:
• Bradycardia
• Fall in cardiac contractility – hypotension
• Cardiac arrest
• NB: Cocaine and adrenaline-containing solutions cause
tachycardia and hypertension
o CNS:
• Paraesthesiae (especially around the mouth)
• Anxiety
• Tremors
• Fitting
• Coma
Types of local anaesthesia:

• Topical anaesthesia:
o Throat lozenges
o ENT procedures
• Infiltration:
o A&E
o Minor surgery
• Ring block:
o Is a quick and effective method of anaesthetising an
extremity (typically a finger or toe)
• Nerve blocks
• IV regional anaesthesia (IVRA or Bier’s block):
o Used to anaesthetise the arm (or occasionally the leg),
classically before reduction of a fractured wrist
o Also used for minor surgery (e.g. relief of carpal tunnel
syndrome)
• Spinal and epidural anaesthesia
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Breast Surgery
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Benign breast pain
Benign breast pain is either cyclical or non-cyclical
The first follows the pattern of the menstrual cycle; the second is
random in timing
Cyclical pain:
• Most commonly affects women <35 years of age
• Onset is during the early phase of the cycle; intensity gradually
worsens to reach a peak just before menstruation, easing with
the start of the period
• In mild cases, the pain affects the upper outer quadrants of the
breasts
• In severe cases, the whole breast may feel engorged, tender and
heavy and physical contact can be unbearable
• Post-menopausal women on HRT can get cyclical breast pain
• Examination:
o Tenderness and a firm nodular feel in the upper outer
quadrants of the breast
Investigation of cyclical breast pain:

• In the presence of a typical history of bilateral cyclical pain,
there is often little reason to embark on any investigations
Management of cyclical breast pain:

• The most important aspect is reassurance that the condition is
entirely benign and is not associated with either carcinoma or a
tendency to its development in later life
• Many women are content to live with their discomfort if they can
be reassured on both these counts
• Three drugs are commonly used:
o Gamma-linoleic acid (evening primrose oil):
• 320mg daily po
• An essential fatty acid
• Thought to render breast cells less sensitive to the
effects of sex hormones
• 60% of sufferers experience relief
• Needs to be taken for 3-4 months before relief is
experienced
o Danazol:
• 200-300mg daily po
• Interferes with the action of oestrogen on breast tissue
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o Bromocriptine:
• Gradually increasing doses up to a maximum of 5mg
daily po
• Blocks the pituitary drive to produce FSH and LH
o Bromocriptine and Danazol can cause menopausal-like
symptoms
Non-cyclical pain:
• May be intermittent or constant and is confined to localised
areas of one breast
• It can be caused by conditions both within and without the
breast, including:
o Mammary duct ectasia
o Periductal mastitis
o Trauma
o Tietze’s disorder – characterised by tenderness over
costochondral junctions
• It is often difficult to identify a specific cause of non-cyclical pain
Investigation of non-cyclical breast pain:

• As with cyclical breast pain, investigation in those <35 years of
age is limited to clinical assessment
• In older women, mammography is often a wise precaution,
particularly if the pain is consistently localised to one spot or is
associated with a lump
• 10% of patients with such features have an underlying
carcinoma
Management of non-cyclical breast pain:

• Is much more resistant to treatment than is cyclical pain
• The following may be helpful:
o Simple NSAIDs
o Treatment of inflammatory conditions
o Local lignocaine/steroid injection
• Most patients end up having to live with their pain until it
resolves by itself, which in the great majority it eventually does
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Breast lumpiness and lumps
Lumpiness:
• Can present on its own but is frequently associated with cyclical
breast pain
• It is a manifestation of the cyclical changes that go on in the
female breast during the menstrual years
• A variety of descriptive terms have been applied to it:
o Fibroadenosis
o Cystic mastopathy
o Fibrocystic disease
o Cystic mastitis
• All are merely descriptive of the changes seen to a varying
degree on histological examination and do not give any insight
into cause
Discrete single lump:

• The commonest causes of a lump are:
o Fibroadenoma
o Cyst
o Very localised fibroadenosis
• The fear uniting them all is the well-defined nature of the lump
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Cysts
Epidemiology and aetiology:

• Occurrence is usually after 35 years of age and up to the
menopause
• There has been some suggestion that multiple recurrent cysts
are associated with an increased tendency to breast cancer
Clinical features:
• The history is of a palpable and occasionally tender lump
• Physical findings are of a tense, discrete, mobile lump anywhere
in the breast
Investigation and management:

• Whenever a clinical diagnosis is made of a cyst, needle
aspiration should be done at once:
• It yields straw-coloured fluid and causes collapse of the cyst
• Equally important, it immediately reassures the patient, although
there have to be some exceptions:
o Failure of the lump completely to disappear
o Bloodstained aspirate
• Failure to disappear completely:
o Re-evaluation must take place within a few weeks
o A persistent lump must be evaluated by mammography
and either be subject to FNAC or excised for histological
examination
• Bloodstained aspirate:
o The simple cause is traumatic aspiration
o However, this must be confirmed by cytological
examination of the aspirate and mammography
o Clinical reassessment, re-aspiration if a lump is present or
excision biopsy is then the appropriate course
• Multiple cysts:
o Some patients have multiple cysts identified at
mammography or which present clinically as a lumpy
breast
o Danazol can be helpful in reducing the incidence of clinical
recurrence
o Given the possible risk of carcinoma, follow-up with
mammography is necessary
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Duct papilloma
This is a relatively uncommon lesion
Clinical features:
• There is a serous or bloodstained discharge from a single aspect
of the nipple, although the patient may not realise that the
discharge is localised
• Other symptoms are rarely present
• The breast is normal, but there is either the spontaneous
appearance of discharge from one aspect of the nipple or
‘milking’ of a segment produces nipple discharge from the duct
draining that segment
Investigations:
• The main concern, particularly if the discharge is bloodstained, is
that occasionally there is an underlying malignancy, although
duct papilloma is benign
• Investigations are the same as for mammary duct ectasia
• In spite of negative cytological findings, it is nearly always
necessary (in a bloodstained single duct discharge) to excise the
involved system to establish that a papilloma is present
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Fibroadenoma
These tend to affect younger women and are infrequent after about
35-40 years of age
Pathological features:
• Many remain static
• A small proportion either regress or increase in size
• In developing countries, they may reach a mass larger than the
breast in which the growth occurs
Clinical features:
• Generally the patient discovers a painless lump
• Well-defined lump
• Consistency is rubbery to firm or hard
• There is much mobility (it may be difficult to find) – hence the
nickname ‘breast mouse’

• As with any lump, they should be subjected to triple
assessment:
o Clinical examination
o Imaging
o Cytology
• Provided all these support a diagnosis of fibroadenoma, small
lesions can be left alone
• Larger lesions (>4cm) or those in older women may be better
removed
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Fibroadenosis
History:
• Usually, the upper outer quadrants are affected but, as with
pain, one side alone may be involved
• Young
• Often in the early years after the menarche
Physical findings:
• May be single or multiple lumps in one or both breasts
• May be acutely tender (particularly premenstrually)
Investigations:
• Mammography:
o Is indicated in those >40 years of age
o In a lumpy breast, the appearances are those of dense
fibrosis with micro- or macrocystic change
• Ultrasound:
o Indicated in those <40 years of age
o May show cystic changes
• Fine needle aspiration cytology (FNAC):
o Suspicious areas are aspirated under image control
o Typical findings are of benign cells
Management:
• Reassurance that the changes are part of the normal spectrum
of the breast’s response to female sex hormones
• If there is associated pain in a large breast, firm support may
help
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Galactorrhoea
This is a rare cause of bilateral milky discharge
It follows lactation and is caused by a persistent elevation of prolactin
Management:
• Bromocriptine is used until the discharge subsides
• Prolactinomas should be considered in long persistent discharge,
but are rare
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Infection of the breast
There are 2 common causes of infection:

• Lactational breast abscess
• Periductal mastitis
Lactational breast abscess:

• Is a complication of lactation and breast-feeding
• The organism involved is nearly always Staphylococcus aureus
• It is believed that the bacteria get into the breast tissue through
cracks in the nipple during feeding
• The abscess may break through into neighbouring segments and
thus become multilocular
Clinical features of a lactational breast abscess:

• History:
o The baby may be anything from a few days to some
months old
o The mother may have noticed an obvious crack in the
nipple (although this is unusual)
o Segmental pain in the affected breast rapidly becomes
severe and sleep is often lost
• Physical findings:
o A tender red segment in the breast is seen
o May be evidence of nipple damage (i.e. a crack in its
surface)
o Fluctuation is not a feature unless the abscess is advanced
and beginning to point towards the skin, which may
ultimately show evidence of necrosis
Management of a lactational breast abscess:

• If detected and treated early, acute mastitis can resolve
• Anti-staphylococcal antibiotics are prescribed in full dose
• If the nipple is obviously damaged, feeding on this side is
stopped and the milk expressed from the healthy segments
• Continued pain and loss of sleep suggest that there is an abscess
which, in its early stages, can be aspirated with a wide-bore
needle under LA
• Ultrasound is a useful means of determining whether there is
any pus to drain
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Periductal mastitis:
• This condition affects young women in their 30s and is
associated with smoking
• Is characterised histologically by a low-grade inflammatory
response around the ducts adjacent to the nipple
• The bacteria involved are nearly always anaerobes
Clinical features of periductal mastitis:

• Tenderness develops on one aspect of the areola
• There is rarely any systemic disturbance
• Recurrent bouts may occur before the patient seeks medical
attention
• A tender swelling at the edge of the areolar is seen, which may
progress to abscess formation with a periareolar sinus and
discharge
Investigation and management of periductal mastitis:

• Because there may be a discrete mass with only a few, if any,
characteristics of inflammation, FNAC and mammography may
be necessary to exclude an underlying carcinoma
• Inflammatory swellings may respond to antibiotics
• Once an abscess has formed – drainage is required
• A complication of abscess is the formation of a mammary duct
fistula:
o Discharges intermittently
o May be associated with recurrent abscess formation
o The duct segment must then be excised because, in the
presence of a duct abnormality, attempts to eradicate
sepsis with antibiotics are usually futile
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Mammary duct ectasia
Aetiology and pathological features:

• The cause, as with many breast disorders, is an exaggeration of
the normal cyclical changes – a wear and tear process
• The ducts adjacent to the nipple become dilated and engorged
with breast secretions
• Secondary infection and a retroareolar abscess may form, but
even if this does not happen, fibrosis can cause nipple retraction
History:
• The discharge can range from milky to dirty green
• Is often (but not always) bilateral
• Occasionally it is associated with pain, usually cyclical
• Acute infection causes pain and swelling
Physical findings:
• The breast may have features of lumpiness
• Nipple retraction:
o Caused by the chronic inflammation often associated with
this condition
o Slit-like appearance
o May be confused with carcinoma
• In acute inflammation, an abscess forms which, if not treated at
am early stage, discharges at the areolar margin:
o A small sinus (mammary fistula) then results which can be
the focus of further attacks of inflammation

• If qualified by age, patients should have a mammogram to
establish the general state of the breast
• Discharge is sent for cytological assessment
• Provided both the above investigations are normal, nothing
further needs to be done other than to reassure the patient
• If a discharge is very troublesome, excision of the duct system
(Hadfield’s operation) provides symptomatic relief
Abscess:
• An abscess in this condition is followed by a mammary fistula
• In consequence, after drainage there is not only often a
persistent discharge but also the risk of recurrence
• The involved duct and its drainage area should be excised
electively
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Nipple discharge
There are 3 common causes:

• Mammary duct ectasia
• Duct Papilloma
• Galactorrhoea
An important point to establish is whether the discharge is from a

single or multiple ducts
That from a single duct, particularly if bloodstained, is more likely to

be associated with a Papilloma
Discharges are commoner in women over 35 years of age
In younger women, they may be associated with the OCP
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Trauma to the breast
Overview:
• Trauma to the breast is relatively rare, although sexual
encounters and love bites may be responsible for local injury
• A blunt impact can interfere with local blood supply and,
together with a haematoma, cause fat necrosis
• Another cause is the use of therapeutic anticoagulants in
patients with very large and pendulous breasts in which very
minor trauma may precipitate extensive haemorrhage which
may go on to necrosis
Clinical features:
• Fat necrosis causes a hard, painful lump, usually following a
story of minor local trauma
• A hard lump is often found, with some irregularity and
occasionally tethering to the overlying skin
• The appearances are suggestive of a carcinoma but the condition
can usually be distinguished because of the history of trauma,
associated bruising and resolution of the lump with observation

• Investigation is the same as for any discrete lump
• The condition resolves with time and specific treatment is not
required
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Cancer Medicine
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Acute leukaemias
Clinical features:
• The symptoms of acute leukaemia are a consequence of bone
marrow failure:
o Symptoms of anaemia:
• Tiredness
• Weakness
• Exertional dyspnoea
o Repeated infections
• There may be few or no abnormal physical signs; but patients
often have:
o Signs of anaemia
o Bruises, petechial haemorrhages, purpura, fundal
haemorrhages
o Signs of infection
o Occasionally, lymph node enlargement and/or
hepatosplenomegaly
Investigations:
• FBC:
o Low Hb
o WCC (may be raised, normal or low)
o Thrombocytopenia
• Peripheral blood film:
o Shows characteristic leukaemic blast cells
• Bone marrow aspirate:
o Shows increased cellularity with abnormal lymphoid or
myeloid blast cells
General principles of management:

• Before starting treatment, the following points must be
considered:
o Correction of anaemia and thrombocytopenia with the
administration of blood and platelets
o Infection should be treated with IV antibiotics
o Leukaemic blast cells can infiltrate the brain and lungs –
resulting in coma and respiratory failure respectively
o If the blast cell count in the peripheral blood is very high
(>100x109/L) the patient may need leucophoresis:
• Blood is collected from a vein and centrifuged so as to
remove leukaemic cells, and the RBCs and plasma are
then returned to the patient via another vein
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• Leucophoresis can be life-saving

o In certain types of leukaemia, where the rate of cell
division is very fast (e.g. B-cell and T-cell ALL), patients
may develop a ‘tumour lysis’ syndrome when
chemotherapy is given:
• Hypercalcaemia
• Hyperphosphataemia
• Hyperkalaemia
• All resulting from a high rate of cellular breakdown
• Is potentially life-threatening and difficult to treat
once it has occurred
Classification:
• Leukaemia can be divided on the basis of the speed of evolution
of the disease into acute or chronic
• Each of these is then further subdivided into myeloid or
lymphoid, according to the cell type involved. Hence the terms:
o Acute myelogenous leukaemia (AML)
o Acute lymphoblastic leukaemia (ALL)
o Chronic myeloid leukaemia (CML)
o Chronic lymphocytic leukaemia (CLL)
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Acute lymphoblastic leukaemia (ALL)
Overview:
• Predominantly a disease of children
• Is potentially curable
• 90% of children respond to treatment and 50-60% are cured
• The cure rate in adults is only about 30%
Treatment:
• The principles of initial treatment are the same as those for AML
• Cyclical chemotherapy comprising:
o Vincristine
o Prednisolone
o L-asparaginase
o Doxorubicin
• The sequence of treatment, however, is different to AML because
ALL has a propensity for involvement of the CNS, thus treatment
includes prophylactic intrathecal drugs (e.g. methotrexate)
• Most patients receive oral maintenance therapy for 2-3 years
Treatment at recurrence:
• A proportion of patients are cured with the initial therapy
• In the rest, the disease recurs and ultimately proves fatal unless
a second remission can be achieved (high-dose treatment and
some form of transplant procedure)
• With such treatment, a further 20-30% of patients will survive
long-term
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Acute myelogenous leukaemia (AML)
Overview:
• AML is a potentially curable disease
• More common in older adults
• Is classified on the basis of the morphological appearance of the
bone marrow into 7 subtypes (M1-M7), which differ by virtue of
the predominant cell type involved
Treatment:
Treatment has traditionally been divided as being in 2 parts –
remission induction (complete remission, CR) and post-remission/
consolidation therapy
• The reason for the continuation of therapy post-remission is as
follows:
o At the point of CR (when there is no morphologically
detectable leukaemia) there are still 108 or109 leukaemic
blast cells present.
o It is, therefore, not surprising that if no post-remission
therapy is given, the majority of patients develop recurrent
leukaemia
• Induction of remission is via chemotherapy:
o An anthracycline drug (e.g. doxorubicin) in conjunction
with cytarabine, with or without another drug (e.g.
etoposide)
o Patient needs to stay in hospital for 4 weeks in the first
instance owing to the risk of infection and bleeding
consequent upon neutropenia and thrombocytopenia
o Subsequent cycles of treatment are given on an outpatient
basis
• Options for post-remission therapy include:
o Further cycles of the same chemotherapy used to induce
remission
o Chemotherapy different from that given to induce
remission
o Myeloablative therapy with allogeneic/autologous bone
marrow transplantation (BMT)
Prognosis:
• Approx. 70% of patients <60 years of age will return to normal
health
• However, within 1-3 years the disease will recur in at least 60%
(the remainder almost certainly having been cured
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• In younger patients with a recurrence, cure is still possible for a

proportion, using myeloablative therapy with allogeneic/
autologous haemopoietic progenitor cell support (HPCS)
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Acute promyelocytic leukaemia (APML)
Is a subtype of AML (M3 subtype)
Clinical features:
• Has a specific association with disseminated intravascular
coagulation (DIC)
• Patients may present with severe bleeding which worsens when
treatment is started as the leukaemic blast cells break down,
leading to further consumption of clotting factors and platelets
Treatment:
• Regular, twice daily platelet transfusion and maintenance of the
fibrinogen level with FFP as the chemotherapy is given
• Provided that remission can be achieved, patients with APML
have a better overall prognosis than patients with other subtypes
of AML
• Oral ATRA (all-trans-retinoic acid) can lead to achievement of CR
in most patients with APML
• Unfortunately, these remissions are not durable and, therefore,
they must be consolidated with conventional chemotherapy
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Breast cancer
Epidemiology:
• Most commonest form of cancer to affect women in the Western
world
• Directly responsible for 19% of all female cancer-related deaths
• Incidence of 30 per 100,000 population
• It is estimated that 1 in 9 women will develop the disease
Aetiology:
• The risk factors include:
o Age:
• Rare <35 years of age
• Incidence increases with age
o Country of birth:
• High risk = northern Europe and north America
o Genetic factors:
• Hereditary and familial breast cancer can be
described using the Lynch system of classification
(see below)
o Early menarche/late menopause
o Nulliparity/late childbirth
o Obesity
o Exogenous hormones:
• High-dose OCP
• HRT
o Previous cancer
o Irradiation
o Previous benign disease (see below)
The lynch classification of inherited susceptibility to breast cancer:

• Hereditary breast cancer:
o A family history of breast cancer and, sometimes, related
cancers (colonic, endometrial) forming part of the Lynch
syndrome type II
o This involves an autosomal dominant, highly penetrant
cancer susceptibility factor
o These patients tend to be younger than average, have
multiple primaries and may also have other tumours
• Familial breast cancer:
o A family history of breast cancer including one or more
first or second degree relative with breast cancer that does
not fit the hereditary breast cancer definition
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o Relative risk of developing breast cancer in relation to

previous benign beast disease:
• No risk:
• Apocrine change
• Ductal ectasia
• Mild hyperplasia (no atypia)
• Slight risk:
• Moderate or florid hyperplasia (no atypia)
• Sclerosing adenosis
• Papilloma
• Moderate risk:
• Atypical ductal or lobular hyperplasia
TNM classification of breast cancer:

Tis Carcinoma in situ (pre-invasive)
T0 No clinical evidence of primary tumour
T1 Tumour <2cm
T2 Tumours 2-5cm
T3 Tumour >5cm
T4 Tumour of any size but with direct extension to chest wall or
skin:
o (a) Fixation to chest wall
o (b) Oedema, lymphocytic infiltration or ulceration
of skin
o (c) Both (a) and (b)
N0 No palpable ipsilateral axillary lymph nodes
N1 Palpable nodes not fixed:
o inflammatory only
o containing tumour
N2 Fixed ipsilateral lymph nodes
N3 Ipsilateral supraclavicular/infraclavicular nodes or oedema of the
arm
M0 No evidence of distant metastasis
M1 Evidence of distant metastasis
Histology:
•Are usually adenocarcinomas and are divided into 2
types:
o Ductal
o Lobular
• There are 3 degrees of differentiation:
o Grade I – well differentiated
o Grade II – moderately differentiated
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o Grade III – poorly differentiated

Carcinoma in situ:
This term refers to the period during which normal epithelial cells
undergo apparent malignant transformation but do not invade through
the basement membrane
• There are 2 forms:
o Lobular (LCIS)
o Ductal (DCIS). DCIS represents all types of in situ
carcinoma that are not identified as lobular. It can be
further subdivided into:
• Comedo (a particularly menacing type of Tis)
• Solid
• Cribiform
• Micropapillary
• The ratio of DCIS to LCIS is approximately 3:1 with 10-37% of
those with LCIS and 30-50% of those with DCIS going on to
develop invasive carcinoma
Types of invasive breast carcinoma:

Ductal 80%
Lobular/ductal combined 5%
Medullary 6%
Colloid 2%
Other 2%
Symptoms:
Lump 76%
Pain 5%
Nipple retraction 4%
Nipple discharge 2%
Skin retraction 1%
Axillary mass 1%
Paget’s disease:
• This condition presents clinically as a chronic, eczematoid
eruption of the nipple
• The diagnosis may be confused with eczema
• It constitutes ~2% of the histological types
• Is almost always associated with an underlying intraductal or
invasive carcinoma
Comparison of Paget’s disease and eczema of the nipple:

Paget’s disease Eczema
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Unilateral Bilateral
Progressive/continuous Intermittent/variable
Moist or dry Moist
Irregular/discrete Indistinct
Nipple always involved Nipple sparing
Pruritus absent Pruritus present
Inflammatory breast carcinoma:

• Comprises ~1% of breast carcinomas
• Is rapidly progressive
• Characterised by:
o Erythema
o Peau d’orange
o Skin ridging
o May/may not be a palpable mass
• The commonest presenting feature is pain (unlike other breast
cancers)
• The characteristic appearance of a diffusely enlarged breast is
consequent upon the dissemination of tumour cells through the
lymphatics of the dermis
Establishing the diagnosis of breast cancer:

• Any palpable breast abnormality should be assessed by the
process of triple assessment:
o Clinical evaluation
o Radiological evaluation
o Cytological/histological evaluation
• During the consultation with the patient, it is important to
convey that only 20% who consult have a breast carcinoma
Physical examination:
• The patient must be undressed to the waist and should sit facing
the examiner
• The breast is initially examined from the front with the arms first
at the side, then raised above the head and finally placed on the
hips
• The patient is asked to point out the supposed area of
abnormality and this is examined first
• The following must always be assessed:
o Asymmetry
o Visible lumps
o Erythema
o Peau d’orange (cutaneous oedema)
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o Contour flattening
o Skin tethering (as identified by puckering, particularly
when the arms are raised)
o Abnormal fixation
o Retraction and altered axis of the nipples
• After this, the patient is asked to lean forward, once again
looking for skin retraction
• The supraclavicular, infraclavicular and axillary lymph nodes
should be examined
• Further palpation of the breast is best performed in the supine
position
• Should a mass be felt, one must assess its:
o Size
o Shape
o Location
o Fixation
o Consistency
Mammography:
• Mammography is not useful in women <35 years of age:
o Dense breasts which may mask an underlying tumour
o Interpretation very difficult
o However, should be done if there is clinical suspicion of a
malignancy
• Mammographic abnormalities that warrant further investigation
include:
o Radiological masses undetected on clinical examination
o Microcalcifications
o Stellate densities
o Architectural distortion
o Change from a previous mammogram
• Mammography has a false-negative rate of 10-15%
Ultrasound:
• Very good at discriminating between solid and cystic masses
• Useful for guiding biopsy
• In younger women, ultrasound may reveal more information
than mammography and most surgeons would perform this test
first in women <35 years of age
• Masses in fatty breasts are difficult to assess
Aspiration cytology:
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• Needle aspiration of a breast lump is dine with a 21-gauge

needle
• The contents of the needle are expressed on to a slide, smeared
and fixed (often in both air and alcohol) for cytological
examination
• Is a false-negative rate of 1%
Wide-bore core needle biopsy:

• This method provides a sample of tissue for histological, rather
than cytological examination
• Because the results are more reliable, this procedure is rapidly
superseding aspiration cytology
Open biopsy – requires a general anaesthetic:

• Excision biopsy:
o Refers to the removal of all gross evidence of disease with
a small rim of normal breast tissue
• Incision biopsy:
o Similar to excision biopsy, except that only a part of the
lump is removed
o It is generally felt that this is not good surgical practice
and is, therefore, restricted to larger tumours
o Has largely been superseded by wide-bore core needle
biopsy
Nipple biopsy:
• Conditions affecting the nipple (especially an eczema-like
appearance) often warrant biopsy
• A wedge of nipple-areolar complex can be excised under local
anaesthetic with minimal cosmetic disruption to confirm or refute
a diagnosis such as that if Paget’s disease
Management of carcinoma in situ:

• DCIS is usually unilateral and is often treated by surgical
excision and postoperative radiotherapy
• LCIS is a marker for a disease that is often bilateral and only
sometimes progresses to invasive ductal carcinoma. Therefore,
the patient can elect to be observed closely or undergo a
curative bilateral mastectomy
• Less than 1% of axillary lymph nodes will be affected and
clearance is not required
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Management of invasive carcinoma:

• This varies widely and is largely dependent on the size of the
tumour and whether or not there is regional lymph node
involvement
• Generally:
o Wide local excision of tumour, either a:
• Lumpectomy
• Quadrantectomy (removal of the involved breast
quadrant)
o Local radiotherapy
o Possible axillary lymph node clearance
o Possible adjuvant chemotherapy
• For more advanced disease:
o Radical mastectomy with axillary node clearance
o Radiotherapy
o Adjuvant chemotherapy
Complications of surgery:
• Haemorrhage/haematoma formation
• Infection
Complications of radiotherapy:
• Cutaneous inflammation
• Photosensitisation
• Fibrosis and distortion of breast shape
• Shoulder stiffness
• Brachial plexus damage
• Lymphoedema of the arm
Adjuvant therapy:
• This encompasses both cytotoxic and hormonal therapy
• Cytotoxic therapy:
o Are 2 main regimens:
• CMF (cyclophosphamide, methotrexate and 5-
fluorouracil)
• CAF (cyclophosphamide, adriamycin and 5-
fluorouracil)
o Chemotherapy is given to all patients at a high risk of
recurrence
• Hormonal therapy:
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o ~30% of all breast tumours respond to an anti-oestrogen

such as tamoxifen 20mg od, this rises to 60% of
oestrogen-receptor positive tumours
o Some tumours are resistant to tamoxifen and even
respond unfavourably, therefore, alternative hormonal
therapies are available:
• Aromatase inhibitors (prevent the conversion of
androgens to oestrogen) such as formestane and
Anastrozole
• Surgical oophorectomy
• Chemical oophorectomy (using Gn-RH agonists)
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Cancer genetics
Overview:
• The development of cancer is associated with a fundamental
genetic change with the cell
• Evidence for the genetic origin of cancer is based on the
following:
o Some cancers show a familial predisposition
o Most known carcinogens induce mutations
o Susceptibility to some carcinogens depends on the ability
of cellular enzymes to convert them to a mutagenic form
o Genetically determined traits associated with a deficiency
in the enzymes required for DNA repair are associated with
an increased risk of cancer
o Some cancers are associated with chromosome ‘instability’
o Malignant tumours represent clonal proliferations of
neoplastic cells
o Some tumours contain mutated oncogenes
• Mutations may occur in the germline and can, therefore, be
present in every single cell in the body, or they may occur in a
single somatic cell and be present only in the tumour following
clonal proliferation
Cytogenetic (chromosome) abnormalities:

• Chromosome changes are often reciprocal translocations
• A non-reciprocal change results in deletion or addition of part of
a chromosome
• Examples of specific chromosome changes associated with
malignancy are:
o Chronic myeloid leukaemia (CML):
• 95% of patients have a reciprocal translocation
between chromosome 22 and chromosome 9
o Acute promyelocytic leukaemia (APML):
• Almost all patients have the chromosome translocation
t(15;17)
o Burkitt’s lymphoma:
• The most frequent change is a reciprocal translocation
between chromosomes 8 and 14
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DNA repair:
• Some autosomal recessive diseases associated with
abnormalities of DNA repair predispose to the development of
cancer:
o Xeroderma pigmentosa (XP):
• Inability to repair DNA damaged by UV light and some
chemicals, therefore leading to a high incidence of skin
cancer
o Ataxia telangectasia (AT):
• These patients have a high sensitivity to ionising
radiation and have an increased incidence of lymphoid
tumours
o Bloom’s syndrome (BS):
• Increased incidence of lymphoid tumours
o Fanconi’s anaemia (FA):
• Increased incidence of lymphoid tumours
Inherited cancers:
• The following are examples of cancer syndromes that exert
dominant inheritance:
o Retinoblastoma:
• An eye tumour found in young children
• May be inherited (40%) or acquired (60%)
• Those with the inherited form have a germline mutation
of the long arm of chromosome 13
o Breast and ovarian cancer:
• 2 genes have been identified – BRCA1 and BRCA2
• These mutations account for most cases of familial
breast cancer and 50% of ovarian cancers
o Wilm’s tumour
o Familial adenomatous polyposis (FAP)
o Neurofibromatosis
o Multiple-endocrine-adenomatosis syndromes (MENS)
Oncogenes:
• Normal cells contain genes known as proto-oncogenes,
activation of which (for example by a mutation or carcinogen to
produce an oncogene) would result in malignant transformation
• It has been demonstrated that specific proto-oncogenes are
associated with specific cancers
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Palliative care in cancer patients
GI symptoms:
• The most frequent symptoms are:
o Anorexia
o Malaise
o Weakness
• Current research suggests that endogenously produced
cytokines (e.g. TNF and ILs) are mediators of the anorexia/
cachexia syndrome
• Nausea and vomiting:
o Occurs in up to 2/3 of cancer patients in the last 6 weeks
of life
o In order to ensure adequate absorption of the antiemetic,
parenteral administration (preferably SC) may be helpful
for the first 24-48 hours
• Antiemetics are classified according to their affinities for NT
receptor sites:
o A prokinetic DA antagonist (e.g. metoclopramide 10mg
tds) would be helpful in vomiting due to upper GI stasis or
liver metastases
o Prokinetics should be avoided in cases of intestinal
obstruction, as they increase peristalsis in the upper bowel
o Centrally acting anticholinergics (e.g. cyclizine 50mg tds)
or centrally acting DA antagonists (e.g. haloperidol 1.5mg
tds) are the drugs of choice in vomiting caused by drugs or
metabolic disturbance
o As with the prescription of analgesics, antiemetics will be
most effective if prescribed on a regular, rather than ‘as
required’ basis
Bowel obstruction:
• May present acutely or in a more chronic manner
• The cause is often multifactorial
• A small number of patients may benefit from surgical
intervention
• Most patients will not be suitable for surgery and can be
managed medically
• The active medical management of malignant bowel obstruction
includes:
o The relief of intestinal colic using an antispasmodic (e.g.
hyoscine butylbromide 60-80mg daily)
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o Treating continuous pain with adequate analgesia (e.g.

diamorphine)
o Treating vomiting if nausea is a problem with a centrally
acting antiemetic (e.g. cyclizine 150mg daily or haloperidol
5-10mg daily)
• It will be necessary to administer all of the above medications
parenterally (the SC route is most appropriate)
• Patients may be allowed to drink and eat low-residue diets which
are mostly absorbed in the proximal GI tract
Respiratory symptoms:
• In particular, dyspnoea
• Management is based on accurate diagnosis of the cause and
active treatment of all potentially reversible situations:
o Treat infections
o Drain pleural/pericardial effusions
o Transfuse symptomatic anaemia patients
• The sensation of dyspnoea and a cycle of respiratory panic may
be partially relieved by the prescription of regular
benzodiazepines
• Regular doses of short-acting opioids (5-20mg qqh) are also
helpful
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Carcinoma of the bronchus
Aetiology:
• Tobacco:
o Latent period of 10-30 years
o The primary determinants are:
• Number of cigarettes consumed
• Age of onset of smoking (those under 16 years of
age at start have irreversible damage to their
bronchial genetic makeup
• Length of time of smoking
• Type of tobacco (cigarettes or pipe, filter or non-
filter)
• Passive exposure to tobacco smoke
o Asbestos exposure
o Irradiation
o Toxic metals
o Certain chemicals
Types of bronchial carcinoma:

• Squamous cell carcinoma (SCC)
• Adenocarcinoma
• Small cell carcinoma (oat cell carcinoma)
• Alveolar cell or bronchoalveolar carcinoma
Squamous cell carcinoma:

• 60% of all lung tumours
• Associated with smoking and is rare in non-smokers
• Squamous metaplasia -> carcinoma in situ -> invasive
carcinoma
Adenocarcinoma:
• 15% of lung tumours
• Has a tendency to be more peripheral, arising in the small
bronchial glands
• Most common in women
• Is the type seen in non-smokers
Small cell (oat cell) carcinoma:

• Arises from the Kulchitsky chromaffin cells
• Highly malignant
• Hormone production by the tumour is common
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• A benign form of a small cell carcinoma is a carcinoid tumour
Alveolar cell carcinoma:

• Arises in the distal airways
• Often diffuse, multifocal and bilateral
• Resistant to radio-/chemotherapy
• Very poor prognosis
Symptoms:
• Cough (50%)
• Haemoptysis (on at least one occasion is frequent but rarely
persistent)
• Chest pain (usually a diffuse chest wall heaviness)
• Upper limb pain/numbness (brachial plexus invasion)
• SOB (is the consequence of loss of lung volume from
consolidation distal to an occluded bronchus)
• Hoarseness (involvement of a recurrent laryngeal nerve)
• Dysphagia (oesophageal involvement)
• General features of malignancy:
o Weight loss
o Malaise
o Fatigue
Signs:
• General:
o Clubbing (30%)
o Hypertrophic pulmonary osteoarthropathy (3%) – with
painful swelling of the wrists and ankles
o Raised JVP and distended veins over the upper arms and
chest (with SVC obstruction)
• Signs of metastases are:
o Tender areas in bones
o Palpable supraclavicular lymph nodes
o An enlarged, irregular liver
o Anaemia
Investigations:
• CXR:
o Defines the lobar position of any mass
o May show:
• Pleural effusions
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• Elevation of the hemidiaphragm (indication of

phrenic nerve involvement)
• Rib erosion
• Thoracic CT or MRI:
o Excellent for accurate localisation
o In particular, CT defines:
• Additional small lung lesions
• Involvement of the pericardium, diaphragm, chest
wall and oesophagus (all of which may indicate
inoperability)
• Enlarged mediastinal glands (suggests malignant
involvement if >1cm)
• The anatomy of the liver and adrenals (both are
frequent sites of secondary spread)
• Mediastinoscopy:
o The aim is to obtain tissue from the mediastinal lymph
nodes around the lower trachea
o Is the most important staging procedure for inoperability
(N2 disease)
• Bone scan:
o Ca bronchus frequently metastasizes to bone
o Should be carried out if there is any clinical suggestion of
bone involvement:
• Bone pain
• Tenderness over the spine and other bony areas
• Raised ALP or serum calcium
o Multiple bone secondaries are an absolute contraindication
to surgery
• Liver ultrasound
• Brian isotope scan:
o Is indicated if neurological abnormalities are found:
• Severe persistent headache
• Syncope
• Ataxia or falls
• Stroke
• Behavioural change
Factors associated with inoperability:

• Oat cell carcinoma
• Poor respiratory function
• Evidence of lymphatic spread
• Presence of malignant cells in pleural effusion or heavy blood-
stained effusions
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• Evidence of distant spread:

o Bone
o Brain
o Liver
o Adrenals
Surgery:
• Thoracotomy and lung resection are performed whenever the
tumour is assessed as operable
• Early ligation of the pulmonary vein may help to prevent
metastatic spread from tumour manipulation
• Surgical mortality depends on patient-related risk factors and
the extent of the resection; with pneumonectomy average
mortality is 6-12% and for lobectomy 3-6%
• Specific risk factors are:
o Age
o Extent of resection
o Chronic lung disease
o Coronary artery disease/previous MI
o Concomitant disease of the:
• Liver
• Kidney
• Diabetes
Prognosis – squamous cell carcinoma:

• 5 year survival of primary lung cancers treated by surgical
resection is ~45%
• Survival depends on:
o Histological type; squamous cell tumours do better than:
• Adenocarcinoma
• Undifferentiated tumours
• Small cell tumours
o Tumour size (stages T1-T4)
o Lymph node spread (stages N0-N3)
Simplified TNM classification 5 year survival is shown below:

• T1 & N0 50-60%
• T2 & N1 30-55%
• T3 & N2 10-25%
• T4 & N3 0-2%
Prognosis – small cell (oat cell) carcinoma:
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• The outcome is particularly poor with resection alone (<5%

survival at 5 years)
• Chemotherapy is now the preferred method of treatment and
trials have shown an improved life expectancy, although still
very poor
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Carcinoma of the prostate
Prostatic carcinoma is a disease of ageing. It is rarely discovered under

the age of 50 and has a peak incidence in the 70s. It is rapidly
becoming the most common malignancy to affect men.
• The tumour is an adenocarcinoma usually arising in the
periphery of the prostate and confined within the Prostatic
capsule
• Its spread is:
o Local in the periprostatic and perirectal soft tissues and
upwards into the pelvis
o Lymphatic to the iliac and para-aortic nodes
o Blood-borne, principally to bone
Symptoms:
• Bladder outflow obstruction
• Metastatic disease:
o Bone pain
o Leg swelling form lymphatic obstruction
• Renal failure from bilateral ureteric obstruction
Signs:
• A nodule in a palpably benign gland
• Hard, irregular prostate in rectal examination sometimes with
perirectal and periprostatic thickening
• Ankle/leg oedema
• Other signs of metastases
Investigation:
• A histological/cytological diagnosis must be made and can be
achieved by:
o Transrectal or transperineal biopsy, preferably US guided
o Aspiration cytology
o Transurethral resection
• Serum prostate-specific antigen (PSA):
o PSA is secreted in the serum by both benign and malignant
prostatic tissue
o Its level correlates with the volume of prostatic tissue
o Not useful for screening but is useful for monitoring the
progression of the disease and response to treatment
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• Abdominal ultrasonography:
o May identify unilateral or bilateral hydronephrosis because
of ureteric involvement
• Renal function tests
• Serum ALP:
o Will be elevated in patients with bony metastases
• Bone scanning:
o Radioisotope bone scans can detect areas of increased
bone activity, irrespective of their cause
Staging:
T1a Incidental finding of tumour with low biological potential for
aggressive behaviour in a prostate removed for clinically benign
disease
T1b Incidental finding of tumour with potentially biological aggressive
behaviour in a prostate removed for clinically benign disease
T1c Tumour identified because of elevated serum PSA
T2a Tumour involving half a lobe or less
T2b More than half a lobe but not both
T2c Both lobes
T3 Tumour extends through capsule and may involve seminal
vesicle
T4 Tumour fixed to invasive adjacent structures other than seminal
vesicle
Management options:
• No treatment with assessment of progress
• Endocrine therapy
• Radiotherapy
• Surgery
Endocrine therapy:
• Most of the proliferating cells of the prostate are dependent on
testosterone
• 60-80% of patients with symptomatic prostate cancer respond to
androgen suppression or ablation therapy
• The mean duration of response is 2 years
• Once the tumour is no longer hormone-sensitive, the mean
survival is 6 months
• Androgen suppression:
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o LHRH analogues initially stimulate the pituitary but after

~7 days the pituitary receptors become blocked and down-
regulation occurs
o Serum testosterone levels fall to castrate levels
o These drugs are long-acting and are administered sc every
1 or 3 months
o Due to the initial stimulation of the pituitary, an anti-
androgen should be given for 7-14 days before the LHRH
analogue is given to prevent disease progression
• Androgen ablation:
o Is by bilateral subcapsular orchidectomy, which can be
done under local anaesthesia as an outpatient
o There is no difference in response between orchidectomy
and LHRH analogue therapy and the choice of treatment
should lie with the patient
Radiotherapy:
• Is effective in controlling the pain of bony metastases
• It is also useful for the treatment of the primary if it is thought
that the tumour is confined to the prostate
Surgical treatment:
• Transurethral resection:
o Is used in patients who present with symptoms of outflow
obstruction or acute retention
• Radical prostatectomy:
o Controversial
o Only useful if the tumour is entirely confined to the
prostate
o Mortality of ~1%
• Morbidity includes:
o Incontinence
o Erectile dysfunction
o Anastomotic strictures
Prognosis:
• In men with prostate cancer confined within the capsule who
undergo radical prostatectomy, approximately 55% survive 10
years
• In comparison with those who have metastatic disease at
presentation, of whom only 25% can be expected to survive 5
years
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Chemotherapy
Overview:
• IV administration of anticancer agents enables therapy to
potentially reach metastatic disease in any part of the body
• However, the toxicity of chemotherapy determines that the
drugs can only be given intermittently and that time has to be
allowed for normal tissues to recover between each
administration of new cytotoxic drugs
• It is also known that tumours rapidly develop resistance to single
agents given on their own
• For this reason, the principle of intermittent combination
chemotherapy has developed:
o Several drugs are combined together
o Chosen on the basis of their differing mechanisms of action
and non-overlapping toxicities
• It has become apparent that normal tissue repairs much more
rapidly than cancerous tissue. This makes it possible to
continually deplete the tumour whilst allowing the restoration of
normal tissues between chemotherapy cycles
Side-effects of chemotherapeutic drugs:

• Nausea and vomiting
• Hair loss
• Bone marrow suppression
• Cardiotoxicity
• Neurotoxicity
• Nephrotoxicity
• Sterility
• Secondary malignancies
Drug resistance:
• This is one of the major obstacles to curing cancer with
chemotherapy
• Some tumours have an intolerably low-level of resistance to
currently available treatment and are often cured:
o Testicular teratomas
o HD
o Childhood acute leukaemia
• Solid tumours (such as small-cell lung cancer) initially appear to
be chemosensitive, with the majority of patients responding, but
most patients eventually relapse with resistant disease
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• In other tumours (e.g. melanoma) the disease is largely

chemoresistant from the start
Adjuvant therapy:
• When a patient first presents with a tumour, it is possible that
small amounts of tumour tissue have already spread to the
lungs, liver, bone marrow and other sites
• This micrometastatic disease consists of relatively few cells with
a good blood supply and might be particularly amenable to the
action of anticancer drugs
• Therefore, if the primary tumour is removed and the tumour has
a great likelihood of relapse, chemotherapy can be given to
destroy the residual micrometastatic disease
• Adjuvant therapy is very useful in childhood cancers
• In adults, adjuvant therapy has been shown to be of use in
breast and colon cancer
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Chronic lymphocytic leukaemia (CLL)
Overview:
• Is an incurable disease of older people
• Is characterised by an uncontrolled proliferation and
accumulation of mature B-cells (although T-cell CLL does occur)
• A proportion of patients remain asymptomatic, dying of an
unrelated cause
• In the remainder, the disease can usually be kept under control
for 9-10 years, infection being the predominant cause of death
Clinical features:
In asymptomatic patients, the diagnosis is often a chance finding on
the basis of a blood count done for a quite different reason
• Symptoms:
o Recurrent infections (resulting from neutropenia and
reduced Ig levels)
o Symptoms of anaemia:
• May develop rapidly in the context of haemolysis
(usually precipitated by infection)
o Painless lymph node enlargement
• Signs:
o Signs of anaemia
o Lymph node enlargement
o Enlarged liver and/or spleen
Investigations:
• FBC:
o Hb low or normal
o Raised WCC (of which at least 40% are lymphocytes)
o Platelets low or normal
• Serum Igs:
o Low or normal
• Coomb’s test:
o Positive if haemolysis is occurring
Treatment:
• The disease may remain stable for several years
• There is no advantage in starting treatment before there is a
clinical indication:
o Anaemia
o Recurrent infections
o Bleeding
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o ‘Bulky’ lymphadenopathy
o Increasing Splenomegaly
• Chlorambucil is most often used, with or without Prednisolone
• Treatment is given intermittently, as and when necessary
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Chronic myeloid leukaemia (CML)
Overview:
• The majority of patients with this disease are older and die
within 5 years of diagnosis
• Has a chronic phase (of 3-4 years duration) and an acute (or
blastic) phase
• The blastic phase of CML is characterised by the development of
acute leukaemia which may be:
o Myeloid (60%)
o Lymphoid (30%)
o Erythroid (10%), in origin
• The blastic phase is generally refractory to treatment, the
median survival being <6 months
Clinical features:
• Symptoms:
o Anaemia
o Night sweats
o Fever
o Weight loss
o Abdominal discomfort owing to splenic enlargement
• Signs:
o Those of anaemia
o Splenomegaly
Investigations:
• FBC:
o Hb normal or low
o Raised WCC (characteristically with the whole spectrum of
myeloid precursors)
o Platelets normal, low or raised
o Shows a hypercellular marrow with an increase in myeloid
precursors
o The Philadelphia (Ph) chromosome is present in most
patients
Treatment:
• Interferon (IFN) therapy:
o Induces haematological remission in most patients
o Induces cytogenetic remission in ~10% of patients
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o Problems:
• Has to be given subcutaneously
• Side-effects can be intolerable (mainly fatigue)
• Myeloablative therapy supported by allogeneic BMT:
o May be curative
o Limited by donor availability and the morbidity/mortality
associated with the treatment itself
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Hairy cell leukaemia (HCL)
Overview:
• HCL is a clonal proliferation of abnormal B (or very rarely T) cells
which, as in CLL, accumulate in the bone marrow and spleen
• Is a rare disease of late middle age
• The bizarre name relates to the appearance of the cells on a
blood film:
o They have an irregular outline owing to the presence of
filament-like cytoplasmic projections
Clinical features:
• Symptoms:
o Those of anaemia
o Recurrent infections
o Abdominal discomfort owing to splenic enlargement
• Signs:
o Those of anaemia
o A palpable spleen
Investigations:
• FBC:
o Pancytopenia
o Shows increased cellularity with characteristic infiltration
by ‘hairy’ cells
Treatment:
• 2-chloroadenosine (2-CDA) has been shown to have specific
activity in this illness, complete remission often being achieved
with just 1 cycle of treatment
• The remissions sometimes last for several years and patients can
be re-treated
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Hodgkin’s disease (HD)
Overview:
• Is one of 2 groups of lymphoma (HD and non-Hodgkin’s
lymphoma)
• Represents abnormal proliferation of B or T cells
• Is now curable in the majority of patients
• All stages are subclassified as A (asymptomatic) or B
Clinical features:
• Symptoms:
o Lymph node enlargement (most often of the cervical
nodes)
o ‘B’ symptoms:
• Fever
• Drenching night sweats
• Weight loss of >10% of bodyweight
o Other constitutional symptoms:
• Pruritus
• Fatigue
• Anorexia
• Alcohol-induced pain at the site of enlarged lymph
nodes
• Symptoms due to involvement of other organs (e.g. bone, lungs,
liver)
• Signs:
o Peripheral lymph node enlargement
o Hepatosplenomegaly
Differential diagnosis of cervical lymph node enlargement:

• Acute infections
• Chronic infections:
o TB
o Sarcoidosis
o Syphilis
o HIV
• Connective tissue disorders:
o RA
• Drugs:
o Phenytoin
• Primary lymph node malignancies:
o HD
o NHL
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o CLL
o ALL
• Secondary malignancies:
o Nasopharyngeal
o Thyroid
o Lung
o Breast
o Stomach
Investigations:
• FBC:
o May be a normocytic normochromic anaemia
• ESR:
o Usually raised
• LFTs:
o Abnormal if the liver is involved
• CXR:
o May show mediastinal widening, with or without lung
involvement
• CT scans:
o May show involvement of intrathoracic, abdominal or pelvic
lymph nodes
o May show involvement in patients with advanced disease
• Lymph node biopsy:
o Is required for definitive diagnosis
o Classically, Sternberg-Reed cells are present
Treatment:
• Treatment is nearly always given with curative intent
• Consists of chemotherapy, radiotherapy or both
• Treatment for HD can usually be given on an outpatient basis
and most people are able to lead a reasonably normal life whilst
having treatment
Prognosis at recurrence:
• Failure to achieve an initial or almost complete response, and
recurrence within 1 year, are both associated with a very poor
prognosis
• Similarly, patients who develop recurrent HD more than once will
almost certainly die of HD
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Myeloablative therapy with haemopoietic progenitor cell

support (HPCS)
Overview:
• High-doses of chemotherapy and radiotherapy kill dividing cells
indiscriminately, so that both normal and malignant cells are
killed
• Since the bone marrow is a highly dividing tissue,
myelosuppression is the main dose-limiting toxicity
• Thus, without a ‘transplant’ as a source of haemopoietic
progenitor cells, the person would die of bone marrow failure
• High-dose treatment may be given using one of the following as
a source of haemopoietic progenitor cells:
o Allogeneic bone marrow transplantation (BMT)/peripheral
blood progenitor cells (PBPCs)
o Autologous BMT/PBPCs
High-dose treatment with allogeneic BMT/PBPCs:

• The recipient patient first undergoes a ‘conditioning’ regimen of
myeloablative therapy over several days, comprising:
o Drugs
o Drugs + total body irradiation (TBI)
• The donor (usually an HLA-identical sibling) has ~1L of bone
marrow aspirated from the posterior iliac crests
• The BM is given IV to the recipient on completion of the
myeloablative therapy
• Immunosuppressive drugs (usually methotrexate and
cyclosporine A) are used to prevent both:
o Rejection
o Graft-versus-host disease (GVHD)
• The patient’ s blood count usually recovers within 3-4 weeks
• Can be very effective but has a 20-30% mortality
• The main causes of death are:
o Infection (bacterial, viral and fungal)
o GVHD
Graft-versus-host disease (GVHD):

• Is a syndrome in which mature T-cells in the donor BM infiltrate
the skin, gut and liver
• Acute GVHD occurs in the first 3 months, but it may also run a
chronic course
• When fatal, patients usually die of liver failure
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• Patients who develop GVHD have a lower incidence of recurrent

leukaemia than those who do not
• Thus, not only does the myeloablative chemoradiotherapy have
an anti-leukaemic effect, but the T-cells within the donor BM
appear to exert an immunologically-mediated ‘graft-versus-
leukaemia’ effect
• The use of allogeneic BMT is primarily limited by donor
availability
• Allogeneic PBPCs are currently being evaluated:
o Granulocyte-colony stimulating factor (G-CSF) is given to
the donor and haemopoietic progenitor cells are collected
from a vein
o Large volumes of blood are phoresed (centrifuged)
o The PBPCs are separated and collected and the RBCs,
granulocytes, platelets and plasma are then returned to
the donor through another vein
• Advantages include:
o Donor does not require a GA
o Donor does not have the discomfort associated with
collecting BM from the pelvic bones
o Incidence and severity of GVHD seems to be lower
High-dose treatment with Autologous BMT:

• Remission is first induced with chemotherapy
• 1L of BM is then aspirated from the patient’s posterior iliac crests
under GA and cryopreserved in liquid nitrogen
• The myeloablative therapy is then given and then thawed BM is
reinfused IV
• Advantages:
o Mortality is less than for allografts (5-10% compared with
20-30%)
• Disadvantages:
o The time to blood count recovery after an autograft is
usually longer than after an allograft
o Risk of reinfusing malignant cells (risk can be reduced
using in vitro techniques)
High-does treatment with autologous PBPCs:

• PBPCs have virtually replaced autologous BMT as support for
myeloablative therapy
• Chemotherapy followed by the growth factor G-CSF alone are
administered to stimulate haemopoietic progenitor cells in the
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BM to proliferate, so that they can be collected from the

peripheral blood
• Because PBPCs are more differentiated than those collected
directly form the BM, the time to blood count recovery is faster
(only 2-3 weeks)
• As the duration of neutropenia is shorter, the treatment is also
safer
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Myeloma
Overview:
• Is part of a spectrum of diseases
• Characterised by the presence of a paraprotein in the serum:
o Is produced by abnormal, proliferating plasma cells that
produce (most often) IgG or IgA (and rarely IgD)
• The paraproteinaemia may be associated with the excretion of
light chains in the urine (known as Bence-Jones protein)
Clinical features:
• Is a disease of the elderly (median age at presentation being 60
years)
• It is a complex illness which represents the inter-relationship
between:
o Bone destruction:
• Vertebral collapse (which can cause spinal cord
compression)
• Fractures
• Hypercalcaemia
o Bone marrow infiltration:
• Pancytopenia
• Production of paraprotein which may (rarely) result
in symptoms of hyperviscosity
o Renal impairment owing to a combination of:
• Deposition of light chains
• Hypercalcaemia
• Hyperuricaemia
Symptoms:
• Bone pain
• Symptoms of anaemia
• Recurrent infections
• Symptoms of renal failure (e.g. pruritus, anorexia, lethargy)
• Symptoms of hypercalcaemia
Investigations:
• FBC:
o All values are normal or low
• ESR:
o Raised
• Blood film:
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o May be rouleaux formation as a consequence of the

paraprotein
• U&Es:
o May be evidence of renal failure
• Serum Ca2+:
o Normal or raised
• Serum ALP:
o Usually normal
• Total protein:
o Normal or raised
• Serum albumin:
o Normal or low
• Protein electrophoresis:
o Characteristically shows a monoclonal band (paraprotein)
• Uric acid:
o Normal or raised
• Skeletal survey:
o May show characteristic lytic lesions, most easily seen in
the skull
• Skeletal survey:
o To assess light-chain excretion
o Shows characteristic infiltration by plasma cells
General treatment:
• Anaemia corrected
• Infection treated
• Bone pain can be helped most quickly by radiotherapy
• Pathological fractures can be prevented by prompt orthopaedic
surgery with pinning of lytic bone lesions seen on the skeletal
survey
• Renal failure needs to be assessed and may need long-term
dialysis
• Patients with spinal cord compression due to Myeloma are
treated with dexamethasone, followed by radiotherapy to the
lesion delineated by an MRI scan
Specific treatment:
• The use of alkylating agents (e.g. melphalan, cyclophosphamide)
in conjunction with prednisolone has improved the median
survival from 7 months to 2 years
Prognosis:
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• Patients presenting with anaemia and renal failure have a very

poor prognosis, with 50% dying within 9 months
• Patients without these 2 features at presentation survive for
about 2 years
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Non-Hodgkin’s lymphoma (NHL)
Classification:
• The Kiel classification (reflects the rate at which the cells are
dividing):
o High-grade
o Low-grade
• Ironically, high-grade lymphomas are potentially curable,
whereas low-grade lymphomas are generally considered to be
incurable with conventional therapy
• A further subdivision is made in the basis of B- or T-cell origin:
o Most NHLs are of B-cell phenotype (although T-cell
tumours are increasingly being recognised)
Clinical features:
• Peripheral lymph node enlargement
• With or without systemic symptoms
Low-grade High-grade
Middle-aged/older people Any age group
Bone marrow infiltration common Bone marrow
infiltration unusual
Incurable with conventional therapy Potentially curable
Investigations:
• FBC:
o Pancytopenia (suggests bone marrow infiltration)
• U&Es:
o Patients may have renal impairment as a consequence of
ureteric obstruction secondary to intra-abdominal or pelvic
lymph node enlargement
• CXR
• LFTs
• CT scans
• Bone marrow aspirate
• Lymph node biopsy
Low-grade lymphomas:
• Are 4 subtypes:
o Follicular lymphoma (median survival is 9 years)
o Lymphoplasmacytoid (LPC) lymphoma (median survival is
5 years)
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o Mantle cell lymphoma (centrocytic lymphoma) (median

survival is 4 years)
o Low-grade T-cell lymphoma
High-grade lymphomas:
• May be of B- or T-cell origin
• Chemotherapy is given with curative intent
• 60-70% of patients respond to treatment
• About 40% are cured
• Recurrent high-grade lymphoma has a grave prognosis
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Pain control in cancer patients
Overview:
• The symptom most feared by cancer patients is pain, although
only 2/3 of patients suffer significant pain throughout the course
of their disease
• Cancer is directly responsible for ~70% of the pain, the
remainder being due to:
o Rapid weight loss
o Pressure sores
o Arthritis, etc
The analgesic ladder:

• The cancer relief programme of the WHO groups drugs into 3
main classes:
1. Non-opioid drugs (e.g. paracetamol, NSAIDs)
2. Weak opioid drugs (e.g. codeine, dextropropoxyphene)
3. Strong opioid drugs (e.g. morphine and diamorphine)
• The analgesic ladder states that, if optimal use of a drug from
the non-opioid class (e.g. 1000mg of paracetamol TDS) does not
result in satisfactory pain relief, the prescription should be
increased up one step to a weak opioid
• If the equivalent of codeine 60mg TDS is not sufficient to control
pain, the patient will require a strong opioid
Strong opioid drugs:

• Morphine is the drug of choice:
o In most circumstances, it should be given by mouth
o The dose can be tailored to the individual patient’s needs
as morphine has no ceiling analgesic effect
o A suitable starting dose of morphine is 10mg qqh (or 5mg
qqh if the patient is elderly or frail)
o Patients with renal failure will have impaired excretion of
morphine metabolites; they should receive a single dose of
morphine and be carefully observed for the return of pain
in order to determine the approximate rate of excretion of
the metabolites
o If a 10mg dose of morphine relieves the pain, but the relief
does not last for 4 hours:
• A 50% increase in the dose should be made
• i.e. 10, 15, 20, 30, 45, 60, 90, 120, 180mg, until
satisfactory pain control is achieved
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• When the patient’s 24-hour morphine requirement has been

established, the prescription may be converted to a controlled-
release preparation:
o There are now both 12-hour and 24-hour release
preparations available
o The appropriate dose may be calculated by simple
addition:
20mg morphine elixir qqh
= 120mg morphine per day
= 60mg bds of a 12-hour preparation or 120mg daily of a 24-hour
preparation
• If the patient is unable to take oral medication because of

nausea/vomiting, GI obstruction or altering levels of
consciousness, the opioid should be given either rectally or
parenterally
• Diamorphine is used for patients who need long-term analgesia:
o Has a greater solubility than morphine
o Given either SC or IM, diamorphine is ~2x as potent as
oral morphine
Side-effects of the strong opioids:

• Morphine is the drug of choice:
o The prescription of a stimulant laxative (e.g. co-
danthrusate 1-3 capsules at night) should be mandatory
o No tolerance develops to this side-effect and laxative
medication must be continued as long as analgesics are
prescribed
• Nausea and vomiting occurs in 30-60% of patients when first
started on morphine:
o Tolerance will develop to this side-effect within 4-5 days
• Confusion, nightmares and hallucinations:
o Occur in a small percentage of patients
o Tolerance to these side-effects does not develop
o A change of opiate drug is usually required
Pain not responsive to opioids:

• Not all cancer pains are relieved by opioids
• In some situations, the addition of co-analgesic drugs will result
in improved pain control
• NSAIDs (e.g. naproxen 500mg bds) used in addition to a weak
or strong opioid are good at relieving bone pain
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• Pains of nerve destruction (called dysaesthetic or deafferentation

pain):
o Are generally only marginally improved by strong opiates
o Steroids have been found to be useful in reducing the
symptoms
o In cases of constant burning dysaesthesia, the TCAs are
helpful (e.g. amitriptyline 10mg at night, increasing
incrementally to 75-100mg is usually sufficient)
o Anticonvulsant drugs are useful in the management of
lancinating, neuropathic pains:
• Carbamazepine, starting at a dose of 100mg bds is
most commonly used
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Staging of cancer
Before a decision about treatment can be made, not only the type of
tumour but also its extent and distribution needs to be established.
Various ‘staging investigations’ are therefore performed before a
treatment decision is made. The staging systems vary according to the
type of tumour
The TNM classification:

T Extent of the primary tumour
N Extent of regional lymph node involvement
M Presence or absence of metastases
Extent of primary tumour:

T0 Excised tumour
T1
T2
T3
T4 Very large tumour
Extent of regional node involvement:

N0 No nodes involved
N1
N2
N3
Presence of metastases:
M0 Not present
M1 Present
Tumour markers:
• There are a number of specific tumour markers which are found
in serum and are useful in diagnosis:
o !-fetoprotein:
• Hepatocellular carcinoma
• Germ-cell testicular tumours
o "-human chorionic gonadotrophin ("-HCG):
• Choriocarcinoma
o Prostate-specific antigen (PSA):
• Prostate carcinoma
• There are a number of other tumour markers available, but
these are of little use in diagnosis
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• Examples include:
o Carcinoma embryonic antigen (CEA) – e.g. colon cancer
o Ca-125 – e.g. ovarian, gut, pancreatic cancer
o Ca-19-9 – e.g. gut, pancreatic cancer
• These markers are non-specific and should only be used to
monitor response to treatment
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Cardiology
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Angina pectoris
Is caused by a mismatch between myocardial oxygen supply and

demand
Overview:
• Diagnosis is largely based on the clinical history
• The chest pain is typically described as ‘heavy’, ‘tight’ or
‘gripping’
• Typically, the pain is central/retrosternal and may radiate to the
jaw and/or arms
• Angina can range from a mild ache to a most severe pain that
provokes sweating and fear
• May be associated breathlessness
Types of angina:
• Classical (exertional) angina
• Decubitus angina
• Variant (Prinzmetal’s) angina
• Cardiac syndrome X
• Unstable angina
Exertional angina:
• The pain is provoked by physical exertion, especially after meals
and in cold, windy weather
• Is commonly aggravated by either anger or excitement
• Pain fades within minutes of resting
• May, occasionally, disappear with continued exertion (‘walking
through the pain’)
Decubitus angina:
• Occurs when the patient is lying down
• Usually occurs in association with impaired LV function, as a
result of severe coronary artery disease
Prinzmetal’s angina:
• Refers to an angina that occurs without provocation, usually at
rest, as a result of coronary artery spasm
• Occurs more frequently in women
• Arrhythmias (both VT and heart block) can occur during the
ischaemic episode
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Cardiac syndrome X:
• Refers to those patients with a good history of angina, a positive
exercise test and angiographically normal coronary arteries
• This forms a heterogeneous group in whom there may be
functional abnormalities of the coronary microcirculation
• Much more common in women than in men
• Good prognosis but are difficult to treat#
Unstable angina:
• Refers to angina of recent onset (less than 1 month), worsening
angina or angina at rest
Examination:
• Usually no abnormal findings
• Occasionally a fourth heart sound may be heard
• Signs that should be sought include:
o Anaemia
o Thyrotoxicosis
o Hyperlipidaemia (e.g. lipid arcus, xanthelasma, tendon
xanthoma)
• It is essential to exclude aortic stenosis as this can present with
angina-like symptoms:
o Slow-rising carotid impulse
o Ejection systolic murmur radiating to the neck
• It is also important to measure the BP to identify coexistent HT
Investigations for angina:

• Resting ECG:
o Usually normal between attacks
o During an attack, transient ST depression may occur
o May be evidence of past MI or LBBB
• Exercise ECG
• Cardiac scintigraphy (myocardial perfusion scans)
• Echocardiography
• Coronary angiography
General management:
• Inform patients of their condition
• Reassure them that the prognosis is good (<2% mortality per
year)
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• Manage coexistent diseases (e.g. DM, HT)

• Minimise risk factors:
o Smoking
o Obesity
o Hyperlipidaemia
• Encourage regular exercise
Medical treatment (those that improve prognosis):

