UMS20 Medical 20 Short 20 and 20 Long 20 Cases 20 Record 20 Second 20 Editi

Medical Short Case and Long Case Record
Second edition
Tai Weng Yew ( chief editor)
Vanessa Ong, Chin Fah Shin, and Chong Ewe Jin

Acknowledgement
Thanks to previous editor: Cheo Seng Wee, Tan Yi Jun, Lee Hui Juin, Shoban Raj
1. Vulvular Heart Disease

2. Prosthetic Heart Valve
3. Bronchiectasis
4. Pleural Effusion
5. Thalassaemia
6. Chronic liver disease
7. Graves disease
8. Rheumatoid arthritis
9. Ankylosing spondylitis
10. Scleroderma
11. Parkinson Disease
12. Stroke
13. SLE
14. Bell palsy
15. CML
16. Acromegaly
17. Cerebellar Disorders
18. Short case of cardiac, respiratory, renal, and endocrine
19. Renal failure (CPG)
20. Malaria ( latest guidelines)
21.Long case approach to diabetes mellitus and hypertension

Case 1 : Valvular Heart Diseases
Presentation :
Sir, I would like to complete my examination by checking the temperature chart, check fundus for Roth Spots,
urine for hematuria. I would also like to measure the blood pressure for her and I would expect a wide pulse
pressure.
On general examination, this is a young lady who appears to be well and not in any forms of distress or pain. She
has no stigmata of infective endocarditis such as Janeway lesion, Osler nodes and splinter hemorrhages. She has a
regular pulse rate of 80 beats/minutes and collapsing in nature. No radio-radio, no radiofemoral disease. She
has no signs of anemia and not cyanotic. She has no signs to suggest heart failure as well, JVP is not raised.
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In the pre-cardium, there is no scar, no deformity. She has a displaced apex beat at left 6 intercoastal space at
anterior axillary line. No parasternal heave, no thrills. On auscultation, first and second heart sound can be
heard. There is a grade 4 harsh pan-systolic murmur at mitral area radiating to axilla, accentuated by
expiration suggestive of Mitral Regurgitation. There is a grade 3 early diastolic murmur, best heart over the left
lower sternal edge that suggestive of Aortic Regurgitation There is no loud P2 or gallop rhythm, no peripheral
signs of aortic regurgitation. Lungs a r e clear. No hepatomegaly.or splenomegaly.
In summary, this is a young lady with mitral regurgitation and aortic regurgitation most likely secondary to
chronic rheumatic heart disease and clinically not in heart failure. No signs of pulmonary hypertension or
infective endocarditis.
What are your differential diagnosis for multiple valvular heart lesions?
Chronic rheumatic heart disease, Infective endocarditis
Name other causes of collapsing pulse.
Pregnancy
Patent Ductus Arteriosus (PDA)
Pagets Disease
Anemia
Thyrotoxicosis
What are the peripheral signs of Aortic Regurgitation?
Corrigans: visible vigorous neck pulsation

Quinckes: nail bed capillary pulsation
De Mussets: head nodding
Duroziezs: diastolic murmur proximal to femoral artery compression
Traubes: pistol shot sound over the femoral arteries
Mullers sign systolic pulsations of the uvula

What are the causes of aortic regurgitation?
Supravalvular: aortic roof disease ( Marfan, artherosceloris and dissecting aneurysm, connecting tissue
disease)
Valvular: congenital ( bscuspid aortic valve, large VSD), Rheumatic, IE
Acute onset: IE, dissecting aneurysm of aortic root, trauma, failed prosthetic valve
What are the causes of mitral regurgitation?

Acute: IE, acute MI, chordae/ papillary muscle trauma/ischemia/ rupture
Chronic: Mitral valve prolapse, congenital cleft leaflets, LV dilatation/ aneurysm ( congestive heart
failure, dilated cardiomyopathy, myocarditis), Marfan syndrome, mitral valve annulus calcification,
rheumatic heart disease
What are investigations, would you like to do ?
ECG
- MR: p-mitrale, atrial fibrillation and previous MI (Q wave)
- AR: Lateral T wave inversion
CXR
- MR: Cardiomegaly, enlargement of the left atrium and pulmonary edema.
- AR: Cardiomegaly, widened mediastinum and pulmonary edema
ECHO
- MR :
a. Severity: size/density of MR jet, LV dilatation and reduced EF
b. Cause: prolapse, vegetation, ruptured papillae and infarction
- AR:
a. Severity: LV ejection fraction and dimensions, root dimensions b.
Cause: intimal dissection flap or vegetation
How would you manage a patient with chronic Mitral regurgitation?
Control rate if fast AF

Anticoagulants are not indicated unless there is: a history of systemic embolism; a prosthetic mitral
valve, either xenograft or mechanical; additional mitral stenosis with a low output or AF.
Diuretics are needed to reduce pulmonary venous congestion and LV preload.
Afterload reduction with intravenous nitrates or nitroprusside is indicated in acute MR by helping to
reduce the regurgitant fraction and increase forward stroke volume. Afterload reduction in acute MR is less
successful than in aortic regurgitation. ACE inhibitors are used routinely but with little evidence of their
long-term benefit.
In acute MR with chordal rupture and pulmonary oedema, a continuous positive airway pressure
(CPAP) mask or artifi cial ventilation and full monitoring as in cardiogenic shock may be necessary
Infective endocarditis prophylaxis should be considered
How would you follow up a patient with aortic regurgitation and name the indication for aortic valve
replacement in such patient.
All patients need antibiotic cover for dental or surgical procedures
Long-acting nifedipine has been shown to delay the development of LV dysfunction in chronic aortic
regurgitation
Indication for surgery
- Aortic valve should be replaced before LV dysfunction develops
- The indications are:
a. Symptoms of increasing dyspnea and LVF
b. Enlarging heart in CXR or ECHO
c. Infective endocarditis that does not responds to treatment
What is the surgical option in AR?
Valve replacement: most patient

Valve repair: very limited role
Aortic roof replacement( bentall procedure) when ascending aortic aneurysm
present, valved conduit used

Case 2 : Prosthetic Valve
Presentation :
Sir, I would like to complete my examination with checking the peripheral signs of Aortic Regurgitation, check the
temperature chart, check fundus for Roth Spots and urine for hematuria. I would also like to measure the blood
pressure for him as well.
My patient is middle aged man lying comfortably propped up in bed at 45 degree supported by one pillow. He is
not cachexic, not pale, not jaundiced and not cyanosed. I can appreciate audible metallic click. Purpura noted
over the extremities (evidence of over warfarinization).
On peripheral examination, there is no evidences of infective endocarditis such as Osler nodes, Janeway lesion,
splinter hemorrhage, no clubbing, no needle marks. He has a regular pulse of 80beats/min, not collapsing in
nature, no radio-radio, no radio-femoral delay. JVP is not raised and no pedal edema.
In the precordium, there is a midline sternotomy scar measuring 15 cm. No chest wall deformity. Visible
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pulsation appreciated all over the precordium. He is a displaced apex beat at left 6 intercostal space, anterior
axillary line. No thrills, parasternal heave or palpable P2.
Upon auscultation, metallic first heart sound is heard and normal second heart sound. Metalic first heart
sound is best heard at the mitral area. No murmur. (Sometimes ESM heard normal)
No basal crepitations. No hepatomegaly or splenomegaly.
In summary, this patient has metallic prosthetic mitral valve and clinically not in heart failure. He has signs to
suggest overwarfarinization. No evidence of IE.
What are the types of prosthetic valve
a. Mechanical valves
Caged ball
Tilting disk
Bileaflet valve
The valves are very durable, but have a higher thromboembolism rate than xenografts. Very occasionally a
patient or his or her partner may be disturbed by the audible valve clicks. The double tilting disc valves have
much better flow profiles than the Caged ball valve and have largely superseded it.
b. Bioprostheses
Porcine
Pericardial
Homograft
Autologous
Biological valves do not have as good long-term durability as mechanical valves and may need replacing at about
810 years (mitral) or 1015 years (aortic).
Common complications of prosthetic valve
Valve dysfunction leakage, dehiscence, obstruction

Systemic thromboembolism stroke
Bleeding - warfarin
Bacterial endocarditis
mechanical hemolytic anemia ( hemolysis at the valve)
How do you want to treat the each complication?
Primary valve failure--- emergent valve replacement

Prosthetic valve endocarditis-- -Administer intravenous antibiotics as soon as 2 sets of blood cultures
are drawn. Vancomycin and gentamicin may be used empirically pending blood cultures and
determination of methicillin resistance.
Thromboembolic complication---start anticoagulation therapy depend on the etiology of stroke
Prosthetic valve thrombosis---Thrombolytic therapy
Mechanical hemolytic anemia--- transfuse blood
What are the considerations involved in choosing mechanical or bioprosthetic valve?
A bioprosthesis is preferred in older patients and in patients in whom lifetime anticoagulation poses
important risks. This includes persons with clotting disorders, and gastrointestinal problems with the
potential for bleeding and persons who may not be able to comply with required anticoagulant
medication and follow-up testing.
The major disadvantage of biologic prostheses is primary valve failure as a result of leaflet
degeneration, which limits their functional life span.
Mechanical heart valves, which have greater durability than bioprosthetic valves, are usually preferred in
patients younger than 65 years without contraindications to long-term anticoagulation.
What are the signs suggestive of prosthetic valve infection?
Change in their valve sounds

New symptom, however vague: dyspnoea, night sweats, myalgia, anorexia.
In mechanical valves the opening and closing sounds of either ball or disc should be clear and sharp, not
muffled. Vegetations may restrict ball or disc movement and muffle the relevant prosthetic sounds.
Check ECG for PR interval prolongation (septal abscess).
What is the pathophysiology of prosthetic valve endocarditis?

The pathologic hallmark of PVE in mechanical valves is ring abscesses. Ring abscess may lead to valve
dehiscence and perivalvular leakage. Local extension results in the formation of myocardial abscesses.
Further extension to the conduction system often results in a new atrioventricular block. Valve stenosis
and purulent pericarditis occur less frequently.
Bioprosthetic valve PVE usually causes leaflet tears or perforations. Valve stenosis is more common with
bioprosthetic valves than with mechanical valves.
Finally, glomerulonephritis, mycotic aneurysms, systemic embolization, and metastatic abscesses also
may complicate PVE.
What is the thing you needs to counsel the patient with a prosthetic heart valve:
Antithrombotic therapy to prevent valve thrombosis and thromboembolism

Evaluation of valve function by serial echo
Endocarditis prophylaxis
Safety of exercise
Pregnancy
How will you follow up the patient?
The first outpatient visit at two to four weeks after hospital discharge is aimed at assessing function of
the prosthetic valve and looking for signs of infection, conduction disturbance, or myocardial infarction.
The evaluation should include an interval history, physical examination, electrocardiogram, and chest x-
ray, appropriate blood tests (complete blood count, creatinine, electrolytes, lactate dehydrogenase, and
INR if indicated). If not obtained before discharge, a baseline transthoracic Doppler echocardiogram
should be obtained.
Routine follow-up visits in asymptomatic patients should occur yearly. The evaluation should include a
complete history and physical examination; other tests are performed as indicated.
In asymptomatic patients without evidence of left ventricular or valve dysfunction, routine annual
echocardiography is not indicated in patients with mechanical valves or during the first five years with
bioprosthetic valves.
Repeat evaluation with echocardiography should be performed any time there is a change in clinical
status.
Can the patient exercise and has a normal life activity?
Patients with a bioprosthetic mitral valve who have normal valve function, normal or near-normal left ventricular
function, and are not being treated with anticoagulation can participate in low and moderate static and dynamic
competitive sports
How do you manage a pregnant mother with prosthetic heart valve?
Women should be informed fully about the importance of therapeutic anticoagulation throughout
pregnancy.
Maternal and fetal risks associated with each anticoagulant regimen should be reviewed in detail.
Women should participate in the decision about which regimen to choose.
in order to balance fetal teratogenic risk and maternal thromboembolic risk:
During the first trimester LMWH, or second line UFH, initiated before the sixth week of gestation, with
the dose adjusted to achieve the manufacturer's peak anti-Xa level (approximately 1.0 U/mL) at 4 hours
after subcutaneous injection of LMWH, or mid-dose aPTT at least twice control measured at least

weekly with UFH. Given the more predictable anticoagulant effects of LMWH, LMWH is preferred to
UFH.
The choice of anticoagulation between weeks 12 and 36 is based on discussion between the patient,
cardiologist, and obstetrician. The preferred options are warfarin or LMWH. Warfarin is dose adjusted to
maintain an INR of 2.5 to 3.5, measured at least every two weeks, and is associated with the lowest
risk of maternal thromboembolic complications. If LMWH is used, it should be administered
subcutaneously twice daily at a therapeutic dose, with dose adjustment to maintain four hour post dose
anti-Xa levels at approximately 1.0 U/mL. Ensure patient compliance with LMWH and monitoring is
critical.
LMWH or UFH from the 36 th week until delivery, with the dose adjusted to achieve the manufacturer's
peak anti-Xa level (approximately 1.0 U/mL) at four hours after subcutaneous injection of LMWH, or
aPTT at least twice control measured at least weekly with UFH.
Management at the time of delivery involves additional hemodynamic and hemorrhagic risks in a woman with a
prosthetic heart valve.
To minimize the risks of maternal and fetal hemorrhage, oral anticoagulants should be switched to LMWH or
UFH, usually no later than 36 weeks.
Women treated with LMWH or SQ UFH should be switched to IV UFH at least 36 hours prior to the
induction of labor or cesarean delivery.
IV UFH should be discontinued four to six hours prior to anticipated delivery, and should be restarted
at 500u/hour at four to six hours after delivery if there are no bleeding complications. IV UFH is then
increased to achieve a therapeutic APTT by 24 to 72 hours postpartum, depending on the mode of
delivery and clinical status of the woman. IV UFH is continued until warfarin achieves a therapeutic INR.
Warfarin can be resumed the same day as delivery. If the woman has had a caesarean section this
should be delayed for one to two days.
What is the endocarditis prophylaxis?
For dental, oral, or upper respiratory tract procedures, use amoxicillin 2 g PO 30-60 minutes before the
procedure.
What is the target INR in prosthetic valve?
Bioprosthetic valves: INR 2-3 for 3 months following implantation; anticoagulation may then be
discontinued unless the patient has another indication, such as atrial fibrillation or development of
prosthetic valve thrombosis.
Mechanical valves: Aortic valve INR is 2-3; mitral valve INR is 2.5-3.5; Patients with atrial fibrillation
should be kept at the higher end of this range. In patients with low hemorrhage risk, low-dose aspirin is
recommended in addition to warfarin.

Case 3 : Bronchiectasis
Presentation :
Sir, I would like to complete my examination by checking the temperature chart and sputum cup for this
patient. I would also like to ask for history of tuberculosis in the past.
On general examination, this is a middle aged man who appears to be well and not in respiratory distress
(Patients in exam are usually not in respiratory distress). He does not appears to be cachexic or in pain. He has a
respiratory rate of 16breaths/min.
In the periphery, he has grade 3 clubbing and nicotine stain. No evidence of HPOA. No evidence of CO2
retention as there is no palmar erythema, no flapping tremor, no bounding pulse. His pulse is regular. His JVP is not
raised, no conjunctiva pallor. No lower limb edema. No palpable cervical lymph nodes.
In the precodium, he has no evidence of mediastinal shifting as trachea is central and apex beat is not deviated. No
chest deformity or scar noted. His chest expansion, vocal fremitus, vocal resonance appears to be equal on both
side. Percussion note is resonance in all lung field.
On auscultation, vesicular breath sound can be heard. There is presence of bilateral end-inspiratory coarse
crepitations. No prolonged expiratory phase/rhonchi. No loud P2.
In summary, this is a middle aged man with bronchiectasis and clinically not in respiratory distress. Most likely
etiology is pulmonary tuberculosis.
What are your differential diagnosis?
Bronchiectasis
Lung fibrosis
Bronchogenic Carcinoma
Chronic Lung abscess
What is Bronchiectasis ?
Chronic suppurative inflammation of the bronchi that results in permanent dilatation of the airways
What are the investigations you would like to do?
Sputum for culture and cytology- common organism are haemophilus influenza, pseudomonas,
Escherichia coli, pneumococcus and staph. Aureus.
CXR tramlines and ring shadows
ventilator function test show restrictive defect or an obstructive pattern
High Resolution CT Thorax - signet ring sign, thickened dilated bronchi larger than the adjacent
vascular bundle.

Causes of Bronchiectasis
Congenital: Kartageners and cystic fibrosis

Mechanical: bronchial carcinoma (suspect if localized bronchiectasis)
Childhood infection: measles and TB
Immune OVER activity: allergic bronchopulmonary aspergillosis (ABPA);
Immune UNDER activity: hypogammaglobulinaemia
Aspiration: chronic alcoholics and GORD
Treatment :
Mainstay physiotherapy
A Antibiotic
B Bronchiodilator
C Corticosteroid
D Drainage ( Postural Drainage)
S Surgery ( occasionally for localized disease)
Complication of bronchiectasis :
Hemoptysis
Cor pulmonale
Secondary amyloidosis ( Dip urine for protein)
Pneumonia
Cerebral abscess
Management of hemoptysis in bronchiectasis :
Medically : Transnexamic acid & mefenamic acid (mild)

Bronchoscopy : Balloon tamponade, iced saline lavage, topical medications, laser therapy, and
electrocautery.
If failed bronchoscopy, proceed to arteriographic embolization of bleeding sites (typically from a
bronchial artery) by an interventional radiology service.
Lastly, surgical treatment by open lung surgery to resects it.

Acute
- Give supplementary 02
-
- Start IV antibiotics
- Chest physiotherapy = aid sputum expectoration and mucous drainage

-
Chronic
-Smoking cessation
- Pneumococcal and influenza vaccination
- Bronchodilator therapy
- Chest physiotherapy
- Long term 02 therapy
Bronchial dilation due to 3 causes=

(a) destruction of elastic tissues
b) contraction of fibrous tissues exerts traction on bronchi
(c) chronic cough leads to rise in bronchial pressure
- Localised bronchiectasis= mechanical obstruction, childhood bronchopulmonary infection
- Generalised bronchiectasis= inherited/ acquired impairment in host defences
What are the test to identify underlying illnesses of the bronchiectasis
Quantitative immunoglobulin levels, to exclude hypogammaglobulinemia

Quantitative serum alpha1-antitrypsin (AAT) levels, to rule out AAT deficiency
Aspergillus precipitins and serum total IgE levels, to diagnose ABPA
Autoimmune screening tests
Cor pulmonale
- right heart failure cause by chronic pulmonary hypertension due to disorders in the lung, chest wall or
pulmonary circulation

Management
(a) treat underlying cause
(b) treat respiratory failure
- Give supplementary 02 cautiously if Pa02 < 60 mmHg
- Start at Fi02 = 24% and monitor with ABG 30 mins later
- Escalate oxygen if PaC02 remains stable
- espiratory stimulant)
- Consider assisted ventilation
(c) treat cardiac failure
- fluid restriction
- diuretics
(d) venesection if hct >55%
(e) heart- lung transplant in young patients
Stage of clubbing
1. Loss of angle between the nail and nail bed
2. Increase in longitudinal and tranverse curvature
3. Positive fluctuating test
4. Drumstick appearance
5. Primary hypertrophic osteoarthropathy
What is primary hypertrophic osteoarthropathy?

Primary hypertrophic osteoarthropathy (PHO), a rare hereditary disorder with digital clubbing.
It is characterized by the presence of periosteal inflammation at the distal ends of long bones, the wrists, the
ankles, the metacarpal and metatarsal bones. There is swelling and tenderness over the wrist and other
involved area. The cause include primary lung carcinoma and pleural fibromas. The subperiosteal new bone
formation, and arthropathy, has been linked mutations in the 15-hydroxy-prostaglandin dehydrogenase (15-
PGDH) encoding gene HPGD, which causes PH

Case 4 : Pleural Effusion
Introduction :
A pleural fluid is fluid in the pleural space. There are 5 types of pleural effusions exudates, transudates,
empyema, haemothorax, chylous thorax. 500 ml of fluid is needed for clinical detection.
Presentation :
Sir, this is a young man who is lying on the bed with 45 degree propped up. He is in respiratory distress as
evidence by usage of accessory muscles while breathing and is tachypnic with respiratory rate of 24 breaths per
minutes. He is on nasal prong with pulse oxymeter monitoring. Otherwise, his body build is moderate and is pink.
On examination, he has no clubbing, no cyanosis, no nicotine staining, and no signs of CO2 retention such as
bounding pulse, palmar erythema and flapping tremor. He has no signs to suggest Horners syndrome, good oral
hygiene, no raised JVP and no ankle oedema.
In the chest has no scars, no deformity, no visible pulsation. He has evidence of mediastinal shifting with
trachea deviated to right. He has evidence of massive left sided pleural effusion as evidence by reduced chest
expansion, reduced tactile fremitus, stony dull on percussion, reduced air entry and reduced vocal resonance over
the left upper, middle and lower zone of the left lung.
No cervical lymphadenopathy and hepatomegaly noted. I would like to complete my examination by checking the
fever chart, sputum pot and do a bedside peak expiratory flow rate.
Besides, I would like to look for the underlying cause of this pleural effusion like cardiac failure, chronic liver
disease, hypothyroidism, rheumatoid arthritis and butterfly rash for SLE.
What is your provisional diagnosis?

Left sided massive pleural effusion most probably due to ?? and is SOB at rest.
What are your differentials for dullness over the left base of the lung?
Pleural thickening
Consolidation and collapse of lung
Elevated diaphragm
How would you like to investigate this patient?
I would order an erect PA CXR to look for obliteration of costophrenic angle and meniscus sign. 175ml of
pleural fluid is needed for it to detect PE in CXR.
Pleural tap can be done and send for pleural analysis like gross appearance, cytology, clinical chemistry like
protein, glucose, pH, LDH, Amylase.
If glucose <3.3mmol/L, pH<7.2, LDH (pleural:serum >0.6), it is suggestive of TB, malignancy, RA, SLE,
Empyema.

In autoimmune disorders pleural fluid for RF, ANA and complement factors can be send. If pleural fluid
analysis is inconclusive, I would consider parietal pleural biopsy with Abrams needle for
histopathological examination and mycobacterial culture.
What are the causes of pleural effusion?
Transudate Exudate
Increase venous pressure cardiac failure, Inflammatory SLE, RA
constrictive pericarditis, fluid overload Malignancy bronchogenic carcinoma,
Hypoproteinaemia cirrhosis, nephrotic malignant metastasis, lymphoma, mesothelioma,
syndrome, malabsorption lymphangitis carcinomatosis
Hypothyroidism Infection TB, pneumonia, pulmonary
Meigs syndrome (Ovarian fibroma and right infarction
pleural effusion)
How you differentiate between transudate and exudates?
If Protein <25 g/L, it is transudate.

If protein >35 g/L, it is exudates.
If protein between 25 35 g/L, Lights criteria is used.

Lights criteria for an exudates are applied:
The ratio of pleural fluid to serum protein >0.5

Ratio of pleural fluid to serum LDH >0.6
Pleural fluid of serum LDH is 2/3 the upper normal limit for blood LDH levels.
How would you manage this patient?
Treat the underlying cause.

Drainage removed <2L/24hours
Pleurodesis by tetracycline, talc poweder, bleomycin
Surgery if persistent collections and increase pleural thickness.
What are the conditions associated with bloody pleural fluid?
Malignancy, pulmonary embolism, tuberculosis, and trauma to the chest
What is the anatomy involved
The pleural space is bordered by the parietal and visceral pleurae. The parietal pleura covers the inner surface
of the thoracic cavity, including the mediastinum, diaphragm, and ribs. The visceral pleura envelops all lung
surfaces, including the interlobar fissures. The right and left pleural spaces are separated by the mediastinum
What is normal pleural fluid?
Clear ultrafiltrate of plasma that originates from the parietal pleura

A pH of 7.60-7.64
Protein content of less than 2% (1-2 g/dL)
Fewer than 1000 white blood cells (WBCs) per cubic millimeter
Glucose content similar to that of plasma
Lactate dehydrogenase (LDH) less than 50% of plasma
What are the causes of exudates with negative cytological findings and pleural fluid lymphocytosis?
TB, malignancy, collagen vascular diseases.
What causes increase amylase of pleural fluid?
Pancreatitis, carcinoma, bacterial pneumonia, oesophageal ruptures.

What information can get from the apperance of pleural fluid ?
What is the complication of the pleural effusion?

empyema
What is the use of streptokinase in pleural effusion?

Intrapleural instillation of fibrinolytic agents to dissolve fibrinous adhesions is intended to improve pleural fluid
drainage and prevent pleural loculations. It is used in the management of parapneumonic pleural effusions and
pleural empyema.

Case 5 : Thalassaemia (Sabah very own cystic fibrosis)
Introduction :
The thalassaemias are a heterogeneous group of genetic disorders with defective synthesis of one or more
globin chains. In Malaysia, the most common types are the and thalassaemias. The thalassaemias
together with its heterozygous interaction with HbE disease constitute the bulk of the patients load.
The East Malaysian state of Sabah had the most number of registered patients standing at 1,272 with the
Kadazan-Dusun ethnic group contributing almost half of these affected individuals.
History :
1. Dx as thallassaemia where? When? By who? How? First presentation?\

2. Blood transufusion when start? How frequent? Usually where? Far from home- why? Recently
increase in frequency? Any acute reaction?
3. Pre and post transfusion drop rate?
4. Start on desfo? When? Why- ferritin increase? How? Compliance? Follow up for desfo toxicity? Any
complication? Electricity prob?
5. Iron overload complication growth retard, Bronze Diabetes, bone pain? When Dx? How? Mx?
6. Follow up(ANE & outpatient attendance) echo? Bone scan? HIV, hep B Hep C screening?
7. Detail Family hx? Screen?
8. Social financial problem? Transport problem? Child care problem?
9. Drugs Vit C? compliance?
10. DIET changes? Increase calcium intake, decrease iron intake?
11. Bone marrow HLA compability
Presentation :
Sir, Muhammad is a 10-year-old boy with pallor and slate gray skin. He has evidence of extramedullary
hemopoesis as evidenced by frontal bossing and maxillary overgrowth. His height and weight appears to be small
for his age and I would like to confirm it by plotting on the growth chart.
On peripheral examination, he has no evidence of chronic liver disease such as leuconychia, palmar erythema,
flapping tremor or bruising. He has conjunctival pallor and tinge of jaundice noted. His oral hygiene appears to be
appropriate.
On inspection of the abdomen, there are multiple injection sites. There is fullness over the right and left
hypochondrium region too. Otherwise, abdomen moves with respiration, umbilicus centrally located and flat. No
visible peristalsis, no dilated veins, no surgical scars, hernia orifices are intact. Abdominal palpation revealed
that there is hepatosplenomegaly with and 8cm liver below left subcostal margin. The liver moves with
repiration, smooth surface, non tender, non pulsatile, well defined margin, firm in consistency, dull on
percussion and no bruit heard. He has a 10cm spleen below left subcostal margin, which move inferior
medially with respiration, cannot get above it, with a splenic notch felt, dull on percussion and splenic rub

heard. No ballotable kidney and no free fluid in the abdomen. Bowel sounds present. There are no cervical or
inguinal lymphadenopathies.
I would like to complete my examination by checking the cardiovascular system for gallop rhythm and lung
basal crackles, do a Tanner staging, check his plasma glucose level and ask for family history of
hemoglobinopathies.
What is your provisional diagnosis?

These findings are in keeping with a diagnosis of chronic hemolytic anemia most likely Beta Thalassaemia
major, currently anaemic and complicated with iron overload.
Differential for hepatosplenomegaly

Liver Cirrhosis with portal hypertension
Hematological disorders myelo/lymphoproliferative disorders
Infection infectious mononucleosis, acute viral hepatitis, CMV
Connective tissue disease
Infiltrative amyloidosis
How do you approach a patient present with you with anaemia?

What are the investigations you would like to do for her?
First, I would like to confirm the diagnosis first, by doing FBC to look for microcytic hypochromic
anaemia, PBF to look for marked anisocytosis, poikilocytosis (including fragments and tear-drop
poikilocytes), hypochromia and microcytosis. Basophilic stippling, Pappenheimer bodies and target cells.
Circulating nucleated red cells showing defective haemoglobinisation and dyserythropoietic features are
present. The total white cell count and the neutrophil count might be increased. If hypersplenism
develops, there is leucopaenia, neutropaenia and thrombocytopaenia.
I would also like to do Hemoglobin electrophoresis. A HbF >90% and complete absence of HbA will
confirm him as Thalasaemia major. This must be done before initiation of blood transfusion.
How would you differentiate between iron deficiency anaemia and Thallasaemia from the result of FBC?
I would like to use Mentzer index, which is product of MCV divided by RBC. If less than 13, it is
suggestive of Thalasaemia. If more than 13, it is suggestive of IDA.
In iron deficiency, the marrow cannot produce as many RBCs and they are small (microcytic), so the
RBC count will be low along with the MCV, and as a result, Mentzer's index is not as low, >13
Comparatively, in thalassemia, which is a disorder of globin synthesis, RBC production is preserved, but the
cells are smaller and more fragile. Therefore, the RBC count is normal with a low MCV and the
Mentzer's index is <13.
What are the HbA2 level in beta Thallasaemia trait?

In heterozygosity or severe thallasaemia trait, HbA2 will be 4 9% while mild thallasaemia trait, the HbA2
would be 3.6% to 4.2 %.
How you manage this case before first transfusion?

How you going to manage during routine admission for blood transfusion?
First, I would like to measure his height, weight, liver and spleen size.
Pretransfusion Hb, platelet count, post transfusion Hb (half an hour after transfusion) is done.
Aim pre transfusion Hb 9 -10 g/dL and post transfusion Hb 12-12.5 g/dL.
3 to 6 monthly check the serum ferritin, liver function test and evaluate growth and development.
Every year or more frequent, endocrine assessment RBS, T4/TSH, Ca PO4, Vit D, PTH level
Pubertal and sexual development from 10 years onwards,
Tanner staging for breast and genitalia
Check the FSH, LH, oestradiol or testosterone level.
Infection screen HIV, Hepatitis B, Hepatitis C, VDRL.
Calculate transfusion indices volume of pure RBD transfused/ median weight).
Evaluate iron balance liver iron assessment.
Bone osteoporosis and skeletal abnormalities.
Cardiac assessment at variable intervals especially after 10 years of age yearly ECG, annual cardiac
echography and cardiac T2*MRI
What are the long term complications of blood transfusion?
In chronic iron overload, endocrine puberty delay, growth retardation, hypothyroidism,

hypoparathyroidism, diabetes mellitus.
Cardiac arrhythmias, pericarditis, cardiac failure.
Liver liver cirrhosis.

What will you advice to the patient regarding his daily activities?
I would advise him to avoid contact sports like football that may injure his spleen, causing splenic rupture.
When will you consider splenectomy and what are the anticipate complication?
I would opt for splenectomy if the transfusion rate has increased to 200-250 ml/kg/year (normally 180
ml/kg/year), evidence of hypersplenism, or massive spleen causing discomfort, risk of infarct and splenic
rupture due to trauma.
Complication would be sepsis (OPSI- overwhelming post splenectomy infection), especially by encapsulated
bacteria like Streptococcal pneumonia, Hemophilus Influenza and Neisseria Gonorrhea. Immunoprophylaxis and
chemoprophylaxis can be given.
Besides, Thromboembolic phenomenon is common more in Thalassemia media and antithrombotic agent can be
given.
Post-splenectomy thrombocytosis is a known complication and the use of low dose aspirin or dypyridamole if
platelet count is more than 800 x 10^9/L may be considered.
When would you start chelation therapy?

It is started when there is >10 units of blood transfusion or ferritin level has increased up to 1000 ng/mL for
more than two occasions two weeks apart.
What are the dietary advice for this patient?

I will give him folate at minimum 1mg OD, low dose Vitamin C augment iron excretion for those on desferral and Vitamin
E. I would ask him to avoid iron rich food such as red meat, eye yolk, green vegetables and iron fortified
cereals and milk. Consumption of tea as it may decrease intenstinal iron absorption.
Would you recommend him for bone marrow transplant?

NO. It depends on the 3 risk groups, hepatomegaly, iron chelation status and liver fibrosis. This patient has at least
2 risks including hepatomegaly and bad iron chelation status and hence has less success rate in BMT.
What are the non-invasive ways of estimating tissue iron overload?

Cardiac MRI T2*, Liver MRI R2/ferriscan
How will you advice your female thalassaemia patient who plan to get pregnant?
With advances in hypertransfusion and iron chelation, some women with beta thalassemia major have had
favorable pregnancy outcomes. However, such pregnancies are recommended only in those with normal cardiac
function and adequate hypertransfusion and iron chelation regimens.
Genetic counseling is strongly advised, since these mothers will be transmitting a thalassemic gene to all of their
offspring, and partnership with a male with beta thalassemia may lead to beta thalassemia major in their
offspring. Anetenatal diagnosis can be done by chrionic villous sampling at 9-11 weeks period of gestation
and also amniocentesis at 16 weeks

Who should receive Hematopoietic cell transplantation (HCT) transplant?
In preparation for possible HCT, all children with BTM receive treatment with a hypertransfusion protocol
along with iron chelation therapy (Grade 1A).
For a child with BTM who has an HLA-matched sibling or HLA-matched unrelated donor and who has undergone
rigorous medical therapy (ie, transfusion plus high-quality iron chelation therapy), we recommend that HCT be
performed as soon as is reasonably practical (Grade 1A).
For those without an HLA-matched donor, children with prior poorly-controlled chelation therapy, and adults,
transplant-related mortality can be as high as 35 to 50 percent. The risks and benefits of undergoing either curative
HCT (with its high incidence of transplant-related mortality), or continuing with non-curative medical therapy (life-
long transfusions and chelation therapy) are very patient specific, and a decision favoring one over the other should
be made on a case-by-case basis, depending upon the values and preferences of the patient/family.
What is the PBF picture of a thalassemia major patient?

Anisocytosis, poikilocytosis, hypochromia, microcytosis, target cells.
What is the PBF picture of a post splenectomy patient?

Howell-Jolly bodies, thrombocytosis, pappenheimer bodies.

What are the difference types of chelation therapy?
What are the crisis in hemolytic anemia?

Hemolytic crises
Aplstic crises
Vasoocclusive or infarction crises
Sequestration cries

What is the cause increase the rate of fall of hemoglobin in thalassemia
Hypersplenism
Alloimmuniztion to RBC
Folate deficiency
What is the action of iron chealting agent?

Deferixamine(DFO) : In the circulation and tissues, DFO binds iron and the iron bound form is excreted
efficiently in the urine and bile
Deferiprone (DFP): chelates iron from parenchymal tissue, reticuloendothelial cell, transferrin
Deferasirox(DFX) : chelates iron from paraenchymal tissue, reticuloendothelial call and myocardial cell
How to choose the use of iron chealting agent?

Deferixamine is the first line therapy. DFP monotherapy is indicated in patients older than 6 years if
DFO treatment is inadequate or intolerable and is indicated in patients who are at risk of cardiac iron
toxicity. DFX monotherapy once daily is indicated in patients from 2 years old where DFO is
unacceptable, inadequate or intolerable.
DFO & DFP combination is indicated in patients with severe iron overload or inadequate chelation with
monotherapy
What is the effect of combination therapy ( desferrioxamine and deferiprone)

Shuttle effect: low molecular weight deferiprone enters cell and transfer intracellular iron to
desferrioxamine in plasma. It is benefit for patient with cardiomyopathy on desferrioxamine.
How is the administration of the deferasirox

It is administer on empty stomach at least 30 minutes before food. To be dispersed in a glass of water
of water or orange juice.
Why is vitamin c given to the patient?

Vitamin c is usually used with desferrioxamine which can increase the availability of the chelatable iron
by mobilizing iron from the intracellular stores. It should be administered 30-60 minute after starting
infusion. But avoid to be given in patient with cardiomyopathy.
Why is vitamin E given to patient?

Vitamin E supplementation helps to reduce platelet hyperactivity,and reduce oxidative stress
Who should be screen for thalassemia ?

Mean corpuscular volume (MCV) & mean corpuscular haemoglobin (MCH)
Red cells are hypochromic (MCH < 27 pg) and microcytic (MCV
< 80 fl) in thalassaemia as
Family history of thalassemia
What do u understand about thalassemia
Thalassemia refers to a spectrum of diseases characterized by reduced or absent production of one or

more globin chains, thus disrupting this closely-regulated ratio.
Beta thalassemia is due to impaired production of beta globin chains, leading to a relative excess of
alpha globin chains.
What is the type of inheritance defect?

Two type: thalassemia ( chromosome 16), ( chromosome 11)
thalassemia
1. Silent carier: deletion of one gene
2. thalassemia trait: deletion of 2 gene
3. Hb constant spring: Abnormal chain variant
4. HbH disease: deletion of 3 gene
5. Hydrops fetalis: deletion of all 4 gene
thalassemia
- 0 thalassemia: no detectable chain synthesis
- + thalassemia: reduced chain synthesis
- thalassemia: both the and chain are deleted
-E thalassemia : Hb E and chain gene deletion
-Hb lepore: fusion of globin leads to unequal crossover of and genes
What is physiology related to hemoglobin?
Adults have mainly hemoglobin A, made up of two alpha and two beta chains, together with
HbA2 <2% (two alpha and two delta chains), and no HbF (two alpha and two gamma-globin
chains)
There are four alpha genes (located on chromosome 16) and two beta genes (on chromosome
11)
At birth HbF accounts for 70-90% in normal individuals, and gamma-chain synthesis is only
replaced by beta chains gradually
Impairment of beta synthesis leads to the patient being asymptomatic at birth
What is the feature of different type of thalassemia?

Clinical feature Laboratory feature
Thalassaemia Major Anaemia Hb : < 7 g/dL
Hepatosplenomegaly HbF : > 90%
Growth failure / HbA2 : normal or high
Retardation HbA : usually absent
Thalassaemia Intermedia Milder anaemia Hb : 8-10 g/dL
Thalassaemia facies HbF : > 10%
Hepatosplenomegaly HbA2 : 4-9%, if > 10% -
suggests HbE
HbA : 5-90%
HbH disease : presence of H
band
b Thalassaemia Trait Normal to mild anaemia Hb : > 10 g/dL
No organomegaly MCH : < 27 pg
HbF : 2.5 - 5%
HbA2 : 4-9%, if > 20% suggests
HbE trait
HbA : > 90%
a Thalassaemia Trait Normal to mild anaemia Hb : > 10 g/dL
No organomegaly MCH : < 27 pg
Hb analysis : normal
H inclusion may be present
DNA studies may be necessary
What do you understand about thalassemia carrier?
beta thalassemia trait, and silent carrier of beta thalassemia, are used to describe heterozygotes who
carry one normal beta globin allele and one beta globin thalassemic allele. The vast majority of these
patients are entirely asymptomatic, but do present an abnormal blood picture that is sometimes
erroneously diagnosed as iron deficiency anemia
What are the cause of skeletal changes ?
Skeletal changes are due largely to the expansion and invasion of erythroid bone marrow, which widen
the marrow spaces, attenuate the cortex, and produce osteoporosis.
What is the x ray seen change in the skull?
Marrow expansion causes dramatic widening of the diploic spaces and produces a characteristic "hair-
on-end" radiographic appearance of the skull
What are feature of skeletal changes?
There is prominent frontal bossing, delayed pneumatization of the sinuses, and marked overgrowth
of the maxillae. As a result, the upper incisors are "jumbled" and the malar eminences are
especially prominent, producing malocclusion and the characteristic facies.
The ribs and the bones of the extremities become box-like and eventually convex, due to expansion
of the bone marrow.
Premature fusion of the epiphyses can result in characteristic shortening of the limbs, particularly
the arms
thinning of the cortices result in pathological fracture
Why there is hepatosplenomegaly in beta thalassemia child?
Hepatosplenomegaly is prominent early in the disease, due to increased red cell destruction as well as
extramedullary erythropoiesis in this organ

What is the overall follow up plan?

What is the management of the complication?
What is the degree of iron overload?

What is the volume of pure red blood cell (PRBC) transfused ?
It is based on the haematocrit of packed red blood cell given ( usually HCT of PRBC from blood bank is
> 50-55%)
Volume of pure RBC transfused = volume of blood given X HCT of PRBC given ( e.g 600 ml x 0.55 =
330mls)
Why we keep the post transfuion Hb at 13.5- 15.5 g/dl

This target allow for normal physical activity and growth, abolishes chronic hypoxaemia, reduce
compensetaroy marrow hyperplasia which cause irrevisble facial bones changes and paraspinal mass
What is hyperspleenism?
Diagnostic criteria for hypersplenism(4 criteria needed)

1.peripheral blood film showing anaemia,leukopenia and thrombocytopenia singly or in a
combinationpancytopenia
2.normocellular or hypercellular bone marrow.
3.splenomegaly.
4.counts of RBC,PLATELET and LEUKOCYTES become normal in peripheral blood film following
splenectomy.
What is the other indication of splenectomy?
Splenectomy usually done in following cases:

1.hereditary spherocytosis
2.hypersplenism causes significant clinical problems
3.portal hypertension due to splenic vein thrombosis
4.chronic idiopathic thrombocytopenic purpura
5.hairy cell leukaemia
What is the test to know diabetes status of a patient but why HbA1c does not use in thalassemia
patient?
Fructosamine , which reflect control over the previous 2-3 weeks
HbA1c is the most widely used measure of average blood glucose control in diabetes. It is not used in
thalassaemia because repeated blood transfusions make it inaccurate.

