Medicine by Ferdaus Tahar

Medicine – RCSI Past Paper Answers 2002-2006 Dear Class of 2007, We have come a long way over the years, and it’s really great and inspiring to see how everyone came together to work on this project in our final year. Hopefully we will all continue this spirit of teamwork and willingness to help each other as we progress into our professional lives and beyond. The work in the “medicine & surgery booklets” is the collaboration of a number of students, and they are as follows (in no particular order): Sonia Masnoona Javid Michelle Schneider Maryam Al Saeed Irene Athanasiou Mariam Al Hilli Layan Akijian Arvin George Sasha Jairam Cormac Mc Carthy Abeer Al Kanderi Fatima Al Oraifi Abdulaziz Al Musallam Ahmad Al Huraiji Maree Daly Olav Sundnes Ali Al Rasheed Lana Khorsheed Sara Al Raisi Nurul Abu Bakar Shwan Karim Wan Norshuhada Rehab Al Maashari Alaa’ Ayyoub Hazem Abuhusain Amal Sahool Faisal Al Shatti* Ashraf Reyad* 1

We all hope that you use these answers as an adjunct to studying for the final written exam. This is not all you need to know, but will come in handy the night before the exam when you don’t know where to begin for a last minute revision. Please keep in mind that the answers reflect the style of the individual student whom attempted the question, and is not necessarily the ideal answer. All answers have come from resources (i.e. no one made them up to mess with your mind – we hope at least), although they were not referenced for the most part. You’ll find that some answers contain more information than needed, and may feel some are insufficient; either way, make the most out of it! Good luck to you all!! Graduation is just around the corner playing “peek-a-boo” with us ☺ Sincerely, ______________ The Waterford & Paeds Group =D NOTE: BOTH BOOKLETS ARE INCOMPLETE! MISSING QUESTIONS (for surgery – some colorectal, neurosurgery; for medicine – just a few random questions) WILL BE INCLUDED IN A THIRD BOOKLET. * I forgot to add Faisal’s & Ashraf’s names in the Surgery document. Seeing that they were among the 1st people to get involved in this project, I just wanted to note this down and apologize for missing them out!

TABLE OF CONTENTS Topic

Pages

A&E

4-7

CVS

8-38

Dermatology

39-44

Endocrine

45-63

Ethics

64-66

GIT

67-81

Haem/Onc

82-88

Infectious Diseases

89-93

Nephrology

94-106

Neurology

107-125

Respiratory

126-141

Rheumatology

142-160

A&E

Case 3: April â&#x20AC;&#x2DC;03 A 29 year old man has been hospitalised with depression for the past 2 months. He left hospital on a pass and returned complaining of abdominal pain and vomiting. Over the next several hours he became more agitated and was found unrousable with decerebrate posturing. Physical exam: Temp 37.6, pulse 120, respiratory rate 35, BP160/100. Fundi normal. Neurologic exam: unresponsive to pain without focal findings. 1. Outline your initial management of the patient 1. Initial management: -Assess airway, breathing, circulation -Consider intubation (GCS <3) and give O2 -IV access and fluids to maintain circulation -Stabilize cervical spine -Check blood glucose immediate 50mL 50% dextrose IV if hypoglycaemic -IV thiamine (if Wernickeâ&#x20AC;&#x2122;s encephalopathy), IV naloxone (if opiate intoxication), IV flumazenil (if BZD intoxication). -Examine, looking for: a)Vital signs b)Signs of trauma (haematoma, laceration, bruising, CSF/blood in nose or ears, skull fracture, subcutaneous emphysema) c)Stigmata of other illnesses (liver disease, alcoholism, diabetes, myxoedema) d)Skin (needle marks, cyanosis, pallor, rashes, poor turgor) e)Smell the breath (alcohol, hepatic fetor, ketosis, uraemia) f)Meningism (neck stiffness, rash, focal neurology) g)Heart/lung/abdominal exam h)Foci of infection (abscess, bites, middle ear) -History (collateral), ask about: Onset, How found, Recent complaints, Recent medical history, Past medical history, Drug or toxin exposure, Travel -Investigations: ABG, FBC, U&E, LFT, ESR, CRP, Ethanol, toxic screen, drug levels, blood cultures, urine culture, CXR 2. What is your differential diagnosis? 2. Differential diagnosis: -Alcohol intoxication -Drug poisoning -Hepatic encephalopathy -Pneumonia -Uraemia 3. His initial blood tests come back as follows: Arterial blood gas: PO2: 12 kPa, PCO2: 2 kPa, pH 7.2, U&E: Serum Na 142mEq/L, K 4.7 mEq/L, Cl 111 mEq/L, HCO3 10mEq/L, Creatinine 100 micromoles/L, Urea: 5mmol/L, Blood glucose: 4mmol/L

What is the acid base disturbance here? 3. Disturbance: Metabolic acidosis with respiratory compensation (Low HCO3 and low CO2) 4. What is the differential diagnosis of this acid-base disturbance and what further specific tests might help your management? 4. Differential diagnosis of acid-base disturbance: -Lactic acid (shock, infection, hypoxia) -Urate (renal failure) -Ketones (diabetes, alcohol) -Drugs (salicylates, biguanides, methanol) -Renal tubular acidosis -Diarrhoea -Drugs (acetazolamide) -Addison’s disease -Pancreatic fistulae -Ammonium chloride ingestion Case 2: October ‘02 A 29 year old man has been hospitalised with depression for the past 2 months. He left hospital on a pass and returned complaining of abdominal pain and vomiting. Over the next several hours he became more agitated and was found unrousable with decerebrate posturing. Physical exam: Temp 37.6, pulse 120, respiratory rate 35, BP160/100. Fundi normal. Neurologic exam: unresponsive to pain without focal findings. 1. What are the initial steps you will take on being called to review this patient? 1. Initial management: -Assess airway, breathing, circulation -Consider intubation (GCS <3) and give O2 -IV access and fluids to maintain circulation -Stabilize cervical spine -Check blood glucose immediate 50mL 50% dextrose IV if hypoglycaemic -IV thiamine (if Wernicke’s encephalopathy), IV naloxone (if opiate intoxication), IV flumazenil (if BZD intoxication). -Examine, looking for: a)Vital signs b)Signs of trauma (haematoma, laceration, bruising, CSF/blood in nose or ears, skull fracture, subcutaneous emphysema) c)Stigmata of other illnesses (liver disease, alcoholism, diabetes, myxoedema) d)Skin (needle marks, cyanosis, pallor, rashes, poor turgor)

e)Smell the breath (alcohol, hepatic fetor, ketosis, uraemia) f)Meningism (neck stiffness, rash, focal neurology) g)Heart/lung/abdominal exam h)Foci of infection (abscess, bites, middle ear) -History (collateral), ask about: Onset, How found, Recent complaints, Recent medical history, Past medical history, Drug or toxin exposure, Travel -Investigations: ABG, FBC, U&E, LFT, ESR, CRP, Ethanol, toxic screen, drug levels, blood cultures, urine culture, CXR 2. What is your differential diagnosis and how will you elucidate this patients problem? 2. Differential diagnosis: -Alcohol intoxication -Drug poisoning -Hepatic encephalopathy -Pneumonia -Uraemia 3. Outline the usefulness of a collateral history under these circumstances. 3. Collateral History: It is useful in determining whether onset was abrupt or gradual, if there was a seizure or suicide note (poisoning), trauma (suspect cervical spine injury). Recent complaints of headache (subarachnoid haemorrhage), fever (pneumonia), depression (alcohol). Recent medical history of sinusitis, otitis, neurosurgery, ENT procedure (infection). Past medical history of diabetes (hypo/hyperglycaemia), asthma, hypertension, cancer, epilepsy. 4. The patients initial blood tests come back. U&E: Serum Na 142mEq/L, K 4.7 mEq/L, Cl 111 mEq/L, HCO3 10mEq/L. Arterial blood gas: PO2: 12, PCO2 2, pH 7.2 What do these findings suggest and how might they explain the patientâ&#x20AC;&#x2122;s unconscious state? 4. ABG: Metabolic acidosis with respiratory compensation (Low HCO3 and low CO2). It is due to increased ketone levels from alcoholic ketoacidosis.

CVS

May 2002 CASE 5 You are called in the cardiac ambulance to see a 75 year old lady who has collapsed while shopping. For several years she has been treated by her family doctor for angina. She states that she felt unwell while shopping and took 2 puffs of her GTN spray. She then felt dizzy and collapsed. She has a history of one episode of amaurosis fugax eight months earlier. On examination she has a systolic murmur heard best in the aortic area and radiating into the neck 1. What are the potential causes of this ladyâ&#x20AC;&#x2122;s problem? Differential diagnosis for collapse Aortic Stenosis Hypotension due to GTN spray (GTN syncope) Arrhythmias (A fib, other SVTs, VTs, sick sinus syndrome) Medications Carotid stenosis Urinary tract infection Vasovagal syncope Postural hypotension Carotid sinus hypersensitivity Myocardial infarction Seizure Hypoglycaemia 2. What investigations should be carried out? -

BP sitting and standing FBC, U&E Blood glucose Urine dipstick Cardiac enzymes CXR ECG 24-hour holter Echocardiography Doppler ultrasound of carotid arteries

The patient is admitted to hospital. ECG shows sinus rhythm and left ventricular hypertrophy. An echocardiogram is performed and shows thickened aortic valve with a gradient across the valve of 90mmHg. 3. In the light of these findings what are the potential mechanisms responsible for this ladyâ&#x20AC;&#x2122;s collapse?

In aortic stenosis the obstructed left ventricular emptying leads to increased left ventricular pressure and compensatory left ventricular hypertrophy. This causes relative ischaemia of the left ventricular myocardium which results in angina, arrhythmias and left ventricular failure. The obstruction to LV emptying is relatively more severe on exercise. Normally, exercise causes a many-fold increase in cardiac output, but severe narrowing in aortic stenosis means that the cardiac output can hardly increase. Therefore, when exercising the BP falls, coronary ischaemia worsens, the myocardium fails and cardiac arrhythmias develop, and perfusion to the brain is decreased. 4. What is the appropriate management for this lady? Management - symptoms is a good index of severity - Asymptomatic patients should have regular reviews for assessment of symptoms and echo - Symptomatic patients have a poor prognosis and should have prompt valve replacement, but this of course depends on her being fit for surgery - Critical aortic stenosis in children and young adults can be treated with valvotomy (if valves arenot calcificed) – often with balloon dilatation, but this is not recommended for a 75 year old lady - May need endocarditis prophylaxis and anticoagulation, especially if having valve replacement October 2002 Question 2 d Write short notes on (d) Management of acute myocardial infarction 1) Oxygen 100% 2) Cyclomorph = cyclazine + morphine; give 5-10 mg morphine 3) ASA 300 mg + clopidogrel 600 mg (decreases risk of MI/Death) [+/- tirofiban if ischemia persists on ECG] 4) GTN sublingual (2 puffs or 2 x 0.6 mg tabs) 5) LMWHeparin – enoxaparin of choice (4 times ++ potent than unfractionated heparin) a. 1 mg/kg bd enoxaparin b. 120 u/kg bd dalteparin (iv only) c. unfr heparin 5000 IU bolus, then increase by 100 IU/hr until APTT x 1.5 – 2 of normal d. Give iv first e. Then SQ – continue until pain free for min 24 hrs, min 3-5/7 od 6) Bblocker – metoprolol 50 – 100 mg tds [+/- ACEI/Ca2+ if ischemia persists, to optimize anti-isch Rx] a. Caution: asthma, CCF (non compensated), COPD, bradycardia

b. If c/I: veparamil or diltiazem 80-120 mg tds po 7) Statin â&#x20AC;&#x201C; may stabilize plaque 8) Consider revascularisation 9) Nitrate ivi if pain persists (50 mg in 50 ml NS @ 2-10ml/hr); maintain systolic BP > 100 mmHg CASE 5 A 52 year old man develops substernal chest pain associated with nausea and diaphoresis. In the A&E department his BP is 110/70, his pulse 60 and regular and there are no signs of cardiac failure. His ECG is as shown below. 1. Describe the findings on the ECG. Do not have the ECGâ&#x20AC;Ś.. The patients is admitted to CCU. The first 2 days in hospital are uneventful. On the 3rd day he notes increasing lethargy, dyspnea and orthopnea. 2. How will you evaluate this patient? Full History: as above and when it started?ankle odema?Chest pain? Physical Examination: Vitals-BP, RR, pulse-irregular-suggest arrhythmia? Temperature and oxygen saturation. evidence of cardiac failure-pulmonary odema-bibasal crepitations, and right cardiac failure-increased JVP, peripheral pitting oedema, ascites, hepatomegaly. Any new murmur-valve lesion/septal or ventricular rupture Investigations CXR: look for signs of heart failure ECG: any arrythmias-conductive defect or new MI Echo: if new murmur looking for valve lesion, changes to septum/ventriclesdilated/mural thrombus Serial Enzymes On physical examination on day 3 you note a pansystolic murmur heard best at the lower left sternal border but heard all over the praecordium. 3. What is your differential diagnosis and how would you confirm the definitive diagnosis? Mitral regurgitation due to rupture of chordae or papillary muscle Ventricular septal defect due to rupture of ischaemic area Confirm diagnosis with echocardiography

4. How would you manage this patient? Do not have the ECG….. CASE 6 Mr Woods, 74 year old man attends his GP with progressive increase in leg swelling and breathlessness on exertion. The GP notes that he has oedema to his thighs. 1. List the causes of generalised oedema. • • • • •

Increased plasma hydrostatic pressure: congestive cardiac failure and vasodilatory drugs-nifedipine Decreased plasma oncotic pressure: liver disease, renal disease, malnutrition/malabsorption Impairment of lymphatic drainage: congenital deficiency of lymphatics Increased capillary permeability: angio-oedema anaphylaxis Compression of pelvic veins: pregnancy, pelvic tumour

2. A dipstick urinalysis shows ++++ protein. What does this tell you about the amount of proteinuria? List the causes of proteinuria. Include non renal causes. -

Renal causes o UTI o Orthostatic proteinuria o Glomerulonephritis o Haemolytic-uraemic syndrome o SLE o Multiple myeloma o Amyloidosis Extra-renal causes o Nephrotoxic drugs: NSAIDs, gold o Fever o Exercise o Pregnancy o Hypertension o Diabetes mellitus o CCF o Post operative o Recent ejaculation o Vaginal mucus

3. What points do you note in the history?

History - Cardiovascular o Dyspnoea, PND, orthopnoea, palpitations - Renal o Haematuria, dysuria, nocturia, frequency - Rheumatological o Stiff joints, skin rash - Systemic symptoms o Weight loss, energy, fever, rigors, night sweats - Past medical history o Recurrent UTIs o Previous MI o Diabetes o Hypertension o Glomerulonephritis, streptococcal sore throat o SLE, vasculitides, amyloidosis o Neoplasms - drugs o NSAIDs o Captopril o Gold o Penicillamine o Lithium o RIfampicine - Allergies - Family history o Family history of kidney disease o Sickle cell disease o Alportâ&#x20AC;&#x2122;s - Social o Alcohol intake o Diet o Travel history What features do you note on examination? Vitals: - HR - Temp - BP - oxygen saturation Signs of heart failure - pulmonary oedema - increased JVP - hepatomegaly - ascites

- pitting oedema - S3 and murmurs Signs of liver disease: - echymosis - jaundice - scoriation marks - clubbing/dupytrens/leuchonychia/palmar erythema/spider nivae - scleral icterus - gynecomastia - hepatomegaly Signs of renal disease: - puritius - grey brown colour - anemia-pallor of palmar creases/conjunctiva/koilonychias - ascites-shifting dullness - facial oedema 4. He is excreting 15g protein in 24 hours, has oedema and hypoalbuminaemia. What is this syndrome called? Nephrotic Syndrome What causes it? -

Minimal change Gn Focal segmental glomerulosclerosis Membranous GN Mesangiocapillary GN Proliferative GN Diabetes mellitus Amyloidosis SLE Henoch-Schonlein purpura

April 2003 2. Write short notes on (a) Clinical manifestations and diagnosis of infective endocarditis Clinical Presentation - cardinal features o Heart murmur o Fever - however, often very varied presentation - Clinical syndromes arise from 4 processes

1. 2. 3. 4.

Systemic features of infection Valvular damage Embolisation Immune vasculitis

Symptoms - Systemic o Fever o Night sweats o Weight loss o Fatigue o Myalgia o Arthralgia - Cardiac Symptoms o Symptoms of heart failure – SOB, oedema - Symptoms of embolisation o Haematuria – renal infarct o Focal neurological signs - stroke o Abdominal pain – mesenteric emboli, splenic abscess o Finger and toe gangrene – emboli - Symptoms of immune vasculitis o Acute renal failure Signs - General o Fever, pallor - Hands and arms o Splinter haemorrhages o Osler nodes, Janeway lesions o Evidence of IVDU -

Head & Neck o Pale conjunctiva o Roth spots on fundoscopy o Raised JVP Precordium o Signs of underlying heart disease o Signs of prosthetic heart valve o New heart murmur Abdomen o Splenomegaly o Ascites (CCF) Lower limbs o Signs of embolisation

Investigaitons

Bloods o FBC o U&E o ESR/CRP o Rheumatoid factor o Complement Blood cultures o Key diagnostic test o Three sets should be taken within 1 hr at 3 different sites o If negative may still be atypical organisms, and ask lab to culture for longer Urinalysis Echo o Allows vegetations to be seen o Also documents valvular dysfunction o May need to do TOE Serology o For Chlamydia, bartonella, legionella

Case 5 A 66 year old man is admitted to the Accident and Emergency department complaining of acute severe dyspnea. He awoke feeling short of breath and his condition deteriorated over the next 30 minutes. He had a myocardial infarction 4 years ago from which he sustained a moderate amount of muscle damage. He has difficulty speaking and is cold and clammy. On examination his blood pressure is 110/60, pulse 110/regular, respiratory rate 24/minute, systolic murmur at the apex radiating to the axilla with a 3rd heart sound. 1. What is the likely diagnosis. Give a list of potential differential diagnoses? Acute pulmonary oedema caused by acute mitral regurgitation most likely due to rupture of papillary muscle Differential diagnoses of acute severe dyspnoea - acute asthma - acute exacerbation of COPD - pneumothorax - pulmonary embolism - acute MI 2. What emergency investigations would you perform? Investigations - ECG - CXR - ABG

FBC/U&E Cardiac enzyme Consider echo later

3. What is your emergency management? Treatment - sit patient up - Give 60-100% oxygen - Iv Access - Treat any unstable arrhythmia, e.g AF - Morphine 2.5-5 mg slowly IV - Furosemide 50-120 mg slow injection, can be repeated if not responding - Give GTN spray 2 puffs - Insert urinary catheter to assess response to diuresis - Repeat ABG - May need GTN infusion - If not responding â&#x20AC;&#x201C; ICU for CPAP/BiPAP/intubation The patient responds well to therapy and is admitted to the cardiology ward 4. Which investigations would you perform? What is your long term treatment plan? Echocardiography o Establishes both the presence of MR and the mechanism o Can sometimes visualise chordal or papillary muscle rupture o Sometimes TOE is needed to assess severity of MR o Also useful in monitoring LV function Cardiac catheterisation - not commonly performed - contrast is seen regurgitating into left atrium during systole Long-term Treatment - sudden severe mitral regurgitation necessitates immediate mitral valve repair - may need antibiotic prophylaxis for endocarditis - possibly anticoagulation if either of the following o prosthetic valve o history of embolus o if patient has mitral stenosis at the same time October 2003 2. Write short notes on (d) Hereditary disorders associated with increased incidence of deep venous thrombosis

Factor V leiden o Due to a single nucleotide substitution in the factor V gene o This eliminates the site which is normally cleaved by protein C o Found in 3-5% of healthy individuals o Found in 20% of individuals with venous thrombosis o Increased risk of thrombosis in women with factor V leiden taking OCP or who are pregnant Protein C & protein S deficiency o Both autosomal dominant condititons o Homozygous deficiencies causes neonatal purpura fulminans, which is potentially fatal Antithrobmin deficiency o Can be inherited as autosomal dominant o Many different variants exist o Can also be acquired due to major trauma, severe proteinuria o Recurrent thrombotic episodes starts at a young age o Patients are relatively resistant to heparin as it requires antithrombin for its action Prothrombin variant o Mutation in the 3â&#x20AC;&#x2122; untranslated region of the prothrombin gene o Leads to increased levels of prothrombin o Causes a 3-fold increased risk of thrombosis o There is interaction with factor V leiden and OCP use Antiphospholipid syndrome o Autoantibodies which have specificity for negatively charged phospholipids o Hallmark of syndrome: arterial and venous thromboses + miscarriages o Responsible for about 20% of strokes occurring under the age of 45 o Diagnosis: anticardiolipin antibodies detection by ELISA

CASE 5 A 66 year old man presents to the A&E department feeling unwell and breathless. He has noted significant exercise limitation in the past 6 weeks. On examination he is dyspneic on minimal exertion, he has a pulse rate of 104 which is irregularly irregular. Blood pressure is 110/70. The jugular venous pressure is elevated to the angle of the jaw and he also has mild ankle swelling. He has a systolic murmur throughout the praecordium. Evaluation of the chest reveals dullness in both bases and decreased bibasal breath sounds. 1. What is the most likely diagnosis? What are the differential diagnoses? The patient has most likely congestive cardiac failure Differential Dx

COPD Pleural effusion Anaemia Interstitial lung disease Aortic stenosis Arrhythmias Bronchogenic cancer

2. What investigations should be arranged? Investigations - ECG o Evidence of ischaemia, hypertension or arrhythmias - CXR o Cardiac size o evidence of pulmonary congestion (first fluid in fissures, then Kerley B lines, then frank pulmonary oedema) o rule out respiratory causes - Echocardiography o Everyone with suspected CHF should have an ECHO o Confirms diagnosis and quantifies severity of disease o Can also reveal cause - Bloods o FBC, LFT, U&E o Cardiac enzymes o Thyroid function o Serum BNP < 100 HF unlikely 100 < x < 500 â&#x20AC;&#x201C; clinical judgement > 500 HF likely - Simple spirometry o Rule out respiratory causes of dyspnoea - Angiography o For certain patients 3. How would you treat this patient? There are two aspects of the treatment of this patient 1. Treatment of the heart failure 2. Treat the possible causes and contributory factors which in this case which may be: o Atrial fibrillation o Mitral regurgitation

Treatment of heart failure General treatment Physical activity - reduction in physical activity during exacerbations - Low level exercise encouraged in patients with compensated heart failure (20-30 minutes walks 3-5 days a week) - DVT prevented by daily leg exercises, TEDs and LMWH Dietary - salt restriction - large meals avoided - Reduce alcohol consumption Vaccinations - pneumococcal and influenza Pharmacological management Drugs useful for symptom relief - diuretics - Digoxin - Anticoagulants - Mechanical intervention Drugs with proven prognostic benefit - ACEI, ARB - Beta-blockers - Mechanical interventions Diuretics - act by promoting sodium excretion with enhanced water excretion o Loop Furosemid, butemanide Most commonly used Potent diuretics used in moderate/sever HF Gives rapid diuresis Produce marked potassium loss and hyperuricaemia When given IV it also produces vasodilatation Monitoring while on diuretics • Daily weight until dry • Remember dry weight for future diuresis goal • Check for pitting oedema, pulmonary oedema, and changes in JVP • Check creat/urea as this will increase with diuretic tx o Thiazides

Bendrofluazide Rarely used But may be used in combination with loop diuretic insufficient diuresis Metolazone if severe chronic HF o Aldosterone Antagonists Improves prognosis in those with severe to moderate heart failure Spironolactone S/E: hyperkalemia (rare, even if used with ACEI) Potassium should be measured 5 days after commencing, and then every 1-3 months once potassium level is stable Vasodilators - ACEI o Interrupts the maladaptive neuroendocrine response, vasodilates and lowers BP o 1st line treatment in all patients with evidence of heart failure o Has shown reduction in mortality o Agents used Captopril 50 mg tds Lisinopril 10-40 od Enalapril 10 mg bd Ramipril 5 mg bd o S/E May provoke profound renal artery stenosis Dry cough Angioedena Hyperkalaemia Hypotension -

ARB o o o o o

Candesartan, losartan Blocks AII No effect on vasodilatation and gives no cough May be beneficial if given together with ACEI and beta-blocker OR if ACEI itolerant

Beta-blocker o Improve both symptoms, exercise tolerance, left ventricular function and mortality o Ejection fraction may initially decrease, but will eventually increase o It also causes vasodilatation which will increase afterload o Common ones: carvedilol, bisoprolol o S/E: nightmares, tremor, hypotension, bronchospasm

Inotropic agents - frequently used to support myocardial function in patients with acute LV failure

Digoxin - Has no mortality benefit, but has a positive inotropic effect in sinus rhythm and reduces the hospital admissions for CCF - Should be given in patient with severe heart failure despite therapy with vasodilators, beta-blockers and diuretics - Also given to patients with rapid AF - Digoxin toxicity o Elderly with hypothyroidism more predisposed o Anorexia, nausea, altered vision o Arrhythmia â&#x20AC;&#x201C; esp ventricular premature beats, V tachy, AV block) o Digoxin levels> 2.5 nmol/L o Treated by stopping the drug, restoration of serum potassium and management of arrhythmias Treatment of mitral regurgitation - if symptomatic needs mitral valve replacement - also need endocarditis prophylaxis Treatment of AF - see other exam question 4. What is the significance of a systolic murmur in this setting? List the possible causes and how you would differentiate clinically between them The systolic murmur might point to a cause of the heart failure. It is most likely due to mitral regurgitation. This is a very common valve lesion which might be silent for years, but when it presents usually does so with symptoms of heart failure. Pansystolic murmurs - Mitral regurgitation o Loudest at the apex, radiating to the axilla o Increases with expiration o Often S3 o Associated signs: sharp upstroke of pulse, displaced hyperdynamic apex beat - Tricuspid regurgitation o Maximal at lower end of sternum o Increases on inspiration o Associated signs: elevated JVP, right ventricular heave, pulsatile liver, peripheral oedema - VSD o Harsh pansystolic murmur, maximal at lower left sternal edge o Louder on expiration

o Associated signs: hyperkinetic displaced apex beat Midsystolic murmurs - aortic stenosis o harsh ejection systolic murmur o maximal over aortic area, radiating to the carotids o loudest when sitting up and in full expiration o Narrowly split or reversed S2 o Associated signs: plateau or late peaking pulse, n - pulmonary stenosis o harsh, loud ejection systolic murmur o heard best in the pulmonary area, and does NOT radiate to carotids o louder on inspiration o Right ventricular S4 may be present o Associated signs: raised JVP, right ventricular heave, pulsating liver - hypertrophic cardiomyopathy o late systolic murmur maximal at the lower sternal edge and apex o murmur is increased by valsalva manoeuvre, bay standin and by isotonic exercise o often S4 o Associated signs: sharp rising pulse, prominent a waves of JVP, double or triple apical impulse Late systolic murmurs - mitral valve prolapse o high-pitched late systolic murmur o starts with a midystolic click and extends the rest of systole o occurs earlier and becomes louder with valsalva manoeuvre and with standing April 2004 1. A 50 year old man has a blood pressure of 160/110mmHg on repeated measurements.He is 9kg overweight, has a family history of hypertension, and smokes one pack of cigarettes per day. Describe your evaluation and treatment. Examination Looking for any specific aetiology - cushingoid facies - radiofemoral delay - BP in both arms - Renal bruit of renal artery stenosis Looking for end-organ damage - displaced apex beat - signs of hear failure

hypertensive retinopathy o Grade 1 – silver wiring o Grade 2 – 1 + AV nipping o Grade 3 – 2 + flame haemorrhages and exudates o Grade 4 – 3 + papilloedema check for protein and sugar in urine examine CNS for signs of previous CVA

Investigations - Confirm hypertension – repeated BP readings or ambulatory BP monitor - Check FBC, U&E, fasting lipids, fasting glucose - Hypokalemia occurs in Conn’s syndrome - Check urine - ECG and echo – if suspected heart disease - 24-hour urinary VMA if suspected phaeochromocytoma Treatment Non-pharmacological - Diet – salt restriction, low cholesterol diet - Physical exercise - Limit alcohol consumption - Stop smoking Pharmacological Indications for drug therapy - sustained systolic BP > 160 or diastolic BP > 100 - Sustained systolic BP > 145 or diastolic BP > 90 in presence of end-organ damage or other risk factors -

Clear mortality reduction from treating hypertension Benefit relates to degree of hypertension No good evidence that any drug is better than any other Individual drugs are particularly suited to some patients

Diuretics - loop diuretics (furosemide) and thaizides are equally effective - thiazides are usually preferred as they have longer action , less severe diuresis and they are also cheaper - Major concern with thiazides are their adverse metabolic effects o Increased cholesterol o Hypokalemia o Hyperuricaemia (can precipitate gout) o Impairment of glucose tolerance

Beta-blockers - Atenolol or metoprolol - reduce heart rate and BP - S/E: lethargy, impotence, cold peripheries, bronchospasm, exacerbation of diabetes, hyperlipidaemia - C/I: asthma, caution in PVD Calcium channel blockers - diltiazem, nifedipine(amlodipine) - vasodilators that lower BP - nifedipine causes a reflex tachycardia unless co-prescribed with beta-blockers - diltiazem causes bradycardia – useful when beta-blockers are C/I - S/E: flushing, ankle oedema, worsening heart failure, headaches Angiotensin-converting enzyme (ACE) inhibitors - captopril, enalapril, lisinopril - block conversion into angiotensin II and block degradation of bradykinin - S/E: first-dose hypotension, dry cough, angio-oedema, proteinuria, rashes, leucopenia in high doses - C/I: renal artery stenosis oraortic stenosis Angiotensin II receptor antagonist - losartan, valsartan, irbesartan, candesartan - - selectively block receptors for angiotensin II - Useful in patient who cannot tolerate ACE inhibitors due to the cough - Comparable efficacy to ACEI Indications for specialist referral - hypertensive emergency - to investigate suspected aetiology - evaluate therapeutic problems or failures - special circumstances – variable BP, white-coat, pregnancy CASE 4 A 25 year old man presents with a recent history of progressive dyspnea on exertion. He has reduced his jogging because of this symptom. He denies orthopnea and paroxysmal nocturnal dyspnea but has chest pain on exertion. His brother was known to have a heart murmur and had died from a ‘heart problem’ at an early age. On examination he has a systolic ejection murmur along the left sternal border which decreases when he lies down but increases when he performs a Valsalva maneuver. 1. What cardiac abnormality explains the patients clinical presentation? Hypertrophic cardiomyopathy

2. How will you make the diagnosis? Investigations - ECG o Normal in 5% o LVH/septal hypertrophy o LAD/RBBB o Q waves in inf/lat leads (septal hypertrophy) o Progressive T wave inversion o Bizarre complexes/waves in general o Arrythmias: Afib, SVT, VT, Vfib, WPW, ventricular ectopics - CXR o Cardiomegaly (LA/RA/LV enlargement0 - Echo - DIAGNOSTIC o asymmetrical septal hypertrophy o LV hypertrophy+small LV cavity + hypercontractile post LV wall o MR/SAM of mitral valve o Midsystolic closure of aortic valve - Cardiac catheterisation o shows narrow outflow tract (hourglass appearance) o CAD o MR - Stress test o in pts with angina, shows severity, allows risk stratification - Holter monitor o allows to pick up: sustained Afib, paroxysmal SVT, paroxysmal VT (aSx), and sustained VT o guides prophylactic management and risk stratification 3. What treatments would you suggest for this condition? Management - overriding concern is prevention of sudden death - Several established risk factors of sudden death o Massiv LV hypertrophy > 30 mm o Genotype o Family history of sudden cardiac death o Abnormal blood pressure response during exercise o Non-sustained ventricular tachycardia on holter monitor o Recurrent syncope - In high risk patients: Implantale defibrillators - In less high risk: amiodarone - Symptomatic control of chest pain dyspnoea with o Beta-blocker o Calcium channel blocker

4. What advice would you give his family members? Pedigree analysis generally shows an AD pattern Genetic analysis is available Important to screen family members, to reduce risk of sudden death October 2004 CASE 1 A 22 year old factory worker presents for a pre-employment medical examination and is noted to be hypertensive. He has a hyperdynamic apical impulse, murmurs are audible at the front and back of the chest and he has weak femoral pulses. 1. What is the most likely diagnosis? Aortic coarctation 2. What further investigations are required? ECG- 50% have LVH CXR- reveals a dilated aorta indented at the site of the coartation 1. A double aortic knuckle as a result of stenosis snd post-stenotic dilatation also referred to as looking like the ‘figure 3’ 2. Rib notching as tortuous dilated collateral intercostals arteries erode the undersurface of the ribs and notching at the scapular margin 3. Normal or large cardiac shadow Associations include, bicuspid aortic valve (70-80% of cases), cerebral artery circle of Willis berry aneurysm, ventricular septal defects, mitral stenosis or regurgitation, patent ductus arteriosus, Marfan’s and Turner’s syndrome. 98% are distal to origin of left subclavian artery. Echocardiography shows bicuspid aortic valve and other associated anomalies, sometimes shows coarctation itself and can show evidence of endocarditis. Aortography will show the defect and digital vascular imaging allows the coarctation to be visualised after the intravenous injection of contrast. CT/ MRI of the aortic arch or CT thorax with mediastinal windows 3. How should this patient be managed? -

Treatment is usually indicated if the pressure gradient across the coarctation is greater than 30mmHg. Involves surgical resection of the coarctation and end-to-end anastomosis of the aorta. If the coarctation is extensive, prosthetic vascular grafts may be needed. When surgery is performed in early childhood, hypertension usually resolves completely.

However when the operation is performed on adolescents or adults the hypertension persists in 70% because of previous renal damage and there is increased risk of accelerated atherosclerosis and strokes Balloon dilatation is used in some centres for either primary repair or postsurgical recurrences, although there is a higher incidence of aneurysm formation and post-dilatation recurrence. The intra-operative mortality is 5%. Due to predisposing congenital abnormalities prophylactic antibiotics are necessary to prevent subacute bacterial endocarditis.

CASE 6 A 68 year old man presents to his family practitioner and is noted to have a rapid heart rate. He is otherwise asymptomatic. His past history is significant for a nondominant hemispheric stroke 6 years ago with little residual defect. On examination he has an irregular pulse with a heart rate of 120 beats per minute and ECG shows atrial fibrillation with a rate of 150 beats per minute. 1. How would you further investigate this man? Haematological investigations: Urea and electrolytes looking for electrolyte abnormalities Cardiac enzymes to rule out AMI Thyroid function tests to rule out hyperthyroidism Specific investigations: • Electrocardiogram looking for absent P waves, irregular and rapid QRS complexes. The untreated ventricular rate is 120-180 BPM. • Chest X-ray looking for evidence of pneumonia, pulmonary embolus, bronchial CA, sarcoidosis, cardiomegaly • Transthoracic echocardiography looking for LA enlargement, valvular disease, cardiomyopathy, LV mural thrombus, LV function (ejection fraction). Note that the size of the LA gives an indication as to whether cardioversion is likely to succeed. Chronic hypertension or chronic A. Fib increases the likelihood of relapse. • 24 hour holter monitor (ECG) to establish the frequency and pattern. Sometimes used to monitor efficacy of rate control on drug treatment. • Stress test -is this exercise-induced A Fib -monitor efficacy of the rate controlling treatment -to rule out ischaemia as antiarrhythmic drugs are C/Indicated • Coronary angiogram looking for coronary artery disease especially in elderly NOTE in this patient consider the following (not routine in A. Fib work up) • Carotid duplex scan in this case as the man has a history of stroke 6 years ago • Consider CT brain to rule out more recent stroke in this particular patient only 2. What are the treatment options for his atrial fibrillation?

Treatment options for atrial fibrillation: Ventricular rate control is achieved by drugs which block the AV node, while cardioversion is achieved by DC shock (electrical cardioversion) or medically (chemical cardioversion) by infusion of an antiarrhythmic drug such as a class Ic or III agent. The choice depends on: • How well the arrhythmia is tolerated- is cardioversion urgent? • Whether anticoagulation is required before considering elective cardioversion. That is whether the AF is present > 48 hours or not. • Whether spontaneous cardioversion is likely? That is if a reversible cause can be found or the patient has a previous history. There is a high rate of spontaneous resolution up to 90% are in normal sinus rhythm in 6-8 weeks. 50% with new onset A. Fib without any structural heart disease go back into sinus rhythm within 24-48 hours. Classification of A. Fib Paroxysmal: self-terminating <48 hours Persistent: intermittent for 6- 12 months and requires DC cardioversion Permanent: accept the A. Fib and rate-control with anticoagulation All patients deserve at least one attempt at cardioversion. The AFFIRM trial in 2002 determined that rate control had a trend towards better survival and that rhythm control had a trend towards higher incidence of stroke. If normal LV then metoprolol 25mg BD is given and if LV hypertrophy is present then digoxin or verapamil is given. Ideal treatment is a beta-blocker +/- amiodarone followed by calcium channel blocker +/amiodarone because digoxin is less effective when sympathetic drive is increased e.g. during exercise. Beta-blockers/Ca channel blockers control rate but do not cardiovert, the patient feels better on these drugs, and they facilitate spontaneous cardioversion therefore they are first line treatment of A. Fib. MANAGEMENT OF ACUTE A Fib (i.e. < 72 hours since onset) When due to an acute precipitating event such as alcohol toxicity, chest infection or hyperthyroidism, the provoking cause should be treated. Control the rate with digoxin PO 0.5mg/12 hrs for the fist two doses then, 0.125mg0.25mg daily. If the ventricular rate is still too fast and LV function is normal start metoprolol 50mg/12hr PO (10mg/8hr if LV function is poor) and gradually increase the dose. If A. fib does not resolve consider chemical or electrical cardioversion. Factors to consider include the likelihood of maintaining sinus rhythm and the safety and tolerability of antiarrhythmic drugs in a particular patient. In general class Ic agents (e.g. flecainide) are employed in patients with no significant heart disease but most consultants never use this agent. Class III agents (e.g. amiodarone) are preferred in patients with significant structural heart disease. Chemical cardioversion is performed with amiodarone via IVI of 5mg/kg over 1hr then 900mg over 24 hour via a central line (max 1.2g/24 hours). Alternatively oral treatment with 200mg TDS for 1 week, then 200mg BD for 1 week, then 100-200mg OD maintenance therapy. It is estimated that 50% have a recurrence by 1 year. Sometimes flecainide 2mg.kg IV over 25 minutes (max 150mg) with ECG monitoring is used if the

patient is haemodynamically stable and no known ischaemic heart disease. Flecainide 300mg stat PO may also work. Electrical cardioversion is indicated either as an elective procedure when following a first attack an identifiable cause is found or, as an emergency if the patient is compromised. DC cardioversion to sinus rhythm is performed immediately if the patient/ doctor is certain that the onset of AF was < 48hrs ago. Firstly though a transoesophageal echocardiogram must be performed to rule out the presence of LA mural thrombus and also to ensure LA size is < 4.5cm because if cause of the hypertrophy is due to hypertension (most common cause today) then cardioversion is unlikely to succeed. The patient may be given aspirin prior to procedure and some consultants also give innohep or a bolus dose of heparin. The patient is kept on warfarin (and heparin for 2-3 days until INR at target of 2.5 â&#x20AC;&#x201C; 3.5) for 4-5 weeks post procedure. DC cardioversion during the R wave of the cardiac cycle with 200 J, then 2 x 360 J is effective in about 80% of patients. Biphasic waveform defibrillation is more effective than conventional monophasic. Otherwise if > 48 hrs since onset of A. Fib, or if the patient/doctor cannot be sure of the exact onset then, anticoagulation with warfarin for 4-5 weeks prior to electrical cardioversion is necessary, and further warfarin therapy for another 4-5 weeks post procedure. Remember that warfarin is pro-coagulant initially and needs to be given with innohep for the first 48 hours. The patient is given a rate-controlling agent (e.g. digoxin, beta-blocker or calcium channel blocker) to slow the AV node conduction while awaiting electrical cardioversion. MANAGEMENT OF CHRONIC A. Fib. Control the rate with digoxin PO: loading dose 0.5mg/12hr for the first two doses, followed by 0.125mg-0.25mg/24 hr. In the elderly load with 0.75mg in total and use 0.0626-0.125mg/24 hr as maintenance. If the rate is still too fast, check compliance and serum levels. Increase the dose or consider adding low-dose beta-blocker (e.g. metoprolol). Alternatively amiodarone PO and consider anticoagulation as necessary. MANAGEMENT OF PAROXYSMAL A. Fib. Recurrent paroxysmal A. Fib may be prevented by oral medication such as sotolol 80mg OD, then increased to 80mg BD, then 160mg BD is necessary. Alternatively amiodarone PO and consider anticoagulation if necessary. Ablation therapy is used in the treatment of paroxysmal and chronic A. Fib especially in young patients (<45 years), without structural heart disease. Catheter is placed into the left superior pulmonary vein and induces A. Fib. The focus can be identified and ablated. Risks of the procedure include stroke and pulmonary vein stenosis. 1. A. Fib ablation is sometimes carried out. It is a very topical issue as to what type of ablation procedure is best. Haissaguerre et al in France 1997 decided the focal source of A. Fib was in the pulmonary veins of the LA. Since then many different ways have been developed to isolate and ablate the pulmonary veins (known as substrate modification) including roof and mitral ischmus line, SVC and intercaval lines. A more recent theory

looking at sites of complex fast electrical activity (CFEA), that happen to be in and around the pulmonary veins anyhow, shows promise. 2. AV node ablation and pacemaker implantation is rarely performed in patients with poor rate control despite optimal medical treatment. These patients require life-long anticoagulation. Other disadvantages are the procedure is permanent and the patient now has life-long dependency on the pacemaker. 3. What can you do to significantly reduce his risk of a further stroke Way to significantly reduce the risk of further stroke: Embolic complications of A. Fib were proven in the Framingham study which showed 5.6 fold increased risk in non-rheumatic A. Fib. and 17.6 fold increased risk in rheumatic heart disease causing A .Fib. Warfarin therapy decreases incidence of stroke by 2/3 rd: from 4.5% to 1.5% risk per year. Target INR is 2.0 â&#x20AC;&#x201C;3.0. Patients under 65 years without risk factors for stroke had incidence of 1% per year with or without warfarin therapy. Thus the following criteria for anti-coagulation in A. Fib were devised: 1. Prior CVA/TIA 2. Uncontrolled hypertension or hypertensive heart disease 3. Diabetes mellitus 4. Recent cardiac failure 5. Low LV ejection fraction on echocardiogram 6. Age > 65 years (But this is still somewhat questionable in certain patients) In most other patients aspirin 300mg is prescribed 4. If a patient with atrial fibrillation has Wolff Parkinson White syndrome how would that alter your management? This is another form of supra-ventricular tachycardia that can degenerate into A.Fib. 1.2/1000 per year with WPW syndrome go into pre-excited atrial fibrillation and subsequently ventricular fibrillation causing sudden death. The AV node protects the rest of the population from developing ventricular fibrillation due to A Fib. In a patient with atrial flutter and WPW syndrome on ablation of the accessory pathway approximately 98% will be cured Management: If the patient presents acutely with symptoms then management is cardioversion either electrical (make sure to synchronise with the R wave) or chemical with amiodarone or flecainide. Never give a beta-blocker, verapamil or digoxin in this situation, as AVN block, hypotension and facilitation of the accessory pathway occur respectively. For permanent cure ablation of the accessory pathway by electrophysiological studies leads to termination of A. Fib. .

April 2005 CASE 3 You are asked to consult on a 73 year old woman who has been healthy in the past apart from occasional wheeziness. In the GP referral letter you read that on a recent trip to America she had her blood pressure checked. The level was 190/94. She presented to her GP and demanded treatment. He determined that it was inappropriate to treat her hypertension given her age. However as she was persistent he prescribed atenolol which she claimed made her breathless and therefore stopped taking it. You are asked to give a second opinion. 1. Are there any points in the referring doctor’s assessment and management with which you disagree? - It is not inappropriate to treat hypertension at her age - Don’t give beta-blocker to a patient who might have asthma 2. As part of your evaluation you arrange for an ambulatory blood pressure measurement . The average daytime reading is 178/96 and the night-time reading is 156/88. What is the significance of this result? What other assessments would you perform on this patient? The ambulatory BP testing confirms that she has hypertension. Normal blood pressure values for adults are < 135/85 mmHg for daytime, < 120/75 mmHg for night-time, and < 130/80 mmHg for 24 hours. It excludes “white coat syndrome” as a cause of her elevated BP Nocturnal dipping of BP is normal and is actually a good prognostic factor in people with hypertension -

Check FBC, U&E, fasting lipids, fasting glucose o Checking for other CV risk factors and for evidence of end organ damage o Hypokalemia occurs in Conn’s syndrome Check urine o For proteinuria ECG o Evidence of coronary artery disease or LVH Echo 24-hour urinary VMA – not appropriate in this setting

3. Describe the non-pharmacological treatment methodologies for this condition -

Diet – salt restriction, low cholesterol diet Physical exercise Limit alcohol consumption Stop smoking

4. Describe the pharmacological treatments for this condition Indications for drug therapy - sustained systolic BP > 160 or diastolic BP > 100 - Sustained systolic BP > 145 or diastolic BP > 90 in presence of end-organ damage or other risk factors - Clear mortality reduction from treating hypertension - Benefit relates to degree of hypertension - No good evidence that any drug is better than any other - Individual drugs are particularly suited to some patients Diuretics - loop diuretics (furosemide) and thaizides are equally effective - thiazides are usually preferred as they have longer action , less severe diuresis and they are also cheaper - Major concern with thiazides are their adverse metabolic effects o Increased cholesterol o Hypokalemia o Hyperuricaemia (can precipitate gout) o Impairment of glucose tolerance Beta-blockers - Atenolol or metoprolol - reduce heart rate and BP - S/E: lethargy, impotence, cold peripheries, bronchospasm, exacerbation of diabetes, hyperlipidaemia - C/I: asthma, caution in PVD Calcium channel blockers - diltiazem, nifedipine(amlodipine) - vasodilators that lower BP - nifedipine causes a reflex tachycardia unless co-prescribed with beta-blockers - diltiazem causes bradycardia â&#x20AC;&#x201C; useful when beta-blockers are C/I - S/E: flushing, ankle oedema, worsening heart failure, headaches Angiotensin-converting enzyme (ACE) inhibitors - captopril, enalapril, lisinopril - block conversion into angiotensin II and block degradation of bradykinin - S/E: first-dose hypotension, dry cough, angio-oedema, proteinuria, rashes, leucopenia in high doses - C/I: renal artery stenosis oraortic stenosis Angiotensin II receptor antagonist - losartan, valsartan, irbesartan, candesartan - - selectively block receptors for angiotensin II - Useful in patient who cannot tolerate ACE inhibitors due to the cough - Comparable efficacy to ACEI

Indications for specialist referral - hypertensive emergency - to investigate suspected aetiology - evaluate therapeutic problems or failures - special circumstances â&#x20AC;&#x201C; variable BP, white-coat, pregnancy October 2005 Write short notes on (2e) Risk factors for developing deep venous thrombosis Aqcuired - Malignancy - Pregnancy and post partum - Oral Contraceptive pill - Surgery less than 12 weeks ago, lasting > 30 minutes o Esp. pelvic and lower limb surgery - Immobility o Post-op o Long distance air-travel - Lower limb fracture and trauma - Family history of DVT/PE - Past history of DVT/PE - Smoking - Obesity Inherited - anti-thrombin deficiency - Protein C and S deficiencies - Factor V Leiden - Hyperhomocysteinaemia - Prothrombin deficiency - Antiphospholipid syndrome April 06 Write short notes: 2a) Describe how you would diagnose infective endocarditis in an individual suspected of having that condition. The Dukeâ&#x20AC;&#x2122;s Criteria for definitive diagnosis: Based on: 2 major criteria or 1 major and 3 minor criteria or all 5 minor criteria ( if no major criterion is met)

Major criteria • Positive blood culture o Typical organism in 2 separate cultures or o Persistently +ve blood cultures (eg. 3, >12h apart, or majority if ≥4) • Endocardium involved o +ve echocardiogram (vegetation, abscess, dehiscence of protstheic valve) or o New valvualr regurgitaion (change in murmur not sufficient) Minor criteria • Predisposition (cardiac lesion: IV drug abuse) o Fever > 38°C o Vascular/immunological signs (vascular manifestations: cardiac failure, changing murmurs, petechiae, splinter hemorrhages, osler’s nodes, janeway lesion, Roth spots, stroke, infarction of viscera, mycotic aneurysm. Immunological signs: arthralgia, clubbing, uremia) o +ve blood culture that do not meet major criteria o +ve echocardiogram that does not meet major criteria How to diagnose: Definite infective endocarditis: 2 major or 1 major and 3 minor or all 5 minor criteria Diagnosis made by 1. Duke’s criteria - Blood culture (take three samples from different sites at peak fever in 24 hrs. 85%-90% are diagnosed from the two first sets. 10% are culture negative. - Echocardiography (Transthoracic echo may show vegetations, but only if >2mm. Transoesophageal echo is more sensitive, and better for visualizing mitral lesions and possible development of aortic root abscess) 2. FBC, (normochromic, normocytic anaemia, neutropnhil leucocytosis) 3. High ESR/CRP 4. U&E, Mg+, LFT 5. Urinanalysis (microscopic haematuria) 6. CXR (cardiomegaly) and ECG (prolonged P-R interval) OCT ‘06 Write short notes on 2c) The therapy of chronic left ventricular failure. Treat the cause (eg, if arrhythmias, valve disease) Treat exacerbating factors (anaemia, thyroid disease, infection, ↑BP) Avoid exacerbating factors, e.g. NSAIDs (cause fluid retention) and verapamil (-ve I Inotrope) Stop smoking. Eat less salt. Maintain optimal weight and nutition.

Drugs: Diuretics: for appropriate fluid balance Initiate with frusemide PO and increase dose as necessary. NB! S/E: K+↓ and renal impairment So monitor U&E and add K+ sparing diuretic (e.g. spironolactone) if 1. K+ <3.2mmol/L 2. predisposition to arrythmias 3. concurrent digoxin therapy (as K+↓ increases risk of digoxin toxicity 4. pre-existing K+-losing conditions. If refractory oedema consider adding metolazone PO ACE-inhibitors: improves symptoms and prolongs life. Captopril /lisinopril NB: First dose HYPOtension! Particular risk in pats receiving large doses of diuretics and K+ supplements (>5.5mmolL( potassium sparing agents should be discontinued, as ACEi promote K+ retention) and hypoNa.(<130mmol/L. SO guyz, stop the diuretics (or decrease the dose) and K+ supplements and start with a low dose. E.g. Captopril 6.25mg/8h or Lisinopril 2.5mg/24hr. NB! C/I to start ACEi Renal Failue (serum creatinine >200µmol/L →not an absolute c/i Hyper K+ (>5.5mmol/L) HypoNa (caution if <130mmol/L, as relates to poorer prognosis) HypoVolemia Hypotension (systolic BP<90mmHg) Aortic stenosis or LV outflow tract obstruction Pregnancy or lactation Severe COPD, or cor pulmonale →not an absolute c/i Renal artery stenosis NB! S/E Hypo tension especially with 1st dose (so make sure you take this dose it around bed time) Dry cough Taste disturbance Hyperkalaemia Renal impairment Urticaria and angioneurotic oediema (rarely: proteinuria, leukopaenia, fatigue) Vasodilators: long acting nitrates ↓ preload by causing venodilation. Isosorbide mononitrate PO. Vasodilators improve arterial haemodynamics and ↓ mortality.

NB! 2nd line agents include arterial vasodilators, which reduce afterload (e.g. hydralazine) or α-blockers ( which are combined arterial and venous vasokilators, (e.g. prazosine) Inotropes: Digoxin improves symptoms even in those in sinus rhythm, though it doesn’t reduce overall mortality in patients with chronic hearth failure and normal sinus rhythm bit it reduces the rate of hospitalisation. Given to patients who remain symptomatic despite diuretics, ACEi and β-blockers and patients with rest dyspnoea or who have a history of rest dyspnoea NB! Monitor U&E and maintain K+ at 4-5mmol/L β-blockers: e.g. carvedilol. ↓ mortality in heart failure. These benefits appear to be additional to those of ACEi in patients with heart failure to LV dysfunction. NB! Used in all patients except those who are haemodynamically unstable or who are intolerant!. C/I: asthma/COPD, peripheral vascular disease, heart failure/heart block S/E: lethargy impotence, nightmares, headache. OCT ‘06 2e) Write short notes on the clinical manifestations and diagnosis of infective endocarditis. CLINICAL MANIFESTATION Manifestations of systemic infection: - fever, rigors, night sweats, anaemia, weight loss, pallor, splenomegaly manifestations of a vasculitic phenomenon - Cardiac failure, changing murmurs, petechiae, splinter hemorrhages, osler’s nodes, janeway lesion, Roth spots, stroke, infarction of viscera, mycotic aneurysm, aortic root abscess causing prolongation of P-R interval, microscopic haematuria - Embolic phenomena: emboli may cause abscessis in the relemvant organ. E.g. brain, heart kidney, spleen, GI tract in right sided endocaditis, pulmonary abscess may occur. Manifestations of immunological reactions - arthralgia, clubbing, uremia DIAGNOSIS OF I.E. Diagnosis made by 1. Duke’s criteria Blood culture (take three samples from different sites at peak fever in 24 hrs. 85%-90% are diagnosed from the two first sets. 10% are culture negative.

2. 3. 4. 5. 6.

Echocardiography (Transthoracic echo may show vegetations, but only if >2mm. Transoesophageal echo is more sensitive, and better for visualizing mitral lesions and possible development of aortic root abscess) FBC, (normochromic, normocytic anaemia, neutropnhil leucocytosis) High ESR/CRP U&E, Mg+, LFT Urinanalysis (microscopic haematuria) CXR (cardiomegaly) and ECG (prolonged P-R interval)

The Duke’s Criteria for definitive diagnosis: Based on: 2 major criteria or 1 major and 3 minor criteria or all 5 minor criteria ( if no major criterion is met) Major criteria • Positive blood culture o Typical organism in 2 separate cultures or o Persistently +ve blood cultures (eg. 3, >12h apart, or majority if ≥4) • Endocardium involved o +ve echocardiogram (vegetation, abscess, dehiscence of protstheic valve) or o New valvualr regurgitaion (change in murmur not sufficient) Minor criteria • Predisposition (cardiac lesion: IV drug abuse) o Fever > 38°C o Vascular/immunological signs (vascular manifestations: cardiac failure, changing murmurs, petechiae, splinter hemorrhages, osler’s nodes, janeway lesion, Roth spots, stroke, infarction of viscera, mycotic aneurysm. Immunological signs: arthralgia, clubbing, uremia) o +ve blood culture that do not meet major criteria o +ve echocardiogram that does not meet major criteria How to diagnose: Definite infective endocarditis: 2 major or 1 major and 3 minor or all 5 minor criteria

Dermatology

April 2005 Write short notes on: (2a) Treatment of psoriasis •General o Education and explanation o Remove triggers •Hydrations o Emollients •Topical o Steroids o Synthetic vitamin D3 analogues (calcipotril) o Vitamin A antagonists/retinoids (tazarotene) o Purified coal tar o Salicylic acid o Dithranol •Goeckerman regimen o Tar + UVB •Ingram’s regimen o Dithranol + UVB •PUVA •Systemic therapy (resistant cases) o Methotrexate o Acitretin o Mycophenolate o Ciclosporin o Hydroxycarbamide October 2005 Case 2 A 19 year old first year trainee hairdresser is referred with an itchy vesicular erythematous rash primarily affecting the dorsum of both hands and the flexural surfaces of both arms. She provides a history of hay fever and mild asthma. Her daily routine involves carrying out 20 - 30 shampoos. 1. What is the likely explanation for her problem? Atopic eczema precipitated by irritants in her work place 2. What other points should be sought from the history? •Time and course of the rash •Distribution of the lesions •Associated symptoms (pain, itch) •Family history o Asthma o Hayfever o Eczema 40

•Medications •Alcohol •Past medical history •Provocating/exacerbating factors o Infection o Detergents/chemicals o Woollen clothes o Cat/dog fur o Food •Previous skin treatments/conditions •Occupation o Was it better on weekends/days out of work o Did she have it last year, i.e. before she trained in this job, or did it start after the job 3. What investigations are required? Diagnosis is made clinically most of the time, but after a full history and thorough examination, I will consider •High serum IgE levels •RAST tests •Peripheral blood esonophilia •Skin swabs if infection 4. How will you treat this patient? •General o Education and explanation o Avoid irritants o Wear cotton clothes o Avoid excessive heat o Manipulate diet •Hydration o Emollients o Bath oils/soap substitutes •Topical o Steroids (hydrocortisone (mild) diflucortolone (very potent)) o Immunomodulators (tacrolimus) •Adjunct therapies o Oral antibodies (flucloxacillin for staph infection) o Sedating antihistamines (oral hydroxyzine) o Paste bandaging •For very severe/non-responsive o UV phototherapy o Prednisolone o Azathioprine o Ciclosporin

April 2004 (+May 2002 Case 2) CASE 5 A 32 year old lady is referred with a silvery scaley rash covering most of the trunk, limbs and scalp. She remembered developing a similar “tear-drop” rash when 13 years old but this had not recurred until now following the birth of her first child. 1. What is the likely diagnosis and what further information should be sought from the history to support this? •Most likely Diagnosis o Extensive plaque psoriasis possibly precipitated by the stress in labour and delivery •I would inquire about o Time and course of the rash o Distribution of the lesions o Associated symptoms (pain, itch) o Family history Psoriasis Eczema o Medications Lithium Beta blockers o Alcohol o Past medical history o Provocating/exacerbating factors UV light Infections – group A strep Local trauma Stress Labour and delivery stress o Relieving factors ?sunlight o Previous skin treatments/conditions o Occupation 2. What may further examination reveal? •Nail changes o Pitting of nail bed o Distal separation of nail plate (onycholysis) o Yellow brown discoloration o Subungual heperkeratosis o Damaged nail matrix and loss of nail plate •Arthropathic changes ( in 5 %) o Assymetrical involvement of small joints of hand including (DIP) o Symmetrical polyarthritis resembling RA o Arthritis mutilans o Ankylosing spondylitis

3. What may have precipitated the initial episode of tear drop rash and what is this type of rash called? The initial episode could have been precipitated by a streptococcal sore throat (preceding it by 2 weeks), and the rash is called guttate psoriasis 4. Your patient expresses concern regarding transmitting her skin problem to her children. How will you advise her? •Psoriasis is not contagious and can be inherited. •Those with a family history of psoriasis have an increased chance of having the disease. •Some people carry genes that make them more likely to develop psoriasis. •When both parents have psoriasis, the child may have a 50% chance of developing psoriasis. •About one third of those with psoriasis have at least one family member with the disease. •It affects all races and sexes equally and has two peaks of incidence, the first 16 to 22 (associated more with a positive family history) and the other 55 to 60. •Prevention o Seek medical advice as soon as symptoms appear o Avoiding environmental factors that trigger psoriasis, such as smoking, sun exposure, and stress, may help prevent or minimize flare-ups of psoriasis. Sun exposure may help in many cases of psoriasis and aggravate it in others. o Alcohol is considered a risk factor for psoriasis in young to middle-aged men. Avoid or minimize alcohol use if you have psoriasis. o Specific dietary restrictions or supplements other than a well-balanced and adequate diet are unimportant in the management of plaque psoriasis. 5. Plan a treatment strategy. •Refer to April 2005 2(a). October 2006 Q2g. Treatment of Psoriasis Def: Non infectious chronic inflammatory skin condition affecting 2-3% of Caucasians It has a chronic fluctuating course Management: • patient education, emphasise the need for compliance and chronicity of disease • remove and treat possible triggers (strep infection, drugs), stress, alcohol 1. topical treatments 2. UV therapy 3. systemic agents

4. intensive inpatient of day patient care with topical agents and UV radiation under medical supervision: less common in current practice Tropical treatments: 1. Emollients: modest effect on reducing scales and decreasing itch 2. Coal tar ointments: usually used in mild disease and for inpatients since they are very messy to use. Cleaner preparations Alphosyl can be used-(applied BD) 3. salicylic acid – to dissolve keratin of thick lesions 4. Dithranol: inhibits DNA synthesis: for stable plaques- used in short contact regimens (20-30 minutes) and in increments starting at low concentration 0.1%, 0.25%, 0.5% and 1% as tolerated. It is pro inflammatory and stimulates hyperproliferation normally but opposite effect in psoriasis. Side effects burnings and staining/ erypthema and brown staining of skin (avoid on face) 5. Calcipotriol: vitamin D3 analogue used for mild to moderate stable plaques max dose 75g per week (used BD) (if ↑ doses are used- hypercalcaemia can occur). It reduces the thickness of plaques and decreases scaling 6. Steroids: can cause local skin atrophy and withdrawalcan induce remission of psoriasis. They are used in flexures where tar and dithranol re too irritant Flexural disease: topical steroids, antibiotics and antifungals (Trimovate) Scalp psoraiss – may respond to dithranol, salicyclic acid, and steroids UV therapy and PUVA: - Mainstay of management in moderate to severe psoriasis - Short term side effect is burning while long term se is skin cancer - Narrow band UVB phototherapy (especially for extensive guttate psoriasis): delivered 2-5 times a week OPD basis - PUVA therapy: psoralens are used- natural photosensitiziong agents taken by mouth in combination with UVA ↑ intensity which cuases activation of psoralins and cross linking of DNA strands – delivered 2-5 times a week with clearance expected within 8 weeks. they are effective for extensive psoriasis yet repeated treatments carry a risk of UV induced skin cancer Systemic therapy: - Immunomodulatory drugs: in severe refractory disease where there has been failure of topical treatment for extensive plaques psoriasis. Also used in treatment of generalised pustular and erythrodermic psoriasis: - Low dose oral methotrexate (7.5-20mg once a week) useful in psoriatic arthritisexerts a cytostatic effect on the immune system. Main side effect is immunosuppresssion and depression of WCC and long term hepatic fivrosis - Others: ciclosporin: ↑ risk of nephotoxicity, neoplasia - Oral retinoic acid derivatives: acitretin or etretinate useful in severe erythrodermic or pustular psoriasis and also for severe chronic plaque psoriasisthey are potentially toxic and teratogenic so are avoided in women of child bearing age

Endocrine

October, 2002: 2e Write short notes: clinical features and diagnosis of hypothyroidism: Clinical features: 1- symptoms: tiredness , malaise , weight gain , cold intolerance , poor memory , change in appearance , depression , poor libido , goitre , puffy eyes , brittle dry un manageable hair , dry course skin , arthralgia , myalgia , muscle weakness / stiffness , constipation , menorrhagia or oligomenorrhoea in women , pychosis , coma , deafness . 2- signs: mental slowness , poverty of movement , ataxia , deafness , psychosis /dementia (rare) , dry thin hair , loss of eyebrows , hypertension , hypothermia , heart failure , bradycardia , pericardial effusion , cold peripheries , carpel tunnel syndrome , oedema , periorbital oedema , deep voice , dry skin , over weight , myotonia , muscular hypertrophy , proximal myopathy , slow- relaxing reflexes , anaemia . 3- diagosis of hypothyrodism ( investigations) : -

T4 : low total or serum T4 level confirm hypothyroidism .

TSH : high TSH confirm primary hypothyroidism , and low or normal if there is hypothalamic and pituitary disease ( secondary hypothyroidism) .

Thyroid and other organ specific antibodies may be present.

anaemia : usually normochromic and normocytic in type , or women due to menorrhagia.

Increased serum aspartate transferase level , from muscle and or liver .

Increase serum creattine kinase levels , associated with myopathy

Hyperchlesterolaemia

Hyponatraemia: due to increase in ADH and impaired free water clearance .

microcytic in

MAY 2002 , CASE 6: A 45 year old man presents with headache, visual deterioration, fatigue and notes that recently he is unable to wear his rings. The results of his glucose tolerance tests are as follows. Time (min) 0 30 60 90 120

Plasma glucose (mmol/L) 8.9 14.2 14.9 13.6 12.6

Growth hormone (mU/L) 14 19 22 43 24

1- THE 2 DIAGNOSES IN THIS PATIENT ARE LINKED. WHAT ARE THEY? Acromegaly and DM. 2- EXPLAIN THE AETIOLOGY AND PATHOPHYSIOLOGY OF THE CONDITION ASSOCIATED WITH THE GH ABNORMALITIES? The aetiology for acromegaly is pituitary tumours n most cases or rarely hyperplasia due to GHRH excess. Physiology of GH control: GH is the pituitary factor responsible for stimulation of body growth in humans. Its secretion is stimulated by GHRH, released from the hypothalamus; it is also under inhibitory control by somatostatin . GH acts by binding to a specific receptor located mainly in the liver . This leads to hepatic synthesis and secretion of IGF (insulin-like growth factor-1) which stimulates growth. .The metabolic actions of the system are: • • •

increasing collagen and protein synthesis promoting retention of calcium, phosphorus and nitrogen, necessary substrates for anabolism opposing the action of insulin.

IGF-1 have negative feed back when GH level increase as it effect the hypothalamus to produce GHRIH (SOMATOSTATIN ) which inhibit the pituitary from producing GH .and the IGF-1 effect the pituitary as well to stop GH secretion . So in acromegaly the pituitary is not responding to the negative feedback of the IGF-1 because of the tumour so threre is continuing secretion of GH and this will lead to increase IGF-1 which will cause acromegaly. 3- DISCUSS THE SYMPTOMS AND SIGNS OF ACROMEGALY?

Signs : prominent supraorbital ridge , prognathism , interdental separation , large tongue , hirsutism , thick greasy skin , spade-like hand and feet , tight ring , carpel tunnel syndrome , visual field defects , galactorrhoea , hypertension , oedema , heart failure , arthropathy , proximal myopathy , glycosuria , plus possible signs of hypopituitarism. SYPMTOMS : change in appearance , increased size of hands / feets , headaches , excessive sweating , visual deterioration , tiredness , weight gain , amenorrhoea / oligomenorrhoea in women , galactorrhoea , impotence or poor libido , deep voice , goiter , breathlessness , pain/tingling in hands , polyuria / polydipsia , muscular weakness, joint pains , symptoms of hypopituitarism may also present. 4- WHAT OTHER INVESTIGATIONS WOULD YOU PERFORM?

Investigations •

•

• • • • •

GH levels may exclude acromegaly if undetectable but a detectable value is nondiagnostic. Normal adult levels are < 1 mU/L for most of the day except during stress or a 'GH pulse'. The glucose tolerance test is diagnostic. Acromegalics fail to suppress GH below 1 mU/L in response to a glucose overlaod , and some show a paradoxical rise; about 25% of acromegalics have a diabetic glucose tolerance test. IGF-1 levels are almost always raised in acromegaly - a single plasma level of IGF-1 reflects mean 24-hour GH levels and is useful in diagnosis. Visual field defects are common. MRI scan of pituitary - will almost always reveal the pituitary adenoma. Pituitary function - partial or complete anterior hypopituitarism is common. Prolactin - mild to moderate hyperprolactinaemia occurs in 30% of patients , In some, the adenoma secretes both GH and prolactin

5- How do you treat this patient? Surgery is the treatment of choice in suitable patient may be trans-sphenoidal , or transfrontal if the tomour is large. Surgery is often combined with radiotherapy because excision is rarely complete with large tumours ( macroadenomas >1 cm in diameter) . External beam radiotherapy is normally used after pituitary surgery fails to normalise GH levels , rather than primary therapy . it may take 1-10 years to be effective when used alone .

Drugs Octreotide and the long –acting preparation , lanreotide, are analogues of somatostatin ( GH-inhibitory hormone) and are given SC injection in resistant cases , they are given to shrink tumours before definitive treatment or to control symptoms . Bromocriptine , or Gabergoline ( dopamine agonists) is usually reserved for elderly and frail people , used as an adjunct or if the patient is not good operative risk . Pegvisomant , a GH- receptor antagonist is new agent for patient where GH levels cannot be safely lowered with somatostatin analogues alone . April, 2003, 1C: write short notes on: Investigation and treatment of Cushing’s syndrome. A. Investigation: There are two phases to the investigation: 1. Confirmation of the presence or absence of Cushing's syndrome 2. Differential diagnosis of its cause (e.g. pituitary, adrenal or ectopic) Confirm raised cortisol: -

The 48-hour low dose dexamethasone suppression test is the most reliable screening test; 0.5 mg 6- hourly is given orally for 48 hours. Normal individuals suppress plasma cortisol by 48 hours. Urinary free cortical is raised (normal<700 nmol/24h). circadian rhythm studies show loss or normal circadian fall of plasma cortisol at 24 hours in patients with cushing’s syndrome.

Establishing the cause of the cushing’ syndrome: -

Adrenal CT or MRI will detect adrenal adenoma and carcinoma as those which produce Cushing’s syndrome are usually large. Pituitary MRI and CT will detect some, pituitary adenomas. Plasma ACTH levels are low or undetected in adrenal gland disease (non-ACTH dependent) and should lead to adrenal imaging. High or inappropriately normal values suggest pituitary disease or ectopic production or ACTH. High dose dexamethasone suression test: dexamethasone 2.0 mg 6 hourly is given orally for 48 hours. Most patients with pituitary dependent Cushing’s disease

suppress plasma cortisol by 48 hours. Failure of suppression suggests an ectopic source or ACTH or an adrenal tumour. -

Corticotrophin-releasing hormone test. An exaggerated plasma ACTH response to exogenous CRH (bolous given IV) suggests pituitary dependent Cushing’s disease. Other tests will depend on the probable cause of the cushing’s syndrome , CXR , bronchoscopy , CT of the body may localize ectopic ACTH producing tumours .selective venous sampling for ACTH will localize pituitary tumours and an otherwise occult ectopic ACTH –producing tumour. Radiolabelled octreotide shows promise in locating ectopic ACTH sites.

B. Treatments of CUSHING’S disease: •

Trans-sphenoidal removal of the tumour is the treatment of choice. Selective adenomectomy nearly always leaves the patient ACTH-deficient immediately postoperatively, and this is a good prognostic sign. Overall, pituitary surgery results in remission in 75-80% of cases - but results vary considerably and an experienced surgeon is essential.

Drugs which inhibit cortisol synthesis ( metyrapone, ketoconazole or aminoglutethimide) may be helpful in cases not suitable for surgery. External –beam irradiation of the pituitary produce a very slow response and restricted to cases where surgery is unsuccessful or contraindicated. Iatrogenic cushing’s responds to a reduction in steroid dosage , immunosuppressant drugs such as azathioprine may used in conjuction with steroids to enable lower doses to be used to control the underlying disease. Medical therapy to reduce ACTH (e.g. bromocriptine, cyproheptadine) is rarely effective. APRIL,2003 ,CASE 4 AND OCT, 2005 ,CASE 1 A 50 year old man with insulin dependant diabetes (type 1) for 10 years attends the diabetic clinic for his yearly regular check up. 1- LIST THE MICROVASCULAR AND MACROVASCULAR COMPLICATIONS OF DIABETES. WHAT ARE THE RISK FACTORS FOR DEVELOPMENT OF THESE COMPLICATIONS? Macro vascular complications: cerebrovascular (stroke) twice likely, cardiovascular (MI) 3-5 times more likely, peripheral vascular.

Micro vascular complications: diabetic retinopathy , diabetic nephropathy , diabetic neuropathy ( autonomic neuropathy , diabetic amyotrophy , mononeuropathy and mononeuritis multicomplex , acute painful neuropathy , symmetrical mainly sensory polyneuropathy(distal) ) . Risk factors for these : duration of diabetes , increasing age , systolic hypertension , hyperinsulinaemia due to insulin resistance associated with obesity and syndrome x , hyperlipidaemia particularly hypertriglyceridaemia , proteinuria ( including microalbuminuria) , smoking . 2- WHAT ARE THE IMPORTANT POINTS IN YOUR HISTORY AND EXAMINATION OF THIS PATIENT AT HIS YEARLY CHEACK UP? Aim of the check up: 1- to educate 2- to find out what problems the patient is experiencing (glycaemic control and morale) 3- to find or empt, complication. In the history • • • • • • • •

Rreview of self-monitoring results and current treatment. Talk about targets and change where necessary. Talk about any general or specific problems. Continued education. Review cardiovascular risk factors. Review self-monitoring and injection techniques. Review eating habits. History of hypoglycaemic attacks

In examination: • • • • • • • • • • • •

Biochemical assessment of metabolic control (e.g. glycosylated Hb test). Measure bodyweight. Measure blood pressure. Measure plasma lipids (except in extreme old age). Measure visual acuity. Examine state of retina (ophthalmoscope or retinal photo). Test urine for proteinuria/microalbuminuria. Test blood for renal function (creatinine). Check condition of feet, pulses and neurology CVS examination for macrovacular complications. Check injection sites for infection, lipotrophy or lipohypertrophy. Check for infection e.g. , cellulitis

3- This manâ&#x20AC;&#x2122;s HbA1c is 9%. What is HbA1c? What advice would you give this man? What % HbA1c is desirable for this man? Why is good glycemic control important? HbA1c is glycosylated haemoglobin, is produced by the attachment of glucose to Hb and measurement of this normally (4-8%) is useful measure of the average glucose concentration over the life of the Hb molecule (approximately 6 weeks). It provides a rapid assessment of the level of glycaemic control in the patient in the last about 2 months. The desirable % for this patient is 7-7.5%, (6 % in upper limit in non diabetic). Advice for this patient: that his glycaemic control is good, and he had to lower the HbA1c to 7 -7.5 % in order to to prevent the complications, and this can be done by good diet, compliant with medication, exercise, change life style. Good glycemic control is important to prevent the complications.

4- This man is also noted to have microalbuminuria. What is the significance of this and how will you treat it? Microalbuminuria is a predictor marker of progression to nephropathy in type1 diabetes and of increased cardiovascular risk in type 2 diabetes. Microalbuminuria may after some years to progress; to intermittent albuminuria followed by persistent proteinuria after this the patient is only 5-10 years from end stage renal failure. Treatment: aggressive treatment of blood pressure with target below 130/85 mmHg, by ACE inhibitors or an angiotensin receptor 2 antogonist, these drugs should also used in normotensive patients with persistent Microalbuminuria. OCT, 2004, CASE 3: A 60 year old woman presents to the endocrinology clinic complaining of increased sweating, thirst, polyuria and poldipsia. She describes frequent headaches and recent onset tingling of her fingers particularly at night. She has an oral glucose tolerance test. Time (min) Blood glucose (mmol/l) Growth hormone (mU/l) 05 6 12 30 13 15 60 15 22 90 14 38 120 12 26

1- WHAT ARE THE LIKELY DIAGNOSIS ? Acromegaly and DM 2- WHAT IS THE MOST LIKELY CAUSE OF THE GROWTH HORMONE ABNORMALITY ? pituitary tumours 3-WHAT OTHER SYMPTOMS SHOULD BE LOOKED IN THIS PATIENT ? SYPMTOMS OF ACROMEGALY : change in appearance , increased size of hands / feets , headaches , excessive sweating , visual deterioration , tiredness , weight gain , amenorrhoea / oligomenorrhoea in women , galactorrhoea , impotence or poor libido. SYMPTOMS OF DM : thirst , polyuria , lethargy , weight lost , polydipsia , lack of energy , visual problem , pruritus vulvae , symptoms of DM complications. 4-HOW WILL YOU MANAGE THIS PATIENT ? Investigations •

•

• • • • •

Surgery is the treatment of choice in suitable patient may be trans-sphenoidal , or transfrontal if the tomour is large. Surgery is often combined with radiotherapy because excision is rarely complete with large tumours ( macroadenomas >1 cm in diameter) . External beam radiotherapy is normally used after pituitary surgery fails to normalise GH levels , rather than primary therapy . it may take 1-10 years to be effective when used alone .

Drugs Octreotide and the long –acting preparation , lanreotide, are analogues of somatostatin ( GH-inhibitory hormone) and are given SC injection in resistant cases , they are given to shrink tumours before definitive treatment or to control symptoms . Bromocriptine , or Gabergoline ( dopamine agonists) is usually reserved for elderly and frail people , used as an adjunct or if the patient is not good operative risk . Pegvisomant , a GH- receptor antagonist is new agent for patient where GH levels cannot be safely lowered with somatostatin analogues alone . TREAT THE DM AS WELL OCT, 2005, 2C: WRITE SHORT NOTES ON: CLINICAL AND LABORATORY FEATURES OF ADDISON’S DISEASE: Clinical features: SYMPTOMS: weight lost , anorexia , malaise , weakness , fever , depression , impotence/amenorrhoea , N&V , diarrhoea , confusion , syncope from postural hypotension , abdominal pain , constipation , myalgia , joint or back pain . SIGNS: pigmentation especially of new scars and palmar creases , buccal pigmentation , postural hypotension , loss of weight , general wasting , dehydration , loss of hair (vitiligo) , fever , tachycardia , shock , coma . Laboratory features: •

•

• • • • • • •

Single cortisol measurements are of little value, although a random cortisol below 100 nmol/L during the day is highly suggestive, and a random cortisol > 550 nmol/L makes the diagnosis unlikely (but not impossible). The short ACTH stimulation test should be performed, an absent or impaired cortisol response is seen, confirmed if necessary by a long ACTH stimulation test to exclude adrenal suppression by steroids or ACTH deficiency. A 0900 h plasma ACTH level - a high level (> 80 ng/L) with low or low-normal cortisol confirms primary hypoadrenalism. Electrolytes and urea classically show hyponatraemia, hyperkalaemia and a high urea, but they can be normal. Blood glucose may be low, with symptomatic hypoglycaemia. Adrenal antibodies are present in many cases of autoimmune adrenalitis. Chest and abdominal X-rays may show evidence of tuberculosis and/or calcified adrenals. Serum aldosterone is reduced with high plasma renin activity. Hypercalcaemia and anaemia (after rehydration) are sometimes seen. They resolve on treatment, but are occasionally the first clue to the diagnosis

Others: lymphocytosis, neutropenia, eosinophilia, abnormal LFT. APRIL , 2005 , CASE 2: A 44 year old woman presents with a gradual increase in tiredness over the past 6 months. This is accompanied by sweating and a change in her facial appearance. Friends have commented on her face and jaw becoming more prominent. She has noted that her rings no longer fit and her shoe size has increased. Her GP performed a number of tests: Hb 13g/dl, WCC 5.4 x 109/L, urea 5.8mmol/L, creatinine 80mmol/L, free thyroxine 15 pmol/L, TSH 3.0 mU/L, blood sugar 12mmol/L. 1- WHAT IS THE LIKELY DIAGNOSIS ? The most likely diagnosis is acromegaly :growth hormone excess due to pituitary tumour in most cases or hyperplasia due to GHRH excess is very rare. Incidence is 4-5 / million per year. 2- WHAT PHYSICAL SIGNS WOULD YOU LOOK FOR THIS PATIENT ? Signs: prominent supraorbital ridge , prognathism , interdental separation , large tongue , hirsutism , thick greasy skin , spade-like hand and feet , tight ring , carpel tunnel syndrome , visual field defects , galactorrhoea , hypertension , oedema , heart failure , arthropathy , proximal myopathy , glycosuria , plus possible signs of hypopituitarism . 3- OUTLINE HOW WOULD YOU MAKE A DEFINITIVE DIAGNOSIS ?

Investigations •

•

• • • • •

4- HOW WOULD YOU TREAT THIS PATIENT ? Surgery is the treatment of choice in suitable patient may be trans-sphenoidal , or transfrontal if the tomour is large. Surgery is often combined with radiotherapy because excision is rarely complete with large tumours ( macroadenomas >1 cm in diameter) . External beam radiotherapy is normally used after pituitary surgery fails to normalise GH levels , rather than primary therapy . it may take 1-10 years to be effective when used alone . Drugs Octreotide and the long â&#x20AC;&#x201C;acting preparation , lanreotide, are analogues of somatostatin ( GH-inhibitory hormone) and are given SC injection in resistant cases, they are given to shrink tumours before definitive treatment or to control symptoms . Bromocriptine , or Gabergoline ( dopamine agonists) is usually reserved for elderly and frail people , used as an adjunct or if the patient is not good operative risk . Pegvisomant , a GH- receptor antagonist is new agent for patient where GH levels cannot be safely lowered with somatostatin analogues alone .

Year? (similar to October 2006, Q1) A 48 yr old woman with type 1 DM diagnosed 10 yrs ago attends your clinic for her annual check-up 1. What are the microvascular and macrovascular complications? What are the risk factors for their development? Type 1 diabetes accounts for approximately 5-10% of patients and is generally due to autoimmune destruction of beta islet cells leading to absolute insulin deficiency. Although typically diagnosed in patients before age 30, it can present at any age due to variablity in the rate of beta cell destruction. Associated with anti-GAD and anti-islet cell antibodies. Microvascular complications: Retinopathy, neuropathy, nephropathy -Pathophysiology of the development of retinopathy => High blood flow in the retina caused by hyperglycaemia triggers capillary endothelial change. This causes increase in vascular permeability, leakage and microaneurysm formation. Obliteration of retinal capillaries leads to intraretinal microvascular abnormalities (IRMA). As capillary obliteration becomes extensive, intraretinal haemorrhages may develop.

Background retinopathy: Microaneurysms (dots), microhaemorrhages (blots), + hard exudates Preproliferative retinopathy: Cotton-wool spots + extensive microhaemorrhages Proliferative retinopathy: New vessel formation. Urgent referral! Maculopathy: More common in Type 2 DM. Suspect if decrease in visual acuity -Neuropathy => Complicated process leads to the development of neuropathy. Dyslipidaemia, hyperglycaemia, decrease in insulin, and growth factor abnormalities all lead to glycosylation of blood vessels and nerves. Types of neuropathy: a) Symmetric sensory polyneuropathy: distal numbness, tingling, and visceral pain that is worse at night. 'Glove and stocking' distribution. b) Mononeuritis multiplex: especially affects the III and VI cranial nerves. c) Amyotrophy: painful wasting of the quadriceps, reversible! d) Autonomic neuropathy: Postural hypotension, urinary retention, impotence, diarrhoea at night. Gastroparesis. -Nephropathy => Nephropathy occurs 10-15 years post-diagnosis and is characterised by macroalbuminuria (>200ug/min albumin excretion, or 300mg/24 hrs). There is also a decreased GFR and increase in BP. 30-40% of patients on dialysis have diabetic nephropathy. Renal failure occurs about 15-30 years post-diagnosis (nephrotic range proteinuria >3g/24 hrs) Pathology: nodular capillary glomerulosclerosis (Kimmelsteil-Wilson nodules). Pathophysiology: There is renal hyperperfusion associated with an increase in GFR. This increased blood flow leads to an increase in extracellular matrix production and endothelial damage. This endothelial damage leads to an increased glomerular permeability to macromolecules. Mesangial expansion and interstitial sclerosis ensues causing the glomerulosclerosis. Micoralbuminuria (>20ug/min albumin excretion) first sign of the developing nephropathy Good glycaemic control will delay the onset of microalbuminuria. ACE inhibitor reducing BP reduces level of microalbuminuria, delaying the onset of renal failure. If ACE inhibitor produces side effects, use an angiotensin receptor blocker.

Macrovascular complications (commonest cause of death in diabetics): Cardiovascular disease, cerebrovascular disease, peripheral vascular disease. -Cardiovascular disease => MI is 3-5 times more likely in a diabetic. May be silent. -Cerebrovascular disease => Stroke is twice as common. -Peripheral vascular disease => Amputation can be avoided with proper control of risk factors and early recognition of developing disease. Treatment: Statin therapy is first line to reduce cholesterol levels. Fibrates are useful if TGs are raise and HDL is low. BP should be maintained <130/80, ACE inhibitors are first line.

Risk factors Poor glycaemic control Hypertension Hyperlipidaemia Smoking Increasing years post-diagnosis

2. Important points in the history and exam at the annual exam -History: What insulin regime is she on? How is she handling the regime? Does she adjust her insulin in accordance to heavy exercise or illness? How has control been? (look at glucose diary) Any hypoglycaemic episodes? How often, what level (e.g. 2.2), when do they occur? Any sever hypos? (requiring the help of someone)

Do they feel sweaty, tremulous, hungry when going low? At what level do they feel symptoms? (assessing for hypo unawareness) Has there been any hospitilisations in the last year? (e.g. DKA, MI) How has she been managing psychologically? Is she motivated? Re: complications. Any recent change in vision? Intermittent claudication? Ulcer formation? Infections? -Exam: BMI BP (aim for <130/80) Dilated fundoscopy (0.5% tropicamide) CVS exam (including carotids, assessing for AAA, peripheral pulses) Assess injection sites (lipoatrophy, lipohypertrophy, infection) Feet (peripheral pulses, monofilament testing, vibration, proprioception, atrophic skin changes, look for ulcers in between toes and at pressure points, any deformities suggestive of a Charcot's joint, look for signs of infection) Dipstick urine If the results are there, review: ECG Lipid profile Microalbuminuria HbA1c (aim for <7%) TFTs (type 1 DM is an autoimmune process a/w other autoimmune conditions such as Hashimoto's)

3. Her HbA1c is 9%. What advice would you give her? What is the target HbA1c? Why is good glycaemic control important?

HbA1c is glycosylated haemoglobin. It approximates the glycaemic control for the past 8 weeks (half-life of red blood cells). The HbA1c is 9% which is above the target of 7%. Tight control is recommended as it delays the onset of microvascular complications. I would re-educate this woman regarding the potential serious complications. Ask her if she has any worries and where she thinks she could improve her control. Advise regarding diet and exercise and the importance of balancing these with her insulin regime. As she is a Type 1 diabetic, I could also consider referring her to the DAFNE program (see note below). Good glycaemic control is important because it delays the onset of microvascular complications. On the one hand, hyperglycaemia can lead to complications and DKA. But on the other hand, sever hypoglycaemia can result in coma and death. Important to try and achieve a balance. Also helps patient feel better to maintain glucose within a target range, not swinging from really high to really low. 4. She has microalbuminuria. What is the significance of this and how will you treat? Significance: the first sign of the development of diabetic nephropathy. Treatment: ACE inhibitor not only reduces BP, it reduces the level of microalbuminuria. First line therapy. Slows progression to chronic renal failure (even if the patient is normotensive before the onset of therapy). ARB if side effects to ACE inhibitor (bad cough).

Diabetes tidbits (extra information): DAFNE program: Dose Adjustment For Normal Eating currently being run in Beaumont Hospital (and a few others in Dublin). A five day program, it runs from 9-5 on a Monday to Friday. Intensive education of patients regarding carbohydrate counting and adjusting doese of insulin accordingly, and also adjusting 'correction doses' of insulin if they are running high. Gives patients more freedom in choosing what they want to eat. It has been proven to reduce HbA1c by up to 1%. Patients are more autonomous in their control. GLP-1 analogues: New drug being licensed for use in Ireland in April. Add-on therapy for Type 2 diabetes. A sub-cut injection twice daily. GLP-1 (glucagon like peptide-1) is a naturally occurring hormone that acts by stimulating beta cells to secrete insulin. Promotes weight loss, no associated hypoglycaemia. Side effect is gastric fullness due to delayed gastric emptying. Kidneys Nerves Infection Vascular Eyes Skin-- complications CSII: Continuous Subcutaneous Insulin Infusion. Insulin pump.

Studies to know => DCCT, EDIC, UKPDS

April 2006 2e) The causes, manifestations, clinical features, and treatment of Addison's disease. Addison's disease is a syndrome due to the inadequate secretion of corticosteroid hormones by the adrenal glands. Primary adrenal insufficiency. Causes: -70-80% are idiopathic (most likely due to an autoimmune process and associated with other autoimmune conditions such as Graves', Hashimoto's, IDDM, pernicious anaemia, hypoparathyroidism, vitiligo) -20% Tuberculosis -Metastases (but only after >90% of adrenal gland is involved) -AIDS (opportunistic infections including MAI and CMV) -surgery, radiation, drugs, amyloidosis, sarcoidosis Symptoms (often non-specific): Weakness, fatigue Anorexia, weight loss Dizziness GI upset: nausea, vomiting, diarrhoea, abdominal pain Salt craving Confusion Depression Arthralgia Myalgia Signs:

Hyperpigmentation (palmar creases, buccal mucosa) Vitiligo Postural hypotension (assess BP when lying and standing) Hypoglycaemia Electrolyte imbalance (increase K+, decreased Na) Addisonian crisis Addisonian Crisis May present in shock (tachycardia, peripheral vasoconstriction, oliguria, weak, confused, or comatose). Or may present with hypoglycaemia. Most often occurs in someone with known Addison's disease on long-term steroids that has forgotten to take their tablets or has not been taking things orally (e.g. severe vomiting without replacing steroids). May be precipitated by trauma, infection, surgery. If suspected, treat before biochemical results come back! -Send blood for cortisol level and ACTH if possible -Hydrocortisone sodium succinate 100mg IV stat -IV fluid resuscitation -Monitor blood glucose (watch for hypoglycaemia! May need to start glucose IV) -Blood culture, MSU, sputum for culture (may have infective precipitator) -Give antibiotics (e.g. cefuroxime 1.5g/8h IVI) -Change to oral steroids after 72 hrs if patient is doing well -Search for cause once crisis is over Investigations: -Synacthen (tetracosactide) test (do plasma cortisol before and 30 mins after administration of synacthen 250ug IM. Exclude Addison's disease if initial cortisol is >140nmol/L and second cortisol is >500nmol/L. -ACTH level will be inappropriately high >300ng/L/

-Generally, K+ will be high, Na and glucose will be low -Plasma renin activity and aldosterone -Adrenal antibodies -CXR: looking for signs of TB Treatment: Replacement therapy -Hydrocortisone 20mg mane, 10 mg nocte PO. -Mineralocorticoid replacement may not be necessary (monitor BP for postural hypotension, electrolytes, and plasma renin activity). If needed, fludrocortisone PO 0.05mg every other day, or 0.15mg daily. Adjust on clinical grounds. Warn about abruptly stopping steroid therapy => Addisonian crisis. Must double steroids if febrile, injured, or in severe stress. If vomiting, give hydrocortisone sodium succinate IM and seek help. All patients should have hydrocortison sodium succinate injections available at home. Medical alert bracelet stating that they're on long-term steroid therapy. -Monitor for other autoimmune conditions, e.g. TFTs -Yearly follow-up.

Ethics

April ’05 Case 6 Richard, a 35-year-old patient, presents with a dry cough having recently returned from a four-month-long business trip to South Africa. On the point of leaving the room, he says “by the way, I’m a bit concerned – I slept with a woman while away, and I’m worried I might have picked up a dose” (acquired a sexually transmitted infection).You counsel him before taking blood for an HIV test. He returns a week later and you have to advise him that the results show him to be HIV positive. He is married with two children, and his wife is also one of your patients. He is very upset when you raise the question of discussing the results with his wife. He says “No Way! Our marriage is in enough trouble as it is. He then threatens to sue you for breach of confidentiality, if his HIV status becomes known to his wife. 1. Do you try to contact his wife? Support your answer with reasons 2. To whom is your Duty of Care? 3. How can you deal with this situation satisfactorily? Include reference to the 4 main ethical principles in your answer. 1) Do you try to contact his wife? Support your answer with reasons. Yes. Breach of confidence would be justified in this situation due to potential harm to another patient. 16.3 Exceptions to Confidentiality There are four circumstances where exceptions may be justified in the absence of permission from the patient: (1) When ordered by a Judge in a Court of Law, or by a Tribunal established by an Act of the Oireachtas. (2) When necessary to protect the interests of the patient. (3) When necessary to protect the welfare of society. (4) When necessary to safeguard the welfare of another individual or patient 16.9 Communicable Diseases Where others may be at serious risk if not aware that a patient has a communicable infection, a doctor should do his/her best to obtain permission from the patient to tell them, so that appropriate safeguards can be put in place. If the patient refuses to consent to disclosure, those who might be at risk of infection should be informed of the risk to themselves. 2) To whom is your Duty of Care? 11.3 Responsibility for Care Doctors using deputising facilities are reminded of their continuing responsibility for the care of their patients- in this case both spouses. 3) How can you deal with this situation satisfactorily? Allow patient time to reflect on diagnosis and come to terms/ acceptance. Try again reasoning with patient to disclose to wife, arrange for a mediator to facilitate discussion if patient wants. Counsel both patients accordingly. 65

April '06, 3b (1 & 2) You are a surgical intern in a busy teaching hospital. Late one night after a hospital party, Sarah, a highly competent and popular junior surgical colleague, (a fellowintern on your team), tells you that she thinks she is Hepatitis C +ve. You have known her since medical school and you often work ’on call’ together. The next morning you are sitting in the hospital canteen when the staff nurse on your ward approaches you and asks “Could I talk to you for a minute?” She is concerned that drugs, in particular morphine ampoules, have been going missing from the controlled drugs trolley on her ward. She is suspicious that Sarah has been taking them. Other nursing staff on the ward are also suspicious. Nobody has done anything about it because of Sarah’s popularity 1. 2.

What ethical issues arise in this case? Illustrate your answer with reference to the major ethical principles. How would you deal with this case?

4.3 A Colleague’s Conduct and Competence Where risk to a patient exists in relation to a colleague’s conduct or competence, doctors should express their concern initially to the colleague concerned and advise remedial action. Where local systems of support or remediation are available they should be availed of as the next step. Should the colleague’s response be unsatisfactory, then the doctor should refer the matter to the Medical Council.

GIT

May 2002 CASE 3 A 26 year old man presents to his doctor with jaundice. His alcohol intake is 10 units/week and he is on no medication. He has been unwell for 8 weeks with anorexia, nausea and malaise and abdominal discomfort. Examination reveals jaundice, mild fever and a tender liver which is normal in size. There is no clinical evidence of chronic liver disease. 1. What additional information is required to help prioritize your differential diagnoses? • Ingestion of contaminated food or water • Place of overcrowding and poor sanitation • Dark urine/pale stools • Recent travel • Vaccinations • Blood transfusions • IVDA • Tattoos • Sexual activity – male homosexuals • Drugs • Recent infections • History of wilson's disease or alpha 1 antitrypsin deficiency 2. What are the clinical signs of chronic liver disease? • Hands: o leuchonychia o Tery’s nails o palmar erythema o dupuytran’s contracture o clubbing o xanthoma o pale palmar creases o hepatic flap • Face: o parotid enlargement o jaundice o xanthalesma o telangectasia o fetor hepatus • Neck and Chest: o spider nevi o gynacomastia o loss of body hair • Abdomen: o hepatomegaly or small liver

•

o scrath marks o ascites o splenomegaly o esophageal varices/distended veins Others: o testicular atrophy o purpura o pigmented ulcers o edema o confusion o coma o bleeding

3. Investigations Test Result Ref Range Bilirubin 98 (1 – 17 mol/l) ALT 1126 (2 - 35 IU/l ) AST 642 (4 - 40 I /l) GGT 198 (0 - 58 I /l) ALP 320 (42 - 121 I /l) How do you interpret these results? • • • •

Hyperbilirubinemia caused by hepatobiliary disease is accompanied by other abnormalities of liver biochemistry; very high levels occur in biliary tract obstruction. AST and ALT are enzymes present in hepatocytes and leak into blood with liver cell damage. Very high levels may occur with acute hepatitis (20-50 times normal) ALP is situated in the canalicular and sinusoidal membranes of the liver and raised concentrations are seen in cholestasis from any cause GGT is a liver microsomal enzyme which may be induced by alcohol and drugs. In cholestasis it rises in parallel with ALP because they have a similar pathway of excretion

4. What serological investigations would you request? Why? Incubation Acute Carrier Recovery HBsAg + + + HBeAg + + +/Anti-HBs + Anti-HBe +/Anti-HBc IgM + +/Anti-HBc IgG + + + Anti HAV IgM – acute infection with hepatitis A virus Anti HCV – infection with hepatitis C virus

Vaccinated +

October 2002 CASE 3 A 32 year old busdriver presents to the A & E Department having “vomited up blood”. He has had upper abdominal pain over the preceding 4 weeks. This has awoken him from sleep on 3/4 occasions. Three years previously he had sustained a back injury in a road traffic accident (RTA) which continued to bother him and for which he took “painkillers”. He has a long history of intermittent “indigestion” which is relieved by antacids. 1 What is your differential diagnosis? • • • • • • • •

Peptic ulcer Mallory-weiss Esophageal varices Reflux esophagitis Malignancy (esophageal/gastric) Drugs – aspirin, NSAIDs, anticoagulants Bleeding disorder Hereditary hemorrhagic telangectasia

2 What additional information from the patient would help you to confirm your diagnosis? • • • • • • • • •

History of peptic ulcer disease History of steroids/ NSAIDs/ aspirin Previous GI bleed Alcohol consumption Any forceful vomiting before hematemesis Any liver disease History of dysphagia, retrosternal burning chest pain Weight loss Pain related to hunger, eating specific types of food, or time of day.

3 What are the important considerations in the clinical evaluation of this patient? Age, signs of shock (systolic BP and pulse rate), co-morbidity's, diagnosis, and signs of recent hemorrhage on endoscopy. Rockall risk scoring system for GI bleeds Score 0 1 Age <60 60-79 Systolic BP >100 mmHg >100 mmHg Pulse Rate <100/min >100/min Co-morbidity No major Cardiac Failure IHD

2 >80 <100 mmHg

Renal failure Liver failure

Metastases

Diagnosis

Signs of recent Hemorrhage on endoscopy

Mallory-weiss tear; No lesion; No sign of recent bleeding

All other diagnoses

None, or dark-red spot

Upper GI malignancy

Blood in upper GI tract; Adherent clot; Visible vessel

Rockall scores help predict risk of rebleeding and death after upper GI bleeding. A score of >6 is said to be an indication for surgery. 4 Outline your management strategy. • Protect airway and give high flow oxygen • Insert 2 large bore IV cannulae and take blood for FBC, U+E, LFT, clotting, cross-match • Give IV colloid • Transfuse until hemodynamically stable • Correct any clotting abnormalities • Monitor pulse, BP, and CVP • Insert urinary catheter and monitor urinary output • Quick History o Peptic ulcer o Aspirin/NSAIDs o Vomiting preceding the hematemesis (Mallory Weiss) o Liver disease (varices) • Organize CXR, ECG, and ABG • Arrange an urgent endoscopy o Determine site of bleed o If varices treat with sclerotherapy or banding IV terlipressin/octereotide Balloon tamponade with sengstaken-blakemore TIPS Surgery o If ulcer inject dilute epinephrine or coagulate the vessel with heater or bipolar probe H. pylori eradication Stop NSAIDs • Notify surgeons of all severe bleeds on admission 5 What is the relationship of helicobacter pylori to peptic ulcer disease? How would you confirm its presence in the stomach?

•

H. pylori is one of the most important causes of peptic ulcer disease, but the mechanism of how this works is not clear. The following factors have been implicated: o H. pylori is found in the gastric antrum and infection with it causes gastritis mainly in the antrum o There is increased acid secretion because of increased parietal cell mass and increased gastrin secretion o H. pylori produce virulent factors/toxins such as Vac A, Cag A, urease, and adherence factor o Decreased inhibition of gastric acid secretion as H. pylori inhibits somatostatin o Genetic susceptibility o Local epithelial damage by cytokines released by H.pylori

•

To confirm presence of H. pylori o Non-invasive 13C urea breath test Serological tests – IgG antibodies Stool test o Invasive (endoscopy) Rapid urease test Culture and sensitivity Histology – on routine Giemsa stained section of gastric mucosa October 2003 2(c) Prognostic criteria in acute pancreatitis See April 2003 Case 6 question 3, but add (Age > 55 years) 2(e) Differences between Crohn’s disease and ulcerative colitis Cause Smoking Macroscopic

Crohn's Unknown Mutations in NOD2/CARD15 gene Increase risk by 3-4 fold Any part of the gut from mouth to anus (oral and perianal disease) Skip lesions Deep ulcers and fissures in the mucosa (cobblestone appearance)

Histology

Transmural inflammation Granulomata

Immunology Clinical Features

Th1 response Diarrhea RIF mass Perianal abscess/fistulae/skin tags 72

Ulcerative Colitis Unknown Protective Begins in the rectum and extends proximally Continuous involvement Red mucosa which bleeds easily Ulcers and Psuedopolyps Mucosal inflammation Goblet cell depletion Crypt abscesses Th2 response Gradual onset of diarrhea +/- blood and mucous Urgency and tenesmus

Anal/rectal strictures Complications Small intestinal obstruction Abscess and fistulae formation Less risk of colon cancer Investigations

Perforation Bleeding Toxic dilatation More risk of colon cancer

Serum iron, folate, B12 Small bowel enema

CASE 1 A 45 year old lady attends her doctor with a swollen abdomen. .On talking to her you find that alcohol intake is constant at 35 units per week. On examination she has 11 spider naevi, facial telangiectasia and palmar erythema. The abdomen is distended with fluid, the liver is impalpabl the spleen is palpated 4 cm below the costal margin. Haemoglobin is 11g/dl, platelet count is 86 x 109 /L, prothrombin time is 17 s (control 13s), aspaminotransferase 54 IU/L, and serum albumin 26g/l 1. What is the most likely diagnosis? What are the potential causes? Liver cirrhosis secondary to • Alcohol (since she consumes 35 units of alcohol/week) • Or biliary cirrhosis or Budd-chiari syndrome (because her enlarged spleen could be as a result of obstruction of the portal vein, within the liver, or the hepatic vein) 2. What further investigations are required? • Liver biochemistry normal or slight elevation in Alk phosph, AST, ALT • U+E low sodium indicates very severe liver disease • Alpha fetoprotein if >400ng/ml indicates hepatocellular carcinoma • Viral serology • Serum autoantibodies • Serum immunoglobulin • Iron, ferretin, TIBC • Copper • Alpha-1 antitrypsin • Abdominal ultrasound • CT abdomen • Endoscopy • MRI • Liver biopsy 3. How should this patient be managed? • 6 monthly ultrasound and alpha fetoprotein to detect hepatocellular carcinoma • No treatment that will arrest or reverse the process although progression halted by correcting underlying cause: o Avoid alcohol, aspirin, NSAIDs, decrease salt intake • Treat complications:

o Portal hypertension + variceal hemorrhage Prophylactic treatment with oral propanolol Endoscopic therapy (sclerotherapy, banding) IV terlipressin/octereotide Balloon tamponade with sengstaken-blakemore TIPS Surgery o Ascites Diuretics (restrict sodium intake, oral spironolactone, frusemide) Paracentesis o Encephelopathy Oral lactoluse, antibiotics, high carbohydrate low protein diet April 2003 2(d) Clinical features and causes of cirrhosis •

Clinical Features of Cirhosis: o Can be asymptomatic o Features of the liver disease: Hands: leuchonychia, Tery’s nails, palmar erythema, dupuytran’s contracture, clubbing, xanthoma, pale palmar creases Face: parotid enlargement, jaundice, xanthalesma, telangectasia Neck and Chest: spider nevi, gynacomastia, loss of body hair Abdomen: hepatomegaly or small liver, scrath marks Others: testicular atrophy, purpura, pigmented ulcers, edema o From complications: Coagulation defects bleeding Encephalopathy hepatic flap, fetor hepatus, confusion, coma Sepsis spontaneous bacterial peritonitis Portal hypertension ascites, splenomegaly, esophageal varices/distended veins

•

Causes of Cirhosis o Common: Alcohol Hepatitis B, Hepatitis C o Others: Primary Biliary Cirrhosis Secondary Biliary Cirrhosis Autoimmune hepatitis Hereditary hemchromatosis Budd-Chiari syndrome Wilson’s disease Alpha -1 antitrypsin deficiency Drugs (methotrexate) Cystic fibrosis

Non alcoholic fatty liver disease Galactosemia Veno-occlusive disease Idiopathic CASE 2 A 46 year old male presents with an intensely itchy vesicular rash on the extensor aspects of his limbs, buttocks and shoulders. He has applied Iodine which only served to make the itch much worse. He has been feeling tired recently and complains of abdominal pain and intermittent loose stools which are offensive and difficult to flush. His FBC shows a Hb of 8.4 g/dl with a raised MCV. 1. What is the likely explanation for his rash and gastrointestinal symptoms? Dermatitis herpitiformis associated with gluten sensitive enteropathy (celiac disease) 2. What further investigations would you recommend? • • •

• • • • • • •

Endomysial (EMA) and tissue transglutamate (tTG) antibodies (IgA) Anti-reticulin antibodies Duodenal/ jejenal biopsy which shows: o Absent/stunted villi with elongation of crypts (subtotal villous atrophy) o Chronic inflammatory cells infilterate in lamina propria o Increase intraepithelial cell lymphocytes Hematological: foalte and iron deficiency, raised MCV Blood film: hypersegmented polymorphonuclear leucocytes and Howell Jolly bodies Small bowel follow through: dilatation of small bowel with change in fold pattern and thickening of the folds. Wireless capsule endoscopy Bone densitometry (because of high risk of osteoporosis) Biochemistry hypoalbuminemia, hupocalcemia, hyperphosphatemia For the itchy rash: o Skin biopsy subepidermal blister with neutrophil abscesses in dermal papillae o Direct IMF studies IgA in dermal papillae and patchy granular IgA along basement membrane

3. How will you manage this patient? After a full history, thorough physical exam, and necessary investigations, I will manage him by: • Life long gluten free diet • Replacement of iron, calcium, and folic acid • Dietry adherence is monitored by serial EMA and tTG • Pneumococcal vaccine (because of splenic atrophy) once every 5 years • Oral dapsone (50-200mg) daily or sulphonamide will help with the rash 75

4. List the common bullous disorders • Pamphigus vulgaris • Bullous pemphigoid • Dermatits herpitiformis • Linear IgA disease – chronic bullous dermatitis of childhood • Epidermylosis bullosa CASE 6 A 56 year old man presents with vomiting and severe pain in the epigastric region radiating into the back. The pain is relieved somewhat by leaning forward. On examination he has tachycardia, epigastric guarding and tenderness, hypoactive bowel and a bluish discoloration around the umbilicus. 1. What are your differential diagnoses? • Acute pancreatitis • Perforated duodenal ulcer • Acute cholecystits • AAA • Small bowel obstruction • Biliary colic • Pyloric stenosis • MI • Pericarditis • Pneumonia 2. Initial blood tests show a markedly raised amylase and you suspect acute pancreatitis. What other conditions are associated with elevated serum amylase and what tests can be performed to determine whether this patient has acute pancreatitis? • Serum amylase is elevated in o Perforated duodenal ulcer o Acute cholecystitis o Biliary peritonitis o Macroamylasemia o Severe uremia o DKA •

Investigations for acute pancreatitis o Serum amylase o Urinary amylase o Serum lipase o Erect CXR – to exclude perforated duodenal ulcer o PFA – gallstones or pancreatic calcification o Abdominal ultrasound – gallstones and swelling of inflamed pancreas

o CT scan and MRCP – evidence of pancreatic necrosis and peripancreatic fluid collection 3. What laboratory tests will you perform on admission and during the initial 48 hours hospitalization to determine the severity of this patient’s condition? Modified Ranson's / Glascow criteria PaO2 < 8 kPa WBC > 15 x 109/L Ca2+ < 2 mmol/L Urea > 16 mmol/L LDH > 600 iu/L AST > 200 iu/L Albumin < 32 g/L Glucose > 10 mmol/L APACHE Score 4. Outline your initial treatment of this patient • NPO • IV access and IV fluids (saline 0.9%) • Analgesia pethidine/tramadol (not morphine because it causes contraction of sphincter of Oddi) • NG suction • Prophylactic antibiotics decrease risk of infective complications • Monitor pulse, BP, urine output • Daily FBC, U+E, Ca, glucose, amylase, and ABG April 2004 Write short notes on 2(c) Differential diagnosis of splenomegaly Massive Hematological Chronic Myeloid Leukemia Myelofibrosis Infectious

Chronic Malaria Kala Azar Schistosomiasis

Inflammation Others

Tropical splenomegaly Gaucher’s

Moderate Lymphoma Leukaemia Myeloprilifeative disorders Haemolytic anemia Acute: endocarditis, typhoid Chronic: TB Parasitic: malaria Rheumatoid Arthritis SLE Sarcoidosis Portal Hypertension Amyloidosis Gaucher’s

October 2005 Write short notes on (2d) Indicators of high risk in people with upper gastrointestinal bleed Rockall risk scoring system for GI bleeds Score 0 1 Age <60 60-79 Systolic BP >100 mmHg >100 mmHg Pulse Rate <100/min >100/min Co-morbidity No major Cardiac Failure IHD Diagnosis Mallory-weiss tear; All other No lesion; diagnoses No sign of recent bleeding Signs of recent None, or dark-red Hemorrhage on spot endoscopy

2 >80 <100 mmHg

Renal failure Liver failure Upper GI malignancy

Metastases

Blood in upper GI tract; Adherent clot; Visible vessel Rockall scores help predict risk of rebleeding and death after upper GI bleeding. A score of >6 is said to be an indication for surgery. CASE 4 A 42 year old man was diagnosed as having ulcerative colitis 3 years ago. Colonoscopy and biopsy at the time showed a mild pancolitis. Over the past 3 months he has become gradually unwell with weight loss, intermittent pyrexia, and bouts of upper abdominal pain. His colitis seems stable. His medications at present are mesalazine 800mg tds. FBC/ESR: Hb 10g/dl, WCC 12.4 x 10 9/l, platelets 540 x 109, , ESR 75mm/hour LFTs: Bilirubin 67mmol/L, GGT 560 IU/L, ALT 230 IU/L, ALP 220 IU/L 1 Outline how you would investigate this man After a full history and a thorough physical exam, I will do the following investigations: • LFT alkaline phosphatase increase initially followed by increase in bilirubin • Immunoglobulins hypergammaglobinemia • Antibodies AMA is negative, but ANA, SMA, ANCA may be positive • ERCP multiple strictures of the biliary tree (characteristic beaded appearance) • MRCP • Liver biopsy fibrous obliterative cholangitis Inflammation of intrahepatic biliary radical associated with scar tissue (onion skin appearance)

2 What is the most likely cause of this man’s problems Primary Sclerosing Cholangitis 3 How is the diagnosis of ulcerative colitis made? • Histological examination of biopsy taken at colonoscopy showing the characteristic findings: o Chronic inflammatory cell infilterate in the lamina propria (mucosal) o Crypt abscess o Goblet cell depletion o Psuedopolyps o Deep ulcers o Glandular distortion • Serology ANCA found in 60% • Radiologically PFA, U/S, CT 4 What is his risk of developing colon carcinoma 15% of those with pancolitis for 20 years will develop colon carcinoma and thus need a 1 to 2 yearly surveillance colonscopy APRIL 06 (2c) Outline the clinical symptoms and signs of Crohn's Disease and how it is diagnosed? Crohn's disease is one of the 2 main recognized Inflammtory Bowel Diseases. It is common in the western world, occurring at any ate but mostly 20-40year olds with both sexes affected. Crohn's disease is a progressive chronic disease involving the whole bowel most commonly the ileocaecal region in 40% of patients. The main symptoms: 1. Abdominal pain and usually weight loss. Sometimes the abdominal pain can be localized to the RIF mimicking appendicitis. 2. diarrohea 3. Bleeding and pain related to defecation. 4. stool or flatus passage from vagina, bladder or skin as a result of fistula formation 5. Malnutrition (vit B12 or iron deficiency) 6. Growth retardation 7. Gallstones formation 8. Kidney stones Extra-intestinal signs: 1. Eyes: uveitis, conjunctivitis 2. Skin: Erythema nodosum, pyoderma granulosum 3. Liver: Fatty liver, Primay Sclerosing Cholangitis, chronic hepatitis, Cirrhosis

4. Arthritis: Ankylosing spondylitis and sacroilieitis Diagnosis is made of the clinical symptoms and signs combined with endoscopic or radiographic evidence. -FBC, showing anemia is common and is usually of a chronic picture so normochromic, normocytic type. Serum iron or B12 def also. - inflammatory markers would b raised ECR, CRP, WCC. Serological marker like Primay Sclerosing cholangitis's ANCA. -A small bowel enema will show an asymmetrical alteration in mucosal pattern with skip lesion suggests crohns dz. Also showing deep transmural ulcerations and areas of narrowing (string sign) commonly affecting the ileum -Rectal biopsy can be taken to show non-caseating granulomatious chronic inflammation and perianal disease. -Colonoscopy and sigmoidoscopy -Stool microscopy and culture - CT and ultrasound would be helpful in delineating abscesses. OCTOBER 06 (2f) write short notes on Clinical features and causes of Cirrhosis Cirrhosis is the irreversible liver damage with diffuse loss of liver architecture resulting with fibrosis and nodule formation. The end result is impairment of liver cell function and might progress to hepatocellular carcinoma. Pathology: Micro and macronodular cirrhosis occurs. Micro is nodules less than 3mm in size, maybe progress to macronodular cirrhosis as nodules can fuse together. Micronodular cirrhosis is a feature of alcohol and heamachromatosis cirrhosis. Macro is when nodules are larger than 3mm and is seen following hepatitis B infection. Clinical Features 1. Portal hypertension 2. Ascites 3. Palmer erythema 4. Clubbing of nails 5. spider nevi, and dilated veins on abdomen Caput medusa 6. gynecomastia 7. testicular atrophy 8. Oesophageal varices 9. variceal hemorrhage 10. could have jaundice and fever 11. Oedema of legs

12. hepato and splenomegaly: or liver can be shrunken in advanced stage of disease 13. hepatic encephalopathy: asterixis, confusion, coma 14. acute renal failure 15. hepatocellular Carcinoma Causes of cirrhosis COMMON 1. Alcohol 2. Chronic Hepatitis B 3. Chronic Hepatitis C OTHER 4. Primary Biliary Cirrhosis 5. Secondary Biliary Cirrhosis 6. Hereditary Haemochromatosis 7. Autoimmune hepatitis 8. Drugs ( methotrexate) 9. Cystic Fibrosis 10. Wilson's Disease 11. Budd- Chiari Syndrome 12. Alpha Anti-trypsin Deficinecy 13. Non- Alcoholic fatty liver 14. inborn Glycogen storage Dz 15. galactosemia 16. Idiopathic

Haem/Onc

October 2003- 2a) Write short notes on the clinical presentation of acute myeloblastic leukaemia. Due to marrow failure: Anaemia: fatigue, palpatations, tinitus. Infections (low WCC): esp. chest, mouth, perianal, skin, bacterial septicaemia, Zoster, CMV, measles, candidiasis, Pneumocystis pneumonia. Bleeding: prolonged bleeding from cuts, easy bruising, purpura, epistaxis, bleeding from gums, menorraghia) Due to infiltration: Hepato-splenomegaly lymphadenopathy (Superficial or mediastinal) Orchidomegaly CNS involvement: CN palsies, meningism General: weight loss fever night sweats October 2004 - CASE 5 A 34 year old woman presents with a history of easy bleeding and bruising which has been present for the last 3-4 weeks. She is found to have a low platelet count. 1. What is your differential diagnosis? Decreased marrow production: Aplastic anaemia (Drugs, chemicals, viruses, paroxysmal nocturnal haemoglobulinuria) Megaloblastic anaemia Myelodysplasia Myelofibrosis Marrow infiltration (leukaemia, myeloma) Marrow suppression (cytotoxic drugs, radiotherapy) Excess destruction: Immune: Immune thrombocytopenic purpura (ITP) SLE CLL Drugs (Heparin) Viruses Post-transfusion purpura

Non-immune: DIC Thrombotic thrombocytopenic purpura (TTP) Haemolytic Uraemic syndrome (HUS) Sequestration (hypersplenism) Dilutional (Massive transfusion) Decreased platelet function: Myeloproliferative disease NSAIDS High levels of Urea 2. What are the key points you should seek in your history? Extent of thrombocytopenia: Any rash? purpura Bleeding: epistaxis, bleeding from gums, menorrhagia Bone marrow malfunction: Low WBC: More susceptible to infections? Low RBC: fatigue, palpatations, tinnitus, were you ever diagnosed with anaemia? Neoplastic: weight loss, fever, notice any swelling (lymphadenopathy)? Drugs: cytotoxic drugs, radiotherapy Excess destruction: Recent infection? HUS, ITP SLE: photosensitivity, arthralgia Drugs: Heparin (HIT) Causes of splenomegaly (sequestration): Portal hypertension (causes of cirrhosis esp. alcohol) Haemolytic anaemia (jaundice) Neoplastic symptoms (as above) 3. What are the key points you should look for in your physical examination? Signs of thrombocytopenia: purpura, bleeding gums, bruising. Signs of infiltration: splenomegaly, hepatomegaly, lymphadenopathy. Signs of anaemia: conjuctival pallor, palmer crease pallor, ejection systolic murmur. Signs of infection: in skin, mouth, peri-anal area. Signs of systemic disease: SLE (malar flush, photosensitivity, arthritis) Signs of portal hypertension: jaundice, spider naevi, caput madusae

4. What investigations should be arranged? Haematological: shows thrombocytopenia (platelet count < 150 x 10^9/L), can be artefactual so ask haematologist to confirm by manual differentiation Bone marrow aspirate: increased megakaryocytes (look for neoplastic blast cells) Antiplatelet antibodies CXR and CT for mediastinal lymphadenopathy if malignancy suspected. October 2004- 2b) Write short notes on the diagnosis of anaemia of chronic disease and its causes. Diagnosis: History: Find a cause: fever, haemoptosis, arthralgia, weightloss, diarrhea Outrule other causes of anaemia: Fe def: haematemesis, malaenia, blood PR, heart burn, haematuria, menorrhagia, decreased Fe intake, etc Alcohol Hx, jaundice? (haemolytic) B12: glossitis, lemon tinged skin (mixed anaemia and jaundice) other autoimmune diseases (pernicious anaemia) hypothyroidism FH: thalasaemia drug hx: cytotoxic, NSAIDS Establish the extent of the anaemia: fatigue, palpatations, tinitus Exam: Find a cause: Temperature, murmur, rheu exam, hepatosplenomegaly, jaundice Signs of anaemia: palmer crease pallor, conjuctival pallor, tachycardia, ejection (systolic) flow murmur. Investigations: Haematology: Mild normocytic anaemia, ferritin could be normal or high, low TIBC *Look for a cause: Mantoux? high WCC? ESR? RhF+? Blood culture? CXR if suspect TB, X-ray if suspect osteomyelitis Causes: Chronic infection: TB, osteomyelitis, IE Vasculitis Rheumatoid arthritis

Malignancy Renal failure Ulcerative colitis, Crohn's disease April 2005- 2b) Write short notes on the causes of thrombocytopenia. Decreased marrow production: Aplastic anaemia (Drugs, chemicals, viruses, paroxysmal nocturnal haemoglobulinuria) Megaloblastic anaemia Myelodysplasia Myelofibrosis Marrow infiltration (leukaemia, myeloma) Marrow suppression (cytotoxic drugs, radiotherapy) Excess destruction: Immune: Immune thrombocytopenic purpura (ITP) SLE CLL Drugs (Heparin) Viruses Post-transfusion purpura Non-immune: DIC Thrombotic thrombocytopenic purpura (TTP) Haemolytic Uraemic syndrome (HUS) Sequestration (hypersplenism) Dilutional (Massive transfusion) Decreased platelet function: Myeloproliferative disease NSAIDS High levels of Urea April 2005- 2c) Write short notes on the staging of Hodgkin's disease. Ann Arbor system: influences treatment and prognosis, done by CXR, CT thorax, abdo, pelvis +/- bone marrow bx if B symptoms or stage III-IV I: Confined to a single lymph node region II: Involvement of two or more nodal areas on the same side of the diaphragm III: Involvement of nodes on both sides of the diaphragm IV: Spread beyond the lymph nodes e.g. liver or bone marrow *each stage is further subdivided to: 'A' : no systemic symptoms other than pruritis 'B': presence of B symptoms:

Weight loss > 10% in the last 6 months Unexplained fever >38'C Drenching night sweats (requiring change of clothes) *B indicates more extensive disease *Suscripted 'E' indicates localised extra-nodal extension (but doesn't advance stage) October 2006 2h. Write short notes on the treatment of Hodgkin’s disease There is no role for surgery in the treatment of Hodgkin’s disease. Chemotherapy and radiotherapy are mainstay of treatment based on stage Stage I- tumour involving a single lymph node region on 1 side of the diaphragm Stage II- 2 or more nodal areas on the same side of the diaphragm Stage III nodes present on both sides of the diaphragm Stage IV spread beyond lymph nodes to liver and bone marrow Localised disease is stage I and II Advanced disease is stage II and IV Radiotherapy: - Indicated in stage I disease and stage IIA with 3 or less areas involved – localised disease - It is also used after chemotherapy to sites where there was originally bulky disease- especially stage IIA with >3 areas involved up to stage IV B - It is also given to lesions causing serious pressure problems - good results are achieved in localised stage IA or stage IIA (disease with no adverse prognostic features) - given as subtotal lymphoid irradiation (no pelvic irradiation) or total lymphoid irradiation women may have an increases risk of breast cancer and should be screened patients who continue to smoke are at a higher risk of lung cancer also risk for melanoma, sarcoma, stomach and thyroid CA Chemotherapy: - indicated for all patients with B symptoms and localised or advanced diseae - stage II disease with more than 3 areas involved, stage III and IV disease - used as initial therapy MOPP regimen: nitrogen mustard, oncovorin, , prednisolone and procarbazine or ABVD (Adriamycin, bleomycin, vinblastine and dicabazole) - over 80% patients respond to this therapy, drugs are delivered on OPD basis every 3-4 weeks for 6-8 cycles (or every 2 weeks for 4-6 motnhs?) - treatment response is assessed by CT - risk: infertility in men and premature menopause in women

Acute toxicity: - nausea - neuropathy - pancytopaenia - alopaecia - pulmonary toxicity Combination of chemo/ radiothearpy: - Administration of radiotherapy to original site of bulky disease previously treated with chemotherapy to reduce the risk of relapse. - This form carries â&#x2020;&#x2018; complications Relapse treatment: - 10-20% risk of relapse - autologous bone marrow transplantation in relapsed disease - use to peripheral stem cell transplantation: autologous or allogenic to restore marrow function Main side effects of treatment: - hypothyroidism: annual TSH levels are needed - lung fibrosis and other side effects of radiotherapy - side effects of chemotherapy: N/V alopecia..etc - secondary malignancies: AML and NHL - iscahemic heart disease Unfavorable factors for localized disease - bulky disease - â&#x2020;&#x2018; ESR - 3 sites involved - B symptoms - Chest x-ray results Poor prognostic factors: - age - male - lymphocytopaenia - low albumin - anaemia - leukocytosis

Infectious Diseases

May 02 1) A 53 year-old woman presents with severe watery diarrhea and abdominal cramps. She is on her 7th day of a 10-day course of antibiotics prescribed for bronchitis. Describe how you evaluate this patient and how she should be treated? Evaluation: History: Diarrhea: How long? How often? Color? Consistency? Blood? Mucus? Pus? GI systems review: Pain? Tenesmus? Fresh rectal bleeding? Constipation? Weight loss? Anorexia? Symptoms of anemia? Recent travel? Non-GI causes: drugs (antibiotics, PPIs, cimetidine, propranalol, cytotoxics, NSAIDS, digoxin, alcohol, laxatives) medical conditions (thyrotoxicosis, autonomic neuropathy, Addisons disease) Exam: Inspection: Weight loss, anemia, dehydration, oral ulceration, clubbing, rashes, abdominal scars Palpation: enlarged thyroid, abdominal masses DRE: impacted feces, rectal mass, FOB Investigations: Blood: FBC, ESR, UE, ESR, CRP, TFTs, celiac serology Stool: microscopy for pathogens, Cl. difficile toxin Rigid sigmoidoscopy: erythema, white plaques, adherent pseudomembrane Colonoscopy Enema Treatment: Rehydration: oral better than IV - 0.9% saline + 20mmol K/L Codeine phosphate 30mg/6h PO reduces stool frequency Antibiotics: metronidazole 400mg 8-hrly PO or vancomycin 125mg 6-hrly PO; treat for 7 -10 days Severe cases: IV immunoglobulin

April 05 CASE 5 A 46 year old homosexual man presents with a 6-week history of liquid diarrhea (56 times daily). He also notes abdominal pain and more recently anorexia and nausea. 1. What are the key points in the history and physical examination?

History: Diarrhea: How long? How often? Color? Consistency? Blood? Mucus? Pus? GI systems review: Pain? Tenesmus? Fresh rectal bleeding? Constipation? Weight loss? Anorexia? Symptoms of anemia? Recent travel? Non-GI causes: drugs (antibiotics, PPIs, cimetidine, propranalol, cytotoxics, NSAIDS, digoxin, alcohol, laxatives) medical conditions (thyrotoxicosis, autonomic neuropathy, Addisons disease) Exam: Inspection: Weight loss, anemia, dehydration, oral ulceration, clubbing, rashes, abdominal scars Palpation: enlarged thyroid, abdominal masses DRE: impacted feces, rectal mass, FOB 2. What is the differential diagnosis? Infectious Diarrhea: Bacterial diarrhea - Salmonella - Shigella - Campylobacter - Atypical Mycobacteria - Cl. Difficle Protozoal diarrhea - Cryptosporidium - Microsporidium - Isospora belli - Cyclospora Viral diarrhea - CMV - Adenovirus Drugs - antibiotics - PPIs - Cimetidine - Propranolol - Cytotoxics - NSAIDs - Digoxin - Alcohol - Laxative abuse Inflammatory Bowel Disease Irritable Bowel Colorectal CA Rarer Causes:

Microscopic colitis Celiac Disease Chronic Pancreatitis Thyrotoxicosis Lactose Intolerance Ileal/Gastric resection Bacterial Overgrowth Autonomic Neuropathy Addisonâ&#x20AC;&#x2122;s disease Ischemic colitis Amyloidosis Tropical enteropathy Gastrinoma / VIPoma Carcinoid syndrome Medullary Thyroid CA Pellagra His lymphocyte count comes back at 0.6 x 109/L. 3. What other laboratory tests will you do to help make a diagnosis? Blood: FBC, ESR, UE, ESR, CRP, TFTs, celiac serology Stool: microscopy for pathogens, Cl. difficile toxin Rigid sigmoidoscopy: erythema, white plaques, adherent pseudomembrane Colonoscopy Enema 4. How will you manage this patient? Rehydration: oral better than IV - 0.9% saline + 20mmol K/L Codeine phosphate 30mg/6h PO reduces stool frequency Clostridium Difficile: Antibiotics: metronidazole 400mg 8-hrly PO or vancomycin 125mg 6-hrly PO; treat for 7 -10 days Severe cases: IV immunoglobulin April â&#x20AC;&#x2122;06 3a. outline the serology changes associated with hepatitis B infection HBsAg: surface antigen of hepatitis virus HBcAg: core antigen HBeAg: present within hepatitis virus in association with core protein

Early infection: HBc Ag it is expressed in intracellular hepatocytes -it is never detectible in serum Acute infection: Anti HBc IgM (1-6 months) appears early and rapidly reaches high titres then subsides gradually: it can be useful in indicating acute infection when HBsAg has disappeared and before anti HBs (IgG) develops (this is known as the window period) Acute hepatitis: HBsAg (1-6 months) -it lasts 3-4 weeks or up to 5 months after exposure normally: if present > 6 months indicates carrier state which occurs in 10% of infections â&#x2020;&#x2018; infectivity and chronic hepatitis: HBeAg (1-4 months) is produced in excess during active viral replication/ infection and when detected it indicates high levels of infectivity and ongoing viral replication in liver Low infectivity: HBsAg with Anti HBe ( 4 months â&#x20AC;&#x201C; years)- indicates recovery from acute infection, while in chronic infection it indicates decreased infectivity (present in acute phase) Anti HBsAg IgG (6 months- years) appears late and indicates immunity- (after 3-6 months) or vaccination Chronic infection: HBsAg > 6 months and anti HBc (IGg) ( 6 months- years) in blood remote infection HBV DNA (in blood by PCR): suggests continued viral replication- it must be measured to determine level of viral replication especially in the case of pre-core mutation. this is more useful in measuring response to treatment

Nephrology

October 2002- 2c) Write short notes on the causes of metabolic acidosis. (answer from Davidsonâ&#x20AC;&#x2122;s â&#x20AC;&#x201C; Principles & Practice of Medicine) The causes of metabolic acidosis (a decrease in plasma bicarbonate levels) can be divided into reduced anion gap, normal anion gap, and increased anion gap. Reduced Anion Gap: Occurs when there is a reduction in unmeasured anions (i.e. hypoalbuminaemia) or an increase in unmeasured cations (i.e. severe hypercalcaemia, hypermagnesaemia, or hyperkalaemia; IgG myeloma; lithium toxicity). Normal Anion Gap: Normal anion gap metabolic acidosis is defined by low bicarbonate levels with acidaemia, and an elevated serum chloride. Increased GI bicarbonate loss: Diarrhoea Ileostomy Uterosigmoidostomy Increased renal bicarbonate loss: Acetazolamide Proximal (type 2) renal tubular acidosis Hyperparathyroidism Tubular damage (e.g. drugs, heavy metals, paraproteins) Decreased renal hydrogen ion excretion Distal (type 1) renal tubular acidosis Type 4 renal tubular acidosis (aldosterone deficiency) Increased HCl production Ammonium chloride ingestion Increased catabolism of lysine, arginine Increased Anion Gap: Increased anion gap metabolic acidosis is defined by low bicarbonate levels with acidaemia, and a normal serum chloride. The aetiology of the condition can be subdivided into endogenous and exogenous acid load. Causes of endogenous acid load include: Disorder Diabetic ketoacidosis Starvation ketosis

Mechanism Accumulation of ketones (including acetoacetate and betahydroxybutyrate) with hyperglycaemia Accumulation of ketones without hyperglycaemia

Lactic acidosis

Tissues hypoxia (type A) or liver disease (type B)

Renal failure

Accumulation of organic acids

Causes of exogenous acid load include: Disorder Aspirin poisoning Methanol poisoning

Mechanism Accumulation of salicylate (assoc. with respiratory alkalosis) Accumulation of formate

Ethylene glycol poisoning

Accumulation of glycolate, oxalate

May 2002- 2c) Write short notes on the aetiology and treatment of hyperkalaemia. (answer from Davidson’s – Principles & Practice of Medicine) Aetiology of hyperkalaemia can be subdivided into the following: 1. Spurious (i.e. artefact) - in vitro haemolysis - very high WBC or platelet count 2. Inadequate K+ intake - Exogenous (diet, IV therapy) - Endogenous (haemolysis, rhabdomyolysis) 3. K+ shift out of cells -acidosis -insulin deficiency -beta-blockers -hyperkalaemic periodic paralysis -severe hyperglycaemia 4. Renal retention of K+ A) Renal Failure (plasma creatinine > 500 micromol/l) *acute renal failure (severe) -especially with acidosis/haemolysis/rhabdomyolysis *chronic renal failure (advanced) -especially with oliguria / K+ load B) Tubular secretory failure (plasma creatinine < 500 micromol/l) *with low aldosterone -Adrenocortical failure (Addison’s disease) -Adrenal enzyme defects -Hyporeninaemic hypoaldosteronism -Drugs (NSAIDs, ACE inhibitors, beta-blockers, cyclosporine, prolonged heparin therapy) *with normal – high aldosterone -Tubular transport defects (pseudohypoaldosteronism) -Tubulointerstitial disease (SLE, renal transplant, amyloidosis, obstruction/infection) -Drugs (amiloride, spironolactone)

Treatment of hyperkalaemia: In the absence of neuromuscular symptoms or ECG changes, then a reduction in the K+ intake and addressing the underlying cause can be sufficient. If not, the protocol of management is as follows: Mechanism Stabilize cell membrane potential1

Mechanism Accumulation of ketones (including acetoacetate and betahydroxybutyrate) with hyperglycaemia Accumulation of ketones without hyperglycaemia

Lactic acidosis

Tissues hypoxia (type A) or liver disease (type B)

Renal failure

Accumulation of organic acids

Causes of exogenous acid load include: Disorder

Mechanism

Aspirin poisoning Methanol poisoning

Accumulation of salicylate (assoc. with respiratory alkalosis) Accumulation of formate

Ethylene glycol poisoning

Accumulation of glycolate, oxalate

CASE 2 A 54 year old man presents to his GP with a 48 hour history of nausea and vomiting. He notes several episodes of haemoptysis over the past 5 weeks accompanied by weight loss. On examination the only significant finding is dullness to percussion and decreased breath sounds at the right lung base. Further significant investigations reveal: Haemoglobin 10g/dl, serum urea 11.7 mmol/L, creatinine 138 micromol/L, sodium 133mmol/L, potassium 3.4 mmol/L, calcium 4.6 mmol/L, phosphate 0.82 mmol/L. 1. What are the causes of hypercalcaemia and what is the most likely cause in this mans case? Excessive Parathyroid hormone (PTH) secretion: Primary hyperparathyroidism Adenoma Hyperplasia Carcinoma Tertiary hyperparathyroidism Ectopic PTH secretion Malignant disease: Myeloma Secondary deposits to bone Production of osteoclastic factors by tumours PTH-related protein section Excess action of Vit D: Iatrogenic/self-administered excess Granulomatous disease e.g. Sarcoidosis, TB Lymphoma Excessive calcium intake: ‘Milk-alkali’ syndrome Other endocrine disease: Thyrotoxicosis Addison’s Drugs: Thiazide diuretics Vit D analogues Chronic lithium use Vitamin A Others:

Long-term immobility Familial hypercalciuric hypercalcaemia Likely cause: Bronchial Carcinoma, consistent with the physical findings. 2. What is the most likely mechanism for this patient’s hypercalcaemia? It could be due to 2 reasons: Non-metastatic: PTH secretion by the tumour (especially with squamous cell Carcinoma Metastatic: Osteoclastic bony metastasis 3. What is the immediate management? Since Ca levels > 3.5mmol/L: Monitor the following regularly: U+E, Mg, creatinine, Ca, PO, alk phos Rehydrate with IVI 0.9% saline 4-6L in 24 hours as needed. Correct hypokalaemia/hypomagnesaemia (mild metabolic acidosis needs no treatment) Furosemide 40mg/12h PO/IV, once rehydrated. (Avoid thiazides) Bisphosphonates: single dose of pamidronate (inhibiting osteoclastic activity) Once electrolytes stable, treat underlying cause: Find the cause: CXR, CT, fiberoptic bronchoscopy and biopsy. Surgery or radiation therapy if squamous cell carcinoma 4. List the potentially useful investigations in hypercalcaemia. Several fasting serum calcium and phosphate samples Serum PTH (if high: phosphataemia: primary hyperparathyroidism) Hyperchloraemic acidosis Renal function for baseline Protein electrophoresis to exclude myeloma Serum TSH: to exclude hyperthyroidism 0900h cortisol +/- synacthen test: to exclude Addison’s disease Serum ACE: Sarcoidosis Hydrocortisone suppression test: hydrocortisone 40 mg 3 times for 10 days leads to suppression of plasma calcium in Sarcoidosis, Vit-D-mediated hypercalcaemia and some malignancies PFA: renal calculi or nephrocalcinosis Hand xray: subperiosteal erosions DXA scan: Parathyroid imaging: U/S, CT, MRI, radioisotope. October 2004- 2c) Write short notes on the treatment of severe hyperkalaemia. (answer from Davidson’s – Principles & Practice of Medicine) Severe hyperkalaemia – plasma K+ > 6.5mmol/l

Ideally treat the underlying cause. The protocol of management is as follows: Mechanism Stabilize cell membrane potential1

Therapy - IV calcium gluconate (10ml of 10% solution over 2 min) Shift K+ into the cells - Nebulized salbutamol (2.5mg) - IV glucose (50ml of 50% solution) and insulin (5 U Actrapid) - IV sodium bicarbonate2 (100ml of 8.4% solution) Remove K+ from the body - IV frusemide and normal saline3 - Ion exchange resin (i.e. resonium) PO / PR - Dialysis 1 If ECG changes suggestive of hyperkalaemia 2 If acidosis present 3 If adequate residual renal function April 2005- 2d) Write short notes on the evaluation of an individual with hypokalaemia. (answer from Davidson’s – Principles & Practice of Medicine) Hypokalaemia – plasma K+ < 3.5 mmol/l A) Clinical Presentation: - muscle weakness + lethargy - cardiac arrhythmias, ventricular ectopics, ECG changes (flattened T wave, prominent U wave, prolonged PR interval, depressed ST segment - functional bowel obstruction (paralytic ileus) - polyuria & polydypsia (due to hypokalaemic nephropathy affecting renal tubules resulting in nephrogenic diabetes insipidus) - in severe hypokalaemia: flaccid paralysis, hyporeflexia, hypercapnia, tetany, and rhabdomyolysis B) Aetiology: 1. Inadequate K+ intake (extremely rare) 2. K+ shift into cells -alkalosis -insulin excess -catecholamine beta-2 agonists -hypokalaemic periodic paralysis 3. Excessive loss of K+ A) Renal (urine K+ > 20-30mmol/day) *with hypertension -Hyperaldosteronism

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i. Primary – Conn’s syndrome ii Secondary – renal ischaemia -Other mineralocorticoid receptor activation i. Cushing’s syndrome / ectopic ACTH ii. corticosteroid therapy iii. apparent mineralocorticoid excess iv. liquorice/carbenoxolone - Liddle’s syndrome *with normal-low blood pressure -with alkalosis i. diuretic therapy (loop & thiazide) ii. Bartter’s & Gitelman’s syndromes -with acidosis i. renal tubular acidosis (type 1 & 2) ii. carbonic anhydrase inhibitor therapy -with variable pH i. post-obstructive diuresis ii. recovery after ATN (acute tubular necrosis) iii. Mg depletion B) GI (urine K+ < 20-30mmol/day) *with alkalosis -vomiting -NG aspiration *with acidosis -diarrhoea -laxative abuse -villous adenoma of rectum -bowel obstruction/fistula -ureterosigmoidostomy C) Investigations Following a full Hx & Exam, direct investigations to isolate the cause is as follows 1. UEC, bicarbonate – will confirm the hypokalaemia and differentiate if it is long standing if the bicarbonate is elevated (seen with patients on a diuretic) Note: an ECG may or may not show any of the typical changes of hypokalaemia, therefore is not a good diagnostic tool. 2. Magnesium – if low, then correcting the K+ is difficult without correcting the Mg2+ 3. ABG – is the patient acidotic or alkalotic? 4. Exclude K+ redistribution into the cells (are they on insulin, beta-2 agonists, etc.); also exclude low K+ intake (based on Hx – diet).

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5. Urinary K+ - determine whether the cause of K+ loss is renal or gastrointestinal 6. Blood pressure – differentiates renal causes 7. Plasma renin & aldosterone – differentiates between the different forms of mineralocorticoid excess Through the above steps (combined with the history & exam), most causes of hypokalaemia can be identified. Sometimes the cause is still unknown, and in such cases, a measure of urinary chloride would be helpful (for metabolic alkalosis only)! - low urinary chloride (<30mmol/l), possibly vomiting - high urinary chloride (>40mmol/l), possibly diuretic usage or tubular disorder (further differentiate using a urinary screen for diuretics). OCT, 2005, CASE 5: A 58year old man with neurofibromatosis and hypertension presents with increasing shortness of breath and diarrhea over the past 2-3 months. He is on no medication and he denies any illicit drug use.. On examination he is afebrile, heart rate 120/min, respiratory rate 32/min, BP 100/60. He is thin and in mild respiratory distress. Lung examination is clear and cardiac exam is normal apart from the tachycardia. Abdominal exam is normal apart from neurofibromata. Because of increasing respiratory distress he is admitted to the ICU. Arterial blood gas: pH 7.23, PaCO2 3kPa, PaO2 15kPa on 4 L O2 Routine bloods: FBC normal, Sodium: 138mEq/L, potassium 3.8mEq/L, Chloride 102mEq/L, creatinine 97 micromoles/L, bicarbonate 10mmol/L, glucose 8.3 mmol/L, lactate 11 mEq/L 1 -What is the acid-base abnormality? Metabolic acidosis as PH is low, bicarbonate is very low and paCO2 is slightly low. 2-What other tests would you order to further elucidate the cause of this abnormality? The first step is to identify whether the acidosis is due to retention of H+Cl-or to another acid. This is achieved by calculation of the anion gap. Anion gap = ( NA+) + ( K+) – ( HCO3-) + (Cl-) , the sum of cations normally exceed the anions by 6-12 mmol/l , if the anion gap increase ( >12mmol/l) , the acidosis is the result of of exogenous acid eg. Salicylates or one of acids normally present in small unmeasured quantites, such as lactate, if anion gap is normal so concluded that HCl is being retained or NAHCO3 is being lost.

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causes of metabolic acidosis with a normal anion gap Increased gastrointestinal bicarbonate loss Diarrhea Ileostomy Ureterosigmoidostomy Increased renal bicarbonate loss Acetazolamide Proximal (type 2) renal tubular acidosis Hyperparathyroidism Tubular damage, e.g. drugs, heavy metals, paraproteins Decreased renal hydrogen ion excretion Distal (type 1) renal tubular acidosis Type 4 renal tubular acidosis (aldosterone deficiency): CHECK PLASMA RENIN AND ALDESTERONE Increased HCl production Ammonium chloride ingestion Increased catabolism of lysine, arginine Causes of metabolic acidosis with an increased anion gap Renal failure (sulphate, phosphate) Accumulation of organic acids Lactic acidosis L-lactic Type A - anaerobic metabolism in tissues Hypotension/cardiac arrest Sepsis Poisoning - e.g. ethylene glycol, methanol Type B - decreased hepatic lactate metabolism Insulin deficiency (decreased pyruvate dehydrogenase activity) Metformin accumulation (chronic renal failure) Haematological malignancies Rare inherited enzyme defects D-lactic (fermentation of glucose in bowel by abnormal bowel flora, complicating abnormal small bowel anatomy, e.g. blind loops) Ketoacidosis ( CHECK ACETOACETIC ACID , HYROXYBUTYRIC ACID , KETONES) Insulin deficiency 103

Alcohol excess Starvation Exogenous acids Salicylate SO YOU NEED TO INVESTIGATE THE ABOVE CAUSES. He subsequently has a CT scan of his abdomen which shows a right supra renal mass 3- What diagnosis does that suggest (particularly given his hypertension and neurofibromata)? How will you make the definitive diagnosis? The diagnosis is phaeochromocytoma Investigation: measurement of urinary metabolite (preferably metanephrines rather than vanillylmandelic (VMA) ) , normal level on three 24 hours collections of metanephrines exclude the diagnosis - plasma and urinary catecholamine are measured directly - clonidine suppression and glucagon stimulation test - CT , MRI , and scanning with ( 131 I ) , METAIODOBENZYLGUANIDINE, (Mibg), produces specific uptake in the sites of sympathetic activity with about, 90% success 4- How will you treat this patient? Surgical excision of the tumour under alpha and beta blockage using phenoxybenzamine and propranolol which is started 2 weeks pre op for careful control of blood pressure. April 2006 2d) What are the causes of hyperkalemia and how should it be treated? Causes • Metabolic: renal failure, metabolic acidosis • Endocrine: Addison’s disease • Drugs: K+ sparing diuretics (spiranolactone) ,ACE inhibitors, suxamethonium, excess K+ therapy • Truma: burns • Others: massive blood transfusion, rhabdomyolysis, and artefact (haemolysis of sample) Treatment: K+ levels of more than 6.5 is an emergency **Acute treatment:

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• •

Cardiao-protection: 10ml of 10% Calcium gluconate IV over 2 minutes, repeated until ECG changes improves Hypokalemic agents ( push K+ into the cells): 1. 10-20 units of short-acting insulin (actrapid) + 50 ml of 50% glucose IV over 10 minutes. 2. nebulized salbutamol 2.5 mg K+ binders: calcium resonium 15g every 8 hours in water PO , if vomiting 30g PR as an enema followed by colonic irrigation after 9 hours to get rid of K+ dialysis if persistently high K+

**Treat the underlying cause. . 3d) Write short notes on: presentation and treatment of gout. Symptoms: • Acute attack usually triggered by infection , sugery ,trauma, diuretics, excess alcohol. • 90% present as actue monoarticular arthritis: Painful swollen erythromatous joint most common being the 1st metatarsaopharangeal joint (podagra) • 10% polyarticular arthritis especially in elderly and if left untreated • recurrent attacks causes deposits of urate crystals in tissues know as tophi( pinna, tendons) Signs: • swelling, wormth, erythema and tenderness in the involved joint • decreased range of movement in the joint involved • fever • typhoi negatively birefringent crystals in joint aspirate X_ray : soft tissue swelling Treatment: Acute attacks: strong NSAID (naproxen) : start with strong one enoprxin ,if CI (peptic ulcer) give colchicine 0.5mg /6-8 hours or 0.5mg/2-3 hours until pain free or D&V occur or till 6mg is givin if in renal failure NSAID and colchicines are problematic, use steroids Maintanace : Allopurinol (reduces serum urate > decrease relapse rate) start 3 weeks after the acute attack, dose: 100-300mg/24 hours with initial NSAID or colchicines cover Prevention: Avoid prolong fast Avoid excess alcohol

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Avoid high purine diet ( oily fish, mussels, crabs, prawns, caffeine, chocolate)(cherries increase urate excretion) Avoid low dose aspirin ( increases urate) Weight loss 3e) Classification and causes of metabolic acidosis. Classification: Depends on level of anion gap which estimates unmeasured anions It is the difference between plasma cations (Na and K+) and anions (CI- and HCO3Normal value 10-18mmol/l. 1. Metabolic acidosis with increased anion gap due to increase production of fixed/organic acid > HCO3- falls Causes: Lactic acid : in shock, infection, hypoxia Urate: renal failure Ketones: diabetes mellitus, alcohol Drugs:/toxins: salicylates, biguanides, ethylene glycol, methanol 2. Metabolic acidosis with normal anion gap: due to loss of bicarbonate or ingestion of H+ ions Causes: Renal tubular acidosis Diarrhoea Drugs: acetazolemide Addison disease Pancreatic fistula Ammonium chloride ingestion

106

Neurology

107

OCTOBER 2006 Write short notes on 2j) Differential diagnosis of collapse in a 75 yr. old woman Syncope is defined as Loss of Consciousness secondary to cerebral hypoperfusion accompanied by loss of postural tone and has a spontaneous recovery. In elderly patients the cause is unknown in 1/3 of cases, 1/3 of patients are injured and 1/3 of patients will have another future episode. Differential diagnosis of collapse in an older patient may include Causes of Syncope 1) Cardiac Causes a. Structural – Aortic stenosis, HOCM, Mitral stenosis b. Electrical – Tachycardia, Bradycardia, Heart Block, Sick Sinus Syndrome c. Functional – Infarction, Angina 2) Cardiovascular Reflex Abnormalities a. Carotid sinus syndrome b. Vasovagal Syncope 3) Situational Hypotension a. Dehydration b. Orthostatic Hypotension c. Micturition/Defecation/;Coughing d. Poet-prandial Hypotension 4) Drugs a. Vasodilators b. Diuretics c. β-blockers d. Ca- Blockers Other causes of collapse: 5) Seizure disorders 6) Cerebrovascular insufficiency 7) Hypoxia 8) Hypoglycaemia 9) Anaemia 10) COPD 11) Pneumonia 12) Pulmonary Embolus

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APRIL 2006 Write short notes on 3(c) Clinical findings and diagnosis of multiple sclerosis. Multiple Sclerosis is an inflammatory demyelinating disorder of the central nervous system. Subsequently it can have a varying degree of symptoms and clinical presentations. There are 4 disease patterns - Relapsing Remitting - Primary Progressive - Secondary Progressive - Relapsing Progressive Clinical features of the condition include: 1) Optic Neuritis – Pain, Blurred Vision, Loss of Vision, Pale Disc, RAPD, Uhtoff’s Phenomenon 2) Nystagmus 3) Internuclear Ophtalmoplegia – Diplopia 4) Vertigo 5) Motor Deficits – Abnormal Gait 6) Sensory Disturbances 7) Urinary incontinence 8) Trigeminal Neuralgia 9) Epilepsy - Rare Investigations CSF – Oligoclonal IgG bands (present in 80%) MRI (T2 weighted image) – assess no. of lesions, usually periventricular plaques (will identify 80% of cases) Visual Evoked Responses Brainstem/Somatosensory Evoked Potentials Diagnostic Criteria Poser’s Criteria - 2 episodes of deficit and objective clinical signs of lesions at more than 1 site in CNS or - 2 episodes of deficit and 1 sign with MRI or VER positive Diagnosis is probable if only 1 episode with positive signs and objective imaging/diagnostic tests

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APRIL 2006 1) A 64 year old man presents to the Accident and Emergency department following collapse and loss of consciousness while out shopping. Witnesses say he was unconscious for a short period of time but there is no other information. Discuss the different causes of syncope and outline how you would investigate and manage this patient. Syncope is defined as Loss of Consciousness secondary to cerebral hypoperfusion accompanied by loss of postural tome and has a spontaneous recovery. There are many causes of syncope and it is important to know which are more likely in certain age groups. Causes of Syncope 1) Vasovagal syncope (Neurocardiogenic) 2) Situational Syncope (micturition or cough syncope) 3) Orthostatic Hypotension 4) Mechanical Left Ventricular Obstruction (HOCM) 5) Aortic Stenosis 6) Ischaemic Heart Disease 7) Arrhythmias a. Heart Block (Stokes Adam Attack) b. WPW syndrome c. Ventricular Tachycardia d. Long QTM syndrome/ Torsades de Pointes 8) Carotid Sinus Syndrome It is important in this case to determine whether this was truly syncope or if it were a seizure. The history and collateral histories may help in this respect. Assessment of the Patient History: - Where event happened? - When it occurred? - Did anything bring it on or precede the event? - Any cough, micturition or other stressor? - Any family history of sudden death? - Nauseated, dizziness, light-headed, sweating? - Witnesses accounts? - Tongue biting? - Tastes/Smells/DĂŠjĂ vu/Jamais vu/Visual hallucinations? Physical Exam: - BP (standing and sitting)

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- Pulse (arrhythmias) - Murmurs (aortic stenosis) - Focal neurological deficits/changes Investigations: Investigations should be tailored to each individual and pay particular attention to the age of the patient. Young Adults think of -Vasovagal -Situational -HOCM Middle Aged Adults think of -IHD Older Adults think of -Carotid Sinus Syndrome - Orthostatic Hypotension - IHD/Arrhythmias All Patients should have 1) BP â&#x20AC;&#x201C; both sitting and standing 2) ECG 3) FBC, U&E, LFTs 4) Echo is usually indicated This Case 1) The patient in this case was a 70 year old man, and the most likely cause is Orthostatic Hypotension. History and exam should be done, paying particular attention to Blood Pressure. A fall in BP on assuming an upright position by 20mmHg systolic or 10mmmHg diastolic. If unsure a tilt table test may be done. Causes of Orthostatic Hypotension A) Diabetes Mellitus B) Addisonâ&#x20AC;&#x2122;s C) Alcohol D) Renal Failure E) Amyloidosis F) Drugs

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Treatment of Hypotension: A) Minimise precipitants B) Non-pharmacological methods- Lower limb compression stockings C) Anti-hypotensive drugs â&#x20AC;&#x201C; midodrine or fludrocortisone 2) Another common cause of syncope in older patients is Carotid Sinus Syndrome This may be brought on by compression of the carotid sinus: in history ask about sudden turning of neck with a tight collar. Investigations may include the reproduction of syncope by use of carotid sinus massage. Treatment of Carotid Sinus Syndrome: Avoid compression of sinus 3) Arrhythmias are another cause in older patients. Investigations may include - ECG - 24 hr Holter monitor - Implantable loop recorder - Electrophysiological testing if v tachy or structural cardiac disease is suspected? Treatment of Arrhythmias: A) Tx underlying IHD B) Anti-arrhythmic drugs (amiodarone, Î˛-blockers) C) Implantable cardioverter-defibrillator D) Pacemaker April 2005 CASE 4 A 55 year old man presents with a 1-year history of progressive dysarthria, trouble swallowing and recurrent chest infections. On exam some wasting of the muscles of his hands is evident. He is also noted to have fasciculations in his tongue and upper limbs. He has no sensory disturbance. 1. What is the likely diagnosis? Motor neurone disease 2. If the patient had sensory disturbances how would that change the diagnostic possibilities? Multiple sclerosis Polyneuropathies 3. What test would you suggest to strengthen your diagnosis?

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An EMG would show muscle denervation but this is not a specific finding. The patient undergoes pulmonary function testing as part of his work-up. His forced expired volume in one second (FEV1) is 45% predicted. His forced vital capacity (FVC) is 42% predicted. The ratio of FEV1 to FVC is >80%. 4. What type of lung function abnormality is this and what is the cause? Restrictive pattern due to Phrenic paralysis What other pulmonary function tests would be of use in defining the degree of his lung impairment? Spirometry to check residual lung volune. Also might have a large fall in FVC on lying down 5. Outline your management plan Full history and examination Multidisplinary approach to care – speech and language therapist Antiglutamate drug, riluzole slows progression slightly. Ventilatory support and feeding via PEG helps prolong survival. Diaphragmatic pacing or night-time assisted ventilation. October 2005 -- (2b) Write short notes on Clinical findings and diagnosis of motor neuron disease •

The clinical hallmark is the combination of upper motor neuron (UMN) and lower motor neuron (LMN) signs and symptoms. UMN findings of weakness, hyperreflexia, and spasticity result from degeneration of frontal motor neurons. The LMN findings of weakness, atrophy or amyotrophy, and fasciculations are a direct consequence of degeneration of LMNs in the brainstem and spinal cord.

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Asymmetric limb weakness is the most common presentation of ALS (80 percent). Bulbar onset, usually manifested as dysarthria or dysphagia, is the next most common pattern (20 percent).

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Cognitive impairment

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Autonomic symptoms may occur as the disease progresses.

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It is a relentlessly progressive disorder with a clinical course that is nearly always linear. Symptoms initially spread within the segment of onset and then to other regions in a relatively predictable pattern. The progressive course leads to muscular respiratory failure and dysphagia.

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DIAGNOSIS ** Cord compression may produce similar clinical picture so need to do MRI of spine and/or myelogram to exclude it. The diagnosis is based upon clinical criteria that include the presence of upper motor neuron (UMN) and lower motor neuron (LMN) signs, progression of disease, and the absence of an alternative explanation. There is no single diagnostic test that can confirm or entirely exclude the diagnosis of motor neuron disease. History and physical examination, supported by electrodiagnostic studies, and not excluded by neuroimaging and laboratory studies. History — The diagnosis is suggested when there are symptoms consistent with UMN and LMN dysfunction that present segmentally and then seem to spread and progress over time. The course should not be relapsing and remitting, but insidiously progressive. Importantly, there should be an absence of pain and other sensory symptoms, ocular dysmotility, ptosis, sphincter dysfunction, tremor, and involuntary movements. Involuntary weight loss is often present. Cognitive dysfunction does not exclude the diagnosis. October 2005 -- Case 3 A 28 year old man presents to the A&E department following 3 days of nausea, vomiting, abdominal cramping and diarrhea, which developed following a summer picnic. Over the prior 24 hrs the patient noted lower extremity weakness, tingling and numbness, initially beginning in the ankles and calves and now involving his thighs. Past history is unremarkable. On exam he is well nourished, in no apparent distress. He weighs 75kg. Lung and cardiovascular exam are normal. He has decreased tendon reflexes at the ankles but other reflexes are normal. 1. What tests will you perform to elucidate his problem? Differential is Guillain-Barre, poliomyelitis, botulism, primary muscle disease or other neuropathy. The diagnosis of Guillain-Barré syndrome (GBS) is confirmed if cerebrospinal fluid (CSF) and clinical neurophysiology studies show typical abnormalities. Cerebrospinal fluid analysis — In patients with GBS, lumbar puncture typically reveals an elevated CSF protein with a normal CSF white blood cell (WBC) count. This finding, known as albuminocytologic dissociation, is present in 80 to 90 percent of patients with GBS one week after the onset of symptoms. A normal CSF protein is found in about onethird of patients when tested earlier than one week after symptom onset.

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2. How will you manage him in the first number of hours post admission? 1) IV high dose gamma globulin during the acute phase to reduce the severity and duration of symptoms (often preferred over plasmapheresis) 2) Plasmapheresis 3) Supportive: heparin to reduce thrombosis, physio to prevent contractures, NG or PEG tubes if dysphagia 4) Ventilatory support if respiratory muscles are affected 3. What is the significance of the gastrointestinal symptoms? Campylobacter jejuni infection. 4. What is happening? An ascending neuropathy, due to cell-mediated hypersensitivity to myelin with or without antibody mediated demyelination. 5. How will you assess and manage the patient given these new symptoms and signs Progressive respiratory involvement is the chief danger. Vital capacity every four hours. Transfer to ICU. Ventilate if FVC falls below 1.5L. Immunoglobulin 0.4g/kg/24 hr for 5 days. April 2004 -- Write short notes on 2a Evaluation of an individual presenting with dementia • • •

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History and Collateral Information Physical Examination Assessment of Cognition – MMSE 30 point minimental state examination – ADAS Cog – CAMCOG Assessment of functional level

Treatment anticholinesterase inhibitors(AChEIs) Improve cognition (ADAS – cog) Improve/Maintain Function Effect on Behaviour NICE Guidelines •

AD with MMSE > 12/30

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Specialist Clinic Follow up and Review

Schedule follow up appointments every 6 months and repeat cognitive and functional tests. April 2004 Q2(e) -Write short notes on clinical findings and diagnosis of multiple sclerosis There are no clinical findings that are unique to multiple sclerosis (MS), but some are highly characteristic of the disease -• Relapses and remissions • Onset between ages 15 and 50 • Optic neuritis • Lhermitte's sign • Internuclear ophthalmoplegia • Fatigue • Uhthoff's phenomenon The typical patient presents as a young adult with two or more clinically distinct episodes of CNS dysfunction with at least partial resolution. Diagnosis Multiple sclerosis (MS) is a clinical diagnosis. Demonstration of lesions in time and space unattributable to other causes. McDonald criteria. • Clinical Examination • MRI scan • Lumbar puncture • Evoked potential • Exclusion of other conditions generated by differential diagnosis . May 2002, 2. Write short notes on (a) Clinical manifestations and diagnosis of multiple sclerosis See solution above.

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October 2004 CASE 1 A 72 year old retired teacher comes in for evaluation of mild memory loss that has gradually progressed over the past two years. She lives alone, drives her own car and has recently noted some errors in calculating her spending over the month. She also forgot the location of her car in a parking area for over 2 hours. How should this patient be evaluated and treated? • • •

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History and Collateral Information Physical Examination Assessment of Cognition – MMSE 30 point minimental state examination – ADAS Cog – CAMCOG Assessment of functional level

Treatment anticholinesterase inhibitors(AChEIs) Improve cognition (ADAS – cog) Improve/Maintain Function Effect on Behaviour NICE Guidelines • • •

AD with MMSE > 12/30 Specialist Clinic Follow up and Review

Schedule follow up appointments every 6 months and repeat cognitive and functional tests. October 2004 CASE 2 A 54 year old male presents to the A&E department with back pain exacerbated by coughing or straining and not relieved by rest. He also notes weakness in the lower limbs and dribbling of urine. On examination he has upper neuron weakness in both lower limbs along with sensory loss 1. What is the your differential diagnosis? Acute cauda equina compression Acute cord compression Degenerative spinal disease Prolapsed disc Malignancy Myeloma

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2. What investigation is required urgently? MRI. 3. How should this patient be managed? • • • •

Acute cord compression is a neurosurgical emergency In those with malignant disease radiotherapy may be the best treatment Tumour, infection and disc disease usually produce anterior compression Surgical decompression should be through an anterior approach

Cauda equina compression is usually due to central lumbar disc prolapse. Although it is not strictly compression of the spinal cord it is still a neurosurgical emergency requiring immediate admission for MRI and decompression. October 2004 - Case 4 A 67 year old man who was previously fit and well presents with pain on his left side first noticed one week ago. This was followed by an odd sensation whenever he touched the area of skin involved. Three days ago he noted a rash over the area characterised groups of small irregular tense vesicles. 1. What is the most likely diagnosis? Shingles – Herpes zoster infection, a syndrome that is characterized by a painful, unilateral vesicular eruption in a restricted dermatomal distribution. 2. What are the risk factors for developing this type of skin problem? Immunosuppression Causes of immunosuppression; • Immunosuppressive therapy o Steriods o Methotrexate o Azothioprine o Alkylating agents • Infections o HIV infection o Measles •

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Disorders of biochemical homeostatis o Diabetes mellitus o Renal dialysis o Liver cirrhosis o Malnutrition Autoimmune disease o SLE o Rheumatoid arthritis Others

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o Nephrotic syndrome o Asplenia Contact with case of Chicken pox when the carrier is in infective state, that is from when the rash appears until all the lesions are crusted over. 3. How would you treat this patient? In herpes zoster (shingles) topical antiviral treatment to reduce the severity and duration of pain, reduce complications, and reduce viral shedding. Treatment with the antiviral should be started within 72 hours of the onset of rash and is usually continued for 7â&#x20AC;&#x201C;10 days. 4. The rash is still present 2 weeks later and shows no sign of resolution. In fact it has become more extensive. What should you now consider? Systemic antiviral treatment with a antiviral treatment should now be commenced. Drug of choice is Acyclovir or Famciclovir. Varicella and herpes zoster treatment, 800 mg 5 times daily for 7 days; child, varicella, 20 mg/kg (max. 800 mg) 4 times daily for 5 days October 2002, Short note, 2a: Clinical manifestations and Diagnosis of Myasthenia Gravis Autoimmune disease, young adults, female: male ratio=2:1 Clinical features: Increasing muscle fatigability Ocular muscles first to be involved in 65% of cases Bulbar, muscles of mastication, speech, facial expression, neck, distal limb, trunk Weakness worse in evening Exacerbating factors: exercise, emotion, pregnancy, change in climate, medications eg. Gentamycin, beta blockers, opiates Association with thymoma and autoimmune diseases: DM, RA, Thyrotoxicosis Examination: Eyes: ptosis, increased weakness with sustained upward gaze for 45 secâ&#x20AC;&#x2122;s Test extra-ocular eye movements: diplopia, strabismus Get patient to smile: they snarl! Speech: count to 50; nasal speech, voice weakens Drift with arms outstretched: slow and downwards Reflexes normal, may be brisk

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Normal sensation and coordination Diagnosis: 1) Serum ACH receptor antibodies 2) Tensilon test: administer anticholinesterase edrophonium injection 10mg, results in rapid temporary improvement in weakness 3) Neurophysiology: repetitive muscle stimulation results in a decremental response 4) Imaging of mediastinum: CXR, CT/MRI of chest and thymus gland October 2002 Q3, CASE 1 A 28 year old man presents to the A&E department following 3 days of nausea, vomiting, abdominal cramping and diarrhea, which developed following a summer picnic. Over the prior 24 hrs the patient noted lower extremity weakness, tingling and numbness, initially beginning in the ankles and calves and now involving his thighs.He has decreased tendon reflexes at the ankles but other reflexes are normal. At 6 hrs the patient began to note shortness of breath and repeat neurologic exam showed decreased motor strength and reflexes in both upper and lower extremities. 1. What is your differential diagnosis? 1) Guillian Barre syndrome (acute inflammatory demyelinating polyneuropathy, weakness and numbness starting distally and ascends over days or weeks, post infectious eg. URTI, mycoplasma, HIV, CMV, EBV, Campylobacter jejuni) 2) Poliomyelitis 3) Botulism 4) Primary muscle disease 5) Toxins causing polyneuropathy: excess alcohol, lead/organophosphorus poisoning 2. What tests would you perform on this patient to elucidate his problem? 1) Nerve conduction studies: slowing of conduction or conduction block 2) CSF: albumino-cytological dissociation i.e. cell count and glucose are normal but protein concentration is raised 3. What is the major danger facing this patient and how would you monitor it? 1) Ascending weakness can affect the muscles of respiration: diaphragm, intercostals which can result in paralysis. Monitoring: vital capacity every 4 hours, if it drops less than 80% of predicted value therefore indication to transfer to ICU and mechanical ventilation (if FVC < 1.5 Litres, PaO2<10kPA, PaCO2>6kPa) 2) Cardiac arrhythmias secondary to autonomic dysfunction and risk of cardiac arrest: Monitoring: ECG for dysrhythmias

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4. How would you manage this patient? 1) IV high dose gamma globulin during the acute phase to reduce the severity and duration of symptoms (often preferred over plasmapheresis) 2) Plasmapheresis 3) Supportive: heparin to reduce thrombosis, physio to prevent contractures, NG or PEG tubes if dysphagia 4) Ventilatory support if respiratory muscles are affected April 2003 Q1) A 67 year old lady presents to the A&E department after recovering from a 60minute episode of difficulty speaking and weakness of the right side of the face and right arm. Describe the important areas which need to be addressed in her history, and physical examination. Outline how you would investigate this patient and discuss the treatment options available. INITIAL GENERAL ASSESSMENT — Sudden loss of focal brain function is the core feature of the onset of ischemic stroke. However, patients with conditions other than brain ischemia may present in a similar fashion. In addition, patients suffering a stroke may present with other serious medical conditions. Thus, the initial evaluation requires a rapid but broad assessment. The goals in this initial phase include: • • • •

Insuring medical stability Quickly reversing any conditions that are contributing to the patient's problem Moving toward uncovering the pathophysiologic basis of the patient's neurologic symptoms Screening for potential contraindications to thrombolysis in acute ischemic stroke patients

Diagnosing hemorrhage — Diagnosing an intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH) as soon as possible can be lifesaving. The history may be helpful in this regard. The presence of onset headache and vomiting favor the diagnosis of ICH or SAH compared with a thromboembolic stroke, while the abrupt onset of impaired cerebral function without focal symptoms factors the diagnosis of SAH. Even with these clues, diagnosing intracranial hemorrhage on clinical grounds is very imprecise, so early triage of the patient to CT or MRI scan is critical. However, it is important to assess and optimize vital physiologic function before sending the patient for an imaging study. History and physical — The history and physical examination should be used to distinguish between other disorders in the differential diagnosis of brain ischemia. As examples, seizures, syncope, migraine, and hypoglycemia can mimic acute ischemia. The most difficult cases involve patients with focal signs and altered level of consciousness. It is important to ask the patient or a relative whether the patient takes insulin or oral

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hypoglycemic agents, has a history of a seizure disorder or drug overdose or abuse, medications on admission, or recent trauma. The physical examination should include careful evaluation of the neck and retroorbital regions for vascular bruits, and palpation of pulses in the neck, arms, and legs to assess for their absence, asymmetry, or irregular rate. The heart should be auscultated for murmurs. Fluctuations in blood pressure occasionally precede fluctuations in clinical signs. The skin should be examined for signs of endocarditis, cholesterol emboli, purpura, or ecchymoses. The fundoscopic examination may be helpful if there are cholesterol emboli or papilledema. The head should be examined for signs of trauma. A tongue laceration may occur with tongue biting during a seizure. The neck should be immobilized until evaluated radiographically for evidence of serious trauma if there is a report or suspicion of a fall. Examination of the extremities is important to detect deep vein thrombosis, which can cause systemic embolization in patients with a patent foramen ovale, and to look for evidence of systemic arterial emboli from other sources. Airway and breathing — Patients with increased ICP due to hemorrhage, vertebrobasilar ischemia, or bihemispheric ischemia can present with a decreased respiratory drive or muscular airway obstruction. Hypoventilation, with a resulting increase in carbon dioxide, may lead to cerebral vasodilation, which further elevates ICP. Intubation may be necessary to restore adequate ventilation and to protect the airway from aspiration; this is especially important in the presence of vomiting, which occurs commonly with increased ICP, vertebrobasilar ischemia, and intracranial hemorrhage. Patients with adequate ventilation should have the oxygen saturation monitored. Patients who are hypoxic should receive supplemental oxygen. Supplemental oxygen should not routinely be given to nonhypoxic stroke victims. Patients with acute ischemic stroke be positioned as flat as possible in bed for at least the first 24 hours from stroke onset, ideally with head-of-bed between 0 and 15 degrees. Immediate laboratory studies — All patients with acute neurologic deterioration or acute stroke should have an ecg. Chest radiography is indicated if lung or heart disease is suspected, and should be evaluated carefully for cardiomegaly, metastases, or a widened mediastinum suggesting aortic dissection. Oxygen saturation or arterial blood gas tests are indicated if hypoxia is suspected. Chest radiography, urinalysis and blood cultures are indicated if fever is present. Emergent brain imaging with CT or MRI is mandatory in all patients with sudden neurologic deterioration or acute stroke. Bloods = •

Complete blood count including platelets, and esr

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• • • • • • • • •

Cardiac enzymes and troponin if there is any suspicion for cardiac ischemia Electrolytes, urea nitrogen, creatinine Serum glucose Finger stick for faster glucose measurement if patient is diabetic, taking insulin or oral hypoglycemic agents, or if there is clinical suspicion for hypoglycemia Liver function tests Prothrombin time and partial thromboplastin time Toxicology screen and blood alcohol level in selected patients Blood for type and cross match in case fresh frozen is needed to reverse a coagulopathy if ICH is present Consider evaluation for hypercoagulable state in young patients without apparent stroke risk factors.

Anticoagulant use is a common cause of intracerebral hemorrhage. Thus, the prothrombin and partial thromboplastin time and the platelet count should be checked in all patients presenting with focal neurologic deficits. It can not be overemphasized that the effects of warfarin need to be corrected as soon as possible with intravenous vitamin K and fresh frozen plasma (typically 4 units) in patients with intracerebral hemorrhage. There is a high likelihood that the hemorrhage will enlarge and the patient will deteriorate if this is not done. As discussed below, it is important to check the blood sugar at the first opportunity since hypoglycemia can present with focal neurologic deficits. A drug overdose can mimic an acute stroke. In addition, cocaine, intravenous drug abuse, and amphetamines can cause an ischemic stroke or intracranial hemorrhage. Hyponatremia and thrombotic thrombocytopenic purpura (TTP) can present with focal neurologic deficits, suggesting the need for measurement of serum electrolytes and a complete blood count with platelet count. Serum glucose — Alterations in serum glucose are common and potentially significant in patients with sudden neurologic deterioration. Hyperglycemia — Hyperglycemia, generally defined as a blood glucose level >7.0 mmol/L, is common in patients with acute ischemic stroke and is associated with poor functional outcome. Hypoglycemia — Hypoglycemia can cause focal neurologic deficits mimicking stroke, and severe hypoglycemia alone can cause neuronal injury. It is important to check the blood sugar and rapidly correct low serum glucose at the first opportunity. It may be reasonable to administer glucose immediately after drawing a blood sample in "stroke" patients known to take insulin or oral hypoglycemic agents. Fever — Fever has special significance in patients presenting with acute neurologic deterioration. Both problems may occur in patients with a primary central nervous system infection such as meningitis, subdural empyema, brain abscess, and infective

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endocarditis. These conditions need to be excluded as the etiology of fever. In addition, common etiologies of fever including aspiration pneumonia and urinary tract infection should also be excluded. BLOOD PRESSURE MANAGEMENT — Acute management of blood pressure (BP) may vary according to the type of stroke. Ischemic stroke — In patients with ischemic stroke, the perfusion pressure distal to the obstructed vessel is low, and the distal vessels are dilated. Blood flow in these dilated vessels is thought to be dependent upon the systemic blood pressure. The mean arterial blood pressure (MAP) is usually elevated in patients with an acute stroke. This may be due to chronic hypertension, which is a major risk factor for ischemic stroke, or to an acute sympathetic response. In many cases, however, the acutely elevated blood pressure is necessary to maintain brain perfusion. A neuroimaging study with CT or MRI is critical to help guide blood pressure therapy in stroke patients. The observation that the BP frequently rises spontaneously following cerebral ischemia is consistent with this protective hypothesis, although a stress response to the acute event and to hospitalization may also contribute. The hypertensive effect is transient, as the BP falls by as much as 20/10 mmHg within 10 days. Interventions — Lowering the systemic blood pressure has been associated with clinical deterioration in patients with acute ischemic stroke. Occasional patients even benefit from pharmacologic increases in blood pressure. On the other hand, severe increases in blood pressure can cause hypertensive encephalopathy, a condition that can mimic stroke. In this case, lowering the blood pressure is the indicated treatment. Recommendations — Most consensus guidelines recommend that blood pressure not be treated acutely in the patient with ischemic stroke unless the hypertension is extreme (diastolic BP above 120 mmHg and/or systolic BP above 220 mmHg), or the patient has active ischemic coronary disease, heart failure, or aortic dissection. In the absence of those conditions, antihypertensive therapy may be withheld for at least 10 days after a thromboembolic stroke. A lesser elevation in BP may be necessary to maintain cerebral blood flow to ischemic brain regions in acute stroke. Furthermore, antihypertensive therapy is more likely to lead to an exaggerated reduction in cerebral flow in this setting, since autoregulation is impaired in ischemic areas. At present, drug-induced hypertension cannot be recommended for the treatment of most patients with ischemic stroke.

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ACUTE THERAPY — Treatment with thrombolytic therapy should be considered for some patients with acute ischemic stroke within 3 hours and ideally in a stroke unit. All patients should have Aspirin 300 mg daily (orally via NG tube or rectally). In addition to intravenous thrombolysis with tPA, a number of interventions for ischemic stroke are associated with either reduced disability, complications, or stroke recurrence, including: •

Antithrombotic therapy

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Prophylaxis for deep venous thrombosis and pulmonary embolism

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Antithrombotic therapy at discharge.

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Lipid lowering therapy.

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Blood pressure reduction, once the acute phase of ischemic stroke has passed.

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Smoking cessation along with management of obesity, diabetes, and metabolic syndrome are unproven but generally recommended as well.

October 2003, Case 4 A 67 year old man presented with a 6 week history of episodic weakness affecting his face, arm and leg on the right side. He had a single episode of visual disturbance affecting the left eye. There have been at least 4 separate attacks lasting a few minutes on each occasion. On examination during his most recent attack he had mild hemiparesis affecting his face and right hand. He had nominal dysphasia. Blood pressure was 170/95. No cardiac murmurs or cervical bruits were heard. 1. Where is the lesion? 2. What is the likely pathological mechanism? 3. Is there any immediate treatment for this disorder? 4. What further investigations are required? 5. What treatment options may then be considered?

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Respiratory

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May 2002 2b) Short notes on treatment of tobacco use and dependence 1. Motivation – Ask, advise, Assist and confirm patient’s intent to quit. Set a date, motivate and follow-up. Outline the risks associated. 2. Psychology of Smoking – break patterns (smoking after meals, first thing in morning, etc…), role of cognitive behavioural therapy. Support groups and counseling. 3. Nicotine Replacement Therapy - patch, inhaler, gum, lozenges, nasal spray. 50% of those on the patch are able to quit and stay off cigarettes. 4. Bupropion - Helps alleviate depression and weight gain. Bupropion, a prescription antidepressant marketed as Zyban®, was approved by the FDA in 1997 to treat nicotine addiction. This drug can help to reduce nicotine withdrawal symptoms and the urge to smoke. Some common side effects of bupropion are dry mouth, difficulty sleeping, dizziness, and skin rash. People should not use this drug if they have a seizure condition such as epilepsy or an eating disorder such as anorexia nervosa or bulimia, or if they are taking other medicines that contain bupropion hydrochloride. 2e) Short notes on treatment of Sarcoidosis 1. Steroids - Prednisone 30mg x 6 weeks and reduce to alternate day 15mg x 612 months for unresolving disease 6 months after initial diagnosis. Topical or systemic for eye involvement/hypercalcemia. Also treat myocardial and CNS disease. 2. NSAIDs - Erythema Nodosum 3. Methotrexate - Non-steroid responsive/intoleratant. nausea, mucositis, and decreased blood counts. Methotrexate and azathioprine can increase the risk for infection. Liver damage so monitor LFTs. 4. Azathioprine 5. Cyclophosphamide - Refractory cases. Hemhorrahagic cystitis, bladder CA. 6. Chloroquinine phosphate - For refractory lung and skin manisfestions monitor with opthalmologist. Not proven in clinical trials. Case 1 An 18 year old man is referred from a paediatric hospital's Cystic Fibrosis unit. He was first diagnosed as a neonate when he presented with bowel obstruction. He reports increasing dyspnea and tenacious sputum over the preceding two weeks. The paediatricians have asked you to take over his care given that he is now 18. 1. How is the diagnosis of cystic fibrosis made and what complication was most likely to have occurred in this individual at time of diagnosis? 1. Diagnosed by Chloride sweat test (sweat sodium concentration of >60mmol/L), family history, DNA Analyses, Radiology, absent vas and epididymis. Most likely complication at age 18 is bronchiectasis due to recurrent necrotizing

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pulmonary infections destroying lung parenchyma. 2. What additional information would you wish to obtain from this patient? 2. Additional information you would glean from this patient include: a. Symptom history - amount/color of sputum, haemoptysis, fever, recent weight loss (basically full resp history) b. Previous admissions and treatment courses c. Pseudomonas and Burkholderia status d. Medications – including current antibiotics, inhaled/nebulised meds, ADEK vitamins, use of exogenous pancreatic enzymes. e. Nutritional Status – Diet, PEG feeding. f. Social History - How disease affects quality of life etc… 3. Describe the management of a patient with CF under the following headings:I) Bacteria and Antibiotics II) Mucolytics and Physiotherapy III) Nutrition IV) Prognosis and counselling 3. Management a. Bacteria and Antibiotics – Pseudomonas - prevalence of 60% in CF patients. Mean age of acquisition is 15yrs. Treatment options include 3 weeks oral ciprofloxacin + nebulised colistin, cipro + tobramycin. Azithromycin MWF + tobramycin inhaled bid 28days on, 28 off. Also ceftazidime, cefepime, piperacillin/tazobactam, imipenem. Staph Aureus - important in adolescence and infancy. Vancomycin and nafcillin IV. Burkholderia Cepacia - Usually resistant to multiple drugs, treatment depends on sensitivity testing. Its presence indicates a poorer prognosis in terms of exacerbations and lung function. Aspergillus Fumigatus - amphotericin B and itraconazole. Usually present in a cavitation due to previous infection. S. Maltophilus - ceftazidine, cipro, ticarcil + clavlanate, co-trimoxaxole b. Mucolytics and Physiotherapy – Intrapulmonary oscillator – oscillate air column under pressure of compressed gas. Vibration – flutter, acapella Classical Physio and Postural Drainage (CPT) - External clapping of chest wall and positioning against gravity to clear mucus. Mucolytic - Pulmozyme is a DNase. c. Nutrition Part of the multidisciplinary team approach to CF management. In general more calories are better. Nutrtionist/Dietician should review and make according recommendations. Special consideration should be given to

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tube feeding, indications which include: BMI <19, lung transplant, end-stage disease, unable to meet requirements. Pancreatic enzyme replacement should be adjusted to maintain normal bowel motions and assist with weight gain. Vitamin supplementation with ADEK often necessary. d. Prognosis and Counseling The severity of cystic fibrosis varies greatly from person to person regardless of age; the severity is determined largely by how much the lungs are affected. However, deterioration is inevitable, leading to debility and eventually death. Nonetheless, the outlook has improved steadily over the past 25 years, mainly because treatments can now postpone some of the changes that occur in the lungs. Half of the people with cystic fibrosis live longer than 28 years. Long-term survival is somewhat better in males, people who don't have pancreatic problems, and people whose initial symptoms are restricted to the digestive system. Despite their many problems, people with cystic fibrosis usually attend school or work until shortly before death. October 2002 1) A 70 year old man with a 60 pack year history of cigarette smoking and a history of congestive carciac failure presents with increasing shortness of breath. He also has soreness particularly on inspiration on the right side of his chest. A chest x-ray reveals a right sided pleural effusion. Describe how you evaluate this man with emphasis on history, physical examination and biochemical, pathological radiological investigations. History: • Shortness of breath • Chest pain (sharp, worsened with cough and deep breaths) • Cough • Sputum (colour) Physical Exam: • Inspection – tachypnoea • Palpation -decreased expansion on affected side -trachea and apex may be deviated to the unaffected side - Tactile vocal fremitus • Percussion - stony dull over affected area • Auscultation - absent breath sounds - absent vocal resonance - bronchial breathing at effusion margin Biochemical: • FBC, U&Es, ESR, CRP etc. 129

• • •

Pleural tap Analysis of fluid differentiates between exudates and transudate Pleural fluid is an exudate if one or more of the following criteria are met - pleural fluid protein: serum protein ratios > 5 - pleural fluid LDH: serum LDH ratio >0.6 - Pleural fluid LDH> two-thirds of the upper limit of normal serum LDH

Radiological • erect PA chest film shows - curved shadow at lung base, blunting of costophrenic angle and ascending towards the axilla - 200ml of fluid required to be detectable on a PA CXR. • Ultra Sound - more accurate at determining the volume of pleural fluid • CT scanning - displays pleural abnormalities more readily than the CXR or US - may distinguish between benign and malignant pleural disease Pathalogical • simple aspiration – info on colour and texture of fluid (appearance alone may suggest empyema, chylothorax) • Gram Stain April 2003 2. e) Short notes on treatment of Community Acquired Pneumonia • CAP with the Following: Chest x-ray: Focal infiltrate CD4: 200 cells/mm3 • Most Likely Pathogen S pneumoniae H influenzae M legionella Salmonella C pneumoniae • Optimal Empiric Therapy Extrapulmonary findings (atypical pathogens): Respiratory quinolone or Doxycycline No Extrapulmonary findings (typical bacteria): Ceftriaxone or Third-generation cephalosporins or Cefepime or Respiratory quinolone •

Features of both typical and atypical: Respiratory quinolone, Doxycycline, Telithromycin 130

Case 1 A 26 year old known asthmatic is brought to the Accident and Emergency department in profound respiratory distress. The patient finds it difficult to speak. Her father reports that she has been progressively dyspnoeic with marked wheeze over the past 12 hours. She has previously been admitted to the intensive care unit with a severe asthma attack. She has taken her regular inhalers but these have provided no relief. 1. What symptoms or signs suggest a severe asthma attack? 1) Symptoms/Signs suggesting Acute severe asthma attack: • PEF 33-50% predicted • Resp rate >25/min • Heart rate > 110/min • Inability to complete sentences in one breath Life threatening features: • PEF 33-50% predicted • SpO2<92% or PaO2 <8kPa • Normal PaCO2 • Silent chest • Cyanosis • Feeble respiratory effort • Bradycardia and arrythmias • Hypotension • Exhaustion • Confusion • Coma Near Fatal Ashtma: • raised PaCO2 and or requiring mechanical ventilation with raise inflation pressures 2. How would you investigate this patient? 2) Investigations: • pulmonary function test • ABG’s • Pulse oximeter • Peak flow meter • Baseline bloods • CXR 3. Outline your management of this case.

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3) Management: • High concentrations of oxygen (maintain O2 sat of greater than 92%) • Bronchodilators – short acting B2 agonists • Systemic corticosteroids • Intravenous fluids • If the patient fails to improve consider iv magnesium(bronchodilation), iv aminophylline 4. What features might suggest the need for mechanical ventilation? 4) Mechanical Ventilation: • Coma • Respiratory arrest • Deterioration of arterial blood gas tensions despite optimal therapy (PaO2<8kPa and falling, PaCO2 >6 kPa and rising • Exhaustion, confusion, drowsiness October 2003 Case 6 A 39 year old nurse presents to the A&E department with reduced appetite, weight loss and cough for 4 months associated with hemoptysis. She has a history of poorly controlled diabetes. Examination revealed a temperature of 37.8oC, reduced respiratory movement over the left upper chest on inspiration with bronchial breathing on auscultation. The chest x-ray showed extensive consolidation in the left mid and upper zones with a number of cavities in this region. 1. What is the most likely diagnosis? 1) TB 2. What would be your initial investigations? 2) Initial Investigations: • Sputum (early morn) • Gastric washing • Bronchiolar lavage • Transhbronchial biopsy • Fluid examination • Tissue biopsy (from affected site) Diagnostic Testing: • FBC (anaemia, WCC), U&E, ESR CRP • Tuberculin Skin test • Stain – Zihel Neelsen, Auramin Fluoresence • Nucleic Acid amplification • Culture solid(Lowenstein Jensen) and liquid (BACTEC)

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Response to empirical antiTB drugs

3. What would be your initial management? 3) Initial Management: • Antibiotics: rifampicin, isoniazid, pirizinamide 4. After 4 weeks of therapy the patient notes nausea and abdominal discomfort. Her liver transaminases are elevated 6 –fold above normal. What will you do? 4) Elevated Liver Tranaminases: • Monitor and follow up • If transaminases are persistently elevated than consider alternate therapy April 2004 Case 6 A 72 year old man with a background of Chronic Bronchitis and Emphysema deteriorates on the ward. His arterial blood gas on room air is as follows: Pa O2 7.9 kPa Pa Co 2 6.5 kPa PH 7.3 1. What are the clinical signs of hypercapnea? 1) Palmer erythema, flushed skin, full pulse, extrasystoles, muscle twitches, hand flaps, and possibly a raised blood pressure, chemosis. In severe hypercapnia (generally PaCO2 greater than 10kPa or 75mmHg), symptomatology progresses to disorientation, panic, hyperventilation, convulsions, unconsciousness, and eventually death. He is commenced on 24% O2 via a Venturi mask. A repeat ABG in 20 minutes shows that his PaO2 is increased but also that his PaCO2 is rising. His Ph has dropped further to 7.2 2. What are the management options available for this patient? What are the indications for mechanical ventilation? 2) • •

A patient with acute respiratory failure generally needs prompt admission to hospital. Most patients with chronic respiratory failure can be treated at home with oxygen as well as therapy for their underlying disease. Airway: ensure an adequate airway.

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• •

• • •

Correction of hypoxaemia: ensure adequate oxygen delivery to tissues, generally achieved with a PaO2 of 60 mmHg or an arterial oxygen saturation (SaO2) of greater than 90%. Beware the prolonged use of high concentration oxygen in chronic sufferers who have become reliant on their hypoxic drive to maintain an adequate ventilation rate. Elevating the PaO2 too much may reduce the respiratory rate so that the PaCO2 may rise to dangerously high levels. Hypercapnia and respiratory acidosis: correct the underlying cause and/or provide assisted ventilation. Mechanical ventilation is used to increase PaO2 and to lower PaCO2. Mechanical ventilation also rests the respiratory muscles and is an appropriate therapy for respiratory muscle fatigue. Appropriate management of the underlying disease.

Indications for mechanical Ventilation: Apnea with respiratory arrest Acute lung injury Respiratory rate >30 breaths per minute Vital capacity <15 mL/kg Minute ventilation >10 L/min Arterial partial pressure of oxygen (PaO2) with a supplemental fraction of inspired oxygen (FIO2) of <55 mm Hg Alveolar-arterial difference in oxygen tension (A-a DO2) with 100% oxygenation of >450 mm Hg Chronic obstructive pulmonary disease (COPD) Clinical deterioration Respiratory muscle fatigue Obtundation or coma Hypotension Tachypnea or bradypnea Blood gases showing persistent hypoxemia A decision is taken to ventilate the patient. He is weaned off ventilation several days later and returns to his baseline respiratory function. Prior to discharge you are asked to assess his suitability for home oxygen therapy. 3. What are the indications for home oxygen therapy and what are the benefits? 3) Chronic Hypoxia (generally long-term use). The conditions with which this may be associated include, but are not limited to: • • • •

Diffuse interstitial lung disease Chronic obstructive pulmonary disease Cystic fibrosis Bronchiectasis

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• • • •

Widespread pulmonary neoplasm Pediatric bronchopulmonary dysplasia (BPD) Pulmonary hypertension Recurring congestive heart failure due to chronic cor pulmonale

Acute Hypoxia (generally short-term use). The conditions with which this may be associated include, but are not limited to: • • •

Pneumonia Bronchiolitis Exacerbation of chronic obstructive pulmonary disease

4. What points would you stress to someone commencing home oxygen therapy? 4) Don’t smoke. October 2004 2a) Laboratory and radiologic investigations of suspected pulmonary embolus: Clinical criteria: • The decision to do medical imaging is usually based on clinical grounds, i.e. the medical history, symptoms and findings on physical examination. The Wells score (predict the likelihood of PE): • clinically suspected DVT - 3.0 points • alternative diagnosis is less likely than PE - 3.0 points • tachycardia - 1.5 points • immobilization/surgery in previous four weeks - 1.5 points • history of DVT or PE - 1.5 points • hemoptysis - 1.0 points • malignancy (treatment for within 6 months, palliative) - 1.0 points Interpretation: Traditional interpretation • Score >6.0 - High • Score 2.0 to 6.0 - Moderate • Score <2.0 - Low New proposed interpretation • Score > 4 - PE likely. Consider CT pulmonary angiography. • Score 4 or less - PE unlikely. Consider D-dimer testing by ELISA to rule out PE. Blood work • In low/moderate suspicion of PE, a normal D-dimer level (shown in a blood test) is enough to exclude the possibility of PE. • When a PE is being suspected, a number of blood tests are done, in order to exclude important secondary causes of PE. This includes a full blood count,

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clotting status (PT, APTT, TT), and some screening tests (erythrocyte sedimentation rate, renal function, liver enzymes, electrolytes). If one of these is abnormal, further investigations might be warranted. Medical imaging • The gold standard for diagnosing pulmonary embolism is pulmonary angiography. Pulmonary angiography is used less often because of wider acceptance of CT scans, which are non-invasive. Imaging to evaluate for pulmonary embolism • Computed tomography with radiocontrast, effectively a pulmonary angiogram imaged by CT and known as CT pulmonary angiography (CTPA), is increasingly used as the mainstay in diagnosis. • Advantages are clinical equivalence, its non-invasive nature, its greater availability to patients, and the possibility of picking up other lung disorders from the differential diagnosis in case there is no pulmonary embolism. • Ventilation/perfusion scan (or V/Q scan), which shows that some areas of the lung are being ventilated but not perfused with blood (due to obstruction by a clot). It is a type of scintigraphy. This study is used less often because of CT technology, however, it may be useful in patients who have an allergy to iodinated contrast. Low probablitity diagnostic tests/non-diagnostic tests • Chest X-rays are often done on patients with shortness of breath to help rule-out other causes, such as congestive heart failure and rib fracture. Chest X-rays in PE are rarely normal,[6] but usually lack signs that suggest the diagnosis of PE (e.g. Westermark sign, Hampton's hump). • Ultrasonography of the legs, also known as leg doppler, in search of deep venous thrombosis (DVT). The presence of DVT, as shown on ultrasonography of the legs, is in itself enough to warrant anticoagulation, without requiring the V/Q or spiral CT scans (because of the strong association between DVT and PE). This may be valid approach in pregnancy, in which the other modalities would increase the risk of birth defects in the unborn child. However, a negative scan does not rule out PE, and low-radiation dose scanning may be required if the mother is deemed at high risk of having pulmonary embolism. Electrocardiogram findings • An electrocardiogram (ECG) is routinely done on patients with chest pain to quickly diagnose myocardial infarctions (heart attacks). An ECG may show signs of right heart strain or acute cor pulmonale in cases of large PEs - the classic signs are a large S wave in lead I, a large Q wave in lead III and an inverted T wave in lead III ("S1Q3T3").[7] This is occasionally (up to 20%) present, but may also occur in other acute lung conditions and has therefore limited diagnostic value; the most commonly seen sign in the ECG is sinus tachycardia. • In massive PE, dysfunction of the right side of the heart can be seen on echocardiography, an indication that the pulmonary artery is severely obstructed 136

and the heart is unable to match the pressure. In the United States, many physicians see this as an adequate indication for thrombolysis (see below). April 2005 Case 1 A 33 year old nurse presents with a 2 week history of pains in her ankle joints, painful red eye and a raised red rash on her shins. The rash has changed colour and now looks â&#x20AC;&#x153;bruise likeâ&#x20AC;?. Her GP has performed a number of blood tests which show calcium 2.8 mmol/L , Hb 15 g/dl, lymphocyte count < 1.5 x 109/L, platelets 300 x 109/L . A chest x-ray shows increased hilar markings. 1. What is the most likely diagnosis? What is the differential diagnosis? 1) Sarcoidosis, differential includes Infections: Tularemia, Streptococcal infections, Campylobacter, Salmonella, Histoplasma and Yersinia. Behcetâ&#x20AC;&#x2122;s Disease, IBD, leukemias/lymphomas. Various autoimmune disorders such as SLE, RA. 2. How would you make a definitive diagnosis? 2) No definitive laboratory test diagnostic of sarcoidosis exists. In the absence of a known etiologic agent, sarcoidosis often remains a diagnosis of exclusion, although a typical presentation may strongly suggest the diagnosis. The diagnosis of sarcoidosis is established when a compatible clinical and radiographic picture is supported by histologic evidence of noncaseating granulomas in affected tissues and exclusion of other granulomatous diseases capable of producing a similar histologic or clinical picture. Other tests that may provide supportive evidence for sarcoidosis include measurement of serum ACE level, gallium Ga 67 scan, bronchoalveolar lavage (BAL) lymphocyte count, and CD4+/CD8+ T lymphocyte ratio; however, tissue biopsy is required for a definitive diagnosis. 3. Outline your management strategy? 3) Oral prednisone or prednisolone is usually initiated at 1-2 mg/kg/d for 4-8 weeks as induction treatment. This treatment is continued until the clinical manifestations of the disease resolve or show significant improvement. Slowly taper dose in patients who respond to steroids over a period of 2-3 months to an appropriate maintenance dose (ie, the lowest dose that controls the activity of the disease, which often is in the range of 10-15 mg/d or a qod regimen). Depending on which organs are involved and on the activity of the disease, maintenance treatment is usually required for at least 6 months for most age groups and then tapered if possible. The patient presents some time later with weakness on the left side of her face. On examination she has obvious facial asymmetry. She is worried that she may have had a stroke.

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4. What complication of this condition has occurred? 4) Bell’s Palsy 5. How can you differentiate this on physical examination from a stroke? 5) A stroke is due to an upper motor neuron lesion and there will be sparing of the forehead. Bell’s palsy is due to a lower motor neuron lesion (no sparing of the forehead). October 2005 Case 6 A 76 year old man with known COPD is brought to the Accident and Emergency department in profound respiratory distress. His family note that he developed increased sputum production one week previously and has gone downhill since then. The patient finds it difficult to speak. This is his third admission to the Accident and Emergency department this year. 1. What are the clinical signs of respiratory failure? 1) Clinical Signs of Respiratory Failure: • Signs or respiratory compensation: - tachypnoea - use of accessory muscles - nasal flaring - intercostals, suprasternal or supraclavicular recession • increased sympathetic tone: - tachycardia - hypertension - sweating • End organ hypoxia: - altered mental status - bradychardia and hypotension(late) • Hemoglobin desaturation: - Cyanosis 2. How would you assess and treat this patient? 2)Assessment and Treatment: Initial Assessment: • Conscious level(response to commands) • CO2 retention (warm periphery, bounding pulses, flapping tremor) • Airways obstruction (wheeze, prolonged expirations, hyperinflation, intercostals indrawing, pursed lips) • Background functional status and quality of life 138

•

Signs of precipitating cause

Investigations • Pulse oximetry saturation (SpO2) ~90% is a critical threshold. Below this level a small fall in PaO2 produces a sharp fall in SpO2 • ABG’s Chest X ray Treatment: • Diagnosis and treatment of underlying cause • O2 therapy • Inhaled B2 agonists • Smoking cessation 3. Some hours after admission an arterial blood gas result is brought to your attention by the nursing staff. PaO2 8kPa, PaCO2 10kPa, pH 7.39. How will this affect your management of the patient? 3) Treatment of type II resp failure: Management: • Maintenance of airway • Treatment of precipitating cause • Frequent physiotherapy +/- pharyngeal suction • Nebulised bronchodilators • Controlled O2 therapy • Antibiotics • Diuretics If PaCO2 continues to rise or patient cannot achieve a safe PaO2 without severe hypercapnia and acidaemia, respiratory stimulants, or mechanical ventilatory support may be required. 4. What antibiotic regimen would you place this patient on? Give reasons for your answer. 4) Anitibiotic Regimen: • antibiotic therapy is directed at the most common pathogens, including Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. • Mild to moderate exacerbations of COPD are usually treated with older broadspectrum antibiotics such as doxycycline, trimethoprim-sulfamethoxazole and amoxicillin-clavulanate potassium. • Treatment with augmented penicillins, fluoroquinolones, third-generation cephalosporins or aminoglycosides may be considered in patients with more severe exacerbations

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Apr 2006 (2b)How do you treat established COPD? NB:air travel is risky if FEV1<50% or PaO2<6.7 • pharmacological: stop smoking,encourage exercise,tr poor nutrition or obesity.influanza and pneumococcal vaccination.pulmonary rehabilitation/palliative care,NIPPV • PHARMACOLOGICAL: 1. Mild:antimuscarinic eg ipratropium or B2 inaled PRN 2. Moderate: regular ipratropium or long acting inhaled B2 agonist (salmeterol) with or without inhaled steroid (fluticasone) if FEV1<50% and >2 exacerbations/yr.oral theophylline. 3. Severe: combination therapy with regular short-acting B2 agnist and anticholinergic.refer to specialist.consider steroids trial; assess for home nebulizers. 4. Pulmonary:assess the need for LTOT 5. Hypertension: treat oedema with diuretics Oct 2006 (2a) Write short notes on the diagnosis and management of patients presenting with sarcodosis. Dx:•

Detailed Hx (recent dry cough,chest pain,progressive dyspnoea,decrease exercise tolerence) • Physical examinations (lymphoadenoadenopathy, hepatosplenomegaly, uveitis, conjunctivitis, KCS, glaugoma, neuropathy, erythema nodousum, cardiomyopathy) Remember: sarcodosis is a triad of 3 things (erythema nodousum+bihilar lymphoadenopathy+joint pain) • Investigations: 1. heam:^ESR,Lymphopenia.^LFT,^serumACE,^Calcium,^immunoglobulins) 2. 24hrs urine:^Calcium 3. CXR:abnormal in 90%: Stage0:normal Stage1: BHL Stage2:BHL+peripheral pulmonary infiltrates Stage3:peripheral pulmonary infiltrates alone Stage4:progressive pulmonary fibrosis; bulla formation (honeycombing; plural involvement 4.ECG: may show arrhythmias or bundle branch block 5.Lung function test:may show reduces lung volumes,restrictive ventilatory defect. 6.Tissue biopsy is diagnostic test and shows non-caeseating granulomata(liver,lung,lymph nodes,skin nodules) 7.BAL: shows ^lymphocytes in active disease,^neytrophils with PF

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9.Bone x-ray: show'punches out' lesions in terminal phalanges 10.CT/MRI: assess severity of pulmonary disease or Dx neurosarcodosis 11.Ophthalmology assessment (slit lamp, flouroscien angiography) Mx: •

Patient with BHL alone do not require Tx since the majority recover spontaneously. • Acute sarcoidosis:bed rest+NSAID • Indications for steroids: -paranchymal lung disease (symptomatic, static or progressive) -uveitis -hypercalceamia -neurological or cardiac involvement Prednisolone (20mg/day) PO for 4-6 wks, then decrease the dose over 1yr according to clinical status (do not forget to prescribe PPI!) Patient with relapse may need a further course or long term therapy In severe illness: IV methylprednisolone or immunosuppressants (Methotroxime, ciclosporin) may needed OCT 2006 (2b)What symptoms or signs suggest a severe asthma attack? • Sleep disturbance: quantity as nights/wk • Inability to complete sentences • Pulse>110 • RR:>25 • PEF:33-50% of predicted

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Rheumatology

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2002,Oct (2b) Diagnosis and treatment of gout Clinical features Hyperuricaemia causes four clinical syndromes: • • • •

acute urate synovitis - gout chronic polyarticular gout chronic tophaceous gout urate renal stone formation

Acute gout presents typically in a middle-aged male with sudden onset of agonizing pain, swelling and redness of the first MTP joint. The attack occurs at any time, but may be precipitated by too much food or alcohol, by dehydration or by starting a diuretic. Untreated attacks last about 7 days. Recovery is typically associated with desquamation of the overlying skin. In 25% of attacks, a joint other than the great toe is affected. In severe attacks, overlying crystal cellulitis makes gout difficult to distinguish clinically from infective cellulitis. A family or personal history of gout and the finding of a raised serum urate suggest the diagnosis but, if in doubt, blood and other cultures should be taken. Investigations The clinical picture is often diagnostic, as is the rapid response to NSAIDs. • •

•

Joint fluid microscopy is the most specific and diagnostic test but is technically difficult. Serum urate is usually raised (> 600 µmol/L). If it is not, recheck it several weeks after the attack, as the level falls immediately after an acute attack. Acute gout never occurs with a serum uric acid in the lower half of the normal range. Serum urea and creatinine are monitored for signs of renal impairment.

Treatment The use of NSAIDs in high doses rapidly reduces the pain and swelling. Initial doses, taken with food, are: • •

diclofenac: 75-100 mg immediately, then 50 mg every 6-8 hours naproxen: 750 mg immediately, then 500 mg every 8-12 hours

After 24-48 hours, reduced doses are given for a further week. Caution: NSAIDs may cause renal impairment. In individuals with renal impairment or a history of peptic ulceration, alternative treatments include:

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• •

colchicine: 1000 µg immediately, then 500 µg every 6-12 hours, but this causes diarrhoea corticosteroids: intramuscular or intra-articular depot methylprednisolone.

Dietary advice Reduce alcohol intake, especially beer, which is high in purines. A diet which reduces total calorie and cholesterol intake is advised. Avoid foods which are rich sources of purines, such as some fish and shellfish and spinach. This can reduce serum urate by 15% and delay the need for drugs that reduce serum urate levels. Treatment with agents that reduce serum urate levels Only when the attacks are frequent and severe, despite dietary changes, or associated with renal impairment or tophi, or when the patient finds NSAIDs or colchicine difficult to tolerate should allopurinol be used. It should never be started within a month of an acute attack and always be started under cover of a course of NSAID or colchicine for the first 2-4 weeks before and 4 weeks after starting allopurinol. Allopurinol (300-600 mg) blocks the enzyme xanthine oxidase, which converts xanthine into urate. It reduces serum urate levels rapidly and is relatively non-toxic but should be used at low doses (50-100 mg) in renal impairment. Skin rashes are the most common side-effect. Bone marrow suppression is very rare. Allopurinol may induce acute gout when it is first introduced. Uricosuric agents are no longer routinely available. ( It used in patient who are allergic to allopurinol ) The angiotensin I-receptor antagonist, losartan, is uricosuric in hypertensive patients on diuretics.

2002,Oct CASE 4 A 16 year old male is referred to hospital with a painful swollen right elbow, vague central abdominal pain and a rash involving the extensor surface of the limbs and buttocks. He had felt unwell for 5 days prior to this, complaining of headache, sore throat and fever. Examination showed a low grade pyrexia, inflamed throat and a palpable purpura more marked on the lower limbs. 1. What is the likely diagnosis?

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Henoch-Schönlein purpura (HSP, also known as allergic purpura) is a systemic vasculitis characterized by prominent tissue deposition of IgA-containing immune complexes, especially in the skin and kidney. 2. What diagnosis must be excluded in any patient with an evolving purpuric rash and systemic manifestations. Meningitis Endocarditis Rocky Mountain spotted fever Systemic lupus erythematosus Clotting disorders Thrombocytopenia 3. Outline the main features of this patients condition. The symptoms of HSP are usually preceded by a viral upper respiratory tract infection. rash --- typically purpuric with normal clotting times and usually in lower legs and arms. Features: • • • •

(100%) rash --- typically purpuric with normal clotting times and usually in lower legs and arms. (82%) arthralgia/arthritis --- usually affecting knees and ankles, are transient and cause no permanent damage (63%) abdominal pain (40%) renal disease.

4. What treatment is required? Recovery is usually spontaneous. Corticosteroids may enhance rate of recovery from arthritis or abdominal pain but does not prevent recurrence. Renal disease. Treatment is only considered in those with marked proteinuria and/or impaired renal function and patients in this setting should get a renal biopsy since the amount of crescentic glomeruli is a prognostic factor. In those with crescentic nephritis (> 50% of glomeruli), a pulse IV methylprednisolone 250-1000 mg/day for three days followed by oral prednisone (1 mg/kg/day for three months) is used. This regimen is used to reverse the inflammation rather than the IgA deposition itself. Plasmapheresis (exchange of plasma) may be curative but data is inconclusive. Intravenous immunoglobulin has also been tried in patients with heavy proteinuria and decrease in glomerular filtration rate. Renal transplant. Can be considered in those with end-stage renal disease

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2002,May (2d) Risk factors, clinical manifestations and diagnosis of osteoporosis Risk factors: Some of these risk factors exert their effect through bone mineral density (BMD) whilst others are independent BMD-dependent BMD-independent Female sex Increasing age Caucasian/Asian Previous fragility fracture Hypogonadism Low body mass index Immobilization Smoking Alcohol abuse Glucocorticoid therapy Low dietary calcium intake High bone turnover Vitamin D insufficiency Increased risk of falling Drugs: Heparin Ciclosporin Anticonvulsants Endocrine disease: Cushing's syndrome Hyperthyroidism Hyperparathyroidism Other diseases: Chronic renal disease Chronic hepatic disease Malabsorption Inflammatory bowel disease Rheumatoid arthritis Mastocytosis Multiple myeloma Osteogenesis imperfecta Clinical features Fracture is the only cause of symptoms in osteoporosis. Sudden onset of severe pain in the spine, localized at the affected level and often radiating around to the front, suggests vertebral crush fracture. However, only about one in three vertebral fractures is symptomatic. Pain from mechanical derangement, 146

increasing kyphosis, height loss and abdominal protuberance follow crushed vertebrae. Colles' fractures typically follow a fall on an outstretched arm. Fractures of the neck of the femur usually occur in older individuals falling on their side or back. Other causes of low-trauma fractures must not be overlooked, including metastatic disease and myeloma. Investigations If fracture suspected Plain radiographs usually show a fracture and may reveal previous asymptomatic vertebral deformities. Where plain films are normal, fractures (especially of pelvis) may be detected by bone scintigraphy. Bone density • •

•

Conventional radiographs are relatively insensitive for detecting osteopenia. Dual energy X-ray absorptiometry (DXA) measures areal bone density (mineral per surface area rather than a true volumetric density), usually of the lumbar spine and proximal femur. It is precise, accurate, uses low doses of radiation and is the gold standard in osteoporosis diagnosis. Because of osteophytes, spinal deformity and vertebral fractures, spinal values should be interpreted with caution in the elderly. Quantitative CT scanning allows true volumetric assessment, and distinction between trabecular and cortical bone. However, it is more expensive, requires higher radiation than other techniques, and to date offers no clinical advantage. Quantitative ultrasound of the calcaneum. This does not require ionizing radiation and is cheaper than other methods. It has been shown to predict fracture risk in men and women.

2003,Oct CASE 3 A 24 year old lady presents to her doctor with a 2 month history of stiff painful fingers and painful feet on walking. Stiffness is most marked for several hours in the morning. On examination the proximal interphalangeal and metacarpal phalangeal joints are tender and swollen. Wrists, elbows and shoulders appear normal. Skin is normal and there is no nail pitting. 1. What differential diagnosis should be considered? • • • • • •

rheumatoid arthritis SLE Postviral arthritis - rubella, hepatitis B or parvovirus Seronegative spondyloarthropathies Polymyalgia rheumatica Acute nodal osteoarthritis (PIPs and DIPs involved) 147

2. What investigations would be helpful? •

•

• •

Blood count. Anaemia may be present. The ESR and/or CRP are raised in proportion to the activity of the inflammatory process and are useful in monitoring treatment. Serology. Rheumatoid factor is present in approximately 70% of cases and ANA at low titre in 30%. RF and the antibody to CCP together are more specific, and anti-CCP indicates a worse prognosis. X-rays of the affected joint(s) to establish a baseline. Only soft tissue swelling is seen in early disease. MRI demonstrates early erosions but is rarely warranted. Aspiration of the joint if an effusion is present. The aspirate looks cloudy owing to white cells. In a suddenly painful joint septic arthritis should be suspected.

3. What management plan would you offer? • • • • • •

•

Establish the diagnosis clinically. Use NSAIDs and analgesics to control symptoms. Try to induce remission with i.m. depot methylprednisolone 80-120 mg if synovitis persists beyond 6 weeks. If synovitis recurs, refer to a rheumatologist to start sulfasalazine or methotrexate. Give a second dose of i.m. depot methylprednisolone. Refer for physiotherapy and general advice through a specialist team. If there is no significant improvement in 6-12 weeks as measured by less pain, less morning stiffness and reduced acute-phase response, use a combination of methotrexate and sulfasalazine. If no better, use an alternative agent, such as gold, d-penicillamine, leflunamide or anti-TNF-αtherapy

4. The patient wishes to start a family. How will this affect her medications before, during and after pregnancy? All DMARD therapy should be stopped in women planning to conceive and in pregnant and lactating women. Because of the evidence of potential teratogencity of Methotrexate, it should be stopped in men and women planning conception (Conception should be delayed for at least 3 months off the drug for either partner). Although safety has not been proven in controlled trials, no evidence exists for risks to the fetus of low dose prednisone (less than 20mg daily) or of NSAIDs used in the first two trimesters. If necessary, joint symptoms are best managed with the lowest possible dose of prednisone. Potential prednisone complications include worsening of maternal gestational diabetes, hypertension and intrauterine growth retardation. NSAIDs should be avoided in the third trimester because of the potential for premature closure of the ductus, prolonged labor and peripartum hemorrhage.

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Although both NSAIDs and prednisone are excreted in the breast milk, both are considered compatible with breast-feeding.

2003,April (2b) Aetiology and treatment of gout In many patients with gout there is no obvious cause. Hyperuricaemia is the major determinant for developing gout. Causes of hyperuricaemia Impaired excretion of uric acid Idiopathic (primary) gout Chronic renal disease (clinical gout unusual) Drug therapy, e.g. thiazide diuretics, low-dose aspirin Hypertension Lead toxicity Primary hyperparathyroidism Hypothyroidism Increased lactic acid production from alcohol, exercise, starvation Glucose-6-phosphatase deficiency (interferes with renal excretion) Increased production of uric acid Idiopathic (primary) gout Increased purine synthesis de novo ( very rare) due to: Hypoxanthine-guanine-phosphoribosyl transferase (HGPRT) reduction (an Xlinked inborn error causing the Lesch-Nyhan syndrome) Phosphoribosyl-pyrophosphate synthase overactivity Glucose-6-phosphatase deficiency with glycogen storage disease type 1 (patients who survive develop hyperuricaemia due to increased production as well as decreased excretion) Increased turnover of purines due to: Myeloproliferative disorders, e.g. polycythaemia vera Lymphoproliferative disorders, e.g. leukaemia Others, e.g. carcinoma, severe psoriasis Treatment The use of NSAIDs in high doses rapidly reduces the pain and swelling. Initial doses, taken with food, are: â&#x20AC;˘ â&#x20AC;˘

diclofenac: 75-100 mg immediately, then 50 mg every 6-8 hours naproxen: 750 mg immediately, then 500 mg every 8-12 hours

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colchicine: 1000 µg immediately, then 500 µg every 6-12 hours, but this causes diarrhoea corticosteroids: intramuscular or intra-articular depot methylprednisolone.

2004,Oct Write short notes on (2d) Differential diagnosis of acute polyarthritis • • • •

Postviral arthritis - rubella, hepatitis B or parvovirus Seronegative spondyloarthropathies Polymyalgia rheumatica Acute nodal osteoarthritis (PIPs and DIPs involved)

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2004, Oct (2e) Risk factors for osteoporosis Some of these risk factors exert their effect through bone mineral density (BMD) whilst others are independent BMD-dependent BMD-independent Female sex Increasing age Caucasian/Asian Previous fragility fracture Hypogonadism Low body mass index Immobilization Smoking Alcohol abuse Glucocorticoid therapy Low dietary calcium intake High bone turnover Vitamin D insufficiency Increased risk of falling Drugs: Heparin Ciclosporin Anticonvulsants Endocrine disease: Cushing's syndrome Hyperthyroidism Hyperparathyroidism Other diseases: Chronic renal disease Chronic hepatic disease Malabsorption Inflammatory bowel disease Rheumatoid arthritis Mastocytosis Multiple myeloma Osteogenesis imperfecta

2004,April Write short notes on (2b) Extra-articular manifestations of rheumatoid arthritis Soft tissue surrounding joints Subcutaneous nodules are firm, intradermal and generally occur over pressure points, typically the elbows, the finger joints and the Achilles tendon.

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The olecranon and other bursae may be swollen (bursitis). Tenosynovitis of affected flexor tendons in the hand can cause a trigger finger. Swelling of the extensor tendon sheath over the dorsum of the wrist is common. Muscle wasting around joints is common. Myositis is extremely rare. Corticosteroidinduced myopathy may occur. Lungs Peripheral, intrapulmonary nodules are usually asymptomatic but may cavitate. When pneumoconiosis is present (Caplan's syndrome), large cavitating lung nodules develop. Other manifestations are: • • • •

serositis causing pleural effusion pleural nodules fibrosing alveolitis obstructive bronchiolitis.

Vasculitis Vasculitis is caused by immune complex deposition in arterial walls. It is uncommon. Smoking is a risk factor. Other manifestations are: • • • •

nail-fold infarcts due to cutaneous vasculitis widespread cutaneous vasculitis with necrosis of the skin (seen in patients with very active, strongly seropositive disease) mononeuritis multiplex bowel infarction due to necrotizing arteritis of the mesenteric vessels (this may be indistinguishable from polyarteritis nodosa).

The heart and peripheral vessels Clinical pericarditis is rare. In strongly seropositive RA, echocardiogram or post-mortem studies, however, show that 30-40% of patients have pericardial involvement. Endocarditis and myocardial disease are rarely seen clinically, although found at postmortem in approximately 20% of cases. These are secondary to vasculitis. Raynaud's syndrome may occur. The nervous system Neuropathies, either mononeuritis multiplex or a sensory loss in a glove and stocking pattern, are due to vasculitis of the vasa nervorum. Compression neuropathies such as carpal or tarsal tunnel syndrome are due to local

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synovial hypertrophy. Atlantoaxial subluxation can cause serious neurological abnormalities. The eyes Scleritis and episcleritis occur in severe, seropositive disease and produce painful red lesions in the eye. Scleritis may lead to perforation of the eye (scleromalacia perforans) and requires active treatment with local and systemic corticosteroids. Sicca syndrome causes dry mouth and eyes (Sjรถgren's syndrome). The kidneys Amyloidosis causes the nephrotic syndrome and renal failure. Presentation is with proteinuria. It occurs rarely in severe, long-standing rheumatoid disease and is due to the deposition of highly stable serum amyloid A protein (SAP) in the intercellular matrix of a variety of organs. Proteinuria in RA is more commonly due to DMARDs. The spleen, lymph nodes and blood Felty's syndrome is splenomegaly and neutropenia in a patient with RA. Leg ulcers or sepsis are complications. The lymph nodes may be palpable, usually in the distribution of affected joints. Anaemia is almost universal and is usually the normochromic, normocytic anaemia of chronic disease. It may be iron-deficient owing to gastrointestinal blood loss from NSAID ingestion, or rarely haemolytic (Coombs' positive). There may be a pancytopenia due to hypersplenism in Felty's syndrome or as a complication of DMARD treatment. A high platelet count occurs with active disease.

2005,Oct Write short notes on (2a) Causes, diagnosis and treatment of osteomalacia Causes: ======= Vitamin D deficiency Inadequate synthesis in skin (inadequate sunlight exposure) Low dietary intake Anticonvulsant therapy (especially phenytoin and phenobarbital) Malabsorption: Coeliac disease Intestinal resection

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Chronic cholestasis, e.g. primary biliary cirrhosis Renal disease Chronic renal failure Bone disease due to dialysis Tubular disorders, e.g. renal tubular acidosis, Fanconi's syndrome Miscellaneous Tumour-induced hypophosphataemic osteomalacia Diagnosis: ======== Clinical features: vague symptoms of bone or muscle pain and tenderness. Pathological fractures may occur. Occasionally a marked proximal myopathy leads to a characteristic 'waddling' gait. Deformity is uncommon. Investigations: • • • • •

•

Increased serum alkaline phosphatase, indicating increased osteoblast activity, is the most common abnormality. Plasma calcium is usually normal, in association with secondary hyperparathyroidism and a raised PTH., but may be low in severe cases. Serum phosphate may be low, owing to increased PTH-dependent phosphaturia, though this is variable. Serum 25-hydroxyvitamin D3 is usually low. X-rays are often normal in adults, but may show defective mineralization, especially in the pelvis, long bones and ribs, with 'Looser's zones' - linear areas of low density surrounded by sclerotic borders. Iliac crest biopsy with double tetracycline labelling is occasionally necessary if biochemical tests are equivocal.

Treatment: ========= Treatment should be directed towards correction of the cause where possible, with increase in vitamin D intake and sunlight exposure. Multiple formulations of vitamin D and its metabolites are available. When deficiency is nutritional, 'replacement' doses of the native vitamin are needed (400-800 IU daily). Higher 'pharmacological' doses, sometimes administered parenterally, may be needed in some patients with gastrectomy, malabsorption or liver disease, although many respond to more conventional doses. Treatment with calcitriol or alfacalcidol is indicated where there is defective 1α-hydroxylation, e.g. chronic renal disease, vitamin D resistance and hypophosphataemic rickets and osteomalacia.

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2003,Oct Q1. A 36 year old lady presents with a history of her fingers turning blue whenever they are exposed to cold temperatures. She also has fatigue, arthralgias and recurrent small painful digital ulcers. How would you evaluate and treat this patient? 2005,April Q1. A 37 year old woman reports that her fingers turn blue when they are exposed to cold temperatures. She also notes fatigue, arthralgia and small painful digital ulcers. Outline how she should be evaluated and treated. This patient describes symptoms suggestive of Raynaud’s syndrome: disorder of vasospasm of small vessels characterised by episodic digital ischemia that is precipitated by emotion or cold and relieved by heat. Vasospasm causes a progressive pattern of discoloration tricolour from pallor (white) to cyanosis (blue) then resolving hyperaemia (red), and it is associated with sensory changes. Causes of Raynaud’s syndrome (DDx) 1. Ideopathic: 3-20% prevalence (male=females). It is diagnosed as idiopathic if it persists for more than 3 years with no associated evidence of underlying CTD. 2. Raynaud’s phenomenon associated with an underlying cause (long list!) - Systemic Sclerosis: Scleroderma/ CREST syndrome: generalised disorder of connective tissue of unknown aetiology that affects the skin, internal organs and vasculature characterised by sclerodactyly and Raynauds (or digital ischaemia)- Raynaud’;s is one of the first manifestations - SLE: raynaud’s very common- most common presentation of SLE is arthritis/ arthralgia associated with Raynaud’s - Dermatomyositis - Mixed connective tissue disease - Sjogren’s syndrome - Rheumatoid arthritis - Leukaemia - Thrombocytosis - Monoclonal gammopathies - PRV (polycythemia rubra vera) - Drugs: Beta blockers, ergot alkaloids and bromocriptine - Working with vibrating tools - Obstructive: thoracic outlet obstruction - Hypotheyroidsim NOTE: Systemic sclerosis= scleroderma (skin fibrosis) and vasculitis. This is divided into: 1. Diffuse systemic sclerosis: skin involvement is widespread along trunk, proximal limbs and profuse organ involvement (heart, lungs, kidney) with early pulmonary hypertension and anti Scl 70 +

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2. Limited systemic sclerosis: aka CREST syndrome: limited to skin of hands, feet and face. Late pulmonary hypertension. Specific organ involvementGIT- oesophageal dsymotility and interstitial lung disease. . anticentromere + I. Assessment of this patient should include 1. A full history inquiring about • duration of symptoms and other precipitating factors • arthralgia - site of pain and distribution ie symmetrical (rheumatoid arthritis) vs asymmetrical - involvement of the small joints of the hand (if DIP- NOT rheumatoid arthritis) – symmetric small joints deforming arthritis ? SLE) - morning stiffness - joint swelling and deformity - timing of symptoms ie at the end of the day or early morning - aggravating and relieving factors - severity and functional ability/ effect on ADL • other constitutional symptoms - fatigue - weight loss - anorexia - fever - mayalgia (DM strong feature) • extra- articular manifestations of connective tissue disease: - iritis/ scleritis - rash on face or hands? (butterfly rash)/ photosensitive rash - renal involvement: haematuria, oedema? • features of scleroderma: - tight skin over face and joints - puffy hands and feet - dysphagia (oesophageal dysmotility) - reflux (GORD/ barret’s oesophagus/ dysmotility) - abdominal pain - diarrhoea (GI dysmotility/ malabsorption/ bacterial overgrowth) or steatorrhoea - shortness of breath (pulmonary fibrosis) and dry cough - history of hypertension (renal impairment) or renal failure • SLE: - fatigue, fever, myalgia (flare up), weight loss - CNS: headache, migraine, seizure, psychosis •

Other symptoms/ features: - History of early pregnancy fetal loss - History of DVT/ clots

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• • •

difficulty squatting, going up stairs, raising hand above head (DM) dysphagia an dsyphonia (DM) dry eyes and mouth (sjogren’s syndrome)

Family history of connective tissue disease RA, scleroderma, SLE Drug history: ? drug induced lupus ( procainamide, isoniazid, hydralazine, chlorpromazine- antihistoen + 100%) Occupation

2. Exam: General -

muscle wasting/ cachexia general well being/ distress

digital infarcts nailfold capillary dilatations (telangiectasia)- scleroderma (limited) pulp atrophy (from ischaemia)- scleroderma/ raynaud’s calcinosis (calcium deposition in digits and fingers) CREST non pitting oedema of fingers and flexor tendon sheaths with smooth shiny indurated skin (sclerodactyly) CREST non erosive arthritis of (scleroderma) muscle wasting (secondary to myositis) anaemia Guttron’s papules: pathognomonic of DM if ↑ CK and muscle weakness: roughened red papules over knuckles- elbows and knees also (Dermatomyosisits DM)

Hands:

Face/ neck: -

Oral ulcers (SLE)microstomia (SS) radial furrowing (SS) thinning of lips (SS) beaked nose (SS) dental carries photosensitive rash (SLE) buttererfly rash (SLE) discoid rash Heliotropic rash (DM) Salivary and lacrimal gland enlargement (sjogren’s syndrome) Thyroid goitre (? Sjogren’s syndrome) Lymphadenopathy (SLE) Alopecia (SLE) EYES: SLE: haorrhage and retinal exudates

GIT

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Respiratory: - fine crackles of lung fibrosis, pleuritis CVS- pulmonary hypertension- loud P2 - pericarditis CNS: retinal exudates (SLE) II. Investigations: tailor to patient’s symptoms Bloods - FBC: normochromic normocytic anaemia - Neutropaenia, lyphopaenia and thrombocytopaemia- SLE - ESR - CRP: if normal with raised ESR think SLE! - U/E - LFT - Serum C3 and C4 (low in SLE) - Albumin - Clotting screen (lupus and antiphospholipid syndrome) Autoantibody screen - Rheumatoid factor - ANA + in 95% SLE - Anti Ds DNA/ Anti Sm - Anti histone antibodies (drug induced lupus_ - Anti SCl 70 and anticentromere antibodies - Anti Jo 1 (dermatomyosistis) - Anti Ro and Anti La (Sjogren’s syndrome) 70% - Antiphospholipid antibodies ( + with SLE): anti cardiolipin antibodies, lupus anticoagulant, + VDRL serology Radiology: - CXR - Joint x-ray: calcification, distal erosions, resorption of tufts - CXR: lung fibrosis - high resolution CT – lung fibrosis Specialized tests: Eosophageal mannometry - reduced peristalsis ECG: myocarditis/ pericarditis (SLE and DM) Cardiac enzymes (myositis) Muscle enzymes: CK and ALT/ aldolase EMG: myopathic changes in DM MRI: muscle inflammation (DM) Schirmer’s test/ labial biopsy (sjogren’s syndrome)

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III.Management: Non pharmacological: - education about disease/ relapses - mouth and facial exercises - soft/ blended food Pharmacological - Analgeisa NSAIDS for arthralgia - Elevate head of bed, avoid NSAIDs..etc for GORD - D- penecillamine (in past) or methotrexate for skin disease (diffuse scleroderma) - Steroids and immunomodulators Management of Raynauds: - keep warm - Stop smoking - Nifedipine calcium antagonist : 10-20 mg/ 18 hr - ACE inhibitor/ ARB - Iliporost IV infusion 0.5ng/kg/ min - * severe cases : sympathetectomy Management of Systemic Sclerosis - Proton pump inhibitor for symptomatic reflux (also cisapride and nifeedipine have been used) - metoclopromide/ domperidone- prokinetic against for dysmotility - pulsed laser therapy for telangiectasia - Epoprost influsion for pulmonary hypertension - Antibiotics: bacterial overgrowth: Ciprofloxacin/ Metronidazoele/ tirmethoprin - Akin ulcers/ infections: â&#x2020;&#x2018; dose IV flucloxacillin - Steroids and D- penecillamine for skin disease - ACEi for renal disease/ crisis - Immunosupressants: TGF B inhibors, mycophenolate mofetil, tacrolimus (new agents) SLE -

control arthritis and pleuritis with NSAIDS/ hydroxychroloquine immunosuppressants for organ involvement starting with prednisoslone IV mainly IV prednisolone/ cyclophosphamide for disease flare up lupus nephritis: cyclophosphamide, IV or azothrioprine skin manifestations: hydroxychloroquine, sun block life long anticoagulation from thormobosis

DM/PM - â&#x2020;&#x2018; dose prednisolone (1mg/kg/day)- follow up with muscle enzyme tests - Immunosuppressants: methotrexate, azothioprine, cyclosporin

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Follow- up: -

annual PFTâ&#x20AC;&#x2122;s OGD U/E and renal function tests Colonoscopy and mammography (â&#x2020;&#x2018; risk of malignancies in DM/ PM) Monitor SLE drug side effects ex/ hydroxychloroquine retinopathy and monitor for infections

* This answer takes into consideration CTDs as a whole- you could tailor this to include SLE or systemic sclerosis only based on your interpretation of the question ** DM= dermatomyositis PM= polymyositis SS= systemic sclerosis

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