• Aspirin 75mg daily (unless contraindicated)
• Lipid-lowering therapy:
o Considered in patients with total cholesterol >4.8mmol/L
despite a low-fat diet
o If the TGs are <3.5mmol/L one of the statins (HMG-CoA
reductase inhibitors) should be used
o If the TGs are >3.5mmol/L a fibrate should be considered
Medical treatment – symptomatic treatment:

• Glyceryl trinitrate (GTN):
o Used sublingually, either as a spray or a tablet
o Gives prompt relief in a few minutes
• ß-blockers:
o E.g/ atenolol 50-100mg daily
o Decrease HR and SV, therefore decreasing myocardial O2
demand
• Ca2+-channel blockers:
o E.g. amlodipine
• Block both calcium flux into the cell and the its utilization
within the cell
o Leads to:
• Peripheral vasodilatation
• Vasodilatation of coronary arteries
• Decreased SV
• Long-acting nitrates:
o E.g. isosorbide mononitrate
o Particularly useful for patients who respond to sublingual
GTN
o Reduce venous return and hence intracardiac diastolic
pressures
o They also relax the tone of the coronary arteries
Invasive therapies:
• Coronary artery bypass grafting (CABG)
• Percutaneous transluminal coronary angioplasty (PTCA)
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Percutaneous transluminal coronary angioplasty:

• Involves the passage of a catheter into a coronary artery
followed by the inflation of a balloon or insertion of a stent into
the artery in order to maintain its patency
• Risks:
o Mortality (1%)
o MI (2%)
o Need for an urgent CABG (2%)
Indications for CABG:

1. Symptom control in patients who remain symptomatic despite
optimal medical therapy and whose disease is not suitable for
PTCA
2. Prognostic disease in patients with severe 3-vessel coronary
artery disease (significant proximal stenoses in all 3 main
coronary vessels)
Coronary artery bypass grafting:

• Vessels that can be used for the procedure:
o Internal mammary artery/arteries
o Saphenous vein
• Mortality is well below 1%
• Perioperative strokes occur in up to 2% of cases
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Aortic regurgitation (AR)
Causes of aortic regurgitation:

• Acute AR:
o Acute rheumatic fever
o IE
o Aortic dissection
• Chronic AR:
o Rheumatic heart disease
o Syphilis
o RA
o Ankylosing spondylitis
o Severe HT
o Marfan’s syndrome
o Osteogenesis imperfecta
Symptoms:
• Significant symptoms do not develop until LV failure occurs
• A common symptom is ‘pounding of the heart’ because of the
increased LV size and its vigorous pulsation
• Dyspnoea
Signs:
Pulse: Sinus rhythm, large volume, collapsing
Blood pressure: Wide pulse pressure
Apex: Displaced, diffuse, heaving
Murmur: (1) High pitched early diastolic at LSE
(2) Ejection systolic at base and into neck
(3) Mid-diastolic rumble at apex (Austin-Flint)
De Musset’s sign Head nodding with each heart-beat

Quincke’s sign Visible capillary pulsation in the nail beds
Pistol shot femorals A sharp bang heard on auscultation over the
femoral arteries in time with each heart-beat
Investigations:
• CXR:
o LV enlargement
o Ascending aortic wall ,ay be calcified in syphilis
• ECG:
o Left ventricular hypertrophy
o Usually sinus rhythm
• Echocardiogram
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Treatment:
• Treat the underlying cause (e.g. IE, syphilis) if possible
• Treatment usually requires aortic valve replacement but the
timing of surgery is important:
o Because symptoms do not develop until the myocardium
fails and because the myocardium does not recover fully
after surgery, it is important to operate before significant
symptoms occur
o The timing of the operation is best determined according
to haemodynamic, echocardiographic or nuclear
angiographic criteria
• Antibiotic prophylaxis against IE is necessary, even if a
prosthetic valve replacement has been performed
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Aortic stenosis (AS)
Aetiology:
• There are 3 causes of AS:
o Congenital AS (develops progressively due to turbulent
flow through a congenitally abnormal (usually bicuspid)
aortic valve)
o Rheumatic fever
o Arteriosclerotic degeneration and calcification (through
wear and tear)
Symptoms:
• Asymptomatic until AS is moderately severe (when the aortic
orifice is reduced to 1/3 of its normal size
• Exercise induced:
o Syncope
o Angina
o Dyspnoea
o Sudden death
• When symptoms appear, the prognosis is poor – death occurs
within 2-3 years without surgical intervention
Signs:
Pulse: Sinus rhythm, low volume, slow rising
Aortic area: Systolic thrill
Apex: Not displaced
Sounds: Ejection click, soft A2, S4
Murmur: Ejection systolic, radiates to the carotids
Investigations:
• CXR:
o Relatively small heart
o Prominent, dilated ascending aorta
• ECG:
o Left ventricular hypertrophy (left axis deviation)
o Usually sinus rhythm, but ventricular rhythms may occur
Treatment:
• Pts should not over-exert themselves or take part in strenuous
physical games
• Angina is best treated with ß-blockade (as GTN aggravates the
exertional syncope)
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• Antibiotic prophylaxis against IE is essential

• When severe, aortic valve replacement is recommended
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Atrial tachycardias
Atrial flutter:
• Atrial rate varies between 280-350 per minute
• Most often, every second flutter beat conducts, giving a
ventricular rate of 150bpm
• Occasionally, every beat conducts, producing a HR of 300bpm
• Regular, sawtooth-like atrial flutter waves (F waves) between
QRST complexes
• If they are not clearly visible, AV conduction may be transiently
impaired by carotid sinus massage or by the administration of
AV nodal blocking drugs (e.g. verapamil)
• Treatment:
o DC cardioversion (50J, 100J and then 360J)
o Class III drugs are often effective (e.g, amiodarone)
o AV nodal blocking drugs (class II or IV or digitalis) may be
used to control the ventricular rate if the arrhythmia
persists
o Treatment of choice is now radiofrequency catheter
ablation
Atrial fibrillation:
• Common (occurs in 5-10% of patients >65 years of age)
• Atrial fibrillation is continuous, rapid (400 per minute) activation
of the atria by meandering wavelets
• Aetiology:
o Thyrotoxicosis
o Alcohol toxicity
o Chest infection
o Raised atrial pressure
o Increased atrial muscle mass
o Atrial fibrosis
o Inflammation/infiltration of the atrium
• Symptoms and signs:
o May be asymptomatic
o May lead to acute cardiac decompensation
o Patient has an irregularly irregular pulse that is
maintained, even during exercise
o The ECG shows fine oscillations of the baseline and no
clear P waves
o The QRS rhythm is rapid and irregular
o Untreated, the ventricular rate is usually 120-180bpm
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Management of atrial fibrillation:

• Treat underlying cause
• If this does not correct the AF, consider at least 1 go at DC
cardioversion (this requires a GA or heavy sedation)
• Warfarinize for 3 weeks before DC shock (100-200J) and for 4
weeks after
• If DC cardioversion fails, treat as chronic AF
• Chronic AF:
o The aim is control of ventricular rate, not sinus rhythm
o Digitalize (loading dose 0.5mg PO x 3 doses in 2 days,
maintenance of 0.25mg PO OD)
• If rate still to fast, check serum levels and cautiously increase
the dose ± low dose ß-blockers (e.g. propranolol 10-20mg PO
TDS)
• Discuss the risks and benefits of anticoagulation with the patient
• In general, expect to use warfarin, aiming for an INR of 2.5-3.5
• However, if the patient is reluctant or the risk of emboli is small
(e.g. lone AF with normal echo and no past emboli or TIA) or the
risk of bleeding is high ± use of warfarin is contraindicated (e.g.
on NSAIDs or past peptic ulcer) aspirin 300mg with food may be
acceptable
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Bundle branch block
If the depolarisation wave reaches the IV septum normally, then the

PR interval will be normal. However, if there is abnormal conduction
through either the right or left bundle branches (‘bundle branch block’)
there will be a delay in the depolarisation of part of the ventricular
muscle. The extra time taken for depolarisation of the whole of the
ventricular muscle causes a widening of the QRS complex. Block of
both bundle branches causes 3rd degree heart block.
Bundle branch block on an ECG:

• Will be wide QRS complexes (>0.12s)
• Look in leads V1 and V6
• WilliaM (W in V1 and M in V6) is LBBB
• MarroW (M in V1 and W in V6) is RBBB
Causes of RBBB:
• Congenital:
o ASD
o VSD
• Pulmonary disease:
o Cor pulmonale
o PE
• Myocardial disease:
o Acute MI
o Cardiomyopathy
• Drugs/electrolytes:
o Hyperkalaemia
o Class Ia antiarrhythimics
Causes of LBBB:
• LV outflow obstruction:
o Aortic stenosis
o HT
• Coronary artery disease:
o Acute MI
o Severe coronary artery disease
• Cardiomyopathy
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Cardiogenic shock (acute heart failure)
This has a 90% mortality. Cardiogenic shock is shock caused primarily

by the failure of the heart to maintain the circulation. It may occur
suddenly, or after progressively worsening heart failure.
Causes:
• Rapidly reversible:
o Arrhythmias
o Cardiac tamponade
o Tension pneumothorax
• Others:
o MI
o Myocardial depression (drugs, sepsis, hypoxia, acidosis)
o Valve destruction (e.g. endocarditis)
o PE
o Aortic dissection
Management:
• Give O2, with the patient placed in the most comfortable position
• Give diamorphine 2.5-5mg IV for pain and anxiety
• Monitor:
o ECG
o Urine output
o Blood gases
o U&Es
o CVP
• Perform a 12-lead ECG every hour until the diagnosis is made
• Correct:
o Arrhythmias
o U&E imbalances
o Acid-base balance
• Give positive inotropes (e.g. dobutamine2.5-10µg/hk/min IVI)
adjusted to keep systolic BP >80mmHg
• Increase renal perfusion by low-dose dopamine (2-5µg/kg/min
IVI)
• Look for and treat any reversible cause (e.g. PE, MI) – consider
thrombolysis
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Cardiac tamponade:
• Pericardial fluid accumulates, intra-pericardial pressure rises, the
heart cannot fill and pumping stops
• Major causes:
o Trauma
o Lung/breast cancer
o Pericarditis
o MI
o Bacteria (e.g. TB)
Signs of a cardiac tamponade:

• Beck’s triad:
o Falling BP
o Rising JVP
o Muffled heart sounds
• Echocardiography may be diagnostic
• CXR will show:
o Globular heart
o Left heart border convex or straight
o Right cardiophrenic angle <90˚
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Chronic heart failure
It is clinically useful to divide heart failure into the syndromes of right,

left and biventricular (congestive) heart failure, but it is rare for any
part of the heart to fail in isolation.
Right heart failure:

• This syndrome occurs in association with:
o Chronic lung disease (cor pulmonale)
o PE or pulmonary HT
o Tricuspid valve disease
o Left-to-right shunts (e.g. ASD and VSD)
• The most frequent cause of right heart failure is secondary to left
heart failure
Symptoms and signs of right heart failure:

• Symptoms:
o Fatigue
o Breathlessness
o Anorexia
o Nausea
• Signs:
o Increased JVP
o Tender, smooth hepatomegaly
o Dependent pitting oedema
o Ascites
o Pleural transudates (commonly right-sided)
Left heart failure:

• Causes include:
o IHD (the most common cause)
o HT
o Mitral/aortic valve disease
o Cardiomyopathies
• Mitral stenosis causes left atrial HT and signs of left heart failure
but does not itself cause failure of the left ventricle
Symptoms and signs of left heart failure:

• Symptoms:
o Fatigue
o Exertional dyspnoea
o Orthopnoea
o Paroxysmal nocturnal dyspnoea (PND)
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• Signs are few and not prominent until a late stage or if the
ventricular failure is acute:
o Cardiomegaly
o Displaced apex
o Left ventricular 3rd or 4th heart sound that, with a
tachycardia, is described as a gallop rhythm
o Functional mitral regurgitation (caused by dilatation of the
mitral annulus)
o Bi-basal lung crackles with possible pulmonary oedema
Congestive (biventricular) heart failure:

• This term is best restricted to cases where right heart failure is
secondary to left heart failure
• The physical signs are thus a combination of the above
syndromes
General/diagnostic investigations:
• CXR
• Blood tests:
o FBC
o LFTs
o U&Es
o TFTs
• Cardiac catheterisation
Functional/prognostic investigations:
• Cardiopulmonary exercise testing
• Resting and stress radionucleotide angiography
• Ambulatory ECG monitoring for 24-28 hours (if an arrhythmia is
suspected)
• Serum ANP levels (a measure of left ventricular systolic
dysfunction)
General treatment:
• Moderate physical exercise
• Weight loss (if appropriate)
• Salt restriction
• Alcohol abstinence (as alcohol has a negatively inotropic effect)
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Drug management:
• Relies on the following categories of drugs:
o Diuretics
o Vasodilators
o Positive inotropic agents
o Digitalis glycosides
o Anti-arrhythmic agents
Diuretics:
• All act by promoting the renal excretion of salt and water
• The resulting loss of fluid reduces preload and produces
consistent haemodynamic and symptomatic benefits in patients
with HF and rapidly removes dyspnoea and peripheral oedema
• Loop diuretics:
o E.g. frusemide, bumetanide
o Act by reducing sodium and chloride reabsorption in the
ascending limb of the loop of Henle
o Cause a brisk and short-lived diuresis
o Produce marked K+ loss and hyperuricaemia
• Thiazide diuretics:
o E.g. bendrofluazide
o Effect the distal convoluted tubule, reducing sodium
reabsorption
o Mild diuretic action
o Less effective in patients with a reduced GFR
o Again, promote K+ loss
o Metolazone is a powerful thiazide diuretic, producing a
profound diuresis acting synergistically with loop diuretics
• Potassium-sparing diuretics:
o Spironolactone:
• Competitive aldosterone antagonist
• Weak diuretic
• Has a potassium-sparing action (since aldosterone
promotes the excretion of potassium)
o Amiloride, triamterene:
• Act at the distal tubule, preventing potassium
secretion in exchange for sodium
• Weak diuretics
• Should be avoided in patients with renal failure and
those taking ACEIs (as both lead to potassium
retention)
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Vasodilator therapy:
• Arteriolar vasodilators:
o !-adrenoreceptor antagonists (e.g. prazosin)
o Direct smooth muscle relaxants (e.g. hydralazine)
o Calcium-channel blockers (e.g. amlodipine)
• Venodilators:
o Short-acting nitrates (e.g. GTN)
o Long-acting nitrates (e.g. isosorbide mononitrate)
o With chronic use, tolerance develops
Angiotensin converting enzyme inhibitors (ACEIs):

• E.g. enalapril
• Decrease TPR and reduce circulating levels of catecholamines
• Should be carefully introduced to patients due to risk of first-
dose hypotension
• Concomitant potassium-sparing diuretics should be discontinued
(since ACEIs can lead to potassium retention)
• ACEIs are contraindicated in patients with bilateral renal artery
stenosis
• Between 10-15% of patients develop a cough, owing to the
inhibition of bradykinin metabolism
Angiotensin II receptor antagonist:

• E.g. losartan
• Similar haemodynamic effects to ACEIs
• Do not affect bradykinin metabolism or produce a cough
ß-blockers:
• E.g. metoprolol
Inotropic agents – usually acute heart failure:

• Digitalis glycosides:
o Is a competitive inhibitor of Na+-K+-ATPase, therefore,
producing high levels of intracellular sodium. This is then
exchanged for calcium – leads to increased cardiac
contractility
o Digoxin is administered orally (1mg loading dose and
0.125-0.25mg daily according to body mass and renal
function)
o Digoxin toxicity (levels >2.5nmol/L) leads to:
• Anorexia, nausea, altered vision
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• Arrhythmia (e.g. ventricular premature beats, VT

and AV block)
Anticoagulants:
• HF is associated with a 4x risk of stroke
• Oral anticoagulants are recommended in patients with:
o Atrial fibrillation
o A previous history of thromboembolism
Treatment summary:
• All patients with clinical HF should receive treatment with
diuretics and an ACEI
• Patients in AF should be digitalized but patients in sinus rhythm
may also be improved by the addition of digoxin or a ß-blocker
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Infective endocarditis (IE)
Overview:
• IE is an infection of the endocardium or vascular endothelium
• The disease may occasionally occur as a fulminating or acute
infection, but more commonly runs an insidious course and is
known as subacute (bacterial) endocarditis (SBE)
• Annual incidence is 6-7 per 100,000 in the UK
• Occurs most commonly on rheumatic or congenitally abnormal
valves (as well as in mitral valve prolapse and calcified aortic
valve disease)
• It also occurs in association with congenital lesions (e.g. VSD)
Aetiology:
• Many organisms cause IE. Currently, the 3 most common
organisms are:
o Streptococcus viridans (50% of cases)
o Enterococcus faecalis
o Staphlococcus aureus (50% of acute cases)
Clinical features of IE:

Malaise 95%
Murmurs 90%
Pyrexia 90%
Haematuria 70%
Cardiac failure 50%
Petechiae 50%
Splenomegaly 40%
Arthralgia 25%
Cerebral emboli 20%
Osler’s nodes 15%
Splinter haemorrhages 10%
Mycotic aneurysm 10%
Clubbing 10%
Janeway lesions 5%
Roth spots 5%
Presentations:
• Subacute endocarditis:
o Fever
o Night sweats
o Weight loss
o Weakness
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o Symptoms due to cardiac failure or embolism

o Another important presentation is a combination of renal
failure and a heart murmur
• Acute endocarditis:
o In IVDUs or following an acute suppurative illness (e.g.
meningitis or pneumonia) the development of acute IE is
suggested by the:
• Persistence of fever
• Development of heart murmurs
• Vasculitis (with petechial haemorrhage)
• Embolism
Investigations:
• Blood:
o Normochromic normocytic anaemia is usual
o Raised ESR and CRP
o Raised WCC
• LFTs:
o Mild disturbances
o Raised ALP
• Immunoglobulins and complement:
o Serum Igs are increased
o Total complement and C3 complement are decreased
(owing to immune complex formation)
• Urine:
o Microscopic haematuria is nearly always present
o Proteinuria may occur
• Blood cultures:
o Are positive in ~75% of cases
• Echocardiography:
o Useful for identifying vegetations
o Useful for documenting valvular dysfunction and to identify
patients in need of urgent surgery
• CXR:
o May show evidence of HF
o Evidence of emboli in right-sided endocarditis
Drug treatment:
• Treat any underlying infection (e.g. drainage of a dental
abscess)
• Treatment is with an appropriate antibiotic to which the bacteria
is susceptible to for 4-6 weeks
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• The first 2 weeks will be IV therapy, followed by 2-4 weeks of

oral therapy
Surgical treatment:
• There are several situations in which surgery is necessary:
o Extensive damage to a valve
o Early infection of prosthetic material
o Worsening renal failure
o Persistent infection but failure to culture an organism
o Embolization
o Large vegetations
o Progressive cardiac failure
• The timing of surgery is important. On the one hand, the
infection should, if possible, be eradicated before surgery is
undertaken, but on the other hand the heart should not be left in
a badly compromised haemodynamic state. In general, early
surgery is preferable
Prognosis:
• The prognosis is worse when:
o The organism cannot be isolated
o Cardiac failure is present
o Infection occurs on a prosthetic valve
o The micro-organisms found are resistant to therapy
• In general, 70% of those affected are treated effectively
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Mitral regurgitation (MR)
Aetiology:
• Rheumatic fever (50% of cases)
• Prolapsed mitral valve
• Any disease that causes LV dilatation;
o Aortic valve disease
o Myocarditis
o Dilated cardiomyopathy
o Hypertensive heart disease
o IHD
• IE
• Connective tissue disorders (e.g. SLE)
• Marfan’s syndrome
Symptoms:
• Asymptomatic for many years
• Palpitations (due to the increased SV)
• Dyspnoea/orthopnoea owing to pulmonary HT
• Fatigue/lethargy due to the reduced cardiac output
• In the late stages of the disease, the symptoms of right-heart
failure also occur, culminating in congestive cardiac failure
• Cardiac cachexia may develop
• Subacute IE is quite common
Signs:
Pulse: Sinus rhythm or AF
Apex: Thrusting, displaced, systolic thrill
Sound: Soft S1, S3
Murmur: Pansystolic
Investigations:
• CXR:
o Left atrial/ventricle enlargement
o Cardiomegaly
• ECG:
o P mitrale (left atrial delay)
o Left ventricular hypertrophy:
• Left axis deviation
o AF may be present
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Treatment:
• Asymptomatic, mild MR can be managed conservatively by
following the pt with serial echocardiograms
• Antibiotic prophylaxis against IE is required
• Any evidence of progressive cardiac enlargement generally
warrants early surgical intervention, by either mitral valve repair or
replacement
• For those patients who are not considered appropriate for surgical
intervention, or in whom surgery will be considered at a later date:
o ACEIs
o Diuretics
o Anticoagulants (possibly)
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Mitral stenosis (MS)
Aetiology:
• Rheumatic fever (almost all cases are due to this)
• Lutembacher’s syndrome (combination of acquired MS and an
ADS)
• Calcification and fibrosis of the valve, valve ring and chordae
tendineae (elderly)
• Congenital mitral stenosis (rare)
Complications of MS:
• Atrial fibrillation
• Systemic embolization
• Pulmonary HT
• Pulmonary infarction
• Chest infections
• Tricuspid regurgitation
• Right ventricular failure
• IE (rare)
Symptoms:
• Asymptomatic until valve orifice is reduced from 5cm2 to 2cm2
• Progressively severe dyspnoea (due to pulmonary HT and
recurrent bronchitis)
• A cough productive of blood-tinged, frothy sputum is quite
common
• Frank haemoptysis may occur
• Symptoms of right-heart failure (fatigue, weakness, abdominal/
lower limb swelling)
• Palpitations (due to AF)
• AF may result in systemic embolization, commonly to the
cerebral vessels
Signs:
Pulse: AF (irregularly irregular)
RV: Heaving
Apex: Tapping, non-displaced
Sound: Loud S1, loud P2, opening snap
Murmur: Mid-diastolic rumble at apex, best heard with pt on
left-side
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Investigations:
• CXR:
o Small heart
o Enlarged left atrium
o Signs of pulmonary oedema may be apparent when the
disease is severe
• ECG:
o In sinus rhythm, the ECG shows a bifid P wave (P mitrale)
due to delayed left atrial activation
o AF is frequently present
o As the disease progresses, there features of right
ventricular hypertrophy may develop:
• Right axis deviation
Treatment:
• Mild MS may need no treatment other than prompt therapy of
attacks of bronchitis
• Antibiotic therapy is advised to prevent IE (although rare)
• Early symptoms of MS (e.g. mild dyspnoea) can be treated with
diuretics
• The onset of AF requires treatment with digoxin and
anticoagulation
• If pulmonary HT develops, surgical relief of the MS is advised
• There are 4 operative measures:
o Trans-septal balloon valvotomy
o Closed valvotomy
o Open valvotomy
o Mitral valve replacement
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Myocardial infarction (MI)
Epidemiology:
• Commonest cause of death in the UK
• Incidence of 5/1000 per year
• 50% survive the acute event. Of these, a further 10% die in
hospital and up to 20% more die in the first 2 years
• 50% of initial survivors are alive at 10 years
Clinical features:
• Severe central chest pain, often described as crushing in nature
• Pain may radiate to the jaw and left arm
• Onset is usually sudden and persists fairly constantly for several
hours (often until diamorphine is given)
• Up to 20% of patients experience no pain – so called ‘silent MI’.
This is commonly seen in diabetics and the elderly
• Other symptoms/signs:
o Sweating
o Breathlessness
o Nausea/vomiting
o Pallor
Diagnosis:
• Requires at least 2 of the following:
o A history of ischaemic-type chest pain
o Evolving ECG changes
o A rise and fall in cardiac enzymes
Investigations – ECG:
• Abnormal Q waves (usually permanent)
• Inverted T waves
• Elevated ST segments
Investigations – cardiac enzymes:

• Creatinine kinase (CK):
o Peaks within 24 hours and is usually back to normal within
48 hours
o Produced by damaged:
• Cardiac muscle
• Skeletal muscle
• Brain
o Cardiac-specific isoforms (CK-MB) can be measured,
allowing greater diagnostic accuracy
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o The size of the enzyme rise is broadly proportional to the

infarct size
• Cardiac-specific troponins:
o Troponin T and I have a very high specificity for cardiac
injury
o Released early (2-4 hours) and can persist for up to 7 days
• Lactate dehydrogenase (LDH):
o Non-specific
o Rarely used
Acute management of an MI:

• Immediate ECG
• If diagnostic ST elevation is present, thrombolysis should be
commenced without delay
• Aspirin given (150mg chewed)
• Adequate analgesia (e.g. diamorphine 5-10mg IV)
• Antiemetics (e.g. cyclizine 50mg IV or metoclopramide 10mg IV)
should be given if required
• Thrombolytic therapy can achieve reperfusion in 50-70% of
patients
• Following initiation of thrombolysis, the patient should be
transferred to the CCU
• An IV "-blocker (e.g. metoprolol 5-10mg) should be given,
especially if the HR is greater than 100bpm
• 60% oxygen is given routinely by a face mask or nasal cannula
Criteria for thrombosis in acute MI:

• Indications:
o Chest pain consistent with MI, within 12 hours
AND
o ST segment elevation (>1mm in 2 or more contiguous
leads) or new LBBB
• Contraindications:
o Stroke or active bleeding in last 2 months
o Systolic BP >200mmHg
o Proliferative diabetic retinopathy
o Pregnancy
• Relative contraindications:
o Prolonged or traumatic resuscitation
o Recent (>2 weeks) surgery or trauma
o Current use of anticoagulants
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Thrombolysis:
• Streptokinase (1.5 million U over 1 hour) is the agent used most
commonly
• Tissue plasminogen activator (t-PA) achieves higher reperfusion
rates but is more expensive and is associated with a higher risk
of stroke
• t-PA tends to be given in preference to patients:
o under 50 years of age with anterior MIs
o with a low BP (systolic <100mmHg)
o who have previously received streptokinase
• t-PA must be followed by IV heparin
• Risks of thrombolysis:
o 1% risk of stroke
o 0.7% risk of a major haemorrhage
o 2% risk of an allergic reaction with streptokinase
Subsequent management in hospital:

• Monitor the patient in the CCU for 48 hours
• Aspirin 150mg daily is given unless contraindicated
• "-blockers unless contraindicated (e.g. COPD)
• Patients with clinical evidence of pulmonary oedema or reduced
ejection fraction on the echocardiogram should be put on an
ACEI
• Gradual mobilization is commenced on the second day
• The patient should be pain-free and fully ambulant before
discharge (6 days in an uncomplicated case)
• Patients should be advised that they cannot drive for 1 month
Follow-up:
• Most will be fully recovered at 2 months and will be able to
return to work
• Most patients should be reviewed as outpatients at 6-8 weeks
• Aspirin should be continued indefinitely
• Lipid-lowering therapy should be considered if the fasting lipid
profile is unfavourable
• ACEIs should be continued indefinitely in those with persistent
impairment of LV function (i.e. an ejection fraction of <40%)
Complications:
• Acute (2-3 days post-infarct):
o Cardiac arrhythmias
o Cardiac failure
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o Pericarditis
• Late:
o Recurrent infarction
o Angina
o Thromboembolism
o Ventricular aneurysm
o Mitral valve regurgitation
Ventricular extrasystoles:
• Commonly occur after MI
• May precede the development of VF, particularly if they are:
o Frequent (>5 per minute)
o Multiform (different shapes)
o R-on-T
Ventricular tachycardia:
• May degenerate into VF
• May itself produce serious haemodynamic consequences
• Can be treated with:
o IV lignocaine
o Synchronised cardioversion (initially 200J)
Ventricular fibrillation:
• May occur in the first few hours or days following an MI
• Treated with prompt defibrillation (200-360J)
• Recurrences of VF can be treated with lignocaine infusion or, in
cases of poor LV function, amiodarone
• When VF occurs in the setting of HF, shock or aneurysm (so-
called ‘secondary VF’), the prognosis is very poor unless the
underlying haemodynamic or mechanical cause can be corrected
• It is prudent to ensure the serum K+ is above 4.5mmol/L
Atrial fibrillation:
• Occurs in ~10% of patients with MI
• May be managed with IV digoxin or IV amiodarone and by
treatment of the underlying pathology
• It is not usually a long-standing problem
Sinus bradycardia:
• Especially associated with acute inferior wall MI
• When symptomatic, treatment consists of:
o Elevating the foot of the bed
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o IV atropine 600µg
Prognosis:
• Variable
• Approximately 25% of patients surviving the initial heart attack
die in the first 2 years
• 5-year mortality approaches 30%
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Pulmonary oedema
This is a very frightening, life-threatening emergency characterised by

extreme breathlessness
Clinical features:
• Patients with alveolar oedema are:
o Acutely breathless
o Wheezing
o Anxious
o Perspiring profusely
o Cough, productive of frothy, blood-tinged (pink) sputum,
which can be copious
o Tachypnoea
o Peripheral circulatory shutdown
o Tachycardia
o Raised JVP
o Gallop rhythm
o Crackles and wheeze are heard throughout the chest
• CXR shows:
o Diffuse haziness
o Kerley B lines (of interstitial oedema)
Treatment:
• Sit the patient up
• Give 60% O2 (unless there is coexisting chronic hypercapnia due
to longstanding respiratory failure)
• IV diuretic therapy with frusemide or bumetanide is given
• Morphine (10-20mg IV) together with an antiemetic (e.g.
metoclopramide 10mg IV or cyclizine 50mg IV) is given:
o This sedates the patient and causes systemic
vasodilatation – it must be avoided if the systolic BP is
<90mmHg
• Venodilators (e.g. GTN) may produce prompt relief by reducing
preload
• Aminophylline (250-500mg or 5mg/kg IV) is infused over 10
minutes:
o Is a PDE i nhi bi tor that causes bronchodi l ati on,
vasodilatation and increased cardiac contractility
o It must be GIVEN SLOWLY due to the risk of precipitating
ventricular arrhythmias
o It is now only used when bronchospasm is present
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Sinus arrhythmias
Normal ECG intervals:

PR interval 200ms (5 small squares)
QRS complex duration 120ms (3 small squares)
QT interval 400ms (2 large squares)
Sinus arrhythmia:
• A normal variation
• During inspiration, parasympathetic tone decreases and the
heart rate increases
• On expiration, the heart rate falls
Sinus bradycardia:
• A sinus rate of <60bpm during the day or <50bpm during the
night
• Normal in athletes and the elderly
• Causes include:
o Hypothermia
o Hypothyroidism
o Cholestatic jaundice
o Raised ICP
o Drugs (e.g. digitalis, ß-blockers)
o Acute ischaemia/infarction of the sinus node
• Treatment:
o IV atropine 600µg
o Pacemaker if unsuccessful
Sinus tachycardia:
• Sinus rate acceleration to >100bpm
• Causes include:
o Fever
o Exercise
o Emotion
o Pregnancy
o Anaemia
o Thyrotoxicosis
o Catecholamine excess
• Treatment:
o Treat underlying cause
o ß-blockers can be used
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Unstable angina
Overview:
• Is a medical emergency which, untreated, will progress to an MI
in over 10% of cases
• Standard therapy (see below) reduces this rate to less than 5%
• However, death within 1 year still occurs in 5-15%
Immediate treatment:
• Heparin 5000U IV bolus then IVI to maintain APPT 1.5-2.5
• Diltiazem 60mg PO TDS
• Atenolol 50-100mg PO OD
• Isosorbide dinitrate 2-20mg/h IVI
• Aspirin 75mg PO OD
• Monitor closely on CCU and exclude (and prevent impeding) MI
Subsequent management:
• Those at high risk:
o Should proceed promptly to angiography, with a view to
proceeding to revascularisation, where appropriate, during
that admission
• Those at low risk:
o Discharged and assessed electively as outpatients
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Ventricular tachyarrhythmias
Types:
• There are 4 main types of ventricular tachyarrhythmias:
o Ventricular premature beats
o Ventricular tachycardia (VT)
o Ventricular fibrillation (VF)
o Torsades de pointes (twisting of points)
Causes of ventricular tachyarrhythmias:

• All but Torsades de pointes:
o Coronary heart disease
o HT
o Cardiomyopathy
• Torsades de pointes:
o Hypokalaemia/hypocalcaemia/hypomagnesaemia
o Organophosphate insecticides
o Acute MI
o Mitral valve prolapse
o Many drugs (especially antiarrhythmic agents)
Ventricular premature beats:

• On the ECG:
o The premature beat has a broad (>0.12s) QRS complex
because it arises from an abnormal (ectopic) site in the
ventricular myocardium
o Following the premature beat, there is usually a complete
compensatory pause because the AVN or ventricle is
refractory to the next sinus impulse
o Early R-on-T ventricular premature beats (occurring
simultaneously with the upstroke or peak of the T wave of
the previous beat) may induce VF, particularly following MI
• Treatment:
o Drugs from classes I, II or III are used
o In the absence of heart disease, ventricular premature
beats may be safely ignored
Ventricular tachycardia:
• Defined as 3 or more ventricular beats occurring at a rate of
>120bpm
• Often the patient will be hypotensive and ill (but some VTs are
well tolerated)
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• ECG shows:
o Rapid ventricular rhythm with broad (often >0.14s)
abnormal QRS complexes
o Dissociated P wave activity may be seen
• Treatment:
o May be urgent depending on the haemodynamic situation
o If the cardiac output and the BP are very depressed,
emergency DC cardioversion must be considered
o On the other hand, if the BP and CO are well maintained,
IV therapy with class I drugs is usually advised
• First-line treatment consists of:
o Lidocaine (50-100mg IV over 5 minutes)
o Followed by a lidocaine infusion (2-4mg IV per minute)
Ventricular fibrillation:
• This is very rapid and irregular ventricular activation with no
mechanical effect
• The patient is pulseless and becomes rapidly unconscious and
respiration ceases
• ECG shows:
o Shapeless, rapid oscillations and there is no hint of
organized complexes
o It is usually provoked by a ventricular ectopic beat
(especially in acute MI), VT or torsades de pointes
o Rarely reverses spontaneously
• Treatment:
o The only effective treatment is electrical defibrillation or
(on rare occasions) IV bretylium (5-10mg/kg over 5
minutes)
o Basic and advanced life support is needed
Torsades de pointes:
• This arrhythmia is usually short in duration and spontaneously
reverts to sinus rhythm
• It does, however, give rise to presyncope or syncope and
occasionally converts to VF, and sudden death may occur
• ECG shows:
o Rapid, irregular sharp complexes that continuously change
from an upright to an inverted position
o Between spells of tachycardia, the ECG shows a prolonged
QT interval
• Treatment:
o Correction of any electrolyte disturbance
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o Cessation of any causative drugs

o Maintenance of the HR with atrial or ventricular pacing
o IV isoprenaline may be effective when QT prolongation is
acquired
o ß-blockade or left stellectomy is advised if QT prolongation
is congenital (isoprenaline is contraindicated for congenital
long-QT syndrome)
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Wolff-Parkinson-White (WPW) syndrome
Overview:
• This is a congenital condition caused by an abnormal myocardial
connection between atrium and ventricle (via the bundle of Kent)
• During sinus rhythm, the electrical impulse can conduct quickly
over this abnormal connection to depolarise part of the ventricles
abnormally
The ECG:
• There is a characteristic ECG pattern of WPW syndrome:
o Short PR interval
o Wide QRS complex
o Slurred upstroke (# wave) to the QRS complex
• About 50% of those with WPW pattern on the ECG have
tachycardias
• The tachycardias are of 2 sorts:
o Atrioventricular re-entry:
• This is a circus movement tachycardia in which a
depolarisation wave travels from the atrium to the
ventricle (usually through the AV node) and from the
ventricle to the atrium through the abnormal
pathway
• I V a d e n o s i n e w i l l t e r m i n at e m o s t o f t h e s e
tachycardias
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Dermatology
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Bullous disease
Overview:
• Primary blistering diseases of the skin are rare
• A variety of skin proteins are important in holding the skin
together
• Inherited abnormalities or immune damage of these proteins
causes abnormal cell separation, inflammation, fluid
accumulation and blistering
• Skin biopsy for light and electron microscopy, together with
immunofluorescence (IMF) studies, is paramount in diagnosis
• One must remember that the most common causes of skin
blistering are:
o Chickenpox
o Herpes
o Impetigo
o Insect bite reactions
Pemphigus vulgaris
Overview:
• Is a potentially fatal blistering disease occurring in all races, but
it is more common in Ashkenazi Jews
• Onset is in middle age
• Males = females
• Is caused by the development of autoantibodies against
desmosomal proteins (dsg3)
Clinical features:
• Mucosal involvement (especially oral ulceration) is common and
may be the presenting sign in up to 50% of cases
• Is then followed by the appearance of flaccid blisters, particularly
involving the trunk
• They tend to become rather itchy
• Blistering usually becomes widespread, but they rapidly denude;
thus pemphigus often presents with erythematous, weeping
erosions
Treatment:
• Very high-dose oral prednisolone (60-100mg daily) or pulsed
Methylprednisolone. This may need to be lifelong
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• Other immunosuppressants (e.g. azathioprine,

cyclophosphamide or cyclosporine) are used as steroid-sparing
drugs
• IV immunoglobulin infusions can be useful in resistant cases
• Whilst treatment is normally effective, up to 20% of patients
may succumb to either:
o Side-effects of the disease
o Side-effects of the treatment (most common)
Bullous pemphigoid
Overview:
• More common than pemphigus vulgaris
• Presents in later life (usually over the age of 60 years)
• Mucosal involvement is rarer
• Is caused by autoantibodies against a hemidesmosomal protein
Clinical features:
• Large tense bullae appear anywhere on the skin, but often
involve:
o Limbs
o Hands
o Feet
• They may be centred on an erythematous or urticated
background and they can be haemorrhagic
• Pemphigoid can be very itchy
Treatment:
• High-dose oral prednisolone (30-60mg daily) and steroid-sparing
agents such as azathioprine
• In general, disease control is easier than with pemphigus
vulgaris
• Often, treatment can be withdrawn after 2-3 years
Dermatitis herpetiformis
Overview:
• Is a rare blistering disorder associated with Coeliac disease and,
occasionally, other organ-specific autoimmune disorders
Clinical features:
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• Is most common in males

• Can present at any age but is most likely to appear for the first
time in young adult life
• It presents with intensely itchy, small blisters of the skin
• Commonest sites are the:
o Elbows
o Extensor forearms
o Scalp
o Buttocks
• The tops of the blisters are usually scratched off; thus crusted
erosions are often seen at presentation
• Remissions and exacerbations are common
Treatment:
• Should always be with a gluten-free diet (GFD)
• Control of the skin disease can be obtained with oral dapsone
(50-200mg daily) or sulphonamides
• If a strict GFD is adhered to, oral medication can often be
withdrawn after 2 years
• The GFD will need to be lifelong – it protects against the rare
complication of small bowel lymphoma
• Use of dapsone:
o Frequently causes a mild dose-related haemolytic anaemia
(which is usually well-tolerated)
o The haemolysis can be devastating if there is G6PD
deficiency
o Liver damage, a polyneuropathy and aplastic anaemia also
occur rarely
o Regular monitoring of a blood count and liver biochemistry
is needed
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Eczema (a.k.a. dermatitis)
Types of eczema:
• Are many types
• The 3 main ones are listed below:
o Atopic dermatitis
o Contact dermatitis
o Seborrhoeic dermatitis
General clinical features – dermatitis:

• Erythema
• Papules
• Vesicles
• Excoriation/pruritus
• Secondary infection
Atopic dermatitis
Aetiology:
• Unknown
• Strong familial tendency
• If one parent has atopic disease, the risk for a child of
developing eczema is about 20-30%
• If both parents have atopic eczema, the risk is >50%
Exacerbating factors:
• Exacerbating factors are not necessarily allergens
• Strong detergents, chemicals
• Woollen clothes
• Severe anxiety, stress
• Cat/dog fur (possibly by both allergic and irritant mechanisms)
Specific clinical features:

• Commonest sites are:
o Front of elbows/ankles
o Back of knees
o Around the neck
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Investigations:
• Diagnosis is usually clinical
• Atopy is characterised by high serum IgE levels or high specific
IgE levels to certain ingested or inhaled antigens:
o Can be tested by radio-immunoabsorbent assay (RAST
tests) of blood
o Skin-prick testing
Prognosis:
• Vast majority of children with early-onset atopic eczema will
improve spontaneously and ‘clear’ before the teenage years,
50% being clear by the age of 6
• If the onset is late in childhood or in adulthood, the disorder
follows a more chronic remitting/relapsing course
Treatment:
• General measures:
o Avoid known irritants (especially soaps or furry animals)
o Not getting too hot
• Topical therapies:
o Are sufficient to control atopic eczema in most people and
the following ‘triple’ combination often helps:
• Topical steroid bds when needed
• Emollient frequently
• Bath oil (e.g. oilatum or balneum) and soap substitute
(e.g. aqueous cream)
• It should be noted that topical steroids can be safely
prescribed for long-term, intermittent, use
• Antibiotics:
o Are needed for bacterial infection
o Usually given orally for 7-10 days
o E.g. flucloxacillin (500mg tds) is effective against
Staphylococcus
o E.g. penicillin V (500mg tds) acts against Streptococcus
o Erythromycin (500mg tds) is useful if there is allergy to
penicillin
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Contact and irritant dermatitis
Overview:
• One may suspect this if the eczema is in an unusual or localised
distribution, especially if there is no personal or family history of
atopic disease
• A history of an exacerbation of eczema at the workplace is also
suggestive
• This can happen by 2 mechanisms:
o Direct irritation
o Allergic reaction (type IV delayed hypersensitivity)
• A detailed history about occupation, hobbies, cosmetic products
and clothing and contact with chemicals is necessary
Irritant eczema:
• Can occur in any individual
• It often occurs on the hands after repeated exposures to irritants
such as detergents, soaps or bleach
• It is, therefore, common in housewives, cleaners, hairdressers,
mechanics and nurses
Contact eczema:
• Occurs after repeated exposure to a chemical substance but only
in those people who are susceptible to develop an allergic
reaction
• Common (up to 4% of the population)
• Most common culprits are:
o Nickel (costume jewellery, buckles)
o Latex
o Chromate (in cement)
Treatment:
• As for atopic eczema, as well as strict avoidance of any causative
agent
• This may involve the wearing of protective clothing (e.g. gloves)
or may involve a change of occupation or hobby
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Seborrhoeic eczema
There is some evidence that the yeast Pityrosporum ovale is important

and may act as an ‘antigenic drive’ to produce the characteristic
inflammation and scaling of seborrhoeic eczema
The condition is more common in Parkinsonism as well as HIV
Clinical features:
• 3 age groups are affected:
• In childhood:
o Common
o Presents in the first few months of life as ‘cradle cap’ in
most babies
o May be, in part, due to the effect of maternal androgens
on infant sebaceous glands
o Yellowish, greasy, thick crusts are seen on the scalp
o A more widespread erythematous scaly rash can be seen
over the trunk, especially affecting the nappy area
o Unlike atopic eczema, the child is normally unbothered as
there is little associated pruritus
o Usually improves spontaneously after a few weeks
• In young adults:
o Males > females
o Occurs in 1-3% of the population
o Presents as an erythematous scaling:
• Along the sides of the nose
• In the eyebrows
• Around the eyes
• Extending into the scalp (giving rise to marked
dandruff)
• May affect the skin over the sternum and of the
glans penis
• In elderly people:
o Can be quite severe and progress to involve large areas of
the body
o May even cause erythroderma
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Treatment:
• The treatment is suppressive rather than curative
• Combination of:
o Mild steroid ointment (e.g. 1% hydrocortisone bds)
o Topical antifungal cream (e.g. miconazole cream bds)
o Ketoconazole shampoo and arachis oil are useful for the
scalp
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Dermatology terminology
Terminology:
Macule Flat, impalpable lesion
Papule Raised lesion that is <1cm across
Nodule Raised lesion that is >1cm across
Plaque Flat raised lesion usually formed by papules
fusing together
Vesicle Fluid-filled lesion <1cm across
Bulla Fluid-filled lesion >1cm across
Orthoketatosis Thick scale
Parakeratosis Silvery scaling
Crust Dried serous exudates
Erythema Red – blanches on diascopy (pressing with
piece of glass)
Purpura Red – does not blanch on diascopy
Hypopigmented Pale
Hyperpigmented Dark
Leukoderma White
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Lichen planus
Clinical features:
• Rash is characterised by small, purple, flat-topped polygonal
papules that are intensely pruritic
• It is common on the flexors of the wrists and the lower legs, but
can occur anywhere
• The lesions may fuse into plaques, especially on the lower legs
and in Africans
• Hyperpigmentation is common after resolution of lesions,
especially in patients with pigmented skin
• If lesions occur in the scalp, they may cause a scarring alopecia
• Mucosal involvement is seen in 50% of cases:
o The mouth is the most commonly affected, but the
anogenital region can be involved
o It can present as lacy white streaks, white plaques or as
ulceration
o Prominent symptom is pain, rather than pruritus
Prognosis:
• The condition often clears within 2 years, but can recur at
intervals
• The hypertrophic and atrophic variants and mucosal disease are
more persistent, lasting years
• Ulcerative mucosal disease is pre-malignant
Treatment:
• Use of potent topical steroids (e.g. 0.05% clobetasol
proprionate)
• Occasional use of oral prednisolone (30mg od for 2-4 weeks)
• Resistant cases may respond to:
o UV therapy
o Oral retinoids (0.5mg/kg daily)
o Azathioprine (50-100mg daily)
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Malignant cutaneous tumours
Basal cell carcinoma (rodent ulcer)
Overview:
• Most common malignant skin tumour
• Most relate to excessive sun exposure
• Common in later life on exposed sites – although are rare on the
ear
• They can present as a slow-growing papule or nodule which may
go on to ulcerate
• Telangiectasia over the tumour or a skin-coloured jelly-like
‘pearly edge’ may be seen
• A flat, diffuse superficial form exists (‘morphoeic’)
• The lesion will grow slowly and erode structures if untreated
• Almost never metastasizes
Treatment:
• Usually surgical excision
• Radiotherapy can be useful for large superficial forms
• Curettage is occasionally used in older patients, although not for
central facial lesions as they often recur
• Very superficial lesions may be treated with Cryotherapy
• Follow-up is advised
Squamous cell carcinoma
Overview:
• Is a somewhat more aggressive skin tumour which can
metastasise
• Most relate to sun exposure and they arise in pre-existing solar
keratoses or Bowen’s disease
• They can also arise as a result of chronic inflammation, such as
in lupus vulgaris
• Rarely, multiple tumours may arise owing to arsenic ingestion in
early life
• Multiple tumours also occur in people who have had prolonged
periods of immunosuppression
• They present clinically as fairly rapidly growing nodules which
often ulcerate
• Examination of regional lymph nodes is essential
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• They are most common on sun-exposed sites in later life

• One should have a high index of suspicion for ulcerated lesions
on the lower lip or ear
Treatment:
• Excision or radiotherapy
Malignant melanoma
Overview:
• Is the most serious form of skin cancer as metastasis can occur
early and it causes a number of deaths, even in young people
• Risk factors include:
o Childhood sun exposure
o Sun burning
o Atypical mole syndrome
o Giant congenital melanocytic naevi
o Positive family history of malignant melanoma
• Is more common in later life but many young adults are also
affected
• It should always be suspected in rapidly growing or bleeding
pigmented lesions
• A halo of erythema or the appearance of satellite lesions should
also alert the examiner
• 4 clinical types exist:
o Lentigo maligna melanoma:
• Is where a patch of lentigo maligna develops a papule
or nodule, signalling invasive tumour
o Superficial spreading malignant melanoma:
• Is a large, flat, irregularly pigmented lesion which
grows laterally before vertical invasion develops
o Nodular malignant melanoma:
• Is the most aggressive type
• It presents as rapidly growing pigmented nodules which
bleed or ulcerate
o Acral lentiginous malignant melanoma:
• Arise as pigmented lesions on the palm, sole or under
the nail
• Usually present late
Treatment:
• Urgent wide local excision of the lesion
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• Metastatic disease is best managed by an oncologist and can

involve surgery to lymph nodes, radiotherapy, immunotherapy
and chemotherapy
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Pityriasis rosea
Overview:
• Self-limiting rash seen in adolescents and young adults
• Unknown cause but is thought to be a viral or post-viral rash
Clinical features:
• The rash consists of circular or oval pink macules with a
collarette of scale
• Is more prominent on the trunk than on the limbs
• The long axis of the oval lesions tends to run along dermatomal
lines, giving a ‘Christmas tree’ pattern on the back
• The rash may be preceded by a large solitary patch with
peripheral scaling (‘herald patch’) and this is most commonly
found on the trunk
• Is usually asymptomatic
• Spontaneously resolves over 4-8 weeks
Treatment:
• Not normally required
• 0.5% menthol in aqueous cream may help relieve the itching
• In persistent cases, UVB may be helpful
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Potentially pre-malignant cutaneous tumours
Solar keratoses (actinic keratoses):

• These frequently develop later in life in white-skinned people
who have had significant sun exposure
• They appear on exposed skin as erythematous silver-scaly
papules or patches with a conical surface and a red base
• The background skin is often inelastic and wrinkled and may
show flat brown macules (‘liver spots’), reflecting diffuse solar
damage
• A small proportion of these keratoses can transform into
squamous cell carcinoma, but only after many years
• Treatment:
o Cryotherapy
o Topical 5-fluorouracil cream
Bowen’s disease:
• This is a form of intra-epidermal carcinoma-in-situ which rarely
can become invasive
• It presents on exposed skin as an isolated scaly red patch or
plaque looking rather like psoriasis, although it has a rather
irregular edge
• The lesions do not clear, but slowly increase in size over the
years
• Treatment:
o Cryotherapy
o Topical 5-fluorouracil cream
o Curettage
Atypical mole syndrome (dysplastic naevus syndrome):

• This is often familial
• A large number of melanocytic naevi begin to appear in
childhood, even on unexposed sites
• Individual lesions may be large with irregular pigmentation and
border
• Individuals with this condition have an increased risk of
developing malignant melanoma
• They should have their moles photographed and be regularly
reviewed
• Suspicious lesions should be excised
Giant congenital melanocytic naevi:

• These are very large moles present at birth
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• They show an increased risk of developing malignant melanoma

• Excision should be considered if it is possible
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Psoriasis
Overview:
• Is a common papulo-squamous disorder affecting 2% of the
population
• Characterised by well demarcated, red scaly plaques
• The skin becomes inflamed and hyperproliferates to about 10x
the normal rate
• Males = females
• The age of onset occurs in 2 peaks:
o Early onset (16-22 years) – more common and is
associated with a +ve family history
o Late onset (55-60 years)
Pathology:
• Skin biopsy shows acanthosis and Parakeratosis, reflecting the
increase in skin turnover
• The granular layer is often absent
• Polymorphonuclear abscesses may be seen in the upper
epidermis
Types of psoriasis:
• Chronic plaque psoriasis
• Flexural psoriasis
• Guttate psoriasis
• Erythrodermic and pustular psoriasis
Chronic plaque psoriasis:

• This is the ‘common’ type of psoriasis
• Is characterised by pinkish red scaly plaques, especially on:
o Knees
o Elbows
o Lower back
o Ears
o Scalp
• New plaques of psoriasis may occur at sites of skin trauma (so-
called Kobner phenomenon)
• The lesions can become itchy or sore
Flexural psoriasis:
• Tends to occur in later life
• Characterised by well demarcated red glazed plaques confined to
flexures such as the:
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o Groin
o Natal cleft
o Sub-mammary area
• Rarely there is any scaling
• In the absence of psoriasis elsewhere, the rash is often
misdiagnosed as candida intertrigo
Guttate psoriasis:
• ‘Raindrop-like’ psoriasis is a variant most commonly seen in
children and young adults
• An explosive eruption of very small circular or oval plaques
appears over the trunk about 2 weeks after a Streptococcal sore
throat
• It usually resolves spontaneously over 1-2 months even without
treatment
Erythrodermic ad pustular psoriasis:

• These are the most severe types of psoriasis, reflecting a
widespread intense inflammation of the skin
• They can occur together (‘Von Zumbusch’ psoriasis) and may be
associated with:
o Malaise
o Pyrexia
o Circulatory disturbance, this form can be life-threatening
• The pustules are not infected, but are sterile collections of
inflammatory cells
• There is also a more localised variant of pustular psoriasis that
confines itself to the hands and feet, but is not associated with
severe systemic symptoms
Associated features:
• Nails:
o Up to 50% of patients develop nail changes and rarely
these can precede the onset of skin disease
o There are 5 types of nail change:
• Pitting of the nail-plate
• Distal separation of the nail-plate (onycholysis)
• Yellow-brown discolouration
• Subungual hyperkeratosis
• Rarely, a damaged nail matrix and lost nail-plate
o Treatment of nail dystrophy is very difficult
• Arthritis:
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o Up to 5% of patients develop psoriatic arthritis and most of

these will have nail changes
o There are 5 patterns of psoriatic arthritis:
• Distal interphalangeal arthritis
• Peripheral mono- or oligoarthritis
• Symmetrical ‘rheumatoid arthritis pattern’ but
seronegative
• Spondylitis or sacro-iliitis (especially HLA-B27 +ve)
• (Rarely) arthritis mutilans – causing destruction and
resorption of bone leading to telescoping of affected
digits
Prognosis:
• Most individuals who develop chronic plaque psoriasis will have
the condition for life
• It fluctuates in severity and there are no available tests to
predict outcome
• Guttate psoriasis resolves spontaneously and in up to 30% of
individuals does not recur
• However, 70% will go on to get recurrent guttate attacks or will
progress to chronic plaque psoriasis
Treatment:
• This is concerned with control rather than cure
• Most patients can be improved with topical therapies:
o Mild-to-moderate topical steroids
o Calcipotriol (a synthetic vitamin D3 analogue)
o Purified coal tar
• Salicylic acid can be a useful adjunct
• All should be applied bds to palpable lesions
• Once lesions have flattened, therapy can be discontinued
• UV therapy is also useful
• Use of methotrexate:
o Normally given once weekly
o Some patients experience extreme nausea on the day they
take it
o Regular blood tests need to be done to monitor for bone
marrow suppression and liver damage
o Alcohol must be avoided as this increases the risk of
Hepatotoxicity
o Long-term users will need a liver biopsy every 2-3 years to
accurately monitor for hepatic damage
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When skin structure or function fails
Epidermis
Disorders of keratinisation:
• E.g. icthyoses
• Caused by inherited genetic defects of protein synthesis
• Produce scaly diseases
Blistering (bullous) diseases:

• Characterised by the spontaneous or post-traumatic formation of
blisters
• Caused either by failure of the:
o Desmosome – causing intra-epidermal blisters
o Adhesion complex at the basement membrane zone –
causing sub-epidermal blisters
• May be inherited structural abnormalities (e.g. epidermolysis
bullosa)
• May be caused by the formation of antibodies against these
proteins (e.g. pemphigus bullous pemphigoid)
Abnormalities of pigmentation:
• Loss of melanocytes leads to depigmentation of the skin
• E.g. vitiligo:
o Common
o Sometimes disfiguring
o Can begin at any age
Abnormalities of DNA repair:

• UV light causes damage to DNA after the first few months of life
• Normally, DNA repair enzymes excise and repair the damaged
strands
• Xeroderma pigmentosa:
o Is a rare inherited disorder which leads to a failure of this
process
o The result is accumulated damage to DNA and inevitable
skin malignancies that are fatal before the age of 20 in
75% of patients
Loss of the whole epidermis:

• This is seen in burns patients and after severe drug reactions
(known as toxic epidermal necrolysis)
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• Leads to fluid and protein loss, failure of temperature regulation

and susceptibility to infection
Adnexal structures (hair shafts, sweat glands, etc)
Absence of sweat glands:

• Seen in a rare X-linked recessive condition called hypohidrotic
ectodermal dysplasia
• Characterised by:
o Absent or reduced sweating
o Hypotrichosis (absence of hair)
o Partial anodontia (absence of teeth)
• It causes heat intolerance and unexplained fevers in infancy or
childhood
Abnormalities of hair:
• Monilethrix – autosomal dominant and causes ‘beading’ of the
hair
• Alopecia areata – very common condition causing patchy hair
loss. It is probably an autoimmune-mediated attack in which the
hair follicle is surrounded by lymphocytes
• Androgenetic alopecia – is age-related baldness which affects
54% of males and 24% of females over the age of 30. It is
caused by a genetically-programmed alteration in metabolism of
androgens by hair follicles
Dermis
Connective tissue disorders:

• E.g. Ehlers-Danlos syndrome
• Is caused by inherited abnormalities of collagen
• Causes:
o Fragility of the skin and blood vessels
o Hyper-extensible skin
o Joint hypermobilty
• Patients develop:
o ‘Cigarette paper’ skin
o Easy bruising
o Recurrent joint dislocations
o Spontaneous rupture of arteries
o Spontaneous pneumothoracies
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Endocrinology
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Acromegaly
This is due to a pituitary tumour in almost all cases. Hyperplasia due

to GHRH is rare.
Clinical features:
• Increased size of hands/feet
• Headaches
• Visual deterioration (especially loss of peripheral vision)
• Weight gain
• Amenorrhoea/oligomenorrhoea
• Galactorrhoea
• Impotence/poor libido
• Deep voice
• Excessive sweating
• Polyuria/polydipsia
• Prognathism
• HT
Investigations:
• GH levels:
o Raised
o In normal adults, GH is usually <1mU/L
• Glucose tolerance test:
o Is diagnostic
o Acromegalics fail to suppress GH below 1mU/L
o Some show a paradoxical rise in GH
o About 25% of acromegalics have a diabetic glucose
tolerance test
• IGF-1 level:
o Is almost always raided in acromegaly
o A single plasma level of IGF-1 reflects mean 24-hour GH
levels and is useful in diagnosis
• Visual field defects are common
• MRI scans of the pituitary:
o Will almost always reveal the pituitary adenoma
• Prolactin levels:
o Mild to moderate hyperprolactinaemia occurs in 30% of
patients
Treatment:
• Untreated, acromegaly results in markedly reduced survival with
deaths from:
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o Heart failure
o Coronary artery disease
o Hypertension-related causes
• Surgery:
o Trans-sphenoidal surgery is generally agreed as the
appropriate first-line therapy
o Results in clinical remission in a majority of cases (about
60%) with pituitary micro-adenoma, but only in a minority
of those with macro-adenoma
• External radiotherapy:
o Normally used after pituitary surgery fails to normalise GH
levels rather than as a primary therapy
• It is combined with medium-term treatment with octreotide (a
somatostatin analogue) or a dopamine agonist because of the
slow biochemical response to radiotherapy, which may take 10
years or more
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Addison’s disease
(primary hypoadrenalism)
Pathophysiology:
• In this uncommon condition
• Destruction of the entire adrenal cortex
• Glucocorticoid, mineralocorticoid and sex steroid synthesis are,
therefore, all reduced
• This differs from hypothalamic-pituitary disease, in which
mineralocorticoid secretion remains largely intact (being
predominantly stimulated by angiotensin II)
• In Addison’s disease, reduced cortisol levels lead (through a
feedback loop) to increased CRF (corticotrophin releasing factor)
and ACTH (adrenocorticotrophic hormone) production
• The increased ACTH production leads, directly, to
hyperpigmentation
• Women > men
Causes of primary hypoadrenalism:

• Autoimmune disease (>90% in UK)
• TB (<10% in UK)
• Infiltration (rare)
Symptoms of Addison’s disease:

• Weight loss
• Syncope (from postural hypotension)
• Anorexia
• Malaise
• Weakness
• Fever
• Depression
• Impotence
• Diarrhoea
• Nausea/vomiting
• Confusion
Signs of Addison’s disease:

• Postural hypotension
• Pigmentation (especially of new scars)
• Loss of weight
• Dehydration
• Loss of body hair
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Investigations:
• Once Addison’s is suspected, investigation is urgent
• If the patient is severely ill or very hypotensive, hydrocortisone
100mg should be given IM together with IV saline
• Single cortisol measurements:
o Are of little value
o A random cortisol of <100nmol/L during the day is highly
suggestive
o A random cortisol of >550nmol/L makes the diagnosis
unlikely (but not impossible)
• The short ACTH stimulation test:
• An absent or impaired cortical response is seen, confirmed
if necessary by a long ACTH stimulation test to exclude
adrenal suppression by steroids
• A 0900hr plasma ACTH level:
o A high level (>80ng/L) with a low to normal cortisol
confirms primary hypoadrenalism
• Electrolytes and urea:
o Hyponatraemia
o Hyperkalaemia
• Blood glucose:
o May be low (with symptomatic hypoglycaemia)
• Adrenal antibodies:
o Present in many cases of autoimmune adrenalitis
• CXR/AXR:
o May show evidence of TB and/or calcified adrenals
• Serum aldosterone:
o Is reduced with high plasma renin activity
ACTH (Synacthen) tests:

• Short (to exclude primary adrenal failure):
1. Tetracosatrin 250µg IV/IM at time 0
2. Measure plasma cortisol at times 0, +30mins
3. Normal test result will show cortisol at time +30mins
>600nmol/L
• Long (to demonstrate or exclude adrenal suppression):
1. Depot tetracosatrin 1mg IM at time 0
2. Measure plasma cortisol at times 0, +1, +2, +3, +4, +5, +8
and +24hrs
3. Normal test result will show a maximum of >1000nmol/L
Treatment:
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• Long-term treatment is with replacement glucocorticoids and

mineralocorticoids.
• TB must be treated if present or suspected
• Adequacy of glucocorticoid dose is judged by:
o Clinical well-being
o Normal cortisol levels during the day whilst on replacement
hydrocortisone
• Fludrocortisone replacement is assessed by:
o Restoration of serum electrolytes to normal
o BP response to posture (it should not fall >10mmHg
systolic after 2 minutes standing)
o Suppression of plasma renin activity to normal
Patient advice:
• All patients requiring replacement steroids should:
o Carry a steroid card
o Wear a medic-alert bracelet (which gives details of their
condition)
o Keep an up-to-date ampoule of hydrocortisone at home in
case oral therapy is impossible
Acute hypoadrenalism:
• The major deficiencies are of salt, steroid and glucose
• Assuming normal CVS function, the following procedures are
required:
o 100mg of IV hydrocortisone
o 1L normal saline given over 30-60mins
o Subsequent saline requirements may be for several litres
within 24 hours (assess with CVP line if necessary)
o Hydrocortisone 100mg IM 6-hourly, until the patient is
clinically stable
o Dextrose should be infused if there is hypoglycaemia
o Oral replacement medication is then started, initially
hydrocortisone 20,g 8-hourly, reducing to 20-30mg in
divided doses over a few days
o Fludrocortisone is unnecessary acutely as the high cortisol
doses provide sufficient mineralocorticoid activity – it
should be introduced later
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Cushing’s syndrome
Cushing’s syndrome is the term used to describe the clinical state of

increased free circulating glucocorticoid. It occurs most often following
the therapeutic administration of synthetic steroids. All the
spontaneous forms of the disease are rare.
Causes of Cushing’s syndrome:

• ACTH-dependent disease:
o Pituitary-dependent (Cushing’s disease)
o Ectopic ACTH-producing tumours
o ACTH administration
• Non-ACTH-dependent causes:
o Adrenal adenomas
o Adrenal carcinomas
o Glucocorticoid administration
• Others:
o Alcohol-induced pseudo-Cushing’s syndrome
Clinical features:
• Centripetal obesity
• Amenorrhoea/oligomenorrhoea
• Thin skin/easy bruising
• Hair growth/acne
• Growth arrest in children
• Polyuria/polydipsia
• Moon face
• Buffalo hump (interscapular fat pad)
• HT
• Poor wound healing
• Osteoporosis
• Oedema poor libido
Diagnosis:
• There are 2 phases to the investigation:
1. Confirmation of the presence or absence of Cushing’s
syndrome
2. Differential diagnosis of its cause (e.g. pituitary, adrenal or
ectopic)
Confirmation of Cushing’s syndrome:

Confirmation rests on demonstrating inappropriate cortisol secretion,
NOT suppressed by exogenous glucocorticoids.
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• 24-hour urinary free cortisol measurements:

o Repeatedly normal values (corrected for body mass) render
the diagnosis most unlikely
• 48-hour low-dose dexamethasone test:
oNormal individuals suppress plasma cortisol to <50nmol/L
oPatients with Cushing’s syndrome fail to show complete
suppression of plasma or urinary cortisol levels
• Circadian rhythm:
o After 48 hours in hospital, cortisol samples are taken at
0900h and 2400h (without warning the patient).
o Normal subjects show a pronounced circadian variation
o Those with Cushing’s syndrome have high midnight cortisol
levels (>100nmol/L), though the 0900h value may be
normal
Differential diagnosis of the cause:

This can be very difficult. Biochemical and radiological procedures for
diagnosis include:
• Adrenal CT or MRI scans:
o Adrenal adenomas and carcinomas are relatively large and
always detectable by CT scan
o Carcinomas are distinguished by:
• Irregular outline
• Large size
• Signs of infiltration/metastases
• Pituitary MRI:
o Of less value than the adrenal scans
o Many adenomas are not seen (as they are so small)
• Plasma potassium levels:
o All diuretics must be stopped
o Hypokalaemia is common with ectopic ACTH secretion
• High-dose dexamethasone test:
o Failure of significant plasma cortisol suppression suggests
an ectopic source of ACTH or an adrenal tumour
• Plasma ACTH levels:
o Low or undetectable ACTH levels (<10ng/L) on 2 or more
occasions are a reliable indicator of non-ACTH-dependent
disease
• CRF test:
o An exaggerated ACTH and cortisol response to exogenous
CRF (with or without vasopressin) suggests pituitary-
dependent Cushing’s disease, as ectopic sources rarely
respond
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• CXR:
o This is mandatory to demonstrate a carcinoma of the
bronchus or a bronchial carcinoid
o Lesions may be very small – whole lung and mediastinal
CT scanning should be performed
Drugtreatment of Cushing’s syndrome:

• The usual drug is metyrapone (an 11!-hydroxylase inhibitor)
• Given in doses of 750mg-4g daily TID or QID
• Plasma cortisol should be monitored, aiming to reduce the mean
level during the day to 150-300nmol/L (equivalent to normal
production rates)
• Ketoconazole and aminoglutethamide are sometimes used.
Treatment of Cushing’s disease:

• Trans-sphenoidal removal of the tumour:
o Treatment of choice
o Selective adenomectomy nearly always leaves the patient
ACTH-deficient postoperatively (this is considered a good
prognostic sign)
• External pituitary irradiation:
o Very slow
o Only effective in 50-60% of patients
o Children respond better (80% being cured)
• Medical therapy to reduce ACTH:
o E.g. Bromocriptine
o Rarely effective
• Bilateral adrenalectomy:
o An option of last resort
o May be performed laparoscopically
Treatment of other causes:

• Adrenal adenomas:
o Should be resected after achievement of clinical remission
with metyrapone or Ketoconazole
o Contralateral adrenal suppression may last for years
• Adrenal carcinomas:
o Highly aggressive with a poor prognosis
o In general, if there are no widespread metastases, tumour
bulk should be reduced surgically
• Ectopic ACTH-secreting tumours:
o Should be removed if possible
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o Otherwise, chemotherapy/radiotherapy should be used,

depending on the tumour
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Diabetes
Comparing T1DM and T2DM
Insulin-dependent DM Non-insulin dependent

(T1DM) DM (T2DM)
Epidemiology Patients are: Patients are:
-Younger -Older
-Usually lean -Often overweight
-European -All racial groups
-Seasonal incidence
(spring /summer)
Heredity -HLA-DR3 or DR4 in -No HLA links
>90% -90% concordance in
-35% concordance in monozygotic twins
monozygotic twins -Glucokinase gene
abnormalities in some
families
Pathogenesis Autoimmunity: -No evidence of
-Islet cell antibody autoimmunity
-Autoantibody to insulin
-Insulinitis
Clinical -Insulin deficiency -Partial insulin

-May develop ketoacidosis deficiency /insulin
-Always need insulin resistance
-May develop non-ketotic
hyperosmolar state
-Sometimes need insulin
Biochemical Eventual disappearance of C-peptide persists

C-peptide
Clinical presentation
Acute and subacute presentations often overlap.
Acute presentation:
• Young people may present with a 2-4 wk history and report the
classic triad of symptoms:
o Polyuria (due to osmotic diuresis)
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o Thirst
o Weight loss (accelerated breakdown of muscle / fat
secondary to insulin deficiency)
• Ketoacidosis may be the presenting feature if these early
symptoms are not recognised and treated.
Subacute presentation:
• Clinical onset may be over several months, particularly in older
patients
• Common features include:
o Polyuria
o Thirst
o Weight loss
• Medical attention is commonly sought for:
o Visual blurring
o Lack of energy
o Pruritis vulvae or balanitis that is due to Candida infection.
Complications as the presenting feature:

• Staphylococcal skin infections
• Retinopathy
• Polyneuropathy causing tingling and numbness in the feet
• Impotence
• Arterial disease (MI or peripheral gangrene)
Investigation of diabetes
Blood glucose levels:

• Blood glucose is so closely controlled by the body that even
small deviations become important
• In symptomatic patients:
o A single elevated blood glucose of > 11.1mmol/L indicates
diabetes
• In asymptomatic patients or mildly symptomatic patients,
diagnosis is made on:
o At least 1 (preferably 2) FBG levels > 6.7mmol/L (the
equivalent FPG is 7.8mmol/L)
OR
o At least 1 (preferably 2) random values > 10mmol/L in
venous whole blood (or > 11.1mmol/L in venous plasma)
Glucose tolerance test:

• This is reserved for true borderline cases
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Urine analysis:
• Glycosuria is measured using sensitive glucose-specific dipstick
methods
• Glycosuria is NOT diagnostic of diabetes but indicates the need
for further investigations
Impaired glucose tolerance (IGT)
Overview:
• If an oral glucose test is administered at random to a large
population, 1-2% will be found to have unsuspected diabetes
• A much larger group (~5%) fall into an intermediate category
referred to as ‘impaired glucose tolerance’ (IGT)
• Follow-up shows that some 2-4% of those with IGT go on to
develop diabetes annually
• Obesity and lack of physical exercise increases risk of
progression to frank diabetes
The oral glucose tolerance test:

1. After an overnight fast, 75g of glucose is taken in 250-350ml
of water
2. Blood samples are taken in the fasting state and 2 hrs after
the glucose has been given
Note: The concentration of glucose measured in plasma is 10%

greater than that of whole blood
Diabetes:
• This is present when the fasting blood glucose (FBG) is >
6.7mmol/L and/or when the 2 hr value is > 10mmol/L
• This corresponds to a fasting plasma glucose (FPG) of >
7.8mmol/L and/or > 11.1mmol/L
IGT:
• Present when the FBG is < 6.7mmol/L and when the 2 hr value
is 6.7 – 10mmol/L
• IGT can only be diagnosed using the oral glucose tolerance test
Principles of insulin treatment
Injections:
Insulin is delivered either via a plastic syringe or a pen-injection device
• Injections are given to a pinch of skin on the:
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o Thighs
o Abdomen
o Upper arm
• The injection site should be changed regularly to prevent areas
of lipohypertrophy
• Rate of insulin absorption depends on local subcutaneous blood
flow and is accelerated by:
o Exercise
o Local massage
o Warm environment
• Rate of absorption (fastest to slowest):
o Abdomen
o Upper arm
o Thigh
Soluble insulin:
• Forms a clear solution which is short-acting when injected.
Prolonged acting insulins:

• Soluble insulin can also be formulated with zinc or protamine to
retard its actions; insulin prepared in this way has a cloudy
appearance
Insulin analogues:
• These are modifications of the human insulin molecule which
allow the hormone a much more rapid effect than the short-
acting preparations
Insulin in clinical use:

• In normal subjects, a sharp increase in insulin occurs after
meals; this is superimposed on a constant background of
secretion
• Insulin therapy attempts to reproduce this pattern, but ideal
control is usually impossible to achieve for 4 reasons:
1. In normal subjects, insulin is secreted directly into the
portal circulation and passes directly to the liver in a high
concentration. In contrast, subcutaneous insulin passes
into the systemic circulation before the portal circulation,
therefore resulting in a higher concentration in the
systemic circulation than the portal circulation
2. Subcutaneous insulin takes 60-90 mins to achieve peak
plasma levels, so the onset and offset of action are too
slow
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3. The absorption of subcutaneous insulin into the circulation

is variable
4. Basal insulin levels in the normal individual are constant,
but injected insulin invariably peaks and declines, with
resulting swings in metabolic control
Treating young patients:

• Can be started on injections of an intermediate-insulin at a dose
of 8-10U BID
• Some recovery of endogenous insulin secretion may occur over
the first few months (the ‘honeymoon’ period) and the insulin
dose may need to be reduced or even stopped for a period
• Requirement s rise thereafter and a multiple injection regimen is
then appropriate for most younger patients
Treating patients with NIDDM:

• There is no consensus for insulin therapy in NIDDM.
• Injections of premixed soluble and isophane insulins (e.g:
Mixtard) BID are widely used and reasonably effective
• Outside the UK, combinations of insulin with sulphonylureas or
Metformin are popular
Multiple injections:
• If glycaemic control is inadequate with the standard approach,
the alternatives are:
o Multiple insulin injections
o Continuous subcutaneous insulin infusion (CSII)
• Multiple injection regimens and infusion devices have the
advantage of flexibility concerning mealtimes, which is of great
value to patients with busy jobs, shift workers and those who
travel regularly
More about infusion devices:

• Continuous subcutaneous insulin infusion (CSII) is delivered by a
small pump strapped around the waist that infuses a constant
trickle of insulin via a needle in the subcutaneous tissues
• Mealtime doses are delivered when the patient touches a button
at the side of the pump
• Disadvantages include:
o Inconvenience of being attached to the pump
o Skin infections
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o Risk of ketoacidosis if the flow of insulin is broken (since

these patients have no protective reservoir of depot
insulin)
Medication for diabetes
Suphonylureas:
• e.g: Tolbutamide, Glibenclamide
• Their principle action is to increase insulin secretion in response
to glucose and other secretagogues
• Mechanism of action:
o Close ATP-sensitive potassium channels on the !-cell
membrane
o The resulting depolarisation promotes calcium influx, which
is a signal for insulin release
• When used?
o Are ineffective in patients without a functional !-cell mass
o Should be avoided in young ketotic patients (who require
early insulin therapy)
o Contraindicated in pregnancy
• Other points:
o Should be used with care in patients with liver disease and
only those primarily excreted by the liver should be used in
those patients with renal impairment.
o All encourage weight gain (therefore, are not the first
choice for obese patients)
• Drug interactions/side-effects:
o Bind to circulating albumin and, therefore, may be
displaced by other drugs
o Interact with warfarin
o Hypoglycaemia is the most common and dangerous side-
effect
Biguanides:
• e.g: Metformin
• Unclear mechanism, but:
o They reduce gluconeogenesis
o This suppresses hepatic glucose output
o Thereby, increasing insulin sensitivity
• Benefits:
o Rarely induces hypoglycaemia
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o Doesn’t induce weight gain

• Side-effects:
o Anorexia
o Epigastric discomfort
o Diarrhoea
o Lactic acidosis in those with liver/renal impairment
!-glucosidase inhibitors:
e.g: Acarbose
• Mechanism of action:
o Inhibits the enzymes which are responsible for the
breakdown of CHOs in the intestine
o This results in poor absorption of dietary CHO and a
reduced postprandial rise in blood glucose
• Side-effects:
o Abdominal discomfort
o Flatulence
o Diarrhoea
Complications of insulin therapy
At the injection site:

• Shallow injections result in:
o Intradermal insulin delivery
o Painful, reddened lesions
o Scarring
o (Rarely) abscesses
• Local allergic responses sometimes occur spontaneously
• There are 2 forms of lipodystrophy that can occur:
o Lipoatrophy (a local allergic response now almost
completely abolished by the use of highly purified insulins)
o Lipohypertrophy (as a result of overuse of a single
injection site)
Insulin resistance:
• The most common cause is obesity
• Are often associated behavioural problems
Weight gain:
• Patients who are non-compliant with their diet and predisposed
to weight gain may show progressive weight gain on treatment
• Insulin makes you feel hungry!
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Hypoglycaemia:
• Most common complication of insulin therapy
• Symptoms develop when blood [glucose] < 3mmol/L
• Symptoms typically develop over a few mins
• Common signs/symptoms:
o Sweating
o Tremor
o Palpitations
o Pallor
• Many patients with long-standing diabetes report
‘hyperglycaemia unawareness’
• These patients are at a greater risk of a more severe
hypoglycaemia, with signs including:
o Drowsiness
o Clumsiness
o Inappropriate behaviour
o Aggression
• Just beyond these symptoms, patients enter a hypoglycaemic
coma, often with convulsions
• 1 in 3 diabetics will enter a hypoglycaemic coma during their
lifetime
• Patients are most at risk of hypoglycaemia just before meals and
at night
• Irregular eating habits, unusual exertion or excessive alcohol
may precipitate episodes
Treatment of hypoglycaemia
Mild hypoglycaemia:
• Administer any form of rapidly absorbed CHO (e.g. glucose
sweets)
• Drowsy individuals should be able to take CHO in liquid form
(e.g. Lucozade)
• Beware of giving too much CHO, since this causes rebound
hyperglycaemia
Severe hypoglycaemia – unconscious patients:

• IV glucose (25-50ml 50% dextrose solution), followed by a flush
of normal saline to preserve the vein
OR
• IM glucagon (1mg)
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• Glucagon acts by mobilizing hepatic glycogen and works

almost as rapidly as glucose
• It is simple to administer and can be given by relatives at
home
• Oral glucose is given to replace glycogen reserves once
the patient revives
Nocturnal hypoglycaemia:
• Basal insulin requirements fall during the night, but increase
from about 4am onwards, at a time when levels of injected
insulin are falling
• As a result, many patients awake with a high glucose level but
find that increasing the dose of insulin at night increases the risk
of hypoglycaemia in the early hours
• Can be minimised in 3 ways:
o Checking that a bedtime snack is taken regularly
o Taking intermediate insulin before bedtime (rather than at
supper)
o Reducing the dose of soluble insulin before supper, since
the effects of this persist well into the night
The diabetic diet
The diet for a diabetic is, in principle, no different from the diet
considered healthy for the population as a whole
Carbohydrate:
• Unrefined rather than simple sugars
• CHO is absorbed slowly from fibre-rich foods, preventing the
rapid swings in circulating glucose seen when refined sugars are
consumed.
Calories:
• Should be tailored to the needs of the diabetic patient
• Composition:
o CHO 50-55%
o Fat 30-35%
o Protein 15%
• An overweight patient is started on a reducing diet of 1000-1600
kcal daily
• A lean patient is put on an isocaloric diet
• Patients who are underweight (because of untreated diabetes)
require energy supplementation
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Macrovascular complications of diabetes
There are 3 main macrovascular complications:

• Ischaemic heart disease (IHD)
• Cerebrovascular disease (CVD)
• Peripheral vascular disease (PVD)
Diabetic risk factors for macrovascular complications:

• Duration
• Increasing age
• Systolic hypertension
• Hyperinsulinaemia due to insulin resistance associated with
obesity and syndrome X
• Hyperlipidaemia (especially hypertriglyceridaemia)
• Proteinuria (including microalbuminaemia)
• Other factors that are the same as for the general population
Cardiovascular disease and DM:

• Overall mortality is:
o 35% of T1DM patients
o 75% of T2DM patients
• Diabetics have:
o 2x risk of an MI
o 5x risk of cardiac failure
o 2-4x risk of CVA
o 2-3x risk of intermittent claudication
Atheroma and DM:

• Compared with non-diabetics, the symptoms are greater, the
lesions are more extensive and severe and hyperlipidaemia is
more common
• Onset:
o T1DM – from 10-15yrs after dx
o T2DM – not related to severity or duration of DM (may be
present at dx)
IHD and DM:

• Angina
• Myocardial infarction:
o More complicated course
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o Increased risk of cardiogenic shock and cardiac failure

o Immediate and long-term mortality is increased
• Heart failure
• Painless MI (probably due to autonomic neuropathy)
• Silent ischaemia
• Non-classical presentation (e.g. may present just with dyspnoea)
MI and DM:
• Mortality during the month following an infarct:
o 42% for diabetics
o 20% for non-diabetics
Syndrome X:
• Hyperinsulinaemia that is due to insulin resistance associated
with obesity is sometimes known as syndrome X
• It is found in patients with NIDDM and comprises:

o Glucose intolerance
o Hypertension
o Central obesity
o Dyslipo-proteinaemia (increased VLDL and reduced HDL)
• Carries a high risk of coronary artery disease
Epidemiology of diabetic foot disease (DFD):

• Prevalence of current or previous foot ulceration in diabetics is
~5-7% (~50,000 in UK)
• 60x risk of amputation in diabetics
• 10% of NHS bed occupancy is due to diabetes-related problems
(of which 50% of these are DFD)
Reasons for foot ulceration:
• Motor neuropathy
• Limited joint mobility
• Autonomic neuropathy
• Trauma
• Sensory neuropathy
• PVD
• Decreased resistance to infection
Types of DFD:
• There are 3 main variations:
o The neuropathic foot
o The ischaemic foot
o The neuroischaemic foot
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The neuropathic foot:

• Numb
• Warm
• Dry
• Palpable foot pulses
• Ulcers at points of high pressure-loading (especially the 1st
metatarsal head)
The ischaemic foot:

• Cold
• Pulseless
• Ulcers at foot margins (e.g. gangrenous toe-ends)
The neuroischaemic foot:

• Numb
• Cold
• Dry
• Pulseless
• Ulcers at both points of high pressure-loading and foot margins
Management of foot ulceration:

• Relief of pressure
• Antibiotics
• Debridement
• Revascularisation (e.g. angioplasty or arterial bypass surgery)
• Amputation (last resort)
Microvascular complications of diabetes
Overview:
• There are 3 main microvascular complications of diabetes:
o Diabetic retinopathy
o Diabetic neuropathy
o Diabetic nephropathy
• The microvascular complications tend to manifest themselves
10-20yrs after diagnosis in young patients
• They present earlier in older patients, probably because these
have had unrecognized diabetes for months or even years prior
to diagnosis
The natural history of retinopathy:
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• Diabetes causes thickening of the basement membrane and

increased permeability of the retinal capillaries.
• Aneurysmal dilatation may occur in some vessels, whilst others
may become obstructed.
• After 20 yrs of IDDM, almost all patients have some retinopathy
and 60% progress to sight-threatening retinopathy
Stages of retinopathy:
• There are 4 types of diabetic retinopathy, each discussed below
• Background retinopathy:
o Most common form
o Hard exudates (caused by cholesterol)
o Microaneurysms (dot haemorrhages)
o Managed by improving blood glucose control
• Pre-proliferative retinopathy:
o Cotton wool spots (‘soft’ exudates). Indicate the 1st stages
of neovascularisation – an indication of retinal ischaemia
o If left alone, the vessels will grow and may bleed.
o We treat with pan-retinal photocoagulation
• Proliferative retinopathy:
o Visible new blood vessels over the surface of the retina
o Treat with pan-retinal photocoagulation
• Maculopathy:
o Hard exudates near the macula
o May threaten direct vision
o Treat with a grid of photocoagulation
The diabetic kidney:

• The kidney may be damaged by diabetes in 3 main ways:
• Glomerular damage
• Ischaemia (resulting from hypertrophy of afferent and
efferent arterioles)
• Ascending infection
Diabetic glomerulosclerosis:
• Manifests itself 15-25 yrs after dx
• Affects 25-35% of patients diagnosed before the age of 30 yrs
• Leading cause of premature death in young diabetics
• Pathophysiology:
o Initial structural lesion in the glomerulus is thickening of
the basement membrane
o We get a progressive leakage of large molecules
(particularly protein) into the urine
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o Earliest evidence of protein in the urine is

‘microalbuminuria’ (amounts of urinary albumin so small
as to be undetectable by dipsticks)
o Microalbuminuria may progress to persistent proteinuria
• At the stage of persistent proteinuria:
o Plasma creatinine may be normal but the patient is 5-10
yrs from ESRF
o A rise in plasma creatinine is a late feature
o Patients typically have a normochromic normocytic
anaemia and hypertension
Ischaemic lesions of the diabetic kidney:

• Arteriolar lesions, with hypertrophy and hyalinization of the
vessels, affect both afferent and efferent arterioles
• The appearances are similar to those of hypertensive disease but
are not necessarily related to the BP in patients with DM
Infective lesions of the diabetic kidney:

• Ascending infection may occur because of bladder stasis
resulting from autonomic neuropathy
• Infections are able to establish themselves more easily in
damaged renal tissue
Diagnosis of diabetic nephropathy:

• The urine of ALL diabetics should be checked regularly for the
presence of protein.
• Many centres also screen for the presence of microalbuminuria,
since there is good evidence that meticulous glycaemic control or
antihypertensive treatment at this stage may delay the onset of
frank proteinuria
Diabetic neuropathy:
• There are two proposed mechanisms for the damage of
peripheral nerve tissue:
1. Vascular hypothesis:
• This postulates occlusion of the vasa nervorum
2. Metabolic hypothesis:
• Hyperglycaemia leads to increased formation of sorbitol
and fructose in Schwann cells, accumulation of these
disrupts function and structure
• There are 6 main types of diabetic neuropathy:
o Symmetrical (mainly sensory) polyneuropathy
o Acute painful neuropathy
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o Mononeuropathy and mononeuritis multiplex:

• Cranial nerve lesions
• Isolated peripheral nerve lesions
o Radiculopathy
o Autonomic neuropathy
o Diabetic amyotrophy
Symmetrical (mainly sensory) polyneuropathy:

• Early clinical signs include loss, from the feet, of:
o Vibration sense
o Pain (deep before superficial
o Temperature
• At later stages patients may complain of:
o A feeling of ‘walking on cotton wool’
o Loss of balance when washing the face or in the dark
(owing to loss of proprioception)
• Involvement of the hands is much less common
• Complications include unrecognised trauma, beginning as
blistering (e.g. due to an ill-fitting shoe) and leading to
ulceration
Acute painful neuropathy:

• The patient describes burning or crawling pains in the feet, shins
and anterior thighs
• The pain is worse at night and pressure from bedclothes may be
intolerable
• It usually remits within 3-12 months if good glycaemic control is
maintained
Mononeuritis and mononeuritis multiplex (multiple Mononeuropathy):

• Any nerve in the body can be involved in diabetic mononeuritis;
the onset is abrupt and sometimes painful
• Radiculopathy (i.e. involvement of a spinal nerve root) may
occur
• Isolated palsies of nerves to the external eye muscles (especially
the 3rd and 6th nerves) are more common in diabetes
• A characteristic feature of diabetic 3rd nerve palsy is that
pupillary reflexes are retained owing to sparing of pupillomotor
fibres
• Full spontaneous recovery is the rule for most episodes of
mononeuritis
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Diabetic amyotrophy:
• Usually seen in older men with diabetes
• Presentation is with painful wasting (usually asymmetrical) of
the quadriceps muscles
• The wasting may be very marked
• Affected area is usually extremely tender
• Diabetic amyotrophy is usually associated with periods of poor
glycaemic control and may be present at dx
• It often resolves with time and careful control of blood glucose
Autonomic neuropathy – cardiovascular system:

• Vagal neuropathy results in tachycardia at rest and loss of sinus
arrhythmia
• At a later stage, the heart may become denervated (resembling
a transplanted heart)
• Postural hypotension occurs owing to loss of sympathetic tone to
peripheral arterioles
• A warm foot with a bounding pulse is sometimes seen in a
polyneuropathy as a result of a peripheral vasodilatation
Autonomic neuropathy – gastrointestinal tract:

• Vagal damage can lead to gastroparesis (often asymptomatic)
but rarely leading to intractable vomiting
• Diarrhoea often occurs at night accompanied by urgency and
incontinence
• Diarrhoea and steatorrhoea may occur owing to bacterial
overgrowth
• Treatment is with antibiotics
Autonomic neuropathy – bladder involvement:

• The following may occur:
o Loss of tone
o Incomplete emptying
o Stasis (predisposing to infection)
• These factors may, ultimately, result in an atonic, painless,
distended bladder
Autonomic neuropathy – impotence:

• Common
• The first manifestation is incomplete erection which may, in
time, progress to impotence
• However, impotence in diabetes is not always due to autonomic
neuropathy
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• Other causes include:

o Depression
o Alcohol excess
o Drugs
o Primary or secondary gonadal failure
o Hypothyroidism
o Inadequate vascular supply owing to atheroma in the
pudendal arteries
Monitoring the control of diabetes
Urine tests:
• Simple to perform using a dipstick and it can usually be assumed
that a patient with consistently negative tests and no symptoms
of hypoglycaemia is fairly well controlled
• It should be noted that the correlation between urine tests and
blood glucose is poor for 3 reasons:
1. Changes in urine glucose lag behind changes in blood glucose
2. The mean renal threshold is ~10mmol/L but the range is wide
(it also increases with age)
3. Urine tests can give no clear guidance concerning blood
glucose levels below the renal threshold
Blood glucose testing:

• Provides the best assessment of day-to-day control
• Patients are taught to record their own blood glucose profiles
using finger-prick blood samples with reagent strips
• Blood should be taken from the side of a fingertip, NOT the tip
(which is densely innervated) using a special lancet
Glycosylated haemoglobin (HbA1 or HbA1c) and fructosamine:

• Glycosylation of Hb occurs as a two-step reaction, resulting in
the formation of a covalent bond between the glucose molecule
and the terminal valine of the "-chain of the Hb molecule
• Glycosylated Hb is expressed as a percentage of the normal Hb
(normal is 4-8%
• Glycosylated plasma proteins (‘fructosamine’) may also be
measured as an index of control
• These measurements provide us with a good impression of long-
term glycaemic control
What should be checked at each visit?
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• Review of self-monitoring results and current treatment

• Talk about targets and change where necessary
• Talk about any general or specific problems
• Continued education
These should be checked at least once a year:

• Biochemical assessment of metabolic control (e.g. glycosylated
Hb test)
• Measure bodyweight
• BP
• Plasma lipids
• Visual acuity
• Examine state of retina
• Renal function tests (e.g. creatinine, proteinuria)
• Check condition of feet, pulses and neurology
• Review CVS risk factors
• Review self-monitoring and injection techniques
• Review eating habits
Diabetic ketoacidosis (DKA)
DKA is the hallmark of IDDM:

• Its main causes can be grouped as follows:
o Previously undiagnosed DM
o Interruption of insulin therapy
o Stress of intercurrent illness
• The most common cause is omission of insulin because the
patient feels unable to eat owing to nausea/vomiting
• Insulin should never be stopped.
Pathogenesis:
• DKA is a state of uncontrolled catabolism associated with insulin
deficiency
• Insulin deficiency is a necessary precondition since only a
modest elevation in insulin levels is sufficient to inhibit hepatic
ketogenesis
• Stable patients do not readily develop DKA when insulin is
withdrawn
• In the absence of insulin:
o Hepatic glucose production accelerates
o Peripheral glucose uptake is reduced
o Rising glucose levels lead to an osmotic diuresis, loss of
fluid and electrolytes and dehydration.
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o Plasma osmolality rises

o Renal perfusion falls
• In parallel, rapid lipolysis occurs, leading to:
o Elevated circulating free-fatty acids (FFAs)
o The FFAs are broken down to fatty acyl-CoA within the
liver cells
o This, in turn, is converted to ketone bodies within the
mitochondria
• Accumulation of ketone bodies:
o Produces a metabolic acidosis
o Typically associated with nausea/vomiting, leading to
further loss of fluid and electrolytes
o The excess ketones are excreted in the urine but also
appear on the breath, producing a distinctive smell similar
to that of acetone
o Respiratory compensation for the metabolic acidosis leads
to hyperventilation (described as ‘air hunger’)
• Untreated, severe DKA is invariably fatal
Clinical features:
• Acidosis
• Hyperventilation (Kussmaul respiration). This becomes less
marked in severe acidosis owing to respiratory depression
• Nausea
• Vomiting
• Abdominal pain (can be so severe as to be confused with an
acute abdomen)
• Severe dehydration
• Most patients are confused and in a stupor
• 5% present in a coma
Management:
• Replace fluid losses with normal saline
• Replace electrolyte losses:
o Potassium levels need to be monitored with great care
o Patients have a total body potassium deficit although initial
plasma levels may not be low
o Insulin therapy leads to uptake of potassium by the cells
with a consequent fall in plasma levels
o Potassium is, therefore, given as soon as insulin therapy is
started
• Restore the acid-base balance:
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o A patient with healthy kidneys will rapidly compensate for

the metabolic acidosis once the circulating volume is
restored
o Only consider bicarbonate if the pH is < 7
• Administer insulin:
o Soluble insulin is given as an IV infusion where facilities for
adequate supervision exist, otherwise as hourly IM
injections
o Do not give subcutaneously as the peripheral blood
flow is reduced in a shocked patient
• Monitor blood glucose closely
• Replace the energy losses
• Seek the underlying cause (especially infection)
Problems of management:
• Hypotension:
o This may lead to renal failure. Give plasma expanders or
whole blood if systolic BP < 80mmHg
• Coma:
o It is essential to pass a NG tube to prevent a drowsy
patient aspirating when vomiting
• Cerebral oedema:
o Rare and believed to be due to excessive rehydration. High
mortality
• Hypothermia:
o Monitor patient’s temperature rectally to avoid this
• Late complications (e.g. stasis pneumonia and DVT)
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Non-ketotic hyperosmolar state
Overview:
• This is where severe hyperglycaemia develops without significant
ketosis. It is the metabolic emergency characteristic of
uncontrolled NIDDM
• Patients present in middle or later life, often with previously
undiagnosed diabetes
Common precipitating factors:

• Consumption of glucose-rich fluids (e.g. Lucozade)
• Concurrent medication (such as thiazide diuretics or steroids)
• Intercurrent illness
Clinical features:
• Dehydration
• Stupor
• Coma
• Impairment of consciousness is directly related to the level of
hyperosmolality
• Evidence of underlying illness may be present (e.g. pneumonia
or pyelonephritis) and the hyperosmolar state may predispose
to:
o CVA
o MI
o Lower limb arterial insufficiency
Treatment:
• Replace fluid with normal saline
• Administer insulin with care (as many patients will be extremely
sensitive to it). Start off infusing at a rate of 3U/hr for the first
2-3 hrs, increasing to 6U/hr if glucose is falling too slowly.
Prognosis:
• Reported mortality is as high as 20-30%, mainly because of the
advanced age of the patients and the frequency of intercurrent
illness
• Unlike DKA, non-ketotic hyperglycaemia is not an absolute
indication for subsequent insulin therapy, and survivors may do
well on diet and oral agents
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Goitre
Causes:
• Physiological:
o Puberty
o Pregnancy
• Autoimmune:
o Grave’s disease
o Hashimoto’s disease
• Thyroiditis:
o Acute (De Quervain’s thyroiditis)
o Chronic fibrotic (Reidel’s thyroiditis)
• Iodine deficiency (endemic goitre)
• Dyshormonogenesis
• Goitrogens (e.g. sulphonylureas)
Types:
• Simple
• Multiple nodular
• Solitary nodular
• Fibrotic
• Malignant:
o Adenoma
o Carcinoma
o Lymphoma
Simple goitre:
• In this instance, no clear cause is found for enlargement of the
thyroid, which is usually smooth and soft
• It may be associated with thyroid growth-stimulating antibodies
Multiple nodular goitre:

• Most common type of goitre (especially in older patients)
• Patient is usually euthyroid, but may be hyperthyroid or
borderline
• Suppressed TSH levels but normal T4 and T3
• Most common cause of tracheal and/or oesophageal compression
and may cause laryngeal nerve palsy
Solitary nodular goitre:

• Presents a difficult diagnostic problem
• A history of:
o Pain
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o Rapid enlargement of the thyroid

o Associated lymph nodes
• These symptoms suggest the possibility of a thyroid carcinoma
• However, the majority of such nodules are cystic or benign and,
indeed, may simply be the largest solitary nodule of a
multinodular goitre
• Risk factors for malignancy include:
o Previous irradiation
o Longstanding iodine deficiency
o Familial history
• Solitary toxic nodules (Plummer’s syndrome) are quite
uncommon and may be associated with T3 production
Fibrotic goitre (Reidel’s thyroiditis):

• Rare
• Usually produces a ‘woody’ gland
• Associated with other midline fibrosis and is often difficult to
distinguish from carcinoma, being irregular and hard
Investigations:
• Thyroid function tests (normal in brackets):
o TSH (0.5-5mU/L)
o T4 (70-140mmol/L)
o T3 (1.2-3nmol/L)
• Chest and thoracic inlet X-rays
• Fine needle aspiration (FNA):
o In patients with a solitary nodule or a dominant nodule in a
multinodular goitre, there is a 5% chance of malignancy
o In view of this, a FNA is performed
• Ultrasound:
o Good for delineating nodules
o Can demonstrate whether the nodules are cystic or solid
• Thyroid scan:
o Uses either 125I or 131I
o Useful in distinguishing between functioning (hot) or non-
functioning (cold) nodules
o A hot nodule is rarely malignant
o A cold nodule is malignant in 10% of cases
Treatment:
• During puberty or pregnancy, a goitre associated with
euthyroidism rarely requires intervention
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• If euthyroid, the patient should be reassured that spontaneous

resolution is likely
• In other situations, the patient should be rendered euthyroid
• Indications for surgical intervention are:
o The possibility of malignancy
o Pressure symptoms on the trachea (or, more rarely, the
oesophagus)
o Cosmetic reasons
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Gout and hyperuricaemia
Causes of hyperuricaemia:
• Impaired excretion of uric acid:
o Chronic renal disease
o Drug therapy:
• Thiazide diuretics
• Low-dose aspirin
o Lead toxicity
• 1˚ hyperparathyroidism
• Hypothyroidism
• Increased production of uric acid:
o Myeloproliferative disorders (e.g. polycythaemia vera)
o Lymphoproliferative disorders (e.g. leukaemia)
o Carcinoma
o Severe psoriasis
Uric acid synthesis:

• Uric acid is the last step in the breakdown pathway of purines
• The last 2 steps are catalysed by xanthine oxidase and are:
1. Conversion of hypoxanthine to xanthine
2. Conversion of xanthine to uric acid
Clinical features:
• Hyperuricaemia causes 4 clinical syndromes:
o Acute urate synovitis – gout
o Chronic polyarticular gout
o Chronic tophaceous gout
o Urate renal stone formation
Acute gout:
• Typically middle-aged men
• Sudden onset of agonising pain, swelling and redness of the first
MTP joint
• The attack occurs at any time but may be precipitated by:
o Too much food or alcohol
o Dehydration
o Commencement of a diuretic
• Untreated attacks last ~7 days
• In 25% of attacks, a joint other than the great toe is affected
Chronic polyarticular gout:

• Is unusual, except for elderly people:
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o On longstanding diuretic treatment

o In renal failure
Chronic tophaceous gout:

• Sodium urate forms smooth white deposits (tophi) in skin and
around joints
• They may occur on the:
o Ear lobe
o Fingers
o Achilles tendon
• Large deposits are unsightly and ulcerate
• There is chronic joint pain and sometimes superimposed acute
gouty attacks
Investigations:
• Joint fluid microscopy
• Serum urate:
o Is usually raised (>600µmol/L)
o If normal, re-check it several weeks after the attack as the
level falls immediately after an acute attack
• Serum urea and creatinine:
o For signs of renal impairment
Treatment:
• The use of NSAIDs in high doses rapidly reduces the pain and
swelling
• Initial doses (taken with food) are:
o Naproxen 750mg immediately, then 500mg 8-12 hourly
o Diclofenac 75-100mg immediately, then 50mg 6-8 hourly
o Indomethacin 75mg immediately, then 50mg 6-8 hourly
• After 24-48 hours, reduced doses are given for a further week
• In individuals with a history of peptic ulceration, alternative
treatments include:
o Colchicine 1mg immediately, then 0.5mg 6-12 hourly (but
this causes diarrhoea)
o Methylprednisolone IM or intra-articular depot
Treatment with agents which reduce serum urate levels:

• Only when the attacks are frequent, severe or associated with
renal impairment or when the patient finds NSAIDs or colchicine
difficult to tolerate should allopurinol or a uricosuric agent be
used
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• They should never be started within a month of an acute attack

and always be under cover of a course of NSAID or colchicine for
the first 4-6 weeks
• Allopurinol (300-600mg):
o Blocks xanthine oxidase, which converts xanthine into
urate
o Reduces serum urate levels rapidly and is relatively non-
toxic (but should be used in low doses (50-100mg) in renal
impairment
o Skin rashes are the most common side-effect
• Uricosuric agents:
o E.g. probenecid
o Increase urate excretion
o Used in individuals who are allergic to allopurinol
o Should NOT be used in renal failure or in patients with
urate stones
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Hypercalcaemia
There are 3 subtypes of hypercalcaemia:

• Primary
• Secondary
• Tertiary
Primary hyperparathyroidism:
• Caused by single (>80%) parathyroid adenomas or by diffuse
hyperplasia of all the glands (15-20%)
• Multiple parathyroid adenomas are rare and parathyroid
carcinoma is even less common (<1%), although it usually
causes severe hypercalcaemia
Secondary hyperparathyroidism:
• Is physiological compensatory hypertrophy of all parathyroids
due to hypocalcaemia (such as occurs in vitamin D deficiency or
renal failure)
• PTH levels are raised but Ca2+ levels are low or normal
• PTH falls to normal after correction of the cause of
hypocalcaemia (if possible)
Tertiary hyperparathyroidism:
• Is the development of apparently autonomous parathyroid
hyperplasia after longstanding secondary hyperparathyroidism
(most often in renal failure)
• Plasma Ca2+ and PO43- are both raised, the latter often grossly so
• Parathyroidectomy is necessary at this stage
Causes of hypercalcaemia:
• Excessive PTH secretion:
o Primary hyperparathyroidism (commonest by far)
o Tertiary hyperparathyroidism
o Ectopic PTH secretion (very rare)
• Excess action of vitamin D:
o Iatrogenic or self-administered excess
o Granulomatous diseases (e.g. sarcoidosis, TB)
o Lymphoma
• Excessive calcium intake:
o ‘Milk-alkali’ syndrome
• Malignant disease (second most common cause):
o Secondary deposits in bone
o Production of osteoclastic factors by tumours
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o Myeloma
• Other endocrine disease (mild hypercalcaemia only):

o Thyrotoxicosis
o Addison’s disease
• Drugs:
o Thiazide diuretics
o Vitamin D analogues
o Lithium administration (chronic)
o Vitamin A
• Miscellaneous:
o Long-term immobility
o Familial hypocalciuric hypercalcaemia
Symptoms and signs:

• General features:
o Malaise
o Tiredness
o Depression
• Renal features (20-40% of patients):
o Renal colic (caused by calculi)
o Polyuria
o Nocturia
o Haematuria
o HT
• Bone pain
• Abdominal pain (sometimes due to PUD)
• Chondrocalcinosis (a form of pseudogout)
• Ectopic calcification
• Corneal calcification (a marker of longstanding hypercalcaemia,
but causes no symptoms)
Investigations:
• Biochemistry:
o Several fasting serum calcium/phosphate should be taken.
The hallmark of primary hyperparathyroidism is
hypercalcaemia and hypophosphataemia, with detectable
intact PTH levels during hypercalcaemia
o A mild hyperchloraemic acidosis
o Renal function is usually normal, but should be measured
as a baseline
o Protein electrophoresis (to exclude myeloma)
o Serum TSH and T3 (to exclude thyrotoxicosis)
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• Imaging:
o Abdominal X-rays may show renal calculi or
nephrocalcinosis
Medical management of primary hyperparathyroidism:

• No effective medical interventions at present
• Should maintain a high fluid intake
• Avoid a high intake of calcium or vitamin D
• Encourage exercise
Surgical management of primary hyperparathyroidism:

• Surgery is indicated for:
o Patients with renal calculi or impaired renal function
o Bone involvement or marked reduction in cortical bone
density
o Unequivocal marked hypercalcaemia (>2.9mmol/L)
o The uncommon younger patient, under 50 yrs
o A previous episode of severe acute hypercalcaemia
Complications of surgery:
• Postoperative hypocalcaemia:
o Most common in patients with significant bone disease (the
‘hungry bone’ syndrome)
o A mild, transient hypoparathyroidism often continues for
1-2 weeks
• Other (rarer) complications – as for thyroid surgery:
o Laryngeal nerve palsy
o Haemorrhage
Acute hypercalcaemia and its treatment:

• Often presents with:
o Dehydration
o Nausea
o Vomiting
o Nocturia
o Polyuria
o Drowsiness/altered consciousness
• The serum Ca2+ is over 3mmol/L and sometimes as high as
5mmol/L
• Whilst investigation of the cause is under way, immediate
treatment is mandatory:
o Adequate rehydration is essential (usually 4-6L of saline on
day 1 and 3-4L for several days thereafter)
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o Intravenous bisphosphonates are now the treatment of

choice. Give pamidronate 15-60mg IV in 0.9% saline/
dextrose over 2-8 hours
o Calcitonin (200U IV 6-hourly)
o Prednisolone (30-60mg daily) is effective in some
instances (e.g. sarcoidosis, myeloma and vitamin D
excess) but in most cases is ineffective
o Oral phosphate (sodium cellulose phosphate 5g TID). Side-
effects include diarrhoea
Familial hypocalciuric hypercalcaemia:

• Uncommon, autosomal dominant
• Usually asymptomatic
• D e m o n s t r a t e s i n c r e a s e d C a2+ r e a b s o r p t i o n , d e s p i t e
hypercalcaemia
• PTH levels are normal or slightly raised
• Urinary Ca2+ is low
• Surgery is NOT indicated as the course appears benign
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Hyperprolactinaemia
Causes of hyperprolactinaemia:
• Physiological:
o Sleep (REM phase)
o Pregnancy
o Suckling
o Stress
o Coitus
• Pathological:
o Neoplasm
o PCOS
o Primary hypothyroidism
o Renal failure
o Liver failure
o Idiopathic
• Pathological:
o Dopamine antagonists (e.g. metoclopramide and
phenothiazines)
o Oestrogens
o Opiates
o Cimetidine (H2-receptor antagonist)
o Methyldopa ("2-adrenoceptor agonist)
Clinical features:
• Galactorrhoea
• Oligomenorrhoea/amenorrhoea
• Decreased libido in both sexes
• Decreased potency in men
• Subfertility
• Symptoms and signs of oestrogen or androgen deficiency (in the
long-term, osteoporosis may result, especially in women)
Investigations:
• At least 3 prolactin levels should be measured
• The following tests are appropriate after physiological and drug
causes have been excluded:
o Visual fields should be checked
o Anterior pituitary function should be assessed
o MRI of the pituitary
Treatment:
• Drugs:
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o Hyperprolactinaemia should be reduced with a dopamine

agonist
o Bromocriptine is the best established therapy
o Initial doses should be small (e.g. 1mg) and taken with
food, or at bedtime
o The dose should be gradually increased, usually to 2.5mg
BID or TID, judged on clinical response and prolactin levels
• Trans-sphenoidal surgery:
o Only really successful in patients with a microadenoma
(not macroadenoma)
• Radiotherapy:
o Slowly effective
o Can sometimes cause eventual hypopituitarism
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Hyperthyroidism
(Thyrotoxicosis)
Epidemiology:
• Common. Affects ~2-5% of all females at some time
• Women 5x more than men
• Nearly all cases (>90%) are caused by intrinsic thyroid disease;
a pituitary cause is extremely rare
Common causes of hyperthyroidism:

• Grave’s disease
• Solitary toxic nodule/adenoma
• Toxic multinodular goitre
• Thyrotoxicosis factitia (secret T4 consumption)
• Exogenous iodine
• Drugs (e.g. amiodarone)
• Metastatic differentiated thyroid carcinoma
• TSH-secreting tumours (e.g. pituitary)
• HCG-producing tumours
• Hyperfunctioning ovarian teratoma (struma ovarii)
Uncommon causes of hyperthyroidism:

• Acute thyroiditis:
o Viral (De Quervain’s thyroiditis)
o Autoimmune
o Post-irradiation
Symptoms of hyperthyroidism:
• Weight loss (despite increased appetite)
• Restlessness
• Tremor
• Palpitations
• Heat intolerance
• Diarrhoea
• Muscle weakness
• Oligomenorrhoea
• Loss of libido
Signs of hyperthyroidism:
• Tachycardia
• AF
• Warm, vasodilated peripheries
• Pretibial myxoedema
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• Exophthalmus
• Lid lag
• Goitre
• Proximal myopathy
Grave’s disease:
• Most common cause of thyrotoxicosis and is due to an
autoimmune process
• Serum IgG antibodies bind to the thyroid TSH receptor and
stimulate thyroid hormone production (i.e. behaving like TSH)
• Yersinia enterocolitco and Escherichia coli contain TSH-binding
sites. It is believed that infection by these organisms may invoke
some form of ‘molecular mimicry’ in a genetically susceptible
individual and lead to the formation of autoantibodies
• Is also associated with other autoimmune diseases, such as:
o Pernicious anaemia
o Myasthenia gravis
• Natural history is one of fluctuation with many patients showing
a pattern of alternating relapse and remission.
• ~40% of patients have a single episode
• Many patients eventually become hypothyroid
Toxic solitary nodule/adenoma (Plummer’s disease):

• Responsible for ~5% of cases of hyperthyroidism
• Does NOT usually remit after a course of antithyroid drugs
Toxic multinodular goitre:

• Commonly occurs in older women
• Again, usually does not respond to antithyroid drugs
De Quervain’s thyroiditis:
• This is transient hyperthyroidism from an acute inflammatory
process (presumed to be viral in origin)
• Clinical features:
o Fever
o Malaise
o Pain in the neck
o Tachycardia
o Local thyroid tenderness
• On investigation:
o Initial hyperthyroidism
o Raised ESR
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o Thyroid uptake scans show suppression of uptake in the

acute phase, although hypothyroidism (usually transient)
may then follow after a few weeks)
• Treatment of the acute phase is:
o Aspirin
o Short-term prednisolone (in severely symptomatic cases)
Investigating hyperthyroidism:
• Serum TSH:
o Is suppressed in thyrotoxicosis (< 0.1mU/L)
o There are, however, rare instances of TSH hypersecretion
leading to thyrotoxicosis
• Most physicians also like to measure serum T3 and T4 levels.
They will be elevated
• TSH receptor antibodies:
o Not measured routinely but are commonly present
o TSI 80% positive
o TBII 60-90% in Grave’s disease
Treatment:
• There are 3 main options:
o Antithyroid drugs
o Surgery
o Radioiodine
• Most patients (90%) with thyrotoxicosis have a diffuse goitre
• Those with large single or multinodular goitres are unlikely to
remit after a course of antithyroid drugs
• Severe biochemical hyperthyroidism is, also, less likely to
respond
Antithyroid drugs:
• Most commonly used antithyroid drug in the UK is carbimazole.
• Occasionally, propylthiouracil is also used
• The main action of these drugs is to inhibit the formation of
thyroid hormones
• They are also, to a lesser extent, immunosuppressants
• Although thyroid hormone synthesis is reduced very quickly, the
long half-life of T4 (~7 days) means that clinical benefit is not
apparent for 10-20 days
• As many of the manifestations of hyperthyroidism are mediated
via the SymNS, "-blockers may be used to provide rapid, partial
symptomatic control
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• "-blockers should not be used on their own to treat

hyperthyroidism, except when the condition is self-limiting, as in
subacute thyroiditis
• Approximately 50% of patients will relapse after withdrawal of
the antithyroid medication
Drug U s u a l Side-effects Remarks

starting
dose
Carbimazole 10-20mg 8- Rash Active metabolite is
hourly Nausea methimazole
Vomiting M i l d
Arthralgia immunosuppressive
Agranulocytosis activity
(0.1%)
Jaundice
Propylthiouracil 100-200mg A s a b o v e ( b u t As above but also
8-hourly with no jaundice) blocks conversion of
T3 to T4
Propranolol 4 0 - 8 0 m g Avoid in asthma
6-8 hourly Use with care in
HF
Antithyroid drugs – toxicity:

• The major side-effect is agranulocytosis:
o Occurs in 1 in 1000 patients
o Usually within 3 months of treatment
o Patients should be warned to seek medical attention if they
develop an unexplained fever or sore throat
• If toxicity occurs with carbimazole, propylthiouracil may be used
and vice-versa
• Side-effects are only very rarely repeated with the other drug
Surgery – subtotal thyroidectomy:

• Should only be performed in patients who have already be
rendered euthyroid
• Conventional practice is to stop the antithyroid drug 10-14 days
before the operation and give potassium iodide (60mg TID),
which reduces the vascularity of the gland
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• Particular indications for surgery include:

o Patient choice
o A large goitre, which is unlikely to respond to antithyroid
medication
• Indications for either surgery OR radioiodine include:
o Persistent drug side-effects
o Poor compliance with drug therapy
o Recurrent hyperthyroidism after drugs
Possible complications of the operation:

• Early postoperative bleeding causing tracheal compression and
asphyxia:
o Is a rare emergency
o Requires immediate removal of all clips/sutures to allow
escape of the blood/haematoma
• Laryngeal nerve palsy:
o Occurs in 1% of cases
o Vocal chord movement should be checked preoperatively
o Mild hoarseness is more common and thyroidectomy is
best avoided in professional singers!
• Transient hypocalcaemia:
o Occurs in up to 10% of cases
o Fewer than 1% of cases have permanent
hypoparathyroidism
• Recurrent hyperthyroidism:
o Occurs in 1-3% within one year, then 1% per year
• Hypothyroidism:
o Occurs in ~10% of patients within one year, and the
percentage increase over time
o It is likeliest if microsomal antibodies are positive
Radioactive iodine:
• 131I in an empirical dose (usually 200-500MBq) accumulates in
the thyroid and destroys the gland by local radiation
• Takes several months to be fully effective
• Patients must be rendered euthyroid before treatment, although
they must stop treatment at least 4 days before radioiodine, and
not recommence until 3 days after radioiodine
Contraindicated in:
• Children
• Pregnancy
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• Whilst breast-feeding
• Early discomfort in the neck and immediate worsening of
hyperthyroidism are sometimes seen:
o If this occurs, the patient should NOT receive carbimazole
for 2-3 days after radioiodine, as it will prevent radioiodine
uptake by the gland
o They should receive propranolol until carbimazole can be
restarted as necessary
o Euthyroidism usually returns in 2-3 months
o Apart from the immediate problems, as outlined above, a
major complication is the progressive incidence of
subsequent hypothyroidism affecting the majority of
subjects over the following 20 years
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Hypocalcaemia
Pathophysiology:
Hypocalcaemia may be due to:
• Deficiencies of calcium homeostatic mechanisms
• Secondary to high phosphate levels
Causes of hypocalcaemia:
• Increased phosphate levels:
o Chronic renal failure (common)
o Phosphate therapy
• Hypoparathyroidism:
o Post-surgical
o DiGeorge syndrome (congenital condition where the
hypoparathyroidism is associated with intellectual
impairment, cataracts and calcified basal ganglia)
o Idiopathic hypoparathyroidism (rare)
o Severe hypomagnesaemia
• Vitamin D deficiency:
o Osteomalacia
o Vitamin D resistance
• Resistance to PTH:
o Pseudohypoparathyroidism
• Drugs:
o Calcitonin
o Bisphosphonates
• Miscellaneous:
o Acute pancreatitis (quite common)
o Citrated blood in massive transfusion
Symptoms of hypocalcaemia:
• At first there is:
o Paraesthesiae
o Circumoral numbness
o Cramps
o Anxiety
o Tetany
• Followed by:
o Convulsions
o Laryngeal stridor
o Dystonia
o Psychosis
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Signs of hypocalcaemia:
• Chvostek’s sign:
o Gentle tapping over the facial nerves causes twitching of
the facial muscles
• Trousseau’s sign:
o Inflation of the sphygmomanometer cuff above systolic
pressure for 3 minutes induces titanic spasm of the fingers
and wrist
Investigations:
• Serum calcium
• Serum and urine creatinine (for renal disease)
• PTH levels (absent or inappropriately low)
• Parathyroid antibodies (present in idiopathic
hypoparathyroidism)
• Serum 25-hydroxy vitamin D level (low in vitamin D deficiency)
• X-rays of the metacarpals:
o Showing short fourth metacarpals in
pseudohypoparathyroidism
Treatment:
• Urgency of treatment depends on the severity of the symptoms
and the degree of hypocalcaemia
• If severe with Tetany:
o IV calcium is given (10mL initially, then 10-40mL of 10%
calcium gluconate in 1L of 0.9% saline over 4-8 hours
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Hypopituitarism
Anterior pituitary gland (adenohypophysis):

• Responsible for the synthesis and secretion of the following
hormones:
o Growth hormone (GH, somatotrophin)
o Prolactin
o TSH (thyroid stimulating hormone, thyrotrophin)
o ACTH (adrenocorticotrophic hormone, corticotrophin)
o LH (luteinizing hormone)
• FSH (follicle stimulating hormone)
Posterior pituitary gland (neurohypophysis):

• Responsible for the secretion of the following hormones:
o VP (vasopressin, ADH, antidiuretic hormone)
o Oxytocin
Pathophysiology:
• Deficiency of hypothalamic releasing hormones or of pituitary
trophic hormones are either selective or multiple
• Multiple deficiencies usually result from tumour growth or other
destructive lesions
• With the latter, there is generally a progressive loss of anterior
pituitary function (GH and gonadotrophins, LH before FSH, are
usually first affected
• Rather than prolactin deficiency, hyperprolactinaemia occurs
relatively early because of tonic inhibitory control by dopamine
• TSH and ACTH are usually last to be affected
• Panhypopituitarism refers to a deficiency of all anterior pituitary
hormones. It is most commonly caused by:
o Pituitary tumours
o Surgery
o Radiotherapy
Causes:
• Congenital:
o Isolated deficiency of pituitary hormones (Kallmann’s
syndrome)
• Infective:
o Basal meningitis
o Encephalitis
o Syphilis
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• Vascular:
o Pituitary apoplexy
o Sheehan’s syndrome (post-partum necrosis)
o Carotid artery aneurysms
• Immunological:
o Pituitary antibodies
• Neoplastic:
o Pituitary or hypothalamic tumours
o Craniopharyngioma
o Meningiomas
o Gliomas
o Metastases (especially from breast)
o Lymphoma
• Traumatic:
o Skull fracture through base
o Surgery (especially transfrontal)
• Infiltrations:
o Sarcoidosis
o Hereditary haemochromatosis
• Others:
o Radiation damage
o Fibrosis
o Chemotherapy
• ‘Functional’:
o Anorexia nervosa
o Starvation
o Emotional deprivation
Clinical features, investigations and treatment:

• All vary depending on the hormones affected – see relevant
notes
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Hypothyroidism
Screening for hypothyroidism:

The incidence of congenital hypothyroidism is ~ 1 in 3500 live births
Untreated, severe hypothyroidism leads to permanent neurological and

intellectual damage (‘cretinism’)
Routine screening of the newborn using a blood-spot (as in the Guthrie

test – for Phenylketonuria) to detect a high TSH level as an indicator of
primary hypothyroidism is efficient
Cretinism is preventable if T4 is started within the first few

months of life
Pathophysiology:
• Underactivity of the thyroid gland may be:
o Primary (due to disease of the thyroid)
o Secondary (due to hypothalamic-pituitary disease)
• Is one of the commonest endocrine disorders in the UK:
o 1.4% of women
o < 0.1% of men
Causes of primary hypothyroidism:

• Congenital:
o Agenesis
o Ectopic thyroid remnants
• Autoimmune:
o Atrophic thyroiditis
o Hashimoto’s thyroiditis
• Defects of hormone synthesis:
o Iodine deficiency
o Dyshormonogenesis
o Antithyroid drugs
o Other drugs (e.g. lithium, amiodarone, interferon)
• Infective:
o Post-subacute thyroiditis
• Post-irradiation:
o Radioactive iodine therapy
o External neck irradiation
• Infiltration:
o Tumour
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Causes of secondary hypothyroidism:

• Isolated TSH deficiency
Symptoms:
• Tiredness/malaise
• Weight gain (despite reduced appetite)
• Cold intolerance
• Depression
• Reduced libido
• Constipation
• Deepening of voice
• Dry, brittle, unmanageable hair
• Poor memory
• Goitre
• Deafness
• Myalgia
Signs:
• Bradycardia
• Psychosis/dementia
• Ataxia
• Poverty of movement
• Hypertension
• Hypothermia
• Oedema
• Dry skin
• Anaemia
• Proximal myopathy
• Large tongue
Investigation of primary hypothyroidism:

• Serum TSH:
o Ix of choice
o A high TSH confirms primary hypothyroidism
• A low total/free T4 level confirms the hypothyroid state and is
especially important if there is any evidence of HP-axis disease,
when TSH may be low or normal
• Thyroid (and other organ-specific) autoantibodies may be
present
• Other abnormalities include the following:
o Anaemia (usually normochromic and normocytic, but may
be macrocytic or microcytic)
o Increased AST levels (from muscle and/or liver)
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o Increased creatine kinase levels

o Hypercholesterolaemia
o Hyponatraemia (due to an increase in ADH and impaired
free water clearance)
Treatment:
• Replacement therapy with T4 is given for life:
o In the young and fit - 100µg daily
o In the small, old or frail – 50µg daily
• Patients with severe IHD - 25µg daily to begin with, including
serial ECGs. The dose would then be increased at 3-4 week
intervals if angina does not occur/worsen and the ECG does not
deteriorate
• Adequacy of replacement should be assessed clinically and by
thyroid function tests (TSH and, possibly, T4) after at least 6
weeks on a steady dose – the aim being to restore TSH to well
within the normal range
• If TSH remains high, the dose of T4 should be increased in
25-50µg increments and the tests repeated six weeks later
• Clinical improvement on T4 may not begin for two weeks or more
and full resolution of symptoms may take up to six weeks
• During pregnancy, about a 50µg increase in T4 dosage is often
needed to maintain normal TSH levels (probably because of the
increased TBG levels)
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Myxoedema coma
Although very rare, severe hypothyroidism (especially in the elderly)

may present with confusion or even coma
Commonly presents with:

• Hypothermia
• Severe cardiac failure
• Hypoventilation
• Hypoglycaemia
• Hyponatraemia
Initial treatment (followed, eventually, by maintenance therapy):

• T3 orally or IV in doses of 2.5-5µg every 8 hrs
• O2 (by ventilator if necessary)
• Insertion of a Swan-Ganz catheter to monitor cardiac output/
filling pressure
• Gradual re-warming
• Hydrocortisone 100mg IV 8-hourly
• Dextrose infusion (to prevent hypoglycaemia)
‘Myxoedema madness’:
• Depression is common in hypothyroidism but occasionally (with
severe hypothyroidism in the elderly) the patient may become
frankly demented or psychotic, sometimes with striking
delusions
• This may also occur shortly after starting T4 replacement
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Osteoporosis
Definition:
• ‘A disease characterised by low bone mass and micro-
architectural deterioration of bone tissue, leading to enhanced
bone fragility and susceptibility to fracture’
• The bone that is present is normally mineralised but is deficient
in quantity, quality and structural integrity
• The WHO defines osteoporosis as a bone density > 2.5 SDs
below the young adult mean value for individuals matched for
sex and race. Values between 1 and 2.5 are termed ‘osteopenia’
Incidence:
• Over 1.3 million osteoporotic fractures in the USA each year,
approximately:
o 50% vertebral
o 25% hip
o 25% Colles’ fractures
Pathogenesis:
• Bone mass increases rapidly up to the age of puberty, rises
slightly in the 20s and 30s and then begins to decline around
age 40
• In men there is a gradual decline, reaching moderate levels of
fracture risk in the 70s and 80s, but a subset of women show a
very accelerated loss in the 10 years following the menopause
• Osteoporosis arises as the end-result of many years of mismatch
between the rates of bone resorption and bone formation during
the remodelling process
• This can arise from ‘high turnover’ osteoporosis (from such
conditions as the postmenopausal state, hyperparathyroidism
and hyperthyroidism) while others may be due to ‘low turnover’
osteoporosis (e.g. as in anorexia nervosa and liver disease)
Risk factors:
• Age
• Gender (women more susceptible)
• White race
• Late menarche/early menopause
• Smoking
• Low calcium intake
• Low BMI
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Signs and symptoms of osteoporosis:

• Asymptomatic (most commonly)
• Fractures (e.g. vertebrae, hip and wrist)
• Bone pain
• Loss of height
• Kyphosis (excessive outward curvature of the spine – causes a
hunched back)
Causes of osteoporosis:
• Endocrine:
o Postmenopausal (especially premature menopause)
o Cushing’s syndrome
o Hyperthyroidism
o Male hypogonadism
• Drugs:
o Corticosteroid osteoporosis
o Heparin osteopenia
• Miscellaneous:
o Simple osteoporosis of ageing
o Immobilisation
o Dietary deficiency of Ca2+, protein or vitamin C
o Malabsorption syndrome
o Idiopathic juvenile osteoporosis
o Idiopathic adult osteoporosis
Fracture investigations:
• X-rays:
o May show the fracture and/or earlier, unrecognised,
fractures
o X-rays showing pedicle destruction are suggestive of
malignant destruction
o Osteopenia is used to describe a non-specific generalised
or regional rarefaction of the skeleton on X-ray
• Bone scans:
o Are sometimes useful to demonstrate fractures
o An osteoporotic fracture can be distinguished from a
Metastatic lesion, as the latter is often associated with
multiple lesions elsewhere
• X-rays are of limited value in evaluating bone density because
up to 30-40% of the bone mineral content has to be lost before
any change in radiological bone density is detectable
Bone density investigations:
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• Dual Energy X-ray Absorption scanning – DEXA

• CT scanning (higher radiation dose than DEXA)
• Ultrasound (of the calcaneum is used occasionally)
Other investigations:
• Iliac crest bone biopsy
• Serum Ca2+, PO43- and ALP (will be normal in osteoporosis as no
disorder of calcium metabolism is involved)
• Biochemical markers of bone resorption:
o Urinary hydroxyproline (not very sensitive)
o Urinary pyridinoline
o Urinary collagen cross-links
Non-drug therapy of osteoporosis:

• Diet:
o At least 1000mg of calcium daily (ideally 1500mg
postmenopausally)
o 400-800 IU of vitamin D daily
o Adequate weight gain in a thin person is necessary, as a
low bodyweight is itself a risk factor for further fractures
• Exercise
• Smoking cessation
Common drug therapy:

• Oestrogen therapy as HRT:
o Is the treatment of choice for postmenopausal women
o The potential side-effects (breast cancer and thrombosis)
remain controversial
o Selective oestrogen receptor modulators (SERMs) such as
Raloxifene are under trial; they do not stimulate the
endometrium but do stimulate oestrogen receptors in
bone, thereby increasing bone mass. They also lower total
and LDL cholesterol
• Androgens:
o Should be given to hypogonadal men (although prostatic
hypertrophy may sometimes be a limiting factor)
• Bisphosphonates:
o Are analogues of normal bone pyrophosphate
o They adhere to hydroxyapatite and inhibit osteoclastic
bone resorption
o Alendronate 10mg daily has been shown to increase bone
mass substantially and reduce the incidence of fractures
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o The only main side-effect of alendronate is oesophageal

ulceration (which can be minimised if the patient takes the
tablet before breakfast with a full glass of water and
remains upright for 30 mins
Lesser used agents:

• Calcitriol:
o This is the active metabolite of vitamin D
o Produces some small improvement in bone density, but
not as much as HRT or bisphosphonates
• Calcitonin:
o Can administer human calcitonin nasally or (the more
potent) salmon calcitonin subcutaneously
o Good for patients who experience vertebral fracture pain
• Fluoride:
o Has been shown to increase bone density
o Is current concern about the quality of the bone formed
o Not currently recommended
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Paget’s disease
(Osteitis deformans)
Definition:
• Is a disorder of bone remodelling
• There is excessive resorption with a subsequent compensatory
increase in new bone formation
• The new bone is structurally abnormal and therefore weak, with
secondary phenomenon like:
o Increased local bone blood flow
o Fibrous tissue in adjacent bone marrow
Epidemiology:
• Most often seen in Europe (and particularly northern England)
• Affects both men and women over age 40 years
• Up to 10% of adults are radiologically affected by the age of 90
Aetiology and pathogenesis:

• Some evidence suggests a viral aetiology, for which canine
distemper virus, measles and respiratory syncitial virus have
been proposed
• The osteoclasts are more numerous than normal and contain an
increased number of nuclei
• Bone resorption is chaotic and the is a haphazard (rather than
linear) deposition of collagen fibres, leading to ‘woven’ bone
formation
• Bone mineralization is normal
• The structure of unaffected bone is normal and continues to
remain so. Thus, Paget’s disease doesn’t spread
Clinical features:
• 60-80% of patients with radiological evidence of Paget’s are
asymptomatic
• The disease may be monostotic or polyostotic
• Most common sites of involvement are:
o Femur
o Pelvis
o Tibia
o Skull
o Lumbosacral spine
• When symptomatic, features can include:
o Bone pain (most often in the spine or pelvis)
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o Apparent joint pain (when an affected bone is close to a

joint, leading to cartilage damage and osteoarthritis)
o Deformities (especially, bowed tibia and skull changes)
• Complications from:
o Nerve compression (most commonly CN VIII)
o Increased bone blood flow (cardiac hypertrophy, high-
output cardiac failure)
o Weakness of the abnormal bone
• Osteogenic sarcoma (rare, <1%)
Investigations:
• X-rays:
o Bone enlargement/expansion
o Osteolytic lesions
o Sclerosis and thickening of bone trabeculae in long bones
and vertebrae
• Bone scans
• Biochemistry:
o Increased serum ALP (a marker of bone formation)
o NORMAL serum Ca2+ and PO43-
• Measurements of bone resorption:
o Increased 24-hour urinary hydroxyproline excretion
Treatment:
• Oral bisphosphonates:
o E.g. Alendronate 10-40mg daily for 6 months
o Responses to bisphosphonates are long-lasting, with
50-70% reduction in serum ALP. The new bone formed is
lamellar, not woven
• Other bisphosphonates:
o IV pamidronate has been used widely as a single or
multiple infusion
• Calcitonin:
o Inhibit bone resorption and turnover but are extremely
expensive
o Side-effects include:
• Flushing
• Nausea
o Nasally administered calcitonin has fewer side-effects
• Surgery:
o Joint replacement or osteotomy are sometimes necessary
o Neurosurgery where there is spinal disease
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Pituitary space-occupying lesions and tumours
Overview:
• Pituitary tumours are the most common cause of pituitary
disease. Problems may be caused by:
o Excess hormone secretion
o Local effects of the tumour
o The result of inadequate production of hormone by the
remaining normal pituitary (hypopituitarism)
• The great majority of pituitary tumours are benign pituitary
adenomas
Investigations:
• The investigation of a possible or proven tumour follows three
lines:
1. Is there a tumour?
2. Is there hormonal excess?
3. Is there a deficiency of any hormone?
Is there a tumour?
• Pituitary and hypothalamic space-occupying lesions can cause
symptoms by infiltration of or pressure on, the:
o Visual pathways
o Cavernous sinus (with III, IV and VI cranial nerve lesions)
o Bony structures and meninges surrounding the fossa
(causing headache)
o Hypothalamic centres (can cause altered appetite, thirst,
somnolence/wakefulness or precocious puberty
o Ventricles (causing interruption of CSF flow, leading to
hydrocephalus)
• The principle investigations when looking for a pituitary tumour
are:
o Lateral skull X-ray
o Tests of the visual fields
o MRI of the pituitary
Is there hormonal excess?