Case 6 : Chronic liver disease
Introduction:
Cirrhosis is defined pathologically as fibrosis and abnormal regenerating nodule of liver
Presentation:
Sir, I would like to complete my examination by checking the external genitalia of this patient, per rectal
examination and take a good history from this patient.
This is a middle age gentlemen who appears to be well with average built and obvious tattoo mark over both
arm. There are signs of chronic liver disease such as palmar erythema, jaundice, loss of axillary hair and spider
naevi, otherwise there is no clubbing, no duputryen contracture, no hepatic flap, no injection mark, no parotid
enlargement, and no gynaecomastia.
On inspection of the abdomen, there is no scar, no dilated vein. Abdomen is flat and umbilicus is centrally
located and move with respiration and hernia orifices are intact. On palpation, there is no hepatomegally
but traubes space is dull suggestive of splenomegaly. There is also evidence of ascites with presence of shifting
dullness and fluid thrill. Normal bowel sound heard
In summary, this gentlemen has chronic liver disease most probably due to hepatitis infection and in
decompensated state with presence of ascites but no encephalopathy.
Causes of chronic liver disease:
1. Chronic alcohol ingestion

2. Viral hepatitis
3. Drug: methotrexate, methyldopa
4. Autoimmune hepatitis
5. Wilson disease
6. Primary biliary cirrhosis
7. Alfa 1-antitrypsin deficiency
8. Hemachromatosis
Investigation:
I would like to check full blood count because patient is prone to anemia due to gastrointestinal bleeding,
folate deficiency, or hypersplenism. Liver function test and coagulation profile to check synthetic function of liver
(albumin and PT). Investigation for the causes of chronic liver disease: hepatitis screening (HbsAg, HbeAg, anti
core antibody, anti-HCV), autoimmune hepatitis screening (antinuclear antibody, anti liver-kidney microsomal
antibody, anti smooth muscle antibody), antimitochondria antibody (for primary biliary cirrhosis), Wilson disease
( low serum ceruloplasmin and increase 24 hours urine copper secretion, serum protein electrophoresis for
alpha-antitrypsin, serum alpha-feto protein and hepatobiliary system ultrasound. Ascitic fluid tapping and send for
analysis.

Management:
Treat the complication and causes.

Treatment for variceal bleeding: resuscitate patient, wide bore needle insertion and cross match blood. Blood
transfusion or use fluid resuscitation while awaiting blood, intravenous proton pump inhibitor, early endoscopy to
indentify bleeding site and treat with endoscopic sclerotherapy with octreotide or ligation. If bleeding i s
u n c o n t r o l l e d , B a l l o o n T a m p o n a d e w i t h Sengstaken- Blackmoore tube can be used.
Surgery by mean of transjugular intrahepatic portosystemic stent shunt can temporarily reduce the portal
pressure. Definitive treatment is liver transplant.
Complication of chronic liver disease :

Portal hypertension (hepatorenal syndrome, variceal bleeding), hepatoma, ascites, infection eg spontaneous
bacterial peritonitis, hepatic encephalopathy, coagulopathy
Precipitating factor of hepatic encephalopathy :

Hemorrhage, electrolyte imbalance, protein diet, alcohol, trauma, infection, constipation, surgery (HEPATICS)
How to grade encephalopathy?

How to assess severity of cirrhosis?
In case of portal hypertension
What is the definition of portal hypertension?

pressure gradient between hepatic vein pressure and wedged hepatic vein pressure (corrected
sinusoidal pressure) >5 mmHg
What is the pathophysiology?
3 sites of increased resistance (remember pressure = flow x resistance)

pre-sinusoidal (e.g. portal vein thrombosis, schistosomiasis, sarcoidosis)
sinusoidal (e.g. cirrhosis, alcoholic hepatitis)
post-sinusoidal (e.g. right-sided heart failure, hepatic vein thrombosis, vena-occlusive
disease, constrictive pericarditis)
What is portal-systemic collateral pathway?
The sites of porto-systemic collateral connections

(a) from the portal vein through the right and left gastric veins to the esophageal veins and the hemiazygos
vein to the superior vena cava(SVC);
(b) from the superior mesenteric vein through retroperitoneal veins to the inferior vena cava (IVC);
(c) from the left portal vein through the (recanalized) umbilical vein to epigastric veins to the vena cava;
(d) from the inferior mesenteric vein through the superior hemorrhoidal vein to the middle and inferior
hemorrhoidal veins to the iliac veins
What is the treatment for portal hypertension?
Treatment is directed at the cause of portal hypertension

Medical care includes emergent treatment, primary and secondary prophylaxis, and surgical intervention
Emergent treatment
1) Promptly resuscitate and restore the circulating blood volume in patients with suspected cirrhosis and
variceal hemorrhage
2) Establish 2 large-bore venous accesses for blood transfusion
3) Insert a nasogastric tube to assess the severity of the bleeding, to decompress the stomach, and to lavage
the gastric contents to improve visualization during endoscopy which done later
4) While the blood is being cross-matched, start rapid infusion of 5% dextrose and colloid solution until the
blood pressure is restored and the urine output is adequate
5) Do baseline investigation, complete blood count (CBC), prothrombin/partial thromboplastin time (PT/PTT),
and international normalized ratio (INR) and liver function test, serum electrolyte levels, including
calcium,as well as serum creatine
6) The goal is to maintain hemodynamic stability and hemoglobin of approximately 8 g/d
7) As soon as the acute bleeding episode is adequately controlled, it is critical to initiate therapy to prevent
recurrent bleeding.
8) Perform endoscopy as soon as possible after the patient has been resuscitated by doing Endoscopic
variceal ligation to establish the cause of and to control the bleeding
9) Give vasoconstrictor, like Octreotide or vasopressin and terlipressin
10) High risk for developing severe bacterial infections, thus prophylactic antibiotic use (norfloxacin 400 mg PO
bid for 7 d; alternatively, PO ciprofloxacin or other broad-spectrum antibiotics) in the setting of acute
bleeding is recommended, including cirrhotic patients with upper GI bleeding with/without ascites. If oral
administration is not possible, intravenous (IV) ciprofloxacin may be used.
11) If there is massive bleeding and is not controlled by endoscopic and/or pharmacologic treatment, Balloon
tamponade should be employed and should serve only as a temporizing measure (should be used for < 24
h owing to risk of esophageal rupture/necrosis) (ie, bridging therapy) until definitive treatment (eg, TIPS,
surgical intervention) can be instituted.
Primary prophylaxis
In patients with small varices (< 5 mm or minimally elevated veins above the esophageal mucosal surface),
surveillance is preferred over other therapeutic modalities.
In patients with medium to large varices (>5 mm or esophageal vein raised beyond mucosal surface
occupying esophageal lumen) without a high risk of bleeding, a nonselective beta-blocker is the preferred first
line treatment and sometime esophageal varices ligation (EVL) may be considered
The average dose of propranolol is usually 40 mg twice daily

Nadolol dosing is half the daily dose of propranolol, administered once daily.
Secondary prophylaxis is used to prevent rebleeding. Usually combined EVL and pharmacotherapy which was
shown to be more effective
1) Non-selective beta blocker : Propranolol and nadolol
2) Endoscopic sclerotherapy is usually performed at weekly intervals. Approximately 4-5 sessions are
required for the eradication of varices
3) Endoscopic variceal ligation (EVL). Sessions are repeated at 7- to 14-day intervals until variceal
obliteration (which usually requires 2-4 sessions)
Long term monitoring: periodic surveillance endoscopy
Surgical intervention:
A transjugular intrahepatic portosystemic shunt (TIPPS) is a viable option and is less invasive for
patients whose bleeding is not controlled. However, if TIPPS is not available, then staple transection of
the esophagus is an option
Devascularization procedures- role in patients with portal and splenic vein thrombosis who are not
suitable candidates for shunt procedure
Orthotopic liver transplantation (OLT) considered for patients with end-stage liver disease (eg,
cirrhotic patients with Child-Pugh score =7 or Model for End-Stage Liver Disease [MELD] score =15

When shall we consider surgical intervention?
When endoscopic treatment and pharmacologic therapy have failed to control the bleeding. And failure is
defined as a single episode of clinically significant rebleeding (transfusion requirement of 2 U of blood or more
within 24 h, a systolic blood pressure < 100 mm Hg or a postural change of >20 mm Hg, and/or a pulse rate
greater than 100
What is the action of nonselective beta blocker?

Noncardioselective beta-blockers are used most commonly for primary prophylaxis of variceal bleeding, and
they include propranolol and nadolol. These nonselective beta-blockers reduce portal and collateral blood flow
as well as have smaller effects on the increase in portal resistance and decrease on portal pressure. Reduction
in cardiac output (via blockade of beta1 adrenoreceptors) occurs, as does splanchnic vasoconstriction (via
blockade of vasodilatory adrenoreceptors of the splanchnic circulation)
What is the contraindication of vasopressin

Vasopressin is the most potent splanchnic vasoconstrictor; it reduces blood flow to all splanchnic organs,
decreasing portal venous inflow and portal pressure. This agent should not be administered via a central line,
especially in elderly patients or patients with coronary artery disease, because of possible coronary vasospasm
and subsequent myocardial infarction (MI).
How to measure portal pressure?

Indirectly: hepatic vein pressure gradient (HVPG)
Direct: Measurement of splenic pulp pressure and direct measurement of the portal vein pressure are.
What is HVPG? And how does it measure?

The HVPG is the difference between the wedged hepatic venous pressure (WHVP) and free hepatic vein
pressure (FHVP).
A fluid-filled balloon catheter is introduced into the femoral or internal jugular vein and advanced under
fluoroscopy into a branch of the hepatic vein. Free hepatic venous pressure (FHVP) is then measured. The
balloon is inflated until it is wedged inside the hepatic vein, occluding it completely and thus equalizing the
pressure throughout the static column of blood. The occluded hepatic venous pressure (ie, wedged hepatic
venous pressure) minus the unoccluded, or free, portal venous pressure (ie, FHVP) is the HVPG.
What are the causes of recurrent portal hypertension and bleeding after a TIPPS procedure
Continued esophageal bleeding

Stent dysfunction due to stenosis, thrombosis, retraction, kinking, or displacement - As many as 50%
of shunts may occlude in 1 year
Hemobilia
Persistent gastric varices associated with spontaneous splenorenal collaterals or with massive
splenomegaly
What is the complication of TIPPS
TIPPS complications related to technique include the following:
Neck hematoma
Cardiac arrhythmia
Perihepatic hematoma
Rupture of liver capsule

Extrahepatic puncture of portal vein
Arterioportal fistula
Portobiliary fistula
TIPPS complications related to portosystemic shunting include:
hepatic encephalopathy (approximately 30%),

increased susceptibility to bacteremia,
liver failure.
TIPS-associated hemolysis (approximately 10%) and
stent infection.
In case of ascites
Pathophysiology of ascites
underfilling, overflow, and peripheral arterial vasodilation
due to portal hypertension, activates the plasma renin, aldosterone, and sympathetic nervous system,
resulting in renal sodium and water retention .
Under filling theory = inappropriate fluid sequestration within splancnic vascular bed secondary to
portal hypertension > decreased intravascular volume > kidneys retain more Na+ and water by
activating RAA system
Overflow theory = primary renal retention of Na+ and water in the abseonse of hypovolaemia
Peripheral arterial vasodilation=portal hypertension produce nitric oxide leads to vasodilation, which
causes decreased effective arterial blood volume.
Hypoalbuminemia and reduced plasma oncotic pressure favor the extravasation of fluid from the
plasma to the peritoneal fluid
What is mortality rate?

Ambulatory patients with an episode of cirrhotic ascites have a 3-year mortality rate of 50%. The development
of refractory ascites carries a poor prognosis, with a 1-year survival rate of less than 50%
High gradient (SAAG > 11g/L) potal hypertension Low gradient ( SAAG<11g/L) non portal hypertension
related related
Cirrhosis with portal hypertension Peritoneal carcinomatosis
Alcoholic hepatitis Peritoneal tuberculosis
Cardiac failure Nephrotic syndrome
Budd chiari syndrome Serositis
Fulminant hepatic failure Pancreatic/ biliary ascites
Massive liver metastasis
Myxedema
What is the meaning Serum albumin value-ascites albumin values > 11g/L
It mean it is related to portal hypertension , and for those < 11g/L mean it is not related to portal hypertension
What procedure you want to done for patient with ascites?

Abdominal paracentesis

What investigation should be sent for peritoneal fluid?
peritoneal fluid should be sent for cell count, albumin level, culture, total protein, Gram stain, and cytology.
What other investigation to be done?

1) Bloods
FBC = WBC (SBP), HCT (hypovolemia)
U/E/Cr to look for renal impairment
LFT to look for liver impairment, low albumin
ESR, CRP
2) ECG, Cardiac enzymes, CXR to look for Congestive cardiac failure
3) Urine
Urine dipstick = proteinuria, hematuria
UFEME
Urine phase contrast microscopy
4) Abdominal x-ray: More than 500 mL of fluid is usually required for ascites to be diagnosed based on
findings from abdominal films.
5) Ultrasonography: for detection of ascites
6) CT scan: can look for the cause and also demonstrate well for ascites.
What is the staging of ascites?

Ascites may be semi-quantified using the following system:
Stage 1+ is detectable only after careful examination.

Stage 2+ is easily detectable but of relatively small volume.
Stage 3+ is obvious, but not tense, ascites.
Stage 4+ is tense ascites.
How do you want to manage patient with ascites?

For non refractory ascites
I. Low salt diet: Sodium restriction 500 mg/d (22 mmol/d)
II. Fluid restriction
III. Diuretics-spironolactone and frusemide
IV. aim for weight loss 0.5-1 kg/d, more if concomitant peripheral edema (which is mobilized quicker than
ascitic fluid); overly rapid weight loss increases risk of renal failure
For refractory ascites

I. Therapeutic paracentesis : performed in patients who require rapid symptomatic relief for refractory or
tense ascites.
When small volumes of ascitic fluid are removed, saline alone is an effective plasma expander.
The removal of 5 L of fluid or more is considered large-volume paracentesis.
Total paracentesis, that is, removal of all ascites (even >20 L), can usually be performed safely.
Supplementing 5 g of albumin per each liter over 5 L of ascitic fluid removed decreases complications
of paracentesis, such as electrolyte imbalances and increases in serum creatinine levels secondary to
large shifts of intravascular volume.
II. Transjugular intrahepatic portosystemic shunts: interventional radiologist places a stent percutaneously
from the right jugular vein into the hepatic vein, thereby creating a connection between the portal and
systemic circulations.

III. Other shunt can be done peritoneovenous shunt
IV. Liver transplantation
What is the primary prophylaxis of SBP?

Primary prophylaxis with norfloxacin in patients with advanced cirrhosis reduced SBP, HRS( hepatorenal
syndrome), and improved 1 yr survival
In case of hepatic encephalopathy
What is the definition of hepatic encephalopathy?

Hepatic encephalopathy is defined as a spectrum of neuropsychiatric abnormalities in patients with liver
dysfunction, after exclusion of other known brain disease.
What is the stage of hepatic encephalopathy?

Stages
I: apathy, restlessness, reversal of sleep-wake cycle, slowed intellect, impaired computational abilities,
impaired handwriting
II: asterixis, lethargy, drowsiness, disorientation
III: stupor (rousable), hyperactive reflexes, extensor plantar responses
IV: coma (response to painful stimuli only)
What are the precipitant of hepatic encephalopathy?

nitrogen load (GI bleed, protein load from food intake, renal failure, constipation)
drugs (narcotics, CNS depressants)
electrolyte disturbance (hypokalemia, alkalosis, hypoxia, hypovolemia)
infection (spontaneous bacterial peritonitis)
deterioration in hepatic function or superimposed liver disease
What clinical test can be used to evaluate hepatic encephalopathy?

Neurophysiologic tests in common use are the number connection test, the digit symbol test, the block design
test, and tests of reaction times to light or sound (eg, critical flicker test).
Current recommendation is psychometric hepatic encephalopathy score (PHES) .The PHES is composed of five
tests, number connection test-A (NCT-A), number connection test-B (NCT-B), serial dotting test (SDT), line
tracing test (LTT) and digit symbol test (DST)
What is management of hepatic encephalopathy?

General management recommendations include the following:
Exclude non-hepatic causes of altered mental function.

Consider checking an arterial ammonia level in the initial assessment of a hospitalized patient with
cirrhosis and with impaired mental function.
Precipitants of hepatic encephalopathy, such as hypovolemia, metabolic disturbances, gastrointestinal
bleeding, infection, and constipation, should be corrected.
Avoid medications that depress central nervous system function, especially benzodiazepines. Patients
with severe agitation and hepatic encephalopathy may receive haloperidol as a sedative.
Patients with severe encephalopathy (ie, grade 3 or 4) who are at risk for aspiration should undergo
prophylactic endotracheal intubation. They are optimally managed in the intensive care unit.
Low-protein diets: decrease dietary protein to 50 g/d; vegetable protein is better tolerated than animal
protein

Take lactulose as a first line treatment, which initial lactulose dosing is 30 mL orally, daily or twice
daily. The dose may be increased as tolerated. The lactulose is titrated to achieve 2 to 3 soft stools
per day
second line treatment is giving Neomycin and other antibiotics, such as metronidazole, oral
vancomycin, paromomycin, and oral quinolones, are administered in an effort to decrease the colonic
concentration of ammoniagenic bacteria. Initial neomycin dosing is 250 mg orally 2-4 times a day.
Doses as high as 4000 mg/d may be administered.
Non-absorbable antibiotic rifaximin also can be used.
Other pharmacological treatment include use of L-ornithine L-aspartate (LOLA), Zinc and L-carnitine.
In case of sleep disturbances, hydroxyzine (25 mg) at bedtime can be given but may used in caution as
it may worsening the hepatic encephalopathy
What is the action of lactulose?

It prevents diffusion of NH3 (ammonia) from the colon into blood by lowering pH and forming non-diffusible
NH4 (ammonium)
What is the side effect of overdosage of lactulose?

Overdosage can result in ileus, severe diarrhea, electrolyte disturbances, and hypovolemia

Case 7 : Graves disease :
Introduction:
Graves disease is autoimmune disease with presence of thyroid stimulating antibodies which bind and
stimulate the receptor. This antibody is found in 90% of patient. Patient will present with hyperthyroid, goiter,
eyes sign, thyroid acropachy and pretibial myxoedema. Commoner in females. Associated with other
autoimmune disease.
Presentation:
This is a young lady who sits comfortably on chair appears well with appropriate attire, thin and not irritable.
There is a diffuse thyroid swelling which move with deglutition and not with protrusion of tongue. The swelling is
butterfly in shape measuring 10 x 15cm, smooth surface, well define margin, soft in consistency with lower border
can be appreciated. The mass is non tender, no increase temperature, no bruit, and not attach to overlying or
underlying structure. Otherwise, tracheal is not deviated, carotid pulse can be felt and no cervical
lymphadenopathy. There is no evidence of retrosternal expansion.
On peripheral examination, the pulse rate is 100 beats per minute regularly regular. There is thyroid acropathy,
sweaty warm palm with tremor, exophthalmos, and brisk deep tendon reflex. Otherwise no opthalmoplegia, no
lids lag or lids retraction, no diplopia, no proximal muscle weakness, and no pretibial myxoedema.
I would like to complete my examination by checking the blood pressure, cardiovascular examination and
respiratory examination.
This lady has diffuse thyroid swelling most probably due to Graves disease and currently in hyperthyroid state.
Differential diagnosis for diffuse goiter :
1. Simple diffuse thyroid

2. Hashimoto thyroiditis
3. Subacute thyroiditis
Investigation:
I would like to check thyroid function test where I expect the TSH will be low and free T4 will be high. Thyroid
stimulating antibodies will be presence in 90% of patient. Neck ultrasound to determine solid or cystic
component of the mass.

