Podmedics LIVE - Clinical Pathology Course

Podmedics LIVE - Clinical Pathology Course
Clinical Pathology
Course
1! © Podmedics 2009
Podmedics LIVE - Clinical Pathology 2010
Aims of the Course
Welcome to our notes for the Podmedics LIVE Clinical Pathology course. The course is available to watch on
our website Podmedics.com and covers basic principles of illness and disease across all the specialties. It
would be relevant to students at all stages of their clinical training.
This course was originally designed as a revision course for the Year 5 Clinical Pathology exam at Imperial
College School of Medicine in London, and it ran at the college for two years to great acclaim. This year
however I have decided to re-record the whole course for use on the website. Do have a browse through the
notes to see what topics exactly are being covered.
These revision notes are not meant to be totally comprehensive, but include lots of space of you to fill in
while you watch the online lectures.
Podmedics.com
The course has been written by Ed Wallitt, an ex-ICSM junior doctor, who founded Podmedics.com in August
2007. For those of you who are unfamiliar with the site, Podmedics.com is a website and podcast developer
run by a group of junior doctors and medical students. All our podcasts are free, and aimed specifically at
medical students. Our ethos is to outline key medical principles and concepts that allow material
encountered in the lecture theatre and hospital to be better understood, and ultimately recalled.
There are currently well over one hundred audio and video podcasts available, either through iTunes or
direct from our website. Please do not hesitate to get in contact with me, or any of the other Podmedics, if
you have any further questions.
I do hope that you enjoy the course.
Ed Wallitt
(ed@podmedics.co.uk)
Table of Contents
Haematology! 4
Anaemia! 4
Haemostatic Disorders! 7
Haematological Malignancy! 10
Systemic disease, porphyria and transfusions! 14
Chemical Pathology! 17
Fluid balance! 17
Electrolye Disorders! 19
Organ Function Tests! 22
Fluid Analysis! 25
Immunology! 29
Immunodeficiency! 29
Allergy! 33
Autoimmunity! 35
Immunology of Transplantation! 37
Therapeutics in Immunology! 38
Microbiology! 39
Basic Classification of Organisms! 39
Anti-Microbial Therapy! 41
Infections by Organ System! 47
Organ System Pathology I ! 53
Pathology of the Heart and Vessels! 53
Pathology of the Lung! 56
Pathology of the Liver and Biliary System! 60
Pathology of the Pancreas! 63
Organ System Pathology II! 65
Pathology of the Gut! 65
Pathology of the Kidneys and Uro-genital System! 69
Pathology of the Nervous System! 74
Pathology of the Endocrine System! 78
Haematology
Classical Signs
Anaemia Conjunctival pallor
Koilonychia
Glossitis
Definition: “[Hb] < reference range for age, sex and gender of an individual.” Angular stomatitis
Post-cricoid webs (Plummer-
• Men < 13.5 g/dl, Women < 11.5 g/dl Vinson Syndrome)
High-flow murmur
May be classified according to size:
1. Size (microcytic, normocytic, macrocytic)

2. Pathophysiology (reduced production vs. increased destruction)
1. Reduced Production (INEFFICIENT/INSUFFICIENT)
Pathology Causes Features
↓ iron Reduced intake ↓ MCV, ↓ ferritin, ↑ TIBC

Malabsorption Hypochromia, poikilocytosis, anisocytosis
Blood loss
↓ vitamin B12
↓ folate
Bone marrow
infiltration
Myelodysplasia
Anaemia of
chronic disease
2. Increased Destruction
With these conditions remember to look for the features of haemolysis:
• Reticulocytosis (> 2%) +/- mild macrocytosis

• ↑ unconjugated bilirubin
• ↑LDH
• ↑ urobilinogen
• ↓ haptoglobin
1. INHERITED DISORDERS
Inheritance Features Diagnostic tests
Spherocytosis
Elliptocytosis
G6PD
Sickle cell
Thalassaemia
2. ACQUIRED DISORDERS
These may be divided into:
1. Immune haemolysis (COOMBS TEST - positive)
Target Examples
Alloimmune Foreign cells
Autoimmune Own cells
2. Mechanical haemolysis (COOMBS TEST - negative)
Target Examples
DIC Foreign cells
HUS Own cell
TTP
Valves
• Endothelial damage results in fibrin deposition/thrombosis in small vessel → SHREDDING OF RBC

(schistocytes)
Haemostatic Disorders
Normal haemostasis has 4 important stages:
1. Vasoconstriction
2. Formation of a loose platelet plug
3. Stabilisation through clotting cascade
4. Fibrinolysis
Factors Investigations
Common Pathway X, V, platelets, prothrombin/thrombin,

fibrinogen/fibrin,
Intrinsic Pathway VIII, IX, XI, XII
Extrinsic Pathway TF, VII
Other tests: thrombin time (increased by FDPs and heparin)
Excess activation is prevented by:
1. Prevention of clotting: ANTI-THROMBIN, PROTEIN C, PROTEIN S
2. Fibrinolytic system - PLASMINOGEN-PLASMIN
Bleeding Disorders
Platelets Coagulation
Site Skin, mucous membranes Soft tissues, joints and muscles
Petechiae Yes No
Ecchymoses Small, superficial Large, deep
Haemarthrosis/ No Yes
muscle
Bleeding after Immediate Delayed (days)

surgery
1. Platelet Problem
Divide this up as follows Important platelet

numbers
• REDUCED FUNCTION (rare)
< 50 x 109 - petechiae,
• Inherited ecchymoses
• Acquired (e.g. aspirin, uraemia) < 20 x 109 - mucocutaneous
bleeds (GI bleeding,
• REDUCED NUMBER (common)
haematuria)
• Reduced production (e.g. marrow failure)
• Increased consumption (e.g. ITP)
Types Typical features Treatment
Acute
Chronic
Drug-related Penicillin, thiazide, oral hypoglycaemics
2. Clotting Problem
Disease Inheritance Presentation Investigations
Haemophilia
vWD
Liver disease
Vitamin K
deficiency
Thrombotic Disorders
Hypercoagulability
VIRCHOWʼs
Stasis Vessel wall
Thrombophilia Features
Factor V Leiden
Prothrombin
G20210A
Protein C deficiency
Protein S deficiency
Anti-thrombin
deficiency
ACQUIRED
Haematological Malignancy
Basic Principles
• Unregulated clonal proliferation derived from a single cell.