• There are 3 major conditions that may be caused by tumour or
hyperplasia:
1. GH excess (leading to acromegaly or gigantism)
2. Prolactin excess
3. Cushing’s disease (caused by excess ACTH secretion)
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Is there a deficiency of any hormone?

• Clinical examination may give clues, thus:
o Short stature in a child with a pituitary tumour is likely to
be due to GH deficiency
o A slow, lethargic adult with pale skin is likely to be
deficient in TSH and/or ACTH
Treatment:
• In general, treatment of a pituitary space-occupying lesion has 3
aims:
1. Removal/control of tumour
2. Reduction of excess hormone production
3. Replacement of hormone deficiencies
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Regulation of calcium metabolism
Calcium ion regulation:

• [Ca2+] is increased by:
o Parathyroid hormone (Parathormone, PTH)
o 1,25 (OH)2 vitamin D3 (Dihydrocholecalciferol)
• [Ca2+] is decreased by:
o Calcitonin
Actions of PTH:
• On the kidneys:
o Increases Ca2+ reabsorption
o Increases PO4- excretion
o Stimulates 1-!-hydroxylase activity (which increases 1,25
(OH)2 vitamin D3 synthesis)
• On bone:
o Stimulates osteoclasts
o Inhibits osteoblasts
• On the small intestine:
o Indirect action (by increasing the synthesis of 1,25 (OH)2
vitamin D3)
• Increases Ca2+ absorption
• Increases PO4- absorption
Synthesis of 1,25 (OH)2 vitamin D3:
Cholecalciferol ---> 25-hydroxyxholcalciferol ---> 1,25-

dihydroxycholecalciferol
The last step is catalysed by Stimulates 1-!-hydroxylase activity (in

the kidneys)
Actions of 1,25 (OH)2 vitamin D3:

• On the kidneys:
o Increases Ca2+ reabsorption
o Increases PO4- reabsorption
• On bone:
o Increases osteoblast activity
• On the small intestine:
o Increases Ca2+ absorption
o Increases PO4- absorption
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Actions of calcitonin:
• On the kidneys:
o Increases excretion of Ca2+, Na+ and PO43
-
• On bone:
o Inhibits osteoclasts
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Gastroenterology
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Acute gastritis
Aetiology:
Gastritis can commonly be caused by:
•Drugs such as Aspirin and other NSAIDs
•I n f e c t i o n s ( e . g . C M V a n d H S V ) , p a r t i c u l a r l y i n t h e
immunocompromised
•Alcohol in high concentrations damages the gastric mucosal barrier
•Severe stress
•Secondary to:
o Burns (Curling ulcers)
o Trauma
o Shock
o Renal disease
o Liver disease
Pathology:
•There is an acute inflammatory infiltrate in the superficial gastric
mucosa predominantly with neutrophils
•This is sometimes accompanied by mucosal erosions
•Multiple small erosions (often with an oedematous mucosa) are
described as acute erosive gastritis
•Acute gastric ulceration occurs in the same setting as erosions but
ulcers are larger and less superficial
Clinical features:
• The correlation between the pathological changes and symptoms
is poor
• The commonest symptoms are:
o Indigestion
o Vomiting
• GI haemorrhage can occur (usually from NSAIDs)
Diagnosis and treatment:

•In many pts, symptoms settle without dx but endoscopy is
necessary in pts with a GI haemorrhage to confirm the presence
of acute ulcers or erosions
•No specific therapy is required apart from removal of the offending
cause (if possible)
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Acute hepatitis
Pathology:
•Most of the parenchymal changes that occur are essentially similar
whatever the cause
•Hepatocytes:
o Show degenerative changes (swelling, cytoplasmic
granularity, vacuolation)
o Undergo necrosis (becoming shrunken, eosinophilic
Councilman bodies)
o Are rapidly removed
•The distribution of these changes varies somewhat with the
aetiological agent, but necrosis is usually maximal in zone 3
•The extent of the damage ranges from spotty or focal necrosis to
massive hepatic necrosis (resulting in fulminant hepatic failure)
Common causes of acute hepatitis:

•Viral infections:
o Hepatitis A, B, (D), C and E
o EBV
o CMV
o Yellow-fever virus
•Non-viral infections:
o Toxoplasma gondii
o Leptospira icterohaemorrhagiae
•Drugs:
o Paracetamol
o Halothane
•Alcohol
•Poisons:
o Amanita phalloides (mushrooms)
o Aflatoxin
o Carbon tetrachloride
•Other:
o Pregnancy
o Wilson’s disease
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Acute hepatitis B virus (HBV)
Viral structure:
•The complete infective virion is a 42nm particle comprising an:
o Inner core (or nucleocapsid)
o Outer envelope of surface protein (HBsAg)
•The surface protein is produced in excess by infected hepatocytes
and can exist separately from the whole virion in serum and
body fluid.
•The nucleocapsid is formed of core protein (HBcAg)
•HBeAg is a protein secreted separately by the cell
•The HBV is not directly cytopathic and the liver damage produced
is by the cellular immune response of the host
•Specific failure of T-cells to recognise HBV Antigens leads to viral
persistence
Epidemiology:
•Worldwide distribution
•Has infected > 2 billion people
•Estimated 300 million carriers
•The UK and USA have a low carrier rate (~0.5%) but it rises to
10-15% in parts of Africa, the Middle and the Far East
•Spread is:
o Intravenously (e.g. IVDUs, blood transfusions)
o Close bodily contact (e.g. sexual intercourse, particularly
amongst homosexual men)
o Vertical transmission (from mother to child during
parturition) is the most important means of transmission
worldwide
Clinical features:
•In many cases, the infection is sub-clinical
•The clinical picture is the same as that for HAV infection, although
the illness may be more severe
Investigations:
•These are generally as for HAV
•Acute infection:
o HBsAg appears in the blood from about 6-12 weeks after
an acute infection and then disappears
o HBeAg rises early and usually declines rapidly
o Antibodies:
• Anti-HBs appears late and indicates immunity
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• Anti-HBc is the first Antibody to appear and high

titres of IgM anti-HBc suggests acute and continuing
viral replication. It persists for many months
• Anti-HBe appears after the anti-HBc and its
appearance relates to a decreased infectivity (i.e. a
low risk)
• Acute infection leading to chronic infection:
o HBsAg persists and indicates a chronic infection (or carrier
state)
o HBeAg persists and correlates with increased severity and
infectivity and the development of chronic liver disease
Course:
• Majority of pts recover completely
• Fulminant hepatitis occurs in ~1%
• Some pts go on to develop chronic hepatitis and hepatocellular
carcinoma (HCC) or become asymptomatic carriers
Treatment:
•Only symptomatic
Chronic asymptomatic carriers of HBV:

•Following an acute HBV infection (which may be subclinical)
~5-10% of pts will not clear the virus and most will become
carriers of HBsAg
•Occurs more readily with neonatal or childhood infection than
when HBV is acquired in adult life
•Carriers:
o Have HBsAg in their serum
o Are HBeAg-negative
o Anti-HBe positive
•No evidence of active liver disease
•NOT highly infective
•There is an spontaneous clearance rate of HBsAg of 1-2%
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Acute hepatitis C virus (HCV)
Epidemiology:
•Identified in 1988 and
•Was found to be responsible for 70-90% of post-transfusion
hepatitis in all countries where blood was tested for HBV markers
•Is believed that ~80% of haemophiliacs and 90% of IVDUs in the
UK are infected
•Limited transmission sexually
•Vertical transmission from mother to child can occur
Clinical features:
•Most infections are asymptomatic
•10% of pts experience:
o A mild ‘flu-like illness
o Jaundice
o Rise in serum transferases
•Most pts will not be dx until they present, years later, with
evidence of chronic liver disease
Diagnosis:
•HCV RNA can be detected 1-2 weeks after infection
•Anti-HCV antibodies take ~12 weeks to develop, by which time the
pt has usually recovered
Treatment:
•Interferon (IFN) has been used in some acute cases with some
success
Course:
•> 50% of pts go on to develop chronic liver disease
•Cirrhosis develops in ~20-30% within 5-30 years (and of these,
15% will develop an HCC)
•The course is adversely affected by alcohol consumption, which
should be discouraged
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Acute hepatitis D virus (HDV or Delta virus)
Structure:
•Is an incomplete RNA particle enclosed in a shell of HBsAg
•It is unable to replicate by itself, but is activated by the presence
of HBV
Co-infection with HBV:

•Is clinically indistinguishable from an acute icteric HBV infection
•Diagnosis is confirmed by finding:
o Serum IgM anti-# + IgM anti-HBc
Super-infection:
•Results in an acute flare-up of previously quiescent chronic HBV
infection
•A rise in serum AST or ALT may be the only indication of infection
•Diagnosis is confirmed by finding:
o Serum IgM anti-# + IgG anti-HBc
Fulminant hepatitis can follow both types of infection, but is more

common after co-infection
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Acute pancreatitis
Pathogenesis:
• Autodigestion of the pancreas by proteolytic enzymes released in
the pancreas (rather than in the interstitial lumen) may also be
involved
• Active enzymes could digest cell membranes, leading to:
o Proteolysis
o Pancreatic/peripancreatic oedema
o Vascular damage
o Pancreatic necrosis
• Mildest and most common form (oedematous pancreatitis –
75%):
o Interstitial oedema
o Inflammatory exudate
o Some fat necrosis
• Most severe form:
o Extensive pancreatic and peripancreatic necrosis
o Haemorrhage
Causes of acute pancreatitis:

• Gallstones
• Alcohol
• Infection (e.g. mumps, coxsackie B)
• Pancreatic tumours
• Drugs (e.g. azathioprine, oestrogens, corticosteroids)
• Post-ERCP
• Hyperlipidaemia
• Trauma
• Scorpion bite
Clinical features:
• Epigastric pain radiating to the back (between the scapulae)
• Pain varies from mild discomfort to excruciating pain
• Nausea
• Vomiting
• On examination:
o Tenderness, guarding and rigidity of the abdomen
o Body wall ecchymoses can occur:
• Umbilical (Cullen’s sign)
• In the flanks (Grey Turner’s sign)
•
Investigations
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• Serum amylase:
o If the serum amylase is 5x greater than normal, acute
pancreatitis is very likely
• Ultrasound:
o Used to detect gallstones in the biliary tree
o Shows pancreatic swelling, necrosis and the presence or
absence of peripancreatic fluid collections
• Contrast-enhanced dynamic CT scanning:
o Is the most valuable technique as it detects:
• Swelling of the pancreas
• Pancreatic necrosis
• Peripancreatic fluid collections
• Diffuse inflammatory changes in the retroperitoneum
• If there is any doubt in diagnosis, an exploratory
laparotomy must be performed in all but the mildest
cases to exclude a potentially fatal, but treatable, non-
pancreatic lesion
Factors during the first 48 hours indicating a poor prognosis:

• Age >55 years
• WBC >15
• Blood glucose >10
• Urea >16
• Albumin <30
• Aminotransferase >200
• Calcium <2
• LDH >600
• PaO2 <8kPa
Treatment:
• In all cases:
o NBM
o Nasogastric suction (to reduce vomiting and abdominal
distension)
o IV Fluids
o Electrolyte replacement
o Opiate analgesia (other than morphine)
• In severe cases:
o Parenteral nutrition
o ITU (if shocked and/or in respiratory failure)
Complications:
• Acute fluid collection
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• Pancreatic necrosis
• Pseudocysts
• Pancreatic abscesses
• Pancreatic ascites (indicates a poor prognosis)
Prognosis:
• Mortality varies from 1% (mild cases) to 50% (severe cases)
• With multiple complications and the presence of all the bad
prognostic signs, the mortality is nearer 100%
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Ascites
Aetiopathogenesis:
•Ascites is the presence of fluid within the peritoneal cavity and is a
common complication of cirrhosis. There are several factors
involved in the formation of ascites:
o Sodium and water retention:
• Occur as a result of peripheral arterial vasodilatation
and consequent reduction in blood volume
•Portal hypertension:
o Exerts a local hydrostatic pressure and leads to increased
hepatic and splanchnic production of lymph and
transudation of fluid into the peritoneal cavity
•Low serum albumin:
o Is a consequence of poor synthetic liver function
o May further contribute by a reduction in plasma oncotic
pressure
Clinical features:
•The abdominal swelling may accumulate over many weeks or as
rapidly as a few days
•Precipitating factors include:
o High sodium diet
o Development of a HCC
•Mild, generalised abdominal pain and discomfort
•Respiratory distress may accompany tense ascites
•The presence of fluid is confirmed by the demonstration of shifting
dullness and a fluid thrill
Investigations:
•Cell count:
o A neutrophil count > 250 cells/mm3 is indicative of an
underlying (usually spontaneous) bacterial peritonitis
•Gram stain and culture
•Protein
•Cytology:
o For malignant cells
•Amylase:
o To exclude pancreatic ascites
Management:
•Diuretic therapy:
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o The aim is to both reduce sodium intake and to increase

renal excretion of sodium and by doing so, produce a net
reabsorption of fluid from the ascites back into the
circulating volume.
o The maximum rate at which ascites can be mobilised is
500-700ml/24 hours
o The diuretic of choice is spironolactone 200mg daily.
Chronic administration of spironolactone results in
Gynaecomastia, so amiloride 10-15mg daily is then
substituted
•Paracentesis:
o This is used to relieve symptomatic tense ascites
o It is also used as a means of rapid therapy in pts with
ascites and peripheral oedema, thus avoiding a prolonged
hospital stay
o The main danger of this approach is the production of
hypovolaemia as the ascites reaccumulates at the expense
of the circulating volume
o This can be somewhat overcome by the administration of
albumin or a plasma expander
o In practice, up to 20L can be removed over 4-6 hours
• This procedure should not be performed in end-stage cirrhosis or
if the pt has renal failure
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Autoimmune hepatitis
Pathogenesis:
•The cause is unknown
•It is proposed, in a genetically predisposed person, that an
environmental agent causes an autoimmune process to develop
against liver antigens, producing a necroinflammatory process
which results in fibrosis and cirrhosis
Clinical features:
•Women >> men
•May be asymptomatic
•25% of pts present as an acute hepatitis with jaundice and very
high aminotransferases
•Examination can reveal:
o Hepatosplenomegaly
o Cutaneous striae
o Acne
o Hirsuites
o Bruises
o Ascites (sometimes)
•An ill pt can also have features of an autoimmune disease with:
o Fever
o Migratory polyarthritis
o Glomerulonephritis
o Pleurisy
o Pulmonary infiltration
o Fibrosing alveolitis
Investigations:
•LFTs:
o Raised aminotransferases
o Lesser elevations in ALP and bilirubin
o Raised serum $-globulins (frequently 2x normal)
•Haematology:
o Mild normochromic normocytic anaemia
o Thrombocytopenia
o Leucopenia
o Prolonged PT
• Autoantibodies:
o Two types of autoimmune hepatitis have been recognised:
• Type I, with antibodies:
• Antinuclear, or
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• Anti-smooth muscle, or
• Antimitochondrial
• Type II, with antibodies:
• Anti-liver/kidney microsomal
• Anti-liver cytosol
• Type II occurs most frequently in girls and young
women
Treatment:
•Prednisolone 30mg daily for two weeks
•Maintenance dose of prednisolone of 10-15mg daily
•Azathioprine 1-2mg/kg daily
Course and prognosis:

•Steroid and azathioprine therapy induce remission in 80% of cases
•The length of treatment is unclear
•Liver transplantation is performed if treatment fails, although the
disease may recur
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Bacterial overgrowth
Aetiology:
•The upper part of the small intestine is almost sterile, containing
only a few organisms derived from the mouth.
•Gastric acid kills most organisms and intestinal motility keeps the
jejunum empty
•The normal terminal ileum contains faecal-type organisms (mainly
E. coli and anaerobes)
•Bacterial overgrowth is normally only found associated with a
structural abnormality of the small intestine (although it can
occur occasionally in the elderly)
Clinical features:
•Steatorrhoea (the bacteria deconjugate and dehydroxylate bile
salts)
•Diarrhoea
•B12 deficiency (as the bacteria metabolize it and interfere with it’s
binding to IF)
Treatment:
•If possible, the underlying lesion should be corrected (e.g. a
stricture should be resected)
•Where it is not possible to correct the underlying lesion, rotating
courses of antibiotics may be needed (such as, metronidazole
and tetracycline or ciprofloxacin)
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Cholestatic jaundice
Pathology:
•This may be divided into extra-hepatic and intra-hepatic
cholestasis
•Extra-hepatic cholestasis:
o Is due to large duct obstruction of bile flow at any point
in the biliary tree distal to the bile canaliculi
•Intra-hepatic cholestasis:
o Due to failure of bile secretion
Clinical features:
•Jaundice
•Pale stools
•Dark urine
•Raised serum conjugated bilirubin
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Chronic gastritis
Aetiology:
•H. pylori is the chief cause of chronic active gastritis affecting the
antrum and body of the stomach
•Autoimmune gastritis affects the fundus and body of the stomach
(pangastritis) and is the cause of pernicious anaemia. AutoAbs to
gastric parietal cells and Ifs are found in the serum
•Chronic ingestion of NSAIDs or Aspirin produces gastritis
•Biliary reflux (possibly)
Pathology:
•Chronic active gastritis consists of an infiltration of the lamina
propria with lymphocytes and plasma cells
•This can lead to the development of atrophic changes in the
mucosa, including loss of parietal and chief cells and subsequent
intestinal metaplasia
Clinical features:
• Most chronic gastritis is asymptomatic and requires no rx
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Chronic hepatitis
Clinically, this is defined as any hepatitis lasting > 6 months.
Pathology:
•Chronic inflammatory cell infiltrates comprising lymphocytes and
plasma cells are usually present in the portal tracts
•The amount of inflammation varies from mild to severe
•In addition, there may be:
o Periportal or periseptal interface hepatitis
o Lobular change, focal lytic necrosis, apoptosis and focal
inflammation
o Confluent necrosis
o Fibrosis which may be mild, bridging (across portal tracts)
or severe
o Cirrhosis
• The overall severity of the hepatitis is judged by the degree of
necrosis and inflammation and the severity of the fibrosis or
cirrhosis.
Causes of chronic hepatitis:

•Viral:
o Hepatitis B ± Delta virus
o Hepatitis C
•Autoimmune:
o Drugs:
• Methyldopa
• Isoniazid
• Ketoconazole
• Nitrofurantoin
• Hereditary:
o !1-antitrypsin deficiency
o Wilson’s disease
• Others:
o Ulcerative colitis
o Alcohol (rarely)
Clinical features of chronic liver disease:

•Xanthelasmas (yellow plaques occurring symmetrically around the
eyelids)
•Parotid enlargement
•Spider naevi
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•Gynaecomastia
•Small/large liver
•Splenomegaly
•Clubbing
•Scratch marks
•Testicular atrophy
•Purpura
•Oedema
•Caput medusae
•Ascites
•Jaundice
•Fever
•Loss of body hair
•Fetor hepaticus
•Hepatic flap
•Disorientation
•Drowsiness
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Chronic hepatitis B infection
Pathogenesis:
•Cytotoxic T-cells recognise the viral Ag via HLA-1 molecules on the
infected hepatocyte
•This mechanism may be defective leading to viral persistence
•Chronic HBV goes through a replicative and an integrated phase
•Replicative phase:
o There is active viral replication with hepatic inflammation
o HBeAg (+ve)
o HBV DNA (+ve)
•Integrated phase:
o At some stage, the viral genome becomes integrated into
the host DNA and the viral genes are then transcribed
along with those of the host
o HBeAg (-ve)
o Anti-HBe Ab (+ve)
o The transferases are slightly elevated
o Liver histology shows little inflammation, often with
cirrhosis
o HCC develops in pts with this late-stage disease, but the
mechanism is still unclear
Clinical features:
•Chronic hepatitis occurs mainly in men and is often not preceded
by an acute attack
•The condition may be asymptomatic or may present as a mild,
slowly progressive hepatitis
•50% of pts present with established chronic liver disease
Investigations:
•LFTs:
o Raised aminotransferases (ALT, AST)
o Slightly raised ALP
o Normal serum bilirubin (often)
•Markers:
o HBsAg (+ve)
o HBV DNA (+ve)
o HBeAg (+ve)
Treatment:
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•The main aim of treatment is the disappearance of the HBeAg and

HBV DNA from the serum with consequent reduction in
inflammatory necrosis of the hepatocyte.
•This seroconversion occurs spontaneously at a rate of 10-15% per
year
•In pts in whom HBeAg disappears, remission is usually sustained.
The pt remains a carrier with HBsAg present, although many will
eventually become HBsAg (-ve)
$-Interferon (an antiviral agent):

•Is the best agent available
•Is given in a dose of 5M units daily or 10M units three times
weekly for 4-6 months
•Drug treatment is sometimes accompanied by systemic symptoms.
Treatment should be continued regardless
•Side-effects of $-IFN include:
o Acute ‘flu-like illness occurring 6-8 hours after the first
injection
o Malaise
o Headaches
o Myalgia
o Depression
o Diarrhoea
o Reversible hair loss
o Bone marrow depression
•The response rate, with the disappearance of HBeAg is 25-40%
Prognosis:
•The progression of the disease is slow and remission may occur
•Established cirrhosis is associated with a poor prognosis
•Primary liver cell carcinoma is a frequent association and is one of
the most common carcinomas in HBV endemic areas, such as
the Far East
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Chronic hepatitis C infection
Pts with chronic hepatitis C infection are usually asymptomatic; the

disease being discovered only following a routine biochemical test
when mild elevations of the aminotransferases (usually ALT) are
noticed.
Diagnosis:
•This is made by finding anti-HCV Ab in the serum
•Liver biopsy is indicated if active treatment is being considered
Treatment:
•Is appropriate for pts with chronic hepatitis on liver histology who
have:
o HCV DNA in their serum, and
o Raised serum aminotransferases for more than six months
•The presence of cirrhosis is NOT a contraindication
•The aim of treatment is to eliminate the HCV DNA from the serum
in order to:
o Stop the progression of active liver disease
o Prevent the development of HCC
$-interferon:
•Is given as a dose of 3M units three times a week for 12 months
•Side-effects are less than when used to treat HBV infection,
because of the lower dose
•After six months of therapy:
o 40-50% of pts will have normal aminotransferases
o 20-25% of pts, however, will relapse after cessation of
treatment
o The remaining 15-25% will have a sustained response
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Chronic hepatitis D infection
Diagnosis:
•Is a relatively infrequent chronic hepatitis
•Spontaneous resolution is rare
•The diagnosis is made by finding:
o Anti-HDV Abs in a pt with chronic liver disease and who is
HBsAg (+ve)
Treatment:
•$-interferon
•given in the high dose of 10M three times a week for 12 months
Prognosis:
• 15-25% of pts will show disappearance of HBsAg from the serum
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Chronic pancreatitis
Pathogenesis:
• Earliest change is deposition of protein plugs with the pancreatic
ducts
• These then lead to ductular dilatation followed by acinar atrophy
• Eventually, only a few acinar and islet cells remain
• Intraluminal calcification of the protein plugs occurs, leading to
stone formation
Causes of chronic pancreatitis:

• Alcohol (>85%)
• Idiopathic
• Tropical (nutritional)
• Hereditary
• Trauma
• Hypercalcaemia
Types of chronic pancreatitis:

• Chronic calcifying pancreatitis:
o Most common form in developed countries
o Usually caused by alcohol
• Tropical pancreatitis:
o Usually affects the young
o Primarily people from a region where there is protein and
fat malnutrition
• Hereditary pancreatitis:
o Rare condition
o Is a lack of a protein stabilizer, thus permitting the
formation of calcifying plugs
• Obstructive pancreatitis:
o Obstruction of the main pancreatic duct, owing to a:
• Scar
• Stricture
• Tumour
• May regress if obstruction is removed
Clinical features:
• Epigastric pain radiating to the back, between the scapulae
• The pain can be severe (sometimes comparable to acute
pancreatitis)
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• Continuing episodes of pain may occur, sometimes mild and

brief, sometimes there is chronic pain interspersed with acute
episodes (relapsing pancreatitis)
• Steatorrhoea (occurs when secretion of pancreatic lipase is
reduced by 90%)
Investigations:
• ERCP
• Endoscopic ultrasound
• CT
Differential diagnosis:
• Carcinoma of the pancreas (especially when the history is short)
Treatment:
• In alcoholic pancreatitis, the patient must be made to stop
drinking
• Analgesia (often with narcotics – there is a frequent problem
with addiction)
• Surgery (for the treatment of intractable pain)
• Steatorrhoea is treated with:
o Low-fat diet
o Pancreatic supplements (e.g. pancreatin 2-4g with each
meal)
• Diabetes mellitus is treated with:
o Oral hypoglycaemics
o Insulin (if required)
Complications:
• Pancreatic pseudocyst (most common)
• Pancreatic ascites (usually in alcoholic ascites)
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Cirrhosis
Pathogenesis:
•Cirrhosis results from the necrosis of liver cells followed by fibrosis
and nodule formation
•The liver architecture is diffusely abnormal and this interferes with
liver blood flow and function
•This derangement produces the clinical features of portal
hypertension and impaired liver cell function
Causes of cirrhosis:
•Alcohol (most common cause in the West)
•Hepatitis B ± D (most common cause worldwide)
•Hepatitis C
•Biliary cirrhosis
•Autoimmune hepatitis
•Hereditary haemochromatosis
•Budd-Chiari syndrome (hepatic vein obstruction)
•Wilson’s disease
•Drugs (e.g. Methotrexate)
•!1-Antitrypsin deficiency
•Cystic fibrosis
•Intestinal bypass operations for obesity
•Galactosaemia
•Glycogen storage disorders
Pathology:
•The characteristic features of cirrhosis are regenerating nodules
separated by fibrous septa and loss of the normal lobular
architecture within the nodules
•Two types of cirrhosis have been described:
o Micronodular cirrhosis:
• Regenerating nodules are usually < 3mm in size and
liver is involved uniformly
• Often caused by ongoing alcohol damage or biliary tract
disease
o Macronodular cirrhosis:
• The nodules are of variable size and normal acini may
be seen within the larger nodules
• Often seen following previous hepatitis, such as HBV
infection
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Investigations to determine type:

•Viral markers
•Serum Autoantibodies
•Serum Igs
•Serum copper and !1-Antitrypsin deficiency (should always be
done in young cirrhotics)
•Serum iron, total iron-binding capacity (TIBC) and ferritin (to
exclude hereditary haemochromatosis)
Investigations to assess severity:

•LFTs:
o Serum albumin is the best indicator of liver function. The
outlook is poor with a level < 25g/L
o The PT is prolonged commensurate with the severity of the
liver disease
o Biochemistry can be normal, depending on the severity of
cirrhosis
o In most cases, there is at least a slight elevation in the
serum ALP and aminotransferases
o In decompensated cirrhosis, all biochemistry is deranged
•Serum electrolytes:
o A low sodium indicates severe liver disease because of
dilution secondary to a defect in free water clearance or to
excess diuretic therapy
•Other:
o Serum alpha-fetoprotein is a useful screening test for HCC
Imaging:
•Ultrasound:
o Can demonstrate changes in size and shape of the liver
o Fatty change and fibrosis produce a diffuse increased
echogenicity
o In established cirrhosis, there may be marginal nodularity
of the liver surface and distortion of the arterial vascular
architecture
o It is useful in detecting HCC
•CT scan
•Barium swallow:
o Can detect varices
Liver biopsy:
•This is necessary to confirm the severity and type of liver disease
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Management:
•Mx is that of the complications seen in decompensated cirrhosis
•Pts should have six-monthly alpha-fetoprotein measurements to
detect the development of a HCC as early as possible
•There is no treatment that will arrest or reverse the cirrhotic
changes
•Alcohol should be avoided, although if the cirrhosis is not due to
alcohol, small amounts are probably not harmful

•This is very variable and is dependent on a number of factors
•Development of any complication usually worsens the prognosis
•In general, the 5yr survival rate is ~50%
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Coeliac disease
(Gluten-sensitive enteropathy)
Incidence:
•Worldwide distribution
•In the UK ~ 1 in 1500
•In Ireland ~ 1 in 300
•Rare in Black Africans
•There is an increased risk to first-degree relatives, with 10-15%
affected
Aetiology:
•Gluten is a high molecular weight heterogeneous compound that
can be fractionated to produce !, " and $-gliadin peptides
•!-gliadin is injurious to the small intestinal mucosa although there
is some disagreement about the toxicity of the other compounds
Pathology:
•The mucosa of the proximal small bowel is predominantly affected,
the mucosal damage decreasing in severity towards the ileum as
the gluten is digested into smaller, non-toxic, fragments
•Is an absence of villi, making the mucosal surface flat
•The crypts are elongated, with chronic inflammatory cells in the
lamina propria
•The lesion is described as subtotal villus atrophy
Clinical features:
•Can present at any age:
o In infancy it presents after weaning on to gluten-
containing foods
o Peak incidence in adults is in the 3rd and 4th decades
o Females >> males
•Tiredness
•Malaise
•Diarrhoea/steatorrhoea
•Abdominal discomfort/pain
•Weight loss
•Intermittent mouth ulcers/angular stomatitis
Investigations:
•Endomysial Antibodies (IgA):
o Ix of first choice
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o These Abs have a high sensitivity and specificity for the dx

of untreated Coeliac disease
•Anti-reticulin antibodies:
o Very sensitive but not particularly specific
o Are seen in other GI conditions also (e.g. Crohn’s disease)
•Jejunal biopsy:
o The mucosal appearance of a jejunal biopsy specimen is
diagnostic
•Haematology:
o 50% of pts have a mild or moderate anaemia
o Folate deficiency is almost always present – gives rise to a
high MCV
o Fe deficiency is common
o B12 deficiency is rare
•Small bowel follow-through:
o May show dilatation of the small bowel with a change in
fold pattern
o Folds become thicker and (in the severer forms) total
effacement is seen
Treatment and mx:

•A gluten-free diet usually produces a rapid clinical and
morphological improvement.
•Replacement haematinics are given initially to replace body stores
•The usual cause for failure to respond to the diet is poor
compliance
Complications:
•Unresponsive ‘Coeliac disease’:
o Often no cause for this is found but, occasionally, the
following may be the cause:
• Intestinal lymphoma
• Ulcerative jejunitis
• Carcinoma
•Risk of malignancies:
o T-cell lymphoma is increased in Coeliac disease
o Carcinoma of the small bowel and oesophagus as well as
extra-GI cancers are also seen
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Conjugated congenital hyperbilirubinaemias
Dubin-Johnson syndrome:
•Autosomal recessive
•Caused by a defect in the cMOAT transporter gene
•Defect in the handling of bilirubin by the liver
•Good prognosis
•The liver is black, owing to melanin deposition
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Constipation
Causes of constipation:
•Simple (low fibre diet)
•Intestinal obstruction
•Colonic disease (e.g. carcinoma)
•Painful anal conditions (e.g. fissure)
•Drugs (many!):
o Opiates
o Aluminium antacids
o Antidepressants
o Codeine
o Iron
•Hypothyroidism
•Hypercalcaemia
•Depression
•Immobility
•Hirschsprung’s disease
Treatment:
•Laxatives should be avoided if at all possible
•Encourage the patient to eat a high-fibre diet
•Glycerol suppositories (which can be used by the patient) are often
useful
•The types of laxatives available are shown below. Bulking agent
should be tried first.
•Stimulant laxatives often cause cramp and their long-term use
should be avoided as they cause an atonic, non-functioning colon
•Magnesium is very useful in severe constipation
Laxatives:
•Bulking agents:
o Dietary fibre
o Bran
o Ispaghula husks
o Sterculia
o Methylcellulose
•Stimulant laxatives:
o Anthraquinones (e.g. Senna)
o Dioctyl sodium sulphosuccinate
o Danthron (for the elderly or for opiate-induced constipation
in the terminally ill)
o Bisacodyl
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•Osmotic laxatives:
o Magnesium (sulphate or hydroxide)
o Lactulose
•Suppositories:
o Bisacodyl
o Glycerol
•Enemas:
o Phosphate
o Sodium citrate
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Dermatitis herpetiformis
This is an uncommon blistering sub-epidermal eruption of the skin

associated with a gluten-sensitive enteropathy
Rarely, there may be gross malabsorption, but usually the jejunal

morphological abnormalities are not as severe as in coeliac disease
The inheritance and immunological abnormalities are the same as for

coeliac disease
The skin condition responds to Dapsone but both the gut and the skin
will improve on a gluten-free diet
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Diarrhoea
Definition:
•With true diarrhoea, there is an increase in stool weight to > 300g
per day.
•This is usually accompanied by increased stool frequency
The mechanisms of diarrhoea:

•There are four main mechanisms:
o Osmotic diarrhoea
o Secretory diarrhoea
o Inflammatory diarrhoea (mucosal destruction)
o Abnormal motility
Osmotic diarrhoea:
The gut mucosa acts as a semi-permeable membrane and fluid enters
the bowel if there are large quantities of non-absorbed hypertonic
substances in the lumen
•This may occur because:
o The patient has ingested a non-absorbable substance (e.g.
a purgative such as magnesium sulphate or magnesium-
containing antacid)
o The patient has generalized malabsorption so that high
concentrations of solute (e.g. glucose) remain in the lumen
o The patient specific absorptive defect (e.g. disaccharidase
deficiency or glucose-galactose malabsorption)
• The volume of diarrhoea produced by this mechanism is reduced
by the absorption of fluid by the ileum and colon
• The diarrhoea stops when the patient stops eating or the
malabsorptive substance is discontinued
Secretory diarrhoea:
•There is both active intestinal secretion of fluid and electrolytes as
well as decreased absorption
•Common causes of secretory diarrhoea are:
o Enterotoxins (e.g. Cholera and E. coli)
o Hormones (e.g. VIP in the Verner-Morrison syndrome)
o Bile salts in the colon (following ileal-resection)
o Fatty acids in the colon (following ileal resection)
o Some laxatives (e.g. dioctyl sodium sulphosuccinate)
• With secretory diarrhoea, the stool volumes may be very high.
Food does not affect the diarrhoea and it, therefore, continues
during fasting
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Inflammatory diarrhoea (mucosal destruction):

•Diarrhoea occurs because of damage to the intestinal mucosal
cells, so that there is a net loss of fluid and blood
•In addition, there is defective absorption of fluid and electrolytes
•Common causes are:
o Infective (e.g. dysentery due to Shigella)
o Inflammatory conditions (e.g. ulcerative colitis)
Abnormal motility:
•Is the cause of the diarrhoea seen in the following conditions:
o Diabetes
o Post-vagotomy
o Hyperthyroidism
• It is due to abnormal motility of the upper gut
• In many of these cases, the weight of the stool is not all that
high, but frequency of defaecation occurs; this, therefore, is not
true diarrhoea
Causes of acute diarrhoea:

•Dietary indiscretion
•Infective:
o Food poisoning
o Viral gastroenteritis
•Traveller’s diarrhoea, e.g.:
o E. coli
o Giardia intestinalis
o Shigella
o Entamoeba histolytica
Causes of chronic diarrhoea:

•Inflammatory bowel disease
•Parasitic/fungal infections
•Malabsorption
•Gut resection
•Drugs
•Colonic neoplasia
•Endocrine:
o Pancreatic tumours (e.g. gastrinoma)
o Medullary carcinoma of the thyroid
o Thyrotoxicosis
o Diabetic neuropathy
o Faecal impaction (in the elderly)
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Dysphagia
This is either due to a local lesion or a generalised disease. Pts will

complain of something sticking in their throat or chest during
swallowing or immediately afterwards.
It is always a serious symptom and the cause must be found.
Causes of dysphagia:
•Disease of the mouth and tongue (e.g. tonsillitis)
•Neuromuscular disorders:
o Pharyngeal disorders
o Bulbar palsy (e.g. MND)
o Myasthenia gravis
•Oesophageal motility disorders:
o Achalasia
o Scleroderma
o Diffuse oesophageal spasm
o Presbyoesophagus
o Diabetes mellitus
o Chaga’s disease
•Extrinsic pressure:
o Mediastinal glands
o Goitre
o Enlarged left atrium
•Intrinsic lesion:
o Foreign body
o Stricture:
• Benign – peptic
• Corrosive
• Malignant – carcinoma
•Lower oesophageal rings:
o Oesophageal web
• Pharyngeal pouch
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Fulminant hepatic failure (FHF)
Pathology:
•Severe hepatic failure in which encephalopathy develops in under
two weeks in a pt with a previously normal liver
•Cases that develop at a slower pace (2-12 weeks) are called
subacute or subfulminant hepatic failure
•FHF is a rare but often life-threatening syndrome that is due to
acute hepatitis from any cause
•Histologically, there is multiacinar necrosis involving a substantial
part of the liver
Clinical features:
•Jaundice
•Small liver
•Signs of hepatic encephalopathy
•The mental state varies from:
o Drowsiness, confusion and disorientation (grades I-II) to
o Unresponsive coma (grade IV)
•Fetor hepaticus
•Fever
•Vomiting
•Hypotension
•Hypoglycaemia
•Cerebral oedema – leads to intracranial hypertension and brain
herniation (the most common cause of death)
Investigations:
•Hyperbilirubinaemia
•High serum aminotransferases
•Low levels of coagulation factors
•EEG to grade the encephalopathy
Treatment:
•When ICP is raised, 20% mannitol (1g/kg bodyweight) should be
infused IV
•Hypoglycaemia, hypokalaemia and hypocalcaemia should be
anticipated and corrected
•Coagulopathy is managed with IV vitamin K, platelets, blood or FFP
•H2-receptor antagonists to prevent GI bleeding
•Infection should be treated with appropriate antibiotics
•Flumazenil (a BDZ antagonist) may give a transient improvement
in encephalopathy
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•Liver transplantation

•In mild cases (grades I and II encephalopathy with drowsiness and
confusion), 66% of pts will survive
•The outcome of severe cases (grades III and IV encephalopathy
with stupor or deep coma) is related to the aetiology
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Gastro-oesophageal reflux disease

(GORD)
Anti-reflux mechanisms:
•The most important mechanism is provided by the lower
oesophageal sphincter (LOS):
o Formed by the distal 4cm of oesophageal smooth muscle
o Rapidly regains its normal tone (following relaxation to
allow a bolus to enter the stomach) and thereby prevent
reflux
o Is capable of increasing tone in response to rises in intra-
abdominal and intra-gastric pressures
• The oesophagus is normally rapidly cleared of any reflux
contents by secondary peristalsis
Factors associated with increased gastro-oesophageal reflux:

•Pregnancy or obesity
•Fat, chocolate, coffee or alcohol ingestion
•Large meals
•Cigarette smoking
•Drugs:
o Anti-cholinergics
o Calcium-channel blockers
o Nitrates
•Systemic sclerosis
•Post-treatment for Achalasia
•Hiatus hernia
Clinical features:
•Heartburn:
o The pain is mainly due to direct stimulation of the
hypersensitive oesophageal mucosa, but is also partly due
to spasm of the distal oesophageal muscle
o The burning is aggravated by bending, stooping or lying
down
o Pain is often relieved by antacids
o Pain seldom radiates to the arms
•Nocturnal cough
Diagnosis and investigations:

GORD is a clinical diagnosis and many pts can be treated without
investigation
•Oesophagoscopy:
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o Is used to show and confirm the presence of Oesophagitis,

with a red friable mucosa and in more severe cases, linear
ulceration
o The mucosa can be normal in GORD
•Barium swallow:
o Less sensitive than endoscopy in demonstrating
Oesophagitis
o May show a hiatus hernia (which, by itself, is of no
diagnostic significance)
•Radiolabelled Technetium:
o Can be used to demonstrate reflux
•24-hour pH monitoring:
o Most accurate test available
o Reasonable correlation between frequency of reflux and
symptoms
o It is often combined with manometry
o The no. of reflux episodes below pH4 occurring over 24hrs
is noted
Management:
•Approx. 50% of pts can be treated successfully with:
o Simple antacids
o Loss of weight
o Raising the head of the bed at night
Precipitating factors should be avoided, with a reduction in alcohol
intake and cessation of smoking
•Magnesium trisilicate:
o Antacid
o Causes diarrhoea
•Aluminium hydroxide:
o Antacid
o Causes constipation
•Alginate-containing antacids:
o Most frequently prescribed agents for GORD
o They form a gel or ‘foam-raft’ with gastric contents and
thereby reduce reflux
•H2-receptor antagonists:
o E.g. Ranitidine
o Are widely available OTC
•Proton-pump inhibitors:
o E.g. Omeprazole, Lansoprazole, Pantoprazole
o Inhibit gastric hydrogen-potassium ATPase
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o They produce almost complete reduction of gastric acid

secretion and are the drugs of choice for all but the mildest
of cases
•Prokinetic agents:
o E.g. Metoclopramide, Cisapride
o These speed gastric emptying
Surgery:
•Surgery should never be performed for a hiatus hernia alone.
•The properly selected case with severe reflux confirmed by pH
manometry and Oesophagitis responds well to surgery
•Repair of the hernia and some sort of additional anti-reflux surgery
is performed laparoscopically
•Results show an improvement in symptoms in up to 80% of cases
Complications:
•Peptic stricture:
o Usually occurs in pts > 60yrs
o The symptoms are those of intermittent dysphagia over a
long period
•Barrett’s oesophagus:
o > 3cm of specialized columnar epithelium extending
upwards into the lower oesophageal mucosa
o Is due to long-standing reflux
o Is seen in up to 20% of pts undergoing endoscopy for
GORD
o Most common in middle-aged men
o Is pre-malignant for adenocarcinoma
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Hepatitis A virus (HAV)
Epidemiology:
•Most common type of viral hepatitis occurring worldwide, often in
epidemics
•The disease is commonly seen in the autumn and affects children
and young adults
•Spread of infection is faeco-oral and arises from the ingestion of
contaminated food or water (e.g. shellfish)
•In the UK, it is a notifiable disease
Clinical features:
•Non-specific features:
o Malaise
o Anorexia
o Distaste for cigarettes
•Many recover at this stage and remain anicteric
o After 1-2 weeks, some pts become jaundiced and
symptoms often improve
o As the jaundice deepens, the urine becomes dark and the
stools pale (owing to intra-hepatic cholestasis)
o There is organomegaly in ~10% of pts
•Thereafter, the jaundice lessens and (in the majority of cases) the
illness is over within 3-6 weeks
•Extra-hepatic complications are rare include:
o Arthritis
o Vasculitis
o Myocarditis
o Renal failure
Investigations:
•LFTs:
o In the prodromal stage:
• Normal serum bilirubin
• Bilirubinuria
• Increased urinary urobilinogen
• Raised serum AST or ALT (sometimes very high)
precedes the jaundice
o In the icteric stage:
• The serum bilirubin reflects the level of jaundice
• Serum AST reaches a maximum 1-2 days after the
appearance of jaundice (may rise > 500IU/L)
• Serum ALP is usually < 300IU/L
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o Post-icteric stage:
• The aminotransferases may remain elevated for some
weeks after and, occasionally, for up to six months
Haematology:
o Raised ESR
o Raised PT (in severe cases)
o Viral markers:
•An anti-HAV IgM = acute infection

• The prognosis is excellent, with most pts making a complete
recovery
• The mortality in young adults is ~ 0.1%, but it increases with
age
• Death is due to fulminant hepatic necrosis
• HAV never progresses to chronic liver disease
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Intestinal resection
Intestinal resection is usually well tolerated, but massive resection is

followed by the short-gut syndrome
The effects of resection depend on the extent and the areas involved
Because the gut is long, a 30-50% resection can usually be tolerated

without undue problems
Ileal resection:
•The ileum has specific receptors for the absorption of bile salts and
vitamin B12
•Therefore, relatively small resections will lead to malabsorption of
these substances
•Removal of the ileocaecal valve increases the incidence of
diarrhoea
•The following occur in ileal resection:
o Bile salts and fatty acids enter the colon and interfere with
water and electrolyte absorption, causing diarrhoea
o Increased bile salt synthesis can compensate for loss of
~1/3 of the bile salts in the faeces. Greater loss than this
results in decreased micellar formation and steatorrhoea
o Increased oxalate absorption is caused by the presence of
bile salts in the colon. This gives rise to renal oxalate
stones
o There is a low serum B12 and macrocytosis
Jejunal resection:
•The ileum can take over the jejunal absorptive function
•Jejunal resection may lead to gastric hypersecretion with high
gastrin levels (unclear mechanism)
•Intestinal adaptation takes place, with an increase in the
absorption per unit length of bowel
Massive resection (short-gut syndrome):

•This occurs following resection in:
o Crohn’s disease
o Mesenteric occlusion
o Trauma
•Severe symptoms occur when there is less than 90-100cm of small
bowel remaining:
o Diarrhoea (with severe water and electrolyte loss)
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o Malnutrition
• Parenteral nutrition (sometimes long-term) is necessary
• With intestinal adaptation most will eventually recover, although
they continue to have diarrhoea and little functional reserve
should another GI problem occur
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Jaundice
(icterus)
Icterus is detectable when the serum Bilirubin > 30-60mmol/L. It is

helpful to separate jaundice into:
•Pre-hepatic (haemolytic jaundice)
•Congenital hyperbilirubinaemias
•Cholestatic
Differential diagnosis of jaundice:

Questions should be appropriate to the particular situation, and the
following aspects of the history should be covered:
•Country of origin/recent travel:
o The incidence of hepatitis B virus (HBV( infection is
increased in many parts of the world (Africa, Middle and
Far East)
•Duration of illness:
o A history of jaundice with prolonged weight loss in an older
pt suggests malignancy
o A short history, particularly with a prodromal history of
malaise, suggests hepatitis
•Recent outbreak of jaundice:
o An outbreak in the community suggests hepatitis A virus
(HAV) infection
•Recent consumption of shellfish:
o This suggests HAV infection
•IV drug abuse, recent tattoos:
o These both increase the risk of HBV and hepatitis C virus
(HCV) infection
•Male homosexuality:
o Increases the chance of HBV infection
•Female prostitution:
o Increases the chance of HBV infection
•Blood transfusion:
o Increased risk of HBV and HCV. In developed countries, all
blood products are screened for HBV and HCV
•Alcohol consumption
•Drugs taken:
o Particularly in the last 2-3 months
o Many drugs cause jaundice
•Family history:
o Enquire about congenital hyperbilirubinaemias (e.g.
Gilbert’s disease)
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•Fevers or rigors:
o These are suggestive of:
• Cholangitis
• Liver abscess
Clinical features:
•The signs of acute and chronic liver disease should be looked for
•Certain additional signs may be helpful:
o Hepatomegaly:
• A smooth tender liver is seen in hepatitis and with extra-
hepatic obstruction
• A knobbly liver irregular liver suggests metastases
•Splenomegaly:
• This indicates portal hypertension in pts when signs of
chronic liver disease are present
•Ascites:
• This is found in cirrhosis, but can also be due to
carcinoma (particularly ovarian) and many other causes
•Palpable gallbladder:
• Can suggest a carcinoma of the pancreas obstructing the
bile duct
Investigations:
•Viral markers
•Ultrasound examination can demonstrate:
o The size of the bile ducts (which are dilated in extra-
hepatic obstruction)
o The level of the obstruction
o The cause of the obstruction in virtually all pts with
tumours and 75% of pts with gallstones
•LFTs:
o Hepatitis:
• Serum AST or ALT tends to be high early in the disease
• Only a small rise in the serum ALP
o Extra-hepatic obstruction:
• ALP is high
• Small rise in the aminotransferases
o Long-standing liver disease:
• The Prothrombin time (PT) is often prolonged
• Serum albumin is low
•Haematological tests:
o A leucocytosis may indicate infection (e.g. cholangitis)
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o A leucopenia often occurs in viral hepatitis

o Abnormal mononuclear cells suggests infective
mononucleosis
• Alpha fetoprotein:
o Raised in hepatocellular carcinoma
Pre-hepatic (haemolytic) jaundice
Haemolytic jaundice:
•Leads to an unconjugated hyperbilirubinaemia
•The increased breakdown of RBCs leads to an increase in the
production of bilirubin
•The resulting jaundice is usually mild (serum bilirubin of
68-102mmol/L) as normal liver function can easily handle the
increased bilirubin derived from excess haemolysis
•Causes of haemolytic jaundice:
o Inherited:
• Red cell membrane defect (hereditary spherocytosis/
elliptocytosis)
• Hb abnormalities (Thalassaemia, sickle cell disease)
• Metabolic defects (G6PDH deficiency, pyruvate kinase
deficiency)
o Acquired:
• Autoimmune
• Alloimmune (haemolytic transfusion reactions,
haemolytic disease of the newborn)
• Drug induced
• Mechanical (microangiopathic haemolytic anaemia,
valve prosthesis)
• Renal/liver failure
• Malaria
• Hypersplenism
• Burns
•Evidence for haemolysis:
o Elevated serum bilirubin (unconjugated)
o Raised LDH
o Reticulocytosis
o Normal serum ALP, transferases and albumin
Unconjugated congenital hyperbilirubinaemias
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Gilbert’s syndrome:
•Common familial hyperbilirubinaemia
•Affects 2-7% of the population
•Asymptomatic – usually detected as an incidental finding of a
slightly raised bilirubin (17-102mmol/L) on a routine blood test
•NO signs of liver disease are seen
•Family history of jaundice in 5-15% of pts
•Most pts have reduced levels of UDP-glucuronosyl transferase
activity
Crigler-Najjar syndrome:
•Very rare
•Two types:
o Type I (autosomal recessive, absence of glucuronosyl
transferase)
o Type II (autosomal dominant, decreased glucuronosyl
transferase activity)
•Only those with type II can survive into adult life
•Transplantation is the only effective treatment
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Malabsorption
In many small bowel diseases, malabsorption of specific substances

occurs, but these deficiencies do not dominate the clinical picture
Major diseases causing malabsorption:

•Coeliac disease
•Dermatitis herpetiformis
•Tropical sprue
•Bacterial overgrowth
•Intestinal resection
•Whipple’s disease
•Radiation enteritis
•Parasite infestation (e.g. Giardia intestinalis)
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Malignant liver tumours
The most common liver tumour is a secondary (Metastatic) tumour,

particularly from the:
• GI tract
• Breast
• Bronchus
Types of malignant liver tumours:

There are 2 main types:
• Hepatocellular carcinoma (HCC)
• Cholangiocarcinoma:
o Intrahepatic
o Extrahepatic
Since HCC is the most common, it will be discussed here.
Aetiology:
• Carriers of HBV and HCV
• Aflatoxin
• Androgenic steroids
• Is an association with the OCP
Pathology:
• The tumour may be single or multiple
• Can metastasize via the hepatic or portal veins to:
o Lymph nodes
o Bones
o Lungs
Clinical features:
• Usually present before the age of 50 years
• Weight loss
• Anorexia
• Fever
• Ache in the right hypochondrium
• Ascites
• Enlarged, irregular, tender liver may be palpable
Investigations:
• Raised serum !-fetoprotein
• Liver biopsy (for diagnosis)
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Treatment and prognosis:

• Surgical resection is occasionally possible
• Chemotherapy and radiotherapy are unhelpful
• Survival is less than 6 months
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Peptic ulcer disease
Epidemiology:
•Duodenal ulcer (DU) >> gastric ulcer GU (3 : 1)
•Approx. 15% of the population will suffer from a DU
Aetiology:
•One factor in the formation of a peptic ulcer is an imbalance
between acid and pepsin against the mucosal defences (mucus,
bicarbonate, PGs)
•Another major factor is infection by Helicobacter pylori. DU pts
with H. pylori infection secrete more acid after stimulation by
gastrin and have more parietal cells in the stomach than healthy
people with H. pylori.
•NSAIDs certainly contribute to the formation of GUs but NOT DUs
•Peptic ulceration is more common in pts with blood group O
Pathology:
•GUs are found in any part of the stomach but are most common on
the lesser curve
•Most DUs are found in the duodenal cap; the surrounding mucosa
appears inflamed, haemorrhagic or friable (duodenitis)
•Histologically there is:
o A break in the superficial epithelial cells penetrating down to
the muscularis mucosa at the site of the ulcer
o A fibrous base
o An increase in inflammatory cells
o H. pylori may be found scattered on the surface of the gastric
mucosa or in the ectopic gastric mucosa in the duodenum
o Associated active gastritis
Clinical features:
•Very well localised epigastric pain
•Pain is relieved by antacids
•The pain of a DU classically occurs at night (as well as in the day)
and is worse when the pt is hungry
•Nausea may accompany the pain
•Vomiting is infrequent but often relieves the pain
•Anorexia/weight loss, particularly with GUs
•Back pain suggests a penetrating posterior DU
•Pts can present for the first time with haematemesis or malaena or
a perforation
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Investigations:
•Serology or breath test to confirm H. pylori status. Further ix is
only indicated in pts with persistent dyspepsia following
successful eradication therapy, or in symptomatic pts who are H.
pylori negative
•Endoscopy:
o To exclude GORD or cancer
o All gastric ulcers should be biopsied
•Barium meal (double contrast):
o Less commonly used than endoscopy in this situation
Treatment of peptic ulcers associated with H. pylori:

•Successful eradication of H. pylori:
o Results in healing rates of 90%
o Prevents recurrence of the ulcer
•Anti-secretory therapy:
o Proton-pump inhibitor (PPI) (e.g. Omeprazole) or,
o H2-receptor antagonist (e.g. Ranitidine)
o Continued for 4-8 weeks to ensure ulcer healing
Treatment of peptic ulcers NOT associated with H. pylori:

•These are mainly due to NSAID ingestion
•Treatment involves acid suppression and discontinuation of
NSAIDs (if possible)
•This may be difficult in pts with severe arthritis, and PPIs, H2-
receptor antagonists or Misoprostol may be used concurrently
with NSAIDs
•Proton-pump inhibitors (PPIs):
o Omeprazole 20mg daily
o Lansoprazole 30mg daily
o Pantoprazole 40mg daily
•H2-receptor antagonist:
o Ranitidine 300mg daily
o Cimetidine 800mg daily
o Famotidine 40mg daily
o Nizatidine 300mg daily
•Misoprostol:
o Is a synthetic analogue of PGE1
o Inhibits gastric acid secretion
o Is mainly used as a cytoprotective agent against NSAID–
associated GUs, particularly in the elderly
o Prophylaxis is 200mg 2-4x daily
o The main side-effects are diarrhoea and abdominal pain
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Surgical management:
•Since the introduction in the 1970s of H2-receptor antagonists,
surgery for peptic ulceration is rarely necessary and is reserved
only for the complications:
o Recurrent uncontrolled haemorrhage – ligation of the
bleeding vessel
o Perforation – oversown
Complications of peptic ulcers:

•Haemorrhage (i.e. an upper GI bleed)
•Perforation:
o DU >> GU
•Gastric outflow obstruction:
o The obstruction may be pre-pyloric or in the duodenum
o In this situation, it occurs for two reasons:
• An active ulcer with surrounding oedema
• The healing of the ulcer has been followed by scarring
•Vomiting (usually projectile and huge in volume):
o Severe or persistent vomiting causes loss of acid from the
stomach and a metabolic alkalosis occurs
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Portal hypertension
Anatomy/physiology:
•The portal vein is formed by the union of the superior mesenteric
vein and the splenic vein
•The pressure within it is usually 5-8mmHg, with only a small
gradient across the liver to the hepatic vein, in which blood is
returned to the IVC
•Portal hypertension can be classified according to the site of
obstruction:
•Prehepatic:
o Due to blockage of the portal vein before the liver
•Intrahepatic:
o Due to distortion of the liver architecture, which can be
either:
•Pre-sinusoidal (e.g. in schistosomiasis), or
•Post-sinusoidal (e.g. in cirrhosis)
•Posthepatic:
o Due to venous blockage outside the liver (rare)
•As portal pressure rises > 10-12mmHg, the compliant venous
system dilates and collaterals occur with the systemic venous
system
•The main sites of the collaterals are the:
o Gastro-oesophageal junction
o Rectum
o Left renal vein
o Diaphragm
o Retroperitoneum
o Anterior abdominal wall (via the umbilical vein)
•The collaterals at the gastro-oesophageal junction (varices) are
superficial in position and tend to rupture
Common causes:
•Prehepatic:
o Portal vein thrombosis
•Intrahepatic:
o Cirrhosis
o Schistosomiasis
o Congenital hepatic fibrosis
•Posthepatic:
o Budd-Chiari syndrome
o Veno-occlusive disease
o Right heart failure (rare)
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o Constrictive pericarditis
Clinical features:
•Pts with portal hypertension are often asymptomatic and the only
clinical evidence is splenomegaly
•Clinical features of chronic liver disease are usually present
•Presenting features may include:
o Haematemesis/malaena from rupture of gastro-
oesophageal varices
o Ascites
o Encephalopathy
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Radiation enteritis
Aetiopathogenesis:
•Radiation of > 50Gy will damage the intestine
•The ileum and rectum are the areas most commonly involved (as
pelvic irradiation is the common cause)
•Radiation enteritis produces:
o Muscle fibre atrophy
o Ulcerative changes due to ischaemia
o Obstruction due to strictures produced by radiation-
induced fibrosis
Clinical features:
•At the time of irradiation there may be:
o Diarrhoea
o Abdominal pain
• The above symptoms usually resolve within six weeks after
completion of therapy
• Chronic radiation enteritis is diagnosed if symptoms persist for
more than three months
Treatment:
•Symptomatic (although often unsuccessful in chronic enteritis)
•Surgery should be avoided if at all possible, being reserved for life-
threatening situations such as:
o Complete obstruction
o Perforation (occasionally)
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Tropical sprue
Aetiology:
•Unknown
•Likely to be infective because the disease occurs in epidemics and
pts improve on antibiotics
Clinical features:
Vary in intensity but include the following:
•Diarrhoea
•Anorexia
•Abdominal distension
•Weight loss
•The onset can sometimes be acute (occurring within a few days) or
may occur several years after being in the tropics
•The disease can also be insidious, with chronic diarrhoea and
evidence of nutritional deficiency
Diagnosis:
•Acute infective causes of diarrhoea must be excluded (particularly
Giardia)
•Malabsorption should be demonstrated (particularly of fat and B12)
Treatment and prognosis:

•Many pts improve when they leave the sprue area and take folic
acid (5mg daily)
•Most pts also require an antibiotic (usually tetracycline 1g daily) to
ensure a complete recovery – may be required for up to 6
months
•The severely ill pt requires resuscitation with fluids and electrolytes
for dehydration
•Any nutritional deficiencies should be corrected
•Vitamin B12 (1000µg) is also given to all acute cases
•Prognosis is excellent
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Vomiting
Definition:
• Vomiting is the forceful ejection of gastric contents through the
mouth
• There are three phases:
1.Nausea – A feeling of wanting to vomit often associated with
autonomic effects (including hypersalivation, pallor and
sweating)
2.Retching – A strong involuntary effort to vomit
3.Vomiting – The expulsion of gastric contents through the
mouth
Control of vomiting:
•The vomiting centres are located in the lateral reticular formation
of the medulla and are stimulated by the chemoreceptor trigger
zones (CTZs) in the floor of the fourth ventricle, and also by
afferents from the gut
•The zones are directly stimulated by:
o Drugs
o Motion
o Metabolic causes
Aetiology:
•There are many causes of vomiting (see below) but nausea and
vomiting without pain are frequently non-GI in origin.
•Large volumes of vomit suggest intestinal obstruction
•Faeculent vomit suggests low intestinal obstruction from a
gastrocolic fistula
•Projectile vomiting is associated with pyloric stenosis
•Chronic nausea and vomiting with no other abdominal symptoms
usually have psychological causes.
•Early morning vomiting is seen in:
o Pregnancy
o Alcohol dependence
o Some metabolic disturbances (e.g. uraemia)
Causes of vomiting:
•Any GI disease
•Acute infections:
o Influenza
o Pertussis
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•CNS disease:
o Raised ICP
o Meningitis
o Vestibular disturbances
o Migraine
•Metabolic causes:
o Uraemia
o Diabetes (ketoacidosis or gastroparesis)
o Hypercalcaemia
•Drugs (many!):
o Digitalis toxicity
o Opiates
o Cytotoxics
•Reflex:
o Severe pain
o Infarction
•Psychogenesis
•Pregnancy
•Alcohol excess
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Whipple’s disease
Incidence:
•Rare disease
•Usually affects males
Pathology:
•Histologically, the villi are stunted and contain diagnostic periodic
acid-Schiff (PAS) positive macrophages
•On EM, bacilli can be seen ‘within’ the macrophages
•The organism is similar to actinomycetes and has been given the
name Tropheryma whippeii.
Clinical features:
•Commonest presenting features:
o Steatorrhoea
o Abdominal pain
o Fever
o Weight loss
Less common presenting features can include:
•Peripheral lymphadenopathy
•Arthritis
•Involvement of the:
o Heart
o Lung
o Brain
Treatment:
•An antibiotic that crosses the blood-brain barrier (e.g.
Chloramphenicol)
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General Medicine
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Acute lumbar disc prolapse
Pathogenesis:
• The central nucleus pulposus may extrude into a fissure in the
surrounding annulus fibrosis and cause acute pain and muscle
spasm
• These events are usually self-limiting
• A disc prolapse occurs when the extrusion extends beyond the
limits of the fibrous annulus fibrosis
• The weakest part of the annulus is posterolaterally – where the
disc may impinge on emerging spinal nerve roots in the root
canal
Clinical features:
• The episode starts dramatically during lifting, twisting or bending
• Produces a typical combination of:
o Lower back pain
o Muscle spasm
o Severe lancinating pains, paraesthesia, numbness and
neurological signs in one leg (rarely both)
• The back pain is:
o Diffuse
o Usually unilateral
o Radiates into the buttock
• The muscle spasm leads to a scoliosis, which reduces when lying
down
Treatment:
• Advise bedrest:
o Lying flat for a lower disc
o Semi-reclining for a high lumbar disc
• Analgesia
• Muscle relaxants
• Physiotherapy
• If the neurological signs are severe and the pain persists and is
severe for >6-10 weeks:
o Microdiscectomy
o Hemilaminectomy
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Acute renal failure (ARF)
Definitions:
• A potentially reversible loss of excretory renal function
• Develops over hours or days
Aetiology:
Can be divided into 3 main areas:
• Pre-renal
• Intrinsic renal
• Post-renal
Pre-renal uraemia:
• Caused by impaired perfusion of the kidneys with blood
• The initial physiological response to kidney hypoperfusion is Na+/
H2O retention:
o Leads to oliguria (<0.5ml/kg/hour)
• If hypoperfusion is not quickly corrected:
o Acute tubular necrosis (ATN) develops
Causes of renal hypoperfusion:

• Shock (MABP <80mmHg):
o Hypovolaemic
o Cardiogenic
o Septic
• Lesser degrees of hypotension + impaired renal autoregulation:
o Age
o Arteriosclerosis
o DM
o ACE inhibitors
o NSAIDs
• Renal vasoconstrictors:
o E.g. radiocontrast agents
o
Measuring CVP is often invaluable in determining if the uraemia is pre-
renal or not
Management of pre-renal uraemia:

• If hypotension is the cause, prompt IV fluid replacement is
essential
• Since pre-renal and intrinsic renal uraemia can coexist and fluid
challenge in the latter situation may lead to volume overload
with pulmonary oedema, careful clinical monitoring is vital
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• BP should be checked regularly

• Signs of raised JVP or of pulmonary oedema should be sought
frequently
Intrinsic renal uraemia:

• This is renal parenchymal disease
• Is responsible for the majority of cases of CRF
The causes of intrinsic renal uraemia can be subdivided into

congenital/hereditary or acquired renal diseases
Congenital/hereditary diseases:
• Developmental abnormalities (hypoplasia)
• Cystic diseases
• Hereditary nephritis
Acquired renal diseases:
• Glomerular:
o Glomerulonephritis (GN)
• Tubulointerstitial:
o Interstitial nephritis
o Myeloma kidney
o Nephrotoxins
• Vascular:
o Inflammation (vasculitis)
o Occlusion (e.g. renal artery stenosis)
Post-renal uraemia:
• Uraemia results from obstruction of the urinary tract at any point
from the calyces to the external urethral orifice
• Important to diagnose as they are readily treatable
• The urinary tract is usually dilated above the level of the
obstruction
• Must affect both kidneys, or a single functioning kidney (or be
below the level of the bladder) to cause renal failure
• May cause complete anuria
Obstructions:
Are 3 types of obstructing lesion:
• Intraluminal (e.g. calculi)
• Intramural (e.g. stricture, tumour)
• Extramural (e.g. tumour, retroperitoneal fibrosis)
Acute tubular necrosis (ATN):
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• Tubuloepithelial cells lose their normal morphology and may

become detached from the tubular basement membrane with the
formation of casts, which block the tubules
• Eventually, the epithelial cells regenerate and renal function is
usually restored
• Urine output in ATN:
• Preceding renal hypoperfusion causes physiological oliguria
(which is often the first clue to the problem)
• Once ATN is established, the patient often remains oliguric
(but this is not invariable)
• Urea and creatinine may continue to rise despite the
production of urine (‘non-oliguric ARF’)
• ATN has an overall mortality of ~50%
Exacerbators of ATN:
• Aminoglycosides (e.g. gentamycin)
• Myoglobin (from muscle breakdown, e.g. crush injury)
• Paracetamol (in overdose)
Clinical features of ARF:

Uraemic symptoms:
• Anorexia
• Nausea
• Pruritis
• Lethargy
Fluid overload/volume dependent HT
Electrolyte disturbances:
• Hyperkalaemia
• Hyperphosphataemia
Metabolic acidosis:
• Loss of acid-base balance
Raised serum urea and creatinine
Acute or chronic uraemia?