Management:
There is three modality of treatment: medical, radioiodine and surgical. The antithyroid drugs are carbimazole and
propythiouracil which decrease thyroid peroxidase. Beta blocker eg: propranolol to control adrenergic
symptom and decrease peripheral conversion of T4-T3. Radiotherapy is treatment of choice when fail medical
treatment. Surgery is subtotal or total thyroidectomy.
WHO grading of goiter :
Grade0: no palpable or visible thyroid

Grade 1: palpable goiter(A), palpable and visible with neck extension (B)
Grade 2: goiter visible at normal position
Grade 3: large goiter visible from a distance
Indication for surgery :

Patient preferences, large goiter, fail medical treatment after trial of 2 years, non compliance, recurrent with no
radioiodine facility.
What are the complications of thyroidectomy?
Immediate: hemorrhage, respiratory obstruction, hoarseness of voice due to recurrent laryngeal nerve
injury
Early: infection
Late: hypothyroidism, hyperthyroidism, hypoparathyroidism
How to manage thyroid storm?
Precipitating factors: infection, surgery, trauma, myocardial infarction

Presentation: agitation, fever, tachycardia, atrial fibrillation, hepatic dysfunction
Treatment: high mortality thus needs to admit to ICU. Give antithyroid drug, propythiouracil is
preferable because decrease peripheral conversion of T3-T4. Sodium iodine or lugols iodine to
decrease hormone releases, which give 1 hour after initial dose of antithyroid drug. Give IV
dexamethasone to decrease hormone release and peripheral conversion. Give IV propanolol if no heart
failure; oxygen, diuretic and digoxin if heart failure presence. Well hydration, tepid sponge with
antipyrexia. Remove or treat the underlying cause.
What is the definition of the Grave disease?

It is a syndrome characterised by hyperthyroidism with any one of: diffuse goiter, ophthalmopathy,
dermopathy.

How to differentiate between hyperthyroidism and hypothyroidism
Clinical feature of thyrotoxicosis
Clinical feature of hypothyroidism ?

What is the pathophysiology of grave disease?
autoimmune disorder due to a defect in T-suppressor cells

B lymphocytes produce TSI that binds the TSH receptor and stimulates the thyroid gland
immune response can be triggered by postpartum state, iodine excess, lithium therapy, viral or bacterial
infections, glucocorticoid withdrawal
Cause of ophthalmopathy uncertain
Dermopathy may be related to cutaneous glycosaminoglycan deposition
What is the cause of thyrotoxicosis? GET A TSH

Graves disease
Exogenous hyperthyroidism( iatrogenic, iodine, factitious)
Toxic multinodular goiter
Adenoma( toxic)
TSH producing tumour ( pituitary,hydatidiform mole, choriocarcinoma)
Subacute ( de Quervain ) thyroiditis
Hashimoto thyroiditis
What is the sign of grave ophthalmopathy? NO SPEC

No sign and symptoms
Only sign of upper lid retraction and stare
Soft tissue involvement
Proptosis
Extraocular muscle weakenss
Corneal involvement
Sight loss- optic nerve compression
What is the cardiac manisfestation of thyrotoxicosis?

High output cardiac failure
Atrial fibrillation
Angina
Thyrotoxic cardiomyopathy
What are the disease that is associated with Grave disease

Addisons disease
Type 1 diabetes mellitus
Hashimotos disease
Pernicious anemia
Myasthenia gravis
Hypokalemic period paralysis
Vitiligo
What is the manifestation of grave disease and its pathophysiology?
Pituitary Suppress THS Decrease expression of

tyrotropin subunit
Heart Increase heart rate and contractility Increase serum natriuretic
peptide
Liver Increase peripheral T3, decrease LDL Increase type 1 5-deiodinase
and LDL receptor
Bone Increase bone turnover, osteoporosis Rises osteocalcin, alk phosand
urinary N-telopeptide
Gental male Decrease libido and erectile dysfunction Increase sex hormone globulin
and decrease testosterone
Genital female Irregular menses Oestrogen antagonism
metabolic Rises thermogenesis and oxygen uses Increases fatty acid oxidation,
and Na-K ATPase
White fat Decrease fat mass Increase adrenergic- mediated
lipolysis
CNS Stiff person syndrome Antibodies to glutamic acid
decarboxylase
Muscle Proximal myopathy Increase sarcoplasmic reticulum
Ca 2+ activated ATPase
thyroid Increase secretion of T3 and T$ Increase type 2 5-deiodinase
What is the action of the propylthiouracil (PTU) or methimazole (MMI), side effect and contraindication
inhibit thyroid hormone synthesis by inhibiting peroxidase-catalyzed reactions, thereby inhibiting
organification of iodide, blocking the coupling of iodotyrosines, and inhibiting peripheral deiodination
ofT4 to T3
major side effects: hepatitis and agranulocytosis
minor side effects: rash, fever and arthralgias
iodinated contrast agents: sodium ipodate and iopanoic acid can inhibit conversion ofT4 to T 3 and are
especially effective in combination with MMI
MMI preferred vs. PTU due to longer duration of action, more rapid efficacy, and lower incidence of
side effects
MMI contraindicated in pregnancy (teratogenicity)
How to you want to give anti-tyroid medication?

Two strategies ( equally effective) by titration and block replace
What is the complication of thyroid ablation with radioactive 1311?

high incidence of hypothyroidism after 131 I, requiring lifelong thyroid hormone replacement, and in active
hyperthyroidism at risk of thyroid storm
contraindicated in pregnancy, lactation
How to treat Grave ophthalmopathy

Mild disease can be treated symptomatically: artificial tears, sunglasses, avoid dust, elevation of bed when
sleeping to reduce periorbital edema)
high dose prednisone in severe cases
orbital radiation, surgical decompression
What do you understand about TSH?

TSH
sensitive TSH (sTSH) is the best test for assessing thyroid function
TSH varies through the day, thus during monitoring , try to do at the same time
hyperthyroidism
primary: TSH is low because of negative feedback from increased levels of circulating T 3 and T 4
secondary: increased TSH which results in increased T 3 and T 4
hypothyroidism
primary: increased TSH because of less negative feedback from T3 and T4
secondary: TSH is low with variable response to TRH depending on the site of the lesion(pituitary or
hypothalamic)

Case 8 : Rheumatoid Arthritis
Introduction :
RA is the most common inflammatory arthritis in women. The typical clinical phenotype of RA is a symmetrical,
deforming, small and large joint polyarthritis, often associated with systemic disturbance and extra-articular
disease.
Before the age of 45, the female : male ratio is 6:1. Prevalence increases with age, with 5% of women and 2%
of men over 55 years being affected.
Examination steps :
1. Greet but dont shake the hand. Offer pillow to allow patients hand to put on it in prone position.
2. General Cushingoid facies, Weight, Dry Eyes, Joint deformity
3. Look - Describe from distal to proximal or vice versa.
a. Nail Psoriatic nails, vasculitic changes, splinter hemorrhage (SLE), periungual telangiectasiae,
Raynauds phenomenon, Pulp atrophy, Ridging, Pitting, Onycholysis
b. PID, DIP - skin changes, swelling, subluxation, deformity Swan neck and boutonniere deformity of
fingers,
OA changes Heberdens nodes, Bouchards, nodes,
Thumb squaring of thumb or Z deformity
c. MCP skin changes, swelling, deformity ulnar deviation, volar subluxation
d. Wrists skin, scars, redness, atrophy, rash, Tight shiny skin, prominent styloid
e. Palm muscle wasting, skin - palmar erythema, scars, vasculitic changes, palmar creases for
anaemia, Raynauds phenomenon
f. Others: Psoriatic plagues ( elbow, hairline)
4. Feel
a. Temperature? Tenderness?
b. Wrist subluxation, CREST sign (Crepitation, Range of movements, Effusions, Synovitis, ulnar styloid
tenderness)
c. MJP, PIP, DIP CRES + subluxation
d. Palmar tendon crepitus

e. Carpal tunnel syndrome Tinels sign
5. Active movement
a. Wrist flexion and extension
b. Abduction and adduction of thumb
c. Opposition of fingers
d. Prayers sign and Reverse Prayers sign
e. Test for trigger finger ask patient flex and extend finger
6. Hand function
a. Practical button, key grip, scratch back
7. Complete
a. PULSE
b. Elbow psoriatic plagues, rheumatoid nodules
c. Face
Eyes (episcleritis), scleromalacia, keratoconjunctivitis sicca, cataract (steroid)
Dry mouth,
TMJ crepitus,
Scalp psoriasis over hairline or back of ear
Neck ask patient flex neck and ask if presence of electrical shock wave suggestive of atlanto-axial
deformity
Precordium Aortic/mitral regurgitation, Loud P2, pericardial rub
Lungs Pleural rubs, Basal crackles interstitial fibrosis, pneumonia
Abdomen splenomegaly
Legs ruptured bakers cyst, ulcers (vasculitis), mononeuritis multiplex
Presentation:
Sir, this is a middle-aged lady sitting on the chair comfortably. She has Cushingnoid features as evidenced by
fullness over the supraclavicular fat pad and round face.
The patient has bilateral symmetrical deforming polyarthropathy affecting the metacarpal and interphalangeal
joints sparing the DIP and wrist joint. I noted volatile subluxation and ulnar deviation over MCP joint. The
significant deformities are swan neck deformities over the (which finger) and boutonnires deformity of
(fingers). I also see Z deformity over right thumb. There is skin thinning and I do not notice any rash or nail
changes such as pitting or ridging.
Over the palmar surface, there is thenar wasting and erythema of the palms. No vasculitic ulcers or raynauds
phenomenon noticed. No scars.
On palpation, there is no raise in temperature and tenderness. No crepitus, no swelling, no effusions over the all
wrist, MJP, PIP, DIP joints.
Active movements limited as patient unable to do prayers sign and opposition of fingers.
In terms of hand function, it is impaired as patient unable to button her clothes and do key grip.

I would like to complete my examination by (Refer above)
Provisional diagnosis:
She has bilateral symmetrical deforming polyarthritis due to rheumatoid arthritis, currently in remission and
functional status is impaired.
Differential Diagnosis:
Lupus arthritis
Infective cause : dengue, lyme, rheumatic fever and other viral infection.
Psoriatic arthritis
Reactive arthritis
Osteoarthritis
Jaccoud arthropathy
How would you manage this case?

I would treat early disease aggressively as there is a window opportunity. My goals would be to relieve
symptoms, prevention of symptoms, preserve function, maintain lifestyles. There are two principles
nonpharmacological and pharmacological.
For the non-pharmacological part, I would opt for multidisciplinary approach and refer her to
physiotherapist, social workers, surgeon and occupation therapist.
For the pharmacological part, I would relief her pain by giving her NSAIDS or COX 2 if severe GI
symptoms. However, I would be watch out for renal impairment, cardiac failure and uncontrolled
hypertension.
Early DMARDS is helpful in stabilizing the disability but not reverse it. Examples include
hydrochloroquine, methotrexate, Sulphasalazine, Leflunomide.
They take 6-12 weeks for symptomatic benefit.
While waiting for DMARDS to work, steroid up to 7.5 mg can be given and stop gradually after 3 to 4
months. Intra-articular steroid can be used as adjunct too.
If patient is resistant, TNF alpha inhibitors like etanercept, adalimumab or infliximab can be given.
However, before initiation of this, TB work out need to be done as it can reactivate TB. If she is positive,
treat her as latent TB by giving isoniazide and start biological agent after 1 month of isoniazide.
In seropositive arthritis, never stop biological agent once it is started.
1. What is definition of RA
It is chronic, symmetric, erosive synovitis of peripheral joints (i.e. wrists, MCPs, MTPs) and is
characterized by a number of extra-articular features.
2. What is the criteria of the RA?
Total score of 6 or more classifies patient as definite RA.

Patient must have at least 1 joint with definite clinical swelling, not better explained by another disease

3. What are the common joint involvement
4. What is the etiology?
The cause of RA is unknown. Genetic, environmental, hormonal, immunologic, and infectious factors may
play significant roles. Socioeconomic, psychological, and lifestyle factors (eg, tobacco use, the main
environmental risk) may influence disease outcome.
Infection agent: Mycoplasma organisms, Epstein-Barr virus (EBV), and rubella virus.

5. What investigation that you want to done on her?
For diagnosis purpose, I would like to check the rheumatoid factors, ACCP and acute phase reactants like
ESR and CRP. On top of it, I would like to do FBC to look for anaemia, increase platelets, renal function
test, liver function test, imaging of the joints to look for progression of destruction of the joints, soft tissue
swelling, juxta-articular osteopenia and reduced joint spaces. USG (detect early stage) and MRI can identify
synovitis more accurately.
6. What are the other causes that can cause RF to be positive?

Rheumatic diseases scleroderma, SLE, Sjogrens, disease, MCTD
Infections bacterial endocarditis, syphilis, TB, hepatitis
Lung Interstitial fibrosis, chronic bronchitis, silicosis
Liver cirrhosis, sarcoidosis
Healthy people 1-2% increase with age
7. What is the complication of RA?

Anemia
Infections Patients with RA are at greater risk for infections; immunosuppressive drugs further
increase that risk
GI problems Patients with RA may experience stomach and intestinal distress; however, lower rates
of stomach and colorectal cancers have been reported in RA patients
Osteoporosis This condition is more common than average in postmenopausal women with RA; the
hip is particularly affected; the risk of osteoporosis appears to be higher than average in men with RA who
are older than 60 years
Lung disease A small study found a high prevalence of pulmonary inflammation and fibrosis in
patients with newly diagnosed RA, but this finding may be associated with smoking
Sjgren syndrome Keratoconjunctivitis sicca is a common complication of RA; oral sicca and salivary
gland enlargement are less common
Felty syndrome This condition is characterized by splenomegaly, leukopenia, and recurrent bacterial
infections; it may respond to disease-modifying antirheumatic drugs (DMARDs)
Lymphoma and other cancers RA-associated immune system alterations may play a role; aggressive
treatments for RA may help prevent such cancers
8. What are the causes of anaemia in RA?

RA can cause all 3 types of anemia :
Microcytic (PUD 2 steroid/NASAIDS),
Macrocytic (associated with pernicious anemia, autoimmune; folate deficiency secondary to
methotrexate)
Normocytic (chronic disease, hypersplenism in felty, aplastic anemia 2 gold/penicilamine).
9. What are the pulmonary manifestations of RA?

The respiratory complications are listed from proximal to distal airway:
Cricoarytenitis
Bronchiolitis obliterans & organizing pneumonia (BOOP)
Pulmonary fibrosis (MTX) / Pulmonary hypertension.
Caplan nodules ( coal dust exposure)
Pleural effusion
10. What are ophthalmic manifestations in RA?
Extraocular muscle (Mononeuritis multiplex, myasthenia secondary to penicillamine)
Sclera (Episcleritis, scleritis, scleromalacia perforans)
Conjunctiva (Pallor, keratoconjunctivitis sicca secondary to Sjogren syndrome)
Lens & vitreous (Cataract & glaucoma secondary to prolonged steroid)
Fundus (Vasculitis, chloriquine Bulls eye maculopathy, gold retinopathy)
11. What are the neurological manifestations in RA?

Peripheral neuropathy glove-and-stocking sensory loss
Mononeuritis multiplex
Entrapment neuropathy eg. Carpal tunnel syndrome
Cervical disease or atlanto-axial subluxation causing cervical myelopathy
12. What are the dermatological manifestations in RA?

Vasculitis (Small vessels Palpable purpura, nail fold/digital infarct; Larger vessel skin ulcer,
digital gangrene).
Palmar erythema
Rheumatoid nodules (20% patient @ olecranon process)
Raynauds phenomenon
13. What is the goal of treatment?

The treatment of rheumatoid arthritis (RA) is directed toward the control of synovitis and the
prevention of joint injury.
Principles include
Early recognition and diagnosis

Care by an expert in the treatment of rheumatic diseases, such as a rheumatologist
Early use of DMARDs for all patients diagnosed with RA
Importance of tight control with target of remission or low disease activity
Use of anti inflammatory agents, including nonsteroidal anti inflammatory drugs (NSAIDs) and
glucocorticoids, only as adjuncts to therapy
14. What are the non pharmacologic treatment of the RA

Nonpharmacologic treatments are including exercise, diet, massage, counseling, stress reduction,
physical therapy, and surgery
15. What is the pharmacologic treatment?

nonsteroidal anti-inflammatory drugs (NSAIDs), nonbiologic and biologic disease-modifying
antirheumatic drugs (DMARDs),analgesics, immunosuppressants, and corticosteroids.
16. What management should be given to the patient if patient become pregnant?
In pregnant patients with RA, no special obstetric monitoring is indicated beyond what is performed for
usual obstetric care. However, some of the medications used in treating RA can have adverse effects
on the fetus and may have to be discontinued several months before conception is planned.
Medications considered low-risk in pregnancy include immunomodulating drugs, low-dose
corticosteroids, antimalarial agents, SSZ, and azathioprine. Patients with RA must be monitored closely
after delivery because of the potential for arthritis flare ups to occur during the postpartum period.
17. How would you suggest this lady about the medication DMARDS if she wants to get pregnant?
If she is on methtrexate, stop for 3 cycles before she conceived.
If she is on Leflunomide, stop for 2 years.
Other option would be ingestion of cholestryramine to wash out the drugs from blood.
18. What drug is contraindicated in pregnancy with RA?

NSAIDs should be avoided in the third trimester.
MTX is contraindicated in pregnancy, because it has teratogenic effects, including craniofacial
abnormalities, limb defects, and central nervous system (CNS) defects
Leflunomide is also contraindicated.
Both MTX and leflunomide should be discontinued at least 3 months before pregnancy,
19. What is the surgical treatment of RA

Surgical treatments for RA include synovectomy, tenosynovectomy, tendon realignment, reconstructive
surgery or arthroplasty, and arthrodesis.
20. What screening should be done before you initiate the pharmacological treatment?
Screening for tuberculosis: In patients with RA who are under consideration for beginning or receiving
biologic agents, screening for latent tuberculosis (TB) infection (LTBI) is recommended, regardless of
whether these individuals have risk factors for LTBI. Nevertheless, clinicians should review patients
medical histories to identify the following LTBI risk factors
21. What vaccination should be given for the patient?
All killed vaccines (pneumococcal, intramuscular influenza, and HBV) and human papillomavirus (HPV)
recombinant vaccine, and herpes zoster virus (HZV) live attenuated vaccine
22. How will you start the medication if this is patients presenting with an initial onset of previously
undiagnosed possible RA?
The patient requires symptomatic treatment with NSAID therapy and rapid referral for definitive
diagnosis and institution of DMARD therapy.
23. How will you treat the patient who has flare of RA?
Treatment consists of rest, NSAIDs, DMARDs, short courses of steroids (2-4 weeks), and, possibly,
intra-articular steroid injections. Pain relief is important and may necessitate short-term use of narcotic
analgesics.
24. What are the nonbiologic DMARDs

It is include hydroxychloroquine (HCQ), azathioprine (AZA), sulfasalazine (SSZ), methotrexate (MTX),
leflunomide, cyclosporine, gold salts, D-penicillamine, and minocycline.

25. What is the choice of DMARD?
The choice of DMARD depends on a number of factors, including the stage and severity of the joint
condition, the balance between possible side effects and expected benefits, and patient preference.
Before treatment begins, the patient and clinician should discuss the benefits and risks of each type of
therapy, including possible side effects and toxicities, dosing schedule, monitoring frequency, and
expected results.
In some cases, one DMARD is used. In others, more than one medication may be recommended.
Sometimes a patient must try different medicines or combinations to find one that works best and that
has the fewest side effects. A patient who does not respond completely to a single DMARD may be
given a combination of DMARDs, such as methotrexate plus another medication.
The most common DMARDs are methotrexate, sulfasalazine, hydroxychloroquine, and leflunomide.
Less frequently used medications include gold salts, azathioprine, and cyclosporine. Methotrexate
(MTX) is recommended as first-line therapy; sulfasalazine (SSZ) or leflunomide can be substituted if
there are contraindications to MTX
26. What are the common side effects of DMARDS?

Myelosuppresion leads to pancytopenia regular FBC monitoring required.
Methotrexate pneumonitis(chest xray), oral ulcers, hepatotoxicity (give Folic acids as supplement)
Hydrochloroquine irreversible retinopathy
Sulfasalazine Rash, reduce sperm count, oral ulcers
Leflunomide teratogenicity
27. What is the side effect of methotrexate? And what should done to monitoring the side effect?
Bone marrow suppression, hepatotoxicity, and lung damage. Thus, a chest x-ray is recommended
before beginning treatment, and regular blood testing is recommended. While taking methotrexate,
most patients take folic acid 1 mg daily or folic acid 5 mg weekly to reduce the risk of certain side
effects, such as upset stomach, sore mouth, low blood cell counts, and abnormal liver function.
28. What is the side effect of Hydroxychloroquine and how to monitoring the side effect?
Side effect is the risk of damage to the retina of the eye in high dose. An eye examination is
recommended before starting treatment and periodically thereafter. It is common to have an eye
check-up done once each year.
29. What are the biological agents?

Biologic agents, sometimes called biologic DMARDs, including etanercept, adalimumab, infliximab,
certolizumab pegol, and golimumab, which are all part of a class of drugs called tumor necrosis factor
(TNF) inhibitors, and a variety of other agents with different targets, including anakinra, abatacept ,
rituximab, and tocilizumab.
30. What is the adverse effect of using biological agent?

Adverse effects associated with the biologic agents include the generation of antibodies against these
compounds, emergence of antinuclear antibodies (ANAs), occasional drug-induced lupus like
syndromes, and infections (including tuberculosis). Rarely, demyelinating disorders and bone marrow
suppression occur.

31. How do you want to monitor the patient in follow up?
Patients with active disease should be monitored every 3 months, and treatment should be adjusted if
there is no improvement at 6 months. Low disease activity or remission should be targeted for all
patients with early or established disease who are receiving a DMARD or a biologic agent.
32. What syndromes is involved in RA

Sjogrens syndrome: keratoconjunctivitis sicca and xerostomia
Caplans syndrome: multiple pulmonary nodule and pneumoconiosis
Felty syndrome: triad of arthritis(RA), neutropenia, and splenomegaly
33. what is the poor prognostic feature of RA

young age of onset, high RF titer, elevated ESR, activity of >20 joints, and presence of EAF.
34. What is the classification of global functional status in RA?

Classification of Global Functional Status in RA (American College of Rheumatology, 1991)
Class 1: able to perform usual ADLs (self-care, vocational, avocational)
Class II: able to perform self-care and vocational activities, restriction of avocational activities
Class III: able to perform self-care, restriction of vocational and avocational activities
Class IV: limited ability to perform self-care, vocational, avocational activities

Case 9 : Ankylosing Spondylitis :
Introduction :
It is one of the four seronegative arthritis. It is common in male with the ratio of 9 : 1. It is associated with HLA
B27 antigen.
Examination steps :
1. Greet, seek permission, chaperone and expose the upper body of the patient.
2. Ask the patient to stand and walk from one end to the other end. Look for stoop posture and stiffness
when he walks.
3. Ask the patient lean against the wall. Measure the occiput to wall distance. Look for question mark
posture and lost of lumbar spine lordosis.
4. Ask the patient take a step forward. Do Schobers test. Examine cervical and lumbar spine mobility
including flexion, extension, lateral flexion and lateral rotation. Feel for spinal tenderness.
5. Ask the patient sit down. Measure the chest expansion by measuring tape.
6. Inspect for red eye, ausculate the lung and heart. Look for psoriatic plaque to exclude psoriatic
arthropathy. Look for Achilles tendinitis and plantar fasciitis.
7. Lie the patient down. Examine for sacroiliac spine tenderness by doing Patricks test.
Presentation :
Sir, this is a middle age gentleman who appears to be well. He does not appear to be in respiratory distress or in
pain. He has a stoop posture and appears to be stiff when he walks.
He has a question mark posture and a positive occiput-to-wall test of 4cm. He is noted to have lost of lumbar
lordosis and his Scobers test is positive.
In term of mobility, he has restricted flexion and extension of cervical and lumbar extension of approximately
0-10 degree. His lateral flexion and lateral rotation are fairly satisfactory. Otherwise, he has no spinal
tenderness. Patricks test is negative as well.
His chest expansion is restricted with 1cm expansion. Otherwise, he has no red eye to suggest anterior uveitis or
psoriatic plaque to suggest psoriatic arthropathy. Per auscultation, lung is clear and first and second heart sound
with no murmur heard. He also has no evidence of Achilles tendinitis and plantar fasciitis.
I would like to complete my examination by abdomen examination to look for hepatosplenomegaly, examine the
peripheral joints and genitalia to exclude possibility of Reiters disease. I would also like to ask the patient for any
history of chronic diarrhea or PR bleeding.
In summary, this is a middle age gentlemen with ankylosing spondylitis and functionally he has restricted
mobility of spine. There is no features to suggestive complications such as pulmonary fibrosis or aortic
regurgitation.

Differential diagnosis :
1. Psoriatic arthropathy
2. Reactive arthritis
3. Osteoarthritis of the spine
4. Enteropathic arthropathy
Investigation :
In term of investigation, I would like to do HLA B27 testing, ESR/CRP, spine x-ray and MRI spine if indicated. HLA
27 is positive in 95% of the cases. However, HLA B27 is not diagnostic of AS. CRP or ESR level is important in
determining inflammatory activity in the patient. In the spine x-ray, I would look for sacroiliac joint
erosion/sclerosis, squaring of vertebral, ossifications of anterior longitudinal ligament, marginal
syndesmophytes and bamboo spine. MRI will be helpful if there is no changes on x-ray.
Management :
The primary goal of management for patients with AS is to maximize long term health-related quality of life. The
treatment aims are to get adequate pain relief, restoration of function, prevention and treatment of
complications.
The treatment options include non-pharmacological and pharmacological. Non-pharmacological treatment is

mainly rehabilitation to prevent joint stiffness and strengthening of the muscles. Pharmacological options
includes paracetamol and NSAIDs for pain relief, glucocorticoids to reduce inflammatory activity, DMARDS for
peripheral artheritis and biological agents for axial and peripheral involvlement. Choices of DMARDS includes
methotrexate and sulfasalazine whereas biological agents includes infliximab, adalimumab, etanercepts. And treat
other extra-articular manifestation.

What are the seronegative arthritis?
Ankylosing spondylitis, reactive arthritis, psoriatic arthritis and arthritis of inflammatory bowel disease.
What are the common features of seronegative arthritis?

They have oligoarthritis presentations, more commonly involve the lower limb and sacroiliac joints. There is
familial tendencies and RF is negative.
What are the complications of AS?

7 As of AS : Apical lung fibrosis, Aortic regurgitation, Achilles tendinitis, Anterior Uveitis, Amyloidosis,
Autoimmune bowel disease, Atlantoaxial subluxation.
How do you diagnose AS?

Most cases of AS can be diagnosed with history taking, clinical examination, simple blood tests and appropriate X-
rays. Currently, there is no universal criteria to diagnose AS. There is criterias to diagnose
spondyloarthropathy which is Assessment of SpondyloArthritis International Society (ASAS) criteria.

enthesitis (inflammation of tendon or ligament at site of attachment to bone)
inflammation osteopenia erosionossificationosteoproliferation (syndesmophytes)
What are the features suggestive of inflammatory back pain?

What is the natural history of AS?
About 40% go on to develop severe spinal restriction, about 20% have significant disability, early peripheral
joint disease, particularly of the hip indicates a poor prognosis.
Remember rule of 2S
AS occurs in 0.2% of the general population, 2% of HLA-B27 positive individuals, 20% of HLA-B27 positive
individuals with affected family member
What is the symptom and sing involve in axial

mid and lower back stiffness, prolonged morning stiffness, night pain, persistent buttock pain, painful
sacroiliac joint ( + Faber test)
spinal restriction (decreased ROM): lumbar (decreased Schober), thoracic (decreased chest wall
expansion, normal >5 em at T4), cervical (global decrease, often extension first)
postural changes: decreased lumbar lordosis + increased thoracic kyphosis + increased
cervical flexion= increased occiput to wall distance (>5 em)
How do you evaluate the patient of AS?

Patient self assessment of pain (1-10)
Bath Ankylosing Spondylitis Disease Activity index (BASDAI)
Daily activities that are limited by disease
Physician's global assessment on a scale of 1 (mild) to 4 (severe)
ESR or CRP
What is the prognosis of AS?
spontaneous remissions and relapses are common and can occur at any age
function may be excellent despite spinal deformity
favourable prognosis if female and age of onset >40 yrs
early onset with hip disease may lead to severe disability; may require arthroplast

Case 10 : Scleroderma :
Introduction :
Scleroderma is derived from the Greek words skleros (hard or indurated) and derma (skin). Systemic sclerosis is
used to describe a systemic disease characterized by skin induration and thickening accompanied by various
degrees of tissue fibrosis and chronic inflammatory infiltration in numerous visceral organs, prominent
fibroproliferative vasculopathy, and humoral and cellular immune alterations.
The American College of Rheumatology (ACR) criteria for the classification of systemic sclerosis require one
major criterion or two minor criteria, as follows:
Major criterion
Proximal scleroderma is characterized by symmetric thickening, tightening, and induration of the skin of the
fingers and the skin that is proximal to the metacarpophalangeal or metatarsophalangeal joints. These changes
may affect the entire extremity, face, neck, and trunk
Minor criteria
Sclerodactyly is characterized by thickening, induration, and tightening of the skin, limited to only the
fingers.
Digital pitting scars or a loss of substance from the finger pad: As a result of ischemia, depressed areas
of the fingertips or a loss of digital pad tissue occurs.
Bibasilar pulmonary fibrosis includes a bilateral reticular pattern of linear or lineonodular densities most
pronounced in basilar portions of the lungs on standard chest roentgenography. These densities may
assume the appearance of diffuse mottling or a honeycomb lung and are not attributable to primary lung
disease.
Exam Stems :
In the exam, the common stem given is Do a general examination and proceed.
Examination Steps :
1. Start with hands. Look for pulp atrophy, Raynauds phenomenon, sclerodactyly, finger tip ulcer,
calcinosis, vasculitis. Examine the hand for joint pain, swelling and movement.
2. Look for telangiectasia. Pinch the skin up and below elbow joint.
3. Look for evidence of proximal myopathy.
4. Look at the face. Demonstrate microstomia by insertion of 3 fingers. Look for perioral furrowing, bird beak
nose, pursed lips
5. Auscultate the lung and heart.
6. Look for proximal myopathy in leg and leg ulcers.
Presentation :
Sir, this is middle-aged lady who appears to be well, not in respiratory distress or in pain. She has typical
features of scleroderma with shinny skin, perioral furrowing and microstomia.
In the hand, she has finger pulp atrophy, sclerodactyly and telangietasia. However, there is no evidence of
Raynauds phenomenon, calcinosis, finger tip ulcer and vasculitis. Skin tightness extends above the elbow.
Besides, she also has fixed flexion deformity of her fingers but no joint pain or swelling noted. Functionally, she has
restricted movement of her hands.
She has no evidence of proximal myopathy with full muscle power of both upper and lower limb proximal
muscle. There is no leg ulcers seen as well.
Besides, she has evidence of pulmonary fibrosis with crepitations heard over the lung and evidence of
pulmonary hypertension with a loud P2 heard.
I would like to complete my examination by abdominal examination, check the blood pressure and check the stool
and urine to look for proteinuria and steatorrhea.
In summary, this is a middle-aged lady who has diffuse systemic sclerosis and functionally has restricted hand
movements. She also has evidences to suggest pulmonary fibrosis and pulmonary hypertension
Investigations :
To confirm my diagnosis, I would like to do blood tests such as anti-topoisomerase and anti-centromere
antibodies. I would expect anti-topoisomerase antibody to be positive in diffuse systemic sclerosis and anti-
centromere antibodies to be positive in limited systemic sclerosis. Other investigations are ANA, urinalysis, renal
profile, ECG, chest x-ray, echo for pulmonary HPT, CT thorax to look for other complications of the disease.
Management:
The principle of treatment of scleroderma is mainly conservative and identify and treat possible complications. The
treatment is mainly organ-based.
Raynauds phenomenon : avoid cold, stress and B-blocker. Calcium channel blocker or sildenafil can be given
for vasodilatory effects. Bosentan and ilioprost are also effective in treating Raynauds.
Renal hypertensive crisis : avoid steroid. ACE inhibitor is effective in treating this.
GERD : PPI.
Malabsorption syndrome : oral antibiotics.
Pulmonary hypertension : bosentan, ilioprost. Lung transplant is another options.
Arthralgia : NSAIDS, paracetamol, low dose steroids
dermatological : good skin hygiene, low dose prednisone, methotrexate
cardiac: for pericarditis give systemic steroids
What are the main types of scleroderma?

Diffuse and limited systemic sclerosis.
What is the diagnostic criteria for scleroderma?
- Major criteria : proximal scleroderma (to MCP and MTP joint)

- Minor criteria : sclerodactyly, fingertip pitting or atropy, bibasal pulmonary fibrosis. At least the major or 2
minor criteria must be fulfilled to diagnose scleroderma.

What is the classification?
The symptoms result from inflammation and progressive tissue fibrosis and occlusion of the microvasculature
by excessive production and deposition of types I and III collagens. The levels of other macromolecules (eg,
glycosaminoglycans, tenascin, fibronectin) found in the connective tissue are also increased
What are the antibody that will be positive in scleroderma?

Anti-topoisomerase for diffuse systemic sclerosis and anti-centromere for limited systemic sclerosis.
What are the possible causes of Raynauds phenomenon?
COLD HAND
Cryoglobulins/Cryofibrinogens
Obstruction/Occupational
Lupus erythematosus, other connective tissue disease
Diabetes mellitus/Drugs
Hematologic problems (polycythemia,leukemia, etc)
Arterial problems (atherosclerosis)
Neurologic problems (vascular tone)
Disease of unknown origin (idiopathic)
What is mixed connective tissue disease?

Scleroderma + SLE + Myositis
Causes of anemia in Scleroderma :

IDA, anemia of chronic disease, megaloblastic anemia (bacterial overgrowth)

What are the systemic complications of scleroderma?
How would you manage renal hypertensive crisis?

st
ACE inhibitor is the 1 line of treatment. If there is contraindication to ACE inhibitor, ARB can be tried even
though the effectiveness is still not well known. Steroids must be avoided as it will worsen the hypertensive
crisis. Creatinine level should be monitored to look for renal failure.
What is CREST syndrome

Calcinosis - calcium deposits on skin
Raynaud's phenomenon
Esophageal dysfunction - acid reflux
Sclerodactyly - tightening of skin on digits
Telangiectasia - superficial dilated blood vessels
What do you understand about Raynaud phenomenon?

Raynaud phenomenon results in characteristic color changes of pallor, cyanosis, and then redness (white, blue,
red), which are usually accompanied by numbness, tingling, or pain. it is defined as sequential color changes in
the digits precipitated by cold, stress, or even change in temperatures. Raynaud phenomenon is due to arterial
vasoconstriction in the digits. The color changes of pallor ("white"), acrocyanosis ("blue"), and reperfusion
hyperemia ("red") are characteristic.
What antibodies are common in scleroderma patients with skeletal muscle involvement and pulmonary disease?
Fibrillarin antibodies , Anti-RNP is present mostly in patients with diffuse disease with overlap syndromes and in
patients with mixed connective-tissue disease.

Case 11 : Parkinsons disease
Introduction :
Parkinsonism is a syndrome characterized by termor, rigidity and bradykinesia. Causes of Parkinsonism include
idiopathic Parkinsons disease and Parkinsons Plus syndrome.
What is the incidence?

It affecting approximately 1% of individuals older than 60 years
Exam Stems :
Do a general examination and proceed.
Examination Steps :
1. Look for expressionless face, pill-rolling tremor.

2. Elicit cogwheel rigidity and bradykinesia.
3. Ask the patient to write. At the same time, look for scar in the head or chest.
4. Do a glabellar tap and assess the speech.
5. Assess the eye movement. Look for vertical gaze palsy.
6. Ask the patient to walk and examine the gait.
7. Do a retropulsion test if time permits.
Presentation :
Sir, my patient is a elderly gentlemen who appears to be well, not in respiratory distress or in pain. He has an
expressionless face and pil-rolling tremor at rest.
For the hands, I could appreciate cogwheel rigidity on the left arm which present throughout the whole range of
movement and exaggerated by distraction. He also has evidence of bradykinesia and micrographia.
He has a positive glabellar tap but the speech appears to be fairly good. He has no evidence to suggest
progressive supranuclear palsy as there is no vertical gaze palsy.
He walks with a fenestating gait and his arm swings are very much reduced. He also has difficulty in turning.
Retropulsion test is negative.
I would like to complete my examination by checking the supine and standing blood pressure. I would also like to ask
for history of neurological disorder in the family and any history of neuroleptics consumption.
In summary, this is a elderly gentlemen who has Parkinsonism most likely idiopathy Parkinsons disease and
functionally he is disabled by bradykinesia.
How would you diagnose Parkinsons disease?

Parkinson disease is a clinical diagnosis. There is no investigations that can confirm Parkinsons disease.

How would you classify tremor?
Resting tremor , as in Parkinson disease
Postural tremor ( also referred to as action tremor or kinetic tremor) it is brought on when the arms are
outstretched and is caused by the following:
Exaggerated physiological tremor, caused by anxiety, thyrotoxicosis, alcohol, drugs/
Brain damage seen in Wilson disease, syphilis
Intention tremor ( aggravated by voluntary movement) in cerebellar disease
Tremor from neuropathy ( postural tremor, arms more than legs)
What are the causes of drug associated tremors?

Drug induced tremors: beta 2 agonists ( eg : salbutamol), caffeine, theophylline, lithium, tricyclic
antidepressants, serotonin reuptake inhibitor, neuroleptics, sodium valproate, corticosteroids
Tremors associated with drug withdrawal: alcohol ( delirium tremens), benzodiazepines, barbiturates,
opiates
How do treat tremor for the Parkinson?

Tremor caused by Parkinson disease can be treated by levodopa, anticholnergic agents, dopamine agonists or
budipine. When all other types of medication are not effective, clozapine is often beneficiall.
What do you understand rigidity, bradykinesia, and dystonia?
Rigidity refers to an increase in resistance to passive movement about a joint. The resistance can be
either smooth (lead pipe) or oscillating (cogwheeling).
Bradykinesia refers to slowness of movement but also includes reduced spontaneous movements and
decreased amplitude of movement. Bradykinesia is also expressed as micrographia (small handwriting),
hypomimia (decreased facial expression), decreased blink rate, and hypophonia (soft speech). Postural
instability refers to imbalance and loss of righting reflexes.
Dystonia in Parkinson disease commonly consists of a foot involuntary turning in (inversion) or down
(plantar flexion), often associated with cramping or aching in the leg. Dorsiflexion of the big toe may
also occur. Another common dystonia in Parkinson disease is adduction of the arm and elbow, causing
the hand to rest in front of the abdomen or chest. Dystonic postures can wax and wane, occurring with
fatigue or exertion.
What are the Parkinsons Plus syndrome?

Progressive supranuclear palsy, multisystem atrophy, cortico-basalganglionic degeneration, diffuse lewy body
disease, Parkinsonism-dementia-amyotrophic lateral sclerosis complex
What are the surgery that can be done for Parkinson?

Deep brain stimulation, pallidotomy, thalamotomy
What is the staging system used for Parkinson?

Hoehn and Yahr Classification :

Stage Features
I Unilateral involvement only, minimal or no functional impairment
II Bilateral involvement, without impairment of balance
III First sign of impaired righting reflexes. Functionally restricted but physically capable, mild-
moderate disability
IV Fully developed, severely disabling disease, still able to walk and stand unassisted but markedly
incapacitated
V Confined to bed or wheelchair unless aided
What are the non-motor complications of Parkinsons disease?

Depression, dementia
Restless leg syndrome,
Autonomic dysfunction : Orthostatic hypotension,constipation, Urinary symptoms, retention, and
bladder infection
Sexual dysfunction,
Dysphagia and laryngeal dysfunction
Restrictive lung disease
What is progressive supranuclear palsy?

akinesia, dementia, vertical gaze palsy, axial rigidity
What is the first sign of Parkinson disease?

Initial finding being an asymmetric resting tremor in an upper extremity
What investigation should be taken in patient younger than 40 years who present with Parkinson sign?
Serum ceruloplasmin concentration is obtained as a screening test for Wilson disease in patients younger than
40 years who present with parkinsonian sign

Case 12 : Stroke
Introduction:
Clinical syndrome characterized by acute onset of focal neurological deficit lasting >24 hours due to
cerebrovascular accident (embolic, thrombotic or hypoperfussion).
Presentation:
Sir, I would like to complete my neurological examination by checking the upper limb, spine, anal tone, cranial
nerve and higher cortical function. I also want examine the cardiovascular system.
This is a middle aged gentlemen with average built and appears to be well. He has a hemiplegic gait with fisting and
pronation of right arm. Neurological examination show that there is upper neuron sign over the right lower
limb with muscle wasting with no contracture, hypertonia, brisk deep tendon reflex, positive Babinski sign but no
clonus. Muscle power is 3/5. The proprioception and coordination test is normal.
In summary, this gentleman has right sided hemiplegia most probably due to left corticospinal lesion.
Differential diagnosis:
1. Metabolic or toxic encephalopathy eg: hypoglycaemia, non ketotic hyperglycaemia

2. Post ictal todd paralysis
3. Structural intracranial lesion: tumor, hematoma, AVM, abcess
Investigation:
First, I would like to take CT brain to exclude or diagnose hemorrhagic stroke or intracranial lesion. Then I
would like to check full blood count to rule out coagulopathy, renal function profile, blood sugar profile to
exclude hypoglycaemia, fasting lipid profile, electrocardiogram to look for arrhythmia, chest x-ray,
echocardiogram to rule out cardiac emboli, carotid Doppler and MRI angiography. Thrombophila and
connective tissue screen in young stroke.
Management:
Early detection, stabilize patient and admit to stroke unit with vital sign monitoring. Maintenance of
electrolyte and glucose level, prevent hyperthermia, give oxygen supplement, wide bore needle insertion with
intravenous fluid and nil by mouth. Acute ischemic stroke patient who present within 4.5 hours after onset can
be thrombolysed with intravenous recombinant tissue plasminogen activator. Give aspirin within 48 hours of
ischemic stroke shown to reduce risk of death and recurrent stroke.
Refer to physiotherapy and occupational therapy to prevent contracture, muscle wasting and improve
outcome. Turn patients position every 2 hourly to prevent pressure sore. Deep vein thrombosis prophylaxis.
Control risk factor: stop smoking, control blood pressure and diabetes, treat hyperlipidemia. Give
antihypertension drug eg labetolol or nicardipine if systolic >220mmHg and diastolic >120mmHg, otherwise just
monitor the blood pressure. Reduce blood pressure slowly with target of about 160-180 mmHg systolic and 100-
110mmHg diastolic.
How to classify stroke?
Bamford clinical classification of stroke:
Common site of hypertensive hemorrhagic stroke :

Rupture of charcot-bouchard aneurysm. Common site: basal ganglia (putamen, caudate nucleus), cerebellum,
internal capsule, external capsule, hypothalamus
Contraindication for thrombolysis :

Stroke or head trauma or myocardial infarction in the past 3 month.
What is the surgical intervention?

1) Carotid Endarterectomy
2) Carotid Angioplasty and stenting
3) Intracranial Angioplasty and stenting

what is the risk factor?
What is transient ischaemic attack?

symptom lasting <24hrs, due to inadequate blood supply as a result of thrombosis/embolism
what is the primary prevention?
3) Smoking and alcohol cessation

4) Post menopausal HRT therapy: reduces risk of stroke 31% (according to progestin study)
5) DM: Try to keep HbA1c <6%
6) Atrial Fibrillation : warfarin therapy if indicated
7) Hyperlipidemia: start statins, keep LDL <2.6,
What is the Secondary Prevention?

1) Antiplatelet therapy
-325mg daily
2) Anticoagulation (Indication : Atrial Fibrillation) - May be commenced within 2-4 days after patient
neurological and hemodynamically stable
a) T warfarin Start 5mg OD 3/7 then check INR and taper accordingly (target INR 2.5 (2-3) )
b) Dabigatran etexilate (150mg BD) new recommendation, does not require INR monitoring
3) Anti-hypertensive: ACEi is recommended or ARB
4) Lipid lowering
5) DM good control
6) Cessationg of smoking
Case 13: SLE
History
1) Ask about presenting symptom
a) General symptommalaise, weight loss, nausea and vomiting, thrombosis of vein or arteries
b) Musculoskeletal symptomsarthralgia and arthritis, myalgia and myositis.
c) Dermatological symptomsskin rash, alopecia
d) Fever
e) Neuropsychiatric symptomdelirium, dementia, convulsion, chorea, neuropath, loss of vision ( optic
neuritis), headache, symptoms resembling multiple sclerosis, anxiety and depression.
f) Renal tract symptom:hematuria, oedema, renal failure.
g) Respiratory symptom- pleurisy
h) Cardiovascular symptom- pericardititis
i) Hematological symptom- lymphadenopathy, anaemia
j) Gastrointestinal symptom- nausea, diarrhea, pseudo bowel obstruction, perforation
k) Thrombophlebitis, recurrent abortion or fetal death in utero ( suggest antiphospholipid syndrome
l) Sicca symptom ( secondary to sjogrens syndrome)
m) Reduced activitis of daily living and ability to work as a result of the effect of this chroic and relapsing
disease on the patient life
2) Ask about any drug history. Drug like procainamide, hydralazine, methylodopa, penicillamine,
chlorpromazine and anticonvulsant can cause drug induced lupus.
3) Ask about the treatment given and any complication of treatment.
4) Ask about any problem during pregnancy and use of contraception
5) Inquire about the family history
6) Inquire abuot the patient understanding of the implication of this chronic and incurable disease and its
prognosis
General : cushingoid , weight, mental state
Hand: look for palmer palor, rash, vasculitis, arthropathy.
Arms:livedo reticularis, purpura, proximal myopathy due to SLE and steroids
Head: alopecia, lupus hair, Eye: scleritis
The palmar is paler and there is not rash, vasculitis, Raynaud phenomenon,
1. How to diagnose SLE ?
ACR diagnostic criteria in SLE, presented in the "SOAP BRAIN MD" mnemonic:

2. What is the etiology?
3. What is the pathogenesis

When cells die by apoptosis the cellular remnants appear on the cell surface as small blebs which carry
self-antigens.
These antigens include nuclear constituents (e.g. DNA and histones) which are normally hidden from the
immune system.
In patients with SLE, removal of these blebs by phagocytes is inefficient so that they are transferred to
lymphoid tissues where they can be taken up by antigenpresenting cells. The self-antigens from these
blebs can then be presented to T cells which in turn stimulate B cells to produce autoantibodies directed
against these antigens.
The combination of availability of self-antigens and failure of the immune system to inactivate B cells and T
cells which recognize these self-antigens (i.e. a breakdown of tolerance) leads to the following
immunological consequences.
Development of autoantibodies that either form circulating complexes or deposits by binding directly
to tissues.
This leads to activation of complement and influx of neutrophils causing inflammation in those
tissues.
Abnormal cytokine production increased blood levels of IL-10 and alpha-interferon are particularly
closely
linked to high activity of inflammation in SLE.
4. What investigation that can be done?
I would like to do a full blood count which may show low hematocrit due to anemia of chronic disease and
autoimmune haemolytic anaemia., leucopenia, lymphopenia and thrombocytopenia. I also would expect
raised ESR. I also would like to do CRP which is usually normal but may be higher when the patient has
lupus arthritis or arthritis or a coexistent infection. I also want to look for lupus nephritis by checking urea
and creatine which will rise with low serum albumin and high urine protein/creatine ratio. Autoantibodies is
also done include which the most significant are ANA, anti-dsDNA, anti-Ro, anti-Sm and anti-La.
Antiphospholipid antibodies are done as it may present in 2540% of cases but not all of these patients. I
also want to do serum complement C3 and C4 levels are often reduced during active disease. I also would
like to do baseline investigation like liver function test which may be mildly elevated in acute SLE or in
response to therapies such as azathioprine or nonsteroidal anti-inflammatory drugs (NSAIDS). Creatine
kinase levels may be elevated in myositis or overlap syndromes.
5. What is the Autoantibody Tests for SLE?

6. What radiological investigation can be done?
Joint radiography-Jaccoud arthropathy with deformity or subluxations

Chest radiography and chest CT scanning-to monitor interstitial lung disease and to assess for
pneumonitis, pulmonary emboli, and alveolar hemorrhage.
Echocardiography-to assess for pericardial effusion, pulmonary hypertension, or verrucous Libman-
Sacks endocarditis
Brain MRI/ MRA-used to evaluate for central nervous system (CNS) lupus white-matter changes ,
vasculitis, or stroke
Cardiac MRI
7. What biopsy can be taken?

Skin and renal biopsy
8. What investigation may tell you that is Flare of SLE?

The combination of high ESR, high anti-dsDNA and low C3 may herald a flare of disease. All these markers
tend to return towards normal as the flare improves but in some patients anti-dsDNA levels remain high
even during clinical remission.
9. What investigation is used for screening of SLE?

ANA has high sensitivity (98%), but poor specificity. It is used as a screening test
10. How to manage SLE patient?

Management of SLE often depends on the individual patients disease severity and disease manifestations
Pharmacotherapy
Medications used to treat SLE manifestations include the following:
Biologic DMARDs (disease-modifying antirheumatic drugs): Belimumab, rituximab, IV immune globulin

Nonbiologic DMARDS: Cyclophosphamide, methotrexate, azathioprine, mycophenolate, cyclosporine
Nonsteroidal anti-inflammatory drugs (NSAIDS; eg, ibuprofen, naproxen, diclofenac)
Corticosteroids (eg, methylprednisolone, prednisone)
Antimalarials (eg, hydroxychloroquine)
In severe flares or organ threating disease , acute SLE : use urgent IV cyclophosphamide, with high dose
prednisolone
Maintenance : use NSAID and hydroxychloroquine for joint and skin disease. low dose steroid may be used
in chronic disease. Steroid sparing agent is added in refractory cases or when steroid doses cannot be
reduced to levels for long-term use. Steroid sparing agent are azathioprine, methotrexate and
mycophenolate
Patients with SLE without major organ manifestations, use glucocorticoids and antimalarial agents may be
beneficial.
Dermatologic:
preventative: use sunscreen, avoid UV light and estrogens
topical steroids, hydroxychloroquine

Musculoskeletal
NSAIDs gastroprotective agent for arthritis (also beneficial for pleuritis and pericarditis)
hydroxychloroquine improves long term control and prevents flares
bisphosphonates, calcium, vitamin D to combat osteoporosis
11. What is the newer agent?

Newer agents such as rituximab (anti-CD20) are used in refractory cases. Rituximab depletes CD20 positive
B lymphocytes and thus reduces levels of autoantibodies.
12. How will you want to monitor the patient?

Periodic follow-up and laboratory testing, including complete blood counts with differential, creatinine, and
urinalyses, are imperative for detecting signs and symptoms of new organ-system involvement and for
monitoring response and adverse reactions to therapies
13. What prevention and caution should be advised to patient?

Patients with SLE should be educated to avoid triggers for flare.
Persons with SLE should avoid ultraviolet light and sun exposure to minimize worsening of symptoms
from photosensitivity.
Diet modification should be based on the disease activity. A balanced diet is important, but patients
with SLE and hyperlipidemia, for example, should be placed on a low-fat diet.
Many patients with SLE have low levels of vitamin D because of less sun exposure; therefore, these
patients should take vitamin D supplements.
Exercise is important in SLE patients to avoid rapid muscle loss, bone demineralization, and fatigue.
Smoking should also be avoided.
To minimize the risks of steroid-induced osteoporosis and accelerated atherosclerotic disease
14. How to manage pregnancy woman who has SLE?

I would like to counsel the patient and inform that the incidence of spontaneous abortion, premature labor,
early preeclampsia/eclampsia, fetal growth restriction, and intrauterine death are somewhat higher in
women with SLE.
The drug of choice for pregnant woman is prednisolone, azathioprine, hydroxychloroquine and low does
aspirin.
Pregnancy should be avoided during active disease (especially with significant organ impairment) due to
the high risk of miscarriage and exacerbation of SLE. Women with SLE should be counseled not to become
pregnant until the disease has been quiescent for at least six months.
Contraception and family planning are important considerations given the risks of disease flare with
exogenous estrogens and pregnancy and with the teratogenic risks of some SLE drugs. Estrogen therapies
have typically been avoided to prevent disease flares; progesterone-only contraception is more often
considered
15. What immunization should be done on SLE patient?

immunization against encapsulated organisms, such as meningococcal vaccine, pneumococcal vaccine, and
routine Haemophililus influenzae childhood vaccination
16. what is the poor prognostic factor of SLE?

Poor prognostic factors for survival in SLE include
Renal disease (especially diffuse proliferative glomerulonephritis)

Hypertension
Male sex
Young age
Older age at presentation
Poor socioeconomic status
Black race, which may primarily reflect low socioeconomic status
Presence of antiphospholipid antibodies
Antiphospholipid syndrome
High overall disease activity (eg, hemolytic anemia, thrombotic thrombocytopenic purpura [TTP],
alveolar hemorrhage, pulmonary hypertension, mesenteric vasculitis)

Case 14: Bell palsy
On inspection, there is facial asymmetry. There is flattened nasolabial fold and wider palpebral fissure on right
side. Mouth on the right side is droops and participates manifestly less while talking. And there is loss of
wrinkles his right forehead. He also cant elevate eyebrow on right. There is weakness of muscles on right side
of the face, the patient is unable to screw his eye tightly shut or move the angle on the affected side.
Otherwise, there is no herpes zoster of the geniculate ganglion on the ear and palatal vesicles. There is no
parotid gland enlargement. There is no scar over the parotid glan
I would like to complete my examination by checking taste on the anterior two third of the tongue. I also want
to check for hearing for hyperacusis resulting from involvement of then nerve to stapedius muscle and also
examine tympanic membrane for otitis media. I would like to test the urine for sugar for diabetes.
The patient has right sided lower motor neuron seventh cranial nerve palsy which most probably due to bell
palsy.
I would like to do the following investigation which include viral ELISA to look for varicella zoster infection,
skull x ray to look for any fracture, ct scan and MRI for the image of seven cranial nerve. I would like to do an
audiology test if there is any hearing loss which I will expect normal in bell palsy and sensoryneural hearing
loss in Ramsay hunt syndrome.i also would like to do EMG for prognosis.
For the management of Bells palsy, I would like to give physiotherapy like massage, electrical stimulation,
splint to prevent drooping of the lower part of face and also protection of the eye with lubricating eye drops
and a patch during sleep. Within 72 hour, early treatment with prednisolone can be given which can improves
the chance of complete recovery at 3 and 9 month. Combination of acyclovir and prednisolone also more
effective which can given to the patient too.
Bell palsy
What is the etiology of seventh nerve palsy
Intracranial:
Vascular- cerebrovascular accident
Tumour- acoustic neuroma
Infection- meningitis( rarely)
Intratemporal
Infection- acute and chronic otitis media, herpes zoster
Idiopathic Bell palsy
Trauma- surgical, accidental( basal skull fracture)
Tumour- paraganglioma, squamous cell carcinoma of external or middle ear, secondary metastasis
Extratemporal
Tumour- parotid gland tumour
Trauma- surgical , accidental: facial laceration

Cause of bilateral lower motor neurone facial weakness
a) Guillaine- barre syndrome
b) Bilateral parotid disease
c) Mononeuritis multiplex
What muscle is testing in facial nerve:

Occipitofrontalis- raises your eyebrow
Orbicularis oculi- close your eye tightly as you can
Orbicularis oris: show your teeth
Buccinators- puff out you cheeks
How would you differentiate between upper and lower motor neuron palsy?
In lower motor neuron palsy the whole half of the face on the affected side is involved. In upper motor neuron
palsy the upper half of the face is spared
How is facial palsy graded?

House brackman grades
I. Normal
II. Mild dysfunctuion, slight weakness, slight synkinesis
III. Moderate dysfunction, obvious weakness, incomplete eye closure, normal symmetry only at rest
IV. Moderately severe dysfunction
V. Severe dysfunction, barely perceptible movement, asymmetry at rest
VI. Total paralysis
Is the facial nerve a motor nerve or a sensory nerve?

The facial nerve is predominantly a motor nerve and supplies all muscles concerned with facial expression and
the stapedius muscle.
What are the motor branches of the facial nerve?

Nerve to stapedius. Nerve to posterior belly of digastric
Five division within the paratid gland- temporal, zygomatic, buccal, mandibular and cervical.
What is other branch of facial nerve?

Secretomotor- via greater superficial petrosal nerve to lacrimal, nasal, and palatine glands
Taste- via chorda tympani to anterior two third of the tongue
Sensory- uncommon sensory component of facial nerve carrying cutaneous impulses from the anterior wall of
the external auditory meatus knows as nervus intermedius or pars intermedia of Wrisberg
What are the reflex involving facial nerve?

Corneal reflex
Palmomentral reflex
Suck reflex
Snout reflex
Orbicularis oculi reflex or glabellar reflex
Palpebral oculogyric reflex
Orbicularis oris reflex

Case 15: Haematological examination (CML)
Overview of the hematological malignancies
In general the patient is lying supine on the bed, comfortably and not in pain. There is no bruising,
pigmentation, jaundice and scratch mark and rashes noted.
On peripheral examination, there is palmer pallor, but there is no clubbing, no koilonychias, no vasculitis,and
no arthropathy. There is no epitrochlear node in the arms. Conjunctiva is pallor but no yellowish sclera and
conjuctival suffusion. Oral hygiene is good with no gum hypertrophy and ulceration. There is no atrophic
glossitis and angular stomatitis. There is no vasculitis, brusing , pigmentation, ulceration and ankle edema on
the both limb.
On abdomen examination, the anterior abdominal wall is move symmetrically with the respiration. There
umbilicus is centrally located and inverted. There is no swelling, mass, scar, pigmentation, dilated vein or
visible pulse noted. The abdomen is soft and non tender. And there is a hepatospleenomegaly.
The liver is enlarged 3cm below the right costal margin which is smooth surfece, regular margin, firm is
consistency, and non-tender. There is also splenomegaly which measure 12 cm below the left costal margin
which is palpable notch, moves inferomedially on respiration, not ballotable, cant get above the border and
dull to percussion. There is no ballotable kidney. Shifting dullness was negative. The bowel sounds were
present with normal intensity.There is not bruit sound heard on the liver and renal.
I would like to complete my examination by checking cervical, axillary lymph nodes, checking for bony
tenderness
Differential diagnosis: myeloproliferative disorder, chronic myeloid leukaemia, myelofibrosis( particulary in

male)
Causes of Massive spleenomeglay

Malaria, kala-azar, Gaucher disease CML

What is differential diagnosis for hepatomegaly
Infection: viral hepatitis, abscess, typhoid, malaria,
Infiltration:
o Benign: fatty liver
o Malignant: hepatoma, HCC, secondary metastasis
o Myelo/lymphoproliferative disease
congestion: congetive cardiac failure
hemolytic: thalassemia
metabolic: Wilson disease
Autoimmune: SLE (lupus hepatitis)
Drugs: alcohol
What is differential diagnosis for splenomegaly?

Infection:
o Bacteria-infective endocarditis, typhoid,
o Viral CMV, infectious mononucleosis
o Parasitic- malaria
o Fungal
Neoplasia: myelo- lymphoproliferative disease
Congestion: congestive cardiac failure, portal hypertension
Hemolytic anemia:Thalassemia, hereditary spherocytosis
Autoimmune: connective tissue disorder
What is CML?
myeloproliferative disorder characterized by increased proliferation of the granulocytic cell line without the loss
of their capacity to differentiate
What is Pathophysiology
Philadelphia chromosome (Ph)
translocation between chromosomes 9 and 22
the c-abl proto-oncogene is translocated from chromosome 9 to "breakpoint cluster region"
(bcr) of chromosome 22 to produce bcr-abl fusion gene, an active tyrosine kinase
What is the clinical phase?

3 clinical phases
chronic phase - 85% diagnosed here
few blasts ( <5%) in peripheral film
slightly elevated eosinophils and basophils
no significant symptoms
accelerated phase - impaired neutrophil differentiation

circulating blasts (10-19%) with increasing peripheral basophils (pruritus)
CBC: thrombocytopenia <100 x 109/L
cytogenetic evidence of clonal evolution
worsening constitutional symptoms and splenomegaly (extramedullary hematopoiesis)
blast crisis - more aggressive course, blasts fail to differentiate

blasts (>20%) in peripheral blood or bone marrow; reflective of acute leukemia (1/3 ALL,
2/3 AML)

What Is the clinical presentation?
20-50% of patients are asymptomatic when diagnosed (incidental lab finding)
nonspecific symptoms
fatigue, weight loss, malaise, excessive sweating, fever
secondary to splenic involvement
early satiety, LUQ pain/fullness, shoulder tip pain (referred)
splenomegaly (most common physical finding)
anemia
bleeding - secondary to platelet dysfunction
pruritus, PUD - secondary to increased blood histamine
leukostasis, priapism, encephalopathy (rare) - secondary to very elevated WBC (rare)
What is the investigation?

high increase in WBC, decreased/normal RBC, increased/decreased platelets, increased basophils
o peripheral blood film
leukoerythroblastic picture (immature red cells and granulocytes present, e.g. myelocytes
and normoblasts)
presence of different mid-stage progenitor cells differentiates it from AML
o bone marrow
myeloid hyperplasia with left shift, increased megakaryocytes, mild fibrosis
o molecular and cytogenetic studies of bone marrow or peripheral blood for Philadelphia chromosome
o abdominal imaging for spleen size
Treatment
o symptomatic:
allopurinol and antihistamines
o chronic phase:
imatinib mesylate (Gleevec'")- inhibits proliferation and induces apoptosis by inhibiting tyrosine kinase
activity in cells positive for bcr-abl
if loss of response or intolerance, trial of 2nd ( dasatinib) or 3rd (nolotinib) generationinhibitors
interferon-a - virtually obsolete with advent of tyrosine kinase inhibitors (TKI)
hydroxyurea in palliative setting
bone marrow transplantation if progression to accelerated or blast phases - CML (curative)
o accelerated phase or blast phase:
refer for clinical trial or 2nd/3rd generation TKI and prepare for allogeneic stem cell transplant
patients, in blast phase typically get standard AML induction
o stem cell transplantation may be curative - to be considered in young patients who do not meet
therapeutic milestones
o treatment success is monitored based on therapeutic milestones:
hematologic - improved WBC and platelet counts, reduced basophils
cytogenetic- undetectable Philadelphia-chromosome in the bone marrow
molecular- reduction/absence of bcr-abl transcripts in periphery and marrow
Prognosis
o survival dependent on response
those achieving complete cytogenetic response (CCR) on imatinib by 18 months of therapy -6 yr
overall survival >90%
those who do NOT achieve CCR on imatinib - 6 yr overall survival of 66%
o acute phase (blast crisis - usually within 3-5 yrs)
2/3 develop a picture similar to AML
unresponsive to remission induction
1/3 develop a picture similar to ALL
remission induction (return to chronic phase) achievable

Case 16: Acromegaly
What is different between acromegaly and gigantism?

Gigantism refers to abnormally high linear growth due to excessive action of insulinlike growth factor I (IGF-I)
while the epiphyseal growth plates are open during childhood.
Acromegaly is the same disorder of IGF-I excess but occurs after the growth plate cartilage fuses in adulthood.
What is the pathophysiology
Causes of excess IGF-I action can be divided into the following 3 categories:
Release of primary GH excess from the pituitary

Increased GHRH secretion or hypothalamic dysregulation
Hypothetically, the excessive production of IGF-binding protein, which prolongs the half-life of
circulating IGF-I
What is the etiology?
Pituitary tumour( 99%) or hyperplasia va ectopic GH releasing hormone from a carcinoid tumor.
Mention other condition with excess growth hormone
Multiple endocrine neoplasia (MEN) type I

McCune-Albright syndrome (the triad of precocious puberty, caf au lait spots, fibrous dysplasia)
Neurofibromatosis
Tuberous sclerosis
Carney complex
Where is the primary production of IGF-1?
Elevated tissue levels of free IGF-I, which is produced primarily in hepatocytes
In what condition that growth hormone secretion can be raised?
Growth hormone can be increase during stress, sleep, puberty, pregnancy. Normal growth hormone secretion
is inhibited by high glucose which make growth hormone hardly detectable
What are the sign and symptom?
ABCDEF
Arthralgia/ Arthritis
Bood pressure raised
Carpal tunnel syndrome
Diabetes
Enlarged organs
Field defect ( visual )

Please mention some cause of macroglossia?
Acromegaly, amyloidosis, hypothyroidism, Down syndrome
What is the complication of acromegaly>
Cardiomegaly
Hypertension
Impaired glucose tolerance
Hypopituitarism
Carpal tunnel syndrome
Arthritis of the hip, knee and spine
Spinal stenosis resulting in cord compression
Visual field defects
Increased risk of premalignant polyps and colon cancer : screening colonscopy should be considered in
all patient with growth hormne excess
What is the indicator of disease activity?
Symptom such as headache, increase in size of ring, shoes and dentures

Excessive sweating
Skin tags
Glycosuria
Hypertension
Increased loss of visual field
What the investigation that can be done? How would you investigate the patient?
Biochemical test
Plasma insulin like growth factor (IGF-1) level marked elevation establish the diagnosis, and it allow the
assessment of the efficacy of the initial therapy and in the post therapeutic period
When IGF-1 level is only moderately elevated, diagnosis is comfirmed by non-suppressibility of growth
hormone level to >1 g/l after oral administration of 75g glucose
Serum thyroxine, prolactin and testosterone
Evaluate pituitary function: static and dynamic test
Calcium level to exclude MEN type 1 syndrome
Radiography
Chest: cardiomegaly
MRI scan to evaluate the extent of tumour growth and To image pituitary adenomas
Computed tomography (CT) scanning: To evaluate the patient for pancreatic, adrenal, and ovarian
tumors secreting GH/GHRH; use chest CT scans to evaluate for bronchogenic carcinoma secreting
GH/GHRH
Radiography: To demonstrate skeletal manifestations of GH/IGF-I excess
o Hand ( terminal phalangeal tufting)
o Foot ( terminal phalangeal tufting , lateral view shows increased thickness of the heel pad)

How you want to perform the measurement of glucose nonsuppressibility test in acromegaly?
Two baseline GH levels are obtained prior to ingestion of 75 or 100 g of oral glucose, and additional GH
measurements are made at 30, 60, 90, and 120 minutes following the oral glucose load.
What is the false positive of this test?
Puberty, pregnancy, hepatic and renal disease, anorexia nervosa, and DM>
What is the aim of the treatment?
The aim is to correct tumour compression by excising the lesion, and to reduce the growth hormone and IGF-1
level to at least a safe level of < 2g/L.
What are the therapeutic option are available?
Neurosurgical intervention , typically trans-sphenoidal, is the primary therapeutic choice for almost all
patient. Diaphoresis and carpal tunnel syndrome often improve within 1 day of surgery. Although
growth hormone level fall immediately, insulin growth factor level fall gradually.
Radiation therapy is a primary treatment option for patient who are not surgical candidates or when
IGF-1 remain elevated after surgery because of residual tumour however this years to works.
The somatostatin receptor antagonist octerotide is valuable as adjunctive therapy to suppress growth
hormone secretion while awaiting radiation.
Pegvisomant is a synthetic growth hormone receptor antagonist that lower IGF-1 in > 90% of patient
is used if resistant or intolerant to somatostatin analogues( octreotide and lanreotide)
How you want to follow up the patient?
Yearly GH, IGF with OGTT, visual field vascular assessment like echo, ECG, BMI and photo of the patient.
What is the common cause of death in the patient?
Cardiac failure
Tumour expansion ( mass effect and haemorrhages)
Effect of hypertension
Degenerative vascular disease

Case 17: Cerebellar Disorders
Examination
Best performed with patient sitting up at the bedside and legs dangling (unless there is truncal ataxia)
a. Upper limb
i. Both arms outstretched and eyes closed
The limb on the affected side will drift away from the normal limb (the limb will drop in
weakness of deltoid and drift upward in proprioceptive disorders)
ii. Both arms outstretched: the patient is asked to maintain both limbs at the same level, and
with a quick push downward, the limb on the affected side will rebound to a higher level
than the normal limb
iii. Finger-nose test
Look for intentional tremor and dysmetria
iv. Rapid alternating movement
Slowness of the limb on affected side to perform:
Pat the palm of the normal hand with the palm and dorsum of affected hand alternately
(dysdiadochokinesia)
Supinate and pronate the affected hand rapidly
Oppose the thumb and each fingers backward and forward in turn
b. Head
i. Horizontal nystagmus
More obvious when looking towards the affected side
ii. Scanning/staccato speech
Speaking syllable by syllable
iii. Titubation
Repetitive head nodding yes-yes
c. Trunk
Sit the patient up without support and patient cannot maintain erect position (truncal ataxia)
d. Lower limb
i. Heel-shin test
Make sure that the leg tested is lifted high before the heel is placed on the patella of the
other leg (to elicit dysmetria of leg)
The clumsy and zig-zag movement of the affected leg on the shin of the other leg is
equivalent to intentional tremor during finger-nose test
ii. Pendular knee jerk
With the patient sitting on the bedside and legs dangling
e. Gait
Broad-base gait, unable to perform tandem gait
Patient reels to the affected side
Rombergs sign to exclude proprioceptive disorder as a cause of unsteadiness

Cerebellum
- fine-tuning and coordinating goal-directed movements initiated by the motor cortex

- planning and learning of skilled movements through its reciprocal connections with the thalamus and
cortex
- controlling speech
Lesion in cerebellar hemisphere causes
- lack of coordination on the same side of the body

- initial part of movement is normal, but as the target is approached, the accuracy of the movement
deteriorates, producing an 'intention tremor'
- distances of targets are misjudged (dysmetria), resulting in 'past-pointing'
- ability to produce rapid, accurate, regularly alternating movements is also impaired
(dysdiadochokinesis)
- central vermis of the cerebellum is concerned with the coordination of gait and posture - disorders of
this part produce a characteristic ataxic gait
Common causes
a. Acute (hours to days)

i. Cerebellar infarct (Wallenberg/PICA syndrome)
Wallenbergs syndrome = Infarction of the lateral medulla due to occlusion of the posterior inferior
cerebellar artery (PICA) that supplies this area
The neurological signs:
Ipsilateral cerebellar sign
Ipsilateral Horners syndrome
Ipsilateral 9th and 10th cranial nerves palsies
Ipsilateral pain/temperature loss on the face
Contralateral loss of pain/temperature on the trunk and limbs
Motor power is preserved on both sides
ii. Cerebellar hemorrhage
iii. Encephalitis
iv. Phenytoin toxicity
b. Subacute (weeks to months)
i. Alcohol abuse
Alcohol is directly toxic to the cerebellum, causing degeneration of the anterior superior vermis and
hemispheres.
ii. Metastases
iii. Paraneoplastic syndrome, e.g. Ca lung
iv. Multiple sclerosis
c. Chronic (months to years)
i. Hereditary cerebellar degeneration (spinocerebellar ataxia) autosomal dominant

Pathophysiology
Anatomy
- Situated in the posterior cranial fossa & covered superiorly by the tentorium cerebelli
- Largest part of the hindbrain & lies posterior to the fourth ventricle, the pons, & the medulla oblongata
- Ovoid in shape & constricted in its median part
- Consists of 2 cerebellar hemispheres joined by a narrow median vermis
- Connected to the posterior aspect of the brainstem by 3 symmetrical bundles of nerve fibers called the
superior, middle, and inferior cerebellar peduncles
- Divided into 3 main lobes: the anterior lobe, the middle lobe, and the flocculonodular lobe
- The cerebellum receives afferents from:
o proprioceptive receptors (joints and muscles)
o vestibular nuclei
o basal ganglia
o the corticospinal system
o olivary nuclei.
- Efferents pass from the cerebellum to:
o each red nucleus
o vestibular nuclei
o basal ganglia
o corticospinal system.
- Each lateral cerebellar lobe coordinates movement of the ipsilateral limbs.
- The vermis (a midline structure) is concerned with maintenance of axial (midline) posture and balance.
- The superior cerebellar artery (SCA) supplies a small brain stem territory, located on the dorsal tegmentum
and the tectum of the upper part of the pons. The superior part of the cerebellum supplied by this artery
includes the following lobules: lobulus anterior, lobulus simplex, lobulus semilunaris superior, and, in the
vermis, lobulus centralis, culmen and clivus. The dentate nucleus belongs to this territory.
- The anterior inferior cerebellar artery (AICA) irrigates a ponto-cerebellar territory. It usually supplies the
lateral territory of the lower part of the pons, the middle cerebellar peduncle, the flocculus and the
neighbouring lobules of cerebellum. When the posterior inferior cerebellar artery (PICA) is hypoplastic,
AICA takes over the territory usually supplied by the lateral branch of the PICA.
- The PICA always gives rami to the group of arteries supplying the dorsal medullary territory, but rarely
participates to the supply of the lateral medullary territory. It supplies the lobulus semilunaris inferior, the
lobulus gracilis, the lobulus biventer, the tonsilla cerebelli, and, in the vermis, the clivus, the tuber, the
pyramis, the uvula and the nodulus. PICA never supplies the dentate nucleus.
- The flocculo-nodular lobe is usually supplied by 2 arteries: the flocculus is supplied by the AICA and the
nodulus is supplied by the PICA.

Localizing features: DASHING
- Dysdiadokokinesis (impaired rapidly alternating movements)/Dysmetria (past-pointing)

- Ataxia (limb/truncal)
- Slurred speech (dysarthria)
- Hypotonia
- Intention tremor
- Nystagmus
- Gait abnormality (broad based, reeling toward the side of lesion, clumsy/unsteady, Rombergs sign
negative)
Lateral cerebellar lobes

- A lesion within 1 cerebellar lobe (e.g. tumour or infarction) causes disruption of the normal sequence of
movements (dyssynergia) on the same side
- Posture & gait: the outstretched arm is held still in the early stages of a cerebellar lobar lesion (cf. the drift
of pyramidal lesions) but there is rebound upward overshoot when the limb is pressed downwards and
released; gait becomes broad & ataxic, faltering towards the side of the lesion
- Tremor & ataxia: movement is imprecise in direction, force & distance (dysmetria); rapid alternating
movements (tapping, clapping or rotary hand movements) become disorganized (dysdiadochokinesis);
intention tremor (action tremor with past-pointing), but speed of fine movement is preserved, cf.
extrapyramidal & pyramidal lesions
- Nystagmus: coarse horizontal nystagmus with a lateral cerebellar lobe lesion the fast component is
always towards the side of the lesion
- Dysarthria: halting, jerking speech scanning speech
- Titubation rhythmic head tremor, either forward & back (yesyes) movements or rotary (nono)
movements when cerebellar connections are involved (e.g. in essential tremor & MS
- Hypotonia (floppy limbs) & depression of reflexes (with slow, pendular reflexes)
Midline cerebellar lesions

- Cerebellar vermis lesions: difficulty standing & sitting unsupported (truncal ataxia), with a rolling, broad,
ataxic gait
- Lesions of the flocculonodular region: vertigo & vomiting with gait ataxia if they extend to the roof of the
IVth ventricle
Investigation
Commonest cerebellar disorders in exam: stroke, tumor, SCA
Stroke
- Urgent CT/MRI
- CXR (cardiomegaly); ECG (AF); Echo (cardiac source of emboli); carotid Doppler ultrasound (carotid artery
stenosis); FBS; FLP; FBC (thrombophilia, polycythemia); ESR, ANA (vasculitis)
Tumor
- CT
- MRI (good for posterior fossa masses)
- Consider biopsy
- Avoid LP before imaging (risks coning)
- SCA
Management
Stroke
- Acute: ensure patent airway, avoid hypoxia or aspiration; monitor blood glucose; monitor BP; urgent
CT/MRI (cerebellar hemorrhage need urgent evacuation); thrombolysis once hemorrhage is excluded; NBM
until swallowing is assessed; keep hydrated; antiplatelet; refer for rehab
- Primary prevention: treat hypertension, DM, lipid and cardiac disease; exercise; folate supplement; quit
smoking; lifelong anticoagulation if rheumatic or prosthetic heart valves on left side and chronic non-
rheumatic AF
- Secondary prevention: antiplatelet (aspirin + dipyridamole / clopidogrel); anticoagulation (warfarin) for
embolic stroke or chronic AF
Tumor
- Benign: remove if accessible

- Malignant: excision; VP shunt if inaccessible but causing hydrocephalus
- Chemo-radiotherapy for post-op gliomas or metastases or if surgery is impossible
- Seizure prophylaxis (phenytoin)
- Headache: codeine
- Cerebral edema: dexamethasone, mannitol

Cardiac short case

Respiratory short case

Renal short case

Endocrine short case

CPG chronic renal failure
What is the presentation of the kidney failure?
Volume Overload
due to increase in total body Na+ content
signs: weight gain, HTN, pulmonary or peripheral edema
Electrolyte Abnormalities
high
K+ (decreased renal excretion, increased tissue breakdown)
POl- (decreased renal excretion, increased tissue breakdown)
Ca2+ (rare; happens during recovery phase after rhabdomyolysis-induced acute kidney injury or in
settings where hypercalcemia contributes to renal failure, such as in multiple myeloma or sarcoidosis)
uric acid
low
Na+ (failure to excrete excessive water intake)
Ca2+ (decreased Vit D activation, hyperphosphatemia, hypoalbuminemia)
What is the staging of CRD?
When to start screening?

METHODS OF SCREENING include proteinuria, haematuria, and renal function

General mangement
For diet,
protein restriction with adequate caloric intake limits endogenous protein catabolism
K+ restriction (40 mmol/d)
Na+ and water restriction
POl - restriction (1 g/d)
avoid extra-dietary Mg2+ (i.e. antacids
For medical
treatment of secondary hyperparathyroidism
calcium supplements (e.g. TUMSe) treats hypocalcemia when given between meals and binds
phosphate when given with meals
consider calcitriol (1,25-dihydroxy-vitamin D) if hypocalcemic
sevelamer (phosphate binder) if both hypercalcemic and hyperphosphatemic
vitamin D analogues are being introduced in the near future
cinacalcet for hyperparathyroidism (sensitizes parathyroid to Ca2+, decreasing PTH)
sodium bicarbonate for metabolic acidosis
erythropoietin injections (Hct <30%) for anemia; target Hct 33-36%
DDAVP for prolonged bleeding time if patient has clinical bleeding or invasive procedures
ACEi for hypertension (target 130/80 or less), loop diuretics when GFR <25 mL/min
statins for dyslipidemia
adjust dosages for renally excreted medications (avoid nephrotoxic medications)
dialysis (hemodialysis, peritoneal dialysis)
renal transplantation

Indication of renal ultrasound
New guidelines issued by the Canadian Society of Nephrology recommend delaying dialysis in CKD patients
without symptoms until their glomerular filtration rate (eGFR) drops to 6 mL/min/1.73 m2 or until the first
onset of a clinical indication (which includes symptoms of uremia, fluid overload, and refractory hyperkalemia
or acidemia)

Sabah Malaria Treatment Guidelines
Principles of Therapy
1. Early diagnosis. Malaria slides should be read and results released within 2 hrs. Positive results should be
conveyed to the doctor in charge by the MLT immediately by telephone or SMS
2. Careful assessment for clinical or biochemical features of severe malaria. All patients with severe malaria
(regardless of species) should receive intravenous artesunate or quinine immediately.
3. Even for patients with non-severe malaria, anti-malarialsmust be given ASAP it is the doctors
responsibility to ensure that the medication is given.
4. Admission for all malaria patients.
5. Close monitoring of vital signs ie BP/ PR/RR/SaO2
6. Careful administration of fluids. Strict Input/Output monitoring for patients with severe malaria.
7. Early referral to the ICU/HDU for patients with severe malaria
8. Refer to the Physician on Call for patients with severe malaria.
9. Discharge when 2 BFMP slides are negative and patient is well.
10. Follow up with repeat BFMP slides at D14 and D28
Criteria for Severe Malaria(any one of the following features constitutes severe malaria)
Clinical features: Biochemical features:

Impaired consciousnessor seizures Hypoglycemia (BSL<2.2mmol/L)
Prostration (severe weakness - inability to sit or stand unassisted) Severe anaemia (Hb<7g/dL)
Respiratory distress (RR>32 and SaO2<94%) Renal failure
Shock (systolic BP<80mmHg) Bilirubin >50mol/L
Jaundice Metabolic acidosis (HCO3<15)
Abnormal spontaneous bleeding Hyperparasitemia (>100,000/L)*
haemoglobinuria
* In Sabah, 4+ refers to a parasite count >4000/L. Since patients with density counts of 4+ may be
hyperparasitemic, it is safest to give at least one dose of iv artesunate (unless you are confident that the
patient does not have severe malaria).
Any patient who is unable to tolerate tablets due to vomiting should be treated with iv artesunate.
Investigations and monitoring
Routine baseline Ix for all malaria patients: BSMP, FBC, BUSE/Cr, LFTs, APTT/PTT, G6PD, DXT
Additional Ix for patients with confirmed or suspected severe malaria: VBG (or ABG if sats<94%), blood
cultures, CXR, urine microscopy.
All patients should have BSMP on admission to ward and repeated daily
FBC should be repeated daily thrombocytopenia usually recovers quickly, but the Hbusually falls
BUSE/Cr/LFTs to be repeated as clinically indicated
Patients with severe malaria should be closely monitored (eg. 1-2 hrlyobs, including RR and O2 sats,
depending on clinical status), with early referral to HDU/ICU if required

Treatment of Severe Malaria(any species)
Intravenous artesunate 2.4mg/kg stat, and repeat at 12 and 24hrs.

If patient has improved after 24 hrs, and can tolerate tablets, change to oral therapy (as for non-severe
malaria see below). A complete course of oral medications must be given.
If patient is unable to tolerate oral medication, continue iv artesunate 2.4mg/kg once daily until oral
therapy is possible.
If a patient has been started on iv artesunate but does not have severe malaria, oral medications may be
commenced after 1 or 2 doses of artesunate.
If iv artesunate is not available, or for pregnant women in the 1st trimester, give:
o iv quinine 7mg/kg over 1hr followed by infusion 10mg/kg over 4 hrs then 10mg/kg 8hlyOR
20mg/kg over 4 hrs then 10mg/kg 8hly until patient is able to take oral medication (minimum of
24hrs iv therapy for severe malaria)
o change to oral therapy (as for non-severe malaria see below) when patient able to take tablets
Treatment of Non-Severe Falciparum and KnowlesiMalaria
P. knowlesi and P. malariae cannot be distinguished by microscopy. In SabahP. malariae is rare, and nearly all
reports of P. malariae are P. knowlesi when tested by PCR. Patients diagnosed by microscopy as P. malariae
should be assumed to have knowlesi malaria.
Riamet (artemether/lumefantrine) 4 tabs (children: 5-14kg 1 tablet; 15-24kg 2 tablets; 25-34 kg 3 tablets)
orallytwice dailyfor 3 days (2nd dose should be given 8 hrs after 1st)
OR
Artequin 600/1500 (artesunate/mefloquine) 3 tabs once daily for 3 days (children: 20-40 kg Artequin
300/750 2 tabs once daily for 3 days; 10-20kg artesunate 50mg + mefloquine 125mg, both orally once
daily for 3 days;<10kg artesunate 25mg once daily for 3 days plus mefloquine 125mg as single dose)
OR(if the above not available, or for pregnant women in the 1st trimester)
Quinine 600mg (adult <50kg: 450mg; child: 10mg/kg up to 600mg) orally, 8 hourly for 7 days
PLUSdoxycycline 100mg (child>8 yrs: 2.5mg/kg up to 100mg) bdOR (for pregnant women and
children) clindamycin 300mg (children: 5mg/kg up to 300mg) orally 8 hrly for 7 days
Chloroquine is also effective for P. knowlesi and may be used for uncomplicated malaria.
For falciparum malaria, a single dose of primaquine (45mg) should be given for patients whose blood films are
persistently positive for gametocyte (if G6PD deficiency has been excluded).
Treatment of Non-Severe Vivax Malaria
Chloroquine 10mg base/kg then 5mg base/kg at 6 hrs, 24 hrs and 48 hrs
Add primaquine 30mg (children and adults <35kg: 0.5mg/kg) daily for 14 days if G6PD normal to prevent
relapse
For mild-mod G6PD deficiency, give primaquine 45mg weekly for 8 weeks
For severe G6PD deficiency, and for pregnant women, seek ID opinion
The above treatments for uncomplicated P. falciparum and P. knowlesi are also effective for P. vivax
Long Case Approach on Hypertension and Diabetes Mellitus
History
Patient Identification Data
Age:
Higher age group suggests that it is due to essential hypertension. Commonly DM type-2
Younger age group, rule out secondary causes of hypertension such as renal disease/artery stenosis, endocrine
problems (hyper/hypothyroidism, phaeochromocytoma,hyperaldosteronism), coartation of aorta and toxic
origin (alcohol, nasal decongestant with adnergic effect, NSAIDs, MAOIs, adrenoreceptor stimulators, combines
oral contraceptive pills). Commonly DM type 1. Therefore, mnemonic ERECT is used to remember the causes of
hypertension as follows:
E:ssential
R:enal
E:ndocrine
C:oarctation of aorta
T:oxic
Chief Complaint
Usually no chief compliant, just came for examination, if present usually is due to complications of the diseases
either hypertension or DM.
History of Presenting Illness
1. Question to clarify the following:

2. When was HPT/DM diagnosed? Duration? Use ERECT to find out cause. DM type 1 or 2? 3 Ps of DM
polyuria, polyphagia and polydidsia.
3. On what medication for HPT? On what medication/insulin for DM?
4. Is BP well controlled? Blood sugar well controlled if insulin?
5. Patients compliance to medication?
6. Any side effects of medication? (Most notorious for HPT is ACE causing chronic cough)
7. Last HbA1c?
8. Family history of HPT/DM?
9. Ask for complication of HPT such as the following (usually attributed by artherosclerotic disease):
a. Ischemic heart disease:
Death from ischemic heart disease or stroke increases progressively as BP increases. For every
20 mm Hg systolic or 10 mm Hg diastolic increase in BP above 115/75 mm Hg, the mortality
rate for both ischemic heart disease and stroke double.
b. Stroke.
c. Hypertensive retinopathy.
d. End Stage Renal Failure.
The Framingham Heart Study found a 72% increase in the risk of all-cause death and a 57% increase in the
risk of any cardiovascular event in patients with hypertension who were also diagnosed with diabetes mellitus
Nephrosclerosis is one of the possible complications of long-standing hypertension. The risk of hypertension-
induced end-stage renal disease is higher in black patients, even when blood pressure is under good control.
Furthermore, patients with diabetic nephropathy who are hypertensive are also at high risk for developing end-
stage renal disease.
10. Ask complications of DM, using mnemonic KANGA(I)ROO:

a. K:etoacidosis/Hyperosmolar hyperketotic state:Usually ask for their sign and symptoms and
history of hospital stay.
b. A:rterial diseaseMI/Stroke
c. N:europathy Compliation of DM. Numbness, loss of sensation, proprioception.
d. G: angrene
e. I:nfection Recurrent infections skin, UTI, URTI. Slow healing
f. R:enal disease ESRF sign and symptoms
g. O:cular HPT and DM retinopathy
h. O:bstetrics DM after pregnancy, History, Macrosomia, Fetal abnormalities, Sudden IUD
11. History of prolonged stay in hospital?
Systemic Review
Cardiovascular : Chest pain, pedal edema, PND, ortopnea, claudication.

Respiratory : As usual
Central Nervous : Loss of consciousness, fits, headache, loss of special senses
Gastrointestinal : As usual
Genitourinary : Nocturia, dysuria
Past Medical History
Rule of causes and other patients PMH.
Past Surgical History
Heart/renal surgery and other patients PSH.

Family History
Ask for family history of DM, Hypertension, parents and living sibling. If positive, as status, if passed on when,
what age and why?
Social History
History of smoking and alcohol comsumption.
Drug/Allergy/Food History
According to patient. Any lifestyle modification. Traditional supplements/herbs usually can complicate DM/HPT.
Summary
Patient identification, chief complaint, history of HPT/DM duration, medication/follow-up, compliance, control,
any complications.
Physical Examination
BP
Fundoscopy is a MUST.
Cardiovascular : Clubbing, radio-femoral delay, look for signs of failure such

displaced apex beat, triple gallop and bibasal crepts.
Respiratory : Usual
Neurological : Sensory, glove stocking distribution, monofilament test,

proprioception, vibration using 512 Hz
Abdominal : Injection marks, skin infection
Ulcer/peripheral vascular disease : As in ulcer/PVD examination
Investigation
This is individualised. Refer Malaysian CPG for Hypertension and DM.
Management
Lifestyle modification utmost important. Increase physical activity. Diet control. Refer Malaysian CPG for
Hypertension and DM.

DM
What is the definition of DM?
syndrome of disordered metabolism and inappropriate hyperglycemia secondary to an absolute/

relative deficiency of insulin, or a reduction in biological effectiveness of insulin, or both
Diagnostic Criteria
any one of the following is diagnostic:
presence of classic symptoms of DM (polyuria, polydipsia, polyphagia, weight loss, blurry vision, nocturia,
ketonuria) PLUS random blood glucose (BG) > 11.1mmol/L (200 mg/dL)
on at least two occasions:
FBG 7.0 mmol/L (126 mg/dL)
2h 75 g OGTT 11.1 mmol/L (200 mg/dL)
HbAlc 6.5% (American Diabetes Association Guidelines, Jan 2011)
What is the epidermiology of diabetes mellitus?

Epidemiology
- Prevalence increases sharply with age

-29 years: 0.5%
-49 years: 7.9%
-69 years: 28.7%
- Gender: Males (8.9%) > Females (7.6%)

- Ethnicity: Indians (15.3%) > Malays (11.0%) > Chinese (7.1%)
- 3-fold increase in mortality mostly due to cardiovascular disease
What is the classification of DM?
- Type 1 DM (IDDM): absolute insulin deficiency resulting from destruction of beta cells
Type 1A: Immune mediated
Type 1B: Idiopathic, not a/w AI disorders, more common locally
Associated AI disorders: Graves Disease, Hashimotos thyroiditis, Addisons disease, myasthenia gravis,
celiac disease, vitiligo, pernicious anaemia
- Type 2 DM (NIDDM): disorder of insulin secretion and action (relative insulin deficiency)
May range from predominantly insulin resistance with relative insulin deficiency to predominantly
secretory defect with insulin resistance
Preceded by a period of abnormal glucose homeostasis (IFG/IGT)
b) Secondary Diabetes: Disease causing pancreatic islet cell damage
- Genetic defects: maturity onset diabetes of the young

- Genetic syndromes: DIDMOAD, Down, Turners, Klinefelter syndrome
- Exocrine pancreatic defects: Chronic pancreatitis, Ca pancreas, CF, haemochromatosis
- Endocrinopathies: Cushings syndrome, acromegaly, hyperthyroidism, PCOS, phaechromocytoma,
glucagonoma
- Drugs: glucocorticoids, thyroxine, diuretics, phenytoin, alpha-interferon
c) Gestational Diabetes )GDM): insulin resistance related to metabolic changes in pregnancy, increased
insulin requirements leading to impaired glucose tolerance
What is the pathogenesis of DM

A. Type 1 DM
- Absolute insulin deficiency resulting from autoimmune destruction of islet beta cells
- Commonly develops in childhood, manifests at puberty and progresses with age. But can occur at any age
(even in 8th, 9th decade of life)
- AI markers: Islet cell Ab; glutamic acid decarboxylase Ab, insulin Ab,
Phases
(a) Prediabetes = autoAb as markers
(b) honeymoon phase = spontaneous decrease in insulin requirement after starting treatment, may last 3
to 6 months, exogenous insulin abates inflammatory process and allows remaining beta cells to function
- Relapse phase = progressive increase in insulin requirements
- Permanent phase = complete destruction of beta cells
B. Type 2 DM
Most common form of DM

- Multi-factorial: genetic, environmental
- no evidence of AI defects
- Associated with metabolic X syndrome = obesity, hypertension, dyslipidaemia and DM
- 2 main metabolic defects = insulin resistance + beta cell dysfunction
What is prediabetes?
A. impaired fasting glucose (IF G): fasting blood glucose (FBG) 6. 1-6.9 mmol/L (110-125 mg/dL)
B. impaired glucose tolerance (IGT): fasting plasma glucose <7mmol/L and 2h 75 g oral glucose tolerance
test (OGTT) 7.8-l1.0 mmol/L(140-200 mg/dL)
1-5% per yr go on to develop diabetes mellitus
50-80% revert to normal glucose tolerance
weight loss may improve glucose tolerance
increased risk of developing macrovascular complications
lifestyle modifications decrease progression to DM by 58%

1. what is the difference between type 1 and type 2
What is the manifestation of DM?

A. Urogenital manifestations of DM
Nephrotic syndrome
Renal failure
Glomerulosclerosis (Kimmelstein-Wilson lesion)
Chronic pyelonephritis
Emphysematous pyelonephritis
Renal papillary necrosis
Type 4 RTA
Contrast nephropathy
Renal Vasculature = Renal Artery Stenosis

Bladder:
Neurogenic Bladder
UTI
Genital
Vaginal candidiasis
Impotence
Retrograde ejaculation
B. Skin Manifestations of DM
a) Suggestive of DM
Acanthosis Nigricans
Vitiligo

Hyperpigmentation over neck, cheek, back of hands (Addisons Disease)
Thick greasy skin (Acromegaly)
Papery thin skin (Cushings)
Bronzed skin (Haemochromatosis)
b) Exclusive to DM
Granuloma annulare
Dermopathy
Necrobiosis Lipodica Diabeticorum
Scleroderma Diabeticorum (Thickening and hardening of skin)
c) Complications of Disease
Xanthelasma and eruptive xanthomata
Carbuncles, folliculitis, gangrene, ulcers, cellulitis, necrotizing fasciitis
d) Complications of treatment
Lipodystrophy
Jaundice (Tolbutamide)
What is the macrovascular complication?
increased risk of coronary artery disease (CAD), ischemic stroke, and peripheral vascular disease (PVD)
secondary to accelerated atherosclerosis
coronary artery disease

risk of MI is 3-5x higher in those with diabetes compared to age-matched controls
CAD is the leading cause of death in Type 2 DM
most patients with DM are considered "high risk'' under the risk stratification for CAD
ischemic stroke
risk of stroke is approximately 2.5x higher in those with diabetes
level of glycemia is both a risk factor for stroke and a predictor of a poorer outcome in patients who suffer a
stroke
HbA1c level is a significant and independent predictor of the risk of stroke
peripheral vascular disease

manifested by intermittent claudication in lower extremities, intestinal angina, foot ulceration
risk of foot gangrene is 30x higher in those with diabetes compared to age-matched controls
risk oflower extremity amputation is 15x higher in those with diabetes
Cardiovascular
- type 2 DM is a major risk factor for atherosclerotic disease

- metabolic changes in DM = hyperglycaemia, HPT, dyslipidaemia, obesity, pro-thrombotic state, endothelial
dysfunction, pro-inflammatory state whinch in the end prone to CVD
- DM is a coronary heart disease risk equivalent (risk of DM patient suffering an AMI is the same as a non-
diabetic patient who has already suffered a previous AMI)

What is the management of DM patient?
a) Patient education
b) Life style modification for 2 to 4 month unless patient is symptomatic or severely hyperglycemic (
random BSL more than 15 mmol/L or fasting BSL > 10 mmol/L)
I. Quite smoking= nicotine promote both macro and micro complication
II. Stop alcohol consumption
III. Exercise regularly: 3-5 time /week , 20-60 min per each time
IV. Lose weight
V. Eat a healty diest
VI. Reduce stress level
VII. Control HPT and HCL
c) Medical nutrition therapy
I. Weight loss to be attempted gradually = aim 0.25- 1 kg per week, ( optimal BMI< 23kg/m2)
II. Weight maintenance dier( when no longer overweight/obese)
i. Saturated fat < 10% Daily calorie intake(DCI)
ii. Carbohydrate 50-60% DCI
iii. Protein 10-20 %
iv. Cholesterol < 300 mg/day
v. Fibre 20-35g/ day
In DM, DCI should not more than 1800kCal/day

In HPT, restricted salt to <2g/day
III. 3 main meals and 3 snack times, eat small but frequency meal, and avoid saturated fat, refined
sugar, sauces, fried food, soft drink , etc
IV. By having a proper nutrition therapy it can abolish the symptom of hyperglycaemia, and help
achieve weight reduction which can reduce insulin resistance, hyperglycaemia and
dyslipidemia.
V. It also can prevent hypoglycaemia and weight gain associated with therapeutic agent ( insulin,
suphonylureas, thiazolidinediones)
d) Pharmacological therapy for those fail for lifestyle modification and symptomatic or severely
hyperglycaemic
I. Aim is to avoid acute complication of hyperglycaemia and DKA as well as avoid micro and
macro complication
II. First line therapy is sulphonylureas (for thin person) and biguanides (for obese)
III. Monotherapy combined therapy insulin
IV. Recommended that each therapy be allowed for 6 week to work before stepping up therapy
V. Insulin started if glucose targets are not achieved with lifestyle medication and OHGA.
e) Monitoring blood glucose control
1) Tight glucose control reduce risk of microvascular disease but increases risk of hypoglycaemia, thus
the targets must be individualized
ideal 4.6-6.45 Not attainable by most diabetic patients

Desired target for pregnant women with GDM or
pregestation diabetes
optimal <7.0% Desired target for diabetic patients
Suboptimal 7.1-8.0 % Attainable for most diabetic patient
unaceptable >8.0% Risk of acute metabolic decompensation and
hyperglycaemia
2) Indication of suboptimal
a) Older patient with significant artherosclerosis
b) Severe DM complication or co-morbidities
c) Pre-adolescent children=unpredictable food intake and activity intake
3) Monitoring by
a) Blood glucose level
b) HbA1c: measure f glycaemic control over the prvious 3 months
c) Fructosamine( glycated plasma protein)= reflect control over the prvious 2-3 weeks , useful in
pregnancy to assess short term control and in haemoglobinopathies which interfere with
HbA1c
4) Self monitoring glucose by using glucometer: pre meal hypocout 4.0-6.0 mmol/L, post meal
hypocount 6.0-8.0 mmol/L
5) Self monitoring of glycosuria is not recommended because inaccurate as raised renal threshold for
glucose might mask persistent hyperglycaemia, it is only used for those patient unable or unwilling
to perform hypocount
6) Self monitoring of ketonuria recommended in type 1 DM and pregnant women with GDM and
pre-gestational DM. it can used when acute illness/stress, persistent hyperglycaemia, and presence
of symptom of ketoacidosis.
f) Screening of chronic complication.

Oral hypoglycaemic agent(OHGA)
Classes of 0HGA
a. Insulin secretagogues promote insulin release
I. Sulphonylurea
II. Meglitinides
b. Insulin secretizers improve tissue response to insulin
I. Biguanides
II. Thiazolidinediones
c. Insulin release spares reduce amount of insulin required
I. glucosidase inhibitors
Sulphonylurea
Mechanism of action: inactive ATP dependent K channels depolarization opening of voltage
gated Ca2+ channels influx of Ca2+ trigger insulin release
1ST generation : Tolbutamide
Well absorbed orally
Rapidly metabolized in liver to inactive carboxytobulamide
Short half life= 4-5 hours ( need TDS dosing)
Advantages: safest sulphonylurea to be used in elderly due to short DOA
s/e: nephrotic syndrome, hypothyroidism, hepatoxicity, teratogenicity
chlorpropamide
-extremely long exting sulphonylurea( half life=36 hours)
s/e= severe hypoglycaemia, SIADH, cholestatic jaundice, bloody dyscrasia, rash,
2nd generation
Gilbenclamide ( daonil)
Metabolized in liver to 3 major hydroxlyted metabolites ( 1 has 15% hypoglycaemic effect that of
parent and accumulates in liver failure
Long half life: 6-12 hours, given as OM dose
s/e: hypoglycaemia, therefore not to be given to elderly who live alone]
CI: heaptic and renal impairement
Glipizide
Metabolized in liver to inactive compounds
Short half life: 2-4 hours
Faster onset and shortest among the second generation drugs
s/e: less like to casue hypoglycaemia, GIT effect nausea, vomiting, LOA), rash
3rd generation
Gilmepiride
-most potent of all the sulphonylurea
Metabolized in liver to inactive compounds
Short half like : 4-5 hours
s/e: allergic reaction9 due to sulphur content urticarial, cardiopulmonary failure, GIT( LOA,
nausea, vomiting, abdominal pain, diarrhea)
less likely to cause hypoglycaemia
Meglitinides Repaglinide
Mechanism of action = act on the binding site distinct from sulphonylureas inactive ATP-
dependent K+ channels depolarization opening of the voltage gated Ca2+ influx of Ca2+
trigger insulin release
Pradial glucose regulator= only to be taken 30 min before a meal( no meal no need to take)
Pharmacokinetics: well absorbed orally
Metaboliased in liver and excreted in bile
Very fast onset( within 1 hour of ingestion)
Used cautiously in patient with hepatic and renal impairment

s/e: hypoglycaemia
advantages: can be used in patient with sulphonylurea / sulphur allergy it does nor has sulphur
content

Dietary advice


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Medical Short Case and Long Case Record

Medical Short Case and Long Case Record

1. Vulvular Heart Disease

Medical Short Case and Long Case Record

Name other causes of collapsing pulse.

What are the peripheral signs of Aortic Regurgitation?

Corrigans: visible vigorous neck pulsation

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What are investigations, would you like to do ?

How would you manage a patient with chronic Mitral regurgitation?

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What are the types of prosthetic valve

Valve dysfunction leakage, dehiscence, obstruction

How do you want to treat the each complication?

Primary valve failure--- emergent valve replacement

What are the considerations involved in choosing mechanical or bioprosthetic valve?

What are the signs suggestive of prosthetic valve infection?

Change in their valve sounds

What is the pathophysiology of prosthetic valve endocarditis?

Antithrombotic therapy to prevent valve thrombosis and thromboembolism

How will you follow up the patient?

Can the patient exercise and has a normal life activity?

How do you manage a pregnant mother with prosthetic heart valve?

in order to balance fetal teratogenic risk and maternal thromboembolic risk:

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What is the endocarditis prophylaxis?

What is the target INR in prosthetic valve?

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What are your differential diagnosis?

What are the investigations you would like to do?

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Congenital: Kartageners and cystic fibrosis

Management of hemoptysis in bronchiectasis :

Medically : Transnexamic acid & mefenamic acid (mild)

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Bronchial dilation due to 3 causes=

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How would you like to investigate this patient?

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What are the causes of pleural effusion?

How you differentiate between transudate and exudates?

If Protein <25 g/L, it is transudate.

Medical Short Case and Long Case Record

The ratio of pleural fluid to serum protein >0.5

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Treat the underlying cause.

What are the conditions associated with bloody pleural fluid?

Malignancy, pulmonary embolism, tuberculosis, and trauma to the chest

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Clear ultrafiltrate of plasma that originates from the parietal pleura

TB, malignancy, collagen vascular diseases.