• Caused by multi-step genetic mutations that leads to cell cycle dysregulation.
Mechanism Examples
Translocation
Deletion
Duplication
Point mutation
Definitions:
• Leukaemia: malignant cells in peripheral blood/bone marrow

• Lymphoma: solid tumour (malignant cells in lymph nodes)
• Myeloma: malignant cells in bone marrow and production of paraprotein
Aetiology/Contributing factors
Examples
Radiation X-rays, nuclear disaster
Chemical Benzene, cytotoxic drugs
Genetic Downʼs syndrome
Viruses HTLV-1

The Leukaemias
Subtypes Features Investigations
ALL
AML
CLL
Myelodysplastic Syndromes
“Various syndromes characterised by bone marrow failure due to abnormal myeloid haematopoiesis.”
Features
Investigations
•
•

Lymphoma
HIGH GRADE: aggressive
but potential for cure
1. Hodgkinʼs Lymphoma
LOW GRADE: indolent but
difficult to cure
• Reed-Sternberg cell
• B lymphocyte lineage with characteristic owl eye appearance.
2. Non-Hodgkinʼs Lymphoma
1. B cell (85%)
2. T cell/NK cell (15%)
Important features:
• Systemic symptoms - fever/night sweats +/- anorexia/weight loss (B SYMPTOMS)

• Painless, discrete, rubbery enlargement of lymph nodes +/- splenomegaly)
• (Occasionally EtOH induced pain)
Multiple Myeloma
Malignancy of B lymphocyte derived PLASMA CELLS --> PARAPROTEIN PRODUCTION

• Suppresses production of normal functioning Ig
• Hyperviscosity
• Deposition into organs (e.g. renal failure)
Important features:
• Fatigue/malaise/anorexia/weight loss
• Bone pain (vertebral collapse)
• Features of hyercalcaemia - “Bones/stones/groans/moans”
• Features of hyperviscosity - Visual loss
Diagnostic findings:
• Blood film - rouleaux formation and occasionally abnormal plasma cells

• ↑ calcium
• β2 microglobulin (prognositcally important)
• Serum/Urine electrophoresis: paraprotein
• Bone marrow - abnormal plasma cells
• Skeletal survey - lytic lesions
MGUS = “Monoclonal Gammopathy of Undetermined Significance”
• Often occurs in elderly

• Paraprotein present but no other symptoms/signs or laboratory findings to suggest myeloma.
Note: MAY progress to myeloma.

Myeloproliferative Disorders
Disease Cell line Features
Polycythaemia RBCs
rubra vera
Essential Platelets
thrombocythaemia
Chronic myeloid Granulocytes

leukaemia
Myelofibrosis

Systemic disease, porphyria and transfusions
ESR
May be influenced by:
• This measures the “sedimentation rate of blood cells.”
• Normal < 20 mm/hr [women > men] a. Red blood cells
• Severe anaemia
• Quantifies ROULEAUX FORMATION b. Plasma environment

• Acute phase protein
• Uses clinically: • Immunoglobulins
• Fibrinogen
1. INVESTIGATION: generally has a low sensitivity and specificity

• Myeloma
• Temporal arterities
• Polymyalgia
2. MONITORING DISEASE COURSE

• Above conditions +
• Relapse in Hodgkinʼs disease
Primary Secondary Others
Neutrophilia NEOPLASIA INFECTION Steroids

-Bacterial infection DKA
e.g. CML
INFLAMMATION
- autoimmune
Eosinophilia NEOPLASIA INFECTION Idiopathic

- Parasitic infection hyperoesinophilic
e.g. HL, T-cell NHL syndrome
INFLAMMATION - allergic disease
(e.g. asthma, atopy, drug reactions)
Monocytosis NEOPLASIA INFECTION -

- This is usually chronic
e.g. CML
e.g. TB, CMV
Basophilia NEOPLASIA INFECTION -

- pox virus
e.g. CML
Lymphocytosis NEOPLASIA INFECTION

- EBV, CMV
e.g. CML/
lymphoma

Porphyria
The major problem is the build up of toxic haem precursors.
NEUROVISCERAL
CUTANEOUS
Acute Intermittent Porphyria
• Autosomal dominant inheritance

• Severe
• Neurovisceral features - usually precipitated by acute stress (e.g. poor nutrition, certain drugs e.g.
ETOH)
• Diagnostic findings:
• ↑ urinary ALA & PBG (urine looks like port)
Porphyria cutanea tarda
• Inherited and acquired

• Not severe
• Cutaneous features (raised vesicles on sun-exposed areas)
• Diagnostic findings:
• ↑ urinary uroporphyrins and coporoporythins

Adverse Reactions to Transfusion
IMMEDIATE (<24h)
Wrong blood
Febrile non-
haemolytic reaction
TRALI
Bacterial infection
Fluid overload
DELAYED (>24h)
Post transfusion
purpura
Delayed haemolytic
transfusion reaction
GVHD
Iron overload

Chemical Pathology
Fluid balance
Fluid and Electrolyte Distribution
• Average 70kg man - 42L (60-70%)

" - ⅔ INTRACELLULAR
" - ⅓ EXTRACELLULAR (plasma, interstitial, transcellular e.g. ocular, fluid, pleural)
The most important electrolytes are:
1. CATIONS
• Intracellular = K+
• Extracellular = Na+
2. ANIONS
• Intracellular = protein and phosphate
• Extracellular = Cl- and HCO3-
Starling Forces:
Osmolality (280-295 mosmol/l) - should be equal between IC and EC
CHARGED + UNCHARGED
∴ (Na++K++Cl-+HCO-) + (urea+glucose) = 2(Na++K+) + urea + glucose
The osmol gap is the difference between calculated and actual osmolalty.
INPUT OUTPUT
Oral 1.5L Urine 1.5L
Food 1L Stool 0.5L
Oxidative water 0.5L Skin 0.5L
Lungs 0.5L
TOTAL 3L 3L

Salt and Water Homeostasis
1) Water deficit/excess
2) Salt deficit/excess
Common errors in fluid balance
TOO MUCH
FLUID
TOO LITTLE
FLUID

Electrolye Disorders
Syndrome of Inappropriate ADH secretion
Sodium (135-145 mmol/l) “For the plasma tonicity there is an inappropriate

elevation of ADH and therefore inappropraite
urinary concentration.”
1. Hyponatraemia
Criteria
• 2 important things here are: 1. Reduced [Na+]

2. Euvolaemia
• FLUID STATUS 3. Inappropriate concentration of Na in the
• URINARY SODIUM urine
• Renal > 20 4. Decreased plasma osmolality
• Extra-renal < 20
• Should be divided into:
i. HYPOVOLAEMIC
Potassium (3.5 - 5 mmol/l)
• Highly dependent on GFR for excretion.

• EXCITABLE CELLS
ii. EUVOLAEMIC • Note: do not equate hypokalaemia with body
depletion/hyperkalaemia with body overload.
1. Hypokalaemia
iii. HYPERVOLAEMIC
i. Reduced intake
ii. Cellular uptake/redistribution
• Treatment should always be slow and iii. Increased loss

according to FLUID STATUS.
2. Hyperkalaemia
2. Hypernatraemia
i. Increased intake
• Common causes:
ii. Cellular loss/redistribution
• Insufficient fluid intake
• Water loss increased relative to iii. Decreased loss
sodium loss (e.g. diabetes insipidus,
osmotic diuresis, sweating)
Treatment is important here:

• Treatment - slow replacement of fluid (5%
dextrose) • Stabilise the myocardium
• Drive potassium into cells
• Mop-up the potassium

Calcium
• Normal serum calcium: 2.2 - 2.6 mmol/l

• 50% unbound/bound
ALBUMIN concentration is therefore important and

needs to be corrected for.
Draw a diagram of calcium balance:
Causes Features Rx
HYPO-
HYPER-

Acid-Base Balance (in a page)
• ALWAYS CONSIDER THE CLINICAL

SITUATION!
• An arterial blood gas tells you about 2 things:
a. ACID-BASE BALANCE
b. GAS EXCHANGE
BASIC EQUATION
COMPENSATION ANION GAP
“Return the pH to normal at expense of other • In normal physiology, primarily due to

values”. ALBUMIN.
• [ANIONS - CATIONS] = (Na + K) - (Cl +
2 types:!! RENAL!! RESPIRATORY HCO) = 18mM
• Increased by UNMEASURED ANIONS:

• Ketones
• Lactate
• Drugs

Organ Function Tests
Renal Function Tests
2 important things to think about with these:
a. The GFR
b. The urine dipstick + microscopy
THE GFR
• 60 - 120 ml/min
• Varies
• Measured by CLEARANCE (depends on exogenous/endogenous

marker)
• INULIN - gold standard
• Endogenous markers
• Urea
• Creatinine
• EQUATIONS: Schwartz, Cockcroft Gault, MDRD
"
Urine Dipstick/Microscopy
Red cell casts
White cell casts
Crystals

Liver Function Tests
Divide into:
• LIVER DAMAGE
• Destructive
• Obstructive
• FUNCTION
• Albumin
• Clotting
(AST/ALT)
ALP
ϒ-GT
Jaundice
• Normal bilirubin: 3 - 17 μmol/l. (not detected clinically until > 35)
Divide up into: 1. PRE-HEPATIC" 2. HEPATIC" " 3. POST-HEPATIC

Important congenital syndromes:
Condition Inheritance Deficiency Presentation
Crigler-Najjar
Gilbertʼs
Dubin-Johnson
Rotor
Endocrine Investigations
Condition Causes Diagnosis
Cushingʼs
syndrome
Connʼs syndrome
Addisonʼs disease
Thyroid disease

Fluid Analysis
Clinical manifestations
Blood Proteins
• Divided into ALBUMIN and the GLOBULIN FRACTION
Causes of a low albumin:
• REDUCED SYTHESIS
• DISTRIBUTION
• INCREASED LOSS
Cerebrospinal Fluid
Indices Normal Abnormality
Appearance Clear and colourless Turbidity (= leucocytes)

Blood stain (traumatic tap/SAH)
Xanthochromia (previous
haemorrhage/high protein)
Microscopy Few cells Neutrophils = Bacterial

Lymphocytes = Viral/TB
Glucose 0.5 - 1.0 mmol less than plasma Reduced in bacterial/tuberculous

meningitis
Protein 100 - 400 mg/l Increased in acute/chronic

inflammation
Massive - acute infection/

neoplasms
Moderate - demyelination
Immunoglobulin Small amount of IgG CSF IgG: plasma IgG ⇑ in:

Traces of IgA and IgM
Multiple sclerosis (oligoclonal
bands)
Neurosyphilis
Subacute sclerosing
panencephalitis

Biochemical Protein Markers
Protein Function Important facts
CRP
α-1 anti-trypsin
Transferrin
Caeruloplasmin
Ferritin
Haptoglobin
β2-microglobulin
PSA
AFP
CA19.9
CA125
CEA
β-HCG

Common nutritional deficiencies
Deficiency Excess Test
FAT SOLUBLE
VITAMINs
A Colour blindness Exfoliation hepatitis + drying Serum

Retinol of mucous membranes
D Rickets/Osteomalacia Hypercalcaemia Serum

Cholecalciferol
E Anaemia/neuropathy Serum
Tocopherol (e.g. abetalipoproteinaemia)
K Defective clotting PT
Phytomenadione
WATER SOLUBLE
VITAMINS
B1 Beri-beri RBC transketolase

thiamin Neuropathy
Wernicke Syndrome
B2 Glossitis RBC glutathione reductas

Riboflavin
B12 Megaloblastic anaemia Serum

Cobalamin
C Scurvy Renal stones Plasma

ascorbate
Folate Megaloblastic anemia Red cell folate

Neural tube defects
Niacin Pellagra
TRACE
ELEMENTS
Iron IDA Haemochromatosis FBC

Ferritin
Iodine Goitre TFT

Hypothyroidism
Zinc Dermatitis and hair loss Impairment of copper and

iron absorption
Copper - Wilson’s disease Cu

Caeruloplasmin

Metabolic Diseases for the Exams
“Metabolic disorder”
• “A disorder in which there is a defective gene for a crucial enzyme involved in intermediary
metabolism.”
Disease is due to either:
• Build-up of precursors
• Lack of product
Over 650 diseases that together account for 40% of deaths in the first year of life.
• Most common is PKU (screened for)
All you should know about the others:
Disorder(s) Defect Examples Clinical characteristics
Amino acid disorders Autosomal recessive defect PKU (↑ phenylalanine) Failure to thrive
in metabolism of single amino Homocystinuria (↑ Seizures
acid Musty skin odour
Organic acidurias Defective late metabolism of Methylmalonic Developmental delay

single amino acid (usually acidaemia Organic acids in urine sample
branched) Propionic acidaemia
Isovaleric acidaemia
Maple syrup urine
disease
Urea cycle defects Deficiency of an enzyme 6 disorders Encephalopathy

involved in the urea cycle → e.g. arginaemia, Irreversible neurological
build up of ammonia citrullinemia damage
Carbohydrate Alteration of carbohydrate Lactose intolerance Hypoglycaemia

disorders cyling in the cell Gycogen storage Lactic acidosis
disorders Cataract formation
Liver/kidney problems
Peroxisomal disease Disorders of lipid metabolism Zellweger syndrome Hypotonia

where there are empty cell Seizures
persoxisomes
Mitochondrial disease Mutations in mitochondrial Mitocondrial Lots

DNA. myopathies
(Most serious when affects e.g. diabetes mellitus
muscle, brain) and deafness, Leber’s
hereditary optic
neuropathy
Lysosomal storage Various defects in lysosomal Gauncher’s disease Present late (adulthood)
disorders function that lead to Niemann-Pick disease
accumulation of toxic Tay-Sachs disease
substances

Immunology
Immunodeficiency
Primary immune deficiencies can include (list the 4 possible deficiencies):
1.
2.
3.
4.
B cell (antibody deficiencies)
Disease Mutation/Problem Clinical Features/Result
X-linked
aggammaglobulinaemia
IgA deficiency
Hyper IgM syndrome
Wiskott-Aldrich
syndrome
CVID

T cell deficiencies
DiGeorgeʼs
Bare L syndrome
Wiskott-Aldrich syndrome
Ataxic telangiectasia
Combined B and T cell deficiency
SCID
Phagocyte deficiencies
These are characterised by:
• Recurrent, deep bacterial infections

• Recurrent fungal infections
• Susceptibility to mycobacteria
Leukocyte Adhesion
Deficiency (LAD)

Chronic
Granulomatous
Disease (CGD)
Kostmannʼs syndrome
(KS)
Cyclic neutropenia
So, if we compare and contrast the important markers we get:
Neutrophil count Pus Leukocyte NBT

adhesion
markers
KS Absent No Normal Abnormal
LAD High No Absent Normal
CGD Normal/high Yes Normal Abnormal
Complement deficiencies
To understand these deficiencies you need to first remember the basic complement pathway. Draw a
diagram here

Components of the complement cascade
Component Function Features of Deficiency
C3a, C5a
C3b
C5-9
Important Complement Tests
• Total C3 & C4
• CH50: Haemolytic complement 50 (CLASSICAL)

• AP50: Alternative pathway 50
Important lupus results:
ACTIVE: ↑ C4, normal C3

SEVERE: ↓ C4 & C3
INACTIVE: normal C4 & C3

Allergy
Before talking about allergy and autoimmunity it is important to understand the Gel and Coombs
classification:
Type Mechanisms Examples
Type I IgE-mediated
hypersensitivity
Type II IgG/IgM reactive with self

antigen
Type III Immune complex-

mediated damage
Type IV T-cell mediated damage/

delayed hypersensitivity

Allergic disease comprises a number of different conditions throughout medicine e.g. asthma, anaphylaxis,
seasonal allergies, rhinitis.
Clinical Features of allergy
Diagnosis of Allergy
Test Advantages Disadvantages
Skin prick tests
RAST test (specific IgE)
Mast cell tryptase
Allergic Diseases
Disease Pathogenesis Treatment
Anaphylaxis
Food allergy
C1 inhibitor deficiency

Autoimmunity
Autoimmunity is “an immune reaction that produced tissue damage due to a reaction against self-
protein”.
It results from a breakdown of SELF-TOLERANCE.

Disease HLA association
Mechanisms Ankylosing spondylitis HLA-B27
Goodpastureʼs sydrome HLA-DR2

1. Central tolerance loss
Graveʼs disease HLA-DR3
SLE HLA-DR3
2. Peripheral tolerance loss
Diabetes Type I HLA-DR3/4
Rheumatoid arthritis HLA-DR4

Risk factors for development of autoimmune disease may be:
• Genetic: sex and HLA-associations
Environmental: infections (molecular mimicry/hyperstimulation of co-stimulators), chronic inflammation.
You can divide up autoimmune disease into:
ORGAN-SPECIFIC:
NON-ORGAN SPECIFIC:

Diagnosis of Autoimmune Disease
Disease Auto-antibodies Important points
SLE
Drug-induced lupus
Sjogrenʼs
RA
Scleroderma
• Diffuse
• Limited/CREST
Dermatomyositis/
polymyositis
Wegnerʼs
granulomatosis
Polarteritis nodosa
Coeliac disease
Pernicious anaemia
Graveʼs disease
Hashimotoʼs thyroiditis
Diabetes Mellitus
Primary biliary cirrhosis
Autoimmune hepatitis
Mixed Connective
tissue disease
Anti-phospholipid
syndrome

Immunology of Transplantation
• The major stimulus for rejection is a difference in HLA (DR>B>A)
• Rejections occurs over varying timeframes, and with different mechanisms:
Timeframe Pathophysiology Treatment
Hyperacute rejection
Acute cellular
rejection
Acute vascular
rejection
Chronic allograft
rejection

Therapeutics in Immunology
There are essentially 3 ways that you can manipulate the immune system.
1. SUPPRESS IT
2. BOOST IT
3. DEVIATE IT
Immunosuppression is not however without complications, the most important ones are below:
• Infection
• Malignancy
• Atherogenicity
Class Examples Effects Side effects
Steroids Prednisolone
Hydrocortisone
Dexamethasone
Anti- Azathioprine
proliferative
agents
Cyclophosphamide
Mycophenylate
mofetil
Inhibitors of cell Ciclosporin

signalling
Tacrolimus
Antibodies to OKT3 (anti-CD3

cell surface antibody)
antigents
Anti-IL2 antibody
(CD25)
Anti-cytokine Infliximab
agents
Etanercept
Adalimumab

Microbiology
Basic Classification of Organisms
Bacteria
Subtypes Examples Investigation
Gram +ve 1. COCCI (clusters & chains)
2. BACILLI
3. BRANCHING
Gram -ve 1. COCCI
2. BACILLI
3. COMMA-SHAPED
Spirals 1. BORRELIA
2. TREPONEMA
3. LEPTOSPIRA
Acid fast 1. MYCOBACTERIUM
Cell wall
deficient

Viruses
• Classification is based upon the

BALTIMORE SYSTEM
• DNA VIRUSES
• RNA VIRUSES
• RETROVIRUSES
Fungi
• EUKARYOTES that are classified according to their appearance (e.g. hyphae, yeasts, moulds and
dimorphics).
• 2 important disease patterns:

1. SUPERFICIAL e.g. thrush, dermatophytoses
2. DEEP e.g. candidiasis, aspergillosis, histoplasma
Parasites
• Unicellular EUKARYOTES:
• APICOMPLEXANS e.g. plasmodium
• FLAGELLATES e.g. giardia lambdia, trypanosomes
• AMOEDBOIDS e.g. entamoeba histolytica

Anti-Microbial Therapy
Anti-virals
Organism Rationale 1st line 2nd line
HSV/VZV Aciclovir Famciclovir

Valaciclovir
CMV Ganciclovir Valaciclovir

Foscarnet
HIV “HAART”
2 NRTI + NNRTI/PI
Chronic HBV 40% success rate Interferon-α Famciclovir

+ Lamivudine
Chronic HCV 60% success rate Peginterferon-α -

Ribavirin
Genotypes 2,3 - better
prognosis. Rx for 6/12
Genotypes 1,4 - worse

prognosis. Rx for 12/12
Influenza Only use in at-risk adults Influenza A - Amantadine -
Must be started within Influenza A + B -

48h of symptoms Neurainidase inhibitor
(Zanamivir/Olseltamivir)
Basic mechanisms of action:
Target Examples
1. Viral binding Fusion inhibitors
2. Uncoating (Important for future)
3. Replication Most current drugs
e.g. acyclovir, ganciclovir
4. Assembly e.g protease inhibitors
5. Release e.g. interferons

Aciclovir
• A nucleoside analogue that inhibits viral DNA polymerase (activated by viral thymidine kinase).
• Poor bioavailablility (∴ administered I.V. for sick patients)

• Alternative: valaciclovir/famciclovir (better absorption)
C.I.s Important S.E.s Interactions
Pregnancy Renal dysfunction (crysalluria) Probenicid decreases

(unlicensed but we use it) excretion
- Myelosuppression -
Ganciclovir
• Acyclic analogue of guanosine

• Alternative: valaciclovir/foscarnet (for resistant HSV or second-line CMV)
• Poor bioavailability (∴ administered IV)
Pregnancy Myelosuppression -
- Central nervous system -

toxicity
Antibiotics
Action Sub-types Drugs
Inhibit cell wall synthesis Β-lactams Penicillin

Cephalosporins
Glycopeptides Vancomycin
Teicoplanin
Carbapenems Imipenem
Monobactams Aztreonam
Inhibit protein synthesis Aminoglycosides Gentamicin
Tetracycline Tetracycline
Doxycycline
Macrolides Erythromycin
Clarithromycin
Others Chormapheicol
Fusidic acid

Action Sub-types Drugs
Inhibit nucleic acid Quinolones Ciprofloxacin

synthesis Ofloxacin
Others Metronidazole
Trimethoprim
Rifampicin
Sulphonamides
1. Penicillins
• Very useful against Gram +ve (some have additional Gram -ve cover).
• 4 major types
1. Basic penicillins (pneumococcus, streptococcus, meningococcus)

• Benzylpenicillin/penicillin G (must be given parenterally)
• Phenoxymethypenicillin/penicillin V (oral but poor bioavailability)
2. Broad-spectrum penicillins (Gram -ve cover e.g. As above + E.coli, H. Influenzae)

• Amoxicillin
3. β-lactamase resistant peniccillins

• Flucloxacillin (for staphulococci)
• Co-amoxiclav (Augmentin)
4. Anti-pseudomonal penicillins
• Pipericillin + Tazobactam = Tazocin
Hypersensitivity Rash Reduced efficacy of COC
Anaphylaxis
Nausea/vomiting
2. Cephalosporins
There are 3 generations whose Gram -ve activity becomes greater as you ascend...
Types Drug Indications
1st generation Rubbish! Rubbish!
Cefalexin is orally active Used for URTIs, refractory cystitis
2nd generation Cefuroxime As for amoxicillin

Types Drug Indications
3rd generation Cefotaxime Meningitis
Ceftazidime Anti-psudomonal
Ceftriaxone Good for serious infections
E.g. Pneumonia, septicaemia
Adverse reactions
Hypersensitivity (10% who are C. Difficile

allergic to penicillin with also
be allergic)
Bleeding
Thrombophlebitis
3. Glycopeptides
! e.g. vancomycin (IE/MRSA/C. difficile), teicoplanin (bad gram +ve infections)
• These agents are generally active against aerobic and anerobic Gram +ve
Ototoxicity Increased risk of ototoxicity

with loop diuretics
Nephrotoxicity Increased risk of

nephrotoxicity with
cyclosporin and
aminoglycosides
Thrombophlebitis
4. Carbapenems
" e.g. imipenem, meropenem
• These agents have a very wide broad specture against Gram +ve and Gram -ve
• Best single choice for nosocomial infection
Nausea/vomiting
Seizures

Aminoglycosides
! e.g. gentamicin (topicals, 2nd line in severe Gram -ve infection), streptomycin (resistant TB)
• These are agents that inhibit protein synthesis through binding to the 30S ribosome.
• They are inactive orally.
• Requre therapeutic drug monitoring (measure 1 hour post-administration)
C.I.s Important S.E. Interactions
Pregancy Nephrotoxicity Loop diuretics and cyclosporin

potentiate nephrotoxicity
MG Ototoxicity (direct damage to Antagonise

C VIII) anitcholinesterases
Thrombophlebitis
Tetracycline
! e.g. tetracycline (acne), doxycycline (chlamydia, lyme disease, anthrax)
• These are relatively broad specturm agents that have particular action against intracellular organisms
Renal impairement Teeth/bone deposits Absorption affected by

Ca2+ (milk)
(do not use < 12y) Iron tablets
Mg2+ (antacids)
Macrolides
# e.g. erythromycin (good respiratory antibiotics, useful in penicillin-allergic), clarithromycin (more
potent)
• These drugs do not cross the blood-brain barrier
Nausea/vomiting CP450 inhibitor
Cholestatic jaundice Stop statins
Quinolones
# e.g. ciprofloxacin, ofloxacin
• These drugs are active against many Gram -ve and Gram +ve organisms (bowel infections,
pseudomonas, cystic fibrosis lung infections, gonorrhoea)

Epilepsy (lower seizure GI disurbance CP450 inhibitor

threshold)
History of tendon damage Tendon damage
Metronidazole
• This agents is very active against anaerobes and protozoal infections (entamoeba histolytics, giardia
lamblia, trichomonas)
• It is a well tolerated drug
Hepatic impairement GI disturbance Increases phenytoin levels
History of tendon damage Antabuse reaction with Increases warfarin levels

alcohol
Drugs used for TB
Drug Indications Problems
Rifampicin Tuberculosis Deranged LFTs

Leprosy
Orange secretions
Contact prophylaxis in
meningitis CP450 inducer
Isoniazed Tuberculosis Peripheral neuropathy

(Rx - pyridoxine)
Hepatotoxicity
Pyrazinamide Tuberculosis Hepatocellular toxicity
Ethambutol Tuberculosis Retrobulbar neuritis

(< 8 weeks therapy)
(if isoniazid resistance is
likley)

Infections by Organ System
In this section we shall review important infections by organ system. You really need to know the following
about each system.
• WHAT ORGANISM
• MANIFESTATIONS
• DEFINITIVE INVESTIGATION
• BROAD/DEFINITIVE TREATMENT
Remember: pattern recognition is the key!
Cerebral Infections
Disease Organism(s) Features/Investigation Treatment
Cerebral
abscess
Encephalitis
Meningitis
(see CSF analysis in chemical pathology)

Lung Infection - “pneumonia”
CAP
HAP
AP
TB

GI Infections
Throat
infection
Upset
tummy
Hepatitis A
Hepatitis B
Hepatitis C

Sexual Infections
Try to split them up into those associated with
• DISCHARGE
• E.g. Gonorrhoea, chlamydia, NGU
• ULCERATION
• E.g. Syphilis, LGV, chancroid + viruses
• HIV
Chlamydia
Gonorrhoea
NSU
Syphilis
LGV
HSV
HPV

Urinary Tract Infections
Disease Organism(s) Features/Investigations Treatment
Simple
cystitis
Pyelonephritis
Skin Infections
Cellulitis
Infected eczema
Dermatophytosis

Tropical Infections (in one page!)
Malaria
Leptospirosis
Lyme Disease
Schistosomiasis
Trypanosomiasis
Leishmaniasis

Organ System Pathology I

Pathology of the Heart and Vessels
• Disease within the cardiovascular system is due to
i. LOCALISED FAILURE --> ISCHAEMIA/INFARCTION

• Thrombosis - “pathological event when haeostatic mechanism abnorally active.”
• Embolism - “detached mass in the circulation system.” (thrombus, fat, septic, amniotic fluid)
ii. GENERALISED FAILURE --> SHOCK +/- multi-organ failure
• Infarction = “necrosis due to ischaemia.”

• ARTERIAL (MI, stroke, bowel infarction, acute limb ischaemia)
• VENOUS (PE, torsion of vascular pedicle)
Atherosclerosis
NON-MODIFIABLE MODIFIABLE
There are 4 key stages:
•
•
•
•
This process results in:

• ISCHAEMIC HEART DISEASE (from chronic angina to acute MI)
• PERIPHERAL VASCULAR DISEASE (from chronic claudication to acute ischaemic limb)
• STROKE
Hypertension
" Defintion:
Primary
Secondary

Important sequelae of hypertension
1.
2.
3.
4.
5.
6.
Cardiac Failure
• Final COMMON PATHWAY of most cardiac disease. “Inability of heart to meet demands of the
body.”
RVF LVF
Cardiomyopathy Causes Features
Hypertrophic
Dilated
Restrictive
ARVD

Valve Disease
• Vavles may be either:

• STENOSED (develops slowly)
• REGURGITANT (develops slowly or quickly)
• Try to appy some general causes to all the different valve problems:
• CONGENITAL
• Bicuspid valve
• ACQUIRED
• Rheumatic fever
• Endocarditis
• Functional e.g. annulus stretched, papillary muscle damage
• Degeneration
Types Pathogenesis Features
Rheumatic
fever
Infective
endocarditis
Congenital Heart Disease
• Not covered in detail here.

• Remember to divide as follows:
REVISE YOUR
• CYANOTIC
PAEDS!
• Tetralogy of Fallot
• TGA/hypoplastic left heart syndrome
• NON-CYANOTIC
• VSD
• ASD (primum vs. secundum)

Pathology of the Lung
• We shall be considering these anatomically. Pathology occurs in 4 basic places:
1. THE BLOOD VESSELS

2. THE AIRWAYS
3. THE INTERSTITIUM
4. THE PLEURA
The Blood Vessels!

Quick review: Risk factors
1. Pulmonary embolism
• 95% from deep vein thrombi

• Effect depends on SIZE
• LARGE --> sudden death
• SMALL --> pulmonary hypertension
• D-Dimers + CTPA + ECG
2. Pulmonary hypertension
• PRIMARY - Unknown cause

• Complication --> Right ventricular failure
• SECONADARY - multiple PEs, pulmonary venous congestion, chronic hypoxia
The Airways
Asthma COPD

Emphysema
• “Destruction and dilatation of the lung parenchyma distal to the broncholes”
2 types:
1. PANLOBULAR/PANACINAR
2. CENTRILOBULAR/PARASEPTAL
PATHOGENESIS:
Bronchiectasis
• “Permanent and abnormal diatation of bronchi”.

Cystic fibrosis
• Causes:
The Interstitium
Pulmonary fibrosis
• “Laying down of fibrotic tissue in the lung parenchyma”.

• RESTRICTIVE PATHOLOGY - FEV1/FVC > 0.7
Idiopathic
Extrinsic allergic
alveolitis
Pneumonconioses

Autoimmune
Drugs
Radiation
Lung Tumours
These may be BENIGN (rare - hamartomas, adenomas) or MALIGNANT (common)
• NON-SMALL CELL
• Sqaumous cell carcinoma
• Adenocarcinoma
• Large cell undifferentiated
• SMALL CELL
Effects of lung tumours:
• LOCAL
• Bronchial obstruction
• Impaired mucus clearance
• Invasion
• Extension through pleura/pericardium/lymphaticx
• DISTANT
• Peptide production
• ACTH
• ADH
• PTH-like peptide
• Paraneoplastic syndrome
• Metastases

The Pleura
Pneumothorax
TENSION SIMPLE
Pleural Effusions
Pleural Effusions
Transudate (< 30) Exudate (> 30)
Asbestos-related lung disease
• BLUE asbestos is the worst.
• Manifestations
1. PLEURAL PLAQUES
2. ASBESTOSIS
3. ADENOCARCINOMA
4. MESOTHELIOMA

Pathology of the Liver and Biliary System
Basic Liver Structure
You need to review the basic structure of the liver and the most basic
cell types:
• Dual blood supply: portal vein + hepatic artery

• Key features: PORTAL TRIADS, HEPTOCELLULAR
PARENCHYMA, HEPATIC VEINS
• Kupffer cells - liver macrophages

• Stellate cells - located in space of Disse. Contain vitamin A +
transform in myofibroblasts if hepatic injury
Consequences of hepatocellular failure
Normal function Failure
Detoxification Encephalopathy/cerebral oedema
Glycogen storage Hypolgycaemia
Production of clotting factors Coagulopathy
Globulin producrion Infections
Homeostasis Circulatory collapse + renal failure
Cirrhosis
• Fibrosis of the whole liver structure with:

• Regenerating nodules Classfied
• Distorsion of liver architecture according to:
1.NODULE SIZE
PATHOGENESIS (draw a diagram) 2. AETIOLOGY

4 important complications of cirrhosis
1.
2.
3.
4.
Important Causes of Cirrhosis
Condition Deficit Features
Alcohol
Viral hepatitis See microbiology See microbiology
Steatohepatitis
Wilsonʼs disease
Haemochromatosis
Alpha-1 anti-trypsin
deficiency
Autoimmune
Review - JAUNDICE (Clinical biochemistry) and VIRAL HEPATITIS (Microbiology)

Hepatic Neoplasia
1. Hepatocellular carcinoma (HCC) - 90%
2. Cholangiocarcinoma - < 5%
• Aetiology unknown
• Gross appearance: pale + firm
• Presentation: Man in sixties with all features of pancreatic tumour (jaundice, weight loss, pruritus and
abdominal pain).
• Very poor prognosis
Gallstone Disease
• Types: 75% cholesterol, 25% pigment (haemolytic states)
• Pathogenesis - AMIRANDʼS TRIANGLE

Pathology of the Pancreas
Basic Principles
• 2 main functions
• ENDOCRINE (5%) - glucagon, insulin, somatostatin, VIP
• EXOCRINE (95%) - proteases, lipasess
• ACINAR structure (alveoli -- ductules -- ductal system)
Congenital Disorders
Annular pancreas “Failure of migration of the ventral bud” duodenal obstruction.

Present in INFANCY with OUTLET OBSTRUCTION (cf. pyloric stenosis)
Pancreas divisum “Incomplete fusion of ventral and dorsal ducts.”

Predisposed to CHRONIC PANCREATITIS + PANCREATIC PANCER
Abberant/ectopic “Pancreatic tissue in the wrong place.” (stomach, duodenum, jejunu)

pancreas Mostly asymptomatic. May cause pain and bleeding
Agenesis “Congenital absence.”

Largely incompatible with life.
Pancreatitis
• “Inflammation of the pancreas”
Acute Chronic

Tumours of the Pancreas
Cystic Tumours
• These are rare and usually benign
Congential cysts Anomalous development of pancreatic ducts e.g. congenital polycystic disease (kidney
and liver also affected)
Pseudocysts Occur as complication of acute pancreatitis.

Complications - pain, haemorrhage, infection
Cystic tumours < 5% of all pancreatic neoplasms (many types e.g. serous cystadenoma, mucinous)
Painless and slow-growing
Solid Neoplasms
• These are common and usually malignant (v. poor prognosis)

• Usually ADENOCARCINOMA (from ductal epithelial cells)
• Most common in the head (60%)
• Clinical features
• Weight loss + pain
• Jaundice if head is affected
• Trousseau syndrome - “migratory thrombophlebitis.”
• 85% are unresectable.

Organ System Pathology II
Pathology of the Gut
OESOPHAGUS
• Pharynx --> stomach.

• Stratified squamous epithelium changes to columnar near GOJ (z-line)
Motor Disorders
Achalasia “Degeneration of myenteric ganglia around oesophagus --> oesophageal aperistalsis”

Primary (idiopathic) or Secondary (Chagas disease)
Young adult with dysphagia
Hiatus hernia “Failure of the gastro-oesophageal spincter with herniation of the stomach.”
2 types: SLIDING (95%), ROLLING (5%)
Common. Associated with REFLUX
Reflux Oesophagitis/GORD
• “Reflux of acidic gastric contents due to a reduction in LOS pressure.”
Pathological sequelae
•
•
•
Tumours of the Oesophagus
Types Associations

STOMACH
Gastritis - “inflammation of the gastric mucosa”
Causes Features
Infection
Autoimmunity
Drugs
Alcohol
Peptic Ulcer Disease

Gastric Tumours
Types Associations
Adenocarcinoma
Others GASTRIC LYMPHOMA
LEIMYOMAS/LEIOMYOSARCOMAS
GASTRIC STROMAL TUMOURS
SMALL AND LARGE INTESTINE
Coeliac Disease
• “Inflammatory disease of the small intestine due to intolerance of gliadin dietary gluten”
• Pathology:
• T cell driven chronic inflammation of small bowel --> loss of absorptive surface --> malabsorption
(iron, folate, NOT B12)
• Lymphocyte enteritis + subtotal villous atrophy
Diagnosis
• Clinical features
Inflammatory Bowel Disease
• Most import thing is to distinguish between UC and Crohnʼs disease.
Ulcerative colitis Crohnʼs disease

Ulcerative colitis Crohnʼs disease
Colo-rectal adenocarcinoma
• May arise anywhere in bowel (RECTUM and SIGMOID most common)

• Major risk factor - WESTERN DIET
• CLASSICAL SEQUENCE due to stepwise build-up of genetic mutations
ADENOMA CARCINOMAA
Risk factors for transformation:
Size
Histological Type
Dysplasia
• Tend to present LATE

• Right-sided tumours: iron deficiency anaemia
• Left-sided tumours: Change in bowel habit, abdominal pain and tenesmus, obstruction/perfortion
Staging systems:
• Dukes: A-D
• TNM:

Pathology of the Kidneys and Uro-genital System
Renal Pathology
• Kindey function – waste excretion, maintenance of ECF, acid-base, hormones (erythropoietin, rennin,
calcitriol)
• 1 million nephrons: each has glomerulus and associated tubular system
• Urine drains to collecting ducts, open onto surface on renal papillae then into calyces.
Renal failure is the common end pathway of disease:
Acute renal failure Chronic renal failure
Sudden Progressive
Reversible loss of function Irreversible loss of function
Oliguria Asymptomatic intially
Hyperkalaemia + acidosis Multi-system disturbance
Divide up kidney pathology by site:
1. Blood vessels
Hypertension
Atherosclerotic
disease
2. Glomerulus
• Capillary tuft (knot of capillaries projecting into Bowmanʼs capsule

• Tuft supported by MESANGIUM
• Filtratium barries - capillary endothelial lining capillary basement membrane, foot processes of
podocytes.

PROLIFERATIVE
STRUCURAL
NECROTISING
3. Tubules
ATN
Toxic ATB
Renal tubular
disorders
4. Interstitium
• All condition result in INTERSTITIAL NEPHRITIS
Acute Dramatic inflammatory infiltration of interstium (usually Type I hypersensitivity) --> ARF
e.g. NSAIDs, antibiotics
Chronic Persistent inflammation, fibrosis --> CRF
e.g. analgesic nephropathy

5. Outflow Tract
Bacterial infection
Obstruction
Polycystic kidney disease (ADPKD)
• Kidneys full of multiple fluid-filled cysts, progressive enlargement destroys renal parenchyma (50% ->
CRF)
• Aetiology – PKD1 mutation coding for polycystin-1
• Presentation – hypertension, flank pain, gross haeaturia.

• Extra-renal manifestation – berry aneurysms & liver cysts.

Urogenital Pathology
• INFECTION, TUMOUR, STONES...
Stones
1. Increased solute
concentration
2. Increased urine
concentration
3. Stasis
Manifestations:
•
•
Tumours
Types Associations
Renal cell
carcinoma
Urothelial tumours Transitional cell carcinoma
Squamus cell carcinoma

Testicular Pathology
Testicular Tumours
Germ cell tumours
Sex cord stromal
Lymphomas
Secondary tumours

Pathology of the Nervous System
Cerebrovascular Disease
2 most important types of stoke
• THROMBOTIC/EMBOLIC
• Sites: Intracerebral arterial, internal carotid artery
• Embolism: post-MU mural thrombus, endocarditis
• HAEMORRHAGIC
• Usuually hypertension related
• BERRY ANEURYSMS: congental weakness in arterieal wall (1% population)
• 80% internal carotid, 20% vertebro-basilar
• Other congenital malformations
• AV MALFORMATIONS
• CAPILLARY TELANGECTASES
• VENOUS ANGIOMAS
• CAVERNOUS ANGIOMAS
Type Location Injury Clinical Features Management
Extra-dural Outside the dura Disruption of arteries from the LOC---lucid period— CT (lens shaped
mater middle meningeal artery deterioration (coning)---death haematoma)
Neurosurgical drainage
Sub-dural Between arachnoid Rupture of bridging vein Insidious onset (alcoholics/ Inv: CT
and dura elderly)
Rx: Surgical evacuation
Headache, sensory/ motor of haematoma
S/S
Subarachnoid Under arachnoid Trauma or ruptured Berry Sudden onset headache Inv: CT, cerebral
aneurysm angiography
Meningism Rx: Conservate/Surgery
(clipping/embolisation)
Intra-cerebral Within brain tissue Damage to brain Compressive and localising Surgical drainage
substance signs
Traumatic Parenchymal Injury
1. CONCUSSION
2. DIFFUSE AXONAL INJURY
3. CONTUSION
4. TRAUMATIC INTRACEREBRAL HAEMORRHAGE

Cerebral Oedema = “swelling of the brain substance.”
Mechanisms
• Acute: Cytotoxicity
• Chronic - Vasogenic activity
Key complication of many CNS pathologies
Generalised Localised
4 important complications
• VASCULAR DAMAGE
• HERNIATION
• OBSTRUCTION TO CSF FLOW
• INTRACRANIAL NERVE DAMAGE
Brain Tumours
• Most common tumours = SECONDARY

• Common origin tumour types = breast/lung
Most important primary types are:
Origin Characteristics Treatment
Glioma Primary from glial cells
1. Astrocytomas
2. Medulloblastomas
3. Ependymomas
4. Oligodendromas
Meningioma Primary from arachnoid cells

Origin Characteristics Treatment
Acoustic Neuroma Primary from schwann cells

of CN VIII.
Note: usually unilateral.

Bilateral if with NF
Pituitary Tumours Adenomas
Lymphoma B cell
T cell
Metastases Breast, lung, kidney and

malignant melanoma
Neuroepithelial Medullablastoma
Retinoblastoma
Neuroblastoma
Ganglioblastoma
Review old age

Neurodegeneration
psyciatry
This encompases a broad spectrum of condition. Due to
• DAMAGE TO NERVE CELLS
• ACCUMULATION OF ABNORMAL PROTEIN\
One key manifestation is dementia. Most significant conditions:

"
Disease Key pathology
Alzheimerʼs disease
Multi-infarct dementia
Pickʼs disease
Huntingdonʼs

Variant cJD
Others
Parkinsonism
Multiple sclerosis
MND

Pathology of the Endocrine System
The Pituitary
Structure Hormones Function
Anterior
Posterior
Pituitary disease present with:
• HYPERPITUITARISM
• HYPOPITUITARISM
• LOCAL MASS EFFECT
Pituitary adenomas
• 10% of intracranial neoplasms
Type Pathology/Features
Prolactinomas
Growth hormone
adenomas
Corticotroph
adenomas

The Thyroid
HYPO-
HYPER-
Goitres
Congenital causes include:
1. Lingual thyroids
• Residual tissues at the base of the tongue
2. Thyroglossal cysts
• Remnant thyroid tissue
• Midline, smooth and cystic mass that moves upwards on swallowing
Acquired causes include
Smooth Nodular
Simple Simple goitre Multinodular goitre
Toxic Grave’s disease Toxic multinodular goitre
Acute suppurative
DeQuervain’s
Inflammatory
Riedel’s
Hashimoto’s
Thyroid Neoplasms
May be:
• Benign - follicular adenoma (common)

• Malignant

Occurrence Age Associations Prognosis
Papillary 70% Young Multi-focal and poor OK

response to radio-iodine
surgery
Follicular 15% Older Good response to radio- Excellent

iodine
Medullary 10% Any MEN Type II Good if no nodes
Anaplastic 5% Older Aggressive V. poor

Possible to shrink with
radiotherapy
"
Adrenal Disease
Layers of the adrenal glands:
• CORTEX
• Zona gloemulosa --> aldosterone
• Zona fasciculata --> glucocosrticoids
• Zona reticularis --> androgens/corticosteroids
• MEDULLA --> adrenaline/noradrenaline
1. Adrenal excess

2. Adrenal Deficiency
This may be PRIMARY or SECONDARY (reduced ACTH e.g. large pituitary adenomas/other brain
neoplasms)
Primary disorder may be either acute or chronic.
Acute
Chronic
Phaechromacytoma
• Tumour that secretes CATHECHOLAMINES --> secondary hypertension
Remember the “rule of 10s”
• 10% are bilateral

• 10% are malignant
• 10% arise outside the adrenal (paragangliomas)
• 10% arise in association with one of the familial syndromes (MEN 2a/2b, von Hippel-Lindau disease,
Sturg-Weber syndrome)
Multiple Endocrine Neoplasia
Type Features
MEN 1
MEN 2a
MEN 2b

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Podmedics LIVE - Clinical Pathology Course

Podmedics LIVE - Clinical Pathology 2010

Aims of the Course

I do hope that you enjoy the course.

Systemic disease, porphyria and transfusions! 14

Organ Function Tests! 22

Basic Classification of Organisms! 39

Infections by Organ System! 47

Organ System Pathology I ! 53

Pathology of the Heart and Vessels! 53

Pathology of the Lung! 56

Pathology of the Liver and Biliary System! 60

Pathology of the Pancreas! 63

Organ System Pathology II! 65

Pathology of the Gut! 65

Pathology of the Kidneys and Uro-genital System! 69

Pathology of the Nervous System! 74

Pathology of the Endocrine System! 78

May be classified according to size:

1. Size (microcytic, normocytic, macrocytic)

1. Reduced Production (INEFFICIENT/INSUFFICIENT)

Pathology Causes Features

↓ iron Reduced intake ↓ MCV, ↓ ferritin, ↑ TIBC

With these conditions remember to look for the features of haemolysis:

• Reticulocytosis (> 2%) +/- mild macrocytosis

Inheritance Features Diagnostic tests

These may be divided into:

1. Immune haemolysis (COOMBS TEST - positive)

Alloimmune Foreign cells

Autoimmune Own cells

2. Mechanical haemolysis (COOMBS TEST - negative)

DIC Foreign cells

HUS Own cell

• Endothelial damage results in fibrin deposition/thrombosis in small vessel → SHREDDING OF RBC

Normal haemostasis has 4 important stages:

Common Pathway X, V, platelets, prothrombin/thrombin,

Intrinsic Pathway VIII, IX, XI, XII

Extrinsic Pathway TF, VII

Other tests: thrombin time (increased by FDPs and heparin)

Excess activation is prevented by:

1. Prevention of clotting: ANTI-THROMBIN, PROTEIN C, PROTEIN S

2. Fibrinolytic system - PLASMINOGEN-PLASMIN

Site Skin, mucous membranes Soft tissues, joints and muscles

Ecchymoses Small, superficial Large, deep

Bleeding after Immediate Delayed (days)

Divide this up as follows Important platelet

Types Typical features Treatment

Drug-related Penicillin, thiazide, oral hypoglycaemics

Disease Inheritance Presentation Investigations

Stasis Vessel wall

• Unregulated clonal proliferation derived from a single cell.

• Leukaemia: malignant cells in peripheral blood/bone marrow

Radiation X-rays, nuclear disaster

Chemical Benzene, cytotoxic drugs

Genetic Downʼs syndrome

10! © Podmedics 2009

Subtypes Features Investigations

11! © Podmedics 2009

• Systemic symptoms - fever/night sweats +/- anorexia/weight loss (B SYMPTOMS)

Malignancy of B lymphocyte derived PLASMA CELLS --> PARAPROTEIN PRODUCTION

• Blood film - rouleaux formation and occasionally abnormal plasma cells

MGUS = “Monoclonal Gammopathy of Undetermined Significance”