Recent record of normal renal function AFR
Normal Hb ARF > CRF
Long history of relevant symptoms CRF > ARF
Tolerating severely deranged biochemistry CRF > ARF
Low Calcium CRF > ARF
Small kidneys on US CRF > ARF
Investigations:
Urine:
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• Dipstick
• Microscopy (RBCs, red cell casts)
• Culture
Serum:
• Urea
• Creatinine
• Calcium
• Phosphate
• Albumin
• ALP
FBC
Blood cultures
Blood levels of nephrotoxic drugs (if appropriate)
Hyperkalaemia:
This is a life-threatening complication owing to the risk of cardiac
dysrhythmias, particularly ventricular fibrillation
On the ECG:
• Tall, tented, T waves
• Widened QRS complexes
• Loss of P waves
Management:
• 10mls 10% calcium gluconate IV (stabilises the myocardium)
• 100mls 50% dextrose IV plus 10U Actrapid IV (drives K+ into
cells)
In many cases, hyperkalaemia will be controlled only by dialysis or
haemofiltration
Pulmonary oedema:
Fluid overload causes a rise in left atrial pressure and leakage of fluid
into the alveolar space
Clinical features:
• Dyspnoea
• Orthopnoea
• Frothy sputum
• Hypoxia
Management:
• Sit patient up
• Give high flow O2
• IV diuretics (e.g. frusemide – note higher doses needed in renal
failure)
• Vasodilators (e.g. IV nitrates)
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• If the diuretics do not induce a diuresis, dialysis or

haemofiltration is necessary
Indications for haemofiltration in ARF:

• Symptoms of uraemia
• Complications of uraemia (e.g. pericarditis)
• Severe biochemical derangement in the absence of symptoms
• Hyperkalaemia not controlled by conservative measures
• Pulmonary oedema not corrected by IV frusemide
• Severe acidosis
• For the removal of drugs causing the ARF (e.g. gentamycin)
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Alcohol abuse
Alcohol dependence syndrome:

There are essential elements to this syndrome:
• A compulsive need to drink
• Is a stereotyped pattern of drinking
• Drinking takes priority over all other activities
• Tolerance to alcohol is altered (however, in the later stages of
dependence, tolerance falls)
• Repeated withdrawal symptoms occur some 8-12 hours after
cessation of drinking (thus, symptoms characteristically appear
on waking)
• There may be relief drinking (i.e. drinking to overcome a
hangover)
• Severely dependent drinkers who drink again after a period of
abstinence are likely to relapse quickly and return to their old
addictive pattern
Extent of the problem:

• At least 300,000 people in the UK have a drink-related problem
(estimated at 5% of men and 2% of women)
• 20% of male admissions to acute medical wards are due to
alcohol-related problems
• About 35% of attendees at A&E have a blood-alcohol level >
legal limit for driving
Clues in the history to help you detect an alcoholic:

• Absenteeism from work
• Frequent attendances for unexplained dyspepsia or GI bleeds
• Hospital admissions for accidents of all kinds
• Fits, ‘turns’ or falls
Signs to help you detect an alcoholic:

• Bloodshot conjunctivae
• Smell of stale alcohol
• Facial appearance resembling Cushing’s syndrome
• Marked tremor
• Signs of alcohol-related diseases
‘At risk’ factors:

• Marital difficulties may conceal heavy drinking or may be used to
justify it
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• Alcohol abusers have 2x as many days off work as their more

sober colleagues
• There may be an affected relative (25% of the male relatives of
alcohol abusers have similar problems)
• High-risk occupations include:
o Company directors
o Salesmen
o Doctors
o Journalists
o Publicans
o Seamen
• There may be associated physical and mental conditions (e.g.
depression)
Common alcohol-related psychological and social problems:

Psychological Social
Depression Marital and sexual difficulties
Anxiety and phobias Family problems
Memory disturbances Child abuse
Delirium tremens Employment problems
Attempted suicide financial difficulties
Pathological jealousy Delinquency and crime
Homelessness
Laboratory markers of alcohol abuse:

• Elevated $-Glutamyl-Transpeptidase ($-GT)
• Elevated mean corpuscular volume (MCV)
• Blood/urinary alcohol levels
Symptoms of alcohol dependence:

• Unable to keep a drink limit
• Difficulty in avoiding getting drunk
• Spending a considerable time drinking
• Missing meals
• Memory lapses
• Restless without drink
• Organizing day around drink
• Trembling after drinking the day before
• Morning retching and vomiting
• Hallucinations, frank delirium tremens
Delirium tremens:
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• This is the most serious withdrawal state and occurs 1-5 days
after alcohol (or barbiturate) withdrawal
• Patients experience:
o Disorientation
o Agitation
o Marked tremor
o Visual hallucinations (e.g. pink elephants)
• Signs include:
o Sweating
o Tachycardia
o Tachypnoea
o Pyrexia
o Dehydration
o Wernicke-Korsakoff syndrome
• If delirium tremens is not treated promptly, death can occur
Management of delirium tremens:

The patient should be hospitalized
• Diazepam 4-100mg for 2 days, then reduced
• Any dehydration/electrolyte imbalance should be corrected
• Any systemic infection should be treated
• B vitamins should be given parenterally
Psychological treatment of alcohol dependence:

• Provision of information concerning safe drinking levels
• Recommendations to cut down where indicated
• Simple support and advice concerning associated problems
• With addictive drinking, the most favoured psychological
treatment is group therapy, which involves identification,
confession, emotional arousal, the implantation of new ideas and
the long-term support by fellow members of the group
Drug treatment of alcohol dependence:

• Long-term treatment with drugs should NOT be prescribed in
those patients who continue to abuse alcohol
• Disulfiram (Antabuse):
• Reacts with alcohol to cause very unpleasant acetaldehyde
intoxication and histamine release
• A daily maintenance dose means that an alcohol-
dependent drinker must wait until the disulfiram is
eliminated from the body before drinking safely
• This drug, therefore, provides a ‘chemical fence’ around
the patient for at least 24 hours
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• Disulfiram implants have been developed that have a

treatment life of about 6 months
Outcome:
• Whereas in the case of non-dependent heavy drinkers the goal
of normal drinking within safe limits can be a very reasonable
one, the alcohol-dependent drinker must be persuaded to
abstain
• Research suggests that up to 40-50% of alcohol-dependent
drinkers are abstinent or drinking very much less up to 2 years
following intervention
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Anaemia of chronic disease
Occurs in patients with:

• Chronic infections (e.g. TB, infective endocarditis, osteomyelitis)
• Chronic inflammatory diseases (e.g. RA, SLE, polymyalgia
rheumatica)
• Malignancies
Pathology:
• Unclear
• There is decreased release of Fe from the bone marrow to
developing erythroblasts
• Inadequate EPO response to the anaemia
• Decreased RBC survival
Treatment:
• Involves treating the underlying disease
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Anxiety disorder
Aetiology:
• Genetic factors:
o Anxiety neurosis occurs in 15% of relatives of affected
patients (compared to 3% of the general population)
• Psychodynamic theory:
o Suggests that anxiety neurosis reflects overwhelming
stress, anxiety and difficulties in the child-parent
relationship in early childhood or even at birth
• Learning theory:
o Regards anxiety as a fear response that has been attached
to another stimulus through conditioning
Types of anxiety:
• More or less continuous:
o Fluctuates to some extent in response to environmental
circumstances
• Panic attacks:
o Sudden and unpredictable attacks of anxiety
o Usually accompanied by severe physical symptoms
• Phobic anxiety:
o Is anxiety triggered by a single stimulus of set of stimuli
that are predictable and that normally cause no particular
concern to others
o E.g. claustrophobia, agoraphobia
• An anxious personality:
o An individual who has a lifelong tendency to experience
tension and anxiety
o Usually have a worrisome attitude towards life and a
constant anticipation of setback and stress
Physical symptoms of anxiety:

• Gastrointestinal:
o Dry mouth
o Difficulty in swallowing
o Epigastric discomfort
o Flatulence
o Diarrhoea (usually frequency)
• Respiratory:
o ‘Hyperventilation syndrome’
o Feeling of chest constriction
o Difficulty in inhaling
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• Cardiovascular:
o Palpitations
o Awareness of missed beats
o Feeling of pain over heart
• Genitourinary:
o Increased frequency
o Failure of erection
o Lack of libido
• Nervous system:
o Tinnitus
o Blurred vision
o Dizziness
o Headache
o Sleep disturbance
Hyperventilation syndrome:
• Panic attacks (fear, terror and impending doom) accompanied by
some or all of the following:
o Dyspnoea
o Palpitations
o Chest pain/discomfort
o Choking sensation
o Dizziness
o Paraesthesiae
o Sweating
• Cause:
o Over-breathing leading to a decrease in PaCO2 and an
increase in arterial pH
• Diagnosis:
o A provocation test – voluntary over-breathing for 2-3
minutes provokes similar symptoms. Re-breathing from a
paper bag relieves them
• Management:
o Explanation and reassurance
o The patient is trained in relaxation techniques and slow
breathing
o The patient is asked to breathe into a closed paper bag
once the symptoms appear
• Psychological symptoms of anxiety:
o Apprehension and fear
o Irritability
o Difficulty in concentrating
o Restlessness
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o Sensitivity to noise
o Depression
o Depersonalization
o Obsessional symptoms
Psychiatric Physical
Depressive illness Hyperthyroidism
Schizophrenia Hypoglycaemia
Pre-senile dementia Phaeochromocytoma
Alcohol dependence
Drug dependence
• Psychological treatment of anxiety neurosis:

o Reassurance
o Relaxation training
o Cognitive behavioural therapy (CBT)
o Individual and group psychotherapy
Drug treatment:
Are 2 types of drugs – those that act on the CNS and those that block
the ANS:
• Centrally acting anxiolytic drugs:
o Benzodiazepines
• ANS blocking drugs:
o E.g. propranolol Involves treating the underlying disease
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Causes of spinal pain
• Mechanical:
o Trauma
o Degenerative disease:
• Spondylosis
• Spondylolithesis
• Spinal stenosis
o Post-surgical back pain
• Inflammatory (non-infective):
o Spondyloarthropathy
o Spondylitis
• Malignant:
o Metastatic disease
o Multiple myeloma
o Primary tumour of bone, spinal cord or nerve root
• Infection:
o Osteomyelitis
o Paravertebral abscess
o Discitis
• Bone disorders:
o Osteoporotic vertebral collapse
o Paget’s disease
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Cerebral infarction
Clinical features:
• The most common stroke is the hemiplegia caused by infarction
in the internal capsule following thromboembolism of a branch of
the middle cerebral artery
• There is weakness of the limbs of the opposite (contralateral)
side which develops over seconds, minutes or hours
• The signs are those of an acute complete contralateral UMN
lesion, including limbs and face
• Aphasia is usual when the dominant hemisphere is affected
• The affected limbs are, at first, flaccid and areflexic
• Headache is unusual and consciousness is NOT lost
• After a variable period (usually several days) the reflexes
recover and become exaggerated and an extensor plantar
response appears
• Weakness is maximal at first, and recovers gradually over the
course of days, weeks or many months
Brainstem infarction:
• Infarction in the brainstem causes complex patterns of
dysfunction depending on the site of the lesion and its
relationship to the cranial nerve nuclei, long tracts and
brainstem connections.
• Lateral medullary syndrome:
o Caused by PICA (posterior inferior cerebellar artery) or
vertebral artery thromboembolism
• Coma:
o Ensues when bilateral brainstem infarction damages the
reticular formation
• Locked-in syndrome:
o Is caused by an upper brainstem infarction
o The patient has a functioning cerebral cortex and is, thus,
aware but cannot move or communicate except by vertical
eye movement
• Pseudobulbar palsy:
o Bilateral infarction of the lower cranial nerve nuclei
o Produces weakness and poverty of movement of the
tongue and pharyngeal muscles
o Emotional lability (inappropriate laughing or crying) often
accompanies pseudobulbar palsy
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Features of a brainstem infarction:

Clinical feature Structure involved
Hemi/tetraparesis Corticospinal tracts
Sensory loss Medial lemniscus/Spinothalamic tracts
Facial numbness 5th nerve nuclei
Facial weakness 7th nerve nuclei
Nystagmus/vertigo Vestibular connections
Dysphasia/dysarthria 9th and 10th nerve nuclei
Horner’s syndrome Sympathetic fibres
Altered consciousness Reticular formation
Clinical signs in the lateral medullary syndrome:

• Ipsilateral:
o Facial numbness (CN V)
o Diplopia (CN VI)
o Nystagmus
o Ataxia
o Horner’s syndrome
o Lesions of CNs IX and X
• Contralateral:
o Spinothalamic sensory loss
Lacunar infarction:
• Lacunes are small (<1.5cm3) areas of infarction seen on MRI or
at autopsy
• HT is commonly present
• Minor strokes are syndromes caused, typically, by single lacunar
infarcts. Examples include:
o Pure motor stroke
o Pure sensory stroke
o Sudden unilateral ataxia
o Sudden dysarthria
• Lacunar infarction is often also ‘symptomless’
Hypertensive encephalopathy:
• This describes various neurological sequelae of severe accelerate
HT with occlusion of small arteries
• Leads to:
o Severe headaches
o TIA
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o CVA
o Subarachnoid haemorrhage (rarely)
Multi-infarct dementia:
• Multiple lacunes or larger infarcts cause the picture of
generalized intellectual loss that is seen in patients with
advanced cerebrovascular disease.
• Signs include:
o Dementia
o Pseudobulbar palsy
o Shuffling gait with small steps
Examination:
• In addition to neurological examination, particular care should be
taken to find a possible source of embolus, e.g:
o Carotid bruit
o Valve lesion
o Evidence of endocarditis
• One must also determine whether HT or postural hypotension is
(or has been) present
Immediate management of a CVA:
• In practice, many TIAs and mild CVAs can be managed at home
and specialist advice sought when necessary
• Patients admitted to stroke wards tend to fare better than those
admitted to a general ward
• Thrombolytic agents (such as tissue plasminogen activator) have
sometimes appeared promising in the immediate treatment of
ischaemic CVA, but are not in general use
Preliminary investigations:
Test Potential yield
Urinalysis, blood glucose Diabetes mellitus
Hb, platelets Polycythaemia
WCC Infection (e.g. endocarditis)
ESR, CRP Possible arteritis
Serology for syphilis Possible neurosyphilis
CXR Neoplasm
ECG Recent infarct, dysrhythmias
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Further investigations of TIA and CVA:

• CT and MRI:
o Location of lesion
o Distinguishes between ischaemic and haemorrhagic lesion
• May reveal unexpected mass lesions, e.g:

o Tumour
o Subdural haematoma
o Abscess
• Carotid doppler and duplex scanning:
o Screening for arterial stenosis and occlusion
• Angiography:
o Very valuable in anterior circulation TIAs to diagnose
surgically accessible arterial stenoses (mainly internal
carotid stenoses)
o There is a high probability of finding a carotid stenosis
when there is a loud localised carotid bruit in the neck
Long-term medical management:

• Antihypertensive therapy:
o The control of HT is the single most important factor in the
primary prevention of stroke
o If the HT is sustained, it must be lowered slowly to avoid a
sudden fall in cerebral perfusion pressure
• Antiplatelet therapy:
o E.g. soluble aspirin 75mg OD PO
o Inhibits COX, which converts arachidonic acid to PGs and
thromboxanes
o The predominant therapeutic effect is to reduce platelet
aggregation
• Anticoagulants:
o Heparin and warfarin should be used when there is:
• Atrial fibrillation
• Other paroxysmal dysrhythmias
• Cardiomyopathies
• Valve lesions (non-infected)
• Are potentially dangerous in the 2 weeks following
cerebral infarction because of the risk of provoking
cerebral haemorrhage
Surgical approaches to stroke:

• Internal carotid endarterectomy:
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o This is considered in TIA or CVA patients who are shown to

have internal carotid artery stenosis that narrows the
arterial lumen by >70%
o In these patients, the risk of further TIA or CVA is reduced
by ~75% following successful surgery
o Mortality rate of ~3%
Prognosis:
• Between 30-50% of patients who die, do so in the first month
following a stroke
• A poor outcome is likely when the following triad is present:
o Coma
o A defect in conjugate gaze
o Severe hemiplegia
• Recurrent strokes are common (10% in the first year)
• In addition, many patients die subsequently from a MI
• Of initial stroke survivors, 30-40% are alive after 3 years
• Of those who survive a stroke:
o 30% return to independent mobility
o 30% have severe disability, requiring permanent
institutional care
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Cerebrovascular disease and stroke
Epidemiology:
• Stroke is the 3rd most common cause of death in developed
countries
• 200 per 100,000 population die per year from strokes in the UK
• The death rate following a stroke is ~25%
Definitions:
• Stroke (cerebrovascular accident, CVA):
o A focal neurological deficit due to a vascular lesion
o Usually of rapid onset
o Lasts longer than 24 hours
• Completed stroke:
o Implies that the neurological deficit has reached its
maximum
o Usually within 6 hours of onset
• Stroke in evolution:
o Describes evolving and deteriorating symptoms and signs
o Usually during 24 hours from the onset
• Minor stroke:
o Patients recover without a significant deficit, usually within 1
week
• Transient ischaemic attack (TIA):
o A focal neurological deficit lasting from a few seconds up to a
maximum of 24 hours
o There is complete clinical recovery
o Usually of sudden onset
o TIAs have a tendency to recur, and to herald thromboembolic
stroke
Pathophysiology of a completed stroke:

• This is usually caused by one of 4 principal mechanisms:
o Arterial embolism from a distant site
o Atheromatous carotid or vertebral artery occlusion
o Atheromatous arterial thrombosis within a cerebral vessel
o Haemorrhage into the brain
• Less commonly, other processes cause the clinical picture of
stroke:
o Venous infarction
o Dissection of the carotid or vertebral arteries
o Air embolism
o Multiple sclerosis – a plaque of demyelination
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o Mass effects of an expanding lesion, e.g:

• Brain tumour
• Abscess
• Subdural haematoma
Risk factors for stroke:

• Hypertension
• Smoking
• Obesity
• Hyperlipidaemia
• Race (more common in Afro-Caribbeans in the UK)
• Family history
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Chronic renal failure (CRF)
Causes of CRF:
• Congenital/inherited:
o Polycystic kidney disease
o Congenital hypoplasia
• Glomerular disease:
o SLE
o DM
o Amyloidosis
o Vasculitis
• Vascular disease:
o Arteriosclerosis
o Microscopic polyarteritis
o SLE
o Systemic sclerosis
• Tubulointerstitial disease:
o Tubulointerstitial nephritis
o Reflux nephropathy
o TB
o Schistosomiasis
• Urinary tract obstruction:
o Calculi
o Prostatic disease
o Pelvic tumours
o Retroperitoneal fibrosis
Symptoms of CRF:
• When serum urea >40mmols/L:
o Anorexia
o Insomnia
o Nocturia/Polyuria
o Pruritus
o Nausea/vomiting
o Diarrhoea
o Paraesthesiae/tetany (due to polyneuropathy/
hypocalcaemia)
o Bone pain (due to metabolic bone disease)
o Peripheral/pulmonary oedema
o Anaemia
o Amenorrhoea in women
o Erectile dysfunction in men
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• When serum urea >50-60mmols/L:

o Mental slowing
o Clouding of consciousness
o Seizures
o Myoclonic twitching
Examination:
• Short stature – in patients who have had CRF in childhood
• Pallor – due to anaemia
• Increased photosensitive pigmentation – may make the patient
look misleadingly healthy
• Brown discolouration of the nails
• Scratch marks – due to uraemic pruritus
• Signs of fluid overload
• Pericardial friction rub
• Flow murmurs:
o Mitral regurgitation - due to mitral annular calcification
o Aortic/pulmonary regurgitation – due to volume overload
Investigations:
• Urinalysis:
o Haematuria (e.g. GN)
o Proteinuria (e.g. UTI, DM, if heavy it suggests glomerular
disease)
o Glycosuria with normal BM is common in CRF
• Urine microscopy:
o WBCs in the urine indicate active bacterial urinary infection
o Eosinophiluria:
• Allergic tubulointerstitial nephritis
• Cholesterol embolism
o Red cell casts strongly suggest GN
• Urine biochemistry:
o 24 hour creatinine clearance to assess the severity of
CRF
o Urine osmolality
• Serum biochemistry:
o Urea and creatinine
o Serum electrophoresis to detect myeloma
o Extreme elevation of CK and hyperkalaemia suggest
rhabdomyolysis
• Haematology:
o Eosinophilia:
• Vasculitis
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• Allergic tubulointerstitial nephritis

• Cholesterol embolism
o Raised viscosity or ESR:
• Myeloma
• Vasculitis
o Haemolysis indicates haemolytic uraemic syndrome
• Immunology:
o Autoantibody screening:
• SLE
• Scleroderma
• Wegener’s granulomatosis
• Microscopic polyarteritis
• Goodpasture’s syndrome
• Microbiology:
o Urine culture
• Radiological investigations:
o Renal US (for renal size and to exclude hydronephrosis)
o Plain AXR (renal calculi)
• Renal biopsy:
o Should be considered in every patient with unexplained
renal failure and normal-sized kidneys, unless there are
strong contraindications
Complications of CRF:
• Anaemia
• Renal osteodystrophy
• Skin disease
• GI complications
• Metabolic abnormalities
• Endocrine abnormalities
• CNS disturbances
• ANS disturbances
• PNS disturbances
• CVS disease
Anaemia:
Anaemia is present in the great majority of patients. Several factors
have been implicated:
• EPO deficiency (most important)
• Bone marrow toxins (retained in renal failure)
• Bone marrow fibrosis (secondary to hyperparathyroidism)
• Haematinic deficiency (Fe, folate B12)
• Haemolysis
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• Increased blood loss (e.g. occult GI haemorrhage)

• ACE inhibitors (interfere with endogenous EPO release)
Renal osteodystrophy:
• Decreased production of 1!-hydroxylase results in decreased
production of 1,25(OH)2D3
• Decreased production of 1,25(OH)2D3 leads to secondary
hyperparathyroidism
• The increased PTH causes:
o Bone resorption
o Hypercalcaemia
o Raised serum ALP
Skin disease:
• Pruritus (itching) is common in severe renal failure and is
caused (mainly) by the retention of nitrogenous waste products
of protein catabolism
• Other causes of pruritus include:
o Hypercalcaemia
o Hyperphosphataemia
o Hyperparathyroidism (even if calcium and phosphate
levels are normal)
o Fe deficiency
GI complications:
• Decreased gastric emptying and increased risk of reflux
oesophagitis
• Peptic ulceration
• Acute pancreatitis
• Constipation (especially patients on CAPD)
Metabolic abnormalities:
• Gout
• Decreased insulin catabolism/excretion (therefore, dose must be
decreased in insulin-dependent diabetics)
• Dyslipidaemia
Endocrine abnormalities:
• Hyperprolactinaemia
• Increased LH levels in both sexes
• Decreased serum testosterone
• Oligomenorrhoea/amenorrhoea
• Decreased thyroid hormone levels
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CNS abnormalities:
• Severe uraemia causes:
o Depressed cerebral function
o Asterixis
o Tremor
o Myoclonus
ANS abnormalities:
• Increased circulating levels of catecholamines
• Impaired baroreceptor sensitivity
• Impaired efferent vagal function
PNS abnormalities:
• ‘Restless legs’ syndrome
• Median nerve compression in the carpal tunnel is common
CVS disease:
• Increased risk of:
o MI
o Cardiac failure
o Sudden cardiac death
o Stroke
• Pericarditis is common and occurs in 2 clinical settings:
o Uraemic pericarditis:
• Haemorrhagic pericardial effusion and atrial
arrhythmias are often associated
• Is a danger of pericardial tamponade
• Anticoagulants should be use with caution
o Dialysis pericarditis
Management of CRF:
• BP control:
o Aim for around 130/80mmHg
o ACE inhibitors are believed to be the most beneficial in
renal failure
• Hyperkalaemia:
o Usually responds well to dietary restriction of potassium
o Drugs which cause potassium retention should be stopped
• Acidosis:
o Correction of acidosis helps to correct hyperkalaemia in
CRF and may also decrease muscle catabolism
o Sodium bicarbonate supplements are often effective, but
may cause oedema and HT (owing to ECF expansion)
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• Control of calcium and phosphate levels:

o Hypocalcaemia and hyperphosphataemia should be treated
aggressively, preferably with regular (e.g. 3 monthly)
measurements of serum PTH to assess how effectively
hyperparathyroidism is being suppressed
o Oral calcium carbonate acts as a calcium supplement and
also reduces the bioavailability of dietary phosphorus
• Dietary restrictions:
o In advanced renal disease, reduction of protein lessens the
amount of nitrogenous waste products generated, and this
may delay the onset of the symptoms of uraemia
o Most patients with renal impairment will require a diet
restricted in sodium and potassium
o Prolonged dietary protein restriction should be avoided. It
is preferable to commence renal replacement therapy a
little earlier than to cause malnutrition
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Cluster headache
(Migrainous neuralgia, Horton’s neuralgia)
Epidemiology:
• Peak age 30s-40s
• Men > women
Clinical features:
• Recurrent bouts of excruciating pain that wake the patient at
night and are centred around one eye
• Can be precipitated by alcohol
• Pain rises to a crescendo over ~30 minutes and lasts for several
hours
• Vomiting occurs
• One side of the face and nostril feel congested
• A transient ipsilateral Horner’s syndrome is common during the
attack
Management:
• Despite the very severe pain, there are no serious sequelae
• Attacks recur at intervals over several years but tend to
disappear over the age of 55 years
• Analgesics during the attack are NOT effective
Prophylaxis:
• Lithium carbonate (400-1200mg daily)
• Inhalation of oxygen can help abort an attack
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Delirium
(acute confusional state)
Consciousness:
• Impaired, with onset over hours or days
• Can be described as either:
o A mild impairment of thinking, attending, perceiving and
remembering
o A mild global impairment of cognitive processes associated
with a reduced awareness of the environment
•Conscious level fluctuates throughout the day with confusion
typically worsening in the late afternoon and at night
Disorientation:
• Disorientation in time (does not know the time, day or year) and
place (often more marked) is the rule
Behaviour:
• Either:
o Inactivity
o Quietness
o Reduced speech
• Or:
o Hyperactivity
o Noisiness
o Irritability (these patients can be very disruptive)
Thinking:
• Slow and muddled
• Commonly with ideas or delusions (e.g. accusing staff of plotting
against them)
Perception:
• Disturbed
• Often with illusions and hallucinations (especially visual but also
auditory and tactile)
Mood:
• Lability
• Anxiety
• Perplexion
• Fear
• Agitation
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• Depression
Memory:
• Impaired during delirium and on recovery
• Amnesia is usual
• If agitated, consider anxiety
• If delusions or hallucinations, consider primary mental illness
(e.g. schizophrenia)
• Remember that in hospitalized ill patients with no psychiatric
history, mental illness is rare and delirium is common
Causes:
• Systemic infection (e.g. pneumonia, UTI)
• Drugs (e.g. opiates, anticonvulsants, recreational)
• Alcohol/drug withdrawal
• Metabolic (e.g. hypoglycaemia, uraemia)
• Hypoxia (respiratory or cardiac failure)
• Vascular (CVA, MI)
• Intracranial infection (e.g. encephalitis, meningitis)
• Raised ICP/space-occupying lesions
• Epilepsy (status epilepticus, post-ictal states)
• Head injury (especially subdural haematoma)
• Nutritional (e.g. thiamine, B12 deficiency)
Management:
1. Identify and treat the underlying cause
2. Reduce distress and prevent accidents
3. Nurse in a moderately lit, quiet room with the same staff in
attendance (minimizes confusion) where the patient can be
watched closely
4. Minimize medication (especially if sedative)
If the patient becomes agitated and disruptive, some sedation may be

necessary:
• Use a major tranquilizer (e.g. haloperidol 0.5-2mg IM/PO)
• Wait 20 mins to judge effect as further doses can be given if
needed
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Dementia
Dementia is a syndrome, with many causes, of global impairment of

cognition in clear consciousness
The patient:
• The key to diagnosis is a good history (usually requiring the help
of a spouse, relative or friend) of progressive impairment of
memory and cognition together with objective evidence of such
impairment
• The impairment should go back at least several months, and
usually several years
• Typically, the patient has become increasingly forgetful, and has
carried out the normal tasks of daily living (e.g. cooking,
shopping) with increasing incompetence:
o E.g. going to the butchers to buy sausages 6 times a day
and then being baffled as to why there was a great mound
of sausages in the kitchen
• Sometimes the patient appears to have changed personality
(e.g. by becoming uncharacteristically rude and aggressive)
• For objective evidence, carry out the mini-mental state
examination (MMS exam – see below)
Commonest causes:
• Alzheimer’s disease
• Vascular dementia (~25% of all cases):
o Essentially multiple small strokes
o Is usually evidence of vascular pathology (e.g. HT,
previous CVAs)
Rarer causes:
• Chronic alcohol/barbiturate abuse
• Huntington’s disease
• CJD
• Parkinson’s disease
• Pick’s disease
• HIV
Ameliorable causes:
• Hypothyroidism
• B12/Folate deficiency
• Syphilis
• Thiamine deficiency
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• Operable cerebral tumour

• Subdural haematoma
Mini-mental state examination (MMS exam):

If dementia is suspected, test memory and other intellectual abilities
formally. The MMS exam is one of many similar tests. It has been
more fully studied than most.
• What day of the week is it? [1 point]
• What is the date today? Day, month, year [1 point each]
• What is the season? [1 point]
• What country are we in? [1 point]
• What is the name of this town [1 point]
• What are 2 main streets nearby [1 point]
• What floor of the building are we on? [1 point]
• What is the name of this place [1 point]
• ‘I am going to give you a piece of paper. When I do, take it in
your right hand. Fold the paper in half with both hands and put
the paper down on your lap’ [1 point for each of the 3 actions]
• Show a pencil and ask what it is called [1 point]
• Show a wristwatch and ask what it is called [1 point]
• ‘I am going to say something and I would like you to repeat it
after me: No ifs, ands, or buts’ [1 point]
• ‘Please read what is written here and do what it says’ (show the
patient a piece of card with CLOSE YOUR EYES written on it [1
point]
• ‘Write a complete sentence on this sheet of paper’ [1 point]
• ‘Here is a drawing. Please copy the drawing’. Show the picture of
2 pentagons intertwined [1 point]
• ‘I am going to name 3 objects. After I have finished saying all 3,
I want you to repeat them. Remember what they are because I
am going to ask you to name them again in a few minutes’ e.g.
APPLE, TABLE, PENNY [1 point each]
• ‘Now I would like you to take 7 away from 100. Now take 7 away
from the number you get. Now keep subtracting until I tell you
to stop’. Score 1 point each time the difference is 7, even if the
previous answer was incorrect. Go on for 5 subtractions [5
points]
• ‘What were the 3 objects I asked you to remember a little while
ago?’ [1 point each object]
The maximum score is 30. 28-30 does not support the diagnosis of
dementia. A score of 25-27 is borderline. <25 suggests dementia but
consider also acute confusional state an depression
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Investigations:
• Urine dipstick
• FBC/blood film
• ESR
• U&Es
• LFTs
• Ca2+
• Syphilis serology
• B12/folate
• TFTs
• CXR
• CT scan (atypical history, young patient, head injury)
• EEG
Management:
There are specific treatments for Alzheimer’s, HIV, myxoedema and
dementia associated with a low B12 and folate
• Treat concurrent illnesses (these may contribute significantly to
confusion)
• In most people the dementia remains and will progress
• The approach to management is that of any chronic illness
• Prepare the spouse for the day when the patient no longer
recognises loved ones
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Depression
Depression is classically divided into endogenous depression and

reactive depression, although the validity of this classification is
doubtful
Endogenous depression – principle criteria:

• Pervasive and unresponsive depression
• Early morning waking
• Diurnal variation of mood (worse in the morning)
• Profoundly depressive ideas (e.g. guilt, suicidal feelings)
• The lack of an obvious precipitating cause
• A stable pre-morbid personality
Reactive depression – principle causes:

• A fluctuating depression responsive to environmental change
• Self-pity rather than self-blame
• A clear precipitating cause
• A vulnerable or predisposed personality
• Absence of the criteria of endogenous depression
Aetiology:
• Genetic:
o 10-15% of first-degree relatives have an affective disorder
(risk in general population is 1-2%)
o 68% of monozygotic twins are concordant for manic-
depressive disorder
• Biochemical:
o Imbalance in NTs (e.g. monoamine NTs are depleted in
depression
o Loss of diurnal rhythm of plasma cortisol
o Hormonal factors (e.g. depression more common after
child-birth and post-hysterectomy)
• Psychological:
o Maternal deprivation
o Learned helplessness
• Social:
o Stressful events (e.g. bereavement, loss of a job)
o Vulnerability factors (e.g. lack of a confiding, intimate
relationship)
Clinical features of depression:

Mood Depressed, miserable, unhappy
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Talk Impoverished, slow, monotonous, incomplete

Energy Lacking, retarded, apathetic
Ideation feelings of futility, guilt, suicidal thoughts
Cognition Verbal memory impaired, pseudo-dementia
Physical Early waking, weight loss, loss of libido, fatigue
Behaviour Retardation/agitation, poverty of movement
Hallucinations Auditory – often abusive, hostile, critical
Differential diagnosis of depression:

• Systemic physical illness:
o Malignancy
o Hypothyroidism
o Hyperparathyroidism
o Infection and post-infection
o CCF
o Cerebral ischaemia
• Drug-induced depression:
o Corticosteroids
• Hormones:
o Oestrogen
o Progesterone
• Hypotensive agents:
o Reserpine
o Methyldopa
o Clonidine
• Anti-parkinsonian drugs:
o Levodopa
o Amantidine hydrochloride
• Anti-cancer drugs:
o Vincristine
• Psychiatric disorders:
o Schizophrenia
o Alcohol abuse
o Drug abuse
o Anxiety neurosis
o Dementia
Drug therapy in the treatment of depression:

• Tricyclic antidepressants (TCAs)
• Selective serotonin reuptake inhibitors (SSRIs)
• Monoamine oxidase inhibitors (MAOIs)
Tricyclic antidepressants (TCAs):
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• e.g. Imipramine, amitryptyline

• The 2 above drugs are given by mouth in initial doses of
25-75mg daily, building up over a week to 150-200mg daily
• Full therapeutic effects can take up to 2-3 weeks to occur
• Act by potentiating the action of monoamines, serotonin and
noradrenaline by inhibiting their reuptake into nerve terminals
• Side-effects:
o Anticholinergic effects:
• Dry mouth
• Constipation
• Tremor
• Blurred vision
• Urinary retention
• Postural hypotension
o Cardiac effects:
• ECG changes
• Arrhythmias
o Convulsant activity:
• Lowered seizure threshold
o Other effects:
• Weight gain
• Sedation
• Mania
Selective serotonin reuptake inhibitors (SSRIs):

• E.g. Fluoxetine (Prozac)
• Fewer side-effects than TCAs
• Faster onset
• Only increase concentrations of serotonin
• Common side-effects:
o Nausea
o Headache
o Insomnia
o Diarrhoea
Monoamine oxidase inhibitors (MAOIs):

• E.g. phenelzine (30-60mg daily)
• Act by inhibiting the intracellular enzymes monoamine oxidase A
and B, leading to an increase of NA, DA and 5-HT in the brain
• Onset of action is within 24-48 hours
• Side-effects:
o Increased appetite/weight gain
o Insomnia
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• MAOIs also produce a hypertensive crisis with foods containing

tyramine or dopamine (therefore, the diet needs to be
restricted):
o Tyramine is present in cheese, marmite and red wine
o Dopa is present in broad beans
o The tyramine reaction is treated with IV phentolamine ("-
adrenoceptor antagonist)
Electroconvulsive therapy (ECT) for depression:

• This is the most rapidly acting of the available physical
treatments of depression. It is treatment of first choice in those
cases where:
o The patient is dangerously suicidal
o A delay in treatment represents a serious risk to health
o The patient is refusing food and drink
o The patient is in a depressive stupor
• The treatment involves the passage of an electric current
(usually 80V for a duration of 100-300ms) across 2 electrodes
applied to the anterior temporal areas of the scalp:
• Patient is anaesthetized (usually with thiopentone 125-150mg)
• Patient receives a muscle relaxant (usually suxamethonium
30-50mg)
• A course of 6-8 treatments over 3 weeks has been shown to be
beneficial
• ECT is controversial but it must be stated that it is extremely
safe with very few long-term side effects

• 65-75% of patients admitted to hospital with a major depressive
illness will suffer at least 1 relapse requiring hospital admission
• Estimated that 15-20% of depressives never fully recover
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Folate deficiency
Causes of folate deficiency:

• Inadequate intake (major cause)
• Excess utilization (physiological):
o Pregnancy
o Lactation
• Excess utilization (pathological):
o Excess RBC production (e.g. haemolysis)
o Malignancy
o Inflammatory disease
o Dialysis
• Malabsorption:
o Small bowel disease
• Antifolate drugs:
o Anticonvulsants (e.g. phenytoin)
o Methotrexate
o Trimethoprim
Clinical features:
• Asymptomatic
• Symptoms of anaemia
• Symptoms of the underlying cause
• Glossitis
• Neuropathy does not occur
Investigations:
• Haematological findings show a megaloblastic anaemia:
o MCV >96fl
o Macrocytosis
o Hypersegmented neutrophils (with >6 nuclear lobes)
o Leucopenia/thrombocytopenia if severe
• Low serum folate
Treatment:
• 5mg of folic acid daily PO with an improvement in the clinical
picture within 48 hours
• Prophylactic folic acid (400µg) is recommended for all women
planning a pregnancy
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Giant cell arteritis

(cranial/temporal arteritis)
Pathology:
• Is a granulomatous arteritis of unknown aetiology
• Affects mainly those >60 years of age
• Other forms of arteritis can present with similar features, e.g:
o SLE
o Polyarteritis nodosa
• Very closely related to polymyalgia rheumatica (both can occur
in the same patient)
Clinical features:
• Headache:
o Pain is felt over the inflamed artery (superficial, temporal
or occipital)
o Touching the skin over the artery causes pain (e.g.
brushing hair)
• Facial pain:
o Jaw, face and mouth pain occurs
o Worse on eating (jaw claudication)
o Opening the mouth and protruding the tongue is difficult
• Visual problems:
o 25% of untreated cases go blind (due to inflammation/
occlusion of the ciliary and/or central retinal artery)
• Systemic features:
o Polymyalgia rheumatica (occurs in 50% of cases):
• Generalized muscle pains
• Proximal limb girdle pain and tenderness
• NO joint effusions
• Weight loss
• Sweating
• Malaise
Investigations:
• Raised ESR
• Raised CRP
• Albumin reduced (occasionally)
• Diagnosis is confirmed by a biopsy of a superficial temporal
artery
Treatment:
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• High dose steroids should be started immediately (e.g.

prednisolone 60-100mg daily), even before the biopsy
• The dose is reduced as the ESR falls
• It is usually possible to stop steroid therapy after some months
to several years
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Guillain-Barre syndrome (GBS)
Pathogenesis:
• A demyelinating neuropathy
• Has an autoallergic basis
• Follows 1-3 weeks after infection (that is often trivial and rarely
identified)
• Campylobacter infection, however, is a recognised cause of GBS
Clinical features:
• Weakness of distal limb muscles and/or distal numbness
ascending over several days or over a period of up to 3 weeks
• In mild cases, there is little disability before spontaneous
recovery begins
• 20% of cases have complete paralysis, including respiratory
muscles
• Weakness, areflexia and sensory loss are found in an ascending
pattern from fingers to toes
Diagnosis:
• Established on clinical grounds
• Confirmed by nerve conduction studies, which show:
o Slowing of conduction
o Prolonged distal motor latency
• Raised CSF protein level
Course and management:

• It is essential (even in the early stages) that particular attention
be paid to measuring ventilatory function (VC and blood gases)
• Prolonged assisted ventilation may be necessary
• Subcutaneous heparin should be given to reduce the risk of
venous thrombosis
• High doses of $-globulin reduces the severity and duration and
should be given to all patients
• Recovery, though gradual over many months, is usual but may
be incomplete
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Haemodialysis
Basic principles:
• Blood is pumped from the patient through an array of
semipermeable membranes, which bring the blood into close
contact with diasylate, flowing counter-current with the blood
• The plasma biochemistry changes towards that of the diasylate
owing to diffusion of molecules down their concentration
gradients
• Blood flow during dialysis is usually 200-300ml per minute and
the diasylate flow is usually 500ml per minute
Access for haemodialysis:

• Adequate dialysis requires a blood flow of at least 200ml per
minute
• The most reliable long-term way of achieving this is surgical
construction of an arteriovenous fistula using the radial or
brachial artery and the cephalic vein
• This results in distension of the vein and thickening
(‘arterialisation’) of its wall, so that after 6-8 weeks, large-bore
needles may be inserted to take blood to and from the dialysis
machine
• If dialysis is needed immediately, a large-bore double-lumen
cannula may be inserted into a central vein
• Stenosis of the subclavian vein is common and the jugular route
is, in general, preferred
Complications:
• Hypotension during dialysis (major problem)
• Haemolytic reactions
• Air embolism
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Haemofiltration
Haemofiltration:
• This involves removal of plasma water and its dissolved
constituents (e.g. K+, Na+, urea and PO43-) by convective flow
across a high-flux semi-permeable membrane, and replacing it
with a solution of the desired biochemical composition
• Can be used for both acute and chronic renal failure
• High volumes need to be exchanged in order to achieve
adequate small molecule removal:
o CRF - 22L exchange 3 times a week
o ARF – 1L per hour
• Expensive and not often used in patients with ESRF
• May be cost-effective in treating ARF
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Hypertension
Definition:
• Very hard to define as it is varies from individual to individual
and within individuals
• In a patient <50 years: 140/90mmHg
• In patient >50 years: 165/95mmHg
• Hypertension can be either primary (‘essential) or secondary
Primary (‘essential’) hypertension:

• Unknown aetiology
• >90% of cases of hypertension are primary
Secondary hypertension:
• Renal causes:
o >80% of the cases of secondary HT
o Chronic glomerulonephritis
o Polycystic kidney disease
o Renovascular disease
• Endocrine causes:
o Conn’s syndrome (hypersecretion of aldosterone)
o Adrenal hyperplasia
o Phaeochromocytoma
o Acromegaly
• CVS causes:
o Coarctation of the aorta
• Drugs:
o OCP
o Steroids
Complications of hypertension:
• Cerebrovascular disease (e.g. CVA)
• Coronary artery disease
• Renal failure
• Peripheral vascular disease
Malignant hypertension:
• Is said to occur when BP rises rapidly and is considered with
severe HT (diastolic BP >140mmHg)
• Are changes in the renal circulation resulting in rapidly
progressive renal failure, proteinuria and haematuria
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• High risk of cerebral oedema and haemorrhage

• Marked changes in the retinal vessels (characteristic of
malignant HT)
• Without effective treatment, there is a 1 year survival of <20%
Investigations:
• Routine investigation of the hypertensive patient should include:
o CXR
o ECG
o Echocardiogram
o Urinalysis
o Fasting blood for lipids and glucose
o U&Es
General treatment measures for HT:

• Weight reduction
• Decrease alcohol consumption
• Salt restriction
• Regular exercise
• Cessation of smoking
Drug therapy:
• The decision to commence specific drug therapy should usually
be made only after a careful period of assessment (of up to 6
months) with repeated measurements of BP
Diuretics:
• Thiazide diuretics:
o E.g. bendrofluazide (2.5-5mg daily)
o Duration of 12-24 hours
o Side-effects include:
• Hyperlipidaemia
• Hyperglycaemia
• Hyperuricaemia
• Hypokalaemia
• Loop diuretics:
o E.g. Frusemide (40mg daily)
o Have a hypotensive effect and are not routinely used in
essential HT
• Potassium-sparing diuretics:
o E.g. Spironolactone (50-200mg daily) or amiloride
(5-10mg daily)
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o Not effective when used on their own, need to be used in

combination with another diuretic
"-blockers:
• Decrease force of cardiac contraction
• Reduce renin secretion
• Reduce anxiety (as anxiety increases BP)
There are major differences between the "-blockers:

• Cardioselectivity:
o Some have less effect on B2-receptors
o E.g. atenolol, bisoprolol
• Intrinsic sympathomimetic activity:
o Some agents have partial agonist activity and cause less
Bradycardia
o E.g. pindolol, oxprenolol
• Lipid solubility:
o The agents that are less lipid-soluble are less likely to
cause CNS effects
o E.g. atenolol
"-blockers side-effects:
• Bradycardia
• Bronchospasm (avoid in asthmatics)
• Cold extremities
• Fatigue
• Nightmares
ACE inhibitors:
• E.g. captopril (50-150mg daily in divided doses), enalapril
(10-20mg daily)
• Block production of angiotensin II (potent vasoconstrictor)
• Inhibit degradation of bradykinin (potent vasodilator)
• Side-effects include severe hypotension on first administration
and a dry cough (caused by the accumulation of bradykinin)
Angiotensin II receptor antagonists:

• E.g. losartan (50-100mg daily)
• Very similar actions to ACE inhibitors except they have no effect
on bradykinin (therefore, do not cause a cough)
• Currently used for patients who cannot tolerate ACEIs because of
a persistent cough
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Calcium channel blockers:

• E.g. amlodipine (5-10mg daily), nifedipine (10-20mg TID)
• Reduce BP by causing arteriolar vasodilatation
• Major side-effects include:
o Headache
o Sweating
o Palpitations
o Flushing
• Side-effects can be lessened by the co-administration of a B-
blocker
!-blockers:
• E.g. doxazosin (1-4mg daily)
• Cause postsynaptic !1-receptor blockade
• Results in vasodilatation and a fall in BP
Drug selection:
• Treatment is normally commenced with a single agent
(monotherapy)
• The target of therapy should be to maintain:
o Diastolic BP in the range 80-90mmHg
o Systolic BP <160mmHg
• Conventionally, thiazide diuretics and B-blockers have been used
as a first line treatment, with the other agents reserved for those
in whom these prove ineffective
Management of severe/malignant Hypertension:

• Admitted to hospital for immediate treatment
• Unwise to reduce the BP too rapidly as this may lead to
myocardial/cerebral/retinal or renal infarction
• The aim is to reduce diastolic BP to 100-110mmHg over 24-48
hours
• The BP can then be normalised over the next few days
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Intracerebral haemorrhage
Aetiology:
• Intracerebral haemorrhage is the cause of ~30% of strokes (the
remainder being due to acute ischaemic events)
• The principal cause of intracerebral haemorrhage is rupture of a
microaneurysm (Charcot-Bouchard aneurysms, 0.8-1mm in
diameter)
• Occurs typically in patients with HT
• There are well-defined sites for the rupture:
o Basal ganglia
o Pons
o Cerebellum
o Subcortical white matter
• Saccular (Berry) aneurysms and arteriovenous malformations
also bleed into the brain, but cause principally subarachnoid
haemorrhage
Haemorrhage vs. ischaemia:

• Clinically, there is no reliable way of distinguishing between
intracerebral haemorrhage and thromboembolic infarction (as
both produce a sudden focal deficit)
• Intracerebral haemorrhage, however, tends to be more dramatic
and accompanied by a severe headache
• Intracerebral haemorrhage is more likely to cause coma than
thromboembolic stroke
• Intracerebral haemorrhage is visualised reliably by imaging
almost immediately (cf. infarction, which takes time)
Management:
• The general management is as for cerebral infarction, although
the immediate prognosis is worse
• Urgent neurosurgical evacuation of the clot should be considered
when an intracerebral haematoma behaves as an expanding
mass, causing:
o Deepening coma
o Coning
• Antiplatelet drugs and anticoagulants are contraindicated
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Iron-deficiency anaemia
Fe deficiency is the commonest cause of anaemia worldwide
Normal daily Fe balance:

Losses:
• Both sexes: 1mg
• Menstruating women: 1.5mg
• Pregnant women: 1.5mg
Requirements:
• Children/adult males/post menopausal women: 1mg
• Women of child-bearing age: 2-3mg
• Adolescents: 2-3mg
Causes of Fe deficiency:
• Blood loss (e.g. menstruation)
• Increased demands (e.g. growth, pregnancy)
• Decreased absorption (e.g. bowel resection)
• Inadequate intake
Clinical features specific to iron-deficiency anaemia:

• Brittle nails
• Koilonychia (spoon-shaped nails)
• Smooth tongue
• Angular stomatitis
• Glossitis
Investigations:
• FBC and film:
o Decreased MCV (microcytosis)
o Decreased MCH (hypochromia)
o Anisocytosis (variation in RBC size)
o Poikilocytosis (variation in RBC shape)
• Serum ferritin:
o This reflects the amount of stored Fe
Treatment:
• Important to discover underlying cause and treat it
• Oral Fe is all that is required in most cases:
o Ferrous sulphate 600mg daily
• Side-effects include nausea and diarrhoea/constipation
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• Failure of response to oral Fe may be due to:

o Poor compliance
o Continued haemorrhage
o Severe Malabsorption
o Another cause for the anaemia
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Meningitis
Aetiology:
Meningitis means inflammation of the meninges
• It may be caused by:
o Bacteria
o Viruses
o Fungi
o Malignant cells
o Drugs and contrast media
o Blood (following SAH)
• Micro-organisms reach the meninges either via:
o The bloodstream
o Direct extension from the:
• Ears
• Nasopharynx
• Cranial injury
• Congenital meningeal defect
Clinical features:
• The meningitic syndrome - a triad of:
o Headache
o Neck stiffness
o Fever
• In acute bacterial meningitis – developing within hours or
minutes:
o Intense malaise
o Fever
o Rigors
o Severe headache
o Photophobia
o Vomiting
o The patient often prefers to lie still. Neck stiffness and a
positive Kernig’s sign appear within hours
• In uncomplicated meningitis, consciousness is not impaired,
although a patient with a high fever may be delirious
Complications:
• Septicaemia
• Venous sinus thrombus
• Severe cerebral oedema
• Hydrocephalus
• Complications may be indicated by:
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o Progressive drowsiness
o Lateralizing signs
o Cranial nerve lesions
• Migraine
• SAH
• Cerebral malaria
Clinical clues in meningitis:

Clinical feature Probable cause
Petechial rash Meningococcal infection
Skull fracture Pneumococcal infection
Ear disease “
Congenital CNS lesion “
Immunocompromised patient HIV opportunistic infection
Rash or pleurodynia Enterovirus infection
International travel Malaria
Management:
• Condition is lethal. Even with optimal care, the mortality is still
~15%
• Immediate parenteral antibiotic treatment should be given
before any investigations
• LP is usually contraindicated if the clinical diagnosis is
meningococcal disease (because coning of the cerebellar tonsils
may follow)
• If there is any suspicion of an intracranial mass lesion. An
immediate CT scan should be carried out
• Immediate LP should be carried out (if deemed safe)
• Blood should be taken for FBC, U&Es, LFTs, glucose and a
culture
Antibiotics and acute bacterial meningitis:

Organism Antibiotic Alternative
Unknown pyogenic Cefotaxime Benzylpenicillin
Meningococcus Benzylpenicillin Cefotaxime
Pneumococcus Cefotaxime Penicillin
Haemophilus Cefotaxime Chloramphenicol
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Metabolic neuropathies
Diabetes mellitus
• Several varieties of neuropathy occur in diabetes mellitus:
o Symmetrical sensory polyneuropathy
o Acute painful neuropathy
o Mononeuropathy and multiple mononeuropathy:
• Cranial nerve lesions
• Isolated peripheral nerve lesions (e.g. median)
oDiabetic amyotrophy
oAutonomic neuropathy
Chronic uraemia:
• Progressive sensorimotor neuropathy occurs in chronic uraemia
• Variable response to dialysis
• Usually improves after renal transplantation
Thyroid disease:
• A mild chronic sensorimotor neuropathy is sometimes seen in
both thyrotoxicosis and hypothyroidism
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Migraine
Definition:
• Recurrent headaches associated with visual and GI disturbance
• The borderline between migraine and tension headaches is
vague
• Over 10% of any population sampled admit to these symptoms
Clinical patterns:
• Migraine can be separated into phases:
o Occasionally, a feeling of well-being prior to the attack
o Prodromal symptoms
o Headache and associated features
Classical migraine (migraine with aura):

• The prodrome lasts from 15 minutes to 1 hour or more. It
usually comprises:
o Visual symptoms (caused by depression of visual cortical
function)
• Unilateral patchy scotomata
• Cortical hemianopic symptoms
• Teichopsia (flashes)
• Fortification spectra (jagged lines resembling
battlements)
o Transient aphasia sometimes occurs
o Tingling, numbness or weakness of one side
o The patient feels nauseated
• Headache follows the prodrome:
o Often begins locally and becomes generalized
o Nausea increases
o Vomiting follows
o Patient is irritable
o Patient prefers to be in a dark room
o Superficial temporal artery is engorged and pulsating
• The attack lasts for several hours and then ceases
• Sleep often follows
Common migraine (migraine without aura):

• This is the usual variety of migraine
• Prodromal visual symptoms are vague
• There is recurrent headache accompanied by nausea and malaise
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Hemiplegic migraine:
• Rare
• Is where classical migraine is accompanied by hemiplegia
• Recovery occurs within 24 hours
Ophthalmoplegic migraine:
• Rare
• Is a 3rd nerve palsy occurring in a migraine attack
• Difficult to distinguish from other causes of a 3rd nerve palsy
without investigation
Basilar migraine:
• The prodromal symptoms are:
o Circumoral tingling
o Numbness of the tongue
o Vertigo
o Diplopia
o Transient visual disturbance
o Complete blindness
o Syncope
o Dysarthria
o Ataxia
• These occur either in isolation or progress to a migrainous
headache
• Meningitis
• Subarachnoid haemorrhage
• TIA (note: headache is uncommon)
• Epilepsy
Management:
• General measures include:
o Reassurance and relief of anxiety
o Avoidance of precipitating dietary factors
• During an attack:
o Paracetamol (or another simple analgesic)
o Antiemetic if necessary (e.g. metoclopramide)
o 5HT1 agonist (e.g. sumatriptan SC, PO Inh) is of value
• Prophylaxis:
o 5HT antagonist (e.g. pizotifen 0.5mg ON PO for several
days, increasing to 1.5mg ON PO)
o Propranolol 10mg PO TID, increasing to 40-80mg PO TID
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o Amitripyline 10-30mg ON PO is sometimes helpful
Mononeuritis multiplex
(multiple mononeuropathy)
This is a pathological process affecting several or multiple nerves
Mononeuritis multiplex occurs in:

• Diabetes mellitus
• Leprosy (still the most common worldwide cause)
• Vasculitis
• Sarcoidosis
• Amyloidosis
• Malignancy
• Neurofibromatosis
• HIV infection
When mononeuritis multiplex is symmetrical, there may be difficulties

separating it clinically from polyneuropathy. Treatment is of the
underlying disease.
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Mononeuropathies
Definition:
• A pathological process affecting a single peripheral nerve
Peripheral nerve compression or entrapment:

• Damage to a nerve by compression can be:
o Acute (e.g. a tourniquet or other sustained pressure)
o Chronic (e.g. entrapment neuropathy)
• In both the above, demyelination predominates (but some
axonal degeneration occurs)
o Acute compression usually affects nerves which are
exposed anatomically (e.g. the common peroneal nerve at
the head of the fibula)
o Entrapment develops where a nerve passes through a
relatively tight anatomical passage (e.g. the carpal tunnel)
Carpal tunnel syndrome:

• This is caused by median nerve compression at the wrist. Many
cases are idiopathic, but this syndrome is sometimes seen in:
o Hypothyroidism
o Diabetes mellitus
o Pregnancy
o Obesity
o RA
o Acromegaly
o Nocturnal tingling/pain in the hand
o Weakness of the thenar muscles follows
o Wasting of abductor pollicis brevis develops
o Sensory loss of the palm and radial 3 1/2 fingers
o Positive Tinel’s sign (tapping on the carpal tunnel
reproduces the pain)
• Treatment to cure is with surgical decompression
Ulnar nerve compression:

• This typically occurs at the elbow, where the nerve is
compressed in the cubital tunnel
• It is usually caused by:
o Ulna fracture
o Prolonged/recurrent pressure on the nerve at this site
o Wasting of hypothenar and interossei muscles
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o Sensory loss in the ulnar 1 1/2 fingers

• Decompression and transposition of the nerve at the elbow may
be necessary
Radial nerve compression (‘Saturday night palsy’):

• The radial nerve is compressed acutely against the humerus,
commonly when the arm is draped over a hard chair for several
hours
o Wrist-drop
o Weakness of finger extension and brachioradialis follow
• Recovery is usual within 1-3 months
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Osteoarthritis
Aetiology:
• Early in the development of OA, the surface of the cartilage
becomes fibrillated and fissured as the collagen matrix breaks
down
• These changes lead to focal erosion of cartilage
• Cartilage ulceration exposes underlying bone to increased stress
(producing microfractures and cysts)
• The bone attempts repair but produces abnormal sclerotic
subchondral bone and overgrowths at the joint margins (called
osteophytes)
The term primary OA is sometimes used when there is no obvious

predisposing factor
Causes of secondary OA:

• Pre-existing joint damage:
o RA
o Gout
o Seronegative spondarthritis
o Septic arthritis
o Paget’s disease
• Metabolic disease:
o Acromegaly
o Hereditary haemochromatosis
o Chondrocalcinosis
• Systemic diseases:
o Haemophilia (recurrent haemarthrosis)
o Sickle-cell disease
• Mechanical factors:
o Trauma (e.g. meniscal/cruciate tears)
o Joint dysplasia
o Joint hypermobility
Risk factors:
• Obesity
• Sex (females > males)
• Family history
• sport
Symptoms:
• Joint pain
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• Evening stiffness
• Joint instability
• Loss of function
Signs:
• Crepitus on movement
• Limitation of range of movement
• Joint instability
• Joint effusion
• Bony swelling
• Wasting of muscles
Most commonly affected sites:

• In decreasing order of prevalence:
o DIPs
o 1st metacarpophalangeal
o 1st metatarsophalangeal
o Cervical and lumbar spine
o Hip
o Knee
Clinical subsets:
• There are 5 main subsets:
o Nodal OA
o Erosive OA
o Generalized OA
o Large-joint OA
o Crystal-associated OA
Nodal OA:
• The joints are usually affected one at a time over several years
• DIPs being most often involved
• Onset may be painful and associated with:
o Tenderness
o Swelling
o Inflammation
o Impairment of hand function
• The inflammatory phase settles after some months or years,
leaving painless bony swellings posterolaterally with Heberden’s
nodes (DIPs) and Bouchard’s nodes (PIPs) along with stiffness
and deformity
Large-joint OA:
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• This affects the hips and the knees independently

• The hips:
o Superior-pole hip arthritis:
• Most common in men
• Affects the weight-bearing upper surface of the
femoral head and adjacent acetabulum
• Unilateral at presentation but may become bilateral
o Medial cartilage loss:
• Most common in women
• Associated with hand involvement
• Usually bilateral
• The knees:
o Generally bilateral
o Strongly associated with polyarticular OA of the hand
o Medial compartment is most commonly affected
Investigation in OA:
• X-rays:
o Characteristic changes (see below) only apparent when the
damage is advanced
• MRI:
o Can demonstrate early cartilage changes
• Arthroscopy:
o Can reveal early fissuring and surface erosion of the
cartilage
X-ray changes in OA:

• Osteophytes
• Joint space narrowing
• Bony cysts
• Subarticular sclerosis
Treatment – physical measures:

• Weight loss
• Exercise
• Hydrotherapy
Treatment – medical:
• Short courses of analgesics
• Intra-articular corticosteroid injections provide short-term
improvement when there is a painful joint effusion
Surgery:
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• Total replacement arthroplasty:

o Complication rate ~1%
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Mechanisms of damage to peripheral nerves
Overview:
• The peripheral nerve consists of 2 principle cellular structures:
o Axon
o Myelin sheath
• Blood supply to a peripheral nerve is via the vasa nervorum
Mechanisms of damage:
• Demyelination (e.g. Guillain-Barre syndrome)
• Axonal degeneration (e.g. toxic neuropathies)
• Wallerian degeneration (describes the changes following section
of a nerve)
• Compression (e.g. carpal tunnel syndrome)
• Infarction (e.g. diabetes mellitus, polyarteritis nodosa)
• Infiltration (e.g. malignancy, leprosy)
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Peripheral oedema
Starling’s principles:
• Distribution of ECF depends on:
• Venous tone (which determines the capacitance of the blood
compartment and thus hydrostatic pressure)
• Capillary permeability
• Oncotic pressure (mainly dependent on serum albumin)
• Lymphatic drainage
• Depending on these factors, fluid accumulation may result in
expansion of interstitial volume, blood volume or both
Clinical features:
• Peripheral oedema is caused by expansion of the ECF volume by
at least 2L (15%)
• Ankles are normally the first to be affected
• Oedema may be noticed in the face (particularly in the morning)
• In bed-bound patients, oedema may accumulate in the sacral
area
• Expansion of the interstitial volume also causes:
o Pulmonary oedema
o Pleural effusion
o Pericardial effusion
o Ascites
• Expansion of the blood volume causes:
o A raised JVP
o Cardiomegaly
o Added heart sounds
o Raised arterial BP
Causes:
• Heart failure
• Hypoalbuminaemia
• Hepatic cirrhosis (owing largely to peripheral vasodilatation)
• Sodium retention
Treatment:
• Treat the underlying cause where possible
• The mainstay of therapy is diuretics
Loop diuretics:
• E.g. Frusemide
• Potent
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• Stimulate excretion of both NaCl and water

• Also increase venous capacitance (resulting in rapid clinical
improvement in patients with LVF)
• Side-effects include:
o Hyperuricaemia (resulting in gout)
o Hypokalaemia
o Hypomagnesaemia
o Decreased glucose tolerance
o Ototoxicity (due to an action on sodium pump activity in
the inner ear)
Thiazide diuretics:
• E.g. bendrofluazide
• Less potent than loop diuretics
• Reduce peripheral vascular resistance by an unknown
mechanism
• Reduce calcium excretion
• Cause relatively more hyperuricaemia, glucose intolerance and
hypokalaemia than loop diuretics
Potassium-sparing diuretics:
• Relatively weak diuretics
• Most commonly used in combination with loop or thiazide
diuretics to prevent hypokalaemia
• Two types:
o Spironolactone (aldosterone antagonist, therefore reduces
Na+ absorption
o Amiloride (inhibits sodium uptake in the collecting duct and
reduces renal potassium excretion)
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Peritoneal dialysis
Basic principles:
• Utilizes the peritoneal membrane as a semipermeable
membrane, therefore avoiding the need for extracorporeal
circulation of blood
• The principles are simple:
o A tube is placed into the peritoneal cavity through the
anterior abdominal wall
o Diasylate is run into the peritoneal cavity under gravity
o Urea, creatinine, phosphate and other uraemic toxins pass
into the diasylate down their concentration gradients
o Water (with solutes) is attracted into the peritoneal cavity
by osmosis, depending on the osmolarity of the diasylate
(this is determined by the dextrose concentration of the
diasylate)
o The fluid is changed regularly to repeat the process
• There are 3 main adaptations of peritoneal dialysis:
o Continual ambulatory peritoneal dialysis (CAPD)
o Nightly intermittent peritoneal dialysis (NIPD)
o Tidal dialysis
Complications:
• Bacterial peritonitis
• Infection around the catheter site
• Constipation
• Pleural effusion (caused leakage of the diasylate through a
diaphragmatic defect)
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Polyneuropathies
Varieties of polyneuropathy:
• Guillain-Barre syndrome (acute post-infective polyneuropathy)
• Chronic inflammatory demyelinating polyneuropathy (CIDP)
• Metabolic neuropathies
• Toxic neuropathies
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Renal transplantation
Successful renal transplantation offers the potential for almost

complete rehabilitation in ESRF. It allows freedom from dietary and
fluid restriction and anaemia and infertility are corrected.
Factors affecting success:

• Matching donor and recipient for HLA type
• Adequate immunosuppressive therapy
• Preoperative blood transfusion
• The ‘centre effect’ (graft survival is higher in those centres with
extensive experience of management of transplant recipients)
The donor kidney:

• Cadaveric donation:
o Organ is removed from a brainstem-dead individual whilst
their heart is still beating
• Living relative donation:
Immunosuppression for transplantation:

• Risk of rejection is highest in the first 3 months (as some degree
of immunological tolerance to the graft does develop)
• Corticosteroids:
o High-dose methylprednisolone is used as the primary
treatment for acute rejection
• Azathioprine:
o Prevents cell-mediated rejection by interfering with nucleic
acid synthesis and preventing the replication of
lymphocytes
• Cyclosporin:
o A fungal metabolite
o Prevents the activation of T-lymphocytes in response to
new antigens
o Highly effective in preventing rejection, whilst leaving the
rest of the immune system largely intact
• Tacrolimus:
o A macrolide (antibiotic)
o Blocks T cell activation by a mechanism very similar to
that of cyclosporin but with fewer rejection episodes
• Mycophenolate mofetil:
o Metabolised to mycophenolic acid
o May supplement azathioprine as an immunosuppressant
o Still in trial stages
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Complications:
• Technical failure:
o Occlusion/stenosis of the arterial and/or venous
anastomoses
o Leaks (owing to damage to the lower ureter)
• Immunosuppression:
o Corticosteroid complications (e.g. moon face, easy
bruising, etc)
o Cyclosporin can produce a rash, nephrotoxicity, tremor,
diabetes
o Tacrolimus can cause nephrotoxicity and neurotoxicity
o Azathioprine can lead to bone marrow suppression
Factors rendering a patient less suitable for transplantation:

• Previous malignancy
• Severe non-renal disease that is likely to limit survival post-
transplantation
• Vascular disease (especially DM)
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Rheumatoid arthritis (RA)
RA is a chronic symmetrical polyarthritis of unexplained cause. It is a

systemic disorder characterized by chronic inflammatory synovitis pf
mainly peripheral joints. Its course is extremely variable and it is
associated with non-articular features.
Pathology:
• Widespread persisting synovitis (inflammation of the synovial
lining of joints, tendon sheaths or bursae)
• Unknown mechanism but the production of rheumatoid factors
(RFs) is thought to be important
• The synovium becomes greatly thickened to the extent that it is
palpable as a ‘boggy’ swelling around the joints and tendons
• There is marked vascular proliferation
• Increased permeability blood vessels and the synovial lining
layer leads to joint effusions
• The hyperplastic synovium spreads from the joint margins on to
the cartilage surface. This ‘pannus’ of inflamed synovium
damages the underlying cartilage by blocking its normal route
for nutrition and the direct effect of cytokines on the
chondrocytes
Rheumatoid factors (RFs):

• These are circulating antibodies which have the Fc portion of Ig
as their antigen
• The nature of the antigen means that they self-aggregate into
immune complexes and thus activate complement and stimulate
inflammation – causing chronic synovitis
• Transient production of RFs is essential for removing immune
complexes
• RFs may be of any Ig class but are most commonly IgM
• ~70% of patients with polyarticular RA have IgM RF in their
serum
• The term seronegative RA is used for patients in whom the
standard tests for IgM RF are persistently negative
Typical presentation:
• ~70% of cases begin as a slowly progressive, symmetrical,
peripheral polyarthritis
• Usual timescale is a few weeks or months
• Women 3x > men
• Peak age of onset is 30-40 (can occur at any age)
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• 15% of patients have a rapid onset of symptoms (occurring over

a few days or even overnight). Surprisingly, these patients have
a better prognosis
• Bad prognostic signs include:
o Female
o Gradual onset over a few months
o Positive IgM RF
o Anaemia occurring within the first 3 months
Symptoms and signs:

• Pain and stiffness of the PIPs, DIPs, MCPs and MTPs
• The wrists, elbows, shoulders, knees and ankles are also affected
• Only 10% of patients present with a monoarthritis (usually the
knee, shoulder or carpal tunnel syndrome)
• Lethargy
• Malaise
• Pain and stiffness significantly WORSE IN THE MORNING and
may improve with gentle activity
• The joints are usually warm and tender with some joint swelling
• Limitation of movement
• Muscle wasting
• Deformities develop as the disease progresses
Complications:
• Of the disease:
o Ruptured tendons
o Joint infection (septic arthritis)
o Ruptured joints (e.g. Baker’s cysts)
o Spinal cord compression
o Amyloidosis
• Of the therapy:
o Anaemia
o Marrow hypoplasia
o Renal impairment
o GI bleeding
Septic arthritis:
• Serious complication with a high mortality
• The joint(s) may be hot, inflamed with accompanying fever
• Increased WCC
• However, these signs can be absent and any effusion
(particularly of sudden onset) should be aspirated
• Staph. aureus is the most common organism
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• Treatment is with systemic antibiotics
Amyloidosis:
• Is found in a small number of cases of severe RA
• RA is the most common cause of secondary amyloidosis
Non-articular manifestations of RA:

• Sclerosis
• Scleromalacia
• Sjogren’s syndrome (dry eyes, dry mouth)
• Atlanto-axial subluxation (rarely causing c-spine compression)
• Vasculitis
• Pleural effusion
• Fibrosing alveolitis
• Small airway disease
• Lymphadenopathy
• Pericarditis
• Bursitis
• Anaemia
• Carpal tunnel syndrome
• Amyloidosis (causes the nephrotic syndrome and renal failure)
• Sensorimotor polyneuropathy (caused by vasculitis of the vasa
nervorum)
• Leg ulcers
• Ankle oedema
• Splenomegaly
Criteria for the diagnosis of RA:

• For 6 weeks or more:
o Morning stiffness for >1 hour
o Arthritis of 3 or more joints
o Arthritis of hand joints and wrists
o Symmetrical arthritis
• For any length of time:
o Subcutaneous nodules
o Positive serum RF
o Typical radiological changes
• 4 or more are necessary for diagnosis
X-ray changes in RA:

• Juxta-articular osteoporosis
• Joint-space narrowing
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• Bony erosions
Drug therapy:
• Essentially comprises 3 main groups of drugs:
o NSAIDs (Non-steroidal anti-inflammatory drugs)
o DMARDs (Disease modifying anti-rheumatic drugs)
o Corticosteroids
NSAIDs:
• Control the pain and stiffness but do not reduce the underlying
inflammatory relapse or the acute flare reactants in the serum
• Always start with a familiar drug. It should be cheap, have a low
incidence of side-effects and a convenient dosage schedule
• Major side-effects of NSAIDs are gastrointestinal:
o Haemorrhage a major problem in the elderly
o Pts with previous PUD should have their H. pylori status
checked, followed by eradication therapy if required
o Risks can be reduced by the co-administration of H2-
receptor antagonists or PPIs
• Other side-effects include:
o Fluid retention
o Tubulo-interstitial nephritis
o Drug interactions
DMARDs:
• Sulphasalazine:
o 1-1.5g BD PO
• Methotrexate:
o 2.5-15mg once weekly PO (remember folate
supplementation)
• Gold:
o 3mg BD PO or 50mg weekly IM
• Penicillmine:
• 250-400mg AC PO
• Antimalarials:
o 400mg OD PO
It should be noted that DMARDs are almost exclusively prescribed by a
rheumatologist and that each drug has numerous side-effects
Corticosteroids:
• The use of oral corticosteroids has a number of problems:
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1. Patients are increasingly anxious about the use of

corticosteroids because of adverse publicity about their
potential side-effects
2. Risk of weight gain
3. Skin becomes thin and easily damaged
4. Monitor for DM and HT
5. Cataract formation may be accelerated
6. Osteoporosis develops within 6 months on doses >7.5mg
daily and HRT and/or calcium and vitamin D or
bisphosphonate is used
• Must be avoided in the long-term
• Intra-articular injections have a powerful but short-lived effect
• IM depot injections (40-120mg depot methylprednisolone) help
to control severe flare-ups of the disease; or can be used before
a holiday or other important event but should be used with
caution and infrequently
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Septic arthritis
Causative organisms:
• Staph. aureus (most common)
• Streptococci
• N. gonorrhoea
• Haemophilus influenzae
Clinical features:
• Is a medical emergency
• In the young the joint is:
o Hot
o Swollen
o Red
o Agonisingly painful
o Held immobile by muscle spasm
• In the elderly/immunocompromised:
o Clinical picture is less dramatic
Investigations:
• Aspirate the joint:
o Send the fluid for urgent Gram stain and culture
o The fluid is usually frankly purulent
• Blood cultures:
o Are usually positive
• Leucocytosis:
o Is usual, unless patient is severely immunocompromised
Treatment:
• Should be started immediately on diagnosis as joint destruction
occurs in days
• IV antibiotics should be given for a week
• It is usual to give 2 antibiotics to which the organism is sensitive
for 6 weeks, then 1 for a further 6 weeks orally
• Immobilize the joint initially
• Physiotherapy should be started early to prevent stiffness and
muscle wasting
Empirical treatment in septic arthritis:

• Usually give:
o Flucloxacillin 1-2g IV QID, plus
o Fusidic acid 500mg PO TID
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• If the patient is allergic to penicillin, replace flucloxacillin with:

o Erythromycin 1g IV QID
o Clindamycin 600mg IV TID
• In immunocompromised patients:
o Flucloxacillin 1-2g IV QID, plus
o Gentamycin IV (to cover anaerobes)
Prognosis:
• Surgical drainage may be required if there is joint destruction
and osteomyelitis
• Patients can start weight-bearing as soon as the inflammation
subsides
• Resolution of the arthritis with complete recovery can occur in a
few days or weeks
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Subarachnoid haemorrhage (SAH)
SAH describes spontaneous, rather than traumatic, arterial bleeding

into the subarachnoid space and is usually clearly recognisable by its
dramatic onset. SAH accounts for 10% of cerebrovascular disease and
has an annual incidence of 6 per 100,000.
Causes:
• Common causes:
o Saccular (‘berry’) aneurysms ~70%
o Arteriovenous malformations ~10%
o No lesion found ~20%
• Rare associations:
o Bleeding disorders
o Mycotic aneurysms
o Acute bacterial meningitis
o Brain tumours (e.g. metastatic melanoma)
o Marfan’s syndrome
Saccular (‘berry’) aneurysms:

• Saccular aneurysms form on the circle of Willis and its adjacent
branches. The common sites of aneurysms are:
o Posterior communicating artery aneurysm (junction of the
posterior communicating artery and the internal carotid
artery)
o Anterior communicating artery aneurysm (junction of the
anterior communicating artery and the anterior cerebral
artery)
o Middle cerebral artery aneurysm (the bifurcation of the
middle cerebral artery)
• Aneurysms cause symptoms either by:
o Spontaneous rupture
o Direct pressure on surrounding structures (e.g. a posterior
communicating artery aneurysm is a cause of a painful
third-nerve palsy)
Arteriovenous malformations (AVM):

• This is a lesion of developmental origin, usually within the
hemisphere
• An AVM may also cause epilepsy (which is often focal)
• Once an AVM has ruptured to cause SAH, there is a tendency to
rebleed at a rate of 10% per year
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Clinical features of SAH:

• Sudden onset of a devastating headache, often occipital
• Vomiting
• Loss of consciousness
• The patient remain comatose or drowsy for several hours to
several days
• Less severe headaches cause diagnostic difficulties (SAH is
possible diagnosis in any sudden headache)
On examination:
• Neck stiffness
• Positive Kernig’s sign:
o Pain and resistance on passive knee extension with hips
fully flexed
• Papilloedema is occasionally present
Investigations:
• CT imaging:
o Is the initial investigation of choice
o Subarachnoid or intraventricular blood is usually seen
• LP:
o Only necessary after CT if the diagnosis is in doubt
o The CSF becomes yellow (xanthochromic) several hours
after SAH
• Carotid and vertebral angiography:
o Usually performed in all patients who are potentially fit for
surgery (i.e. <65 years and not in a coma) to establish the
cause and site of bleeding
• Severe migraine
• Acute bacterial meningitis (caused by the rupture of a meningeal
microabscess)
Complications:
• Hydrocephalus:
o Caused by blood clots in the subarachnoid space
obstructing the flow of CSF
o Is a cause of deteriorating consciousness level a few days
or weeks after the initial bleed
o Shunting may be required
• Severe spasm of the intracranial arteries:
o Is an occasional complication
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o Is a poor prognostic sign

Management:
• Where angiography demonstrates aneurysm, a direct
neurosurgical approach to clip the neck of the aneurysm is
carried out
• In selected cases, the results of surgery are excellent
• Immediate treatment:
o Bedrest
o Supportive measures
o Control HT
o Dexamethasone is often prescribed to reduce cerebral
oedema
• All cases of SAH should be referred to a specialist centre for a
decision about angiography and possible surgery
Prognosis:
• 50% of cases are dead or moribund before they reach hospital
• Of the remainder, a further 10-20% die in the early weeks in
hospital from further bleeding
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Tension headache
Aetiology:
• Worry
• Depression
• Noise
• Concentrated visual effort
• Fumes
Clinical features:
• Tight band sensation
• ‘Pressure behind the eyes’ sensation
• Throbbing
• ‘Bursting’ sensations
Signs:
• Tenderness/tension in the nuchal and scalp muscles
Management:
• Firm reassurance
• Avoiding the causes (where possible)
• Analgesics
• Physical treatments:
o Massage
o Icepacks
o Relaxation
• Antidepressants (where indicated)
• Imaging is occasionally needed to confirm the benign nature of
the problem
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Thiamin (vitamin B1) deficiency
Overview:
• Dietary deficiency causes the clinical syndrome of beriberi
• The principle features are polyneuropathy and cardiac failure
• It also leads to an amnesic syndrome called Wernicke-Korsakoff
syndrome
• Alcohol abuse is the commonest cause of thiamin deficiency in
the UK
Wernicke-Korsakoff syndrome:
• Composed of a classic triad of:
o Ocular signs
o Ataxia
o Confusion
• It is due to ischaemic damage to the brainstem and its
connections owing to thiamin dietary deficiency, alcohol or other
causes (e.g. anorexia nervosa)
• Clinical features include:
o Ocular signs:
• Nystagmus
• Bilateral lateral rectus palsies
• Conjugate gaze palsies
o Ataxia:
• Broad-based gait
• Vestibular paralysis (absent response to caloric
stimulation)
o Confusion:
• Apathy
• Decreased awareness
• Restlessness
• Amnesic syndrome
• Coma
• Thiamin should be given parenterally if the diagnosis is in
question. The drug is harmless, the condition is not
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Transient ischaemic attacks (TIAs)
Clinical features:
• Anterior circulation (carotid system) affected:
o Amaurosis fugax
o Aphasia
o Hemiparesis
o Hemisensory loss
o Hemianopic visual loss
• Posterior circulation (vertebrobasilar system):
o Diplopia, vertigo, vomiting
o Choking and dysarthria
o Ataxia
o Hemisensory loss
o Hemianopic visual loss
o Transient global amnesia
o Tetraparesis
Amaurosis fugax:
• This is sudden, transient loss of vision in one eye
• A TIA causing amaurosis fugax is often the first clinical evidence
of internal carotid artery stenosis, which may herald a
hemiparesis
• Also occurs as a benign event in migraine
Transient global amnesia:

• Episodes of amnesia with confusion lasting for several hours
• Occurs principally in people >65 years
• Complete recovery
• Caused by ischaemia in the posterior cerebral circulation
• Space-occupying lesion
• Focal epilepsy
• Migraine
Prognosis:
• Within 5 years of a TIA:
o 40% of patients will have suffered a stroke
o 25% of patients will have died, usually from heart disease
or stroke
• A TIA in the anterior circulation carries a more serious prognosis
than one in the posterior circulation
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Clinical patterns of UMN disorders
2 main patterns of UMN (pyramidal) lesions are recognizable:

• Hemiparesis
• Paraparesis
Hemiparesis means paralysis of the limbs of one side. It is usually (but

not always) caused by a lesion within the brain.
Paraparesis means paralysis of both lower limbs and is
characteristically diagnostic (but again, not always) of a spinal cord
lesion.
Hemiparesis:
• The level within the corticospinal tract (CoST) is recognized by
various accompanying features
• Motor cortex:
o Paralysis localized to one contralateral limb (monoplegia)
or part of a limb (e.g. a weak hand) is characteristic of an
isolated lesion of the motor cortex (e.g. a secondary
neoplasm)
o There may be a defect in higher cortical function (e.g.
aphasia if the speech area is affected)
o Focal epilepsy may be present
• Internal capsule:
o Since all CoST fibres are tightly packed in the internal
capsule (occupying ~1cm2) a small lesion causes a large
deficit
o E.g. an infarct of a small branch of the middle cerebral
artery causes a sudden contralateral hemiplegia that
includes the face
• Pons:
o A pontine lesion (e.g. a plaque of MS) is rarely confined
only to the CoST
o As adjacent structures such as the 6th and 7th cranial nerve
nuclei, MLF and PPRF are involved, there are other
localizing signs:
o VI and VII nerve palsies
o Intranuclear nuclear ophthalmoplegia (INO)
o Lateral gaze palsy
• Spinal cord:
o An isolated lesion of a single lateral CoST within the cord
(which is unusual) causes an ipsilateral UMN lesion, the
level of which is indicated by:
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o A reflex level (e.g. absent biceps jerk)

o The presence of a Brown-Sequard syndrome
o Muscle wasting at the level of the lesion
Paraparesis:
• Paraparesis (and tetraparesis when all 4 limbs are involved)
indicates bilateral damage to the CoSTs
• Spinal cord compression or other cord disease is the usual cause,
but cerebral lesions can occasionally produce paraparesis
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Venous thromboembolic disease
Thrombosis can occur in any vein, but the veins of the leg and pelvis
are the most common sites.
Risk factors for venous thromboembolism:

• Increasing age
• Obesity
• Varicose veins
• Immobility (bedrest >4 days)
• Pregnancy
• OCP
• Previous DVT
• Thrombophilia
• Trauma/surgery
• Malignancy
• Infection
Superficial thrombophlebitis:
• Commonly involves the saphenous vein
• Often associated with varicosities
• Occasionally the axillary vein is involved (usually as a result of
trauma)
• Local, superficial inflammation of the vein wall, with secondary
thrombosis
• The clinical picture is of a painful, tender, cord-like structure with
associated redness and swelling
• Treatment:
o Rest
o Elevation of the limb
o Analgesics (e.g. NSAIDs)
o Anticoagulants are NOT necessary as embolism does not
occur from superficial thrombophlebitis
Deep vein thrombosis (DVT):

• Thrombosis commonly occurs after periods of immobilization, but
it can occur for apparently no reason
• A DVT in the leg occurs in 50% of patients after prostatectomy
or following a CVA
• 30% of patients with a MI have a DVT
• Thrombosis can occur in any vein of the leg but it is particularly
found in the veins of the calf
• Is often asymptomatic
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Clinical features of a DVT:

• Asymptomatic
• Calf DVT:
o Pain
o Redness
o Swelling
o Engorged superficial veins
• Iliofemoral DVT:
o Severe pain
o Thigh swelling
o Ankle oedema
PE can occur with any DVT but is more frequent from an iliofemoral
thrombosis and is rare with thrombosis confined to veins below the
knee
Investigations of DVT:
• Doppler ultrasound
• Venography
Treatment:
• All patients with thrombi above the knee are anticoagulated
• Anticoagulation of below-knee thrombi is controversial but is
usually recommended for 6 weeks
• Heparin is usually given for 2-3 days whilst warfarin (which is
started immediately) becomes effective
• Target INR should be 2.5
• Warfarin is usually continued for 3 months
• Thrombolytic therapy is sometimes used for patients with a large
iliofemoral thrombosis
Prognosis:
• Approximately 50% of patients with a DVT will have destruction
of the deep vein valve. This produces a:
o Clinically painful, swollen limb
o Made worse by standing
o Oedema
o Venous eczema
• Elastic support stockings are required for life
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Vitamin B12 deficiency and pernicious anaemia
Vitamin B12 absorption and storage:

• Only found in animal sources:
o Meat
o Fish
o Eggs
o Milk
• It may take 2 years or more after absorptive failure before B12
deficiency develops as the daily losses are small
• Vitamin B12 is absorbed from the terminal ileum by its binding to
intrinsic factor (IF)
• IF is secreted by gastric parietal cells
Causes of vitamin B12 deficiency:

• Low dietary intake:
o Vegans
• Impaired absorption:
o Pernicious anaemia (most common)
o Gastrectomy
o Ileal disease/resection
o Bacterial overgrowth
o Tropical sprue
• Abnormal metabolism:
o Nitrous oxide (inactivates B12)
Pathogenesis of pernicious anaemia:

• Pernicious anaemia (PA) is a condition in which there is atrophy
of the gastric mucosa with consequent failure of IF production
and B12 malabsorption
• 1 in 8000 people over 60 years affected (females>males)
• Is an association with other autoimmune diseases (especially
thyroid and Addison’s)
• Increased risk of gastric carcinoma
• There is associated achlorhydria
Clinical features of PA:

• Insidious onset
• Progressively increasing symptoms of anaemia
• Glossitis
• Angular stomatitis
• Lemon-yellow colour (owing to a combination of pallor and mild
jaundice)
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• Neurological changes (which can become irreversible if

untreated):
o Symmetrical paraethesia in the fingers and toes
o Loss of vibration sense and proprioception
o Progressive weakness and ataxia
o Paraplegia may result
o Dementia can also occur
Investigations:
• FBC:
o Shows a megaloblastic anaemia
• Bone marrow:
o Shows the typical features of megaloblastic erythropoiesis
• Serum bilirubin:
o May be raised (as a result of ineffective erythropoiesis)
• Serum vitamin B12:
o Usually well reduced
• Serum folate level:
o Is normal or high
o The red cell folate is normal or reduced (owing to the
inhibition of normal folate synthesis)
The Schilling test:

Part 1:
• Give 1µg radio-labelled B12 orally to fasting patient
• Give 1000µg B12 by IM injection to saturate B12-binding proteins
and to flush out the radio-labelled B12
• Collect urine for 24 hours
• Normal subjects excrete more than 10% of the radioactive dose
Part 2:
• Repeat part 1 with oral IF capsules
Part 3:
• If excretion is now normal, diagnosis is PA or Gastrectomy
• If excretion is still abnormal, lesion is in the terminal ileum or
there is bacterial overgrowth
• Vitamin B12 malabsorption due to bacterial overgrowth may be
corrected by antibiotic therapy
Treatment:
• Hydroxycobalamin 1000µg IM to a total of 5-6mg over the
course of 3 weeks
• 1000µg is then necessary every 3 months for the rest of the
patients life
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• Clinical improvement may occur within 48 hours

• Improvement of the polyneuropathy may occur over 6-12
months (but longstanding spinal cord damage is irreversible)
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General Surgery
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Adult umbilical hernia
True umbilical hernia:

• The protrusion is through the umbilical scar, everting the
umbilicus whose attenuated fibres are at the apex of the hernial
sac
• The cause is often secondary to an increase in the volume of
contents of the abdominal cavity (e.g. obesity, ascites or large
benign/malignant intra-abdominal tumours)
Para-umbilical hernia:
• The weakest area of the scar is at the superior aspect between
the umbilical vein and the upper margin of the umbilical ring
• It is at this point that a para-umbilical hernia develops
• The emerging sac displaces the umbilical scar which lies below
and slightly to one side
• More common than true umbilical hernias
• Typically found in the obese middle-aged patient
• Women are 5x more likely than men to suffer from a para-
umbilical hernia
• The neck of the hernia is often narrow. In consequence, tissues
that enter have great difficulty leaving:
o Adhesions form
o Hernia becomes irreducible
o The sac progressively acquires more contents and may
become very large
o The contents are usually omentum, often with small bowel
or transverse colon
• Unsurprisingly, these hernias are at great risk of strangulation
Clinical features – true umbilical hernia:

• Symptoms:
o Are often of an underlying cause (e.g. ascites) or there
may merely be gross obesity
o Very rarely, the patient will give a history which dates back
to infancy or childhood
• Signs:
o Ascites may be obvious
o The umbilicus is attenuated and sometimes paper-thin
o Evidence of underlying malignancy should be sought (both
in the abdomen as a whole and at the umbilical opening
where a nodule or nodules may be palpable)
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Clinical features – para-umbilical hernia:

• Symptoms:
o There is local pain and a swelling at the navel
o Non-specific GI symptoms are common
o Features of recurrent intestinal obstruction may have
occurred
• Signs:
o The umbilicus assumes a crescent shape
o Inspection and palpation reveal a swelling just above the
umbilicus whose centre (in contrast to a true umbilical
hernia) is not attached to the apex of the protrusion
o However, in grossly obese patients, the swelling may not
be obvious to the naked eye and moreover is barely
palpable
o In others, the hernia may be enormous
o Usually it is (at least in part) reducible and there is a
cough impulse
Management:
• True umbilical hernia:
o Any underlying cause should be sought and dealt with
o In the rare event that nothing is found and the hernia is
causing symptoms, it is treated as a para-umbilical hernia
• Para-umbilical hernia:
o Symptomatic hernias require treatment
o There is a high risk of strangulation and repair should be
advised, even in the absence of symptoms
o The usual procedure is to mobilise the sac and its contents,
return the latter to the abdomen, close the neck and repair
the abdominal wall by overlapping its layers
• Strangulated umbilical hernia:
o The patient with severe abdominal pain and vomiting and a
soft non-tender umbilical hernia is a diagnostic trap
o The loculated nature of the hernia allows a strangulated
portion of bowel (often of the Richter’s type) to go
unnoticed clinically
o In other instances, the local features of strangulation may
be obvious
o The operative approach is as for an elective case, and the
strangulating contents are dealt with according to their
state
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Anti-emetic drugs
The reflex mechanism of vomiting:

• Emetic stimuli:
o Chemicals in blood
o Neuronal input from GI tract, labyrinth and CNS
• Impulses from chemoreceptor trigger zone (CTZ), and various
CNS centres, relay to the vomiting centre
• Numerous chemical transmitters involved:
o Histamine (H1-receptors)
o Acetylcholine (muscarinic receptors)
o Dopamine (D2 receptors)
o 5-Hydroxytryptamine (5-HT3 receptors)
• Antiemetic drugs:
o H1-receptor antagonists (e.g. cyclizine)
o Muscarinic antagonists (e.g. hyoscine)
o 5-HT3 antagonists (e.g. ondansetron)
o D2-receptor antagonists (e.g. metoclopramide)
o Cannabinoids (e.g. nabilone)
H1-receptor antagonists:
• E.g. cyclizine, cinnarizine, promethazine
• Little or no activity against vomiting produced by substances
acting directly on the CTZ
• Effective in motion sickness and against vomiting caused by
substances which act locally in the stomach
• Most effective if given before the onset of nausea and vomiting
• May have some action in controlling it when established
Muscarinic-receptor antagonists:
• E.g. hyoscine
• Active against nausea and vomiting of labyrinthine origin and
against vomiting due to local stimuli in the stomach
• Ineffective against substances which act directly on the CTZ
• Not very useful once sickness has occurred
• Main side-effects:
o Drowsiness
o Dry mouth
5-HT receptor antagonists:

• E.g. ondansetron
• 5-HT is released in the CNS and gut and is an important
transmitter in emesis
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• Very effective at treating vomiting caused by cytotoxic drugs

o Headache
o GI disturbances
DD-receptor antagonists:
• E.g. metoclopramide
• Acts in the CTZ
• Is a pro-kinetic (increases gut motility)
o Extrapyramidal effects
o Dizziness
o Hyperprolactinaemia
o Amenorrhoea
o Diarrhoea
Cannabinoids:
• E.g. nabilone
• Decreases vomiting due to agents which stimulate the CTZ
• Its antiemetic effect is antagonised by naloxone (which implies
that opioid receptors may be important in the action of this
drug)
o Drowsiness
o Dizziness
o Dry mouth
o Mood changes
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Prophylactic antibiotics in gut surgery
Wound infections:
• Occur in 20-60% of those undergoing GI surgery
• Sepsis may lead to:
o Delayed mobilisation
o Haemorrhage
o Wound dihescence
o A fatal chain of events
• Prophylaxis substantially reduces infection rates
Rules for success:

• Give the antibiotic just before (e.g. 1 hour) surgery
• Give the antibiotic IV or IM (or as a suppository for
metronidazole)
• Usually the antibiotic can be stopped after 24 hours
• Use antibiotics which will kill anaerobes and coliforms (e.g.
metronidazole and gentamicin)
Antibiotic regimens:
• There is usually a local preference
• Examples include:
o Biliary surgery:
• Broad spectrum penicillin (e.g. ampicillin 500mg IV/8h
for 3 doses), or
• Cephalosporin (e.g. cefuroxime IV/IM 1.5g/8h for 3
doses)
o Appendicectomy:
• A 3-dose regimen of metronidazole suppositories (1g/
8h) plus cefuroxime 1.5g/8h IV or gentamicin IV
o Colorectal surgery:
• Cefuroxime 1.5g/8h IV/IM for 3 doses plus
metronidazole 500mg/8h IV for 3 doses
o Vascular surgery:
• Co-amoxiclav 1.2g IV on induction
• If penicillin-allergic, use cefuroxime 1.5g IV/IM plus
metronidazole 500mg IV
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Blood groups
The blood groups are determined by antigens on the surface of RBCs;

more than 400 blood groups have been found
The ABO and Rh systems are the 2 most important blood groups, but
incompatibilities involving many other blood groups (e.g. Kell, Duffy,
Kidd) may cause haemolytic transfusion reactions and/or haemolytic
disease of the newborn (HDN)
ABO system:
This blood group system involves naturally occurring IgM anti-A and
anti-B antibodies, which are capable of producing rapid and severe
intravascular haemolysis of incompatible RBCs
Phenotype Genotype Antigens Antibodies Frequency (%)

O OO None Anti-A/anti-B 44
A AA or AO A Anti-B 45
B BB or BO B Anti-A 8
AB AB A and B None 3
Rh system:
• There is a high frequency of development of IgG RhD antibodies
in RhD-negative individuals after exposure to RhD-positive red
cells
The antibodies formed are of major importance in causing HDN and
haemolytic transfusion reactions
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Blood, blood components and blood products
What is available to be transfused?

• Whole blood
• Packed red cells
• Red cell concentrates
• Buffy-coat depleted red cell concentrates - most WBCs and
platelets removed
• Leucocyte-depleted red cell concentrates – used to prevent
alloimmunisation to leucocyte antigens (e.g. in aplastic anaemia
patients who are potential recipients of allogeneic BM
transplants)
• Washed red cell concentrates – used in patients who have had
anaphylactic reactions
• Platelet concentrates
• Granulocyte concentrates
• Fresh frozen plasma (FFP) – contains all the coagulation factors
present in fresh plasma
• Cryoprecipitate – contains factor VIII, vWF and fibrinogen
• Factor VIII and IX concentrates
• Albumin
• Normal immunoglobulin – used in patients with
hypogammaglobulinaemia
• Specific immunoglobulins – e.g. anti-hepatitis B
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Complications of blood transfusion
Immunological complications:
• Alloimmunisation (doesn’t cause problems with the first
transfusion)
• Incompatibility
• Haemolytic transfusion reactions:
o Immediate (usually due to ABO incompatibility):
• Rigors
• Lumbar pain
• Dyspnoea
• Hypotension
• Haemoglobinuria
• Renal failure
• DIC (disseminated intravascular coagulation)
o Delayed:
• Anaemia and jaundice ~1 week post-transfusion
• Non-haemolytic (febrile) transfusion reactions:
o Usually caused by leucocyte antibodies in the recipient’s
serum acting against transfused leucocytes, leading to the
release of pyrogens
• TRALI (transfusion-related acute lung injury):
o Is caused by potent leucocyte antibodies in the plasma of
donors (who are often multiparous women)
o Characterised by:
• Dyspnoea
• Fever
• Cough
• Shadowing in the perihilar and lower lung fields on
the CXR
• Anaphylaxis:
o Transfusion should be stopped
o Adrenaline 0.5mg IM
o Chlorpheniramine 10mg IV
o Endotracheal intubation may be required
Non-immunological complications:
• Transmission of infection (all rare):
o Hepatitis (<1 in 200,000 units in UK)
o HIV (<1 in 3,000,000 units in UK)
o Other viruses (e.g. CMV, EBV)
o Parasites (e.g. malaria, toxoplasmosis)
o Syphilis
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• Circulatory failure due to volume overload

• Iron overload (multiple transfusions)
• Massive transfusion of stored blood may cause bleeding and
electrolyte changes
• Thrombophlebitis
• Air embolism
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Burns
Major burns should be dealt with in a specialised unit. Only the

principles of management of a severe burn will be addressed
Pathophysiology:
• Loss of integument and direct tissue injury lead to a generalised
fluid leak into the burn area
• This results in fluid loss and oedema formation
• Secondary problems include myocardial depression (which
usually recovers within 24 hours)
• There is also a degree of immunosuppression, with the major
late problem of infection
Assessment:
• The area of burn should be determined
• The method used is to assess the percentage of the total body
surface area which has been damaged and the depth of the
injury
• There are graphical charts available for this
Problems associated with a large burn:

• Fluid loss
• Myocardial depression
• Oedema formation:
o Airway obstruction
o Compartment syndromes
• Airway burn – hypoxia
• Tissue damage – myoglobinuria
• Immunosuppression – infection
Management:
• The rules of ABC (airway, breathing and circulation) apply
• The airway must be assessed and, if necessary, protected by
intubation
• Indications for endotracheal intubation include:
o Lung injury with hypoxia from inhalational burns
o Oedema (in the case of head and neck burns – can
develop rapidly and occlude the airway)
• There are massive fluid losses post-burn injury due to the
formation of oedema and loss of the cutaneous barrier
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• Various formulae have been produced to guide fluid

management in the resuscitation, an example of which is the
Parkland formula using Ringer’s lactate solution:
Volume (mL)/24h = 4 x weight (kg) x percentage of total body surface

area burnt
• These formulae are rough guides and resuscitation should be

more accurately guided by clinical assessment using:
o Tissue perfusion
o Blood pressure
o Urine output
• The other important aspect of management is the control of pain
and anxiety
• Pain may be very severe initially but anxiety becomes a growing
problem as the patient becomes aware of the predicament
Specific treatment:
• Do NOT apply cold water to extensive burns – this may intensify
shock
• Do NOT burst blisters
• Covering extensive partial thickness burns with sterile linen prior
to transfer to a burns unit will deflect air currents and relieve
pain
• Use morphine in 1-2mg aliquots IV
• Suitable dressings (which should be changed every 1-2 days)
include:
o Vaseline gauze
o Silver sulfadiazine under absorbent gauze
• Ensure tetanus immunity
• Give 50ml whole blood for every 1% full-thickness burn, half in
the second 4h of IV therapy and half after 24h
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Principles of fluid and electrolyte balance
Body composition:
• In a 70kg male, body composition is approximately:
o Fat (15kg)
o Protein (12kg)
o Water (42kg)
o Glycogen and minerals (1kg)
Fluid compartments:
• Total body water (TBW) is divided into 2 main compartments:
o Extracellular fluid (ECF) – water around cells
o Intracellular fluid (ICF) – water in the cytoplasm
• The ECF is further subdivided into:
o Interstitial (15L)
o Intravascular (3L)
o Transcellular (1kg):
• Mainly GI secretions and glomerular filtration
• High turnover (12L/day for GI tract and 170L/day for
glomerular filtration)
Body fluid composition:

• Extracellular fluid:
o Na 124mmol/L
o K 4mmol/L
• Intracellular fluid:
o Na 10mmol/L
o K 150mmol/L
• These concentrations are maintained by the Na-K-ATPase pump
in the cell membrane
24 hour intake and output of water and electrolytes in health:
Substance Intake Excretion and route

Water 2000-2500ml Kidney (1500ml)
Insensible losses (1000ml)
Sodium 100mmol Kidney (although sweat can have up to

120mmol/L)
Potassium 40-80mmol Kidney (note: restricted input is NOT

followed by a fall in excretion)
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Response to injury and fluid balance:

• As part of the response to injury, the secretion rate of cortisol,
aldosterone and ADH increases in the first 24-48 hours leading
to:
o A reduction in renal excretion of Na and, therefore, water
so that osmolality remains constant
o An increase in renal excretion of K, some of which is the
result of the amount of the tissue damage and breakdown
of cells
o Decreased renal water excretion with a urine of low
volume and high concentration, unresponsive to the
normal effect of any increase in water intake
• After this time, and depending on the degree of surgical trauma
and the presence or otherwise of sepsis, Na (and water
passively) retention may continue, with increased K excretion
Fluid management:
• Water and electrolyte therapy are divided into maintenance
needs, restoration of pre-existing deficits and replacement of
ongoing losses
• Provision of maintenance requirements:
o Water – 100 ml/hr (adjusted upwards for fever and/or high
ambient temperature)
o Sodium – 75mmol/day (but can be further reduced over
the first 2 days)
o Potassium – 60mmol/day
• Replacement of pre-existing deficits:
o Loss of ECF fluid:
• Is combined loss of Na and water
• Replaced with fluids which have a Na content close
to that in the extracellular space
• E.g. normal saline, Hartmann’ solution
o Loss from the stomach:
• Although H+ is lost, renal compensation takes place
with H+ reabsorption increased and excretion of K
and bicarbonate are raised
• In consequence, hypochloraemic alkalosis and
hypokalaemia may develop
o Pure water loss:
• Occurs only when either access to water is
impossible (e.g. trapped patients after injury) or
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there is a high obstruction to the GI tract (usually

oesophageal)
• Replacement is enteral if the obstruction can be
bypassed or by isotonic (6%) dextrose solution IV
• Replacement of ongoing losses:

o GI – Nasogastric aspiration, vomiting, fistulae and
diarrhoea
o Loss into an abnormal third space – usually the result of
inflammation (e.g. the retroperitoneal effusion that occurs
in pancreatitis)
In losses GI fistulae or diarrhoea, increased amounts of K are usually

required
The more distal in the intestine the source, the higher the K content
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Hernia
Definition:
• A hernia is a ‘protrusion of a viscus or other structure beyond
the normal coverings of the cavity in which it is contained or
between two adjacent cavities, such as the abdomen and the
thorax, or into a subcompartment of a cavity’
• The first category is commonly called external and the second
and third are internal
• The most frequent hernias are external ones of the abdominal
wall in the:
o Inguinal
o Femoral
o Umbilical, regions
Classification
• Hernias are best classified as congenital or acquired
• Congenital:
o There is a pre-formed sac which occurs as a consequence
of the ordered or disordered process of intra-uterine
development
o The patent processus vaginalis is a good example
• Acquired – are 2 types:
o Primary hernias – occur at natural weak points
o Secondary hernias – develop at sites of surgical or other
injury to the wall which normally constrains the contents of
a body cavity (usually the abdomen)
Aetiology:
• The 2 main factors predisposing to hernia are increased
intracavity pressure and a weakened abdominal wall
• Using the abdomen as an example:
o Increased intra-abdominal pressure:
• Heavy lifting
• Persistent cough (e.g. COAD)
• Straining to pass urine (e.g. BPH)
• Straining to pass faeces (>15% of men with large
bowel cancer present with an inguinal hernia)
• Abdominal distension (faeces, fat, flatus, fluid, foetus)
• Weakened abdominal wall:
• Abnormal collagen metabolism
• Advancing age
• Malnutrition
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• Damage to, or paralysis of, motor nerves
Anatomical features:
• A hernia consists of:
o A sac
o Its coverings
o Its contents
• The sac comprises a:
o Mouth
o Neck
o Body
o Fundus
• The coverings of a hernia refer to the overlying layers which are
attenuated as the hernia emerges
• Working from the outermost layer inwards, these are as follows:
o Skin
o Subcutaneous fat
o Aponeurosis
o Muscle
o Endo-cavity fascia
o Endothelial lining (peritoneum in the abdomen)
• The contents of hernias vary, but most intracavity viscera have
been reported
• In the abdomen, the commonest contents are the small bowel
and the greater omentum
• Other possibilities include:
o The large bowel and appendix
o Meckel’s diverticulum
o The bladder
o The ovary (with or without the fallopian tube)
o Ascetic fluid
Natural history and complications:

• The natural history of hernia development is progressive
enlargement, not spontaneous regression
• With the passage of time, the likelihood of a life-threatening
complication increases
• Hernias may be:
o Reducible
o Irreducible
o Obstructed
o Strangulated
o Inflamed
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Reducible hernia:
• The contents can be returned from whence they came, but the
sac persists
• The contents do not necessarily reappear spontaneously, but do
so when assisted by gravity or raised intra-abdominal pressure
Irreducible hernia:
• The contents cannot be returned to the body cavity in this type
of hernia
• The causes of irreducibility are:
o Narrow neck with rigid margins, often in association with a
capacious sac (e.g. femoral, umbilical)
o Adhesion formation between the contents and the sac
(usually long-standing hernias)
• Irreducible hernias have a greater risk of obstruction and
strangulation than do reducible ones
Obstructed hernia:
• Contains intestine in which the lumen has been occluded
• Obstruction is usually at the neck of the sac but may be caused
by adhesions within it
• If the obstruction is at both ends of the loop, fluid accumulates
within it and distension occurs (closed-loop obstruction)
• Initially, the blood supply to the obstructed loop of bowel is
intact, but with time this becomes impeded and strangulation
supervenes
• The term ‘incarcerated’ is sometimes used to describe a hernia
that is irreducible but not strangulated. Thus, an irreducible,
obstructed hernia can also be called an incarcerated one
Strangulated hernia:
• 10% of groin hernias present for the first time with strangulation
• The blood supply to the contents of the hernia is cut off
• The pathological sequence is:
o Venous/lymphatic occlusion and oedema causing further
swelling
o Venous haemorrhage develops and a vicious circle is set
up, with swelling eventually impeding arterial inflow
o The tissues undergo ischaemic necrosis
• If the contents of the sac of an abdominal hernia are NOT bowel
(e.g. omentum) then the necrosis is sterile, but strangulation of
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bowel is by far the most common and leads to infected necrosis

(gangrene):
o The mucosa sloughs
o Bowel wall becomes permeable to bacteria
o The bacteria translocate through the wall and into the sac
and from there into the bloodstream and peritoneal cavity
(causing peritonitis)
o Septic shock ensues with circulatory failure and death
Inflamed hernia:
• The contents of the sac are inflamed by any process that causes
this in the tissue or organ that is not normally herniated, e.g.:
o Acute appendicitis
o Meckel’s diverticulum
o Acute salpingitis
• It may be impossible to distinguish an inflamed hernia from one
that is strangulated
Surgical techniques:
• Herniotomy:
o Is the removal of the sac and closure of its neck
o It is the first step in nearly every hernia repair
• Herniorrhaphy – involves some sort of reconstruction to:
o Restore the anatomy if this is disturbed
o Increase the strength of the abdominal wall
o Construct a barrier to recurrence
Prognosis:
• Mortality:
o For elective repair, the overall mortality is <0.5%
o Increases with age to 0.5-1% for those over 60 years of
age
o For emergency operations, the mortality is 10x greater
o Mortality for strangulated hernia is ~20%
o Death is dependent on:
• Age
• Contents of the sac – gangrenous intestine (present
in 10% of strangulated hernias) is associated with a
40% mortality rate
• Morbidity:
o The overall complication rate is ~7%
o Specific complications include:
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• Persistent wound pain – often ascribed to a neuroma

which forms after damage to or division of the ilio-
inguinal or other nerve
• Cutaneous anaesthesia – division of a nerve
• Recurrent hernia
• The rate of recurrence is between 1-10% for primary hernias
and 5-30% for recurrent hernias
• Recurrence is associated with:
o Age
o Presence or absence of predisposing factors
o Site
o Size – the larger the hernia, the more likely it is to have
distorted the surrounding anatomy
o Emergency or elective operation – more likely to recur with
an emergency procedure
o Operation on a recurrent hernia – more difficult and more
likely to fail
o Experience of the surgeon
Inguinal hernia
Epidemiology:
• Account for 80% of all external abdominal hernias
• Most common in infants and the elderly
• Inguinal hernias are 20x more common in men than in women
• Occur most frequently on the right-hand side
Classification:
• Indirect inguinal hernia:
o This passes through the internal ring lateral to the inferior
epigastric artery and along the canal to emerge at the
external ring above the pubic crest and tubercle
o Its coverings are the attenuated layers of the cord
• Direct inguinal hernia:
o This hernia bulges out through the posterior wall of the
canal medial to the inferior epigastric artery
o Is, therefore, not covered by the layers of the cord
• Pantaloon hernia:
o This is a combination of both an indirect and a direct
inguinal hernia
Aetiology:
• Indirect hernia:
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o There is a congenital sac or potential sac which is the

remnant of the processus vaginalis
o If the processus does not close, then an indirect hernia
occurs in early life, but other factors may lead to it
reopening at any age
o Indirect hernias are 20x more common in men than in
women
o 60% occur on the right side (possibly contributed to by
damage to the motor nerves of the abdominal muscles at
open appendicectomy)
o 40% on the left
o 20% are bilateral
• Direct hernia:
o This is an acquired lesion
o For reasons unknown, the posterior wall of the inguinal
canal becomes attenuated
o Direct hernia is, therefore, a condition of later life and is
rarely seen under the age of 40 years
Differences between an indirect and a direct inguinal hernia:
Indirect Direct
Patient’s age Usually young Older
Cause May be congenital Acquired
Bilateral 20% 50%
Protrusion on coughing Oblique Straight
Appearance on standing Full size delay Full size
immediately
Reduction on lying Not immediate Immediate
Descent into scrotum Common Rare
Occlusion of internal ring Controls Does not control
Neck of sac Narrow Wide
Strangulation Not uncommon Unusual
Relation to inferior Lateral Medial
epigastric vessels
Clinical findings:
• If it is impossible to get above a groin swelling, it is most likely
to be an inguinal hernia
• In addition to the features listed above, an indirect hernia that
extends beyond the external ring appears above and medial to
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the pubic tubercle (in contrast to a femoral hernia, which is

below and lateral)
Other causes of groin swelling:

• Femoral hernia
• Hydrocele
• Undescended or ectopic testis
• Lipoma of the cord
• Epididymal cyst
Management:
• Most adult inguinal hernias are repaired by open operation under
local or general anaesthesia as a day case procedure
• Open operation usually means:
o A layered suture technique (Shouldice), or
o Insertion of a non-absorbable prosthetic mesh
(Lichtenstein)
• Alternatively, mesh repair may be done laparoscopically
Specific complications:
• Urinary retention:
o Because of the proximity of the inguinal region to urine
excretion in the male, temporary problems may be
encountered
o Rare with modern techniques (unless BPH has been
overlooked in the preoperative evaluation)
• Scrotal haematoma:
o May follow extensive dissection
• Damage to the ilio-inguinal nerve:
o Produces an area of anaesthesia over the:
• Pubic tubercle
• Scrotum/labia
Outcome:
• Recurrence rates for groin hernias should be <1%
• It is more widely quoted as 3% for primary hernias and up to
30% in the management of recurrence
Recurrent inguinal hernia:

• Factors involved in the recurrence include:
o Inadequate preoperative selection:
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• Those with unforgettable precipitating factors or

high-dose steroid therapy which interferes with
healing
o Type of hernia:
• Indirect hernias: 1-7% recurrence rate
• Direct hernias: 4-10% recurrence rate
o Type of operation:
• Repairs under tension do not heal with adequate
protection against recurrence
o Postoperative wound infection
Management of recurrence:
• Recurrent inguinal hernias should be repaired in order to avoid
the same complications that occur in primary hernias, which are
even more likely when recurrence has taken place
• Because of scarring, the dissection can be difficult and, in the
male, orchidectomy is sometimes performed to allow closure of
the deep ring
Femoral hernia
Overview:
• Femoral hernias are acquired downward protrusions of
peritoneum into the potential space of the femoral canal
• 33% of groin hernias in women and 5% in men
• Rare in children
• 20% are bilateral
History:
• Patient is typically a middle-aged or elderly female, often of thin
build
• Intermittent lump in the groin
• However, a major problem is that she may not have noticed the
lump and the first clinical presentation is with strangulation
(which occurs in 20%)
Signs:
• In a small hernia, a cough impulse is rare
• A larger hernia may be seen to bulge on straining just below the
medial part of the inguinal ligament
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• An irreducible hernia is a lump whose consistency varies

according to its contents, which may straddle the inguinal
ligament
• In consequence, it can be difficult to distinguish from an inguinal
hernia; although the upper medial border of a femoral hernia is
always below and lateral to the pubic tubercle
Strangulation:
• In contrast to a strangulated inguinal hernia, in a strangulated
femoral hernia, there are often no localising symptoms and signs
and the lump is often small, unimpressive and overlooked by the
patient
• The classic presentation is that of small bowel obstruction
• It is not unheard of for a femoral hernia to only be diagnosed
after gut perforation with spreading peritonitis
Management:
• All femoral hernias should be repaired without delay because of
their great risk of strangulation
• In elective operations, repair is usually by direct incision over the
hernia, excision of the sac and sutured closure of the femoral
canal
• For operation on a patient with obstruction or strangulation, it
may be necessary to open the abdomen to find the segment of
gut that has been trapped, should it reduce before it can be
dealt with
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Indications for referral to ITU
Sites for the care of the critically ill:

• Intensive care/therapy unit (ICU/ITU):
o An area where patients are treated for actual, impending
or potential organ failure
o Require a high degree of organ support, including
mechanical ventilation
o 1:1 nursing
o Medical cover immediately available
• High-dependency unit:
o An area where patients at high risk are continuously and
invasively monitored
o Mechanical ventilation is not normally required
o 1:2/3 nursing
o Medical cover immediately available
Criteria:
• It is very difficult to have set rules for who should be admitted
and who should not as patients in ITU are such a heterogeneous
group
• There are, however, some common criteria:
o Shock (systolic BP <90mmHg or 40mmHg fall from
baseline) not responding to therapy
o Respiratory failure:
• Type I - PaO2 <8kPa and PaO2 <6kPa
• Type II - PaO2 <8kPa and PaO2 >6kPa
o Severe acidosis (pH <7.25, BE<-8)
o Exhaustion, drowsiness or coma
o Respiratory arrest
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Pain and its relief
Overview:
• Surgical intervention almost always causes pain
• As it can have serious physiological and psychological
consequences, prevention is best, but if that cannot be
completely achieved, rapid and adequate relief is essential
• The intensity of postoperative pain that is perceived by the
patient is influenced by:
o Cultural and family background, upbringing, personality,
constitution, past experiences and motivation
o Amount of information provided preoperatively – the more
the better is a good guide
o Psychological factors which are often situation-specific,
such as emotional arousal and fear; a calm reassuring
attitude from the team is of great value and is helped by
close interpersonal relations with the patient
o Preoperative and postoperative support provided by the
whole team, which includes nurses and physiotherapists
Effects of postoperative pain:

Effect Outcome
Decreased respiratory excursion Hypoventilation
Pulmonary collapse/consolidation
GI atony Ileus, nausea/vomiting
Bladder atony Urinary retention
Catecholamine release Vasoconstriction, increased
blood viscosity, increased platelet
aggregation, increased cardiac
demands
Management:
• Management has increasingly become a specialised province of
either the anaesthetist or a pain management team
Prevention:
• A caring, sympathetic and informative approach by the team
does much to reduce the patient’s perception of pain, as does
assurance that any pain felt will be relieved at once
• Physical methods for preventing pain include:
o Gentle surgical technique with minimal tissue damage
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o Adequate immobilisation of areas that have been operated

when this is possible – limbs in particular and after
orthopaedic procedures
o Blockade of nerve impulses which may be achieved at a
number of sites on the afferent pathway
Therapy:
• All agents are better given on a regular basis rather than
withheld until relief is asked for
• NSAIDs, aspirin and Paracetamol:
o Are often sufficient for mild postoperative pain provided
the patient can swallow
• Narcotic (opioid) analgesics:
o Have long been the main agents used to counteract
postoperative pain
o Morphine sulphate remains the drug most widely used
o Immediately after the operation, they are given by the
parenteral route (IM or IV)
o It is now common for continuous infusion to be used so
that saturation of the opioid receptors in the brain is
achieved
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Postoperative chest infections
Definition:
• Infection of the respiratory tract includes a wide range of
conditions:
o Bronchitis
o Pneumonia
o Lung abscess
o Empyema
• An element of alveolar under-expansion after operation is
common – this can cause mild pyrexia
Organisms:
• Pneumococcus
• Haemophilus influenzae
• Gram (–ve) organisms can also be found in postoperative chest
infections
Symptoms:
• Fever
• Cough
• Breathlessness
• Confusion (from hypoxia)
Signs:
• Cyanosis
• Green sputum
• Consolidation on chest examination
Investigation:
• CXR
• Culture (sputum or bronchial washings)
• ABG
Management:
• Prophylaxis:
o Do not undertake elective surgical procedures in the
presence of uncontrolled respiratory infection
o In the postoperative period, provide adequate
postoperative analgesia, physiotherapy and early
mobilisation
• Treatment:
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o Initial administration of oxygen with the aim of restoring

normal blood gas tensions
• Antibiotic administration:
o A combination of penicillin and erythromycin is a common
first-line treatment which can be altered on the outcome of
sputum culture
o Drainage of focal collections (e.g. purulent pleural effusion
or an empyema)
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Postoperative circulatory collapse
Causes of postoperative circulatory collapse:

• Haemorrhage
• Severe sepsis, including septicaemia
• Myocardial infarction
• Pulmonary embolus
• Hypersensitivity reaction
Haemorrhage:
• Major postoperative haemorrhage can be recognised by:
• Evidence of overt bleeding including heavily bloodstained fluid
from a drain
• Cold and wet (clammy) peripheries
• Distension after abdominal procedures
• Usually, the diagnosis is self-evident but occasionally it may not
be apparent that major bleeding has occurred, particularly if the
patient is obese or if the drain malfunctions because of
obstruction by clot
• In such circumstances the diagnosis may need to be confirmed
by urgent, repeated Hb estimation and by US examination
• Management:
o The loss is stopped by control of the source of bleeding or
by correction or coagulopathy
o Either at the same time or immediately subsequently,
transfusion corrects the deficit
o Re-operation may be required to control a bleeding point
Severe sepsis and septicaemia:

• Septic circulatory failure is associated with:
o Surgical procedures carried out in the presence of sepsis
o Technical failure (e.g. anastomotic dihescence) with
intraperitoneal or intrathoracic leakage of GI contents
o General spread from a focus
o Bloodstream contamination from a device (most commonly
a central line)
o A direct effect of circulating cytokines, and other
inflammatory mediators, is to cause arteriolar dilatation so
that, in contrast to other forms of circulatory failure, the
peripheries may be warm
o In addition, there is loss of circulating blood volume as a
result of capillary leakage
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o High pyrexia
o Hypotension
o Tachycardia
o Warm periphery
• Management:
o Resuscitation is with IV fluids and IV antibiotics
o Re-exploration may be indicated to deal with a septic focus
or a technical failure
Hypersensitivity reactions:
• This may develop as an immune response to a blood infusion or
to drug administration (e.g. IV antibiotic)
• There is usually pyrexia and the circulatory collapse may also be
accompanied by respiratory distress and urticaria
• Management:
o Discontinue the drug/infusion
o IV corticosteroids
o Circulatory support
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Postoperative monitoring
Specific signs that may be important in the early postoperative period:

Sign Possible meanings
Respiratory distress Hypoxia
Tachypnoea
Cyanosis
CNS depression Over-sedation
CO2 retention
Agitation Blood loss
Hypoxia
Pain
Disorientation Inappropriate sedation
Hypoxia
Severe inappropriate pain Local complication at site of operation
e.g. bleeding, ischaemia, leakage of
secretions
Bleeding Uncontrolled blood vessel
Soft tissue haematoma Clotting disorder
Irregular pulse Unrecognised cardiac disorder,
hypoxia
Skin pallor, empty veins, Hypovolaemia
hypotension, tachycardia
Routine postoperative monitoring of clinical signs:

Measurement Possible significance
Low temperature Excessive heat loss during surgery
Reduced metabolic rate (possibly from
poor peripheral perfusion)
High temperature Core but not peripheral – peripheral
vasoconstriction, possibly from blood loss
Core and peripheral – 1-2˚C normal in
Pulse rate, BP Changes beyond minor variations imply
possible circulatory instability
CVP Sensitive guide to venous return to the
heart
Increased resp rate CO2 retention, hypoxia
Decreased resp rate Over-sedation
Urine output (hourly) Indirect measure of renal perfusion
Fluid intake/output Ensures that neither over- or under-
perfusion occurs
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Additional vital signs often measured in the ICU:

Measurement Possible significance
Arterial manometry Earlier detection of changes in BP
Continuous CVP monitoring Assessment of venous return
Pulmonary artery pressure Detection of left heart strain
Pulse oximetry Arterial oxygen saturation
Continuous ECG Detection of arrhythmias
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Pressure sores
(decubitus ulcers)
Overview:
• These occur in the:
o Elderly
o Immobile
o Unconscious
o Paralysed
• They are due to skin ischaemia from sustained pressure over a
bony joint, most commonly the heel and sacrum
• Normal individuals feel the pain of continued pressure and, even
during sleep, movement takes place to change posture
continually
• 70% of pressure sores occur in hospital
• 70% appear in the first 2 weeks of hospitalisation
• 70% are in orthopaedic patients (especially those on traction)
• 80% of patients with deep ulcers involving the subcutaneous
tissue die in the first 4 months
• Altered sensation of the skin increases the risk of ulceration, and
patients with diseases that affect the circulation and tissue
nutrition are also predisposed, e.g.:
o Rheumatoid arthritis
o Diabetes mellitus
o Peripheral vascular disease
• General illness, anaemia, malnutrition and oedema may affect
skin breakdown
• Other predisposing factors include:
o Anaesthesia
o Surgery
o Sedation
o Dehydration
o Urinary incontinence
o Faecal impaction
• The early sign of red/blue discolouration of the skin can lead
rapidly to ulcers in 1-2 hours
• Leaving patients on hard A&E trolleys, or sitting them in chairs
for prolonged periods, must be avoided
Management:
• General measures should include identifying at-risk patients
• Those with non-fading marking of the skin on pressure sites
need immediate attention
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• The following are used in management:

o Bedrest with pillow to keep pressure off bony areas (e.g.
pelvis and heels)
o Regular turning, but avoid pressure on hips
o Fleece over lower 1/3 of bed for heels
o Roto cushions for patients in wheelchairs
o Treatment of general circulation
o Special mattresses and beds to relieve pressure areas
o Topical treatment:
• Keep ulcer clean and moist
• Many topical therapies are HARMFUL
o Pain relief (may need diamorphine)
o Plastic surgery
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Procedure for blood transfusion
Blood grouping:
• The ABO and RhD groups of the patient are determined
Antibody screening:
• The patient’s serum is screened for atypical antibodies that may
cause a significant reduction in the survival of the transfused
RBCs
• The patient’s serum is tested against RBCs from at least 2 group
O donors, expressing a wide range of RBC antigens, for detection
of IgM RBC alloantibodies and IgG antibodies
• If there is a positive result, the blood group specificity of the
antibody should be determined using a comprehensive panel of
typed RBCs
Selection of donor blood and cross-matching:

• Donor blood of the same ABO and RhD group as the patient is
selected
Cross-matching procedures:
• Patients without atypical RBC antibodies:
o The full cross-match involves testing the patient’s serum
against the donor RBCs suspended in saline in a direct
agglutination test, and also using an indirect antiglobulin
test
• Patients with atypical RBC antibodies:
o Donor blood should be selected that lacks the relevant RBC
antigen(s), as well as being the same ABO and RhD group
as the patient
o A full cross-match should always be carried out
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Scrotal swellings
A non-inflammatory swelling of the scrotal contents may be a:

• Testicular tumour
• Epididymal cyst (spermatocele)
• Varicocele
• Hydrocele
• Hernia
Clinical examination:
• The following points enable distinctions to be made:
o If it is possible to get above the swelling and palpate a
normal cord, the swelling is NOT a hernia
o If there is a cough impulse in the groin or, with the patient
lying flat, the scrotal mass disappears or is reducible, the
swelling is a hernia
o If the testicle lies anteriorly and the epididymis posteriorly,
gentle palpation establishes where the swelling lies and
therefore its origin
o Hydroceles transilluminate
o Varicoceles are more apparent with the patient standing
and feel like a bag of worms
Testicular tumours
Aetiology and epidemiology:

• Maldescended testes (particularly those retained within the
abdomen) have a 40% greater chance of malignant change than
does a normal testes
• Otherwise the cause is unknown
• Incidence is 2-3 per 100,000 per year
• Are rare before puberty
• Teratomas have a peak incidence at 20-30 years
• Seminoma have a peak incidence at 30-40 years
• Lymphomas (which are often bilateral) have a peak incidence at
60-70 years
• Classification of germ cell tumours is as follows:
o Seminoma
o Teratoma
o Mixed:
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• These consist of both seminomatous and

teratomatous elements, but should be treated as
teratomas
• Teratomas of the testis:

o Differentiated – teratoma differentiated (TD)
o Intermediate – malignant teratoma intermediate (MTI)
o Undifferentiated – malignant teratoma undifferentiated
(MTU)
o Trophoblastic – malignant teratoma trophoblastic (MTT)
Symptoms:
• 10% give a history of previous orchidopexy and in 5% the
tumour is bilateral
• Often a recent history of trauma (is not a cause but merely
draws the patient’s attention to the presence of a lump)
• Painless swelling which causes a dragging sensation in the
scrotum
• In 30%, the swelling is painful
• Patients with choriocarcinoma may develop gynaecomastia
• Others present with symptoms from secondary deposits such as:
o Backache
o Haemoptysis
o Neurological complaints
Signs:
• A hard lump in the body of the testis
• Diffuse testicular enlargement
• Absence of tenderness on gently squeezing the testicle
• Hydrocele
Investigation:
• Tumour markers:
o !-fetoprotein (AFP)
o ß-human chorionic gonadotrophin (ß-HCG)
o LDH
o Placental ALP (seminomas)
• Ultrasound:
o Helpful for determining the nature of the mass if this is not
possible clinically
o The normal testis has a homogeneous appearance
o Malignant tumours are inhomogeneous, may be cystic and
are often associated with speckled calcification
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• CT scan of the chest and abdomen:

o To identify pulmonary deposits and lymphadenopathy
Staging:
Stage Findings
I Tumour limited to testis
II Tumour of testis and retro-peritoneal lymph nodes
III Involvement of infra- and supra-diaphragmatic lymph
nodes
IV Extra-lymphatic metastases
Management:
• Improvements in therapy mean that the majority of testicular
tumours should be regarded as curable
• Surgery:
o Orchidectomy is done through a groin incision (operations
through the scrotum have a high incidence of tumour
implantation)
o In order to reduce the risk of disseminating malignant cells
by manipulation of the testis, the cord is mobilised and
occluded with a non-crushing intestinal clamp before the
testis is delivered from the scrotum
o In men with a small or atrophic contralateral testis, or a
history of subfertility, a biopsy from the contralateral testis
should be taken:
• Up to 5% of men will have carcinoma in situ
involving the other testis
• Supplementary management:
o If chemotherapy is to be used, the patient should be
advised to store semen prior to the chemotherapy
o Patients with testicular tumours are often subfertile and
chemotherapy may result in irreversible germ cell damage
Supplementary mx of seminoma/teratoma after orchidectomy:
Stage Seminoma Teratoma

I Pelvic and para-aortic irradiation Surveillance
Platinum-based
chemotherapy
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IIa/b Irradiation Platinum-based

chemotherapy
IIc Radical retroperitoneal Platinum-based
l y m p h a d e n e c t o m y
chemotherapy
Prognosis:
• Stage I – 100% of patients survive
• Stage II/III – 5-year survival is between 80-90%
• Seminoma:
o For a tumour localised to the testis, >95% of patients
should survive 5 years
o For those who present with metastatic disease, the 5-year
survival is ~75%
• Non-seminomatous germ-cell tumours:
o For those with a tumour confined to the testis and low
tumour markers, 90% survive 5 years
o If the tumour markers are grossly elevated and
metastases are confined only to the lungs, 80% survive 5
years
o If there are visceral metastases and grossly elevated
tumour markers, the 5-year survival falls to 45%
Epididymal cysts and spermatoceles
These may be single or multiple and are usually related to the head of
the epididymis
They lie posterior to the testicle and may transilluminate
Management:
• Asymptomatic cysts do not require treatment
• If they cause discomfort, simple aspiration is often satisfactory:
o Spermatoceles – turbid milky fluid
o Epididymal cysts – lemon barley coloured fluid
o Should recurrence occur after aspiration, surgical excision
is required
Varicocele
Aetiology and pathological features:
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• The venous valve at the junction of the left spermatic vein with
the renal vein is incompetent or becomes so
• It is most uncommon for the same to take place on the right
• Very occasionally, a tumour in the kidney with extension along
the renal vein may be present
• Varicocele is a common finding in men presenting with
subfertility but is equally common in men requesting vasectomy
for contraception
• The veins of the pampiniform plexus become enlarged and
tortuous
Clinical features:
• There is a dragging sensation in the scrotum which is worse in
hot weather and on prolonged standing
• Subfertility may be mentioned
• Physical examination reveals the ‘bag of worms’ which becomes
more obvious if the patient stands
• A cough impulse is present in the same position
• The left testicle may be smaller than the right
Management:
• Treatment is required for those with symptoms and for those
with subfertility
• The procedure of choice is embolisation of the testicular vein
under radiological control
Hydrocele
Aetiology:
• May be congenital or acquired
• Congenital:
o Follow failure of obliteration of the processus vaginalis
o Peritoneal fluid can then enter the scrotum
• Acquired:
o The great majority are of unknown origin
o 10% are associated with testicular tumour or infection
Clinical features:
• A infant presents with a large scrotal sac and the hydrocele is
easily demonstrated by transillumination
• In adult life, there is a firm, painless transilluminable swelling
which it is possible to get above
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Management:
• Congenital:
o Majority resolve by the age of 3 years
o Persistence beyond this time requires operative treatment
by division and ligation of the processus
• Acquired:
o Aspiration is first done to allow examination of the testicle
for any underlying cause
o Sometimes this is therapeutic and the hydrocele does not
recur
o If it does, surgical excision of the outer wall of the
hydrocele is required
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Wound healing
Phases of wound healing:

• Inflammatory (preparative)
• Reparative
• Consolidative
Inflammatory phase:
• Bleeding followed by clotting and then clot lysis
• Inflammatory cytokine release with:
o Cell swelling
o Increased capillary permeability
o Intercellular oedema
o Migration of leucocytes into the damaged area
• Phagocytosis (by macrophages) of dead cells and other debris
• The inflammatory phase lasts ~3 days
Reparative phase:
• Formation of new capillary loops in the damaged area. These
provide a blood supply for subsequent events
• Fibroblasts appear:
o These are capable of producing strands of collagen.
• Deposition of extracellular collagen – at first provisional and
apparently untidy but gradually becoming orientated along any
lines of stress applied to the wound
• This mass of granulation tissue begins to contract (probably
through the effects of specialised myofibroblasts)
• A distinction is drawn between this active process of contraction
of the whole wound mass and the later shrinkage of mature
collagen, which may lead to distortion of a healed area – known
by the general term contracture
Consolidative phase:
• Collagen synthesis = degradation (both accelerated)
• Ratio of collagen reverts back to normal
• Increased cross-linkage of collagen
• Increased tensile strength (maximum 80%)
• Vascularity of the wound gradually decreases
Collagen:
• Are >14 types
• Ratio of type I: type III
o 4:1 in normal skin
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o 2:1 in granulation tissue
Local factors inhibiting wound healing:

• Infection
• Ischaemia
• Foreign bodies
• Tumour
Systemic factors inhibiting wound healing:

• Malnutrition
• Vitamin A and C deficiency
• Diabetes
• Jaundice
• Renal failure
• Steroid or cytotoxic treatment
• Radiotherapy
• Age
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Wound management
Haemorrhage
Overview:
• A dry wound (i.e. one with minimal oozing) is an essential
prerequisite for successful closure to achieve the best result with
minimal formation of fibrous tissue
• Failure to achieve adequate control of bleeding:
o Keeps the wound edges apart and thus requires a larger
gap to be bridged, which leads to a greater deposition of
fibrous tissue
o May result in a haematoma:
• An accumulation of clot which is lysed and may require
release before the wound edges can be opposed
o May lead to infection:
• A haematoma is an ideal place in which bacteria can
multiply
• The 3 main techniques used to stop bleeding are:
o Compression
o Ligation
o Thermal coagulation
Compression:
• Packing a bleeding cavity or applying pressure to a bleeding area
are both particularly useful if there is widespread oozing
• 5 minutes of compression allows normal haemostasis to take
place by:
o Contraction of the mouths of small vessels
o Platelet aggregation
o Clotting
• However, these processes must be normal for the effective
arrest of bleeding
Ligation:
• The mouth of the divided vessel which bleeding is picked up with
special forceps (haemostats) and tied off with a ligature (either
absorbable or non-absorbable)
• Absorbable sutures:
o Have a clear advantage in that, once the vessel has been
occluded and has thrombosed behind the point of ligature,
the suture ultimately disappears so that the foreign body
reaction is minimal
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o However, they may degrade too fast, especially in the

presence of sepsis and, in consequence, secondary
haemorrhage may occur
• For this reason, large vessels are more often ligated with non-
absorbables, which may be braided for easy handling
• Blood vessels and other small tubes (e.g. the cystic duct) may
also be closed with stainless steel clips carried on a special
forceps
• Larger vessels may be transected using vascular stapling
instruments
Thermal coagulation:
• This involves the use of diathermy (or cautery in the USA)
• Is a high-frequency electric current
• The pathway of current is either:
o Unipolar (from the point of application through the body of
the patient to a large area contact plate and thence to
earth )
o Bipolar (between 2 points of the instrument)
• Small blood vessels can be precisely dealt with using either
technique and the method is also used for cutting soft tissues
with minimal bleeding when a continuous waveform is produced
and an arc is generated between the electrode and the tissue
• Vaporisation of the water in the cells occurs with disruption of
tissue continuity (so-called cutting diathermy)
Infection
Wound classes:
• There are 4 classes:
o Incised – of recent origin without significant contamination
o Lacerated – of recent origin, with tissue damage and/or
contamination
o Late – 6-18 hours after injury
o Infected – wounds seen beyond 18-24 hours. Must be
regarded as infected
Bacteria can be assumed to be present in all accidental wounds and in

those sustained at a surgical operation when an area that is colonised
by organisms is involved (e.g. the colon)
Good wound care is the first essential for the prevention of infection:
• In accidental injury:
o Debridement
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o Delayed primary closure

• In surgical incisions:
o Debridement is unnecessary
o Delayed closure is sometimes useful if there is
contamination at operation
• Many wounds can be assumed to be contaminated the moment
they are sustained (e.g. when the abdomen is opened to deal
with an intraperitoneal infection):
o In the early part of the preparative phase (when bacterial
proliferation is just beginning) it may be possible to
eliminate these organisms by establishing a high
concentration of antibiotic in the tissues by parenteral
administration
o This prophylactic use of antibiotics over a short period of
time is now common in many circumstances
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GI Surgery
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Acute appendicitis
Epidemiology:
• Most common surgical emergency
• Lifetime incidence of 6%
Pathogenesis:
• Gut organisms invade the appendix wall after lumen obstruction
by:
1. Lymphoid hyperplasia
2. Faecalith (a small, hard mass of faeces)
3. Filarial worms
• There may be impaired ability to prevent invasion, brought about
by improved hygiene (so less exposure to gut pathogens), the so
called ‘hygiene hypothesis’
Symptoms:
• As inflammation begins – central abdominal colic
• Once peritoneum inflamed – pain shifts to RIF and becomes
more constant
• Anorexia
• Constipation
• Vomiting (occasionally)
• Diarrhoea (occasionally)
Signs:
• Tachycardia
• Pyrexia (37.5˚-38.5˚)
• Shallow breathing
• Furred tongue
• Coughing hurts
• Lying still
Signs in RIF:
• Tenderness
• Guarding
• Rebound tenderness
• Painful PR on right
Differential dx (in no particular order):

• Ectopic pregnancy
• Mesenteric adenitis (inflammation of mesenteric lymph nodes)
• Food poisoning
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• Diverticulitis
• Salpingitis (inflammation of one/both Fallopian tube(s))
• Cholecystitis (inflammation of the urinary bladder)
• Perforated ulcer
• Crohn’s disease
• Cystitis
Management:
• Prompt appendicectomy
• 3 doses IV A/Bs starting 1 hr pre-op decreases wound infections
(Metronidazole 1g/8h + Cefuroxime 1.5g/8h)
Complications:
• Perforation leading to peritonitis (with later infertility in girls)
• Appendix mass (inflamed appendix surrounded by omentum)
• Appendix abscess
Appendicitis in pregnancy:
• 1 in 2000 pregnancies
• Pain/tenderness is higher due to displacement of appendix by
uterus
• Appendicectomy is well tolerated but foetal mortality approaches
30% after perforation
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Acute cholangitis
Aetiopathogenesis:
• Organisms enter the biliary tree either from the GI tract via the
duodenal papilla or by excretion in the bile after reaching the
liver via the bloodstream.
• In the bile, these organisms multiply in the presence of an
obstruction to cause inflammation
• In the Western world, the most common cause of this
obstruction is a common bile duct stone(s)
• Infected bile in the biliary tree is potentially fatal because it may
lead to septicaemia and hepatorenal failure.
• Long-term sequelae of repeated attacks of cholangitis include:
o Liver abscesses
o Secondary biliary cirrhosis
o Liver failure
o Portal hypertension
Clinical features:
• Charcot’s triad:
o Abdominal pain
o High fever with rigors
o Jaundice
• Past history of biliary disease may be obtained
• The liver may be somewhat enlarged and tender
Investigation:
• Full blood count:
o Leucocytosis
• LFTs:
o Cholestasis (raised ALP)
• Blood cultures:
o Positive in most instances
• Ultrasound:
o Gallbladder stones
o Dilated duct
o Ductal stone (occasionally)
Management:
• Resuscitation with IV fluids and parenteral A/Bs are begun on a
best guess basis
• A prompt response will result in:
o Relief of symptoms
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o Resolution of fever
o Rapid reduction in jaundice
• Failure to achieve this indicates the need for bile duct drainage
by urgent ERCP
• If possible, stones should be extracted, but effective biliary
drainage is the first essential requirement
• Treatment of cholelithiasis can be deferred until the acute
episode has settled
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Acute cholecystitis
Clinical features:
• The symptoms are similar to biliary colic but:
o Pain is more severe and persistent
o Nausea/vomiting
o Fever
o Tenderness/guarding in the RUQ
o Murphy’s sign:
• Lay a hand lightly on the upper right abdomen and ask
the patient to take a deep breath in
• A positive sign will be revealed by the pt ‘catching their
breath’ caused by the inflamed gallbladder impacting
on the examining hand
Investigations:
• Blood tests:
o Leucocytosis
o Raised Bilirubin
o Moderately elevated serum amylase
• Imaging:
o Ultrasound shows an enlarged gallbladder with:
• Stone(s)
• Thickened wall
• Surrounding rim of fluid from local oedema
Management:
• Conservative (the initial treatment):
o Analgesia
o Systemic A/Bs
o IV fluids
• Operative (if conservative treatment fails):
o Cholecystectomy is curative and must be performed if
initial treatment fails to work due to the risk of perforation
or the formation of an empyema
Perforation:
• This is caused by a progressive rise in tension in the gallbladder
• The blood supply of the wall becomes reduced and gangrene
occurs (usually at the fundus)
• Abdominal pain becomes increasingly severe and more
generalised
• Perforation may lead to diffuse peritonitis
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• A variant is local perforation with abscess formation
Empyema and pericholecystic abscess:

• The infection remains localised, with the accumulation of pus
within the gallbladder.
• Swinging fever
• Tachycardia
• Tender mass in the RUQ
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Acute peritonitis
Acute peritonitis may be localised or general
Localized peritonitis:
• There is virtually always some degree of localized peritonitis with
all acute inflammatory conditions of the GI tract
• Pain and tenderness are largely features of this localized
peritonitis
• Rx is of the underlying disease
General peritonitis:
• Serious condition resulting from irritation of the peritoneum
• Caused by:
o Infection (e.g. perforated appendix)
o Chemical irritation due to leakage of intestinal contents
(e.g. perforated ulcer)
• The peritoneal cavity becomes acutely inflamed with production
of an inflammatory exudate that spreads throughout the
peritoneum leading to intestinal dilatation and paralytic ileus.
Clinical features:
• When the peritonitis is due to perforation:
o Sudden onset
o General collapse
o Shock
o Pt may improve temporarily, only to deteriorate later as
generalized toxaemia develops
• When the peritonitis is secondary to inflammatory disease:
o Onset is less rapid
o Initial features being that of the underlying disease
Investigations:
• Erect CXR (to detect free air under the diaphragm)
• Serum amylase (to diagnose acute pancreatitis)
• US or CT is becoming popular for diagnosis
Management:
• Peritonitis is always treatment surgically after adequate
resuscitation with the re-establishment of a good urinary output
• Insertion of a NG tube
• IV fluids
• A/Bs
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• Is two-fold:
o Peritoneal lavage of the abdominal cavity
o Specific treatment if the underlying condition
Complications:
• Delays in treatment produces more profound toxaemia and
septicaemia
• Local abscess formation can occur and should be suspected if the
pt continues to remain unwell post-op with a:
• Swinging fever
• High WCC
• Continuing pain
• Abscesses are typically pelvic or subphrenic:
o Treatment is with drainage and A/Bs
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Large bowel neoplasms
Benign
Epidemiology:
• Up to 10% of the Western world’s population may have a benign
tumour(s)
• Adenomas are the most common and important benign large
bowel neoplasms.
• Arise from glandular or epithelial cells
• The tumour is most often a polyp with a stalk but flat (sessile)
lesions also occur
• May be single or multiple (and in the polyposis syndromes,
hundreds may be present)
Classification of colorectal polyps:

• Neoplastic:
o Adenoma
• Tubular
• Tubulovillous
• Villous
• Non-neoplastic:
o Hamartoma
• Juvenile
• Peutz-Jegher’s
o Inflammatory:
• Lymphoid
• Inflammatory
o Miscellaneous:
• Metaplastic
• Connective tissue polyps
Clinical features:
• Most adenomas are asymptomatic and devoid of signs
• Diagnosis is usually made either as the result of a screening
programme or on incidental examination of the large bowel by
colonoscopy or Barium enema
Management:
The finding of an adenomatous polyp (particularly if > 1cm) requires
the following action:
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• Complete examination of the large bowel by colonoscopy to

exclude or identify other similar neoplasms
• Removal of all lesions (usually endoscopically)
• Regular lifelong surveillance for recurrence and/or development
of large bowel cancer
Malignant
Epidemiology:
• Second most common malignancy (behind ca bronchus)
• Peak age incidence is in those > 60yrs
Aetiological factors:
• Diet:
o Bile salt conversion:
• It is believed that a diet rich in animal fat is a major
risk factor
• Such a diet (common in the Western world) produces
an environment within the gut which favours the
bacterial conversion of bile salts to carcinogens
o Low intake of fibre:
• This slows down gut transit time and, therefore,
increases the time of exposure of the mucosa to
carcinogens
• Adenomatous polyps
• Genetic factors:
o FAP is an inevitable cause of cancer
o 2-3x increased risk to a first-degree relative of a pt with
adenocarcinoma
o This hereditary non-polyposis colon cancer (HNPCC)
probably accounts for ~10% of colon malignancies
• Inflammatory bowel disease (CD and UC)
• Distribution:
o Rectum 57%
o Sigmoid colon 21%
• Synchronous lesions:
o Up to 3% of pts have one or more synchronous cancers
o 75% of pts have a benign adenoma
• Macroscopic classification:
o Polypoid
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o Ulcerative
o Annular
o Combination of the above
• Spread:
o Direct extension
o Lymphatic (largely upwards to the aorta and portal vein)
o Haematogenous (mainly to liver)
o Transcoelomic (can lead to ascites)
o Direct implantation (iatrogenic)
Staging – Dukes classification:

• Duke’s A:
o The tumour is confined to the mucosa
o 5yr survival is 90%
• Duke’s B:
o The tumour has extended through all the muscle layers
and has possibly reached the serosa
o There are NO metastases to lymph nodes
• Duke’s C:
o As for stage B but with lymph node metastases:
• Duke’s C1 – Local lymph node involvement only
• Duke’s C2 – Distant lymph node involvement
• Duke’s D:
o This was not part of the original classification
o Indicates distant metastases or residual disease following
surgery
Clinical features:
• Alteration in bowel habit
• Rectal bleeding
• Weight loss
• Abdominal pain
• Malaise
• Tenesmus
Clinical features – Right-sided tumours:

• Malaise
• Weight loss
• Vague abdominal pain
• (Occasionally) a self-detected mass in the abdomen
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Clinical features – Left-sided tumours:

• These are much more likely to present with obstructive
symptoms:
o Colicky abdominal pain
o Change in bowel habit (diarrhoea or constipation)
Clinical features – rectal tumours:

• Rectal bleeding (usually on defaecation)
• Tenesmus
• A growth that has spread locally may cause:
o Faecal incontinence from invasion of the anal sphincters
o Back pain because of involvement of the sacral plexus
o UTIs, retrovesical fistula or renal failure through infiltration
of the renal tract
Investigation:
• PR exam
• Sigmoidoscopy:
o Biopsy of any mucosal abnormality
• Barium enema (if colonoscopy is unavailable)
• Colonoscopy
• Assessment of extent of disease and of spread:
o Carcinoembryonic antigen (CEA) is a useful marker of the
elimination of disease and the emergence of recurrence
o CT scan
Management – Colon carcinoma:

• Duke’s A-C:
o Surgical excision
• Duke’s B-C:
o As above + adjuvant therapy
• Right-sided tumours are removed by a right hemi-colectomy
• Left-sided tumours are removed by a resection tailored to the
segment of bowel involved.
Management – Rectal carcinoma:

• Mid or upper rectal tumour:
o Removed by resecting the distal colon and involved rectum
and restoring the continuity by joining the large bowel to
the stump of the rectum (known as an anterior resection)
• Low rectal tumour:
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o Requires the removal of the whole rectum and adjacent

sphincters (abdominoperineal resection and colostomy)
and operation usually only carried out by two surgeons –
one working within the abdomen and the other from the
perineum
Complications of colectomy and rectal excision:

• Haemorrhage
• Ureteric damage
• Damage to bladder function
• Damage to sexual function
• Damage to duodenum (right hemi-colectomy)
• Damage to spleen (left hemi-colectomy)
• Anastomotic complications (stenosis/leakage)
• Complications of stoma
• Diarrhoea/constipation
Adjuvant therapy:
• Radiation:
o Pts with Duke’s B and C rectal carcinoma should receive
local deep X-Ray therapy
• Chemotherapy:
o Although solid-tumours such as colorectal cancers are not
very sensitive to chemotherapy, there is evidence that
results can be improved in Duke’s B and C by the use of
chemotherapy with 5-fluouracil
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Biliary colic
Caused by a stone impacted within the gallbladder – usually within

Hartmann’s pouch or the cystic duct
Clinical features:
• Waves of pain in the epigastrium and right upper quadrant
• Pain radiates through to the back, in the region of the inferior
angle of the scapula
• Attacks of pain last for between 15mins to 7hrs
• Pain is often exacerbated by ingestion of fatty foods (as these
stimulate the release of CCK, which causes gallbladder
contraction)
• Vomiting is common
Investigations:
• Plain X-Ray:
o Reveals only 10% of gallstones (the remainder have
insufficient radio-density)
• Ultrasound:
o Detects 98% of gallbladder stones
o Less reliable at detecting stones within the bile ducts
o Provides additional information on:
• Thickness of the gallbladder wall
• Diameter of the common bile duct
• Architecture of the liver and pancreas
Management:
• Parenteral analgesics (e.g. Morphine, Pethidine) to relieve the
acute exacerbations of pain
• Condition nearly always resolves over the course of a few hours
• If the diagnosis is confirmed by imaging, subsequent
cholecystectomy is usually indicated
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Cancer of the oesophagus
Epidemiology:
• Far East >> West
• In Europe 2-8 per 100,000 population
Aetiology:
• Squamous cell carcinoma (55%) – 40% in middle 1/3, 15% in
upper 1/3:
• Diet is probably of the most importance:
o High intake of nitrosamines derived from nitrates used in
food preservatives
o Low intake of both vitamin A and nicotinic acid
o Fe deficiency anaemia
• Adenocarcinoma (45%) – occurs in the lower 1/3:
o Metaplastic change in the oesophageal mucosa from
Squamous to columnar epithelium as a result of reflux
(Barrett’s oesophagus) predisposes to the development of
adenocarcinoma
• Nearly all lesions are a combination of narrowing and ulceration,
although the extent of each varies
• Spread takes place by:
o Direct invasion:
• Into adjacent structures such as:
• Trachea
• Bronchi
• Pericardium
• Chest wall
• Diaphragm
• Once a fistula into the air passages has occurred, the
condition is incurable and the life expectancy is short
o Submucosal infiltration
o Lymph node involvement:
• In the mediastinum and, in distal lesion, around the
stomach
• Upward spread in the mediastinum may produce a
sentinel node in the supraclavicular fossa
o The bloodstream:
• Unusual in the early stages
• By the time of death, 90% of pts may have distant
metastases (liver, lung and brain)
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Symptoms:
• Early ill-defined symptoms:
o Feeling of an oesophageal obstruction
o Retrosternal discomfort
o Belching
o Dyspepsia
• Progressive dysphasia:
o Most common and important presenting symptom
o At first there is dysphagia for solids only, only later is there
difficulty with liquids
• Weight loss
• Acute obstruction:
o Usually precipitated by the impaction of a large (usually
inadequately chewed) bolus of food
• Hoarseness:
o Caused by the involvement of the recurrent laryngeal
nerve
Signs:
• Lymphadenopathy (25%) – usually of the supraclavicular region
• Is an indication of metastatic disease
Investigations:
• Barium swallow:
o Preferred first-line ix
o High sensitivity in the diagnosis of a stricture (although
this does not, necessarily, mean that it is malignant)
o Accurate determination of the anatomical site
o Simple
o Cheap
• Endoscopy:
o This is done under LA and allows:
• Biopsy and brush cytology
• Partial assessment of the extent of the lesion
• Concurrent dilatation and temporary relief of
obstruction
• However there are some dangers, such as:
• Failure to detect a small lesion
• Perforation of a growth
• Ultrasound:
o May demonstrate liver metastases and/or enlarged lymph
nodes
• CT:
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o Helpful in determining the size of the primary tumour and

whether it is attached to surrounding structures
o To detect metastases
Surgical resection:
• In the overwhelming no. of cases, surgical intervention is purely
palliative (e.g. to relieve dysphagia)
• There are two main procedures available for resecting tumours
of the oesophagus that do not require a thoracotomy
• These are described below
• Trans-hiatal removal:
o The abdomen alone is opened and the oesophagus freed in
the chest by blunt dissection through the diaphragmatic
hiatus
o Stomach or colon for reconstruction is then passed through
the posterior mediastinum to the neck, where it is
anastomosed to the upper oesophagus through a cervical
incision
• Endoscopic removal:
o The whole procedure can now be done endoscopically by
dissection within the chest (thoracoscopy) and abdomen
(laparoscopy), although there is no evidence that this
method is better than an open operation.
Other methods of alleviating dysphagia:

• Radiotherapy:
o Relief is not immediate and up to 1/3 of pts develop a
fibrous stricture
• Chemotherapy with 5-Fluouracil (5-FU):
o Can lead to total disappearance of the local tumour in 25%
of pts. However, recurrence after some months is
inevitable
• Dilation and intubation
• Local endoscopic destruction of the tumour by laser
• Local injection of absolute alcohol
Prognosis:
• When tumour is confined to the mucosa – 5yr survival of 60%
• If tumour has penetrated the full thickness of the gullet – 5yr
survival is < 5%
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Carcinoma of the pancreas
Epidemiology:
• Fourth leading cause of death from cancer in the Western world
• In the UK ~ 5000 deaths per year
• Peak incidence is 50-70 yrs (although it occasionally occurs in
those as young as 30 yrs)
Aetiology:
• Putative factors in exocrine pancreatic cancer:
o ‘Western’ lifestyle
o Cigarette smoking (perhaps due to nitrosamine inhalation)
o High-fat diet
o Working in chemical industries:
• Beta-naphthylamines
• Benzidine
• Petroleum
• Dry cleaning
• Nuclear fuels
• Coke and coal gas
• Men >> women (2 : 1)
• 95% of tumours are adenocarcinomas, originating from the
pancreatic ducts
• 70% of tumours occur in the pancreatic head
• Spread of the tumour is by four typical routes:
o Direct invasion
o Lymphatic
o Haematogenous
o Transcoelomic
•Direct invasion:
o Cancers arising from the pancreatic head invade and
obstruct the lower end of the common bile duct to produce
extra-hepatic obstructive jaundice
o The development of obstruction causes the biliary tree to
dilate
o Of those pts with a tumour of the head of the pancreas,
15-20% have direct invasion of the duodenum, resulting in
gastric outflow obstruction and vomiting
•Lymphatic:
o The most common nodes involved are the:
• Pre-aortic coeliac nodes
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• Nodes of the porta-hepatis

•Haematogenous:
o The tumour drains into the portal vein and liver
metastases are most common
•Transcoelomic:
o Spread across the peritoneal cavity resulting in:
• Peritoneal seedlings
• Ascites
Clinical features:
•Obstructive jaundice
•Pruritus
•Weight loss
•Epigastric pain, which radiates through to the back and can
sometimes be alleviated by sitting crouched forward
•Recent dx of diabetes mellitus
•Vomiting (if duodenal invasion has occurred – a sign of advanced
disease)
Signs:
•Virchow’s node (a palpable, hard, left supraclavicular lymph node)
•Abdominal distension
•Ascites
•A palpable, enlarged, gallbladder
•A palpable mass in the epigastrium which characteristically
transmits aortic pulsation
•Choledocholithiasis
•Malignant compression of the bile duct by metastases in portal
lymph nodes
•Drug-induced cholestatic jaundice
•A carcinoma of the duodenum or papilla at the lower end of the
common bile duct
•Carcinoma of the bile duct
•Mirizzi’s syndrome:
o Cholecystitis and a gallstone in Hartmann’s pouch with
local inflammation and oedema and sometimes erosion
into the common hepatic duct
•Sclerosing cholangitis
Investigations:
•LFTs:
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o Show an obstructive pattern

•Impaired glucose tolerance
•Prolonged INR
•Ultrasound:
o Excludes gallstones in the gallbladder
o May show a normal common bile duct
o Dilated intra- and extra-hepatic biliary tree
o May show a mass in the head of the pancreas
o Possible liver metastases
•Endoscopy:
o Can demonstrate a malignant mass infiltrating the medial
wall of the second part of the duodenum (from which a
biopsy may be taken)
o ERCP may indicate a malignant stricture of the common
bile duct or pancreatic duct
•Percutaneous Transhepatic Cholangiography (PTC):
o Done by direct puncture of the bile duct through the liver
substance
o Usually reserved for pts in whom ERCP has failed
•CT:
o Valuable in demonstrating the relationship of the tumour
to the superior mesenteric vessels and portal vein
o May show lymphatic and hepatic metastases
•Specific serum tumour markers:
o Elevated CEA (Carcinoembryonic antigen)
o Elevated CA 19-9 (Carbohydrate antigen 19-9):
• This is 90% specific for pancreatic cancer
Management:
•Resection of the primary lesion for cure (feasible on < 20%)
•Alleviation of obstructive jaundice:
o Stenting
o Palliative surgical decompression (either
cholecystojejunostomy or hepaticojejunostomy)
•Pain control:
o Narcotics
o Coeliac plexus nerve block by alcohol injection
•Treatment of exocrine/endocrine failure:
o Replacement therapy
•Radiation and chemotherapeutic palliation:
Prognosis:
•Very poor
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•Most pts are dead within two years of dx – more than 50% within
6 months
•Even for those pts fortunate to present with a surgically resectable
lesion, the 5yr survival after successful removal is < 20%
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Carcinoma of the stomach
Epidemiology:
• Third most common cause of death from cancer in men and
fourth in women
• More common in the Eastern world (China/Japan) than in the
West
• Peak age distribution is 50-70yrs, however 5% of pts are <
35yrs
• Male > female (3:1)
Aetiology:
• The cause is largely unknown
• The most likely proximate pathological event is gastric atrophy
which causes hypochlorhydria and is a consequence of:
o Prolonged H. pylori infection after initial active chronic
gastritis
o Pernicious anaemia
o Gastric operations for peptic ulcer, particularly partial
gastrectomy.
• At time of presentation, most gastric cancers are both micro-
and macroscopically advanced
• The great majority of tumours are adenocarcinomas
• The adenocarcinoma is a locally invasive tumour which directly
infiltrates the full thickness of the gastric wall to involve the
serosal layer and contiguous structures such as:
o Pancreas
o Transverse mesocolon
o Left lobe of the liver
• The tumour also spreads via the lymphatic system to local and
regional lymph nodes
Symptoms of carcinoma of the stomach:

• Weight loss (72%)
• Pain (51%)
• Nausea/vomiting (40%)
• Anorexia (35%)
• Abdominal discomfort (22%)
• Dysphagia (22%)
• Upper GI bleeding (11%)
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Signs:
• Weight loss
• Abdominal mass (17%)
• Abdominal tenderness (15%)
• Hepatomegaly (13%)
• Cervical lymphadenopathy (left supraclavicular fossa – Virchow’s
node) (4%)
• Ascites (3%)
Investigations:
• Faecal occult blood testing:
o Positive in 80%, but the ix is non-specific
• Oesophagogastroscopy:
o Most sensitive procedure for determining the presence or
absence of a gastric neoplasm
• Imaging:
o Double contrast barium meal
o CT
o Ultrasound
• Full blood count:
o Microcytic hypochromic anaemia
• Laparoscopy:
o Detects irresectability, particularly by the detection of
small liver or peritoneal metastases
Cure:
• The only curative procedure is surgical resection
• In the UK, only 30-40% of pts are suitable for an attempt at
cure (although up to 70% of lesions may be resectable)
Palliation:
• Surgical resection:
o May be done in spite of nodal or metastatic disease that
makes cure impossible
o Often alleviates troublesome symptoms such as abdominal
pain, dysphagia, blood loss and vomiting
o However, because of late diagnosis and advanced disease,
bypass of an obstructing lesion in the distal part of the
stomach may be all that is possible
• Laser ablation:
o For unresectable tumours at the cardia
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o Can dramatically improve swallowing by using a laser

through an endoscope so as to core out a passage through
an obstruction
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Chronic cholecystitis
This is the result of recurrent attacks of obstruction and inflammation

which results in the changes of chronic inflammation in the gallbladder
wall and, often, in the adjacent liver
Clinical features:
• May be a past history of attacks of acute cholecystitis
• Chronic discomfort in the RUQ which is often punctuated by
intermittent acute exacerbations
• Intolerance to fatty foods
• May be some tenderness in the RUQ
Investigation:
• Gallstones are detected on ultrasound
Management:
• Cholecystectomy results in a cure
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Common bile duct stones

(Choledocholithiasis)
The majority of common bile duct stones originate in the gallbladder

but some may form within the duct system
Between 10-14% of pts with gallstones also have stones in the

common bile duct
Ductal stones are responsible for three clinical entities:

• Obstructive jaundice
• Acute cholangitis
• Acute pancreatitis
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Inflammatory bowel disease
Crohn’s disease
Epidemiology:
• Incidence is 5-8 per 100,000 and rising
• Worldwide distribution, but is more common in the West
• Incidence is lower in the non-white races with a particular
penchant for Jews
Aetiopathogenesis:
• The aetiology is unknown but it is believed that both genetic and
environmental influences are important
• Familial:
o CD is more common amongst relatives than in the general
population
• Diet:
o Possible relationship with a high sugar diet
• Smoking:
o Strongly predisposes to and aggravates CD
• Infective agent:
o Both mycobacterium and the measles virus have been
loosely associated
Pathology:
• Chronic inflammatory condition affecting any part of the GIT
from the mouth to the anus
• Most commonly affects the terminal ileum and ascending colon
(ileocolonic disease)
• ‘Skip lesions’
Macroscopic changes:
• The involved small bowel is usually thickened and narrowed
• Deep ulcers and fissures in the mucosa – cobblestone
appearance
Microscopic changes:
• Inflammation is transmural
• Increase in chronic inflammatory cells and lymphoid hyperplasia
• Granulomas present in 50-60% of pts
Clinical features:
• Is a remitting and relapsing disease
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• There are two distinct peaks:

o 20-40yrs
o >60yrs (mainly colonic disease)
• Diarrhoea (often bloody in colonic disease)
• Abdominal pain (ranging from discomfort to severe colicky pain)
• Weight loss
• Constitutional symptoms of:
o Malaise
o Lethargy
o Anorexia
o Nausea
o Vomiting
o Low-grade fever
• May present insidiously or acutely
Examination:
• Aphthous ulceration of the mouth is common
• In colonic CD (80%) examination of the anus may show:
o Oedematous skin tags
o Fissures
o Perianal abscesses
• Eyes:
o Uveitis
o Episcleritis
o Conjunctivitis
• Joints:
o Monoarticular arthritis
o Sacroiliitis
• Skin:
o Erythema nodosum
o Pyoderma gangrenosum
• Other:
o Fatty liver
o Kidney stones
o Gallbladder stones
Investigations:
• Blood tests:
o Normocytic normochromic anaemia of chronic disease is
common
o Fe/folate deficiency also occurs
o Raised ESR/CRP/WCC
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o Hypoalbuminaemia in severe disease

• Stool cultures:
• Small bowel follow-through:
o Shows an asymmetric alteration in the mucosal pattern
o Deep ulceration and areas of narrowing largely confined to
the ileum
o ‘Skip lesions’ with normal bowel in between are also seen
• Colonoscopy:
o Performed if colonic CD is suspected
• CT scanning:
o Useful in delineating abscesses, masses, thickened bowel
wall and mesentery
Differential Diagnosis:
• All chronic diarrhoeas
• Malabsorption
• Malnutrition
Complications:
• Toxic dilatation (more common in colonic CD)
• Obstruction (e.g. strictures)
• Perforation
• Abscesses
• Fistulae
Medical Management:
• Control diarrhoea with:
o Loperamide 2-4mg tid, or
o Codeine phosphate 30-60mg tid
• Acute attacks:
o Anti-inflammatory drugs (e.g. prednisolone 30-60mg/
daily)
o Fluid/electrolyte correction
o Azathioprine (2mg/kg/daily) is helpful in maintaining the
steroid-induced remission
Surgical Management:
• Approx. 80% of pts will require an operation at some time
• Surgery should be avoided as much as possible as recurrence
(15% per year) is almost inevitable
• Indications for surgery are:
o Failure of medical management with acute/chronic
symptoms producing ill-health
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o Complications
o Failure to grow in children
Ulcerative colitis
Epidemiology:
• Incidence is stable at 6-15 per 100,000
• Worldwide distribution, but is more common in the West
• Incidence is lower in the non-whites with a particular penchant
for Jews
Aetiopathogenesis:
• Unknown aetiology but is thought to involve both genetic and
environmental factors
• Familial:
o UC is more common amongst relatives than in the general
population
• Smoking:
o ‘Protective’ to some degree (higher incidence of UC in non-
smokers)
Pathology:
• Always affects the rectum (proctitis)
• May extend to infect the sigmoid and descending colon (left-
sided colitis)
• May involve the rectum and entire colon (total colitis)
Macroscopic changes:
• The mucosa looks reddened, inflamed and bleeds very easily
Microscopic changes:
• The mucosa shows a chronic inflammatory cell infiltrate in the
lamina propria
• Crypt abscesses
• Goblet cell depletion
Clinical features:
• Peak age of onset is 20-40yrs
• Women > men
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• Diarrhoea with blood and mucus

• Lower abdominal discomfort
• Malaise
• Lethargy
• Anorexia
• Aphthous ulceration of the mouth
• The disease may be mild, moderate or severe
• When the disease is confined to the rectum:
o Blood mixed in with the stool
o Urgency
o Tenesmus
• In an acute attack:
o Bloody diarrhoea (occasionally just blood and mucus are
passed)
o 10-20 liquid stools per day
o Diarrhoea also occurs at night
Examination:
• The abdomen may be slightly distended
• PR exam will show the presence of blood
• Sigmoidoscopy is always abnormal and shows an inflamed,
bleeding, friable mucosa (a biopsy should be taken to confirm
the diagnosis)
Extra GI manifestations:
• Eyes:
o Uveitis
o Episcleritis
o Conjunctivitis
• Joints:
o Monoarticular arthritis
o Sacroiliitis
• Skin:
o Erythema nodosum
o Pyoderma gangrenosum
• Other:
o Fatty liver
o Sclerosing cholangitis
Investigations:
• Blood tests:
o Normocytic normochromic anaemia of chronic disease
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o Fe/folate deficiency occurs

o Raised ESR/CRP/WCC
o Hypoalbuminaemia in severe disease
• Stool cultures
• Plain AXR:
o Look for signs of colonic dilatation
• Colonoscopy
Complications:
• Toxic dilatation
• Perforation
• Severe haemorrhage
• Ca colon
• Perianal abscess
Medical Management:
• All pts are treated with a 5-ASA (5-Amino Salicylic Acid)
compound. It is used to decrease the no. of relapses when taken
long-term
• Mild attacks:
o Local rectal steroids in the form of enemas or foam.
• Moderate attacks:
o Prednisolone (40mg/daily po). Pts with their first attack or
those who do not respond quickly should be admitted to
hospital
• Severe attacks:
o Prednisolone (60mg/6h IV) or Hydrocortisone (100mg/6h
IV)
o IV correction of fluid/electrolytes
o A/Bs for concomitant sepsis
• In UC, the disease is confined to the colon and, therefore, a
colectomy is curative.
• The usual indication for surgery is usually a severe attack which
fails to respond to medical treatment
• A prophylactic colectomy is sometimes performed in those who
have a high cancer risk
• Protocolectomy with an ileostomy:
• This is the standard operation in which the colon and rectum are
removed and the ileum is brought out through an opening in the
RIF
• Problems associated with ileostomies include:
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o Mechanical problems
o Dehydration (particularly in hot climates)
o Psychosexual problems
o Infertility in men
• Colectomy with an ileorectal or ileoanal anastomosis:
o These procedures avoid the need for an ileostomy
o Ileorectal anastomoses leave a diseased rectum in situ and
frequent diarrhoea still occurs
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Diverticular disease
Diverticulum = an out-pouching of the wall of the gut

Diverticulosis = the presence of diverticula
Diverticulitis = inflammation of a diverticulum
Pathology:
• Most occur in the sigmoid colon (95% of complications occur at
this site)
• Lack of dietary fibre is thought to lead to high intraluminal
pressures which force the mucosa to herniate through the
muscle layers of the gut
• 1/3 of the western world population has diverticulosis by age
60yrs
Diagnosis:
• PR exam
• Sigmoidoscopy
• Barium enema
• Colonoscopy
• Colorectal cancer
• Pelvic abscess
Complications:
• Painful diverticular disease:
o Altered bowel habit
o Left-sided, colicky pain that is relieved by defaecation
o Nausea/flatulence
o Treatment is:
• High fibre diet
• Antispasmodics (e.g. Mebeverine 135mg/8h po)
• Surgical resection (occasionally)
• Diverticulitis:
o All of the above + signs of inflammation (pyrexia, inc WCC,
inc ESR)
o Colon is tender
o Local/general peritonism
• Treatment is:
o Bed rest
o NBM
o IV fluids
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o A/Bs (Cefuroxime 1.5g/8h IV + Metronidazole 500mg/8h

IV) until culture results available
• Perforation:
o Ileus
o Peritonitis ± shock
o Treatment is emergency laparotomy (perform Hartman’s
procedure – temporary colostomy + partial colectomy)
o Mortality is approx. 40%
• Haemorrhage:
o Sudden and painless
o Diverticular disease is a common cause of big rectal bleeds
o Bleeding usually stops with bed rest
o Transfusion may be necessary
o Other treatment:
• Embolization
• Colonic resection
• Fistulae:
o May form between the colon and the:
• Bladder (leading to pneumaturia/intractable UTIs)
• Vagina
• Small bowel
• Rx is surgical
• Abscesses:
o Swinging fever
o Leucocytosis
o Localizing signs (e.g. boggy rectal mass)
o If NO localizing signs, remember:
• “Pus somewhere, pus nowhere = pus under the
diaphragm”
o Do urgent US to exclude subphrenic abscess (a ‘horrible
way to die’)
o Rx is drainage and A/Bs
• Post-infective strictures:
o May form in the sigmoid colon
o Rx is surgical
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Familial adenomatous polyposis (FAP)
This is an autosomal dominant condition with a high degree of

penetrance
It is caused by a mutation of the apc gene
• Multiple adenomatous polyps develop in the colon, usually
between the ages 13-30yrs
• Progression through the polyp-cancer sequence is inevitable
Clinical features:
• The condition is initially asymptomatic, although a family hx may
be present
• Blood from the rectum is the most common symptom
• Tenesmus
• Diarrhoea
Diagnosis and Management:

• Diagnosis is made by endoscopy
• Siblings should be examined
• Total colectomy is essential because of the universal progression
to cancer
• An ileoanal reconstruction is usually possible
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Gallstone ileus
Aetiology:
• A gallbladder which contains stones erodes into adjacent small
bowel, usually the duodenum
• Stones can then be shed through this cholecystenteric fistula
into the gut
• A stone that has a diameter greater than the narrowest part of
the small bowel (the terminal ileum) may impact to produce
lower small bowel obstruction.
Clinical features:
• Vague attacks of colic as the stone passes down the gut
• Eventually, signs of a low small bowel obstruction
Investigations:
• In addition to the characteristic features of a small bowel
obstruction on an AXR, it may be possible to see:
o Aerobilia (air in the biliary tree)
o A gallstone in the RLQ
Management:
o Surgical
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Gallstones
(Cholelithiasis)
Epidemiology:
• Prevalence of ~10%
• ‘Fair, fat, females in their fifties’
• Can occur at any age in any sex
• 2-4x more common in women than in men
• There are two main types of stone:
o Pure cholesterol stones (20%)
o Mixed cholesterol and bile pigment, mainly Bilirubin (75%)
Aetiology:
• There are three main predisposing factors:
• Cholesterol supersaturation:
o Cholesterol is insoluble in water
o In bile, it is normally solubilised in lecithin-bile acid
aggregates (micelles)
o If the concentration in bile is high, the capacity of this
mechanism becomes exceeded and nucleation of
cholesterol occurs
• Stasis:
o This may be caused by:
• Fasting
• TPN
• Truncal vagotomy (loss of stimulation to gallbladder
emptying)
• Increased Bilirubin secretion in bile or deconjugation:
o Bilirubin is kept in solution by conjugation with glucuronide
o Pigment stones form when there is:
• Haemolysis
• Failure of conjugation
Complications:
• Gallstones anywhere in the biliary tree can be asymptomatic
(silent) and lie undetected for many years
• They become clinically evident by the complications they cause:
o Gallbladder:
• Biliary colic
• Acute cholecystitis
• Chronic cholecystitis
• Empyema
• Mucocele
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o Common bile duct:

• Obstructive jaundice
• Cholangitis
• Pancreatitis
o Small intestine:
• Gallstone ileus
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Intestinal obstruction
Features of obstruction:
• Anorexia
• Nausea/vomiting
• Colicky abdominal pain with abdominal distension
• Constipation (although need not be absolute if obstruction is
high)
• Active ‘tinkling’ bowel sounds
Is the obstruction small or large bowel?

• Small bowel:
o Supine AXR shows central gas shadows with NO gas in the
large bowel
o Vomiting occurs earlier
o Less abdominal distension
o Pain is higher in the abdomen
• Large bowel:
o Supine AXR shows gas proximal to the obstruction
o Constant pain
Is there ileus or mechanical obstruction?

• Ileus = functional obstruction due to decreased bowel motility
• In ileus:
o There is no pain
o Absent B/S
Is the bowel strangulated?

• Signs:
o Pt is more ill than you would expect
o Pain is sharper and more constant than the central colicky
pain of the obstruction
o Localized pain
o Peritonism
o Fever/inc WCC (occasionally)
Causes:
• Small bowel:
o Adhesions (common)
o Hernias (common)
o Crohn’s disease
o Gallstone ileus
o Tumour
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o Intussusception (only in infants <18mths)

• Large bowel:
o Tumour (common)
o Diverticulitis (common)
o Faeces
o Sigmoid/caecal volvulus (twisting of part of the gut)
Management:
• Conservative:
o Pass NG tube
o IV fluids to rehydrate and correct electrolyte imbalances
• Surgery:
o Strangulation requires urgent surgery (<1h), as does large
bowel obstruction with gas dilatation (>8cm) and
tenderness over the caecum (as perforation as close)
o For less urgent large bowel obstructions, there is time for
an enema to try to clear the obstruction and correct fluid
imbalance
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Obstructive jaundice
Impaction of a stone in the common bile duct (usually at the duodenal

papilla) causes obstructive jaundice
Clinical features:
• Jaundice
• Pruritis
• Dark urine
• Pale stools
• Preceding biliary colic
Investigations:
• Ultrasound:
o Shows dilatation of the bile ducts
o May identify ductal stones
• ERCP (Endoscopic Retrograde CholangioPancreatoGraphy):
o Confirms the diagnosis
o Makes the distinction between a stone and other causes of
obstructive jaundice
Management:
• The treatment of choice is ERCP and extraction of the ductal
stone(s) after division or dilatation of the sphincter of Oddi
• Subsequently (if it has not been done already) the gallbladder
should be removed unless the pt is elderly or at a high operative
risk
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Small bowel neoplasms
Epidemiology:
• Primary tumours of the small bowel are relatively uncommon
• Account for 5% of GI neoplasms
• May be benign or malignant
• Commonest benign tumours are leiomyomas (smooth muscle
tumours)
• There are 4 factors associated with small bowel malignancies:
o Developmental disorders
o Immunocompromisation
o Geographical location
o Crohn’s disease
Developmental disorders:
• Polyposis coli
• Peutz-Jegher syndrome:
o An ill-understood inherited relationship between intestinal
polyps mainly in the jejunum and marginal pigmentation
around the buccal and anal mucosa – the usual
presentation is with intussusception
• Gardner’s syndrome:
o A rare disorder in which small bowel adenomas and
carcinomas are associated with skeletal abnormalities and
desmoid tumours
Immunocompromisation:
• Coeliac disease
• Acquired immunodeficiency (e.g. AIDS)
• Immunosuppression (chiefly in transplant pts) is associated with
small bowel lymphomas
Geographical location:
• Lymphomas are more common in the Middle East than
elsewhere
Benign tumours – pathological features:

• Are commoner in the duodenum
• Progression to carcinoma can occur
• Are three main types:
o Leiomyomas
o Lipomas (more common in the large bowel)
o Neurofibromas
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Malignant tumours:
• Are, again, three main types:
o Lymphomas
o Adenocarcinomas (most common in the duodenum)
o Secondary tumours (rare, but occur in lung and breast
cancer)
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Upper GI bleeds
Typical signs of an upper GI bleed:

• Haematemesis = the vomiting of blood
• May be bright red if blood
• However, appears ‘coffee ground’ if retained in the stomach for a
short period due to the action of acid
• Malaena = altered blood (black and tarry) passed PR
• It implies bleeding proximal to the splenic flexure
Causes:
• Common:
o Gastric/duodenal ulcer (50%) (GU more likely to bleed/
higher mortality than DU)
o Oesophageal varices (5-10%)
o Gastritis
o Mallory-Weiss tear (oesophageal tear due to vomiting)
o Portal hypertensive gastropathy
o Drugs:
• NSAIDs
• Steroids
• ThrombolyticsAnticoagulants
• Rarer:
o Nose bleeds (swallowed blood)
o Oesophageal/gastric malignancy
o Oesophagitis
o Haemobilia
o Peutz-Jegher’s syndrome (Benign small intestinal
hamartomartous polyps occurring with dark freckles on
lips, oral mucosa, face, palms and soles)
Assessment:
• Swift, relevant history and examination
• History:
o ‘Do you feel faint when you sit up?’ If yes, put up an IVI
before continuing
o Drugs (NSAIDs, steroids, anticoagulants)
o Alcohol abuse
o Previous GI bleed, peptic ulcer or its symptoms?
o Any other serious concomitant disease?
• Examination:
o Vital signs (pulse, BP standing/lying, JVP, urine output)
o Signs of chronic liver disease?
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o Jaundice (biliary colic + jaundice + Malaena suggests

haemobilia)
Assess whether the patient is in shock:

• Cool and clammy to touch (especially nose, toes, fingers)
• Pulse >100bpm
• JVP <1cm H2O
• Systolic BP <100mmHg
• Postural drop
• Urine output <30mL/h
Immediate management if shocked:

• Protect airway
• Insert 2 large-bore ‘drips’
• Send bloods
• High flow O2
• Give IV colloid quickly then blood (ORh-ve until cross-match
done). Aim for Hb of >10g/dl
• Correct clotting (Vitamin K, FFP)
• Set up CVP line to guide fluid replacement (aim for >5cm H20)
• Catheterize and monitor urine output
• Urgent diagnostic endoscopy – notify surgeons of all severe
bleeds
Death from upper GI bleeds depends, chiefly, on 3 factors:

• Age
• Concomitant disease in the cardiopulmonary system
• Cause of bleeding
Indications for surgery:

• Severe bleeding
• Rockall score >6
• Re-bleeding
• Active bleeding during oesophago-gastro-duodenoscopy (OGD)
• Continuing bleeding after transfusion (if >60yrs, 6 units; if
<60yrs 8 units)
• Varices:
o Oesophageal transaction with gun stapler re-anastomosis
o Transthoracic transoesophageal ligation
• Gastric ulcer:
o Under-running
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o Excision
o Partial gastrectomy
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Respiratory Medicine
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Acute respiratory distress syndrome (ARDS)
Definition:
• Defined as:
o Diffuse pulmonary infiltrates
o Non-cardiogenic pulmonary oedema
o Refractory hypoxaemia
o Stiff lungs
o Respiratory distress
• Commonest predisposing factor, by far, is sepsis (20-40% of
patients with severe sepsis will develop ARDS)
Disorders associated with ARDS:

• Shock
• Infection (e.g. sepsis, pneumonia)
• Trauma
• Pulmonary aspiration
• Inhalation injury (e.g. smoke, corrosive gases)
• Haematological (e.g. DIC, massive transfusion)
• Obstetric (e.g. amniotic fluid embolism)
• Drug overdose (e.g. heroin, barbiturates)
• Miscellaneous (e.g. pancreatitis, CP bypass)
Pathophysiology:
• ARDS can be considered as the earliest manifestation of a
generalized inflammatory response and is, therefore, frequently
associated with the development of MODS (multiple organ
dysfunction syndrome)
Non-cardiogenic pulmonary oedema:

• Cardinal feature of ARDS
• Is the first and clinically most evident sign of a generalized
increase in vascular permeability (caused by the microcirculatory
changes and release of inflammatory mediators)
• The pulmonary epithelium is also damaged in the early stages of
ARDS, reducing surfactant production and lowering the threshold
for alveolar flooding
Pulmonary hypertension:
• Common feature of ARDS
• Initially, mechanical obstruction of the pulmonary circulation
may occur as a result of vascular compression by interstitial
oedema and, subsequently, oedema of the vessel wall itself
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• Later, constriction of the vasculature may develop in response

to increased ANS activity and circulating substances (e.g.
catecholamines)
Fibrosis:
• Starts to occur within 7 days of the onset of ARDS
• Is progressive, and causes a loss of elastic tissue and
obliteration of the lung vasculature, together with lung
destruction and emphysema
Physiological changes:
• Increased dead-space
• Decreased compliance
• Evidence of airflow limitation
Clinical presentation of ARDS:

• Unexplained tachycardia
• Increasing hypoxaemia
• Dyspnoea
• Laboured breathing
• Fine crackles bilaterally
Management of ARDS:
• This is based on treatment of the underlying cause and
supportive measures
• Limit pulmonary oedema:
o Fluid restriction
o Diuretics
o Haemofiltration (if severe)
• Body position changes:
o When the patient is changed from the supine to the prone
position, lung densities in the dependent regions are
redistributed and gas exchange may improve
o Repeated position changes between prone and supine
may, therefore, allow reduction in airway pressures and
the inspired oxygen concentration
• High dose steroids:
o Only shown to be beneficial when administered during the
late fibroproliferative phase of ARDS
• Inhaled nitric oxide:
o Can improve V/Q matching and oxygenation by increasing
perfusion in ventilated lung units
o Also reduces pulmonary hypertension
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• Aerosolized prostacyclin:
o Has similar effects to inhaled NO
• Aerosolized surfactant:
o Yet to be established
o Beneficial in animal models of ARDS
Prognosis:
• Mortality is >50%
• Prognosis is very dependent on aetiology
• When ARDS occurs in association with septic shock, mortality
can be as high as 90%
• ~40% of uncomplicated cases die
• The major cause of mortality is not so much impaired gas
exchange but MODS and haemodynamic instability
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Asthma
Characteristics:
• Asthma has 3 characteristics:
1. Reversible airflow limitation
2. Airway hyperresponsiveness
3. Inflammation of the bronchi
Prevalence:
• Affects 15-20% of people in their 20s
• Commoner in the West
Classification:
• 2 classes:
o Intrinsic or cryptogenic (when no causative agent can be
identified)
o Extrinsic (implying a definite external cause)
Extrinsic asthma:
• Occurs most frequently in atopic individuals who show (+ve)
skin-prick reactions to common inhaled allergens
• (+ve) skin tests to inhalant allergens are shown in 90% of
children and 50% of adults
Intrinsic asthma:
• Often starts in middle age
• Many show (+ve) skin tests and on close questioning give a
history of respiratory symptoms compatible with childhood
asthma
Aetiology and pathogenesis:

• There are 2 major factors involved in the development of
asthma:
o Atopy and allergy
o Airway hyperreactivity
Atopy and allergy:

• Atopic individuals readily develop antibodies of IgE class against
common materials present in 30-40% of the population
• There is a link between serum IgE levels and both the
prevelance of asthma and airway responsiveness to histamine or
methacholine (cholinergic agonist)
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Airway hyperreactivity:
• Demonstrated by asking the patient to inhale gradually
increasing doses of histamine or methacholine
• This induces a transient episode of airflow limitation in
susceptible individuals (~20% of the population)
• The dose of the agonist (provocation dose) necessary to produce
a 20% fall in FEV1 is known as the PD20FEV1
• Patients with clinical features of asthma respond to very low
doses of methacholine, i.e. they have a low PD20FEV1 (<11µmol)
Precipitating factors:
• Occupational sensitizers
• Cold air
• Exercise
• Atmospheric pollution, irritant dusts, vapours and fumes
• Emotion
• Drugs (e.g. NSAIDs)
Clinical features:
• Wheezing
• Episodic SOB
• Cough (especially nocturnal)
• Chest ‘tightness’
Investigations:
• Lung function tests:
o The diagnosis of asthma is based on the demonstration of
a greater than 15% increase in FEV1 or PEFR following the
inhalation of a bronchodilator
• Peak flow charts
• Exercise tests
• Histamine or methacholine bronchial provocations test:
o This test should NOT be performed on individuals who
have poor lung function (FEV1 <1.5L)
• Trial of corticosteroids (as for COPD)
• CXR:
o Useful in excluding other possible diagnoses
• Skin-prick tests
• Blood and sputum tests
Management:
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• The aims of management are as follows:

o To abolish symptoms
o To restore normal or best possible long-term airway
function
o To reduce the risk of severe attacks
o To enable normal growth to occur in children
o To minimise absence from school or work
Drug therapy:
• "2-adrenoceptor agonists:
o E.g. salbutamol 100µg (2 puffs PRN) or salmeterol
(50-100µg 1 puff daily)
o Cause relaxation of bronchial smooth muscle
o Very effective at relieving symptoms but does little for the
underlying inflammatory nature of the disease
o Only the mildest asthmatics, with intermittent attacks
should rely on bronchodilator treatment alone
• Anticholinergic bronchodilators:
o E.g. ipratropium bromide 20-40mg TID by inhalation
• Inhaled corticosteroids:
o E.g. inhaled beclomethasone (available in doses of 50, 100
and 250µg per puff)
o Unwanted effects of inhaled corticosteroids include:
• Oral candidiasis
• Hoarsenes
• Abnormalities of bone formation (with very high steroid
doses)
• Growth retardation in children if inhaling >400µg daily
• Oral corticosteroids:
o Used for those patients who are not controlled on inhaled
corticosteroids
o Keep dose as low as possible to avoid side-effects
• Leukotriene receptor antagonists:
o E.g. Montelukast (single tablet daily)
o Improves control when used with an inhaled steroid
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Bronchial carcinoma
Epidemiology:
• Most common malignant tumour in the western world
• Third most common cause of death in the UK (after heart
disease and pneumonia)
• 32,000 people a year die from bronchial carcinoma in the UK
• Males affected more than females (3.5:1)
• The link between bronchial carcinoma and smoking is
overwhelming
Cell types:
• Bronchial carcinoma is divided into 2 classes:
o Non-small cell carcinoma
o Small-cell carcinoma
Non-small cell carcinoma:

• 4 types:
o Squamous cell carcinoma (SCC) – accounts for 40% of all
carcinomas, metastasises late
o Large-cell carcinoma – 25% of all tumours, metastasizes
early
o Adenocarcinoma – 10% of all tumours, commonly
metastasizes to bone and brain. Most common bronchial
carcinoma associated with asbestos exposure
o Alveolar cell carcinoma – 1-2% of lung tumours, large
quantities of sputum produced
Small-cell carcinoma:
• Also known as an oat-cell carcinoma
• Accounts for 20-30% of all lung tumours
• Secrete many polypeptide hormones
• Responds well to chemotherapy
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Clinical features of bronchial carcinoma:

Symptom Frequency (%)
Cough 41
Chest pain 22
Cough and pain 15
Haemoptysis 7
Chest infection <5
Malaise <5
Weight loss <5
SOB <5
Hoarseness <5
Distant spread <5
Asymptomatic <5
Direct spread:
• The tumour may directly involve the pleura and ribs
• Carcinoma of the apex of the lung can erode the ribs and involve
the lower part of the brachial plexus (C8, T1 and T2) causing
severe pain in the shoulder and down the inner surface of the
arm (Pancoast’s tumour)
• The sympathetic ganglion can also be involved, producing
Horner’s syndrome
• Further extension may involve the recurrent laryngeal nerve as it
passes down the aortic arch, causing unilateral vocal cord
paresis with hoarseness and a bovine cough
• Bronchial carcinoma can also directly invade the phrenic nerve,
causing paralysis of the diaphragm
Metastatic complications:
• Commonly metastasises to:
o Brain (causing personality change, epilepsy or a focal
neurological lesion)
o Bone (severe pain and pathological fractures)
o Liver
Investigations:
• CXR:
o Very valuable but very insensitive (the tumour must be
>1-2cm to be visible)
o About 70% of bronchial carcinomas arise in the hilar region
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o At the time of clinical presentation, the chest CXR will

demonstrate >90% of carcinomas
• CT scans:
o Particularly useful for identifying pathological changes in
the mediastinum (such as lymphadenopathy or local
spread of the tumour)
o Also good for identifying secondary spread of the
carcinoma to the opposite lung by detecting masses too
small to be seen on the CXR
• MRI:
o Is being increasingly used for staging
• Fibre-optic bronchoscopy:
o Used to obtain biopsy specimens
o If the carcinoma involves the first 2cm of either main
bronchus, the tumour is inoperable
o Vocal cord paresis on the left indicates involvement of the
left recurrent laryngeal nerve and inoperability
• Transthoracic FNA biopsy:
o This involves the direct aspiration, through the chest wall,
of peripheral lung lesions under appropriate X-ray or CT
screening
o Pneumothorax occurs in 25% of patients
o Mild haemoptysis occurs in 5%
• Blood tests:
o FBC (to detect anaemia)
o LFTs (t detect liver involvement)
Prognosis:
• Only 20% of patients are alive one year after diagnosis and only
6-8% after 5 years
Surgery:
• The only treatment of any value for non-small cell cancer of the
lung is surgery
• Only 20% of all cases are suitable for resection and of these,
only 25-30% survive for five years
Radiation therapy for cure:

• Useful for those patients with SCC
• It is the treatment of choice if the tumour is inoperable
• Radiation pneumonitis develops in 15% of cases:
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o Defined as an acute infiltrate precisely confined to the

radiation area and occurring within 3 months of
radiotherapy
Chemotherapy – small-cell cancer:

• Single or combination chemotherapy has resulted in a fivefold
increase in survival from 2 months to 10 months
• A small number of patients enjoy several years of remission
Chemotherapy – non-small cell cancer:

• Non-small cell cancer can no longer be regarded as resistant to
chemotherapy
• Response rates with single-agent treatment with newly
introduced drugs exceed 20%
• Median survival can be increased to 6-12 months
Palliative treatment:
• Endobrachial irradiation
• Tracheobronchial stents
• Laser ablation via a fibre-optic bronchoscope
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Cor pulmonale
Cor pulmonale is right-heart failure caused by chronic pulmonary

hypertension induced by chronic hypoxia secondary to diseases of the
lung, its vessels, or the thoracic cage.
Causes of cor pulmonale:

• Pulmonary vascular disorders:
o PE
o Pulmonary hypertension
• Disease of the lung and parenchyma:
o COPD
• Musculoskeletal disorders:
o Poliomyelitis
o Myasthenia gravis
• Disturbance of respiratory control:
o Obstructive sleep apnoea
o Cerebrovascular disease
• Left-heart disorders:
o Mitral stenosis
o LVF
Acute
Acute cor pulmonale (pulmonary embolus – PE):

• A thrombus formed in the systemic veins may dislodge and
embolize into the pulmonary arterial system
• After PE, lung tissue is ventilated but not perfused, leading to
impaired gaseous exchange
• After some hours, surfactant is no longer produced by the non-
perfused lung
• Alveolar collapse occurs and exacerbates hypoxaemia
• The haemodynamic consequence of PE is an elevation of
pulmonary arterial pressure and a reduction in cardiac output
Clinical features of PE:

• Many Pulmonary emboli occur silently, but there are 3 typical
clinical presentations:
o Small/medium PE:
• In this situation, an embolus has impacted in a
terminal pulmonary vessel
• Symptoms are:
• Pleuritic chest pain
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• Breathlessness
• Haemoptysis (in ~30%, occurring >3 days
after the initial event)
• On examination:
• Tachypnoea
• Localized pleural rub
• Coarse crackles over the involved area
• A pleural effusion can develop
• There may be a fever
• Normal CVS
o Massive PE:
• Much rarer scenario
• Sudden collapse occurs due to an acute obstruction
of the right ventricular outflow tract
• Symptoms:
• Severe central chest pain (cardiac ischaemia
due to lack of coronary blood flow)
• Shock
• Death can occur
• On examination:
• Tachypnoea
• Tachycardia
• Hypotension
• Peripheral vasoconstriction
• Raised JVP
• Right ventricular heave
• Gallop rhythm
• Widely split second heart sound
o Multiple recurrent pulmonary emboli:
• Symptoms:
• Increasing breathlessness (often over weeks
or months)
• Weakness
• Syncope on exertio
• Angina (occasionally)
• On examination:
• Signs of right ventricular overload
• Right ventricular heave
• Loud pulmonary second heart sound
Diagnosis of PE:
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• PE should be considered if patients present with symptoms of

new-onset AF (or other tachycardia), unexplained breathlessness
or cough, if no other obvious cause is present
Investigations for PE:

• CXR:
o Usually normal in small/medium PE
o May show pulmonary oligaemia with a massive PE
• ECG:
o In small/medium PE, there is usually sinus tachycardia or
AF
o In massive PE there is:
• Tall peaked T waves in lead II
• Right axis deviation
• Right bundle branch block
• Blood tests:
o Hypoxia and hypercapnia
o Raised ESR/LDH due to pulmonary infarction
• Plasma D-dimer:
o If undetectable, it excludes the diagnosis of PE
• Radionucleotide ventilation-perfusion scan (V/Q scan):
o Ultrasound:
• To detect clots in pelvic/lower limb veins
• Spiral CT scans
• MRI
Acute management:
• High-flow O2, unless they have significant chronic lung disease
• In severe cases:
o IV fluids
o Inotropic agents
• Analgesia
• Dissolution of the thrombus:
o Streptokinase 250,000U IVI over 30 minutes, followed by
streptokinase 100,000U IV hourly is often used following a
major embolism
• Prevent further emboli:
o The basis of therapy is IV heparin
o Give a bolus of 10,000U of unfractionated heparin followed
by a continuous infusion of 1000-2000U per hour
o Oral anticoagulants are usually begun after 48 hours and
the heparin is tapered off as the oral anticoagulant
becomes effective
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Oral anticoagulants are continued for 6 weeks to 6 months
Chronic
Pathophysiology of chronic cor pulmonale:

• The Pathophysiology varies with the cause. COPD is discussed
here
• Pulmonary vascular resistance (PVR) is increased because of loss
of pulmonary vascular tissue and because of pulmonary
vasoconstriction caused by hypoxia and acidosis.
• The increased PVR leads to pulmonary HT
• The pulmonary HT becomes chronic and progressively more
severe
• Right ventricular function is progressively compromised because
of the increased pressure load
• Hypoxia further impairs right ventricular function and, as it
develops, left ventricular function is also depressed
Clinical features:
• Symptoms:
o Chest pain
o Exertional dyspnoea
o Syncope
o Fatigue
o Sudden death
• On examination:
o Right ventricular (parasternal) heave
o Loud pulmonary component to the second heart sound
o Mid-systolic ejection murmur
o Early diastolic murmur (due to pulmonary regurgitation)
o Pansystolic murmur (if tricuspid regurgitation develops)
Investigations:
• CXR:
o May show right ventricular enlargement and right atrial
dilatation
o Prominent pulmonary artery
• ECG:
o Right axis deviation (indicating right ventricular
hypertrophy)
o Tall peaked T waves in lead II (P pulmonale)
• Echocardiography:
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o Will usually demonstrate right ventricular dilatation and/or

hypertrophy
o May also reveal the cause of the pulmonary hypertension
o If no other cause is found, then the diagnosis of primary
pulmonary hypertension is made. This disease typically
affects young females (20-35 years)
Treatment:
• Treatment is determined by the underlying condition
• Diuretic therapy in right ventricular failure:
o Use with care as excessive fluid depletion will result in a
reduced output from the impaired ventricle
• Oxygen therapy
• Primary pulmonary hypertension:
o Treated with anticoagulation (because the possibility of
recurrent thromboembolism can seldom by fully excluded)
o Vasodilators (e.g. verapamil) are sometimes of
symptomatic benefit
• Usually there is a progressive downhill course
• Heart and lung transplantation is recommended for young
patients
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Chronic obstructive pulmonary disease (COPD)
COPD has become the most popular term to describe patients with
chronic bronchitis and emphysema. The distinction between COPD and
asthma is blurred as most patients with COPD have some reversible
airflow obstruction.
Definitions in COPD:
• Chronic bronchitis:
o Cough productive of sputum on most days for at least 3
months of the year for more than 1 year
• Emphysema:
o Dilatation and destruction of the lung tissue distal to the
terminal bronchioles
Clinical observations in COPD:

• It is believed that there are two distinct types of patients, type A
and type B:
o Type A fighter (pink and puffing):
• The person is very breathless
• Arterial tensions of O2 and CO2 are relatively normal
• NO cor pulmonale
• These patients are thought to be suffering,
predominantly, from emphysema with little bronchitis
o Type B non-fighter (blue and bloated):
• Person does not appear to be breathless
• Marked:
• Arterial hypoxaemia
• CO2 retention
• Secondary Polycythaemia
• Cor pulmonale
Epidemiology:
• 18% of male and 14% of female smokers
• In the UK, COPD causes approximately 18 million lost working
days for men and 2.1 million lost working days for women per
year (approximately 7% of all days off sick from work)
Aetiology:
• Smoking is a major factor in the development of COPD
• Is virtually only a disease of smokers
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• Climate and air pollution play an important role, with a great

increase in mortality from COPD during periods of heavy
atmospheric pollution
• Hereditary deficiency of "1-antitrypsin is responsible for 2% of
cases of emphysema
Pathophysiology of chronic bronchitis:

• Hypertrophy of the mucus-secreting glands of the bronchial tree
• The hypertrophy of these mucus glands is evenly distributed
throughout the lung and is mainly seen in the larger bronchi
• The number of mucus-secreting goblet cells increases
• This leads to increased mucus production and the regular
expectoration of sputum
• The small airways are particularly affected early in the disease,
initially without the development of any significant
breathlessness. This initial inflammation accounts for the
improvement in airway function if smoking is stopped early
• Further progression of the disease leads to progressive
squamous cell metaplasia and fibrosis of the bronchial walls
• The consequences of these changes is the development of
airflow limitation
Pathophysiology of emphysema:
• Most commonly, distension and damage of lung tissue is
concentrated around the respiratory bronchioles, whilst the more
distal alveolar ducts and alveoli tend to be well preserved
• Emphysema leads to expiratory airflow limitation and air
trapping
• The loss of lung elastic recoil results in an increase in TLC
• The loss of alveoli results in decreased gas transfer
Symptoms of COPD:
• Productive sputum
• Wheeze
• Shortness of breath
Signs of COPD:
• In mild disease:
o No signs except wheeze throughout the chest
• In severe disease:
o Tachypnoea
o Prolonged expiration
o Use of the accessory muscles
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o Intercostal indrawing on inspiration

o Pursing of the lips on expiration
o Poor chest expansion
o Lung hyperinflation
• The ‘pink puffer’:

o Always breathless
o Not usually cyanosed
• The ‘blue bloater’:
o Oedematous
o Deeply cyanosed
o Hypoventilation
o These patients are likely to have hypercapnia, so the
following are present:
• Peripheral vasodilatation
• Bounding pulse
• CO2 retention tremor
• Severe hypercapnia leads to CO2 narcosis:
o Confusion
o Progressive drowsiness and coma with papilloedema
Complications of COPD:
• Respiratory failure:
o Usually defined as one or both of the following:
• PaO2 less than 8kPa
• PaCO2 of greater than 7kPa
• Cor pulmonale:
o Heart disease secondary to disease of the lung
o Pulmonary HT
o Right ventricular hypertrophy
o Right heart failure
Investigations:
• Lung function tests:
o Evidence of airflow limitation
o FEV1 : FRC is reduced
o Low PEFR
• CXR:
o Often normal but may show hyperinflation
• Hb level and PCV:
o Can be elevated as a result of persistent hypoxaemia
(secondary polycythaemia)
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• Arterial blood gases

• Sputum Gram stain and culture
• ECG:
o In cor pulmonale, the P wave is taller (P pulmonale)
o May be right bundle branch block (RSR complex)
• Echocardiogram
• !1-antitrypsin levels:
o The normal range is 2-4g/L
Treatment:
• Stop smoking:
o Even at a late stage of the disease this may slow down the
rate of deterioration
• Bronchodilators (e.g. salbutamol 200µg every 4-6 hours)
• Corticosteroids:
o Initial 2 week trial pf prednisolone 30mg daily
o If lung function improvements, gradually replace with
inhaled corticosteroids (e.g. beclomethasone 100-500µg
TID)
• Antibiotics:
o Patients should be given a supply of antibiotics to use once
their sputum turns yellow or green
o The antibiotics of choice are cefaclor 500mg TID or
cefixime 400mg OD
• Diuretics (for all oedematous patients)
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How to use an inhaler
1. The canister is shaken

2. The patient exhales to FRC (not RV) – i.e. normal expiration
3. The aerosol nozzle is placed into the open mouth
4. The patient simultaneously inhales rapidly and activates the
aerosol
5. Inhalation is completed
6. The breath is held for 10 seconds (if possible)
Even with a good technique, only 15% of the contents is inhaled and
85% is deposited on the wall of the pharynx and ultimately swallowed.
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Pleural effusion
Definition:
• An excessive collection of fluid in the pleural space
• Can be detected by X-ray when >300ml of fluid is present
• Can be detected clinically when >500ml of fluid is present
Clinical signs:
• Decreased chest expansion on affected side
• Mediastinum displaced away from lesion (in massive effusions)
• Stony dull to percussion
• Vesicular breath sounds – reduced or absent
• Reduced or absent vocal resonance
• No added sounds
Diagnosis:
• Pleural aspiration
• The fluid that accumulates may be a transudate or an exudate
Transudates:
Causes include:
• Heart failure
• Hypoproteinaemia (e.g. nephrotic syndrome)
• Constrictive pericarditis
• Hypothyroidism
• Ovarian tumours
Exudates:
Causes include:
• Bacterial pneumonia (common)
• Bronchial carcinoma
• TB
• Connective tissue disease
Treatment is of the underlying pathology
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Pneumonia
Definition:
• Inflammation of the substance of the lungs
• It is usually caused by bacterial infection
Classification:
• Pneumonia may be classified both anatomically and on the basis
of the aetiology
• Classification by site:
o Lobar
o Diffuse (bronchopneumonia)
• Classification by aetiology:
o Infective (by far the most common)
o Chemical causes (e.g. the aspiration of gastric contents)
o Radiotherapy
o Allergic mechanisms
• Note, the last 3 are generally referred to as ‘pneumonitis’
Precipitating factors:
• Viral respiratory infection
• Hospitalized patients
• Smoking
• Alcohol excess
• Bronchiectasis (e.g. in cystic fibrosis)
• Bronchial obstruction (e.g. carcinoma)
• Immunosuppression (e.g. AIDS or treatment with cytotoxic
drugs)
• IV drug abuse (frequently associated with Staph. Aureus
infection)
Clinical features:
• Varies according to the immune status of the patient and the
infecting agent. In the most common type of pneumonia (caused
by Strep. pneumoniae) there is often:
o Preceding history of viral infection
o High fever (up to 39.5˚C)
o Pleuritic pain
o Dry cough that progresses (after ~ 2 days) to a productive
cough with rusty coloured sputum
o Patient breathes rapidly and shallowly
o Decreased chest expansion on the affected side
o A pleural rub
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Investigations:
• CXR:
o Confirms areas of consolidation
o May show areas of collapse
• Blood tests:
o FBC (will show WCC of <4 or >20, may also show
polycythaemia if chronic)
o LFTs (some organisms can affect liver function – e.g.
Legionella)
o U&Es (signs of dehydration – increased urea/creatinine)
o ESR
o CRP
• Arterial blood gas:
o Will usually show hypoxaemia and hypercapnia
• Blood culture
• Sputum (only useful for proving the existence of an atypical
infecting organism)
o Gram stain
o Culture
Types of pneumonia:
• Strep. pneumoniae – very common cause
• Mycoplasma pneumoniae – teens and adults in their 20s
• Haemophilus infuenzae – commonly infects patients with COPD
• Chlamydia psittaci – transmitted by infected birds (especially
parrots)
• Chlamydia pneumonia – person-to-person transmission
• Staph. aureus – IVDUs and patients with central lines
• Legionella pneumophilia – air-conditioning and shared water
systems
• Pneumocystis carinii – immunocompromised (especially AIDS
patients)
• Pseudomonas – cystic fibrosis (bad prognostic sign)
Management of pneumonia:
• Antimicrobials (see below for details)
• IV fluids (to rectify dehydration and maintain a good urine
output)
• Oxygen
• Analgesia (for pleuritic pain, e.g. NSAIDs)
Antimicrobial treatment of pneumonia:

• Community acquired:
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o Erythromycin 500mg/6h PO, or

o Clarithromycin 250-500mg BD PO
• Hospital acquired:
o COPD/post-influenza:
• Amoxicillin 250-500mg/8h PO
• Aspiration:
o Clindamycin 450-900mg/8h IV, or
o Cefoxitine 2g/8h IV
Complications of pneumonia:
• Lung abscesses:
o Common in aspiration pneumonias
o Clinical features:
• Persistent or worsening pneumonia
• Production of large quantities of foul-smelling
sputum
• Swinging fever
• Empyema:
o This is the presence of pus within the pleural cavity
o Usually arises after the rupture of a lung abscess into the
pleural space or from bacterial spread from a severe
pneumonia
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Pneumothorax
Definition:
• Air in the pleural space
Causes:
• Trauma to the chest wall
• Spontaneous
Pathophysiology:
• Pneumothorax is localised if the visceral pleura has previously
undergone adhesion to the parietal pleura, or generalized if the
whole hemithorax contains air
• Normally, the pressure in the pleural space is negative but this is
lost once a communication is made with atmospheric pressure
• The elastic recoil pressure of the lung then causes it to partially
deflate
• If the communication between the airways and the pleural space
remains (an open pneumothorax), a bronchopleural fistula is
created
• It takes about 40 days for a 50% collapse of the lung to
reabsorb completely once the pneumothorax is closed
Tension pneumothorax:
• A valvular mechanism may develop through which air can be
sucked during inspiration but not expelled during expiration
• The intrapleural pressure remains positive throughout breathing,
the lung deflates further, the mediastinum shifts and venous
return to the heart decreases – with increasing respiratory and
cardiac embarrassment
• A tension pneumothorax is very rare, unless the patient is on
positive ventilation
Spontaneous pneumothorax:
• Usually occurs in young males (male:female is 6:1)
• It is caused by the rupture of a pleural bleb, usually apical and is
thought to be due to congenital defects in the connective tissue
of the alveolar walls
• Both lungs are affected with equal frequency
• Often these patients are tall and thin
• In patients >40 years, the usual cause is underlying COPD
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o Sudden onset of unilateral pleuritic pain

o Increasing breathlessness
Treatment:
• Essentially involves aspirating the air in the pleural space
• If the air reaccumulates, insert an intercostal drainage tube with
underwater seal for 2-3 days
• If the air reaccumulates after this, a pleurectomy is sometimes
required
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Respiratory failure
Definition:
Respiratory failure occurs when pulmonary gas exchange is sufficiently
impaired to cause hypoxaemia, with or without hypercapnia
• It can be divided into 2 types:
o Type I respiratory failure (‘acute hypoxaemic failure’):
• PaO2 <8Kpa
• PaCO2 is normal or low
o Type II respiratory failure (‘ventilatory failure’):
• PaO2 <8kPa
• PaCO2 >7kPa
Common causes of type I failure:

• Pulmonary oedema
• Pneumonia
• ARDS
• Pulmonary fibrosing alveolitis
• Right-to-left shunts
• V/Q mismatch
Common causes of type II failure:

• CNS (e.g. drugs, tumour, trauma, infection)
• PNS (e.g. phrenic nerve damage, myasthenia gravis, Guillain-
Barre syndrome)
• Muscular (e.g. dystrophies, hypokalaemia, hypophosphataemia)
• Chest wall (e.g. fractured rib, thoracic surgery, obesity)
• Airway (e.g. obstruction, bronchospasm)
Disturbances in acid-base balance:

• Remember:
H+ + HCO3- CO2 + H2O
• There are 4 situations in acid-base disturbance:

o Respiratory acidosis (e.g. respiratory depression)
o Respiratory alkalosis (e.g. anxiety attacks)
o Metabolic acidosis (e.g. DKA)
o Metabolic alkalosis (e.g. vomiting)
Normal ranges for blood gases:

• pH 7.35-7.45
• PO2 10-13.3kPa
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• PCO2 4.7-6.4kPa
• HCO3- 20-25mmol/L
• SaO2 95-100%
Management of respiratory failure:

• Always seek to treat the underlying cause
• There are 5 aims in management of respiratory failure:
1. Supplemental O2
2. Control of secretions
3. Treatment of pulmonary infection
4. Control of airways obstruction
5. Measures to limit pulmonary oedema
6. Correction of electrolytes/malnutrition
Oxygen therapy:
• Oxygen is, initially delivered via a face mask or nasal specs. If
this is proving inadequate, there are several other techniques for
respiratory support available:
• Non-invasive positive pressure ventilation:
o Bi-level positive airway pressure (BPAP) (insp and exp
pressures can be set separately)
o Continuous positive airway pressure (CPAP) via a face
mask (constant pressure but can vary volumes)
• Invasive positive pressure ventilation:
o Intermittent positive pressure ventilation (IPPV) (may be
given with positive end expiratory pressure – PEEP)
• CPAP via an endotracheal tube
• High frequency jet ventilation (HFJV) (useful for patients with a
lung leak)
IPPV:
• This is achieved by intermittently inflating the lungs with a
positive pressure delivered by a ventilator and applied via an
endotracheal tube or a tracheostomy
• Beneficial effects:
o Improved CO2 elimination
o Relief from exhaustion
o Reduction in total body O2 demand
• Dangers of IPPV:
o Airway complications
o Mechanical faults with ventilator
o CVS complications (the intermittent application of positive
pressure impedes venous return and distends alveoli,
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thereby stretching the pulmonary capillaries and causing

an increase in pulmonary vascular resistance
o Pulmonary infection
o Barotrauma
o Abdominal distension associated with an ileus (unknown
cause)
o Increased ADH secretion, therefore causing salt and water
retention
Complications of endotracheal intubation:

• Immediate:
o Tube in one or other (usually the right) bronchus
o Tube in oesophagus
• Early:
o Migration of tube out of trachea
o Leaks around the tube
o Obstruction of the tube due to kinks or secretions
• Late:
o Mucosal oedema and ulceration
o Tracheal narrowing and fibrosis
Complications of tracheostomy:
• As for endotracheal tubes, plus the following:
• Early:
o Pneumothorax
o Haemothorax
o Subcutaneous emphysema
• Intermediate:
o Erosion of tracheal cartilages
o Erosion of innominate artery (may lead to fatal
haemorrhage)
o Infection
• Late:
o Tracheal stenosis at level of stoma
o Collapse of tracheal rings at level of stoma
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Sarcoidosis
Sarcoidosis is a multisystem granulomatous disorder, commonly

affecting young adults and usually presenting with:
• Bilateral hilar lymphadenopathy
• Pulmonary infiltration
• Skin lesions
• Eye lesions
Diagnosis is confirmed on the histological evidence of widespread,
non-caseating, epithelioid granulomas in more than one organ
Epidemiology:
• Unknown aetiology
• 19 per 100,000 in the UK
• Peak incidence is in the 30s and 40s
• Females > males
Clinical features:
• Respiratory symptoms
• Abnormalities found on CXR (e.g. bilateral hilar
lymphadenopathy)
• Fatigue (~5%)
• Weight loss (~5%)
• Peripheral lymphadenopathy (~5%)
• Fever (~4%)
Bilateral hilar lymphadenopathy:

• A characteristic feature of sarcoidosis
• Often asymptomatic and only detected by a routine CXR
• Evidence from CT scanning shows that the lung parenchyma is
nearly always involved
• The differential diagnosis of bilateral hilar lymphadenopathy
includes:
o Sarcoidosis
o Lymphoma (although it is rare for this to only affect the
hilar lymph nodes)
o Pulmonary TB
o Carcinoma of the bronchus (with malignant spread to the
contralateral hilar lymph nodes)
Pulmonary infiltration:
• This type of sarcoidosis may be progressive and may lead to:
o Increasing effort dyspnoea
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o Cor pulmonale
o Death
• Pulmonary function tests show a typical restrictive lung defect
Extrapulmonary manifestations of sarcoidosis:

• Skin lesions:
o Lupus pernio (a chilblain-like lesion) is seen in 10% of
cases
o Erythema nodosum (sarcoidosis is the most common
cause)
• Ocular and associated effects:
o Anterior uveitis:
• Misting of vision
• Painful eye
• Red eye
o Posterior uveitis:
• Progressive loss of vision
• Metabolic manifestations:
o Hypercalcaemia in 10% of established cases:
• Caused by the high circulating concentration of
1,25-dihydroxycholecalciferol
• This is because there is a high concentration of 1"-
hydroxylase in sarcoid macrophages in the lung
o Hyperuricaemia
• These 2 factors can lead to the formation of renal calculi
• CNS:
o Involvement is rare (<2%)
o Can cause severe neurological disease
• Hepatosplenomegaly
• Cardiac involvement:
o Occurs in ~3% of patients
o Can cause:
• Ventricular dysrhythmias
• Conduction defects
• Cardiomyopathy
• CCF
Investigations:
• Imaging:
o CXR
o CT
• Blood tests:
o FBC (there is a mild normochromic normocytic anaemia)
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o ESR (raised)
o Biochem (hypercalcaemia and hypergammaglobulinaemia)
• Transbronchial biopsy:
o Is the most useful investigation
o This test provides histological evidence of a granuloma in
~50% of patients with clinically extrapulmonary
sarcoidosis in whom the CXR is normal
• Serum level of ACE:
o Is 2 SDs above normal in 75% of patients with untreated
sarcoidosis
Lung function tests:

• Show a restrictive lung defect with pulmonary infiltration
• Decreased:
o TLC
o FEV1
o FVC
o Gas transfer
Treatment:
• If the disease is not improving spontaneously within 6 months of
diagnosis, treatment should be started
• Prednisolone 30mg daily for 6 weeks, reducing to alternate-day
treatment with prednisolone 15mg for 6-12 months
Prognosis:
• The disease is fatal in <5% of patients in the UK
• Most deaths are from respiratory failure and cor pulmonale
• The disease remits within 2 years in over:
o 65% of patients with hilar lymphadenopathy alone
o 50% of patients with hilar lymphadenopathy plus CXR
evidence of pulmonary infiltration
o 30% of patients with X-ray evidence of infiltration without
any demonstrable lymphadenopathy
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Tuberculosis (TB)
Epidemiology:
• TB is the world’s leading cause of death from a single infectious
disease
• 2,000,000 deaths in 1990
• This is the result of:
o Inadequate programmes for disease control
o Drug resistance
o Co-infection with HIV
• In the UK, there are 7,000 new cases per year
• In the UK, the highest risk groups are immigrants from the Asian
subcontinent and the West Indies
• TB is a notifiable disease
Pathology:
• The initial infection with M.tuberculosis is known as primary
tuberculosis
• It is usually subpleural, often in the mid to upper zones
• Within an hour of reaching the lung, tubercle bacilli reach the
draining lymph nodes at the hilum of the lung and a few escape
into the bloodstream
• The initial reaction comprises:
o Exudation
o Infiltration with neutrophil granulocytes (these are rapidly
replaced by macrophages which ingest the bacilli)
• Granulomatous lesions consist of a central area of necrotic
material of a cheesy nature (called caseation) surrounded by
epithelioid cells and Langerhan’s giant cells
• Subsequently, the caseated areas heal and many become
calcified
• It is known that at least 20% of these calcified primary lesions
contain tubercle bacilli, initially lying dormant but capable of
being reactivated by depression of the hosts immune system
• Reactivation leads to typical post-primary pulmonary TB with
cavitation, usually in the apex or upper zones of the lung
• Post-primary TB refers to all forms of TB that occur after the first
few weeks of the primary infection when immunity to the
mycobacterium has developed
Clinical features of primary TB:

• Asymptomatic in the majority of individuals
• Cough
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• Wheeze
• Small, transient, pleural effusion
• Erythema nodosum
What can cause reactivation?

• Increasing age
• Malnutrition
• Immunosuppression
• AIDS
• Lymphoma
Miliary TB:
• Is the result of acute diffuse dissemination of tubercle bacilli via
the bloodstream
• Is universally fatal unless treated
• It may present in an entirely non-specific manner with a gradual
onset of:
o Vague ill-health
o Weight loss
o Fever
• Occasionally it presents as tuberculosis meningitis
• Positive Mantoux test
• Transbronchial biopsies are frequently positive before any
abnormality is visible on the CXR
Adult post-primary TB:

• Typically, there is a gradual onset of symptoms over weeks or
months:
o Tiredness
o Malaise
o Weight loss
o Fever
o Cough
• Sputum in TB may be:
o Mucoid
o Purulent
o Blood-stained
• A pleural effusion or pneumonia can be the presenting feature of
TB
On examination:
• Very few signs
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• Finger clubbing (if disease is advanced and associated with

considerable production of purulent sputum)
Investigating adult post-primary TB:

• CXR:
o An abnormal CXR is often found with no symptoms, but
the reverse is extremely rare (pulmonary TB is unlikely in
the absence of any radiographic abnormality)
o Typically shows:
• Patchy or nodular shadows in the upper zones
• Loss of volume
• Fibrosis (with or without cavitation)
• Calcification may be present
Diagnosis:
• The diagnosis is made on the basis of the following
investigations:
o Imaging:
• CXR
• CT
• Staining:
o The sputum is stained with Ziehl-Nielsen (ZN) stain for
acid-fast and alcohol-fast bacilli (AAFB)
• Culture:
o The sputum is cultured for 4-8 weeks
o Cultures to determine the sensitivity of the bacillus to
antibiotics take a further 3-4 weeks
• Fibre-optic bronchoscopy with washings from the affected lobe
(s):
o Useful if no sputum is available
• Biopsies of the:
o Pleura
o Lymph nodes
o Solid lesions within the lung (tuberculomas)
Treatment:
• Directly observed therapy (DOT):
o In order to improve compliance, special clinics are used to
supervise treatment regimens directly
o Incentives to attend (e.g. free meals) may be helpful
• Six-month regimen:
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o This is standard practice for patients with pulmonary and

lymph node disease
o Daily administration of:
• Rifampicin 600mg, and
• Isoniazid 300mg
• Pyrazinamide 1.5-2g (for the first two months only)
o These are given as combination tablets and are taken 30
minutes before breakfast (since the absorption of
rifampicin is influenced by food)
• Longer regimens:
o Treatment of bone TB should be continued for a total of 9
months
o Tuberculosis meningitis should be treated for 1 year
o The drugs are the same as for pulmonary TB
Unwanted effects of drug treatment:

• Rifampicin:
o Induces liver enzymes
o Drug should only be stopped if the serum bilirubin
becomes elevated (which is extremely rare)
o Stains body secretions pink (urine, tears, sweat
o Due to the induction of liver enzymes, other drugs will be
affected (e.g. the OCP is ineffective whilst taking
rifampicin)
• Isoniazid:
o Very few unwanted effects
o Skin rash, fever and hepatitis occur in <1% of patients
o If hepatitis occurs, isoniazid must be stopped
o May produce a polyneuropathy in high doses (therefore,
give pyridoxine 10mg daily to prevent this)
• Pyrazinamide:
o The main unwanted side-effect of this drug is severe
hepatic toxicity, although it is not very common
o Gout may occur owing to hyperuricaemia
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Vascular Surgery
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Abdominal aortic aneurysm (AAA)

• Present in 5% and responsible for the death of 1% of men over
60 years of age
• The principle cause of death is rupture, but distal embolism from
thrombus in the aneurysm sac and, rarely, a thrombotic
occlusion can also set the scene for death
• An aortic aneurysm inevitably expands, a process made much
more likely by hypertension
• Eventually, rupture takes place through all the attenuated
layers, with either the:
o Initial formation of a retroperitoneal clot, or
o Immediate free bleeding into the peritoneal cavity
sufficient to cause death
• The risk of rupture is related to the size of the aneurysm – the
normal aorta is 1.5-2.5cm in diameter and is defined as
aneurysmal when it is >4cm
• The reported annual risk of rupture is probably in the region of:
o 4cm 1-2%
o 5cm 5-10%
o 6cm 10-15%
o 7cm >20%
• Only 30% of patients with rupture live long enough to reach
hospital , and of those operated upon, only 50% survive
• Thus, the overall (community) mortality for rupture is as high as
80-90%
Clinical features:
• In thin patients, the aneurysm itself as well as its transmitted
pulsation may be visible on inspection
• On palpation, there will be a pulsatile, expansile swelling in the
midline of the abdomen, usually extending towards the left-hand
side
• However, clinical examination alone is very unreliable at
confirming the presence or absence of an AAA
• Any suspicion of AAA should therefore prompt an US
investigation
• There may be a bruit on auscultation in association with origin
stenoses of the branches of the abdominal aorta (coeliac axis,
superior mesenteric, renal arteries)
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• There is an association between AAA and aneurysms elsewhere,

so one should specifically exclude the presence of femoral and
popliteal aneurysms
Management:
• The unpredictable nature of this process means that vascular
surgeons usually organise repeat US examination at 3-6 monthly
intervals for those who do not require urgent management
Indications for elective repair:

• The decision to operate involves weighing the known risk of
leaving the AAA in place against that of the operation
• The first depends on:
o Size
o Presence of symptoms
o Age and physiological state
• The risk of operation depends primarily upon cardiorespiratory
status
• There is no advantage to be gained in repairing a small
aneurysm at low risk of rupture in an elderly patient with severe
myocardial disease whose cardiac prognosis is poor
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Arteriovenous malformation (AVM)
These types of malformation are congenital but not hereditary

abnormalities
Clinical features:
• Symptoms:
o Patients present at almost any age; onset of symptoms
may be related to the appearance of the menarche, to
pregnancy or to an episode of minor trauma
o Swelling
o Discolouration
o Bleeding
o Pain
o High-output cardiac failure
o Limb hypertrophy
• Signs:
o Lesions with an arterial component are usually pulsatile
o A machinery-type murmur is heard on auscultation
o Venous lesions engorge and empty with dependency and
elevation, respectively
Diagnosis:
• Appearance in later life requires distinction from malignant
lesions such as sarcoma and metastatic deposits
• Apart form biopsy to exclude malignancy in cases of doubt, the
diagnosis is usually clinical
Investigation:
• A CXR allows assessment of cardiac size
• US can be used to assess venous lesions
• CT and particularly MRI give valuable information about deep
extent when excision is contemplated
Management:
• AVMs may not require treatment except for counselling and the
reassurance for both the patient and, in children, the parents
• Occasionally operation may be required to exclude malignancy
• Complete excision provides good long-term control but is rarely
feasible
• Amputation is sometimes required as a last resort
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• Therapeutic embolisation, in which the lesion is filled from within

with thrombogenic coils or gel, is the mainstay of treatment:
o Carries a risk of ischaemia in surrounding or distal vital
tissues
• Venous lesions can be treated by direct injection of sclerosant
and/or partial excision of prominent veins once the normality of
the deep venous system (sometimes absent or hypoplastic) has
been assured
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Carotid artery disease
• ~80% of all strokes are ischaemic rather than haemorrhagic
• Of these, as many as 50% are caused by atherosclerosis at the
carotid artery bifurcation
• This leads to either distal or thrombotic occlusion
Symptoms:
• Amaurosis fugax:
o Microembolism to the eye leads to ipsilateral transient loss
of vision
o Described as a black curtain coming across the eye
o Usually lasts from a few seconds to a few minutes
o A larger embolus may cause permanent blindness due to a
retinal infarct
• Embolisation to the middle cerebral artery leads to hemispheric
symptoms:
o Usually a contralateral hemiparesis
o Loss of speech (if the dominant hemisphere is affected)
• Transient ischaemic attack (TIA):
o A focal neurological deficit lasting less than 24 hours. The
major complication of carotid artery disease is a stroke
Signs:
• The neurological findings and their duration are consistent with
the size of the area of brain affected
Diagnosis and intervention:

• Carotid artery stenosis may be visualised by angiography, but
this technique may be associated with a 1-2% stroke rate and is
not suitable as a first-line investigation
• Colour-flow duplex scanning can give accurate information on
the presence and degree of stenosis
• A CT brain scan before operation is commonly done to define the
presence of pre-existing cerebral damage or to exclude other
pathology
Management:
• Indications for carotid endarterectomy (CEA):
o In cases of amaurosis fugax, TIA or stroke with good
recovery plus an internal carotid artery stenosis of >70%,
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the risk of future stroke is significantly reduced by CEA

carried out as a supplement to best medical therapy alone
o Most stenoses <70% should be treated medically
• Technique for CEA:
o The major complication of CEA is a stroke
o The benefits of the operation depend crucially upon a low
perioperative stroke rate, which should be less than:
• 7.5% after a previous stroke
• 5% in amaurosis fugax or TIA
• 3% in those who are asymptomatic
• Balloon angioplasty:
o Early data suggests that the immediate complication rate
from endovascular treatment is higher than that associated
with CEA
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Critical limb ischaemia (CLI)
Overview:
• Defined as ‘rest pain which requires strong (opiate) analgesia for
a period of 2 weeks or more, and tissue loss, in association with
an ABPI of <50mmHg’
• The inference is that, without intervention, a patient with CLI will
come to major amputation within weeks or months
Symptoms:
• Rest pain is indicative of severe ischaemia, usually felt in the
forefoot and, typically, the pain is worse at night and disturbs
sleep
• The reasons for this are:
o Metabolic rate in the foot is increased under the warm
bedclothes
o Cardiac output and BP fall during sleep
o The beneficial effect of gravity on pedal BP is lost
• For these reasons, relief at night is often sought by hanging the
leg over the side of the bed or walking about on a cold floor
Signs:
• In addition to the findings of arterial insufficiency, there may be
evidence of multilevel disease
• Constant pain in the foot with single level arterial disease is
uncommon and should lead to a search for other causes
• Ischaemic tissue is extremely sensitive to injury; even minor
wounds fail to heal and ulceration follows
• Minor damage quickly leads to infection and bacterial toxins
destroy yet more tissue
• Frank gangrene then ensues and can spread extremely rapidly,
especially in diabetics
Medical management:
• In contrast to a presentation with claudication, rest pain is a
warning that tissue loss is imminent
• In the great majority, CLI does not improve without surgical
intervention but medical therapies have important roles:
o Assessment and treatment of heart failure, intercurrent
infection and anaemia
o Control of diabetes
o Antibiotic therapy for local infection
o Pain relief
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o Use of anticoagulants and, occasionally, prostacyclin-based

drugs when tissue loss is minimal
• All of these measures can ensure that an optimum condition is
achieved before surgical intervention is performed
Balloon angioplasty:
• In patients with early rest pain and/or minimal tissue loss
(subcritical ischaemia), PTA may tip the balance just enough to
salvage the limb when surgical reconstruction is not feasible
• However, some believe that all patients with CLI should in the
first instance be managed with PTA and that operation should be
reserved for those who do not respond
Amputation:
• This is a last resort
• Primary amputation can be the best option in the elderly frail
patient with extensive tissue loss, but mortality is inevitably high
Surgery:
• Bypass surgery and, to a far lesser extent, local endarterectomy
are the mainstays of treatment, although the frequently present
multisystem medical and vascular problems dictate a mortality
for limb salvage surgery of up to 10%
• Aortoiliac disease:
o In CLI, this is usually associated with infra-inguinal disease
o In younger, fitter patients who are considered unsuitable
for PTA, the standard operation is aortobifemoral bypass
graft
o In those not fit for aortic surgery, an extra-anatomical
bypass may be suitable. For example, if there is an iliac
occlusion on one side and a relatively disease-free vessel
on the other, a femorofemoral crossover graft is possible
• Femorodistal bypass:
o This refers to an arterial reconstruction below the inguinal
ligament in which common femoral or superficial femoral
arteries are the site of proximal anastomosis and the
popliteal or tibial vessels are the site of distal anastomosis
• The requirements for a successful distal bypass are:
o Good inflow
o A reliable conduit
o Good outflow
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Management of thrombosis in a graft:

• The options are:
o If the leg is viable then it may be sensible to do nothing
and wait for collaterals to develop
o Thrombolysis – if successful, the underlying lesion which
caused the graft to block can then be identified and
corrected by either surgery or PTA
o Thrombectomy – mechanical removal of thrombosis,
followed by an operative angiogram to identify the
underlying lesion and surgical correction
o Construction of a new graft
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Intermittent claudication (IC)
Overview:
• Is the mildest manifestation of lower limb ischaemia (LLI)
• Affects ~5% of men >60 years of age
• In the majority, it is the consequence of narrowing or occlusion
of the superficial femoral artery in the thigh
Symptoms:
• Ischaemic muscle pain on walking that is relieved by rest
• To begin walking again causes re-arrest after the same distance
has been travelled
• At rest, the blood requirement is met by the collateral circulation
through the profunda femoris system:
o Joins the popliteal artery below the blockage usually just
above the knee
• However, exercise produces a demand which cannot be met and
the calf muscles become ischaemic
• Cycling may be used as an alternative to walking as this relies
predominantly on the thigh muscles
• If stenosis is more proximal (aortoiliac), then pain is felt in the
whole leg and even the buttock if the blood flow to the internal
iliac artery is compromised
• Leriche syndrome:
o Difficulty or impossibility of sustaining an erection
o Consequent upon an aortoiliac obstruction
Signs:
• The limb may be obviously ischaemic
• Pulses are usually diminished or absent below the femoral but, if
they are present, exercise causes their disappearance
Diagnosis:
• There are many causes of pain in the leg, of which arterial
disease is only one
• Much of the time of a vascular service is spent excluding other
disorders
• Pain that radiates from the back, hip and knee joint, OA and
venous outflow obstruction (venous claudication) may all be
difficult to distinguish from true arterial claudication
Management:
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• Arterial claudication is common, but progression to critical

ischaemia is unlikely
• Anxious patients should be reassured that amputation is unlikely
• The risks for arterial surgery or amputation are <1-2% per year
• However, certain patients are at risk of disease progression,
including those who:
o Present with severe claudication of less than 50m
o Have low ABPI (<0.5)
o Have multilevel or distal disease
o Are diabetic
o Continue to smoke
• Such patients need careful assessment, aggressive treatment of
risk factors and the offer of reconstruction or endovascular
therapy if and when critical limb ischaemia develops
Medical therapy:
• For many years, the standard treatment for the majority of
patients has been to stop smoking and keep walking
• All should be:
o Reassured that the legs are not in imminent danger
o Warned about the hazards of continued smoking
o Screened and treated for correctable risk factors (e.g.
diabetes, hyperlipidaemia)
o Told to exercise regularly to the point of pain in order to
develop collateral circulation
• The majority accept the wisdom of this advice and attempt to
alter their lifestyle
• However, a proportion will not comply and/or will not accept
their level of disability and in these, intervention may have to be
considered
Surgical intervention:
• Percutaneous transluminal angioplasty (PTA)
• Operation
Operation:
• Aortoiliac (supra-inguinal) disease:
o There is a lower threshold for reconstruction in this arterial
segment because:
• The ability to compensate for aortoiliac occlusion by
formation of collaterals is not as good as it is in infra-
inguinal disease
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• The long-term result of aortoiliac reconstruction is

considerably better than in infra-inguinal bypass; more
than 80% of aortobifemoral grafts for claudication are
patent at 10 years
• Bilateral claudication can be corrected by a single
operation
• Those affected by aortoiliac disease are generally
younger and more likely to have their livelihood
threatened by their disability
o Infra-inguinal disease:
• By contrast, there is much less enthusiasm for infra-
inguinal bypass because:
o Compensation by collateral development is often
good
o At 5 years, less than 70% of femoropopliteal grafts
are still patent
o Bilateral claudication is common, requires 2
operations and so doubles the risk
o Insertion of a bypass graft leads to involution of
collateral pathways; if the graft blocks, the patient
nearly always returns to a worse level of ischaemia
than that present before operation
• Rest pain may develop after a failed graft and force re-
operation; the long-term results of such procedures are less
impressive than those of primary reconstruction
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Raynaud’s phenomenon
Overview:
• Raynaud’s phenomenon (RP):
o Is the general term which describes the clinical features of
episodic digital vasospasm in the absence of an identifiable
associated disorder
• Secondary Raynaud’s syndrome (RS):
o This is when the phenomenon occurs secondary to one of
the conditions listed below
Conditions associated with Raynaud’s syndrome:

• Connective tissue disorders:
o Systemic sclerosis 90%
o Systemic lupus erythematosus (SLE) 30%
o Mixed connective tissue disease 80%
o Dermatomyositis/polymyositis 30%
• Macrovascular disease:
o Thoracic outlet obstruction
o Atherosclerosis
o Buerger’s disease
o Radiation arteritis
• Occupational trauma:
o Vibration white finger (VWF)
o Chemical exposure (e.g. nitrates, polyvinyl chloride)
o Repeated exposure to extreme cold
• Drugs:
o Cytotoxic drugs
o Ergotamine
o Beta-blockers
o Cyclosporine
• Miscellaneous:
o Malignancy
o Arteriovenous fistula

• 10x commoner in females than males
• Affects (in a mild form) up to 25% of the young female
population
• Risk factors include:
o OCP
o Some migraine drugs
o Tobacco
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Clinical features:
• There are 3 phases:
o Pallor – because of digital artery spasm
o Cyanosis – from the accumulation of deoxygenated blood
o Redness (rubor) – reactive hyperaemia as blood flow
returns
• Pain is usual unless there are other complications (e.g. digital
ulceration and gangrene)
Diagnosis:
• In the majority, the diagnosis of RP can be made on symptoms
and physical findings; additional investigations are not required
unless secondary RS is suspected
• Only a minority have clear evidence of connective tissue disease
at presentation
• Presentation for the first time in childhood or over the age of 30
increases the likelihood of RS
• 80% of those who present >60 years of age have an underlying
disorder (although it is most likely atherosclerosis)
Medical management:
• Most often, reassurance about the usually benign nature of their
condition, advice to stop smoking and to avoid exposure to cold
are sufficient
• Numerous drugs have been used, the best of which appears to
be the calcium-channel blocker nifedipine, although side-effects
are common
• Vasodilators may also be useful
• In those with severe attacks:
o Admission to hospital for a 5-day infusion of prostacyclin
may provide great symptomatic relief in the winter months
and, for unknown reasons, the beneficial effects may last
up to 6 weeks
• Secondary RS caused by macrovascular arterial disease is
nearly always unilateral and may progress rapidly to tissue loss
in the hand if the underlying lesion is not identified and treated
• Sympathectomy is useful in the long-term treatment of RS in
the feet, but NOT in the hand
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• In the variant CREST syndrome, digits affected by severe

ulceration or calcium deposits may require amputation
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The diabetic foot
Clinical features:
• Diabetics have a tendency to develop, often quite suddenly,
severe ischaemia and infection in the feet which progresses to
rapid tissue necrosis and amputation
• There are 4 reasons for this:
o Vascular disease
o Sensory neuropathy
o Autonomic neuropathy
o Motor neuropathy
Vascular disease:
• In diabetics, this develops earlier in life and tends to be more
extensive and distal
• The clinical features are similar to non-diabetic vascular disease
except that a palpable popliteal pulse is more frequently present,
due to the more distal distribution of the disease (particularly
affecting the tibial vessels)
Sensory neuropathy:
• Reduces or abolishes protective reactions to minor injury and to
symptoms of infection or ischaemia
Autonomic neuropathy:
• Causes a lack of sweating and the development of dry, fissured
skin which permits entry of bacteria
Motor neuropathy:
• Results in:
o Wasting and weakness of the small muscles
o Loss of the longitudinal and transverse arches of the foot
o Development of abnormal pressure areas, such as over the
metatarsal heads
Management:
• Tissue loss is neuropathic or ischaemic, or more commonly a
combination of both (neuroischaemic)
• The principles of management are:
o Best medical care for the diabetes
o Wide debridement of devitalised tissue
o Drainage of pus
o Revascularisation (if ischaemia is present)
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Traumatic arteriovenous fistula
If, as a result of trauma, there is damage to an adjacent artery and

vein, a fistula between them may develop
Clinical features:
• Pain
• Swelling
• Other features of distal ischaemia
• If the shunt is large, then, over some weeks and months, cardiac
failure may develop
• Palpable thrill
• Machinery bruit on auscultation throughout the cardiac cycle
• Distal venous engorgement may develop
Management:
• Surgical repair is indicated
• Other techniques may be used:
o Embolisation
o Covering the fistulous opening in the artery with a stent
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Varicose veins
Epidemiology:
• Female:male ratio of 3:1
• ~2% of the population
• Up to 50% of 65-75 year olds may have them
• The major complication is the nutritional change in the skin
which may eventually go on to ulceration
Classification:
• Primary:
o Poorly understood aetiology
o There is deep to superficial incompetence only
o The varicosities appear without an obvious underlying
cause
• Secondary:
o The varicosities occur because of some other cause:
• Obstruction
• Thrombo-inflammatory destruction of valves, in both
the communicating and deep veins
Secondary varicose veins:

• Less common than the primary type
• Causes include:
o Deep or (less common) superficial venous thrombosis with
recanalisation and consequent deep and/or deep to
superficial valve destruction
o Obstruction with venous HT – a proximal injury or
obstruction from a tumour
o Congenital or acquired arteriovenous fistulae with
increased pressure and flow being transmitted from the
arterial side of the circulation
• Secondary varicose veins are associated with the syndrome of
chronic venous insufficiency, which is considered below
Secondary effects of varicose veins:

• Perivenous tissue changes:
o Interstitial oedema
o Possible decreased oxygenation of cells, with nutritional
disturbance
• Ulceration
• Skin changes:
o Lipodermatosclerosis:
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• Pigmentation (due to extrusion of RBCs (diapedesis)

and their subsequent dissolution
• Thickening if the subcutaneous tissues
• Skin atrophy
Symptoms of varicose veins:

• Ugly appearance
• Aching
• Pain on exercise
• Ankle swelling
• Restless legs
• Pigmentation and depigmentation
• Eczema
• Attacks of superficial phlebitis
• Ulceration
• Bleeding into the subcutaneous tissues
Investigations:
• The investigations described below are for localisation of
incompetent deep to superficial communications and for
identification of valvular insufficiency in deep veins
• Continuous wave ultrasound:
o Used to detect points of incompetence, e.g. at the
saphenofemoral junction
• Duplex Doppler scanning:
o The anatomy can be clearly shown
o Valves can be visualised
o Reflux is demonstrated by the reversal of the direction of
flow using the same principle as with continuous flow
Doppler
• Venous pressure studies:
o Not used routinely
o Helpful in sorting out a complex problem of recurrence
after surgery or of deep venous insufficiency
• Venography
Management of primary varices:

• By definition, these are the varices in the superficial system
with:
o Deep to superficial incompetence at one or more sites
o No evidence of disease in the deep veins
• Once it is certain that the symptoms and signs in the leg are
associated with the varices, there are 3 options:
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o Compression hose
o Sclerotherapy
o Surgery
Compression hose:
• The indications are:
o Mild symptoms
o Those without skin changes
o The elderly
o Those who refuse other treatment
o Most pregnant women
• Patients should be instructed to apply compression hose before
they get up in the morning and only remove the support last
thing at night
Compression sclerotherapy:
• The principle is to produce sterile chemical inflammation in a
vein kept empty by compression; thrombosis and obliteration of
the lumen follow
• The solutions most commonly used are 5% ethanolamine oleate
or 3% sodium tetradecyl sulphate
• The method is suitable only for isolated varices without a large
site of deep to superficial incompetence, because if this exists,
recurrence rates are very high
• Further uses are:
o Obliteration of isolated incompetent perforating veins,
especially after surgery
o Vulval varices which persist after pregnancy
Surgery:
Clinical feature Indication Contraindication

Pain Definite Doubts as to the cause
Phlebitis Varicose veins the onlyOther causes not excluded
cause
Bleeding Episode of considerableMinor bleeding
bleeding
Skin changes To prevent ulceration
Ulceration Adjunct to healing Cannot correct venous HT
Technique:
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• Aim is to interrupt, by ligation, the major points of incompetence

between the superficial and deep venous systems
• To remove, if appropriate, the varices for both functional and
cosmetic reasons
• Can be done as day-surgery cases
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Vascular trauma
Mechanisms:
• The commonest non-iatrogenic cause of injury to blood vessels
in the UK is RTAs (usually blunt injuries)
• Penetrating injuries (e.g. knife and gunshot wounds) are much
less frequent
• Iatrogenic injury to the brachial and common femoral arteries
form angiography and angioplasty are by far the commonest
examples
• If the injury is caused by a sharp instrument, such as a knife,
the arterial or venous wound tends to be limited to the area of
immediate injury and the remaining vessel is uninjured
• In some, particularly high-velocity, missile wounds or in blunt
trauma, the extent of the injury is often more extensive, in
terms of both the vascular injury and the associated injuries in
other systems
Clinical features:
• The 2 principle consequences of arterial injury are:
o Haemorrhage:
• Blood loss tends to be greater if there is only partial
rather than complete transaction
• This is because in partial transaction, the laceration
is held open by the continuity part of the wall,
whereas in complete transaction vasospasm and
intimal retraction with thrombosis occur, which limits
loss
o Ischaemia:
• This is often severe because the injury is acute and
the vasculature has previously been normal; there
has not been any opportunity for collaterals to
become established
Physical findings:
• In young people, provided that systolic BP is >100mmHg,
peripheral pulses should be readily palpable
• Absent or diminished pulsation should immediately alert the
clinician to the likelihood of vascular injury
• In a closed injury, an expanding haematoma may be palpable
• Doppler examination:
o An audible Doppler signal may be present from a collateral
circulation even if the artery is transacted proximally
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o However, in the lower limb, if the ABPI does not equal that of
the uninjured side, vascular injury should be suspected
Investigation:
• Angiography should be considered in any instance where there is
doubt about the diagnosis or where the site of injury is uncertain
Management:
• Resuscitation
• Immediate control of haemorrhage by direct pressure and then
operation rapidly to restore flow are essential
• The latter is achieved either by direct repair of the artery and
accompanying large veins , if possible, or by means of a bypass
graft
• Because of the risk of infection, prosthetic materials should be
avoided wherever possible
• All patients who sustain vascular trauma should receive
appropriate antibiotics and, when indicated, tetanus prophylaxis
• The use if thromboembolic prophylaxis has to be decided on an
individual basis and must balance the risks of thrombosis against
those of haemorrhage
• The risk of reperfusion injury is greatest in vascular trauma and
fasciotomy is frequently indicated for prevention
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Venous leg ulceration
Epidemiology:
• 80-85% of leg ulcers are of venous origin
• 70% of those with active ulcers are >70 years of age
• Female:male ratio of 3:1
Aetiology:
• Oedema from venous HT and raised pressure at the venular end
of the capillary loop, skin and subcutaneous hypoxia are and an
episode of minor trauma are the usual pathological antecedents
of ulceration
• They are most likely to occur when there is damage to the
valves of the deep veins, but long-standing superficial HT caused
by deep to superficial incompetence alone is also a well
recognised cause
• Once an ulcer is established, healing of the poorly nourished skin
is difficult and granulation tissue and a fibrous base develops
• The build-up of fibrosis with reduced input into the tissue from
the arterial side of the circulation is a further impediment to
healing
• Secondary infections by skin residents such as staphylococci are
common
Causes of ulceration of the leg:

• Venous disease
• Arterial disease
• Trauma
• Rheumatoid arthritis
• Pyoderma gangrenosum
• Systemic sclerosis
• Malignant disease
• Blood disorders (e.g. sickle cell disease)
Clinical features:
• The lesion occurs almost exclusively just above or in relation to
the medial malleolus
• It is usually:
o Oval
o Flat, without a raised edge
o Looks relatively healthy
o Has a granulating base
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o Concomitant infection (with either surrounding erythema

or extensive cellulitis) may be present
Distinctive characteristics of venous and arterial ulcers:
Venous Arterial
History Previous DVT, varices I n t e r m i t t e n t
claudication, IHD, HT,
DM
Pain Uncommon Nearly always present,
worse at night
Site Usually m e d i a l Toes, heal, foot, lateral
malleolus aspect
Size V a r i a b l e , i n c r e a s e s Variable but increases
slowly rapidly
Oedema C o m m o n , w o r s e a t Uncommon
night
Skin Pigmentation, white Shiny, thin, atrophic
patches nails
Temperature Usually warm Cool
Foot pulses Present Reduced or absent
Management:
• Most venous ulcers which are correctly diagnosed and treated
early respond readily to conventional treatment, but even
relatively small lesions can take up to 3 months to heal
• More chronic lesions require a more precise regimen, as follows:
o Step 1:
• Establish if there is correctable superficial venous HT
which is the consequence of deep to superficial
incompetence only
• If this is so, surgery is indicated
o Step 2:
• If there are multiple points of incompetence or, what
almost always amounts pathophysiologically to the
same thing, deep venous damage, the starting point is
non-operative management
• The majority of leg ulcers fall into this category
• The essential component is to apply effective
compression to the limb and sustain it until the ulcer
has healed
524
www.garrypettet.com
• All venous ulcers heal if the patient is confined to bed

with the foot elevated above the heart so that venous
HT is abolished, the microenvironment improved and
healing promoted
• However, bed rest is a costly and, therefore, usually
inappropriate method
• Adequate local compression in a patient who is
otherwise mobile is an effective alternative
o Step 3:
• This runs concurrently with steps 1 and 2
• Is local management of the lesion
• The inappropriate use of topical agents, included
impregnated bandages, prescribed by either a physician
or a nurse should be AVOIDED
• Dressings are kept simple and pharmacologically active
substances applied only for specific and logical reasons
– which means hardly ever
• Systemic antibiotic therapy is only indicated if there is
spreading cellulitis – topical applications are ineffective
in controlling contamination unless the causes of the
ulcer are dealt with
Surgical measures in ulceration:

• Severely contaminated long-standing ulcers with infected
granulation tissue at the bas may benefit from surgical
debridement before non-operative treatment is begun
525

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The MedSurg Handbook

Notes on medicine and surgery

Written by Garry KJ Pettet

ACUTE PAIN AND THE ANAESTHETIST ..............................................................9

BREAST SURGERY ............................................................................19

BENIGN BREAST PAIN ..............................................................................20

CANCER MEDICINE ..........................................................................33

ACUTE LYMPHOBLASTIC LEUKAEMIA (ALL) ......................................................36

ANGINA PECTORIS ..................................................................................83

BUNDLE BRANCH BLOCK ...........................................................................93

BULLOUS DISEASE ................................................................................121

ACUTE GASTRITIS .................................................................................211

GENERAL MEDICINE ......................................................................274

ACUTE LUMBAR DISC PROLAPSE .................................................................275

GENERAL SURGERY ........................................................................366

ADULT UMBILICAL HERNIA .......................................................................367

SCROTAL SWELLINGS .............................................................................403

ACUTE APPENDICITIS .............................................................................415

RESPIRATORY MEDICINE ...............................................................462

ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) .........................................463

VASCULAR SURGERY ......................................................................499

ABDOMINAL AORTIC ANEURYSM (AAA) ........................................................500

CRITICAL LIMB ISCHAEMIA (CLI) ...............................................................506

Acute pain and the anaesthetist

• This is where regional block, in the form of epidural or spinal

Simple analgesic drugs:

Non-steroidal anti-inflammatory drugs (NSAIDs):

• Pethidine derivatives (e.g. fentanyl and alfentanil) are very

• Nausea and vomiting

Intermittent positive pressure ventilation (IPPV)

Beneficial effects of IPPV:

Indications for IPPV:

• Intubating patients in severe respiratory failure is an extremely

A commonly used grading system is that described by the American

The scoring system allows easier communication between

However, it gives only limited prognostic information about the

Significant factors (including the type of procedure, a history of

Preoperative grading system of the ASA:

Local and regional anaesthesia

Regional versus general anaesthesia:

Hazards of local anaesthetic agents:

Types of local anaesthesia:

Benign breast pain

Benign breast pain is either cyclical or non-cyclical

Investigation of cyclical breast pain:

Management of cyclical breast pain:

Investigation of non-cyclical breast pain:

Management of non-cyclical breast pain:

Breast lumpiness and lumps

Discrete single lump:

Epidemiology and aetiology:

Investigation and management:

This is a relatively uncommon lesion

Investigation and management:

This is a rare cause of bilateral milky discharge

It follows lactation and is caused by a persistent elevation of prolactin

Infection of the breast

There are 2 common causes of infection:

Lactational breast abscess:

Clinical features of a lactational breast abscess:

Management of a lactational breast abscess:

Clinical features of periductal mastitis:

Investigation and management of periductal mastitis: