PEARLS OF MRCP

PART 2 – PASTEST

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Table of Contents
CARDIOLOGY.............................................................................................. 2
ENDOCRINOLOGY...................................................................................12
RHEUMATOLOGY.................................................................................... 18
RESPIRATORY.......................................................................................... 24
GASTROENTEROLOGY........................................................................... 35
NEUROLOGY............................................................................................. 45
OPTHALMOLOGY.................................................................................... 61
PSYCHIATRY............................................................................................. 63
INFECTIOUS DISEASES..........................................................................65
RENAL MEDICINE.................................................................................... 74
HAEMATOLOGY & IMMUNOLOGY......................................................82
ONCOLOGY & PALLIATIVE...................................................................89
DERMATOLOGY....................................................................................... 93
THERAPEUTICS & TOXICOLOGY........................................................95

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CARDIOLOGY  Best dx: TEE
 Tx:
o Thrombolytic therapy in APO/hypotensive
Peripartum cardiomyopathy o Stable: surgery for L sided and thrombolytic agents for R sided
 Uncertain etiology o Serial echo
 Diagnosis
o Absence of other causes Valve haemolysis
o No prior evidence or identifiable cause of heart failure  Clinical features
o During last month of pregnancy (antepartum) or within first 5 months o Recent valve replacement
postpartum o Anaemia
o Documented systolic dysfunction  Haemolysis usually mild and subclinical
 Therapy o Heart failure
o Sodium restriction o Fragented red cells
o Diuretics - loop
o Digoxin Stable angina
o Afterload-reducing agents: ACE-I (not in pregnant ladies), hydralazine,  Initial therapy
inotropic support with dobutamine o BB: prognostic benefit in HF
 Risk of thromboembolism: hypercoagualable state of pregnancy and stasis of blood o CCB: in patients who cannot take BB
in LV  If symptoms uncontrolled, other agents can be considered
 Systolic dysfunction in LV o Slow release nitrates
o CXR: cardiomegaly o Ivabradine
 Prognosis: reasonable o Nicorandil
o Recovery of ventricular function in 50%
o Risk of recurrence in future pregnancies ~ 40% ACS
o If no EF recovery and symptomatic: heart transplant  NSTEMI
 Management o CURE: clopidogrel
o Digoxin, diuretics  Reduction in non-fatal MI
o Vasodilators o CLARITY: aspirin + clopidogrel
o Anticoagulation  Management
o PCI superior to thrombolytic therapy
Tocolysis-associated pulmonary edema  tPA preferable to streptokinase if thrombolysis is only option
 APO can occur with B-agonists used for tocolysis o beta-blocker:
o Usually 24hours after administration of these agent 
o CXR: pulmonary infiltrates and normal heart size  Complications
o Risk can be increased with concomitant corticosteroids for lung maturation o PVCs and NSVT common in early post MI period
 NSVT: ≥3 consecutive beats at a rate ≥100bpm that last ≤30s
Prosthetic valve thrombosis  If no haemodynamic compromise, no treatment needed
 More common in mitral prosthesis and with subtherapeutic anticoagulation

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  If haemodynamic compromise or sustained VT: anti-  Investigations
arrhythmic therapy o TEE
 If NSVT occurs late (after 48hrs), KIV electrophsiological cardiac MRI
studies and ICD
 Hypokalemia increases incidence of NSVT, VT, VF Mitral stenosis
 GISSI-2: K < 3.6 associated with 2x risk of VF  Bifid P wave (P mitrale) & diastolic murmurs
o Maintained above 4  pAF
 Concomitant hypomagnesemia present in hypokalemia,  Tx:
thus should be maintained above 1 o Beta-blockers: prevent atrial tachyarrhythmias, slow down heart rate
o Acute mitral regurgitation increasing diastolic time and augmenting cardiac output
 Cause: ruptured chordae tendonae o Digoxin: not helpful in pAF
 Signs: HoTN, tachycardiac, LV failure, PSM o Amiodarone: resistant cases
 Management: diuretics, ACE-I o Flecainide: CI in structural heart disease
 Surgical repair has high operative risk
o Ventricular septal rupture Mitral valve prolapse
 Determinant of early outcome – development of heart failure  5% of population, more common in females
 Associated cardiogenic shock -> end-organ malperfusion  Management
(may be irreversible) o Beta-blocker
 Management: SURGERY (high operative mortality) o Echo every 2-3 years
o Regular aerobic exercise
Inferior MI o MVR: severe MR, LV dysfunction
 AV block is common as blood supply to AV node is from RCA
o Usually resolves in first 24hrs Early Repolarisation Variant
o But if it occurs in anterior MI: poor prognosis as it signify extensive event  Benign: expresses an early uptake of ST segment before descending limb of R wave
o Can also occur as drug toxicity (Bblockers, digoxin, verapamil) has reached baseline
 Widening QRS – indicates more extensive ischaemic territory  Features
o ST elevation during early exercise but returns to normal as heart rate
Anterior MI increases further
 AV block indicative of extensive infarction -> significant likelihood of permanent o Black males
complete heart block o Usually seen in precordial leads
o Indication for temporary pacing and permanent pacing almost invariably o Clinical evaluation entirely normal
required
o CARISMA trial: high degree AV block – strongest predictor of mortality Pericarditis
 Cardiogenic shok occurs in 7%: 10% at admission, 90% develop in hospital (high  Triad: chest pain (worse on lying down), pericardial friction rub and ECG changes
mortality)  Investigations:
o Management o Raised Tw/ESR/CK
 Circulatory support  Complications: pericardial effusion
 Vasopressors: IV dopamine & IABP  Tx:
o High dose aspirin or NSAIDs
Sinus of Valsalva aneurysm rupture o Colchicine: both acute and as prophylaxis for recurrent episodes
 Rare cause of acute chest pain and heart falure
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 o Prednisolone: if NSAIDs and colchicine therapy fails o Relative risk decreased by around 80% in drug eluding stents with DAPT x 1
o Pericardectomy only indicated if medical therapy fails yr
o Reduce physical activities for a few days after o Pioglitazone reduce ISR but can worsen heart failure
 Causes  BMS re-stenosis more commonly in patients with DM
o Infections: Coxsackie B, mumps, influenza, adenovirus, echovirus
o Autoimmune phenomenon: recurrent attacks of what appeared to be Heart Failure
idiopathic acute pericarditis  Improved outcome:
o Drugs: pergolide, cabergoline (can also be a/w cardiac valve regurgitation, o Ramipril
pericardial effusion, pulmonary HTN) o Bisoprolol: B-CONVINCED
o Spironolactone
Acute viral myocarditis  RALES: small dose of 25mg reduced mortality by 30% when added
 Management to conventional therapy for patients with severe clinical heart
o High flow oxygen failure and EF < 35% and already on ACE-i/loop diuretics
o Improve haemodynamic status  PATHYWAY-2: most effective BP lowering med in doses up to 50mg
 If PCWP > 15mmgHg: give inotropic support o Eplerenone
 If pulmonary edema: diuretics  Improved outcomes /mortality in NYHA class II
 If PCWP < 15mmgHg: cautious IV fluids (colloids 100-200mls) o Carvedilol: COPERNICUS
o Small amount of dimorphine  Improve survival rates in severe heart failure
 Vasodilates and reduces anxiety o Enalapril: SOLVD
o Ivabradine
PFO  Outcome benefit in patients HR > 75bpm
 Common in young people, can be up to 30% o LVAD: REMATCH
o Increased risk of stroke 2’ paradoxical embolus  52% overall survival in 68 non-transplantation candidates
o Associated with migraine development  50% survival 1 year survival
 Symptoms relief:
ASD o Furosemide
 30% of congenital heart disease in adults: often first diagnosed in adulthood o Digoxin: DIG
 Female to male ratio: 2:1  Reduced hospitalization and mortality rate
 75% are ostia secunda  Diastolic heart failure
 Allows left to right shunting -> increase right heart output -> pulmonary HTN o Treatment: aimed at reducing pulmonary venous pressure and congestion
 Atrial fibrillation  Diuretics
 Fixed S2 splitting and MSM in pulmonary area  ARBs: losartan, telmisartan, irbesartan, candesartan
 CXR: pulmonary plethora  ACE-I, antiplt aggregation, hypouricemic, antiDM, anti-AF
 ECG: RBBB  CHARM: Candesartan reduces CHF admissions in patients
 Tx: with EF > 40%
o Closure: surgically or percutaneously if shunt is >1.5:1  CRT
 QRS > 120, NYHA ≥ class II and LBBB
Coronary stents  If no LBBB, use ICD if RS between 120-149
 40-50% restenosis at end of 6/12 in T2DM patients
Pericardial effusion
 Pulsus paradoxicus: significant drop in BP on inspiration
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 Causes: o RBBB: RSR complex in V1
o Midline radiotherapy -> inflammatory pericarditis with effusion o LAHD (left anterior hemi-block): QRS axis in lead II –ve

Atrial Flutter Wolff-Parkinson-White (WPW)

 Rhythm control  Type A
o Flecainide: used in patients with no h/o IHD/structural heart disease o Short PR interval: best seen in aVF and V4
o Amodarone: used in presence of structural heart disease o Dominant R wave in V1
 Rate control  Type B
o Digoxin o Predominantly negative delta wave in V1
o Verapamil  Investigations
o Electrophysiological studies
Atrial Fibrillation  Management
 When associated with MS, fast AF tolerated poorly o Radiofrequency ablation
o Achieve rate control as quickly as possible o Ant-arrhythmic:
 Rhythm control alone has no survival benefit over rate control  Amiodarone and felcanide (prophylaxis against AF)
o Rate control not inferior for mortality and morbidity as compared to  Sotalol: prolongs myocardial refractiveness
electrical cardioversion o Avoid verapamil/adenosine (acts on AV node): may lead to preferential
o AFFIRM/RACE: no significant differences in QoL, M&M between rate and conduction down accessory pathway -> can ppt VF
rhythm control strategies
 High risk patients need to be anti-coagulated Supraventricular tachycardia
 Management  Commonest: re-entrant SVT
o In absence of structural heart disease/isceamic heart disease o Can occur in young healthy and structural heart disease
 Cardioversion with IV flecainide  Cause: presence of dual AV nodal pathways
o B/g structural/ischaemic heart disease  Can present any time from teenage years to 7th decade
 Amiodarone  Can be precipitated by amphentamine, cocaine
 Management
Sinus arrhythmia o CCB: verapamil
Most commonly due to respiration  Blocks calcium influx -> Decreases conduction of AV node ->
 Slight beat to beat variation – heart rate variability in synchrony with respiration decreases conduction velocity and prolongs refractory period
o Normal in children and young adults o BB – can worsen MI in context of cocaine overdose
o R-R interval decreases with inspiration and increases with expieration o Adenosine (CI in asthmatic) -> give IV flecainide/verapamil
 In sinus arrest/pause, sinoatrial exit block: R-R interval does not have rhythmic  Can cause bronchospasm/bronchoconstriction
and cyclical variation o Post termination ECG: examine for pre-excitation
o Unexpected disappearance of P wave for variable interval
o Wenkebach-type fashion Ventricular fibrillation
 Management
Heart Block o Cardioversion
Trifascicular block: RBBB, LAHB and long PR interval (1st degree block) o Pharmacological
 ECG:  Amiodarone infusion (IV then oralise)
o PR grossly prolonged

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  Flecainide and propafenone: increased mortality in patients with o First letter: chamber being paced
arrhythmias post MI o Second letter: chamber being sensed
 Lignocaine: negatively inotropic (2nd choice) o Third letter: response to sensing
o Forth letter: rate modulation
Polymorphic ventricular tachycardia o Fifth letter: multi-site pacing
 Management  Complications
o IV magnesium o Atrial fibrillation
 Decreases calcium influx, reducing the amplitude of VT, helping o Thromboembolic events
terminate runs of torsades o Heart failure
 Effective even when serum magnesium
Atrial Myxoma
Pacemaker syndrome  Most common primary heart tumour
 Suboptimal AV synchrony or AB dyssynchrony  Symptoms
 VVIR: single ventricular lead pacemaker – sense and paces ventricle, and inhibits o Distant embolization
responses to a sensed event o Finger clubbing
o Untimely contraction of atria caused by retrograde conduction of ventricular o Normocytic anaemia
pacemaker impulse mimics complete heart block o Positional murmur
o Pounding feeling: atria contracting against a closed TV causing cannon o Intracardiac calcification
waves in neck o Fainting spells: transient LV inflow obstruction
 Risk factors
o Mechanical interference with cardiac function
o Low heart rate prior to pacemaker implantation
 Obstruction of mitral valve: dizziness/syncope
o High programmed lower rate limit
 Exertional dyspnea
o VA conduction o Constitutional
o Non-compliant venricles and diastolic dysfunction: sensitive to loss of atrial  Fever
contribution to ventricular filling (e.g. cardiomyopathy, elderly patients)  LOW
 Clinical features  Arthralgias
o Decreased cardiac output  Signs
o Loss of atrial contribution to ventricular filling o Loud S1 (delay in mitral valve closuer due to prolapse of tumour into orifice)
o Loss of total peripheral resistance response and nonphysiologic pressure o Diastolic tumour plop
waves o TR/MS
o Neuro: dizzinesss, near syncope, confusion  ¾ in females and 15% with sudden death
o Cardiac: dyspnea, orthopnea, paraoxysmal, nocturnal dyspnea, edema  Mostly sporadic but AD variety can exist
o Hypotension, seizure, AMS< diaphoresis, orthostatic hypotenson, shock
o Fatigue, weakness, SOBOE, lethargy, lightheadness HOCM
o Palpitations  Familial (chromosome 14q) and sporadic
o Choking sensation, jaw pain, RUQ pain, headache  Marked hypertrophy of myocardium with disproportionate increase in size of septum
 Treatment:  Prone to sudden death related to cardiac arrhythmias
o Upgrade to dual chamber pacemaker  Treatment:
 Allow atria to sense retrograde electrical impulse and inhibits o Cardiac failure: Beta-blocker
native atrial depolarization o Where outflow gradient > 50mmg Hg: surgical myomectomy
 Nomenclature
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 o Ventricular arrhythmias: implantable defibrillator o ECG appearance
 Diagnosis
Restrictive cardiomyopathy o IV drug testing (ajmaline – class Ia anti-arrhythmic agent: lengthen
 Amyloidosis: RA and speckled myocardium refractory period by inhibiting Na channel and interfere w hERG potassium
o CI: digoxin (?dioxin binding in amyloid fibrils – patients are extremely ion channel) and causes AP to become longer and cause bradycardia and
sensitive) electrophysiological testing
 Brings out ST segment elevation above baseline
Endocarditis  ECG abnormalities can be unmasked by Na channel blockers such
 Rare complication associated with colonic resection as flecainide
o Commonly: S. bovis (gallolyticus), Bacteroides  Treatment
 Bacteria endocarditis o No treatment
o Blood c/s +ve in 75% o Prophylactic ICD to tx life threatening arrhythmias (may improve QoL)
o Associated conditions  Prognosis
 Sydenham’s chorea – a/w rheumatic fever (?pre-existing valve o Majority likely remain asymptomatic and at low risk of relapsing
lesion)
 Dental works – vector for infection Arrhythmogenic right ventricular dysplasia (ARVD)
o Organisms  ECG: ST E in right precordial leads & RBBB (rare occurrence)
 Strep. Viridans (a/w dental work & 60% of subacute)
 Staph. Aureus (prosthetic valves, acute, IVDA) Significant PVC/PVE
o Treatment  Occurring frequently: ≥6 beats/min
 Benzylpenicillin & gentamicin  PVE in bigeminal rhythm
 PVE in short runs of ventricular tachycardia
Brugada Syndrome  PVE exhibiting R on T phenomenon
 Autosomal dominant  PVE a/w serious organic heart disease and LV decompensation
 Sodium channel in myocytes of the heart (gene SCN5A) abnormality associated with
sudden death arising from ventricular fibrillation Carotid sinus hypersensitivity
 Male predominance with onset in early years of life  Exaggerated response to carotid sinus stimulation
o Family history of sudden death  Must exclude IHD or rhythm disturbances first
o History of syncope and ECG appearance  Can be
 Inherited form of cardiac arrhythmia o Cardioinhibitory (bradycardia)
o ECG: STE in V1-V3, incomplete/complete RBBB, TWI in V1  Dual chamber pacemaker
 Changes may be transient overtime, can have at least 1 normal ECG o Vasodilatory (hypotension)
 Genetic defect: SCN5A gene  Support stockings
o Encodes sodium channel controlling depolarization phase of cardiac action  Fludrocortisone
potential  Midodrine
o Usually no structural abnormalities, pure electrical abnormality of
myocardial cells AICD
 Clinical features Indications
o Syncope (die to VT)  Late-onset VT post ischaemic event + LV impairment on TTE
o Cardiac arrest – usually by 3rd or 4th decade of life, usually at rest or during o Superior wrt survival as compared to anti-arrhythmic therapy
sleep  NSVT
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 Inducible arrhythmias on electrophysiological testing o When symptoms appear, survival without surgery is ~2-3yrs
 LV EF < 35% and NYHA III or less o Sudden death in 1-2% of asymptomatic patients/year
 Familial conditions: long QT, HOCM, Brugada, ARVD, post TOF repair  Causes
o Congenital
CRT o Rheumatic heart disease
Indications o Bicuspid valve
 EF < 35% o Degenerative calcification
 Drug refractory symptoms o HOCM
 QRS > 120ms  CI: ACE-I in severe AS
 Management
Pacemaker o AVR
Indications  Symptomatic
 Third degree block  Asymptomatic
 Symptomatic Wenckebach phenomenon  Pressure gradient > 50mmHg
 Asymptomatic type II 2nd degree heart block
o In v/o likelihood of progressing to complete heart block or episodes of Aortic dissection
syncope  Types
 Pauses > 3s o A: ascending aorta
Complications o B: descending aorta
 Lead displacement  Management
 Haematomas o Reduction of blood pressure:
 Infection  IV BB
 Erosion of PPM box through the skn  Reduce rate of LV ejection and shear on the aortic wal
 Reduce SBP to 100-120 and pulse to near 60
 IV sodium nitroprusside can be added if BP not well controlled with
Aortic regurgitation BB but should not be used alone as it may increase rate of LV
 Treatment: Medical ejection (hydralazine should be avoided by same reason)
o ACE-I o Pain relief
 Treatment: Surgical  Investigations
o Valve replacement o CT scan: assess extent of dissection and suitability of surgery
 Dilated LV (suggest rapid deterioration)  Complications
 Impaired EF o Haemopericardium
 Follow up o Cardiac tamponade
o Regular echo  If pericardiocentesis performed: increase intra-aortic pressure and
reopen closed communication between false lumen and
Aortic stenosis pericardium
 Signs  Recurrent cardiac tamponade
o ESM, loudest in aortic area, with radiation to carotids, axilla  Prognosis
o Slow rising, small volume pulse in severe stenosis o Poor if hypotension & ischaemia present
o Reversed splitting of S2  Type A dissection extends proximally to involve coronary arteries
 Symptoms: syncope, angina, dyspnea
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  Tx challenging but usually managed with endovascular  Surgery only after pharmacological alpha and beta-adrenergic
stenting approach blockage

Hypertension Hypertensive encephalopathy

 Beta-blockers  Symptoms
o Associated with impaired glucose tolerance o Gradual onset
 ARBs o Headache, nausea, vomiting, confusion, hypertensive retinopathy
o In Afro-Caribbean: preferred to ACE-I as 2nd agent  Management
 ASCOT: BB and thiazide increase risk of new onset T2 DM o Nitroprusside: 1st line agent
 NICE guidelines  IV and can be titrated closely to response
o CCB in >55yo, or thiazide diuretic if CB CI o Long acting CCB: 2nd line agent
o ACE-I in < 55yo, or ARB if ACE-I not tolerated  BB used to be 2nd line agent but avoided now as they may worsen
 Blood pressure & response to exercise isachemia
o SBP increases progressively till maximum exercise  Clonidine and methyldopa avoided for the same reasons
o DBP remains the same and may decrease slightly with progresisive exercise
o Abnormal in heart disease Kartagener’s syndrome
 Fall in BP or failure to rise or exercise rise (SBP > 250) is in  Dextrocardia, bronchiectasis
indication to terminate exercise  ECG:
 Isolated systolic hypertension: treat with anti-HTN o Lead I: Inverted P waves in with a negative QRS deflection
o SHEP: reduced incidence of stroke and major cardiovascular events o Lead aVR: Upright P waves with positive QRS deflection
o Lead aVL: mirror image findings in aVR
Pheochromocytoma o Abnormal R wave progression from V1-V6
 10% of tumours are extra-adrenal (paragangliomas), 10% bilateral and 10% are
malignant Lutembacher syndrome
 Clinical features  Combination of MS and ASD
o Hypertension with paroxysms of headache, palpitations and sweating o Can be congenital or due to rheumatic fever or other causes
o Severe hypotension from catecholamine-induced cardiomyopathy  Higher incidence in females due to higher incidence of congenital ASD
 Investigations  Usually present later in life with fatigue or AF
o Elevated catecholamine levels in 24hr urine sample  Management
o Iodine labeled metaiodobenzlguanidine (MIBG): tumour confirmed o Early surgery to prevent Eisenmenger’s syndrome
biochemically but cannot be identified on CT/MRI
 Pre-operation: Romano-ward syndrome
o Alpha-blockade with phenoxybenzamine at least 7-10 days before to allow  6 mutations (LQT1-6)
for expansion of blood volume o 87%: LQT1 & LQT2
o Beta-blockade after  Cardiac potassium channel gene mutations
 If started too early: unopposed alpha stimulation can precipitate  Treatment shows a loered rate of SCD
hypertensive crisis  LQT1: events uaully preceded by exercise or swimming
o CCB: if further anit-HTN needed  Sudden exposure of face to cold water can elicit vagotonic
 Treatment reflex
o <6cm in diameter: KIV laparoscopic surgery  LQT2: arrhythmic events after emotional event, exercise, exposure
to auditory stimuli (doorbells, telephone ring)
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 o LQT3: events during night sleep o Myocarditis
 Dx: QTc but can be normal at rest o Congenital heart disease
 Holter monitoring is recommended o Rheumatic fever
 Genetic testing  Electrolytes imbalances
o LTQ4 associated with pAF o Hypocalcemia
 JLN mutations: Jervell-Lange-Nielsen syndrome o Hypomagnesaemia
o Associated with deafness
o Sudden death: in 30% occurs with first episode of syncope Driving guidelines
 Or during exercise, emotional stress, rest, sleep  Vocational drivers
 Management of long QT syndrome o Has to complete stage 3 of Bruce protocol exercise tolerance test with no
o Beta-blockade – reducing adrenergic demand residual chest pain or significant ECG changes
o Implantable defibrillators
Thrombotic thrombocytopenic purpura
Long QT  Fever, AMS, right hemiparesis, anaemia, thrombocytopenia and renal impairment
 Drugs  Can occur in <1% of patients receiving clopidogrel or ticlodipine
o Antibiotics  Investigations
 Erythromycin o PBF: fragmented RBCs (schistocytes, spherocytes, segmented RBCs, burr
 Ketoconazole cells, helmet cells)
o Anti-arrhythmics  Other S/E of clopidogrel: rash, urticarial, pruritus, GI upset
 Amiodarone
 Procainamide Pre-op workup
 Quinidine  Routine echocardiogram: LV function and valvular disease
 Sotolol o THR: haemodynamic changes ca occur
 Disopyramide  Significant LV impairment or valvular disease may impact
 Bretylium significantly on operative prognosis
o Anti-psychotics  SPECT scanning, repeat exercise ECG, stress echo, cardiac MRA: state of coronary
 Phenothiazines arteries
 TCAs
 Lithium IHD & DM
 Haloperidol  Tight glycemic control
o Others o ACCORD/VADT: increased risk of cardiac death
 Quinine o ADVANCE (sulphonylureas): no increased risk
 Tacrolimus  Insulin
 Cispride o DIGAMI-1: survival advantage when insulin initiated post MI
 Carbamazepine o DIGAMI-2: no survival advantage
 Familial long QT syndrome  Increased risk for MI in insulin patients
 Jervell-Lange-Nielsen syndrome  Pioglitazone
o a/w congenital deafness o Can cause fluid retension
 Cardiac disorders o Best avoided in immediate period post MI
o Congestive heart failure  Repaglinide
o Myocardial infarction
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 o Useful in early period of DM diagnosis when post-prandial hyperglycemia is  Prolonged PR interval
a problem
Carotid endarterectomy
Heparin induced thrombocytopenia  Indications
 Clinical features o Symptomatic & > 50% stenosis
o Necrotic skin lesions  NASCET: Greater than 70% stenosis
 Investigations  50-69% - marginal benefit and appears to be greater for male
o Low platelets patients
o ELISA to antiheparin-platelet factor 4 antibody o Asymptomatic & > 60% stenosis
 Type 1: non-immune condition which occur within 5 days of starting heparin and plt  >70% stenosis
count rarely drops below 100  60-69%: significantly less benefit
o Occurs within two days of heprin initiation
o Not a/w increased risk of thrombosis Fat embolus
o Normalizes with continued use  ARDS
 Type 2: >50% fall in platelet count and associated with very high incident of venous  Initial resuscitation
thromboembolism o High flow oxygen
o If heparin naïve: can take 7 days to develop o IV fluids – maintain high RV filling pressures
o Not heparin naïve: can occur within 24 hours o CPAP – assist in management of pulmonary edema
 Management o Steroids in ARDS – at later stage
o Withdrawl of all heparin, including flushes
o Alternative anticoagulation used until platelet count normalies Becker muscular dystrophy
 Hirudin – direct thrombin inhibitor  X-linked recessive genetic disorder – mutation in dystrophin gene
 Bivalirudin, argatroban  Milder than Duchenne’s
 Danaparoid: heparin and dermatan sulphate  Usually present at ages 5-15 yo but can also present late at 4th or 5th decade
 Lepirudin: recombinant direct thrombin inhibitor  May present with heart failure 2’ dilated CMP
o Long term anticoagulation
 Non-heparin based Cholesterol embolism
 Lepirudin or factor Xa inhibitor  Due to instrumentation of aorta during angiography: embolisaion of plaque debris
dislodged from large and medium sized arteries
Rheumatic fever  Clinical features
 Diagnostic criteria o Peripheral cyanosis
o Major o Petechial rash
 Migratory arthritis o Deteriorating renal function
 Carditis and valvulitis o Eosinophilia
 CNS involvement  Risk factors
 Erythema marginatum o Male gender
 Subcutaneous nodules o >50 years old
o Minor o Known atherosclerosis
 Arthralgia o History of HTN
 Fever o Smokking
 Elevated acute phase reactants
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o Elevation of CRP before arterial instrumentation
o Co-existence of MV annular calcification

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ENDOCRINOLOGY
Necrobiosis lipoidica
 Occurs more often in diabetic/family history of diabetics/increased tendency to get
Diabetes mellitus diabetes
 Oral medications  Predictive of future DM development
o DPP IV inhibitor  Clinical features
 E.g. Linagliptin o Usually in pretibial, face, scalp, trunk and UL
 Promote modest weight loss, does not increase risk of o Red brown patches -> yellow depressed, atrophic
hypoglycemia  Investigations
 Metabolized by liver, not affected in renal patients o DM screen
 Risk of pancreatitis o Biopsy: granuloma formation with infiltration of lymphocytes, plasma cells
o Sulfonylureas
and eosinophils
 E.g. Gliclazide  Management
 Increases weight gain, hypoglycemia o Difficult to treat
o Thiazonlinediones
o Topical/intralesional steroids
 E.g. Pioglitazone
o Aspirin: inhibition of platelet aggregation
 Promotes weight gain and fluid retention
o GLP-1 agonist
Somogyi effect
 E.g. Liraglutide
 Nocturnal hypoglycemia -> reactive release of counter-regulatory hormones
 Risk of pancreatitis (adrenaline, rebound hyperglycemia)
 GIT upset
 Complications Familial combined hyperlipidaemia
o Autonomic neuropathy  1 in 250 people, a/w premature CVS disease
 Postural hypotension  Most common type of familial dyslipidaemia and may be responsible for up to 10%
 Gastroparesis of CVS disease
 Erectile dysfunction  Management
 Management o Lifestyle management
o Phosphodiesterase inhibitors o Statin therapy
o 2nd line: Prostaglandin E1: intraurethral pessary or
intracavernosl injuection Familial hypertriglyceridaemia
o Vacuum pump devices, penil prosthesis,  Clinical features
apomorphine o Eruptive xanthoma
o Restenosis in coronary stent o Retinal vein thrombosis
 40-50% risk by 6/12 o Recurrent pancreatitis
 DES w 1 yr dual anti-plt reduce RR of re-stenosis by 80%
 Management
o DKA
o Fenofibrate: PPAR alpha agonist
 Increased risk of venous thromboembolism due to volume
 Drives increased lipoprotein lipase activity, reduces apoprotein CIII
depletion, hyperglycemia and decreased GCS
-> eliminate TG rich particles from plasama
 DVT prophylaxis
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 o Restriction of dietary fat o Type 1: increased blood flow
o Medium chain TG for cooking o Type 2: decreased blood flow
 Similar Tx
Graves’ disease o Discontinue amiodarone unless cardiac conditions disallow
 Graves’ opthalmopathy
o Local accumulation of glycosaminoglycans Sick euthyroid syndrome
o 75% develop Graves’ disease within a year of opthalmopathy  Low T3 and T4 but normal TSH
o Worsened by smoking, hypothyroidism post RAI  A/w severe illness and frequently seen in patients in ICU
 Patient’s usually stabilized on block replace regimen before RAI
o Optic neuropathy: visual impairment/blurring/visual field deficits or pain Thyroid & Pregnancy
 Refer to ophthalmologist  TSH can be suppressed in 13.5% in 1st trimester, 4.5% in 2nd trismeter due to
 Tx: systemic steroids, radiotherapy, orbital decompression thyrotrophic effects of b-HCG
 2x increase in thyroid binding globulin levels due to reduced hepatic clearance of
Hypothyroidism thyroid binding globulin and increased synthesis in response to estrogen
 Weight gain, menorrhagia, hypertriglyceridaemia o Plateaus at 20/52 then falls
 Investigations
o Elevated TSH, low T3/T4 Post-partum thyroiditis
 Causes  Variant of hashimoto’s thyroiditis
o Most common: Hashimoto’s thyroiditis  Occur in 10% of women during first year after delivery
 Management  Investigations
o Thyroid hormone replacement o Presence of antimicrosomal antibodies
o Histo: destructive lymphocytic thyroiditis
De Quervain’s thyroiditis o Radioiodine Thyroid scanning: lack of increased uptake
 Acute onset of thyroid tenderness after a short viral illness  Clinical features
 Raised ESR but anti-thyroid Ab –ve o Hyperthyroidism within 4/12 post delivery
 Characterized by early period of thyrotoxicosis (radioisotope scanning -> decreased o Fatigue
thyroid uptake) -> euthyroidism -> hypothyroidism -> recovery -> euthyroid o Hypothyroidism within 3-7/12 post delivery
 Management  Tx
o Pain: NSAIDs, steroids o Thyroxine replacement but withdrawal can be eventually possible
o Symptomatic: beta-blockers  Prognosis
o In pregnany: reassurance o Recurrence in subsequent pregnancies common and 40% develop
 Symptomatic with simple analgesias permanent hypothyroidism
 Avoid steroids, BB, NSAIDs
Lithium & thyroid
Amiodarone induced hyperthyroidism (AIT)  Hypothyroidism common in patient on long term lithium therapy
 Type 1: high iodine content induced release of thyroid hormone (Jod-Basedow effect) o Lithium inhibits coupling of iodotyrosine residues and release of T3 and T4
o Tx: high dose antithyroid drugs  Management
 RAI not effective due to reduced uptake due to high iodine levels o Start thyroxine
 Type 2: destructive thyroiditis o Can continue lithium but best to seek psychiatrist consult KIV alternative
o Tx: steroids + antithyroid durgs medications
 US colour flow Doppler to differentiate between the two
15
  b/l hilar LAD
Thyroid cancer o Disseminated infection: b/l adrenal enlargement in 79%
 Risk factors: endemic goitre, Hashimoto’s thyroidiits (lymphoma), FAP, history of  Adrenal insufficiency
thyroid adenoma, females (3x), >40yo, exposure to RAI and RT o Dx: adrenal biopsy or FNA
 Investigations  Groccott stain for the organism
o US thyroid o Tx: itraconazole
o FNA
 Papillary cancer Addison’s disease
o Good prognosis  Symptoms
 20-45yo o Weakness
 Tumour size < 1.5cm o Nausea/vomiting
 No distant metastases o Anorexia
 No previous cancer treatment o Hyperpigmentation
o Brain mets: less than 1 year survival o Hypotension
 70-90% are due to autoimmune adrenalitis
Wolman’s syndrome  High ACTH (> 80 ng/L) and poorly responsive Synacthen test -> diagnostic
 Primary adrenal failure
 Hepatosplenomegaly Acute adrenal insufficiency
 Steatorrhea  Clues: infection, previous suppression of adrenocortical asix by exogenous steroids
 Can present with hypotension and confusion
Wolfram’s syndrome/DIDMOAD  Investigations:
 Diabetes insipidus, diabetes mellitus, optic atrophy and deafness o HypoNa, hyperK, hypoglycemia, increased urea
 Management
Polyglandular syndrome o Correction of hypoglycaemia
 Type 1: ≥2 of (i) hypoparathyroidism (90%), (ii) primary adrenal insufficiency (60%), o Glucocorticoids
(iii) chronic mucocutaneous candidiasis, (iv) primary gonadal failure and (v) primary o adequate hydration
hypothyroidism
 Type 2: primary adrenal insufficiency, primary hypothyroidism and T1DM, +- primary Conn’s syndrome
gonadal failure  Adrenal adenoma -> 6-% of hyperaldosteronism
 Both are a/w vitilligo and pernicious anaemia o Small unilateral adrenal adenomas common in younger women
o b/l adrenal hyperplasia occurs in older me
PUO & b/l adrenal swelling  Profound hypokaelaemia and resistant HTN
 DDx: lymphoma, TB, histoplasmosis  Investigations
 Histoplasamosis: Histoplasma capsulatum (dimorphic soil fungus) o Renin/aldosterone ratio with anti-HTN stopped 3/52
o Slowly progressing chronic form that occurs in fit and immunocompetent  Raised aldosterone and suppressed renin
patients o Salt loading test: raised aldosterone levels
o Dissemindated infection occurs in weak, very young, very old or
immunocompromised Pseudo-cushing
o Acute infection: TB like illness  Causes
 Malaise, fevers, headache, anorexia o Obesity
 Dyspnea, cough, haemoptysis
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 o Substantial alcohol consumption o Drugs: fluoxetine, carbamazepine, vincristine, vinblastine,
 Investigations cyclophosphamide, chlorpropamide
o Post-dexamethsone suppression test  Management
 Only just above upper limit of normal range o Treat underlying causes
o Fluid restriction < 1L/day
Congenital adrenal hyperplasia o Dimethylchlorotetrcycline to indice nephrogenic DI in severe cases (neuro
 17-OH deficiency mutation deficits, seizures)
 Clinical features o Hypertonic saline
o Delayed puberty in girls
o Increased pigmentation Hypercalcemia
o Hypertension  >3.5 mmol/L: cardiac arrhythmias, coma, pancreatitis
o Marked hypokalemia  a/w severe dehydration that increases renal damage
 Management  Initial management: aggressive hydration
o OCP: restore mensus o Primary PTH: bisphosphonate – pamidronate, calcitonin (2nd line)
o Steroid supplementation o Sarcoid: prednisolone
o Adenomas: surgery
Growth hormone deficiency
 Features: Familial hypocalciuria hypercalcaemia (FHH)
o Impairmed well being  Hereditary disease with AD transmission
o Reduced energy/vitality  Hypercalcemia, relative hypocalciuria, slight hypermagnesaemia, inappropriately
o Reduced muscle mass and exercise tolerance normal-high PTH
o Decreased sweating  Investigations
o Increased # risk and osteoporosis o Elevated Ca, normal PTH/serum ACE
o Increased CVM risk o Ca-Cr Ratio < 0.01: reduced excretion of Ca
 Dx:  Defect in calcium-sensing receptor (plasma membrane G-protein)
o Insulin tolerance test  No treatment needed
 Peak GH at time of hypoglycemia < 10mU/L (3 ug/L)
 If 10-2, partial deficiency Hyperparathyroidism
o GHRH testing  Primary hyperparathyroidism
o PTH can be normal (normal response to hyperca2+ is suppression of PTH,
SIADH hence levels within reference range are inappropriately high and suggestive
 Diagnostic criteria of parathyroid disease)
o Low sodium < 125mmol/l  Tertiary hyperparathyroidism in renal failure
o Low plasma osmolality with an inappropriately high urine osmolality o Raised phosphate and PTH
o High urinary sodium exretion > 30mmol/l o Management
o In euvolaemic patient with no evidence of renal, adrenal, thyroid, hepatic or  Cinacalcet (PTH antagonist)
cardiac diseases  Low phosphate and phosphate binder (Sevelamer)
 Causes  Only if patient unable to undergo surgery
o Lung disorders: malignancy  Management
o Intracerebral event: SDH o Early stages of hyperPTH in renal failure (when calcium levels are low-
normal, PTH above twice the upper limit of normal range)
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  Vitamin D (1-alpha-calcidol)  Pregnancy a/w increased risk of aortic rupture
o Low phosphate diet  Tx:
 Indications for surgery o BP control
o Markedly elevated Adj Ca > 3  Prevent progression to aortic dissection
o Previous marked hypercalcaemic episode  Prophylactic betablocker/ACE-I
o Impaired renal function
o Renal stones, nephrocalcinosis Homocystinuria
o Substantially elvated urinary calcium  a/w mental retardation
o Reduced bone mineral density
 Monitoring Ehler’s Danlos
o Annual Ca, renal function  Normal height
o Blood pressure
o BMD 2-3 yrly Turner’s syndrome
o Renal US  Short stature

Paget’s disease Acromegaly

 Investigations  Usually related to pituitary adeoma, occasionally due to ectopic secretion y
o XR: osteolysis with new bone formation, increased bone density malignant cells
o Only ALP is deranged and is a useful marker of disease activity and response  Signs & symptoms
to bisphosphonates o Soft tissue swelling, HTN, DM
o Serum calcium normal o Increase in size of lower jaw (prognathism)/fingers
o Radionucleotide bone scan: determine extent of disease o Coarsening of facial features, macroglossia
 Management  Increased risk of CVS disease, HTN, DM
o Prolonged oral or intermittent IV bisphosphonates  Management
 Inhibit osteolysis, reduce serum ALP and pain o Curative: transphenoidal removal of adenoma
o Calcitonin as alternative o Medical
 Somatostatin
Oncogenic osteomalacia  Pegvisomant (GH antagonist – 2nd line)
 Certain tumours (including mesenchymal, adenocarcinoma, haematological):
prostatic, myeloma, CLL can produce phosphaturic substance Klinefelter’s syndrome (47XXY)
 Clinically: bone pain/fracture, profound proximal myopathy and severe  Small testes, sparse sexual hair, depression, problems with sexual function
hypophosphateaemia with marked reduction in 1,25 OH Vit D  Gynaecomastia & infertility
o Renal: glucosuria, aminoaciduria  Tx:
 Managmenet o Testosterone: improve bone mineralization
o Vitamin D metabolites o Can improve sexual function and depressive symptoms
o Phosphate supplements o Intracytoplasmic sperm injection
o Removal of primary tumour  **Mumps only cause testicular failure when contracted after puberty

Marfan’s disease Polycystic ovary disease

 1/3 spontaneous mutation (usually occurs in fathers of older age)  LH/FSH > 2

18
MEN 1 syndrome  Investigations
 Pancreatic islet tumour + hyperparathyroidism (90% present with hyperCa) + o TVUS: 91% diagnostic sensitivity
pituitary tumour (often macroademoa)  >8follicular cysts, less than 10mm and increased ovarian stroma
 AD inheritance  Management
 Screening: genetic mutation, serum calcium, prolactin o Cyproterone acetate: suppression of ovarian androgens
o Electrolysis: useful for reducing hirsuitism
MEN 2A syndrome o Metformin: increases insulin sensitivity and has positive effects on
 Pheochromocytoma, primary hyperparathyroidism, medullary thyroid cancer associated metabolic features and helps restore ovulatory function
 Investigations o Weight loss: gold standard treatment
o Pentagastrin test: MTC  Improves ovulation, androgen levels, hirsuitism, metabolic features
 Measures calcitonin levels at 2-5 minutes associated with insulin resistance
 Rise in levels is suggestive
 Basal calcitonin levels can be elevated in pregnancy, carcinoid, Androgen insensitivity syndrome
pernicious anaemia, CKD and thyroiditis  Clinical features
o Ultrasound thyroid o Normal external female genitalia but absent pubic/axillary hair
o Calcitonin level o Primary amenorrhoea
o FNA of thyroid mass  Investigations
o Screen for pheochromocytoma o 46XY karyotype
o Absent ovaries, undescended testes
Liddle’s syndrome
 Hypokalaemic alkalosis with suppressed renin and aldosterone with hypertension Vitamin C deficiency/Scurvy
 AD, mutation in chromosome 16 -> abnormality in beta/gamma subunit of highly  Powerful reducing agent involving in hydroxylation of proline to hydroxyproline ->
selective epithelial sodium channel in distal nephron necessary for formation of collagen
o Activation of Na/K exchange independent of circulating mineralocorticoid o Scurvy: defective collagen formation -> impaired wound healing, capillary
 Tx haemorrhage, abnormal platelet function
o Amiloride: acts directly on the sodium channel  Clinical features
o Bleeding into joints or muscules
Water deprivation test  Commonly in
 Deprived of fluids for 8hr or until 5% of body weight lost o Elderly people on “tea and toast” diet
o Weighed hourly o Alcoholics
o Plasma osmolality Q4H o Smokers: ascorbate consumed in removing free radicals from soke
o Urine volume & osmolality Q2H  Investigations
o Given 2ug IM desmopressin o Plasma ascorbate or leucocyte ascorbate content
 If serum osmolality rises > 305 mosmol/kg -> DI  Management
 If urine osmolality < 300 momol/kg after fluid deprivation, then rising to > 800 o Ascorbic acid replacement
mosmol -> cranial DI, if remaining less than 300 mosmol/kg -> nephrogenic DI o Dietary education
 If urine osmolality > 800 without desmopressin -> primary polydipsia o Iron and folate supplement PRN
 If urine osmolality intermediate (300-800) then fails to rise > 800 -> partial DI or
polydipsia Autoimmune polyglandular syndrome

Polycystic ovarian syndrome

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 Type 1 (autoimmune polyendocrinopaty candidiasis ectodermal dystrophy/Whitaker
syndrome): rare sporadic AR inheritance, presenting I childhood
o Candidiasis – mucocutaneous (may be absent in adolescent)
o Hypoparathyroidism
o Adrenal failure
 Type 2 (Schmidt syndrome): most common and occurring primarily in adulthood
o Adrenal failure: Addison disease
o Thyroid autoimmune disease (Hashimoto thyroiditis/Graves disease)
o T1DM
o Also a/w primary hypogonadism. Myasthenia gravis, celiac disease
 X-linked polyendocrinopathy, immunodeficiency diarrhea syndrome
o Thyroid deficiency + 2 other autoimmune disorders
 Pernicious anaemia
 T1DM
 Vitilligo
 Alopecia

20
RHEUMATOLOGY Psoriasis
 Management
o Topical steroids -> vitamin D analogues
Nail fold capillaroscopy o If still not improving: methotrexate or cyclosporine
 Dilated, distorted, missed nail fold capillary loops o Last line: TNF monoclonal antibodies: infliximab or t cell modulating
 Used to provide clarification with regards to association systemic CTD monoclonals
 Erythrodermic psoriasis
Felty’s syndrome o Management
 In long standing seropositive RA, 2/3 females  Cold dressings and emollient
 RA, leucopenia, LAD and splenomegaly  Ciclosporin +- systemic corticosteroids
o Can have leg ulcers, recurrent infections and episcleritis o Contraindicated stuff:
 ANA +ve in 90%  Isotretinoin: will worsen condition
 Treatment
o Splenectomy Psoriatic arthritis
o DMARDs, (cyclophosphamide in severe disease)  Management
o Colony stimulating factor -> production of granulocytes o Analgesia: NSAIDs
o Acute control
Palindromic arthritis  Predsiolone
 Pain/swelling/erythema affecting an articular/periarticular site which lasts less than  But be careful of rebound of cutaneous symptoms
72hrs before recovering completely o DMARDs
 50% may progress to RA especially if small joints affected/RF+ve/CCP+ve  Methotrexate
 DDx for recurrent arthritis  Sulphasalazine (for peripheral psoriatic arthritis)
o Crystal arthritis o Biologics (if DMARDs fail)
o Periodic fever syndromes  Etanercept (TNF antagonist)
o Whipple’s disease  Plaques psoariasis: Adalimumab/infliximab (TNF antagonist)
o Arthritis a/w hyperlipidaemia Ustekinumab (IL12 and IL23 inhibitor)
o Intermittent hydrarthrosis  Severe disease
 Not responded to standard tx including cyclosporine,
Gonococcal arthritis methotrexate, PUVA
 Dermatitis-polyarthritis-tenosynovitis syndrome  Intolerant or CI to standard tx
 Most common cause of acute infective arthritis in sexually active
 Spreads from infected mucosal to the joints Multicentric recticulohistiocytosis
 Common symptoms: Fever, rashes, migratory arthritis  Rare non-Langeherhan’s cell histiocytosis with skin and joint involvement (nearly all
 Diagnosis ogans can be involved)
o Culture of synovial fluid o a/w with AI disease, cancers (25%)
o Culture of skin lesions  Clinical features
o Culture from urethral swab o Nail fold nodules -> coral beads appearance
 Can be numerous and as large as 2cm

21
  Can involve mucosal surfaces o C3/C4 reduced in lupus
o Joint pain
 Investigations Raynaud phenomenom
o Microscopic: histiocytic nodular infiltrate made of giant cells with ground-  Primary Raynaud
glass appearance and PAS+ve cytoplasm o Management
o Hand XR: erosive changes in joints, DIP erosions and pseudowidening of  Vasodilating CCB: nifedipine or amlodipine
joint spaces  BB can WORSEN symptoms
Discoid lupus
Dermatomyositis  Well demarcated macular rash with erythema, scales, plaques and atrophy
 Signs and symptoms o Photosensitivity
o Facial rash o Scarring alopecia
o Dysphagia  Variant of SLE: skin involvement is main feature
o Proximal myositis o Rare: mild systemic features
 Labs  More common in African-Carribbean females
o ANA+ve  Investigations
o Anti-Jo, Anti-Mi +ve o Biopsy of lesion
o Elvated CK
 Muscle biopsy is diagnostic Lupus pernio
 Management  Cutaneous form of sarcoidosis
o Corticosteroids o Dusky purple infiltration of nose
o Azathioprine & cyclophosphamide as 2nd line steroid sparing agents
o IVIg in aggressive or resistant disease Drug induced lupus
 Symptoms usually appear some 3/52 to 2 yrs after nset
Polymyositis  Common in 50-70yo, affects both gender equally but Caucasians affected more
 Labs  Symptoms: skin rash, joint pains, malaise, Raynauds (25%)
o CK may be elevated 5-50x normal upper limit  Labs
o Anti-Jo-1 a/w ILD, Raynaud’s phenomenon, peripheral rthritis o Anti-histone antibodies more likely to be positive
 Management o Anti-dsDNA less likely to be positive
o Prednisolone 1mg.kg.day o C3/4 usually normal
o DMARDS  Drugs: simvastatin, captopril, valproate, penicillamine, carbamazepine, methyldopa,
procainamide, minocycline, griseofulvin, hydralazine, quinidine, sulfasalazine
Systemic lupus erythrosus  Treatment
 Neuropsychiatric lupus: headache, mood changes, major psychotic episodes, grand o Withdrawal of medications
mal seizures o Low dose corticosteroids
o Often a/w amenorrhea (interference with gonadotrophin release or
autoimmune ovarian failure) Relapsing polychondritis
 Labs  Episodic inflammation and destruction to cartilaginous and connective tissues
o ANA: 95% sensitivity but not specific  Onset typically in middle age and equal incidence in both gender
o Anti-dsDNA: 100% specific for SLE  Common symptom: inflammation of external ear and nasal cartilage
 Levels correlates with activity o a/w arthritis involving both small and large joints

22
 Bouts of inflammation that heals over weeks  Seronegative arthritis (asymmetrical affecting large joints)
o Recurrent inflammation -> cartilaginous tissue destruction -? Floppu ears  Thrombophlebitis, DVT
and saddle nose  Gastrointestinal ulceration
 Investigations
Cryoglobulinaemia o Pathergy sign: formation of erythema and pustules around venipuncture
 Joint symptoms + purpuric rash + RF+ve -> cryoglobulinaemia & SJogren syndrome sites
o Mild anaemia
Sjogren’s syndrome o Elevated inflammatory makers
 Diagnosis o HLA-B51 and B5 common in males
o Schirmer tear test: wetting of < 5mm in 5 min (defective tear production) o Anti-phosphlipid antibodies (25%)
o Rose Bengal staining: punctuate or filamentary keratitis  Common in Mediterranean
o Raised Ig, RF +ve  Management
o ANA+ve in 60-70% o Steroids
o AMA +ve in 10% o Azathioprine
o Anti-Ro & La (70% of Primary Sjogren syndrome0  Complications
 Treatment  Venous thrombosis
o Artificial tears o Portal vein thrombosis
o Saliva replacement solution  Dull epigastric/RUQ pain
o Ocular & Mucosal lubrinats  Features of cirrhosis
o Vaginal lubricatnt  CT: caudate lobe hypertrophy (in chronic disease)
o Trial of immunomodulators
 Rituximab Raynaud phenomenon
 Occur in 2nd or 3rd decade of life
Behcet’s syndrome  Inciting drugs: methysergide, atenolol, ergotamine, vinblastine, bleomycin, OCP
 Inflammation of small blood vessels -> recurrent ulceration especially in oral and  Causes: systemic sclerosis, mixed CTD< SLE< RA, polycythaemia, thromboangiitis
genital mucosa (painful) obliterans
 Commonly manifest as underlying thrombotic disorders  Betablockers may precipitate worsening of symptoms
o Budd-Chiari  Management
o Myeloproliferative disorders o ACE-I: best evidence for reno-protection
o Paroxysmal noctunarl haemoglobinuria o Dihydropyridine CCB (e.g. amlodipine)/: improve symptoms
o Pregnancy/tumours
o Chronic inflammatory diseases Systemic sclerosis
o Clotting disoders  Renal disease
o Infections o Interlobular renal arteries affected wth intimal thickening
 Clinical features: 4 major features o Fibrinoid changes in afferent glomerular arterioles
o Oral and genital ulcerations o Management
o Eye diseases: , iridocyclitis, choriorentinitis, retinouuveitis  ACE-I
o Skin disease: erythema nodusum, subcutaneous throbophelbitis, folliculitis,  Steroids and immunosuppressants no effects
pathergy  Prostacyclin infusion in rapidly deteriorating renal function
o Other symptoms
Fibromyalgia
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 1-2% of general population, female 9x than males, 30-50yo o NSAIDs
o Substantial overlap in depressive, anxiety, multiple regional pain symdromes  May precipitate sodium and water retention
and chronic fatigue syndrome  Worsen creatinine
 MSK pain with multiple trigger points and poorly defined
 Classification criteria (1990 ACR) Pseudogout
o Presence of widespread pain >3/12  Accumulation of calcium pyrophosphate crystals
o Pain not just tenderness that can be elicited by manual pressure at ≥11  Symptoms tend to be insidious and may occur over several days
defined tender points  Joint involvement, evidence of chondrocalcinosis & pyrophosphate crystals
 Normal ESR and CRP o Rhomboidal crystals with positive refringene
 Management  Management
o Reassurance o Analgesia
o TCAs for sleep disturbances o Physiotherapy
o Aerobic exercises (e.g. swimming)  Associated with haemochromatosis, Wilson’s disease

Ankylosing spondylitis Charcot’s arthropathy

 Management  Individuals lacking sensations in a joint are predisposed to developing severe damage
o Early: analgesia & physiotherapy (maintenance of function)  Diagnosis
o Sulfasalazine: improving peripheral joint arthritis o Severe joint destruction with minimal symptoms and normal joint
o TNF-a blocker (etanercept): used only after traditional 2nd line agents movements
 Causes
Gout o Syphilis – tabes dorsalis affect large joints of LL
 Accumulation of monosodium urate monohydrate crystals, overproduction or o Syringomyelia – affects large joints of UL/meningomyelocele
reduced excretion of uric acid o DM neuropathy - foot
 Symptoms develop rapidly over few hours o Spinal cord/peripheral nerve injury
 Diagnosis o Leprosy
o Knee tap o Multiple sclerosis
 WCC > 50 000 with > 75% polymorphonuclear leukocytes
 Needle shaped intracellular and extracellular crystals with negative  Management
birefringence o Immobilization in a cast for 3-6/12
 Management o Complemented with bisphosphonates: reduction in bon reabsorption
o Colchicine: can cause increased INR thought to accelerate healing
 Can be increased up to a dose of 3mg to be given in 600mcg o Control of blood glucose to reduce risk of microvascular complications
divided doses
o Rasburicase (recombinant urate oxidase) Osteoporosis
 Can be given during acute gout attack  Primary
 Allow allopurinol therapy to be commenced without the initial o Management
worsening of symptoms  HRT: reduce loss of bone mineral density and # risk at vertebral and
 Not licensed to be used for gout other site
o Prednisolone  But increased risks of thrombosis, CVS and cancers
 S/E: sodium and water retention (not for heart failure patients),  Bisphosphonates (1st choice therapy)
worsen glucose control
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  S/E: esophageal symptoms  Diagnosis
 Calcium/Vitamin D supplementation o Temporal artery biopsy from affected side
 Raloxifene: selective estrogen receptor modifier  Intimal hypertrophy, inflammation of intima/sub-intima, breaking
 a/w reduction in risk of ER+ve breast CA up and giant cell infiltration of internal elastic lamina
 Secondary causes  Management
o Secondary ovarian failure (can be due to low BMI) o High dose prednisolone
o Hyperthyroidism o Low dose aspirin: reduce risk of visual loss and strokes
o Steroid therapy  Clopidogrel if aspirin allergy
 T score -1.5 taken as cut off o Steroid sparing if long case of high dose steroids needed
 Management: bisphosphonates  Azathioprine
 Strontium & PTH hormone used in case of intolerance or  Associated with polymyalgia rheumatica
lack of response o Morning stiffness, b/l shoulder and pelvic girdle pain
 Denusomab also an alternative o Elevated ESR
o Management
Osteomalacia  15mg PO Prednisolone OD
 Inadequate mineralization of bone due to Vitamin D deficiency/inadequate
sunlight/dietary deficiency Buerger’s disease (thrombangiitis obliterans)
o Other cause: CKD, renal osteodystrophy, malabsorption, renal tubular  Disease of small and medium sized arteries and veins resulting in inflammation and
defects ulceration
 Symptoms o No excessive atheroma
o Skeletal pain, tenderness o Does not involve coronary arteries
o Proximal muscles weakness (often first presentation)  Usually in cigarette smokers
o Spontaneous fractures  Clinical features
 XR o Arterial ischaemia
o Normal but may show defective mineralization o Migratory phlebitis
o Looser’s zone (pseudofractures): low density bands extending from cortex o Digital gangrene
inwards in the shafts of long bones  Investigations
 Labs o Arteriogram: occlusion of distal arteries of hands and fee
o Low calcium, low normal phosphate, vitamin D level and elevated ALP  Management
 Management o Supportive
o Vitamin D and calcium supplements o Smoking cessation

Temporal arteritis Pulmonary hypertension

 Systemic inflammatory vasculitis of unknown etiology affecting medium & large sizes  PASP > 40mmgHg
arteries  Iloprost + Sildenafil more beneficial than iloprost alone (Ghofrani)
 Occurs commonly in women and > 50yo  Primary pulmonary hypertension
 Clinical features o Present around 36 yo
o Visual loss o Clincial features
 Commonest cause: AION 2’ ischaemic of optic nerve head supplied  SOBOE, syncope
by posterior ciliary arteries  RHF
 Chalky white edematous optic disc
25
 o Investigations o IL6 produced by variety of cell types including T and B cells, monocytes and
 Echocardiogram fibroblasts: closely involved in pathogenesis or RA
 Right heart catheterisatio  Anti-CD20: rituximab
 CT PA/V/Q scan TRO significant thromboemobolic diseases o Present on B lymphocytes
 Anti-SCL70/centromere TRO CTD o Targeting it down regulates antibody production and B to T cell signaling
 Anti-CD28: TGN1412
Proprionibacterirum acnes o T lymphocyte receptor and also widely expressed on other white blood cells
 Slow growing gram positive bacterium -> poorly virulent  Anti-IL1: Canakinumab
 May occur many years after original arthroplasty o Used in treatment of inflammatory arthritis, including gout
 Management  Anti-IL13: tralokinumab
o Prolonged IV Abx at time of revision arthroplasty (90% resolution) o Treatment in asthma and psoriasis
o Penicillins, clindamycin, carbapenems
IgA deficiency
Alkaptonuria  Most common of primary antibody deficiencies
 Hereditary disease: homogentisic oxidase deficiency (responsible for degradation of  Total deficiency: undetectable serum IgA <0.05g/L
homogentisic acid produced from phenylalanine and tyrosine)  Blood products often contain small amounts of IgA and preformed anti-IgA
 Accumulation of homogentisic acid -> pigmentation of urine, sclera and connective antibodies can driver severe transfusion reaction
tissues  Clinical features
 Deposition in joints causes cartilage pigmentation (ochronosis) and denegeration o GIT infections, blood transfusion reactions
 Homogentisic acid -> reducing agent: false positive GLucostix but normal CLinitest
 Urine after standing becomes dark coloured due to oxidation IgG deficiency
 Knees and spine commonly affected  Predisposes to recurrent lower respiratory tract, sinus infections

Medications Common variable immunodeifiency

Immunosuppresants  Rare defect of Bcell maturation
 Methotrexate o Reduced immunoglobulin production
o Highly teratogenic  Clinical features
o Can switch to Azathioprine for RA o Multiple infections: otitis media, pneumonia, Campylobacter infection
 Or infliximab (but to discontinue in 3rd trimester)  Investigations
Biologics o Low levels of both IgA and IgG
 TNF-alpha blockers  Management
o S/E: neutropenia, reactivation of TB, depression, injection site reactions o Immunoglobulin replacement (reduce risk of infection)
o Withhold TNF blockers 2-4/52 prior to major surgery
 Stopping earlier may lead to disease flare Complement deficiency
 May be restarted postoperatively if no evidence of infection and  Deficiency in the terminal pathway (C5-C9) increases the risk of Neisseria
once wound healing is satisfactory meningitides infection
o E.g. etanercept o 7000t10000x risk of meningococcal disease
 Monoclonal antibody to IL-12/23
o E.g. Ustekinumab Vancomycin, red man syndrome
 S/E: dental infections  Related to infusion rates for vancomycin that are too high
 Anti-IL6 receptors: Tocilizumab
26
 May be direct activation of mast cells in skin by vancomycin
 NOT an IgE mediated reaction

Vitiligo
 Investigations
o Wood’s light: lesions appear blue white or yellow green
 Management
o Limited disease: topical corticosteroids
 If response poor, topical calcineurin inhibitors
o Severe progressive disease: systemic therapies

Alkaptonuria
 Hereditary disease: deficiency of enzyme homogentisic oxidase (responsible for
degradation of homogentisic acid produced from phenylalanine and tyrosine)
 Clinical features
o Accumulation of homogentisic acid
 Pigmentation of urine, sclera and connective tissues
 Urine after standing becomes dark coloured due to
oxidation of product
o Deposition in joints
 Cartilage pigmentation: ochronosis
 Degeneration
 Knees and spine commonly affected but SIJ may be spared
 Investigations
o Normal Clinitest, false positive Glucosticx test
 Homogentisic iacid s a reducing agent
 No curative treatment

27
RESPIRATORY Staphylococcus
 Investigations
o CXR: bilateral cavitating bronchopneumonia
Guillain Barre Syndrome
 Autonomic signs: tachycardia, postural hypotension Streptococcus pneumonia
 Impt to monitor FVC/NIV for prognosis/respiratory failure  Commonest cause of CAP in elderly
o Threshold for increased respiratory intervention  Pneumonia & bacteremia no. 1 cause of mortality in CAP
 FVC: 20ml/kg  Associated with herpes labialis
 Poor prognosis
o Rapid progression of symptoms Legionella pneumophila
o Advanced age  Middle aged men, more severe in smokers
o Prolonged ventilation (>1 month)  Incubation period of 2-10 days
o Severe potential reduction on neuromuscular testing  Aerobic, waterborne, gram-negative, non-motile bacillus
 Epidemiology
Small left apical pneumothorax o Outbreak:
 Synchronous click with heart sounds: recognized sign!  Fit individuals: Contaminated water-cooling
 BTS guidelines systems/aircon/showers
o If PA CXR is normal and small PTX is suspected: lateral decubitus CXR  Immunosuppressed: steroids/chemotherapy
provides 14% more information o Sporadic: 40-70yo, smokers, chronic illness (chest disease, DM, alcoholics)
 Treatment  Disease entities
o Primary PTX in non smoker with no underlying lung disease, <50yo and rim o Legionnaires disease: pneumonia
of air <2cm and no SOB o Pontiac fever: milder self limiting illness
 D/c and f/u outpatient  Fever and myalgia (no pneumonia)
 Inserts BTS guideline  Symptoms
o Fever, malaise, myalgia, headaches
Pneumonia o Cough (often non-productive), SOB, confusion
 CAP: Strep. Pneumonia o 50% GIT: diarrhea, vomiting
 Post influenza/IVDA: Staph o Pleuritic chest pain, haemoptysis
o Causes cavitation and multiple lung abscesses o Pleural effusion up to 50% of patients
 Lymphoid interstitial pneumonitis  Investigations
o Infiltration of alveolar tissue by lymphocytes and plasma cells o Moderate leukocytosis (neutrophilia, lymphopenia)
o Presents with dry cough, dyspnea and reticulonodular shadowing o Hyponatraemia -> SIADH
o Uncommon in adults but rather common in paediatric HIV infection o Deranged LFTs
 HAP o Proteinuria
o IV meropenem (broad spectrum: gram positive and negative including o Haematuria
pseudomonas) and levofloxacin (broad spectrum: gram positive and o Myoglobinuria
negative including common respiratory pathogens)
o Hypoxia
o Abnormal renal function
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 o CXR: bibasal consolidation (may take 4/12 to resolve) o +ve DCT
 Diagnosis o Hyperbilirubinaemia
o Serology o Elevated LDH
o Urinary antigen testing  Extra-pulmonary symptoms
o Rise in specific IgM and IgG titres in urine/blood/sputum o Pericarditis, myocarditis
o Direct IF staining of organisms via bronchial washings/sputum/pleral fluid o Erythema multiforme/nodosum, SJS
o CXR: lobar then multilobar shadowing, small pleural effusions may occur o CN/peripheral nerve palsies
 Treatment o Meningoenphalitis, meningitis, ascending paralysis, transient myelitis, CN
o Macrolide: clarithromycin if quinolones cannot be tolerated or CI palsies, peripheral neuropathy, bullous myingitis
o 1st line Quinolones: ciprofloxacin as alternative to macrolids o Hepatitis, pancreatitis, N/V, anorexia
 Rapid recovery and shorter hospital stay o Cold AI haemolytic anaemia, thrombocytopenia, DIC
o 2 weeks in mild disease o Glomerulonephritis
o 3 weeks for severe or immunocompromised o Arthralgia, arthritis, bullous myringitis
 Complications  Investigations
o Pericarditis, encephalitis, renal failure o CXF: patchy bilateral consolidation
 Prognosis  Management
o 10% mortality in fit patients o Macrolide
o 50% in nosocomial infection
Haemophilus pneumonia
Pneumococcal pneumonia  Rare in patients over 6yo unless immunocompromised
 Significant cause of mortality due to ability of organism to replicate in host tissues  Investigations
 Clinical features o CXR: alveolar infiltrates in patchy or lobar distribution
o Fever & rigours
o Malisem anorexia Histoplasma infection
o Cough, SOB, purulent sputum  Common in mid western US states, Ohio, Mississippi river valleys
o Pleuritic chest pain  Clinical features
o Herpetic cold sores o Acute
o Tachycardia, tachypnea, hypoxia  Fever, cough
 Investigations  Purulent sputum
o CXR: lobar consolidation  Investigations
o CXR: bilateral pulmonary infiltrates
Mycoplasma pneumonia o Histoplasma antigen
 Usually in young adults  Management
 Usually associated with out breaks of pneumonia o Amphotericin B
o Pleuritic chest pain, wheeze o Itrazonazole
 Labs
o WCC may be normal Coxiella burnetti
o Thrombocytopenia  Associated with Q fever: 60% asymptomatic
o Haemolytic anaemia with reticulocytosis  Incubation 2-6 weeks
o Cold agglutinins + in 50%  Disease entities

29
 o Self limiting flu like illness, abrupt onset of fever, headache, myalgia and
arthralgia Renal tract tuberculosis
o Pneumonia: mild severity and often incidental finding  Renal tract common site for TB infection after lungs and commonl involved in
 Dry cough, SOB, pleuritic chest pain primary TB infection
o Hepatitis: mild elevation of LFTs  Clinical features
 Nausea, vomiting o Long standing urinalysis abnormalities
o Weight loss
Chlamydia psittaci o Bladder irritation
 Acquired from avian reservoir, classically a/w parrots  Investigations
 Incubation 5-14 days o Urinalysis
 Disease entities o Elevated inflammatory markers
o Pneumonia: psittacosis o Mild anaemia
 Fever, chills, malaise, dry cough, sore throat, epistaxis, severe o May require repeated early morning urine cultures or urinary tract biopsy
headache on cystoscopy

Tuberculosis Anti-TB Drugs

TB effusions  Isoniazid
 Small to moderate effusion, rich in lymphocytes o Toxicity: convulsions, metabolic acidosis, coma, rhabdomyolysis
 Investigations  Inhibit conversion of pyridoxine to active form and LDH
o AFB stains +ve in 5-10% (10-20% in effusions)  Management
o AFB c/s +ve in 25-50% over 2-6/52  Pyridoxine
o Pleural biopsy c/s +ve in ~75%  IV diazepam for seizures
o Pleural biopsy ay show granulomas but lesser sensitibity than culture and  Thiopentone: refractory convulsions
cannot give bacterial sensitivity  Haemodialysis for isoniazid removal
o Pleural biopsy culture + histology: 90% o S/E: pyridoxine deficiency
o Induced sputum/PCR/pleural biopsy  Confusion, seborrhoeic dermatitis, stomatitis, peripheral
 Fluid volumes may increase during antiTB therapy, corticosteroids a/w reduced fluid neuropathy, MC anaemia
volume but no effect on outcome  Also causes an increase in peripheral metabolism of levodopa
 Complications  Ethambutol
o Pleural thickening and calcification occurs commonly o Overdose: headache, confusion, pyrexia, GI upset
 Pyrazinamide
Latent TB o Overdose: abnormal LFTs, hyperurcaemia
 In HIV patients: dual therapy – rifampicin & isoniazid
Thoracoplasty
Pott’s disease (Tuberculous Spondylitis)  Treatment prior to use of antiTB chemotherapy
 Usually secondary to extraspinal source of infx: primary lungs or mediastinal glands o Resection of multiple ribs to reduce thoracic volumne, collapse underlying
through blood stream lung
 Symptoms o Aim: close tuberculous cavity and “rest the lung”
o Spine: pain, rigidity, deformity, cold abscess, paraplegia 2’ vertebral collapse  Results:
 Usually lower thoracic and upper lumbar o Good control of pulmonary TB with good survival
o Constitutional: fever, LOW
30
 o Severe chest deformity and associated respiratory compromise and  Inhaled allergens provoking hypersensitivity reaction in lungs -> diffuse inflammation
restrictive defect involving small airways and alveoli
 Chronic: lymphocytic and giant cell infiltration -> pulmonary fibrosis
Aspergillus  Typical allergens: microbial spores (Micropolyspora faeni in mouldy hay – farmer’s
Aspergilloma ling, avian protein – bird fancier’s lung)
 Ball of fungus forming inside area of damaged lung tissue most commonly 2’ TB but  Diagnosis
can be due to bronchiectasis/neoplasm/abscess cavity o Imaging
 CXR: round opacity in upper zone with a surrounding halo of air o Respiratory function tests
 Management o Serum precipitins
o Surgical excision of affected lung segment provided adeuquate reserve of o Bronchoalveolar lavage
lung function o CT: multiple small ill-defined nodules, ground-glass opacity in basal
o If unable to undergo surgery: itroconazole (effective in 60% of patients) segments
o Life-threatening haemoptysis: arterial embolization  Management
o Avoidance of causative allergen
Allergic bronchopulmonary aspergillosis o Long term steroid therapy
 Patients with pulmonary infiltrates, blood eosinophilia and asthma
o DDx: Churg-Strauss or ABPA Invasive aspergillosis
 Most common cause: sensitivity to Aspergillus fumigatus spores
 Diagnostic criteria: Loeffler’s syndrome
o Asthma  Mild self limiting illness with transient migratory pulmonary shadows
o Peripheral blood & sputum eosinophilia (5-20% of WCC)  Associated with parasitic infections, drug allergies and exposure to inorganic
o Abnormal CXR: infiltrates, segmental or lobar collapse chemicals
o Positive skin tests/RAST to an extract of A. fumigatus  Investigations
o A. fumigatus IgG serum-precipitating antibodies o Eosinophilila (~10% of WCC)
o Raised total IgE > 1000ng/ml o CXR: fleeting pulmonary infiltrates
o Fungal hyphae of A. fumigatus on sputum microscopy
 Other investigations Tropical pulmonary eosinophilia
o CXR: fleeting infiltrates, lobar collapse (2’ mucus plugging)  In tropical countires due to migrating larvae of filarial worms (Wucheria Bancroft and
 Central bronchiectasis also usually seen Brugia malayi)
 L UL collapse -> veil sign  Investigations
 Diffuse pulmonary infiltrates o Eosinophilila (>20% of WCC)
 Pulmonary, lobar or segmental collapse -> transient features
Chronic/prolonged pulmonary eosinophilia
 Complications  Investigations
o Bronchospasm -> bronchiectasis, upper lung zone fibrosis o Eosinophilila (>20% of WCC)
 Management o LFT: obstructive/restrictive/mixed picture
o Oral prednisolone KIV maintenance steroids o CXR: predominant peripheral or pleural based disease
o Adjunct: itraconazole o BAL: eosinophilia
 Chornic debilitating illness
Extrinsic allergic alveolitis o Malaise

31
 o Weight loss, night sweats  Recommended for those with very low serum levels and abnormal
o Fever lung function
o Progressive Dyspnea o Lung transplantation – advanced disease
 Management o Smoking cessation
o Prednisolone 0.5mg/kg/day
Yellow nail syndrome
Bronchiectasis in young adults  Rare condition: hypoplasia of lymphatics with impairmed drainage
 Clinically: coarse inspiratory crackles and clubbing  Triad of primary lymphedema, recurrent pleural effusion and dystrophic yellow nails
 History of copious purulent sputum & cough o Pleural fluid: clear exudate and lymphocytic
 Causes  A/w bronchiectasis and sinusitis
o Heterozygosity for cystic fibrosis CFTR  Subungual edema

Bronchiectasis Extrinsic allergic alveolitis

 Proximal bronchiectasis  Investigations
o HRCT: bilateral centrally dilated thickened airways with signet rings o CXR nodular pattern bilaterally with predominance for upper lobes
 ABPA: IgE will be elevated during flare up  Chronic changes (insidious process or multiple acute attacks):
 IgG can be low in bronchiectasis 2’ hypogammaglobulinaemia fibrosis
 Young’s syndrome: bronchiectasis a/w azzospermia and sinusitis  Ground glass changes tend to reverse with symptoms resolution
o Spirometry reversible restrictive defect
Alpha-1 antitrypsin deficiency o BAL increased mast cells, high lymphocyte count > 40%
 Rare AR disease with development of premature panlobular emphysema, most o Lung biopsy: mononuclear cell infiltrate with non-caseating granulomas
severe in basal areas o Identify potensial source of antigen
o Emphysema: imbalance in lug between neutrophil elastase (destroys  Precipitins to Micropolyspora faeni
elastin) and elastase inhibitor alpha1-antitrypsin (protects against  Causes
proteolytic degradation by elastin) o Bird fancier’s lung: inhaled avian serum proteins (usually IgA) in pigeon’s
o Decline in lung function accelerated in smokers feathers and excreta
 Presents with progressive increasing SOB and LOW  Hypersensitivity pneumonitis
 Later: cor pulmonale and polycythemia o Farmer’s lung: Micropolyspora faeni, Thermactinomyces in mouldy hay,
 CXR: bilateral bibasal emphysema straw and grain
 LFT: obstructive picture, RV:TLC ratio is raised (Gas trapping), transfer factor reduced o Bagassosis 2’ thermactnomyces sacchari in sugar cane processing
 Phenytotype o Malt worker’s lung: Aspergillus calvatus
o PIMM: nomrla o Mushroom worker’s lung: termophilic actinomycetes
o PiMs: 80% o Ventialation/water contamination: thermophilic actinomycetes
o PiMZ: 60%, shown in longitudinal study to correlate with rapid deterioration o Veterinary workers and animal handlers
in lung function o Workers in miling and construction: wood dust pneumonitis due to
 Prevalent in patients who also smoke Alternaria spp
o PiSZ: 40%, liver cirrhosis, premature emphysema  Clinical features
o PiNullNull: premature emphysema o Acute: several hours after exposure to high concentrations
 Management  SOB, flu-like symptoms
o Alpha1-antitrpysin replacement (weekly or monthly)  Headaches, fever, myalgia
 Symptomas usually resolve within 48 hours
32
 o Chronic disease o Usually in 50yo and more in females
 Interstitial lung disease with fibrosis o 60% have asthma, 90% are non-smokers
 Clubbing o May be irreversible
 Management o CXR: dense bilateral peripheral infiltrates (outer two thirds of lung)
o Avoidance of exposure to source: resolution/improvement of symptoms  Labs
o Acute: corticosteroids o IgG raised in 2/3
o Elevated ESR
Bronchiolitis obliterans syndrome o Sputum & BAL: eosinophilia
 Progressive obliterative bronchiolitis affecting terminal bronchioles
 Presents with increasing SOB and progressively worsening fixed airways obstruction Hypereosinophillic syndrome
picture on LFT  > 20% of eosinophils
 Risk factors:  Eosinophilic infiltrations of various organs
o Early acute graft rejection o Lungs, heart, bone marrow
 Can occur as early as 3 months post transplant o Can be associated with eosinophilic arteritis
o CMV infection
 Prognosis Hypersensitivity pneumonitis
o 50% of death in 1st year post transplant  Cladosporum -> ceiling mould -> hot tub lung

Loefler’s syndrome (acute eosinophillic pneumonia) Restrictive lung diseases

 10% of WCC eosinophils  Reduced lung volumes due to alteration in lung parehcnhyma or disease of
 Mild self-limiting illness with transient migratory pulmonary shadows pleura/chest wal/neuromuscular apparatus
 Associated with parasitic infections, drug allergies, exposure to inorganic chemicals  Transfer coefficient will be reduced

Tropical pulmonary eosinophilia Idiopathic pulmonary fibrosis

 > 20% of eosinophils  Finger clubbing, crepitations
 Usually in tropical countires due to migrating larvae of filarial worms (Wucheria  Investigations
Bancroft and Brugia malayi) o CXR
o CT Thorax
Chronic/prolonged pulmonary eosinophilia o Histology: normal lung, interstitial fibrosis, inflammation, honey comb
 Rare respiratory pathology changes
o Characterized by pulmonary infiltrates and pulmonary eosinophilia  Management
o > 20% eosinophils for more than 1/12 o High dose corticosteroid
o Can be 2’ drugs, parasites, systemic diseases o Oxygen if significant hypoxia
 Acute (over few days)
o Symptoms: acutely unwell Interstitial lung disease
 Fever, tachycardia, tachypnea  Clinical features
o CXR: bilateral diffuse infiltrates a/w effusion o Slowly progressive SOB
 Chronic debilitating illness (months to years)  Investigations
o Symptoms o Type 1 hypoxia
 Constitutional: Malaise, LOW, fever, dyspnea o Restrictive lung function tests: reduced TLCO and KCO
 Cough and wheeze
33
 o CXR: reticular nodular shadowing o BAL: lymphocyosis in active sarcoidosis
o Kveim reaction: granulomatous reaction 4/52 after intradermal injection of
Upper zone fibrosis sarcoid spleen or LN extracts (positive in 50-60%)
 Progressive massive fibrosis/coal worker’s pneumoconiosis o hypergammaglobulinaemia
 Ankylosing spondylitis  Complications
 Sarcoid/silicosis o Pulmonary fibrosis
 Tuberculosis o Cystic changes
 Extrinsic allergic alveolitis o Cor pulmonale
 Radiation  Management
o Corticosteroids
Amiodarone induced fibrosis o 2nd line: methotrexate
 Usually seen in bases of lungs
 Management Small cell carcinoma
o Stop amiodarone  Paraneoplastic
o Steroids o Peripheral neuropathy
o SIADH – hypoNa
Sarcoidosis o Lambert-Eaton myasthetnic syndrome (proximal weakness, hyporeflexia
 Clinical features and autonomic features)
o Pulmonary  Rapid progression and spread
o Anterior uveitis
o Erythemanodosum Bronchial carcinoma
 Diagnosis:  Central lesion
o Transbronchial biopsy: best modality  Investigations
 Non-caseating granulomata o CT TA (including liver & adrenals)
o HRCT: upper lobe ground glass shadowing, perivascular beading from small o Bronchoscopy: tissue diagnosis
non-caseating granulomas, micronodules in subpleural and bronchioalveolar  Can be a/w polymyositis
distribution, fissural nodularity and bronchial distortion
 Can have air trapping due to endobronchial granulomas and Squamous cell carcinoma
“honey combing”  PTHrp: Hypercalcemia, hypophosphatemia
o ACE/Ca levels may be elevated  A/w gynaecomastia, hyperthyroidism, HPOA
 Overproduction of vitamin D by sarcoid granulomas
 Serum ACE levels best used to assess response to steroid therapy Bronchial carcinoids
and nto diagnostic test  Occurs at younger age (50-70yo) and not a/w smoking
o Immunoglobulins can be raised in active disease  Lesions often peripheral
o BAL: finding of lymphocytes may be non-specific  Thought to arise from Kulchitsky’s cells in bronchial mucosa
o CXR: bilateral hilar and right paratracheal adenopathy o Bronchial carcinoid tumours most indolent form of neuroendocrine tumours
o LFT: restriction, decreased compliance, impaired diffusing capacity of lung (small cell most malignant)
o Kveim test (no longer performed due to danger of inection)  Usually secrete serotonin and arise from large bronchi
 Other findings  May present
o Leucopenia 5-10% o Mass: centrally located/R upper lobe collapse

34
 o Recurrent chest infections o FEV1 > 2L
o Haemoptysis o Complication
o Chest pain  Chylothorax 2’ damage to thoracic duct
o Wheeze  Pleural fluid
o Flushing: ppt by alcohol/food/stress/emotion  Milk coloured
o Diarrhea  Elevated protein content
o Pellargra: may occur due to tumour uptake of tryptophan (precursor of  TG > 1.2 mmol/L
nicotinic acid)  Management
o Mostly asymptomatic and mass found incidentally  Conservative
 Carcinoid syndrome occurs when there are 2’ in liver which release serotonin into  If no resolution: surgical ligation
systemic circulation
o Rarely occur in bronchial carcinoid in absence of metastases as bronchial Berylliosis
tree drains straight into systemic circulation  Granulomatous lung disorder -> chronic form leads to restrictive lung disease
o Diagnosis: detection of 5-HIAA (hydroxyindoleacetic acid – metabolite of  Associated with metal recycling
serotonin) in urine  Investigations
 Paraneoplastic: o Beryllium lymphocyte proliferation test (BeLPT)
o Serotonin secreting tumours o HRCT: ground glass changes (pulmonary fibrosis) and nodule formation
o ACTH secreting tumours o Lung biopsy: granuloma formation
o GH secreting tumours  Management
 Diagnosis o Prevention
o Biopsy o +- Corticosteroids
 Solitary lesion with occasional nuclear pleomorphism and Silicosis
absent/late mitoses  Fibrotic lung disease a/w inhalation of silica -> highly fibrogenic
o Urinary 5-HIAA o In quarrying and mining tunneling occupations
o Bronchoscopy & biopsy: bronchial carcinoid o Sandblasters, ceramic workers, potteyr workers and stonemasons
 Management  Acute silicosis: acute illness within 12 months of exposure to very heavy exposure
o Surgical resection o Dry cough and SOB
o Somatostatin analogues o Deteriorate rapidly over 1-2 years
 Chronic silicosis: gradual worsening of SOB a/w restrictive lung function, reduced
Hypertrophic pulmonary osteoarthropathy transfer factor
 Seen in patients with bronchial carcinoma and may predate discovery of underlying o Silicotic nodule formation 3-5mm in diameter -> usually upper lobes
lesion  May coalesce and cause progressive massive fibrosis
 Characterized by finger clubbing and long bone pain  Diagnosis
 Investigations o History of exposure
o Isotope bone scan: in long bones, around periarticular surfaces, mandible o CXR: hilar eggshell calficifcation (pathognomonic)
and scapulae
 Symptoms may resolve with removal of tumour Asbestosis
Mesothelioma
Surgery in cancer patients  Histo subtypes: mixed, sarcomatous and epithelial
 Pneumonectomy  CXR: metothelioma & calcified pleural plaques

35
 o Holly leaf pleural plaque o NIV
 Diagnosis
o Thoracoscopy with biopsy (with prophylactic radiotherapy to operation site) Pickwickian syndrome
o Avoid CT guided/blind biopsy -> risk of tract spread  Severe obesity, plethoric face, OSA -> hypoxia, hypercapnia resulting in marked
 Rarely suitable for surgical resection and not responsive to chemotherapy daytime somnolence
 +- Palliative radiotherapy
 Prognosis: very poor Pulmonary hypertension
o Average survival 1-2 years from diagnosis Primary

ARDS Secondary
 Acute respiratory failure with non-cardiogenic pulmonary edema 2’ severe Causes
pulmonary or systemic illness  Chronic thromboembolic disease
o Increased permeability of pulmonary microcirculation due to inflammation
causing leakage of fluid into lungs Asthma
 May be associated with multi-organ failure  Management
 Most common cause: sepsis o Cromoglicate: effective for asthma prophylasix by inhalation 3-4x/day, only
 Later stages: considered after therapy failure on multiple agents including ICS, LABA,
o Pulmonary vasoconstriction monteleukast
o HTN 2’ hypoxia and lung exudates o Theophylline: can be added if failure on high dose ICS
 Management o Tiotropium: failure on ICS and LABA
o Airway support  Life threatening asthma
 High PEEP: reduce progression of ARDS o Confusion/AMS, exhaustion, coma
 Low Vt: reduce excessive lung stretch o Bradycardia, hypotension
o Circulatory support: inotropes o PEFR < 30% of best, severe hypoxaemia
o Treatment of sepsis o SpO2 < 92%m PaO2 < 8kPa
o Inhaled NO2 o Normal PaCO2 (4.6-6kPa)
o Haemofiltration o Silent chest
 Prognosis: 20-30% mortality o Cyanosis
o Arrhythmia
Diaphragmatic weakness o Poor respiratory effort
 Bilateral: due to paroxysmal movement of diaphragm
o Commonly presents with SOBOE and on lying flat Occupational asthma
o A/w sleep apnea -> daytime solnolence & headaches  Obstructive airways, bronchial hyper-reactivity
 Supine: expansion of ribs results in movement of abdominal contences into chest  Investigations
 Standing up in water: counteracts effects of gravity and prevents outward movement o LFT: obstructive picture
of abdomen during inspiration o Histamine challenge test: hyper-responsive
o Similar situation in supine position o Peak flow diary
 Diagnosis: SNIF test
o Paradoxical movement of diaphragm seen on US, particularly on sniffing COPD
 Management  TORCH: high dose fluticasone + salmeterol
o Borderline significant effect on mortality
36
 o Reduction in exacerbations o Plasmapheresis (1st line in primarily renal disease, when Cr>500)
o Increase in pneumonia  Prognosis
 Investigations o Untreated: ~5 months
o CT expiration phase: assess air trapping in COPD
 Management Microscopic polyangiitis
o LTOT improves mortality by reducing progression of RHF and pulmonary
HTN than by reducing exacerbations Goodpasture’s syndrome

Fixed extrathoracic airflow obstruction SLE/Polyarteritis nodosum/Henoch-Schonlein purpura

 Flow-volume loop
o Flow tends to be constant throughout the first part of expiration rather than Churg-Strauss syndrome
decelerating  Asthma, vasculitis (in ≥2 non-lung organs), eosinophils >1.5
o Inspiratiory flow more reduced  Can have prodromal period for many years: AR + difficult to control asthma of late
 Extrathoracic obstruction prevents negative IT pressure form onset
pulling the IT airways open  Diagnosis (4 out of 6 of the following)
 Causes o Asthma
o Goitre o Eosinophils > 10% in peripheral blood
o Tracheal stenosis o Neuropathy in vasculitic pattern
o Transient pulmonary infiltrates
Variable extrathoracic obstruction o Sinus disease/polyps
 Expiratory flow not affected o Evidence of intravascular eosinophils on biopsy
 Causes  Other clinical features
o Tracheal tumours o Nodular or purpric skin rash
o Vocal cord paralysis o Renal/intestinal/cardiac involvement
o Pharyngeal muscles o Malaise
o LOA/LOW
**PULMONARY RENAL SYNDROMES**  Diagnosis
Granulomatosis with polyangiitis (Wegener’s) o Systemic symptoms
 Triad: URT (nasal polups & sinusitis), LRT & renal involvement o Asthma
 Small vessel vasculitis a/w granulomas o Eosinophils > 1.5
 Labs o Evidence of vasculitis in two or more non lung organs (Lanham’s criteria)
o C-ANCA: PR3  Cutaneous vasculitis
o Antibody to proteinase 3  Mononeuritis multiplex
 CXR: single or multiple nodules, fixed infiltrates or cavities, pleural effusions and  Cardiac history
pulmonary infitrates  Investigations
 Diagnosis: biopsy o Eosinophilia 5-20% of WCC
 Management o Raised serum IgE
o IV cyclophosphasmide & Prednisolone (reduced mortality to ~ 10%) o CXR: nodules, transient hilar LAD, pulmonary infiltrates
o Methotrexate & methylprednisolone (can be considered in non-ogran/life  +- Pleural or pericardial effusions
threatening cases) o pANCA +ve in ~50%, myeloperoxidase antibody

37
 o Renal involvement rare
 Management Bronchiolitis obliterans
o High dose corticosteroids  Clinical features
 Life threatening organ involvement: pulse dose IV steroids + o Dry cough
cytotoxic o SOB
o Cytotoxic (in < 20%) o Decreased effort tolerance
 Azathioprine or cyclophosphamide  Nvestigations
o Other o CXR
 IVIg o LFT
 Interferon-alpha  Management
 Plasma exchange (does not improve course of disease) o Azithromycin
 Prognosis
o Morbidity and mortality mainly due to myocarditis and MI 2’ coronary Altitude illness
arteritis 3 types
o With tx: 1 year 90% and 5 year 62% survival  Acute mountain sickness
o Without tx: 5 year 25% survival  High altitude cerebral edema (HACE)
o Untreated: 50% die within 3 months o The lake Louise Score
 In setting of recent gain in altitude
Pulmonary embolus  Headache one of the following
 Clinical features  GIT: anorexia, nausea, vomiting
o Triad: haemoptysis, SOB, pleuritic chest pain  Fatigue/weakness
o Massive PE:  Dizziness or light headedness
 Hypotension due to acute RHF  Difficulty sleeping
Lymphangioleiomyomatosis o Ataxia & drowsiness (end stage AMS)
 Rare idiopathic disease, affecting women of reproductive years o Management
o Consider tuberous sclerosis if this occurs in men  Immediate descent
 Charactersed by infiltration of immature muscle cells into bronchiolar and alveolar  Oxygen
walls  IV dexamethasone
o Destruction of airways o Prevention
o Cyst formation  Acetazolamide
o Progressive decline in lung function  Causes intracellular acidosis
 Investigations  Diuretic effect
o CXR  Shifts O2-dissociation curve to right and at lower partial
 Interstitial lung disease pressure: more oxygen released to tissues
 Recurrent pneumothoraces  High altitude pulmonary edema (HAPE)
 Chylous effusions
 Management Physiological hyperventilation of pregnancy
o Lung transplant  Clinical features
o Avoid OCP/pregnancy/long gaul flights o Increased SOB at rest, improves when moving
o Progresterone supplements

38
39
GASTROENTEROLOGY  Clinical features
o Diarrhea, constipation
o Lower GI blood: frank haemorrhage or occult losses
Coeliac disease o Iron deficiency/anaemia
 Clinical features o Acute diverticulitis: inspissation of faecal material in neck of diverticulum ->
o Anaemia: Iron/V12/Folate deficiency
resultant bacterial replication
o Hypocalcemia: malabsorption of Ca and vitamin D
o Dermatitis herpetiformis: intensely pruritic, vesicular rash that affects Ulcerative colitis
elbows, scalp, extensor surfaces of forearm and buttocks  Acute flare
o Small bowel malabsorption o Local or systemic steroids to induce remission
o Hepatic steatosis o 5-ASA to maintain remission
o Symptoms may improve with periods of fasting o Severe: cyclosporine (bridging therapy) & Infliximab (can be used in both
 More common in males acute & chronic situations)
 May occur at any age but more common in young adulthood  If no improvement within 48-72hrs, colectomy
 a/w gluten sensitive enteropathy o Colonic dilatation > 6cm or caecal dilatation > 9cm -> colectomy
 Diagnosis  If repeated relapses despite maintenance treatment: steroid sparing drugs
o Anti-tissue transglutamase antibody o Azathioprine
o Anti-endomysial and gliadine (requires detection of IgA antibodies to these o 6-mercaptopurine
antigen, thus inaccurate in IgA deficiency) o Anti-TNF (if 2nd line agent fails
o Absence of serum and secretory IgA (failure of maturation if IgA positive B  Surgery
cells – immature forms present in normal numbers) o Colectomy offers possibility of cure but only be used if all medical therapy
o Esophagogastroduodenoscopy +- small bowel biopsy fails
 Management  Smoking protective in UC
o Strict adherence to gluten free diet  Extra-GIT symptoms
o Dapsone: rash (may have haemolytic anaemia) o Derm: erythema nodosum
 Haemolysis (dramatic in G6PD deficiency)  Truelove criteria (determine disease severity)
 Monitor LFT and FBC o Stool frequency with macroscopic blood > 6
 Complications o ESR > 30
o Increased risk of metabolic bone disease o HR > 90
o Increased risk of GI malignancy o T > 37.8 in 2 out of 4 days
 Enteropathy associated T cell lymphoma o Anaemia <75% of predicted
 Raised viscosity, LOW, night sweats
 Management
 Poor compliance to coeliac diet may increase the propensity for
o Severe UC
malignancy
 Steroids
Diverticular disease
 Fluids
 Sigmoid most commonly affect (>90%)
 SC heparin
 Low fibre diets, high consumption of red meat and animal fats
 Elemental diet
 Rare under age of 40yo  Ciclosproin (late stage salvage therapy)
40
  Infliximab  50% occur in associated with systemic illness
 Colectomy o IBD, RA, seronegative spondyloarthropathies, liver disease (esp. AI
hepatitis), haematological conditions (lympho.myeloproliferative disease)
Crohn’s disease  Biopsy
 Management o Neutrophil inflitration, haemorrhage and epidrmal necorsis
o Biological therapy: Infliximab (monoclonal antibody to TNF-alpha)
 Management
 For use in steroid and immunosuppressant resistant CD
o Topical corticosteroids
 Useful in healing fistulae
 Induce remission in 60-80% o Systemic corticosteroids for refractory disease
 If patient responds to initial dose, then further four infusions at 8 o Severe disease: immunosuppressants (cyclosporin, MMF, anti-TNF alpha
weekly interval agents)
 5% allergic reactions
 Exclude TB before start of treatment Autoimmune hepatitis
 Complications  Type 2
o Small bowel stricture o Anti-LKM antibodies
 Management  Management
 Azathioprine o Corticosteroids + azathioprine
 Dilatation of strictured segment if fail to respond to o Alternative: ciclosporin
medical therapy o Liver transplant if treatment failure: continued LFT abnormalities
 Surgery as last choice
o Short bowel syndrome Primary biliary cirrhosis
 Undergone multiple bowel resection  Slowly progressive inflammation and destruction of intrahepatic ducts leading to
 Oxalate renal stones eventual cirrhosis
 Management  Associated with RA, Sjorgren, CREST
o Increase fluid intake  40-70yo, 90% females
o Supplementation with calcium citrate  Chronic fatigue, progressive itching, jaundice
o Low oxlate diet  Diagnosis
o Cholestatic liver function
Pyoderma gangrenosum o AMA: 90-95% of patients
 May start as small papule that is often mistaken for an insect bite -> rapidly spreads  98% specific for disease
to ulcerating lesion with pain being predominant  Especially M2 subtype
o Violaceous border  Management
 Facial vegetative pyoderman gangrenosum o Ursodeoxycholic acid: improves liver biochemistry and delays disease
o Management progression (only if used very early in the course of diease)
 Systemic high dose corticosteroids o Immune modifying agents: tried but clinical benefit unproven and S/E can
 Then steroid sparing agent: cyclosporine, mycophenolate be significant
o Liver transplant (16% recurrence after 5 years)
 Can occur around stoma post formation
o Local trauma from applying and removing stoma bags increases the risk of
Primary sclerosing cholangitis
recurrence  70% are men, around 40yo
 Common in 4-5th decade  90% have co-existent IBD, usually UC
41
 Genetic association with HLA-B8, DR3, DRw52a  Moratlity ~80%
 Progressive leading to cirrhosis, portal HTN and liver failure Small bowel malabsorption
 10-15% develop cholangiocarcinoma  Biospy from 2nd part of duodeum: villous shortening
 Clinical features  Subtotal villous atrophy
o Hepatomegaly o Coeliac disease
o Intermittent jaundice o Giardiasis
o PUO o Whipple's disease
o Pruritus o Lymphoma
o Abdominal pain
o Hypohlobulinaemia
o Weight loss
o Infectious enteritis
 Diagnosis
o True lactose intolerance
o Cholestatic LFTs
o pANCA
o Cholangiographic: generalized beading and stenosis of intra/extrahepatic Tropical Sprue
biliary tree  Clinical features
o Histo: concentric obliterative fibrosis of interlobular bile ducts with o Persistent diarrhea
presence of intrahepatic cholangiectasis with ductal obliteration o Watery diarrhea
 Management o Abdominal cramps
o Dietary replacement of vitamin A/D/E/K o Nausea and vomiting
o Dilation of strictures  Investigations
o Endoprosthesis o Endoscopy: partial villous atrophy
o Liver transplant  Management
o Tetracycline
Intestinal angiona
o Folic acid
 Uncommon condition, usually occurs in elderly smokers with vascular disese
 Due to atheromatous occlusion of coeliac axis and superior and inferior mesenteric
arteries **INFECTIVE**
 Clinical features CVM associated colitis
o Post prandial colickly abdominal pain  Presents with colitis
o Immunocompetent: infection self limiting and requires no treatment
o Diarrhea
o Immunosuppressed: IV ganciclovir + oral maintenance therapy
o Rectal bleeding
o Weight loss (fear of eating due to pain or malabsoprtion)  Investigations
o Histo: round intranuclear or intracytoplasmic inclusion bodies within
o Abdominal bruit
epithelial cells of intestinal mucoa (pathognomonic)
 Investigations
o Angiography
Lymphocytic colitis
 Meandering mesenteric artery with areas of stenosis
 Chronic diarrhea
 Management
 Histo: increased number of intraepithelial lymphocytes with epithelial surface
o Vascular reconstruction
damage
 Prognosis
 Management
o Progress to acute intestinal ischaemic if undiagnosed
o Sulphasalazine or prednisolone (but only some success)
42
 o Usually asymptomatic or may present with slowly progressive hepatitis
Microscopic colitis o Other causes: autoimmune (AntiLKM), antibody associated, drugs
 Associated with drugs (methyldopa, isoniazid), rare: alpha-1 antitrpysin deficiency or UC
o PPI  Associated wth IV drug abuse
o ACE-I  Associated with cryoglobulinaemia and mononeuritis multiplex
o Low dose aspirin  Management
o NSAIDs o Interferon: prevent viral replication and allow seroconversion
 Affect permeability of bowel mucosal, increasing antigen presentation -> driving  Pregnancy
lymphocytic inflammatory response o Treat with anti-virals with attempt to eradicate before conception
o Otherwise limited options but to
Collagenous colitis  Measure hep C RNA during 1st year of infant life and tailor
 Microscopic colitis where colon appears normal on colonoscopy but diagnosis is treatment accordingly
made based on abnormal histology of colonic biopsies  4-9% vertical transmission
 Affects women predominantly, 4x in the 5th and 6th decade of life Hepatitis E
 Associated with NSAIDs, coeliac disease, autoimmune disorder  Distribution similar to hepatitis A
 Clinical features  Transmission via faeco-oral route
o Chronic watery diarrhea, worse during day than nigh  Incubation 15-60 days
o Crampy, diffuse abdominal pain  Clinical features
 Diagnosis o Acute self-limiting hepatitis lasting 1-2 weeks
o Histo: thickened subepithelial collagen band, moderate inflammatory cell o Increased risk of fulminant hepatitis in pregnancy and in
infiltrate, increase in intraepithelial lymphocytes immunocompromised patients
 Management
o Anti-diarrhea: loperamide Whipple’s disease
o 5-ASA  Rare multi-system disease
steroids  Middle-aged men
o Bile acid sequestrants  Caused by Tropheryma whippeii
 Clinical features:
Hepatitis o Cardiac: pericarditis, endocarditis, conduction defects
 Hep B and C easily contracted from blood transfusion o Pulmonary: pleurisy, lung infiltrates
Hepatitis B o Neurological: fits, myoclonuc, CN lesions, cerebellar signs
 Chronic active hepatitis: histo: piecemeal necrosis  Diagnosis
 Can be associated with membranous nephropathy o Histo: PAS macrophages in small intestinal mucosa
o Mesangiocapillary glomerulonephritis (rare cause in hep B) o EM: widened, flattened villi with small gram positive bacilli inside
 a/w red cell casts macrophages
 Management  Management
o Lamivudine/Telbivudine: RESISTANT o Penicillin, tetracycline, sulphonamides
o Tenofovir: good for treating hepatitis B in HIV patients o Relapse occurs in 30%
o Interferon-alpha o Fatal if untreated
Hepatitis C
 50% higher risk of chronic active hepatitis in C than B Hydatid disease

43
 Due to ingestion of dog tapeworm: Echinococcus granulosus  Live in colon, more common in temperate climates
 Starts in pigs/cattle/sheep, passed to humans by direct contact with dogs/faeces ->  Can cause pruritus ani
penetration through duodenal wall permits parasite to pass into liver -> spread to
any organ (liver – 60%, lungs – 20%) **MALIGNANCY**
 Can be asymptomatic but enlarging cysts can cause mass effect: pain/jaundice Barrett’s esophagus
o Usually present with hepatomeagaly, obstructive jaundice, fever and  Superficial dysplasia: cryotherapy
cholangitis  Low grade dysplasia: 8-12/52 of continuous high dose PPI then re-endoscopy
o Rural sheep farms (China, Russia, Wales, Japan) o If improvement seen: 6 monthly review until stable or improved disease on
 Investigations 2 successive endoscopies -> 2 yearly scopes
o 1/3 can have peripheral eosiophillia  High grade disease: esophagectomy if functional status allow
o Complement fixation/haemagglutination tests +ve
o 40% cytst calcfy Gastric MALToma
 Management  Characterized by large numbers of immunocompetent cells in lamina propria
o Albendazole/Mebenazole (shrink cyst)  B-cell lymphomas comprising large numbers of lymphocytes with irregular nuclear
o Aspiration with chemotherapy cover contours and abundant cytoplasm
o Addition of Praziquantel in extensive diseases  Higher grade lymphomas: clusters or sheets of blast like cells
 75% of small low grade lymphomas may regress completely after antibiotic therapy
Hookworm infection for helicobacter eradication
 Necator americanus & Ancylostoma duodenale o Chemotherapy may be required to treat refractory cases
 Commonest cause of FE deficiency anaemia with marked microcytosis  If medical treatment fails:
 25% of global population o Surgical therapy +- radio and chemotherapy
 Infection occurs when larvae invade exposed skin (via contaminated soil/water o Imatinib mesilate (Glivec)
bodies)  Post antibiotic: Carbon 13 urea breath test co confirm eradication
 Clinical features
o Intestinal blood loss Hepatocellular carcinoma
 Investigations  Management
o Eosinophilia o Hepatic resection
o Microcyticc anaemia  HCC and non-cirrhotic liver
o Iron deficiency o Liver transplantation
 Management  HCC (single small, < 5cm or up to 3 <3cm lesions) + cirrhosis
o Mebendazole or albendazole o Non-surgical therapy: when surgery not possible and if metastatic
 Percutaneous ethanol injection: necrosis of small HCC< suited for
Trichuris trchiura (whipworm) peripheral lesions
 Infests diatal ileum and colon  Chemoembolisation: tumour necrosis
 Heavy infestation -> diarrhea and GI bleeding  Increase survival in patients with good liver reserve

Strongyloides stercoralis Hereditary non-polyposis colorectal cancer syndrome

 Not visible to naked eye and may cause malabsorption  AD syndrome with early onset CRC
o 1-2% of all CRC
Enterobius vermicularis (threadworms) o 55-60% are right sided
o Increased risk of endometrium, stomach, small bowel, GUT
44
 Diagnosis o Related to degree of glycaemic control
o Related cancers in ≥3 relatives: one if first degree of other two  Diagnosis
o CRC affect ≥2 generations o Excluding other pathology
o ≥1 more diagnosed before 50yo o Scintography: significant dealy of gastric emptying
 Screening o Electrogastrography: uncoordinated increase in number of gastric
o 2 yearly colonoscopy from age 20-25 up to 40yo then yearly colonoscopy pacemaker contractions (tachygastria)

Cowden’s syndrome Fatty liver of pregnancy

 Inherited condition from a defect in the PTEN tumour suppressor gene  Presents with nausea/vomiting, pain in epigastrium/right upper quadrant, anorexia,
 Clinical features lethargy, ascites, progressive jaundice
o Hamartomatous polyps of GI tract o Develop voer few days to weeks
o Characteristic muco-cutaneous lesions such as oral mucosal papillomas,  Usually present ~ 37 weeks (may occur in 28-42 weeks range)
palmoplantar keratosis and trichilemmomas (benign tumours of hair  Common in first pregnancies or multiple pregnancies
follicles)  Investigations
 Complications o Hypoglycemia, low albumin
o High risk of malignancy: breast & thyroid o Elevated ALT/WCC/ammonia
 Thyroid dysfunction is common even in absence of cancer o DIC
o US
Familial juvenile polyposis  Prognosis
 Multiple polyps in colon o Spontaneous resolution follows delivery
 Management
Peutz-Jeghers syndrome o Stabilization in HD/ICU
 Polyps with classicl histological appearance of smooth muscle arborisation  IV fluids & glucose
 Perioral hyperpigmentation  Correction of coagulopathy with FFP
 Mutation of serine threonine kinase 11 gene  Reduction of exogenous ammonia: protein restriction, dietary
 Significant risk of eventual malignant transformation laxatives (speed evacuation of nitrogenous wastes)
o ~50% develop and die from cancer by 57yo
o Mean age of cancer diagnosis ~43yo Fetal alcohol syndrome
o Stomach, colon, pancreas and breast  Fetus relies on maternal hepatic detoxification of alcohol
o Regular survillance examinations, endoscopies and US yearly recommended o Alcohol appears to cross freely between mother and fetus but fetal liver
only 10% of adult liver capacity to detoxify alcohol
MEN 2B  Clinical features
 Histo: ganglioneromas and usually asymptomatic o Mental retardation
 Associated with medullary cell thyroid cancer o Growth retardation
o Mid-facial abnormalities
Gastroparesis o Later life
 Vomiting temporally removed from eating and vomitus has recognizable food from  Behavioural difficulties
hours before: hallmark of gastric emptying disorder  Alcoholism
 No outflow obstruction would lead to diagnosis of functional delayed gastric  Criminal activity
emptying
 Can occur in over 50% of diabetics Alcoholic liver disease
45
 Associated with hepatocellular damage  Porto-systemic shunting: usually reserved for re-bleeding
o Rise in ALT less than AST patients and with symptoms of worsening portal hypertension
o Relatively lower rise in ALT -> hepatic deficiency of pyridoxal 5’-phosphate in due to risk of chronic encephalopathy
alcoholics (co-factor for ALT enzymatic activity)  Transplantation: indicated in patients with complications of
 ALT is inappropriately low liver disease resulting from alcohol
 Portal hypertension
Zieve’s syndrome o Low platelet count: hypersplenism
 Clinical features o Varices – esophageal
o Epigastric/RUQ pain, hyperlipidaemia, jaundice, non-AIHA  Hepatic encephalopathy
 Seen in patients with history of fatty liver who stopped drinking o Precipitants: HEPATICUS
 Grossly elevated TG lead to haemolysis  Hypoglycemia
o Gradual resolution over few days  Electrolyte disturbances
 Protein meal (GIT bleed)
Liver abscess  Alcohol/analgesia
Entamoeba histolytica  Tumour (hepatoma)
 Investigations  Infection
o Mil anaemia, elevated WCC  Constipation
o Abnormal LFTs, especially ALP  Uraemia
o Eosinophilia  Surgery (esp. if portosystemic shunting)
o CT liver: low attenuated lesions o Investigations
Echinococcus granulosus  EEG: diffuse symmetrical triphasic sharp waves
 Hydatid disease  Prolonged clotting
 Liver cyst: coplex  Low albumin
o Management
Chronic Liver Disease  Lactulose
Complications  Antibiotics
 Esophageal varices  Protein restriction
o Prevention of encephalopathy after large GI bleed
 Lactulose & neomycin Ascites
o Reduce portal hypertension  Management
 Propranolol (high hepatic first pass metabolism): to be given in o Large volume ascites drainage
all patients with Childs-Pugh B/C with significant varices at  Complications
endoscopy  Spontaneous haemoperitoneum 2’ mesenteric variceal
o Endoscopic bleeding
 Band ligation  Clinical features
 Injection sclerotherapy: trials as primary prophylaxis produced o Drop in systolic BP
mixed results gradual build up of abdo pain
o Antibiotic prophylaxis
 Reduce risk of secondary bacterial infection after haemorrhage Lithium & hepatic function
 Quinolones: ciprofloxacin  ACE-I may lead to increase in lithium levels
o Surgery o GGT sensitive measure of effects of lithium on liver
46
 Other drugs which can increase lithium levels: o Capsule endoscopy
o Metronidazole  Management
o NSAIDs o Endoscopy therapy: cautery, sclerotherapy
o Thiazide diuretics o Angioembolisation
o ARBs o Surgical resection
 Symptoms
o Ataxia, nystagmus, nausea, vertigo Investigations for BGIT
o Cardiac arryhytmia, thyroid dysfunction, nephrogenic DI  Mesenteric angiogram: most effective during active blood loos
 Monitoring of lithium lelves o Usually > 1ml/min
o 2 monthly for stable patient  Meckel’s scan: Meckel’s diverticulum
o Increased if changes in status or new interacting drugs  Capsule endoscopy
 Octreotide scan: neuroendocrine tumour
Paracetamol toxicity
 Single ingestions > 250mg/kg or > 12g over 24 hour Sphincter of Oddi dysfunction
 If > 350mg/kg -> severe liver toxicity  Non-calculous obstruction of flow of biliary and/or pancreatic fluid
 Paracetamol ingestion -> NAPQI produced -> rapidly conjugated by hepatic  Sphincter is hypertonic >40mmHg on manometry but may also be dyskinetic
glutathione -> forming non-toxic cysteine and mercaptate that are excreted in urine  Usually in middle aged women but can occur to any one
 Paracetamol overdose: glucuronidation pathways saturated  Symptoms
o Liver unable to deactivate NAPQI -> causing massive hepatic necrosis and o Biliary type pain
failure o Recurrent episodes of idiopathic pancreatitis
 Symptoms: nausea, vomiting, anorexia  3 types
o After 72hr: liver and renal failure o I: typical biliary pain, abnormal liver enzymes, radiological evidence of
 Management impaired biliary drainage
o NAC (Methionine if allergic to NAC) o II: typical biliary pain, either abnormal LFTs or radiological evidence of
o Referral for liver transplantation impaired biliary drainage
 Encephalopathy or raised ICP o III: only typical biliary pain
 Signs of CNS edema: BP > 160/90 sustained or brief rises  Diagnosis
SBP > 300, bradycardia, poor papillary response o Manometry
 SBP < 80 despite fluid resuscitation o ERCP: delayed drainage of contrast > 45mins (5x increased risk of post ERCP
 pH < 7.3 or bicarbonate < 18 or arterial lactate > 3 after adequate pancreatitis)
fluid resuscitation (15% chance of survival – failure to clear lactate  Management
by liver) o Smooth muscle relaxants: Nifedipine
 PT > 100, Cr > 300 with grade III and IV encephalopathy o Endoscopic sphincerotomy (esp. in type I but no benefit in type III)
 INR < 2 before 48 hours or > 3.5 at 72 hours o Botulinum toxin injection in type III
 Hypoglycemia
o Rise in serum Cr is a bad prognostic marker, a/w 70% mortality Bile acid diarrhea
 Investigations
Angiodysplasia o SeHCAT testing
 Second cause of LBGIT in patients older than 60 years  Normally retained at level ≥15% after 7 days
 Ascending colon and caecum most commonly affected sites  Levels lower than this imply excessive loss via faeces
 Diagnosis
47
Pancreatitis  Low volume < 2ml/kg and normal HCO3 > 90meq/L and
 Glasgow prognostic score normal enzymes -> pancreatic duct obstruction
o PaO2 < 8kPa  Faecal elastase
o Age > 55yo  Check for pancreatic insuffieicny
o Neutrophillia WCC > 15 x 10^9/L  Causes: alcohol abuse, gallstones, cystic fibrosis, haemochromatosis, sclerosing
o Calcium < 2 mmol/L cholangitis
o Renal Urea > 16 mml/l  Inflammatory condition: irreversible damage to both exocrine and endocrine
o Enzymes LDH > 600 IU/L, AST > 200 IU/L pancreas
o Albumin < 32g/L  Management
o Sugar glucose > 10mmol/L o Pancreatic enzyme supplementation
 Increasingly recognized in association with azathioprine therapy o Complete abstention from alcohol
o Homozygotes for HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype – 17% o Usually becomes diabetic -> monitor!!
increased risk of acute pancreatitis
 Management Pancreatic cancer
o Early feeding in severe acute pancreatitis: reduce mortality, multiple organ  Slightly more common in men
failure, systemic infection  Predisposing factors
o Chronic pancreatitis
Post burn pancreatitis  Clinical features
 High degree of full thickness burn injury/significant inhalation injury and high o Vague and non-sepcific
percentage of overall skin damage o Significant weight loss
 Management o Mid epigastric pain with radiation to lower back (indicating retroperitoneal
o Supportive: fluid resuscitation invasion of splanchnic nerve plexus)
o Management of associated hypoxia o New onset DM
o Hypocalcemia o Painless obstructive jaundice
o Depression
Chronic pancreatitis  Investigations
 Investigations o Mild NCNC anaemia
o AXR (later stage): calcification of pancrease o Thrombocytosis
o ERCP o Elevations in bilirubin, ALP, GGT
o CT AP o Lower elevataions in AST, ALT
o 72hr fat test: insensitive for pancreatic exocrin dysfunction o Lipase/amylase not elevated
 Steatorrhea does not occur until lipase output is < 10% of normal
o Secretin test (most sensitive test for pancreatic exocrine function0 VIPomas
 Tube in dudodenum and collecting pancreatic secretions  Rare pancreatic endocrine tumours producing vasoactive intestinal peptide
stimulated by IV secretin w or w.o cholecystokinin  Clinical features
 Duodenum contents are collected for volume determination, HCO3 o Facial flushing
and enzyme collection o Diarrhea despite fasting
 Normal volume < 2ml/kg, low HCO3 < 80 meq/L -> chronic  Investigations
pancreaitits o Hypokalaemic metabolic acidosis
o Plasma VIP levels >10x normal

48
 o CT/MRI/somatostatin receptor scintigraphy for pancreatic imaging
Esophageal cancer
Zollinger-Ellison syndrome  Management
 Clinical features o Stenting
o Multiple duodenal/jejunal ulcers o Complications
o Diarrhea: due to acid deconjugation of bile salts and inactivation of lipases  Stent migration: presents with obstructive symptoms
resulting in fat malabsorption  Can occur in 50%
o Vitamin B12 deficiency  Management: stent removal via endoscopy or
 Investigations gastrostomy
o Elevated fasting serum gastrin levels  If partial migration, insert a further stent to anchor fierst
o Radioisotope scans: hot spots of tumour expressing somatostain receptors one
 Management
o High dose PPI Angio-edema of bowel
o Octreotide: reduce gastrin secretion  Hereditary: present earlier in life, associated with C1 esterase deficiecnt
 Prognosis  Non-hereditary: Associated with recent use of ACE-I
o Malignant in ~60% o Can occur minutes up to years from start of treatment
o Low levels of angiotensin II -> increase in bradykinins
Ischaemic colitis
 Atheroma of mesenteric vessels, typically affecting watershed areas: splenic flexures Wilson’s diease/hepatolenticular degeneration
& rectosigmoid junction  AR disorder of copper metabolism -> accumulation in liver, kidneys, cornea and brain
 AXR: mucosal edema, thumb printing  Presenting complaint
 CT: bowel wall and mesenteric blood supply o Neurological: parkinsonism, tremor, facio-oropharyngeal rigidity
o Psychiatric: behavioural changes
Achalasia o Chronic hepatitis
 Primary esophageal motility disorder o Kayser-Fleischer rings (pathognomonic)
o Failure of hypertensive lower esophageal sphincter to relax o RTA type II
o Absence of normal esophageal peristalsis  Investigations
o Degeneration of myenteric plexus, causing failure of relaxation of the lower o Low serum copper (free and total) & caeruloplasmin
esophageal sphincter and absent peristalsis in the body of esophagus o 24hr urinary copper excretion > 10ug
 Thought to result from viral or autoimmune destruction of the o Penicillamine challenge
plexus o Liver biopsy
 Diagnosis  Treatment
o Esophageal manometry (gold standard) o Trientine/penicillamine
o Barium swallow: sharp narrowing of lower esophagus (bird’s beak
appearance) Haemochromatosis
o OGD: TRO cancer  Mutation C282Y on HFE gene
 Management  Clinical features
o CCB or nitrates o Weakness/fatigue
o Endoscopic: botulinum toxin injection o Arthralgia/arthritis
o Heller’s myotomy o Impotence

49
 o Late onsent DM  Reduce acute episodes of fever and decrease progression of
o Cirrhosis amyloidosis
o Bronze pigmentation o Canckinumab (IL-1 antangonist)
 Investigations  Reserved for use in patient with diseases resistant to colchicine
o Transferrin saturation > 55% o Renal transplantation
o Liver biopsy: cirrhosis and histo grading of Fe concentration  Prognosis
 Management o Mortality 2’ declining renal function
o Weekly venesection until transferrin < 16%

Pellagra
 Dementia, diarrhea
 Dermatitis: photosensitive, normally affects face, neck and forearm
 Death
 Causes
o Primary: niacin or tryptophan deficiency
o Secondary: carcinoid syndrome, AN, chronic alcoholism, GI TB, HIV

Familial Mediterenean fever

 AR disorder characterized by sporadic paroxysmal attacks of fever and serosal
inflammation
 In region around Mediterranean sea of Jewish or Arab descent
 Clinical features
o Constipation w fever (paroxysms fever)
 Diarrhea follows its resolution
o Abdominal pain
 Surgery done for Appendicectomy but usually no conclusive
findings
o Pleurisy/pericarditis
o Synovitis/small joint arthropathy/chronic arthritis
o Amyloidosis manifesting as proteinuria
 Nephrotic syndrome
o Each episode can last up to 5 days, but usually last 24-72 hours
 Investigations
o ESR, CRP elevated
o Serosal (peritoneal or pleural) or synovial fluid: large numbers of neutrophil
with no organism
o Gradual progression of proteinuria -> renal failure in 60% (? 2’ amyloidosis)
 Management
o Colchicine 1mg.day

50
NEUROLOGY o OCP
o Obesity
o Tetracycline use
**HEADACHE**
 Clinical features
Cluster Headache
o Headaches worse in the morning/with coughing/straining
 Excruciating unilateral headache accompanied by conjunctival injection and
o Blurred vision/scotoma/horizontal diplopia/visual loss
lacrimation
o Pappiloedema
 Ipsilateral ptosis, eyelid edema, forehead and facial sweating
 Investigations
 Nasal congestion
o LP: increased opening pressure
 Each episode can last form 15mins – hours
o MRV: TRO venous sinus thrombosis
o Frequency can be 1-8 or more /day
 Management
 Management
o Weight loss if obese
o Abortive treatment
o Serial LP to control intracranial pressure
 High dose oxygen
o Acetazolamide and thiazide diuretics
 Steroids
o Large volume LP for visual loss and KIV shunting or optic nerve fenestration
 Sumatriptan
o Maintenance prophylaxis
Paroysmal hemicrania
 Verapamil: vasodilatation
 Increasing in frequency, potentially disabling, very responsive to treatment
Migraine o Differs form cluster headache
 Recurrent headache causing sleep disruption, depression  Females more affected
 Increased frequency of daily attacks (up to 50 as compared to 1-4)
 Dominantly inherited disorder, affecting women more
 Shorter duration of attacks (2-25 minus as compared to 10-60 min)
 Typical headache: throbbing/pulsatile
 Management
o Begins unilaterally and anteriorly, progressing posteriorly over 1-2 hours
o Indomethacin
o Lasting several hours to several days
 Aura: precede or accompany headache or in isolation
**NEUROPATHY**
o Visual: flashing zigzag lights in centre of visual hemifield which expand
Trigeminal neuralgia
peripherally and a/w scotoma, dots/spots in visual field, jumbling of words
 Clinical features
on a line
o Presents with paroxysmal pain in distribution of one or more branches of
 Triggers
trigeminal nerves
o Dietary: chocolate, aged cheese, meats, alcohol, citrus fruits, anxiety, travel,
o Sharp, burning, superficial or electric shock like
exercise
o Episodes lasting from seconds to several minutes
o Triggered by touching specific area of face, chewing, talking, washing face or
Idiopathic intracranial hypertension
cleaning teeh
 Raised ICP in absence of mass lesion/hydrocephalus
 Managment
 Women 3-8 x more
o Pharmacological
 Risk factors
 Carbamazepine: reduce frequency and severity
o Smoking
o Surgery: for patient refractory to medical therapy
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  Decompression of region of trigeminal root entry of impinging  Entrapment of lateral cutaneous nerve of thigh
vascular structures (not commonly done) o Passes through a tunnel formed by lateral attachment of inguinal ligament
o Percutaneous radiofrequency ablation of portion of trigeminal ganglion and ASIS
o Anaesthetic blocks of trigeminal ganglion o Entrapment occurs ually when crossover into thigh

Subcuate combined degeneration of cord **MUSCLE/NMJ**

 Caused by vitamin B12 deficiency Myotonic dystrophy
 Investigations  Clinical features
o Vitamin B12 levels o Frontal balding, myotnia, cataracts, wasting of SCM, dysphagia, muscle
o Megaloblastic anaemia weakness
 Causes  Inherited in AD fashion, usually presents in 3rd – 4th decades
o Pernicious anaemia  EMG: waxing and waning of potentials (dive bomber effect)
o Crohn’s disease
o Post-gastrectomy Inclusion body myositis
o Atrophic gastritis  Most common acquired myopathy after 50yo
o Vegan diet  More common in men
o Blind loop syndrome  Clinical features
 Management o Selective muscle involvement with wasting
o Vitamin B12 replacement: hydroxocobalamin injections  Weakness of quadripces and long finger flexors
o Asymmetrical involvement of muscle
Refsum’s disease  Rate of progression slowly than polymyositis or dermatomyositis
 Autosomal recessive disorder that causes a sensorimotor peripheral neuropathy  Investigations
 Caused by defective alpha oxidation of phytanic acid leading to accumulation in o Elevated CK, around 1000 (not as high as PM or DM)
tissues o EMG
 Phytanic acid present in wide variety of foods including dairy products, fish, beef and o Muscle biopsy
lamb  Management
 Onset of disease normally in late teens or 20s o Less responsive to immunosuppressants
 Neurological features include
o Sensorineural deafness Hereditary spinal muscular atrophies
o Anosmia  Autosomal recessive disorders characterized by progressive LMN weakness
o Cerebellar ataxia  Progressive loss of AHC in spinal cord and CN nuclei
o Pes cavus  Type 3: chronic juvenile
o Night blindness, visual problems occur 2’ retinitis pigmentosa o Symptoms appear after 18 months of age
o Cardiac conduction abnormalities and cardiomyopathies o Normal life expectancy
o Epiphyseal dysplasia -> characteristic shortening of fourthe toe o Near normal motor function except mild proximal lower limb weakness
 Serum phytanic acid levels are elevated o Bulbar palsy can occur late in disease
 Treatment
o Dietary restriction of food containing phytanic acid Gentamicin induced neuromuscular blockade
 May rarely be associated with both peripheral muscle weakness and central
Meralgia paraesthetica neurological effects including

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 o Confusion, drowsiness, hallucinations o Paraneoplastic -> antibodies
 Amyphiphysin
Botulism  Gephysin
 Caused by neurotoxins produced by anaerobic spore forming bacterium Clostridium
botulinum Cataplexy
 Binds irreversibly to presynaptic membranes of peripheral neuromuscular and  Abrupt loss of voluntary muscular function and tone
automomic nerve junctions  Provoked by emotional stimuli
 Toxin binding blocks Ach release, resulting in weakness, flaccid paralysis and often  Rarely found in isolation, found in 70% of individuals with narcolepsy
respiratory arrest  HLA DQB1*0602 in 95% of patients with both narcolepsy and cataplexy
o Also has autonomic features: vomiting, abdominal pain, dry mouth
 Onset of symptoms occurs between 2h to 8 days after ingestion Diabetic amyotrophy
 Clinical features  More common in T2 than T1
o Descending symmetrical flaccid paralysis o Partially immune driven, associated with periods of inadequate glucose
o CN palsies control and may be precipitated by period of rapid improvement in glucsove
o Respiratory muscles involvement levels
o Autonomic signs: dry mouth, fixed or dilated pupils  Clinical features
o Diarrhea, nausea and vomiting o Weakness and wasting limited to proximal muscle
 After neuro signs -> constipation occurs o Sensory loss minimal
 Causes: food borne, wound infection (IVDA)
 Diagnosis Lambert-Eaton myasthenic syndrome
o Toxin in blood/urine/stools  Occurring in context of paraneoplastic syndrome, more often in patients with oat cell
o NCS/EMG: incremental responses to repeated nerve stimulation carcinoma of lung/breast/prostate/stomach/rectum/lymphoma
o Can cause false positive Tensilon test  Characterized by temporary increase in muscle power during first few contractions
 Management o Followed by increasing weakness after exertion
o Supportive until effect of toxin has worn off  Muscles of pelvic/shoulder girdbles and trunk become weak and fatiguable
o Botulinum antitoxin: IV  Tendon reflexes often diminished
 But ineffective once the toxin has bound to an Ach receptor side  Autonomic disturbances: dry mouth, impotence, constipation, difficulty in
o Guanidine hydrochloride: reduce neuromuscular blockade micturition, non-reactive pupils
 CN: ptosis
Stiff person syndrome  Investigations
 Persistent spams particularly of proximal LL and lumbar paraspinals -> exaggerated o NCS: repetitive nerve stimulation reveals incremental response (marked
lumbar lordosis increase in amplitude of action potential)
o Spams disappear in sleep o Antibody against VGCC +ve
 Onset insidious, usually in middle life o PET/CT scan: to detect tumour
 Males and females equal incidence  Management
 No trimus as in tetanus o 3,4 –diaminopyridine 20mg 5x/day +- pyridostigmine
 Investigations  helps to maintain depolarization of nerve terminal by preventing
o EMG: normal repolarization leading to more calcium entering nerve terminal
o Sporadic cases -> antibodies o +- IVIg, plasmapheresis, corticosteroids
 Anti-GAD o Excision of primary tumour

53
Myasthenia gravis o Procainamide (acute pulmonary failure), verapamil, quinidine, chloroquine
 Females more affected than males o Phenytoin
 Two age groups o Prednisolone
o One peak in 2nd and 3rd decade – women o Anticholinergices
o Second peak in 6th – 7th decade - men o NM blocking agents: vecuronium, curare
 Acquired autoimmune disorder characterized by weakness typically of periocular,
facial, bulbar, neck and girdle then distal limbs and trunk Acid maltase deficiency (glycogen storage myopathy type 2)
o Muscles demonstrate fatigability  Clinical features (3 types)
 Other causes: drugs (penicillamine) o Adult form: slowly progressive weakness of shoulder, pelvic girdle and
 Associated with truncal muscles, diaphragmatic weakness
o Thyrotoxicosis, hypothyroidism o Infantile form
o RA. Dematomyositis, SLE  Investigations
o DM, pernicious anaemia o Muscle biopsy: sarcoplasm is vacuolated
o Thymic tumour  Vacuoles contain PAS +ve diastase digestible material
 Investigations  Glycogen particles lie in aggregates
o EMG: abnormal jitter (variable in time interval between firing of adjacent o EM: occupy lysosomal vesicles and others lie free
single muscle fibres from same motor unit -> variation in NMJ transmission o Normal ischaemic forearm test
time)  Positive in other glycogen storage disease (e.g Cori disease,
o ≥10% decrement in compound muscle action potential amplitude is McArdle disease, Tarui disease)
observed in response to slow repetitive stimulaton in 50-70% in generaiised  Prognosis
MG o Adult form: better than infantile form
o Serum Anti-Ach receptor Ab (in the postsynaptic membrane of NMJ)  Survive until 6/7th decade
 90% in generalized, 75% in ocular
o Tensilon test: immediate improvement in muscle weakness (short acting McArdle disease (myophosphorylase deficiency)
cholinesterase inhibitor)  Carbohydrate metabolism disorder
o CXR/CT Thorax: evaluate for thymoma  Clinical features
 Management o Pain and fatigue in early exercise
o Symptom control  Carbohydrate cannot be mobilized to provide energy substrate to
 Oral anticholinesterase: pyridostigmine muscle
o Thymectomy  With prolonged exercise, fatty acid metabolism provides energy
o Immunosuppression with corticosteroids and symptoms lessen
o IVIg o Dark urine = myoglobinuria following rhadomyolysis
o Plasmapheresis  Investigations
 Exacerbated by o Biopsy
o Antibiotics: aminoglycosides, ciprofloxacin, erythromycin, ampicillin o Enzyme analysis
 Tetracyclines have NM blocking effects 2’ calcium chelation and o CK
hence impaired Ach release Kennedy disease
o Bblockers including timolol  X_linked recessive, onset around 40-60yo
o Lithim  Polyglutamine repeat expansion
o Magnesium  Clinical features

54
 o Proximal myopathy o ALS
o Bulbar muscle weakness o Progressive multiple sclerosis
o Normal sensation  Oligoclonal band synthesis in CSF only
 MRI Brain: white matter lesions tend to be periventricular
**INFLAMMATORY/DEMYELINATING**
Multiple Sclerosis Guillain-Barre syndrome
 Chronic idiopathic relapsing/remitting inflammatory demyelinating disorder that  Immune mediated attack on peripheral nerves
causes plaques of demyelination at sites throughout CNS o 2/3 post viral infection (e.g. EBV, CMV, IM, Campylobacter)
 Female 2X incidence  Clinical features
 Clinical features o Back pain radiating to LL common early presentations
o Optic neuritis o Fine paraesthesia initially
 Visual field defect, INO, abnormal pupillary responses, loss of o Ascending weakness
smooth eye pursuit  CN in 50%
o Leg weakness  Bulbar & mastication in 30%
o Numbness/tingling (posterior columns/brainstem) o Diminished tendon reflexes/areflexia
o Cerebellar symptoms: diplopia, nystagmus, ataxia, vertigo o Sensory loss, usu not profound, +- glove & stocking
o Uhthof’s symptom: exacerbation of features during hot bath  Impaired 2 point discrimination, joint position and vibration
 Investigations o Autonomic dysfunction
o MRI: white matter lesions adjacent to corpus callosum, periventricular  Sweating, labile BP, tachybradyarhythmias, bowel/bladder
region dysfunction
o CSF  Investigations
 Oligoclonal bands may be negative o LP: elevated protein (peaks in 4-6/52), acellular
o Serum oligoclonal bands o NCS: slowed conduction velocity and conduction block (due to impaired
 Management transmission along demyelinated nerves, reduction in amplitude of muscle
o Acute relapses action potential (usually unhelpful if made within first 2 weeks after
 IV steroids: speed up recovery but do not improve recovery symptoms onset)
o Chronic management  May demonstrate evidence of denervation and axonal involvement
 Beta-inteferon: reduce relapses in severe later-stage cases and can be useful for prognosticaion
 Inclusion criteria: o Anti-GM1 ganglioside (30% and represents worse prognosis)
o Diagnosis of relapsing remitting MS/secondary o Myelin protein 2 antibodies
progressive MS with superimposed relapses o MRI: enhancement of cauda equine nerve roots
o In patient with mild moderate baseline disability  Monitoring
 Azathioprine and MTX occasionally used bu efficacy less well o Respiratory function twice daily: NIV, FVC
established  FVC < 15ml/kg or 30% predicted
 Prognosis o Cardiac monitoring: autonomic instability
o Better: onset with optic neuritis, onset < 40yo, ≥1yr of first remission,  Management
female o Supportive especially respiratory
o Poorer: male, onset with pyramidal symptoms, large extent of white matter o DVT prophylaxis
lesions on MRI and clinical deterioration, progressive type o IVIg
 Types o Plasmapheresis

55
 Prognosis o Associated with URTI, surgery, trauma, radiological investigations,
o Mortality ~3% vaccination (esp. influenza, tetanus, diphtheria, pertussis)
o 15-20% left with minor residual motor deficits  Investigations usually not required unless systemic disease suspected
 Management
Chronic inflammatory demyelinating polyneuropathy (CIDP) o Analgesia and physiotherapy
 Causes of chronic demyelinating neuropathy
o CIDP **INFECTIVE**
o Paraporteinaemic neuropathies Subdural empyema
o Hereditary neuropathies (Charcot-Marie-Tooth Type 1, Refsum’s disease)  Originates from infection in frontal/ethmoid sinuses, less commonly from middle ear
 CMT: ascending weakness in intrinsic muscles of feet  Common organisms: Strep -> Staph -> E. coli -> proteus -> pseudomonas
o Drug related neuropathies: Amiodarone  Clinical features
 Management o Inattention
o 1st line: oral prednisolone or intermittent IVIg o Epilepsia partialis
o Immunosuppressants (little evidence but Azathioprine commonly used) o Meningeal irritation
o Continued focal neurological deteriorate and reduced consciounsness:
Neuroborreliosis (Lyme Disease) expanding focus of infection
 Clinical features  Investigations
o Flu-like illness and arthralgia o LP
o Rash: erythema migrans caused by tick bite (will fade 3-4/52 post bite) o MRI
o Mononeuritis multiplex: involving multiple CN  Management
 Investigations o High dose IV abx
o Lumbar puncture: lymphocytic pleocytosis, intrathecal oligoclonal band  Beta-lactamase penicillin, metronidazole, cephalosporin
production o IV lorazepam (for seizures)
o MRI: demyelinating or inflammatory disorder
 Diagnosis Bacterial meningitis
o Borrelia-burgdoferi serological testing with ELISA or IFA  5% of cerebral herniation
 Management o 30% of mortality
o Oral doxycycline x 2/52  LP: turbid or purulent CSF
 If CI, can use amoxicillin or cefuroxime o 200-300 PMN
o IV ceftriaxone used in patient with 2nd or 3rd degree heart block or serious o 0.5-2g/l protein
neurological sequelae o Glucose < 50% of blood value

Brachial neuritis Listeria meningitis

 Rare inflammatory condition affecting brachial plexus lower motor neurons  Motile non-spore forming gram positive rods/bacillus
 Clinical features  Second most common in elderly and immunosuppression and pregnant women
o Pain on shoulder palpation o Not to eat unpasturised cheese
o Severe increased pain on shoulder movement  Clinical infection often spreads to involve brain parenchyma especially the brainstem
o Right shoulder more affected than left o Meningoencephalitic picture
 Causes o Headache, meningism
o CN palsies

56
 o Meningitis o Amphotericin B + Flucytosine x 2/52
o Hemiparesis: mimicking a stroke o Prognosis
 Investigations  Prognosis
o CSF: yields an organisms <50% o Raised CSF a/w poor prognosis
 Differs from bacterial meningitis with a lower WCC and protein
 Some may resemble viral picture CMV meningitis
 Manangement  LP
o IV Ampicillin and Gentamicin o Mildly elevated opening pressure
 Rarely: Bactrim + Chloramphenicol o Clear CSF with raised protein, decreased ___
 Only ampicillin/amoxicillin in pregnant women as gentamicin is o Lymphocytic pleocytosis
teratogenic  MRI: ependymal enhancement with ventricular enlargement, cerebral atrophy
o Listeria RESISTANT to cephalosporin  Management
o Alternative: erythromycin if penicillin allergic o IV gancyclovir: induction course then maintenance therapy for life
o Steroids in paediatric
 Prognosis Aseptic meningitis
o >60% even with treatment  Inflammation of meninges caused by non-bacterial organisms or other disease
processes
Tuberculous meningitis  More common in children
 Subacute meningitis (other DDx cryptococcal, histoplasmal, partially treated  Investigations
bacterial, neoplastic, granulomatous infiltration) o LP: normal/increased pressure, clear CSF, protein 0.5-2g/L, glucose > 50% of
 Associated findings: blood levels
o CN 6 palsies or other CN palsies due to involvement of basal meninges
o SIADH Mumps meningoencephalitis
o CXR changes  Clinical features
 Investigations o LAD and parotid swelling
o Culture: 50-80% +ve o Meningitic feautures
o PCR o Headache, confusion
o LP: lymphocytic, very high protein, very low glucose o Pancreattis: elevated amylase, epigastric pain
 50% can have normal protein level, 16% can have aceelular CSF  Investigations
(HIV pateints) o LP: aseptic meningitic picture
 Management  Marginally raised protein, normal glucose, monocytosis
o 12 months of anti-TB therapy
o Obstructive hydrocephalus: surgical stenting Neurosyphillis
 Clinical features
Cryptococcal meningitis o Proprioceptive loss: difficulty walking in dark
 Investigations o CN palsies
o India Ink o Cognitive impairment
o LP: elevated opening pressure, turbid appearance to CSF, raised protein and o Autonomic dysfunction
mixed lymphocytic/neutrophil picture  Diagnosis
 Management o VDRL

57
 o Treponemal haemagglutination test o Nausea and vomiting
 Management o Non-specific rash
o High dose penicillin o Transient meningitis or frank meningoencephalitis
 DDx of single lesion causing absent ankle reflexes and upgoing planatars o 15% coma
o Syringomyelia  Diagnosis
o Friedreich’s ataxia o Serological confirmation
o MND  Management
o Conus medullaris lesion o Supportive
o Subacute degeneration of cord
o Taboparesis of tertiary neurosyphillis Progressive multifocal leucoencephalopathy – JC virus
 Infection of oligodendrocytes with JC virus – polyomavirus latent in healthy adults
Cryptococcal meningitis o When CD4 < 100, virus becomes active leading to progressive neurological
 Enters through the lungs: 1/3 patients report pneumonitis in weeks preceeding deterioration
cyptococcal infection o Occurs almost exclusively in immunosuppressed individuals
 Can also have skin lesions which resemble molluscum contagiosum  HIV, treatment w cytotoxic drugs/irradiation
 Investigation  Multiple focai of varying size
o LP: high opening pressures, elevated protein, reduced glucose o May occur anywhere but often in cerebral hemispheres
o Less in cerebellum and brainstem
Cerebral toxoplasmosis o Rarely in spinal cord
 Do not classically cause meningitis but cerebral abscesses resulting in seizures and  Clinical features: insidious onset (evolves gradually with impairment of mental
focal neurology fucntion and disturbance of speech and vision)
 Clinical features o Right hemiparesis, expressive dysphasia,
o Fever, seizures, focal neurological symptoms o Behavioural changes in clear consciousness, mental changes
 Investigations o Visual field defects
o Seropositive for Toxoplasma gondii o Ataxia/movement disorders
o Brain imaging: multiple ring enhancing lesions, thin walled cavitating lesions o Absence of fever or depressed conscious level
 Propensity for basal ganglia involvement o Progresses rapidly -> severely disabled -> demented, blind and paralysed
 Differential o Coma and death
o Primary cerebral lymphoma  Diagnosis
o TB o LP: normal except protein may be elevated slightly
o Cryptococcal disease o MRI T1 weighted: hypotense lesions, T2: hyperintense lesions +- grey matter
o Progressive multifocal leucoencephalopathy involvement with scalloped appearances
 Management o Brain biopsy: asymmetric foci of demyelination and intranuclear includsions
o Sulfadiazine & pyrimethamine with folinic acid containing JC virus
o Steroids if cerebral edema or mass effect o Viral PCR
 Management
West Nile disease o No effective treatment
 Single stranded RNA flavivirus transmitted via culex mosquito o Progressive can be slowed with HAART
 Clinical features
o Sudden onset fever and myalgia Herpes simplex encephalitis

58
 Clinical features
o Malaise, fever, headache, nausea **VASCULAR**
o Lethargy, confusion, delirium Right inferior division of MCA
 Progressive confusion, decreased consciousness and memory  Occlusion of inferior division of MCA is nearly always embolic
deficit  Non-dominant hemisphere
o Seizures, focal deficits o Apractagnosia
o Aphasia, CN deficits o Anosognosia
o Meningism o Unilateral neglect
 Investigations o Agnosis for L half of external space
o Renal impairment o Dressing apraxia
o Signs of infection o Constructional apraxia
o MRI: temporal (commonly inferomedial portion) lobe involvement with o Superior quadrantanopsia: involvement of optic radiations deep to second
early white matter involvement temporal convolution
o CT: monitoring of encephalopathic foci and cerebral edema with low density
lesions, especially in temporal lobes 3-4 days after onsent Vertebral artery dissection
o EEG: focal temporal changes or diffuse slowing, periodic complexes and  Cause: trauma/injury (blow to back of neck)
periodic lateralising epileptiform discharges  Clinical features: ischaemic of brainstem and cerebellum
o LP: mildly elevated protein, normal glucose, moderate leukocytosis +- RBC, o Lateral medullary dysfunction
PCR (remains positive up to 5 days), cortical brain biopsy  Ipsilateral facial dysaethesia, loss of taste, limb or trunk numbness
 Dysarthria, hoarseness, dysphagia
Neurocysticercosis  Vertigo
 Most common parasitic disease of nervous system  Contralateral loss of pain and temperature sensation
o Accidental ingestion of eggs of Taenia solium (not destroyed due to o Medial medullary dynsfuction (rare)
inadequate cooking) – undercooked pork  Contralateral numbness S(medial lemniscus)
 Clinical features  Contraclateral weakness/paralysis
o Epilepsy (70% of cases) o Ipsilateral Horners (1/3)
o Gradual neurological deterioration  Investigations
 Focal deficit: loss of vision in L eye o MRI Brain/MRA
 Investigations o 4 vessel cerebral angiography
o Elevated ESR  Management
o Elevated eosinophil count o Anti-coagulation: to prevent thromboembolic sequelae
o Multiple stool samples to look for ova/parasites (eggs are shed
intermittently) Carotid endarterectomy
o CT: multiple areas of parenchymal calcification, 2-3 hypodense lesions with  Beneficial in symptomatic patients > 70% stenosis of carotids
peripheral enhancement and peri-lesional edema  Increasing benefit
 Management o Male
o Symptomatic relief o Increased age
 Anticonvulsant o Increased medical co-morbidity
 Corticosteroids for cerebral edema o Prior hemispheric event
 Antiparasitic drugs: albendazole o Ulcerated plaque

59
 o Early intervention  Primary ICH: deep to white matter and specific locations: pons, basal ganglia,
cerebellum
Cerebral venous thrombosis  Cortical bleed should alert to other possibility
 Causes  >65yo, cerebral amyloid angiopathy common and can result in multiple bleeding
o Septic episodes
 Otitis media, facial cellulitis, meningitis o Association with ApOE4 genotype
o Non-septic  Younger patients: TRO underlying tumour/vascular malformation
 Pregnancy, thrombophilia, Behcet’s syndrome
 Clinical features: headache, seizures, focal signs, evidence of raised ICP SAH: subarachnoid haemorrhage
 Investigations  Characterized by history of an unusually severe headache of sudden onset: as if
o CT Brain being hit on the back of the head
 Absent delta sign: filling defect in venous sinuses  Headfrom from aneurismal rupture develops in secondas
 Aneurysm is the cause in 85%
Lateral medullary syndrome (Wallenberg’s syndrome)  Risk factors
 Infarction of lateral medulla and inferior surface of cerebellum o Familial predisposition (5-20% with positive family history)
 Deficits due to o Heritable disorders of connective tissue
o Nucleus ambiguous, trigeminal/vestibular nuclei, cerebellar peduncle, o Smoking
spinothalamic tract and autonomic fibres o HTN
o Nystagmus, ipisilateral CN V, VIII, Horner’s ataxia, dissociated sensory loss o Excessive alcohol consumption
(pain, temperature sensory loss on ipsilateral face and contralateral trunk &  ~4% occurs after sexual intercourse
limbs)  Investigations
 Vessesl involved o CT: hyperdense appearance of extravasated blood in basal cisterns
o Posterior inferior cerebellar artery o LP if CT scan –ve
o Vertebral artery  Management
o Superior/middle/inferior lateral medullary arteries o IV fluids
o Close monitoring and control of BP: SBP <130 + nimodopine
Locked-in syndrome o Surgical obliteration of aneurysm: mainstay of treatment
 Infarction of basis pontis due to occlusion of proximal and middle portions of basilar  Early clipping within 3 days of initial bleed: prevent cerebral
artery (lesion in ventral pon) ischaemia
o Disrupts corticobulbar and corticospinal pathways  Complications
o Spares somatosensory pathways and ascending neural functions responsible o Post SAH hydrocephalus: LP and KIV shunting
for arousal and wakefulness and certain mid brain elements o SIADH
 Sparing of tegmentum of pons leads to preservation of consciousness, blinking and o Symptomatic vasospasm: most commonly seen up to day 7
upward gaze
 MRI: high level of sensitivity in confirming posterior ischaemia Anterior spinal cord syndrome
 Prognosis  Ischaemic or infarction of spinal cord in distribution of ASA
o Poor with 80% mortality in acute basilar artery occlusion o Which supplies the ventral 2/3 of spinal cord
o Associated with atherosclerosis of aorta, dissection of aortic aneurysm,
ICH dissection of ASA
 Majority due to HTN  Clinical features

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 o Sparing of posterior column sensation: vibration preserved o The side most affected by PD appears to adopt
o Weakness/Complete paralysis below the levels near normal movementduring REM sleep
o Loss of pain and temperature sensation at and below level of lesion  Commonly a/w anti-psychotic neuroleptic medications
o Autonomic dysfunction  Labs
 Prognosis  Creatine phosphokinase > 60000 U/L
o Worst out of all cord syndromes  Myoglobinuria
o Good if recovery evident and progressive during first 24hr  Renal failure
o If after 24hr no signs of sacral sensibility to pinprick/temp +ve, prognosis for  Treatment
further functional recovery are poor and only 10-15% has functional  Bromocriptine 5mg TDS, up to 20mg TDS
recovery  Prognosis
 15-50% mortality
Extracranial carotid artery dissection  Treatment must be started early when consciousness is
 Clinical features first altered and temperature rising
o Neck swelling 2’ expanding haematoma  Progressive supranuclear palsy
o Ipisilateral CN palsies o Symmetrical Parkinson, postural instability, supranuclear palsy (inability of
o Ipsilateral Horer’s syndrome: compression of sympathetic chain lateral & upward gaze)
 Causes  Impaired up gaze can be seen in normal elderly but impaired
o Blunt trauma downward gaze is always pathological
o Arteriopathies (e.g. fibromuscular)  Both vertical directions become impaired before horizontal eye
o Collagen vascular disorders movements
o Pseudobulbar palsy: dysarthria and spastic tongue movements
**MOVEMENT DISORDERS** o Axial rigidity, bradykinesia
Parkinson’s disease o Postural instability with multiple falls early in disease
 Complications o Falls, dementia
o Neuroleptic malignant-like syndrome: sudden withdrawal of L-dopa o Dysphagia/dysarthria
treatment o Cognitive impairment: frontal & executive function
 Lead to an acute deficiency stage in patient who has an iatrogenic
increase of dopaminergic transmission Hemiballismus
 Symptoms  Clinical features
 Generalized rigidity o Unilateral involuntary flinging movement of proximal UL
 Hyperthermia  Lesion in contralateral subthalamic nucleus of Luys
 Stupor  Causes
 Unstable blood pressure o Elderly:
 Profuse sweating  Vascular: stroke
 REM sleep behavior disorder: associated with imperfect o Younger:
abolition of muscle tone (potentially caused by lesions in  Infectious
area of Pons) -> REM sleep atonia  Inflammatory
o Early feature of idiopathic RD  Management
o Seen to kick/laugh/punch/fight during REM sleep o Treat underlying etiology
o Rarely get out of bed and walk o Treat symptoms

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  Dopamine receptor blocking agents: suppress choreic and ballistic o Myoclonic jerks
movements o Progressive global cognitive dysfunction
 Haloperidol o Dysphasia
 Catecholamine-depleting agents o Cerebellar signs
 Tetrabenazine (when long term therapy is required) o Frontal release sign
**DEMENTIA**  Investigations
Lewy body dementia o EEG: 2/3 patients will show generalized bi or triphasic periodic sharp waves
 2nd most common cause of dementia after Alzheimer’s disease complexes with a frequency of around 1-2 per second
 Cognitive impairment with extrapyramidal symptoms  Normal electrical rhythms are gradually lost: deterioration in
 Clinical features normal background rhythms
o Progressive dementia o CSF: unremarkable, typically no inflammatory cells, total protein may be
o Parkinsonism elevated, matched oligoclonal bands in CSF and serum arise where systemic
o Visual hallucinations inflammatory response has been provoked
o Fluctuating cognitive abilities  14-3-3: normal neuronal protein, released into CSF in response to
o Executive function variety or neuronal insults
o Increased risk of falls  Needs to exclude other conditions: Herpes encephalitis,
o Autonomic failure SAD, glioblastoma
o Impairment of ability to judge distances and carry out simple actions o MRI: TRO other illnesses
o Psychosis  CJD: cerebral atrophy, signal abnormalities in anterior basal
o Significant sleep disturbances ganglia, cortex, characteristic signal change in putamen and
o Movement disorder caudate
 Differential diagnosis
o Idiopathic Parkinson’s disease Variant CJD
o MSA  Clinical features
o PSP o Rapid cognitive decline in young person
o Lead poisoning o Myoclonic jerks
 Diagnosis  Investigations
o Cortical brain biopsy o EEG: non specific changes
o Post mortem examination o MRI
 Management  Characteristic abnormality in posterior thalamic region with high
o Safe, non-threatening environment signal in pulvinar nuclei (pulvinar sign) – best seen on FLAIR
o Good caregiver sequence
o Cholinesterase inhibitors (not licensed)  Rule out other disease processes
o Tonsillar biopsy
 Rivastigmine for chronic cognitive impairmentrea
o Avoid neuroleptics: can worsen tremor and rigidity  14-3-3 protein marker
 Can also be detected in CSF
 Prognosis
 And also be associated in glioblastoma, herpes
o 6 years from diagnosis
encephalitis
Sporadic CJD
**TUMOURS**
 Clinical features
Most brain tumours are not chemosensitive
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Chemo only used specifically in cerebral lymphoma, +- anaplatic oligodendrogliomas with o Median survival 1 year
specific karyotypes, paediatric brain tumours where potential damage to developing
brain limits use of RT Carcinomatous meningitis
 Whole brain RT: multiple brain mets  5% of breast, lung, GIT, melanoma, lymphoma
 Focused RT: local advanced tumour  Clinical presentation
o Headache
Ependymomas o Sciatic pain
 T2 weighted MRI: area of intense signal enhancement o Causda equine syndrome
 Glial tumours which arise from ependymal cells in CNS o Multiple cranial nerve palsies
o Affect filum terminale: chronic back pain +- sciatica o Confusional state
 Usually of myxopapillary type o Seizures
 More common in younger male o Focal neurological deficits
 ~13% of epndymomas o Poly-rediculopathy
 Investigations
Glomus Tumour o LP
 Pulsatile tinnitus, CN 10, 11, 11 palsies  Tumour cells in CSF identified via cytospin, Millipore filtering, flow
cytometry
Glioblastoma multi-forme  May require generous quantities as tumour cells may not always be
 Most frequent primary brain tumour: 12-15% of all intracranial neoplasms seen on initial sample
 Rapidly growing tumour consisting of poorly differentiated small round cells  CSF opening pressure increased and lymphocytic pleocytosis up to
 Male 1.5x risk 100cells/mm3
 Clinical features  Elevated protein
o Slowly progressive neurological deficit or present with rapidly increasing  Low glucose (<0.6 of plasma level)ƒ
headache/seizures  Management
o Symptoms of raised ICP: headache, N/V, AMS, seizures o Intrathecal chemotherapy
o Temporal lobe signs  Prognosis
 Seizures o Medial survival 6 months
 Auditory hallucinations
 VF: superior contralateral quadrantanopia **SEIZURES**
 Wernicke-like aphasia Juvenile myoclonic epilepsy
 Spatial disorientation  One of the commonest idiopathic generalized epilepsies
 Impaired perception of verbal commands  Strong genetic predisposition, linkage to chromosome 6 in some patients
 Investigations  Starts in teenage years
o CT scan w contrast: primary brain tumour wth surrounding edema isodense  Clinical features
to surrounding brain tissue o Myoclonic jerks affecting 1 or both UL
o Biopsy: highly atypical poorly differentiated small round cells o Tonic clonic or absence seizure also noted
 Management o Usually occur in mornings, particularly on waking
o Surgical debulking – excision impossible o Intelligence NOT impaired
o Radiotherapy o Condition NOT progressive
o Chemotherapy: temozolamide (oral alkylating agent)  Precipitating factors
 Prognosis
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 o Sleep deprivation  Horizontal nystagmus (at least 20mg/l or 80mmol/l)
o Anxiety  Ataxia (at least 30-40mg/l or 120-160mmol/L)
o Alcohol  Management
o Menstruation  Within 1hr: gastric lavage/charcoal
 Investigations
o EEG: bursts of generalized 4-6Hz irregular polyspike-wave complexes Non-epileptic signs
 Management  Active resistance to eye opening
o 1st line: Sodium valproate (lifelong treatment)  Weeping, stuttering ad vocalisations during seizure episode more common
o Levetiracetam can be added as 2nd line therapy
o Carbamazepine and phenobarbitone may worsen seizures and should NOT Normal pressure hydrocephalus
be given  Triad: gait apraxia, cognitive impairment, urinary incontinence
 Investigations
Complex partial seizures o CT brain: enlarged ventricles in presence of normal sulci
 Temporal lobe origin o Large volume (20-50mls) lumbar puncture: neuropsychological testing and
o Typical aura: visual hallucination, perceptual illusion psychic illusion: deja- timed walking test performed before and after removal
vu/jamais vu  Gait is most likely to improve after shunting
o Motoer: lip smacking, chewing or gestural automatism  Management
 2/3 are prone to secondarily generalized o VP or VA shunting
 Seizures: 2-3mins followed by post ictal confusion  Factors that increase likelihood of benefit of shunting
 Investigations o Cause of NPH: meningitis/SAH
o EEG: extra scalp leads in anterior frontal and temporal region in sleep stage o Relatively preserved cognition
may up the paroxysmal discharges not seen in routine records o Large volume LP with measurable improvement in gait
o MRI: structural abnormalities such as mesial temporal sclerosis, glial scars, o Absence of vascular risk factors and no evidence of vascular disease on
porencephalic cysts, tumours, heterotopias CT/MRI
o Short progressive history
Antiepileptic drugs
 Generalized tonic clonic seizure Friedreich’s ataxia
o Sodium valproate most effective  Most common hereditary early-onset ataxia due to degeneration of a multiple spinal
 Reduced levels (60-100% in 2/7) when co-administered with cord pathway and PNS axon degeneration
carbapenem o Autosomal recessive, trinucleotide reeat disorder
nd
o 2 line: lamotrigine  Peak incident: 8-15yo
o Carbamazepine will aggravate and should NOT be given  Defect on chromosome 9
 Partial seizures with or without secondary generalization  Clinical features
o Levetiracetam o Progressive limb and gait ataxia before 25yo
 Phenytoin  Predominant leg weaknes
o Mental slowing, unsteadiness, cerebellar like syndrome o Ataxia, dysarthria
o Nystagmus o Horizontal nystagmus + decreased visual acuity
o Abnormal liver function test o Spastic paraparesis
o Toxicity o Bilateral pes cavus
 1-2hr: nausea and vomiting o Absent knee and ankle reflexes

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 o Extensor plantars  Management
o Absent position and vibration senses o IVIg
 Distal sensory loss o Cyclophosphamide
o Preserved cognition
 Investigations Homocytinuria
o ECG: widespread T wave inversion and evidence of LVH in ~65%  AR trait: aminoaciduria
o MRI: shrinkage of cervical spinal cord  Clinical features
o Tall with slender habitus
Amyotrophic neuralgia o Large arm span
 Sudden onset of pain followed by muscle wasting over the next few days o Kyphoscoliosis
 Condition improves spontaneously over a prolonged period o Arachnodactyly
 Management o Cutaneous: livedo reticularis, malar flush
o Physiotherapy o Hair: blonde sparse, brittle, ectopic lentis (dislocated downwards)
o Adequate analgesia o Mild mental retardation
o Thrombosis: platelet abnormality favouring clot formation
Narcolepsy
 Presents in teens or 20s Fabry’s disease
 Tetrad:  X-inked recessive trait
o Excessive daytime sleepiness o Enzyme alpha galactosidase A
o Cataplexy (sudden loss of voluntary muscle tone) – often triggered by o Accumulation of ceremide trihexoside in damaged viscera
emotional stimuli  Manifest in childhood or adolescence with intermittent lancinating pain of
o Sleep paralysis extremities
o Hypnagogic/hypnapompic o Evoked by vigorous exercise, hot weather or febrile illness
 Associated with DR2, DQB1*0602  Diffuse vascular involvement
 Diagnosis o Hypertension
o Multiple sleep latency test o Cardiomegaly
 Management o Renal failutre
o Excessive sleepiness: moafinil o Thrombotic infarction in different viscera
 Cutaneous
Multifocal motor neuropathy o Characteristic angiokeratomas: most prominent periumbically
 Autoimmune neropathy presenting with progressive weakness affecting isolated limb  Management
without sensory involvement o Enzymes replacement
 Clinical features
o Early: profound weakness disproportionate to wasting Von Hippel Lindau disease
o Fasciculations  Rare AD condition with carrying penetrance
o Rare: CN or respiratory involvement  Usually present at 30yo
o Depressed reflexes  Diagnosis
o Lower motor neurone treatment o Haemangioblastomas of CNS/PNS/retina /abdominal
 Associated with viscera/kidney/pancreas
o Elevated anti-GM1 ganglioside antibody in 80% o Presence of one associated VHL tumour: RCC, islet cell tumours, adenomas

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  AD disorder with 100% penetrance and anticipation
Fibromuscular dysplasia  Trinucleotide repeat disorder
 Segmental, non-atheromatous, non-inflamamtory arterial disease  Clinical features: triad
 Affects medium sized arteries in young females o Movement disorders
 Stroke  Chorea
o ICA 95%  Dystonia, myoclonus
o Vertebral 12-43%  Eye movement: slow saccades
o Intacerebral arteries o Behavioural disturbance
 Claudications limb pain  Affective
 50% depression: response well to SSRIs (1st line)
MELAS  othe rcasses or ECT used if poorly responsive/CT
 Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes  Suicide rate 5x higher
 Clinical manifestations  Psychosis: esp. paranoid delusion
o Seizures  Bipolar disorder (less common than depression)
o Transient ischaemic attacks, strokes o Cognitive impairment
o History of migraines  No curative treatment
o Glucose intolerance
o Short stature Sarcoidosis
o Proximal myopathy  Can cause basal meningitis, causing
 Investigations o Lower CN palsies
o CT Brain: cortical and immediate subcortical white matter low densities o Dry cough
o MRI: multiple cortical lesions that do no respect vascular territories but have o Optic neuritis
predominance in occipital lobes o Mononeuritis multiplex
o Myelopathy
CADASIL: cerebral autosomal dominant arteriopathy w subcortical infarcts and o Seizures
leukoencephalopathy o Granulomas: mass effect
 Arteriopathy characterized by media thickening and loss of smooth muscle o Neuropsychiatric manifestations
 Causes strokes in young migraineurs
 Absence of extra neurological features, normal lactate and rareness of cortical Restless legs syndrome
lesions on MRI imaging  Often associated with sleep disturbance
 Clinical features  Associated with
o Migraine o Iron deficiency anaemia/folate/B12/magnesium deficiency
o Personality changes: frontal lobe involvement o ESRF
o Multiple TIA o COPD
 Investigations o Gastric surgery
o MRI: periventricular and deep white matter hyperintensities on T2 weighted o CVI
scan with involvement of temporal poles o Hypothyroidism/DM/hyperuricaemia
o NOTCH-3 genetic testing: >90% have mutations o Drugs: BB, H2 antagonists, neuroleptics
o Polyneuropathy
Huntington’s disease o Parkinosim

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 o Spinal disorders o Benzodiazepines
o Rheumatoid arthritis/Sjogren syndrome o IV vitamin B
o Amyloidosis o IV fluids
 Management  Severe withdrawal is a medical emergency!
o Dopamine agonists  Prognosis
o 5-10% mortality
Gilles de la Tourette
 Dopaminergic abnormality in basal ganglia
 Clinical features
o Multiple tics
o Sniffing, snorting
o Involuntary vocalisations
o Repetitive and annoying motor behavior
o ADHD and OCD
 Management
o Dopamine (particularly D2 receptor blockers)
 Haloperidol
Wernicke’s syndrome
 Medical emergency
 Chronic alcohol excess with poor nutrition
 Clinical features
o Ataxia, nystagmus, opthalmoplegia
o Acutely impaired cognition
 Management
o IV Vitamin B
 Prognosis
o Early treatment can rapidly reverse opthalmoplegia and improve ataxia and
early mental confusion
o Advanced cases: severe prolonged deficiency has led to permanent
structural damage, permanent deficits most often manifested as amnestic
state and severe ataxia

Alcohol withdrawal
 Features develop within 10hrs and maximal at 48hrs
 Clinical features
o Hyperarousal
o Nausea
o Autonomic instability
o Visual hallucinations
 Management

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OPTHALMOLOGY  Affects Caucasians and females more
o Usually young healthy adults
o 2x increased risk in females
Herpes simplex virus conjunctivitis o History of preceding viral illness
 Red and watering eye with concomitant eyelid skin involvement with multiple
 Clinical features
vesicles in localized areas
o Rapid decline in visual acuity associated with pain exacerbated by eye
 Eyelids may be swollen
movement and dyschromatopsia (change in colour perception)
 Ulcerative blepharitis o Fundoscopy
 Discharge: clear, mucus like
 Acute: may appear normal (2/3 ON are retrobulbar)
o If yellow: usually indicates primary/secondary bacterial infection
 Chronic: pale optic disc
 Others o Investigations
o VZV: dermatomal pattern of vesicles  LP may be useful if MS is suspected
o Molluscum contagiosum: chronic follicular conjunctivitis a/w small,  MRI: assess inflammatory changes in optic nerves and exclude
elevated, umbilicated nodule near lid margin structural lesions
o Management
Molluscsum contagiosum conjunctivitis  Look for evidence suggestive of MS
 Chronic follicular conjunctivitis associated with small, elevated, umbilicated nodules  Majority of cases no treatment indicated unless
near lid margin  History of previous neuropathy or systemic systems
suggest MS
Acute iritis  Short course steroid therapy
 Usually in young people and occasionally associated with systemic conditions (e.g.
AS, sarcoidosis, Reiter’s syndrome, syphilis, herpes, toxoplasmosis, IBD, psoriatic Central retinal vein occlusion
arthropathy)  Important cause of visual impairment in middle-aged/elderly
 Clinical features  History of DM/HTN/coagulopathy/vasculitis predisposes to CRVO
o Red and painful eye  Types
o Impaired visual acuity (Not present in episcleritis or conjunctivitis) o Ischaemic haemorrhagic retinopathy
o Constricted or irregular pupil, reacts poorly to light  Marked reduced acuity at presentation
 Management  Peripheral field deficits
o Slit lamp diagnosis withtin 24 hrs  Relative afferent pupillary defect
o Topical steroids and mydriatic drops (Reduce risk of acute glaucoma due to o Non-ischaemic venous stasis retinopathy (80%)
iris sticking to cornea)  Clinical features
o Blurred vision on waking
Toxoplasma gondii chorioretinits  Fundoscopy
 Ocular toxoplasmosis: unilateral, mild ocular pain, blurred vision, new onset of o Cotton wool spots
floating spots o Blot & Flame haemorrhages
 Management
Optic neuritis
o Panretinal photocoagulation
 Demyelinating inflammation
o Intravitreal VEGF
 Strongly associated with multiple sclerosis
68
 o Local/systemic anticoagulation o Haemorahges
o Local/systemic steroids  Stage IV: stage III plus:
o Plasmapheresis o Swollen optic disc -> papilloedena
o Surgical decompression  Stage III and IV are medical emergencies -> malignant hypertension
 Complications  Isolated microaneurysms, haemorrhages, cotton-wool spots strongly a/w subclinical
o Neovascularization cerebrovascular disease -> predict clinical stroke, CCF, mortality
o Macular edema
 Prognosis Holmes-Aides Pupil
o Non-ischaemic relatively benign  Dilated
o Ischaemic type: a/w severe blinding complications  Slowly responsive to light
 Optic atrophy  Reacts normally to accommodation
 Vitreous haemorrhage  Caused by damage to post-ganglionic parasympathetic fibres
 Anterior segment neovascularization -> neovascular glaucoma  Clinical features
o Anisocoria
Posterior vitreous detachment o Blurred vision (esp from dark to light room)
 Causes
o Traction injury from new vessel formation Holmes-Adie syndrome
 Clinical features  Most commonly seen in young women
o Changes close to optic disc  Clinical features
o Flashing lights o Large irregular and sluggishly reactive pupil with absent deep tendon
o Floaters reflexes
 Management o Visual acuity and reaction to accommodation usually normal
o Photocoagulation o Dilated pupil
o Control of BP and blood glucose  Slowly reactive to light (both direct and consensual)
o Ankle reflexes absent
Hypertensive retinopathy o Plantars flexor
 Fundoscopy  DDx: interruption of efferent parasympathetic pathway
o Optic disc edema
o Cotton-wool spots Retinitis pigmentosa
o Wide spread AV nipping  Present in late childhood but AD form may present later in adulthood with preserved
o Flame shaped retinal haemorrahges vision up to 5th decade
o Hard exudate: collect around fovea producing macula star  Deterioration of light sensitive retinal cells
 Stage I: focal/diffuse thinning of arterioles relative to venules  Clinical features
 Stage II: obvious arteriolar narrowing with foa areas of attenuation o Visual disturbances
o Copper wiring o Night blindness then peripheral loss of vision
o Silver wiring o Daytime BOV: occurs late in disease
o AV nipping o Loss of central vision: seen last in late stage disease
 Stage III: stage II plus:  Retinal photograph
o Cotton wool sports o Spicules of retinal pigment accumulating in periphery
o Exudates

69
Charles Bonnet syndrome
 Clinical features
o Visual hallucinations
o In context of severe ocular disease
o Absence of other neurological impairment
 Management
o Reassurance

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PSYCHIATRY  Develops over hours with
o Characteristic hypomania,
o Drowsiness
Neuroleptic malignant syndrome o Myoclonus, ataxia, hyperreflexia
 Can occur few days of starting a neuroleptic agent o Hyperthermia, restlessness, tachycardia
o Can occur after single dose/change in dose/change in agent
o Pronounced autonomic symptoms (happy drunk state), sweating
o Common agents: haloperidol, fluphenazine depot, chlorpromazine
o Catatonia
 Clinical features o Autonomic, neuromotor, cognitive-behaviour function
o Rigidity often with severe akinesia
o Mydriasis
o Autonomic dysfunction
 Management
o AMS
o Supportive: IV fluid rehydration (mainstay)
o Fever
o Benzodiazepines for anxiety
o Dysautonomia: sweating, tachypnea, tachycardia, labile blood pressure
o Cyproheptadine, propranolol: block serotonin
 Risk factors o Blood pressure control
o Young age
o Female sex Cotard’s syndrome
o High dose escalation of neuroleptics  Belief that they have actually died and no longer exists
 Investigations
o Elevated CK, Tw Somatization disorder
 Complications  Often occurs with psychiatric disorders: depression and anxiety
o Rhabdomyolysis  Management
o Renal failure o Resolving underlying depression with combination of cognitive and anti-
 Management depressant therapy
o Mainly supportive
o Autonomic monitoring Adjustment disorder
o Aggressive cooling measures  Diagnosed when emotional or behavioural symptoms develop in response to an
 IV fluid, rehydration identifiable stressor or stressors within 3 months of onset
 Antipyretics  Must have either/both
o Bromocriptine (can be used in combination with dantrolene sodium) o Marked distress out of proportion to severity or intensity of stressory
 Dantrolene NOT to be used as monotherapy -> a/w increased o Significant impairment in social, occupation or other areas of functionin
mortality  Disturbance must not meet criteria for another mental disorder or
an exacerbation of pre-existing mental disorder
Serotonin Syndrome
 Rarely seen unless MASSIVE overdose Olanzapine
 Uncommon but potentially fatal complication of SSRI  Atypical anti-psychotic shown to be associated with increasing risk of developing
o Triggered by increased serotoninergic stimulation T2DM with increasing dose
 Especially when combined with other serotonin enhancing agents including TCA, o Related to weight gain, insulin resistance, impaired glucose tolerance
MAO-I, herbal treatment St John’s Wort (hypericum)

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Depression
 Management
o 12-18yo
 Psychological therapy ~ 3/12
 Individual CGT
 Interperonsal therapy
 Family therapy
 Psychodynamic psychotherapy
 Medical therapy only if psychological therapy fails
 SSRI: fluoxetine
o Other SSRIs should be avoided due to increased
suicide risk in this population
 Admission to adolescent unit if suicide risk high and unresponsive
to other intervention
Schizophrenia
 Management
o Atypical anti-psychotic
 Risperidone
 Clozapine (for resistant cases due to risk of agranulocytosis)
 Olanzapine (best efficacy for acute agitation, low risk of
extrapyramidal side effects at low does 5mg or less, but associated
with weight gain and metabolic dysfunction)
o Traditional anti-psychotics
 Haloperidol
 Due to extrapyramidal effects: usually NOT first line
o Benzodiazepines
 2nd line therapy after atypical anti-psychotics for significant
agitation
 Acute manic episode
o IM lorazepam effective sedation agent: 1.5mg-5mg Q4H
o IM Haloperidol as alternative
 Avoid in young women due to risk of acute dystonias
o PO risperidone
 For significant delusions and sedatives (e.g. lorazepam) unable to
control behavior
o Long term
 Carbamazepine/lithium/sodium valproate
 Lithium can increase agitation in the short term

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INFECTIOUS DISEASES o PO metronidazole or vancomycin
 Prognosis
o Significant mortality in elderly population
Meningococcal Infection
 Prophylaxis Clostridium perfringens infection
o PO Ciprofloxacin (first line)/Rifampicin (4 doses over 2 days)  Management
o IM Ceftriaxone (single dose) – choice in pregnant women o Gas gangrene: penicillin, gentamicin, metronidazole
 Management o IV benzylpenicillin
o IV Ceftriaxone immediately if suspicion high o Alternatives: chloramphenicol, clindamycin, metronidazole
 Do NOT wait for other measures or investigations  If penicillin allergic
o In penicillin allergy: IV Chloramphenicol (100mg/kg/day, max 4g/day)  Clindamycin has direct action in reducing production of CP toxin
but very high resistance
Burkholderia pseudomallei o Debridement of dead tissue
 Meliodosis  Prognosis
o Aerosolised and enter respiratory tract via inhalation or haematogenous o Recognition of infection
spread o Appropriate early intervention
o Incubation period: 10-14 days o Severe shock and myonecrosis = poorest outcome
 Clincial features
o Pulmonary: pneumonia, pulmonary abscesses and pleural effusions Toxic shock syndrome
 Endemic in Thailand  Staphylococcal exotoxin (TSST-1)
 Management o Women who use tampons
o IV ceftazidime or meropenem x 2/52 + Co-trimoxazole x 2/52  Toxin damages vascular endothelium and triggers release of vascoactive agents from
platelets and leucocytes
B pertussis o Increases vascular permeability and contribute to tissue damage
 Whooping cough  Investigations
 Vaccination is NOT 100% effective and does not confer life long immunity o High vaginal swabs
 Clinical features  Management
o Paroxysms of coughing o Removal of tampon
o Mildly elevated CRP o Anti-staphylococcal Abx: Vancomycin, flucloxacillin
o Clear CXR  Prognosis
 Investigations o 10% mortality
o Serological testing
Botulism
Clostridium difficile diarrhea  Occur due to defective canning of meat/fish
 Two toxins  Neurotoxin produced leads to
o A: enterotoxin o CNS
o B: cytotoxic -> bloody diarrhea o ANS
 Management o Respiratory muscle weakness -> ypoventilation
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 Management  Management
o ITU setting o Metronidazole
o Supportive therapy: intubation, ventilation
o Antitoxin Typhoid fever
 Prognosis  Seen in travellers returning from developing countries
o Recovery occurs between 30-100 days  Stages
o Severe cases may require ventilation for months o Week 1: pyrexia with inappropriate bradycardia
o Week 2: maculopapualr rash that blanches on pressure, LAD,
Swimmer’s Ear hepatosplenomegaly
 Pseudomonas infection o Week 3: complications (pneumonia lobar, endocarditis, haemolytic
 Severe spreading infections can occur cmonnly in patients with DM anaemia, meningitis, acute cholecystitis, osteomyelitis)
 Management  Clinical features
o Systemic and local antibiotic o Fever
o +- ENT surgical opinion o Myalgia
o Headache
Pseudomonas infection o Diarrhea/constipation
 Characteristic sweet smell o Rose spots: faint, salmon coloured, maculopapular, blanching lesions
 DM increased risk of pseudomonal skin infection  Investigations
 Management o Microscopy
o Aminoglycoside/anti-pseudomonal penicillins  GNR
o Surgical exploration +- debridement  Management
 Pseudomonas in cystic fibrosis o IV Ceftriaxone (fluoroquinolone resistance): severe disease
o Management o PO azithromycin: stable patients
 Ciprofloxacin/gentamicin o Vaccination: incomplete and short lived protecntion
 Colonized
 Nebulized tobramycin Lyme disease
 Chronically colonized  Borrelia burgdorferi, transmitted through tick bites
 6/12 PO Azithromycin  Clinical features
o Expanding skin lesion around tick bite, erythema migrans, malaise and joint
Urinary tract infection aches
 Uncomplicated UTI: PO Bactrim x 3/7 o Neurologica, cardiological, joint involvement
o Bilateral facial weakness
Bacterial vaginosis  Management
 Most common cause of abnormal vaginal discharge in women of childbearing age o Doxycycline if >8yo and non-pregnant
o Twice as common as vaginal candidiasis o Early use of antibiotics can prevent persistent, recurrent and refractory
 Caused by replacement of usual vaginal lactobacilli with anaerobic bacteria, genital Lyme disease
mycoplasma  Shortening clinical course and progression
 Risk factors
o Douching Leptospirosis
o Washing with scented soaps and gels  Prevalent in tropical climates with heavy rainfall

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 o Associated with recreational watersports and raw sewage
 Incubates for 7-12 days Prosthetic joint infection
 First phase: septicaemic/leptospiraemic  In late infection: Actinomyces (gram positive bacillus with hyphae like structures)
o CSF/Blood c/s +ve o Found in female genital tract: cause of UTI
o Flu like symptoms o Can spread haematogenously to prosthetic joints
o Then better x 3/7 o Management
 Immune/leptospiruric stage  Penicillin/Amoxillin
o Circulating antibodies/organisms in urine  Surgery
o Aseptic meningitis  Other organisms
o Haemorrhagic shock o Propionibacterium acnes (gram positive rod)
o Renal failure  Tolerates low levels of oxygenation: recognized as cause of acne
 Management and late prosthetic joint infection
o Supportive management  Management
o Doxycycline/penicillin  Penicillin
 Ceftriaxone
Infective endocarditis  Vancomycin
 Microbial infection of endothelial surface of heart  Clindamycin
 Blood cultures positive in >95%
o Incubated for up to 3/52 to grow fastidious oganisms Yaws infection
o Common organisms  Endemic in tropical areas of America, Asia, Africa and Oceania
 Staphylococcus aureus  Caused by Treponema pertenue
 Viridans streptococci  Clinical features
 Streptococcus gallolyticus o Skin lesions: papillomatous
 Nutritional variant strains: granulicatella spp, Abiotrophia  Sores over shins
defective  Investigations
 HACEK: haemophilus, aggreatibacter, Cardiobacterium hominis, o TPHA +ve
EIkenella spp, Kingella kingae  Management
 Community acquired enterococci o Penicillin
 Management
o Triple therapy antibiotics: gentamicin, rifampicin, vancomycin Weil’s disease
o Indications for surgery  Clinical features
 Development of mod-severe heart failure due to valve dysunfction o Fever, headache
 Partial dehiscence of prosthetic valve o Dry cough
 Persistent bacteremia despiste appropriate antibiotics o Joint pains
 S. aureus/fungal prosthetic valve endocarditis o Nausea/vomiting
 Persistent fever for 10/7 in culture negative prosthetic valve o Jaundice
endocarditis with no other explanation for fever o Epigastric tenderness
 Absence of effective antibiotcs o Bruising
 Relapase of endocarditis after optimal antibiotics  Investigations
 Perivalcular extension of infection o Anaemia with leukocytosis
 Poorly responsive S. aureus endocarditis involving AV/MV
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 o Thrombocytopenia o Night sweats
o Abnormal LFT o Neuropsychiatric symptoms
o AKI o PUO
o Leptosira serology o Hepatosplenomegaly
 Management o BM suppression
o IV penicillin  Investigations
o BM aspiration and culture
Tetanus o Blood cultures (≥4/52 of incubation)
 Clinical features o Serum agglutination
o Increased tone and muscle spams o Elevated CRP
 Investigations  Management
o Inflammatory: increased WCC, CRP o 6/52 of doxycycline with streptomycin/rifampicin
 Management o Quinolones
o Supportive o Treatment failure due to inadequate duration –> chronic disease
 Intubation, ventilation
 Diazepam for muscle spams SEXUALLY TRANSMITTED DISEASES
o IV anti-tetanus immunoglobulin **HIV**
o Wound debridement: but can cause release of further tetanus toxin into Antiretrovial therapy
circulation  Zidovudine
 AVOIDED UNTIL human tetanus immunoglobulin given, delay of o S/E: fat redistribution, insulin resistance
few hours may be needed  Stavudine
 Can given Abx in the meantime: Benzylpenicillin, metronidazole o S/E: proximal tubular dysfunction/Fanconi syndrome
 NRTI: reduce vascular responsiveness to acetyl choline -> endothelial dysfunction
Mycobacterium leprae  Mitochondrial dysfunction from HAART -> decreased myocardial contractility
 Clinical features o Cardiac myocytes utilitise energy less leading to decreased EF and dilative
o Hypopigmented cutanoues lesions CMP
o Decreased sensation  Abacavir
 Investigations o S/E: acute interstitial nephritis
o Skin biops: granuloma formation, neuriris, presence of acid-alcohol fast  Nelfinavir/Inidinavir
bacilli o S/E: renal colic
o Lepromin test: resistance to M Leprae
o Serology & PCR Acute HIV Infectious
 May be negative in early disease  Clinical features
o Lymphatics: persistent LAD
FARM RELEATED INFECTION o Skin: shingles
Brucellosis o GIT: oral thrush, oral hairy leukoplakia
 Cattle in Mexico -> ecdemic, Portugal o GUT
 Small slow growing intracellular organism -> chronic granulomatous disease o Bone marrow: anaemia, thrombocytopenia
 Clinical features o Nervous system
o Bone pain/Joint pains o Secondary OI

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 Investigations o Anaemia
o P24 antigen +  Management
o HIV RNA+ve o CD4 count below 50 should receive prophylaxis: clarithromycin
o Triple antibiotics in HIV patients
HIV seroconversion illness  Clarithromycin, ethambutol, rifabutin
 1/3 develop clinical seroconversion illness, usually occurs 6-8/52 after primary
infection Cutaneous disorders
 Clinical features  Eosinophillic folliculitis
o Similar to glandular fever o Most common papular pruritic disorders in HIV infection
o Fever, malaise, rash, sore throat, diarrhea, LAD, meningo-encephalitis, o Investigations
arthralgia  Biopsy: mixed infiltrate of mainly eosinophils with some
o Maculopapular rash neutrophils
o CNS symptoms  Occurs when CD4 < 300
 Investigations o Management
o Negative HIV antibody test  Resistant to most treatment but HAART improve
o P24 antigen  Topical steroids
o HIV rNA-PCR  Antihistamines
o CD4: may hard marked early decline  Systemic antibiotics
 Phototherapy
AIDS Cholangiopathy
 Result of inflammation of gallbladder and biliary tree Genital Warts
o Acute acalculous cholecystitis -> papillary stenosis -> sclerosing cholangitis  Management
 Usually a/w CMV but can be a/w cryptosporidium or microsporidium o Podophyllin ointment
 Clinical features o Imiquimod
o Spiking temperature o Trichloroacetic acid
o RUQ pain o If extensive/recalcitrant
o Abnormal LFTs  Cryotherapy
 Investigations  Electrocautery
o US Abdo  Laser ablation
o CT Scans
Chlamydia trachomatis
o MRCP/ERCP
 Lymphogranuloma venereum: systemic disease caused by one of three invasive
 Management
serovars (L1, L2, L3)
o Endoscopic sphinceterotomy (but liver function usually fails to improve)
o Clinical features
o Treatment of associated infections
 Proctitis with PR bleeding, mucus, tenesmus and rectal pain, a/w
LAD
Mycobacterium avium intracellulare
 Can be severe causing fistulas (mimick Crohn's dosease)
 Clinical features
o Investigations
o Hilar/abdominal LAD
 Positive Chlamydia serology
 Investigations
 Isolation of Chlamydia trachomatis from infected site or histological
o CXR: pulmonary infiltrates
identification in infected tissue
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 o Management  Meningovascular syphilis
 Azithromycin: safe in pregnancy and its single dose  Cardiovascular syphilis (usually 10-25yrs after original inoculation)
 Alternative: Doxycycline  Asymptomatic aortitis
Gonorrhea  AR
 Management  Aortic aneurysm
o Screen for other STDs  Late latent
o Pregnant women:  Jarisch-Herxheimer reaction
 Single dose IM ceftrixzone 500mg o 50% in primary syphilis
 Single dose PO azithromycin 1g o 90% in secondary syphillis

Sexually acquired reactive arthritis (SARA) Non-gonococcal urethritis

 Symptoms developing within 30 days of unprotected sexual intercourse and mean  Caused by Chlamydia in 60% of cases
lag of 14 days between symptoms of urethritis and joint symptoms  Other organisms: Ureaplasma urelyticum, Mycoplasma hominis
 Clinical features  Non-infective causes:
o Conjuctivitis/iritis o Heavy alcohol consumption
o Dysuria o Antiseptics: clean urethra
o Spondylitis o Post-vigorous sex/masturbation
o Arthralgia  Investigations
 Investigation o Microscopy: no gonococci seen
o Knee tap >5 PMN cells/HPF  Management
o Azithromycin
Syphillis o Doxycycline
 Primary
o Clinical features HSV infection
 Primary chancre at site of inoculation  Management
 Painless (2-3/52 to heal) ulcer w rolled edges o If ≥6 episodes yearly: for prophylactic treatment
 Associated inguinal LAD  3/12 oral acyclovir with aim of suppression
o Investigation o For treatment : acyclovir (5x/day) or valacyclovir (2x/day)
 EIA IgM
o Management Genital ulcers
 Single dose IM Benzylpenicillin  Differentials
 Alternative: 2/52 doxycycline, single azithromycin, erythromycin o Genital herpes: most common cause of multiple shallow ulcers
 Secondary o Syphillis
o Clinical features o Chancroids: Haemophilus ducreyi
 Generalized symmetrical rash  Primary genital herpes
 Condylomata lata o Clinical features
 Painless generalized LAD  Flu-like symptoms
 Constitutional symptoms  Inguinal LAD
 Tertiary  Urethral discharge
o Clinical features  Urinary rentention
 Neurosyphillis
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 o Investigations
 HSV PCR Parvovirus infection
 Cultures: often give false –ve results  Investigations
 Haemophilus ducreyi o Anaemia without reticulocytosis
o Chancroid infection o Red cell aplasia on BMA
o Endemic in Caribbean basin, Africa, South-WEst Asia o PCR B19 DNA
o Commoner in non-white uncircumscribed populations  Management
o Clinical features o IVIg
 Single or multiple genital ulcers
 Painful lymphadenopathy in 40-60% CMV infection post -enal transplant
o Investigations  Recipient –ve, donor +ve
 Gram stain: 'school of fish' collection of short, thick GNR  Symptom can appear any time from 6-60 days after surgery
 Culture on enriched chocolate agar (diagnostic)  Clinical features
 Screened for other diseases TRO co-infection o Pyrexia
o Management o Flu like symptoms
 Macrolides o Infectious mononucleosis
 Quinolones  Management
o IV Ganciclovir
VIRAL INFECTIONS  Complciations
Hepatitis A o Accelerated failure of transplanted kidney
 Incubation period: up to 6 weeks
 Clinical features E coli
o Flu-like prodromal illness then icteric illness  Management
 Transmission o Supportive therapy
o Anal intercourse o Not for antibiotics or steroids
o Enteral transmission  ABx increses risk of microangiopathic disease
o Parenteral transmission
 Management PROTOZOAN/FUNGAL INFECTION
o Post-exposure prophylaxis: Hepatitis A vaccination, Immunoglobulin Visceral leishmaniasis
 2 weeks of exposure to an infected individual  Southern Europe: Leishmaniasis infantum
 Clinical features
Epstein Barr virus o Hepatosplenomegaly due to extra medullary production of phagocytic WBC
 Clinical features o LAD
o Oral hairy leukoplakia: painless white patches affecting lateral borders of o Darkening of skin
tongue o Diarrhea
 Due to reactivation of EBV in immunosuppressed patients o Intermittent fever, weight loss, night sweats
 Investigations  Investigations
o EBV demonstrated in epithelial cells with immunohistochemical staining o Pancytopenia
 Management o Raised globulins
o HIV testing and treatment o Direct agglutination test
o No specific therapy required for oral hairy leukoplakia
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 o Ks30 dipstick  Often seen in East Africa
o ELISA testing  Clinical features
o Culture (splenic/BM/hepatic) o Urinary symptoms
 Management o Katayam fever (more frequent with S mansoni and japonicum)
o Sodium stibogluconate  Hepatomegaly, cough, wheeze, fever
o Amphotericin B
Malaria
Cutaneous Leishmaniasis Plasmodium vivax malaria
 Caused by Leishmania tropica minor  Clinical features
 Reservoir is dog o Slowly progressive diease
 Urbanareas of Middle East, Mediterranean, India, Pakisatan, Africa o Anaemia, thrombocytopenia
 Clinical features o Nephrotic range proteinuria
o Cutaneous: chronic dry lesion, rarely ulcers o Hepatosplenomegaly
 Investigations  Management
o Dental scrapings o Chloroquine
 Management o Primaquine to prevent recurrence
o Antimony-based drugs Falciparum malaris
o Amphotericin B  Management
o Ketoconazole o IV artesunate (for severe malaria)
o IV quinine if artesunate unavailable
Schistosomiasis
 Caused by trematodes: Schistosoma Babesiosis
o Infect freshwater snails -> release cercariae (fork-tailed 1mm long 1mm long  Tick borne malaria like illness -> intraerythrocytic protozoan Babesia
free swimming larvae -> survive up to 48hr – must attach to human o Endemic in Long Island, New York, Massachusetts, Nantucket, Martha’s
skin/host mammal or will die) Vineyard
o Migrate through skin to dermal veins then to pulmonary vasculature to  Patients without spleen has a more fulminant, prolonged course with overwhelming
systemic circulation to portal veins infection and fatal outcome
o Mature and mate and produce eggs  Clinical features: similar to malaria
 Clinical features o Fever, chill, rigors
o Acute: urticarial: react to antigenic eggs  Investigations
o Serum sickness: rashes, pruritus, arthralgia, fever, LAD, malaise, HoTN, o Haemolytic anaemia (organism destroy RBC)
splenomegaly, glomerulonephritis, proteinuria, haematuria, shock o Haemoglobinuria
o Night sweats, fever, arthralgia o Hypergammaglobulinemia (b lymphocyte response with secondary reactive
o Hepatosplenomegaly, RUQ tendnerness, bloody diarrhea polyclonal)
 Investigations
o Eggs in stool/urine Hookworm infection
 Management  Helminth nematode: NEcator americanus and Ancylostoma duodenale
o Praziquantel  Infection occurs when larvae invade exposed skin
o Supportive therapy  Clinical features
Schidtosomia haematobium o Intestinal blood loss

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 o Eosinophilia  Stage 4: atonic esophagus
o Microcytic anaemia o Large increase in esophageal volume, atonie and elongated esophagus
 Management  Management
o Proper sanitation and footwear o Benznidazole
o Single dose albendazole 400mg or mebndazole 500mg
Hepatic amoebic abscesses
Strongyloides  Single masses in R liver lobe
 Infection may be chronic o Swelling and migrate upwards, causing elevated right hemidiaphragm
 Symptoms can occur many years after infection  Clinical features
 Clinical features o High swinging fever
o Severe watery diarrhea o Sweats
o Abdominal pain, bloating o RUQ pain and tenderness
o Dry cough, SOB o Raised WCC
o Recurrent rash o LFTS NAD but mechanical obstruction can occur
o Heart burn  Investigations
 Investigations o CXR: elevated R hemidiaphragm
o Anaemia of chronic disease o CT/US abdomen: isolate abscess particularly in right lobe
o Eosinophilia o Serology: 95% +ve but can be past or present infection
o Larvae in stool o Stool: entamoeba histolyrica, blood and pus cells
o CXR: patchy pulmonary infiltratres o Stool antigen
o Serology  Management
 Management o PO Metronidaole x 10/7
o Ivermectin o Aspiration if no improvement after 72hrs
o HIV patients
 Repeated courses of thiobendazole/albendazole may be required Katayama fever
 a/w liver toxicity  Occurs 4-6 weeks after infection (thought to coincide with initial egg release)
 Ivermectin can be used as alternative o High worm and egg stimuli are thought to lead to immune complex
formation and a serum sickness type illness
Chagas disease: Trypanosoma cruzi  Investigations
 Stage 1 disease o Stool sample
o Normal esophageal diameter o Serology (but does not differentiate between acute or previous illness)
o Minimal contrast retention  Management
o Presence of residual air column above contrast o Praziquantel
 Stage 2: moderate esophageal enlargement with motor incoordination
o Moderate dilatation with some contrast retention VACCINATIONS
o Uncoordinated motor activity Live vaccines
o Relative hypertonicity of inferior third  Varicella zoster
 Stage 3: hypotonic and large achalasic esophagus  BCG
o Large increase in diameter and substantial contrast retention  Yellow fever
o Weak or absent motor activity  MMR

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 Oral Polio

Toxoid/Inactivated
 Tetanus
 Hepatitis A
Hepatitis B
 Influenza
 Pneumococcal

Sporadic Creutzfeld-Jakob Disease

 Prion disease: diseased form of prion proteins mainly in beta sheet structure (normal
= alpha helix structure)
 Peak incidence in 7th decade of life
 Clinical features
o Rapidly progressive dementia from few weeks to 2 years
o Cerebellar ataxia
o Pyramidal & Extrapyramidal
o Myoclonus
 Investigations
o Definitive diagnosis: post mortem

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RENAL MEDICINE Primary hyperoxaluria
 Causes
o Increased dietary intake
IgA nephropathy/Berger’s disease/Mesangioproliferative GN o Malabsorption
 Disease of young adults o Inherited enzyme deficiency -> excessive metabolism of oxalate
o Common in Far East: a/w high incident of HLA DQW7 haplotype
 3 types
 Commonest cause of GN o I & III: enzyme defect in liver glyoxalate pathway
o Thought to occur due to exaggerated immune response to viral/other  I: most common and results in widespread calcium oxalate
antigens deposition throughout body
o May follow after respiratory/GIT infection o II: failure of reduction of glyoxalate to glycolate
 Clinical features  Management
o Young male with asymptomatic persistent microscopic haematuria or o Increase urinary pH for oxalate to be more soluble
episodic macroscopic haematuria o Administer citrate and magnesium supplement
 Usually a/w URTI
 Prognosis
o Proteinuria
o Renal insufficiency common
o 5% nephrotic
o Often require combined liver/kidney transplant in type I
o Precipitated by infections
o Recovery rapid between attacks Chronic malarial infection
 Investigations  Plasmodium malariae may be a/w membranous GN
o Biopsy: focal proliferative GN with mesangial IgA deposits  Falciparaum malarial: blackwater feverom
o IgA elevated in 50% o Massive hemolysis, black urine, renal failure
 Management o Management
o Aggressive control of HTN, with ACE-I as main agent  IV quinine
o Corticosteroids to manage rising Cr/proteinuria
 Prognosis Genitourinary TB
o Good in patients with normal BP, kidney function and absence of  Develops in approximately 5% of pulmonary TB, usually due to haematogenous
proteinuria at presentation spread to renal cortex during primary phase of infection
o 20% develop renal failure 20 years from diagnosis o Cortical lesion may then ulcerate into pelvis, involving bladder, seminal
vesicles and prostate
Hyperkalemia  Presents in 20-40years old
 Cardiotoxicity  Clinical features
o Peaked T waves o Haematuria
o PR prolongation o Urethral strictures
o QRS widening o Cold abscesses
 Management o Chronic epididymo-orchitis
o IV Calcium gluconate: stabilizes nerve and muscle membrane excitation o Renal failure: extensive destruction of kidneys or obstruction 2’ fibrosis
o Nebulized salbutamol, insulin and dextrose: reduction in serum potassium  Investigations
o IVU
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 o US  Hyperchloraemic, hypokalaemic metabolic acidosis
o CT scan  Urinary pH > 6 and increased urinary calcium excretion
o In combination with several early morning urine samples for TB culture  History of dry mucous membrane (suggest Sjogren’s syndrome)
 Management  Compensated metabolic acidosis with relatively high urinary pH and low potassium
o Same as for pTB o Unable to acidify urine
 Clinical features
Diabetic nephropathy and pregnancy o Recurrent UTI
 Worsening renal function in up to 45% of pregnant patients with pre-existing o Urinary calculi
nephropathy  Management
 Worsening HTN strongly a/w degree of renal progression o Correction of hypokalaemia
 Generally poorer prognosis during pregnancy is associated with lupus as underlying o Then oral bicarbonate supplementation
cause of renal impairment Type 2 (proximal)
 Hypokalemia metabolic acidosis
Liddle’s syndrome  Failure of proximal tubular cells to reabsorb bicarbonate
 Young hypertension with profound hypokalemia, alkalosis, suppressed renin and Type 4
aldosterone  Hyperkalaemic metabolic acidosis
 Rare AD condition: mutation in highly selective epithelial sodium channel in distal  Deficiency/resistance of aldosterone
nephron
o Sodium retention independent of mineralocorticoid activity Laxative/diuretic abuse/bulimia
 Hypokalaemic metabolic alkalosis
Gitelman’s syndrome  Laxative abuse
 Sporadic or AR condition o Methycellulose: bulk forming laxative
 Hypokalaemic metabolic alkalosis, hypomagnesaemia, hypocalciuria  Must be taken with adequate fluids
 More severe than Bartter’s and present earlier o Sodium docusate: stool softener and bowel stimulant
 Clinical features o Lactulose: osmotic laxative
o Low-normal BP o Senna/Dantron: Anthraquinone stimulant laxatives
o Low urinary calcium excretion (if > 6.9mmol/24hr, more likely to be  Associated with melanosis coli
Bartter’s) o Investigations
o Muscle cramps and severe fatigue fro hypoK and hypoMg  Urinary concentration of K < 1mmol/L
 Managmenet  Hypokalemia
o K+ and Mg2+ supplements
 Prognosis Alport’s syndrome
o Very good!  X-linked dominant inheritance (85%)
o Women usually present with milder and later onset disease
Bartter’s syndrome  Clinical features
 Usually presents in childhood due to failure to thrive o Nephritis causing microscopic haematuria and progressive renal failure with
 Hypokalaemia and hypotension episodic frank haematuria
o Ocular pathology: corneal ulcerations, bilateral anterior lenticonus, bilateral
Renal tubular acidosis dot-fleck marks around fovea
Type 1 (distal) o Progressive high frequency sensorineuronal deafness
 Failure of alpha intercalated cells (collecting tubules) to secrete H+ and reclaim K+
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 Investigations  Investigations
o LM: unremarkable o Elevated creatinine
o EM: focal, segmental glomerulosclerosis, interstitial fibrosis, tubular o Peripheral blood eosinophilia
atrophy, infilatration of lymphocytes and plasma cells o Urine: red cells, protein and white cells
 Management
HIV-associated nephropathy (HIVAN) o Discontinuation of causative agent
 Clinical features o High dose prednisolone may help in acute situation
o Nephrotic range proteinuria  Prognosis
o Normal BP o Slow recovery over 6/52 is possible
o Tend to occur exclusively in black patients o 40% may also progress to CRF
o Loss of weight
 Investigations Chronic interstitial nephritis
o Lymphopenia  Causes
o Normal or increased kidney size on US o Long term use of NSAIDs
o Biopsy: collapsing variant of secondary focal segmental glomerulosclerosis  Investigations
 Management o CT: papillary microcalcification
o Aggressive ART  Management
o ACE-I o Withdrawal of offending agent
o Aggressive control of BP: ACE-I/ARB first choice
Acute tubulointerstital nephritis  Prognosis
 Clinical features o Some may require RRT
o Arthralgia o Increased risk of urothelial malignancy
o Skin rashes
o Fever Diabetic glomerulosclerosis
o Renal failure  Investigations
 Caused by o Biopsy: mesangial expansion with Kimmelstiel-Wilson nodule
o Drug reactions  Management
 NSAIDs o ACE-I: improve albuminuria by reduction in glomerular capillary pressure
 Abx: penicillin, sulphonamides, cephalosporins, rifampicin,  Inhibit production of angiotensin II
quinolones  Reduce metabolism of bradykinin (vasodilator)
 Allopurinol
 Phenytoin Chronic glomeurolonephritis
 Investigations  End stage condition of all forms of acute GN and affects majority of glomeruli
o Eosinophilia  Investigation
o Urinary eosinophils o Biopsy: different degrees of hyalinization and eventual hyalinosclerosis (all
o Raised IgE glomeruli and Bowman’s space replaced by hyaline)
 Hyaline = homogenous, amorphous pink material
Acute interstitial nephritis  Glomeruli that are hyalinised are atrophic and non functional
 Causes  Abundant inflammatory infiltrate mainly of lymphocytes in
o Drugs: sulphonamides, penicillins, cephalosporins, diuretics, NSAIDs interstitial tissues

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  Remaining functional nephrons have dilated tubules o Fluid intake: 2-3L/day
o Control BP
Membranous glomerulonephritis  Prognosis
 20-30% of adult nephrotic syndromes, a/w underlying malignancies in 10% o 25% has full recovery of renal function
 Other causes: drugs (NSAIDs, gold, penicillamine), AI (SLE), infections (Hepatitis)
 1/3 will progress to ESRF within 10-20ys of diagnosis Membranoproliferative glomerulonephritis
 Recurrence rate post transplant ~ 30%  Associated with 30-90% recurrence rate post renal transplant
 Clinical features o Type 2 > type 1
o Pitting edema
o Frothy urine Post-streptococcal glomerulonephritis
o Marked proteinuria, low albumin  Clinical features
 Investigations o 1-2/52 after strep throat infection
o LM: capillary loop thickening, normal architecture o Nephritic picture
o Biopsy: subepithelial IgG deposits with staining for antibodies to o Edema
phospholipase A2 receptor  Management
 Management o Diuretics
o Restrict sodium and start diuretics (control edema & blood pressure) o ACE-I
o Anticoagulation (increased risk of thromboembolism due to nephrotic
syndrome – loss of anti-thrombin II and underlying malignancy) Goodpasture syndrome
o Chlorambucil  Circulating anti-GBM antibodies in blood with linear deposition in glomerular
o Cyclophosphamide basement membrane resulting in rapidly progressive cresentic glomerulonephritis
and pulmonary hemorrhage
Analgesia nephropathy  Often occurs in young men
 Chronic tubule interstitial nephritis with papillary necrosis 2’ prolonged heavy use of  Clinical features
compound analgesia o Severe haemoptysis
o Drugs: NSAIDs, codeine o Dyspnea
 Usually in females (2x risk), middle aged, depressed and neurotic o Rapidly progressive renal failure
 Investigations o Anaemia
o IVU: bilateral clubbed calyces, ring signs o Haematuria, proteinuria
o Microscopy: casts, renal papillae, cells, leukocytosis  Investigations
o Biopsy: interstitial fibrosis, tubular atrophy o Anti-GBM
 Complications o CXR: bilateral asymmetrical shadowing of pulmonary haemorrhage
o AKI/CRF  Management
o HTN o Pulse methylpred
o Increased risk of uroepithelial tumours o Cyclophosphamide
o Urinary tract obstruction (2’ sloughing of renal papillae) -> recurrent o Plasma exchange
UTI/sterile pyuria
o Salt losing nephropathy Granulomatosis with polyangiitis/Wegener’s
 Management  Necrotizing granulomatous arteritis of upper and lower respiratory tract and kidney
o Withdrawal of drug  Rare, incidence of 5-10/million

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 Clinical features o Long term anticoagulation
o Lung 95%: sinus congestion, epistaxis, pulmonary haemorrhage, SOB, o More aggressive if bilateral: including thrombolysis
haemoptysis
o Renal 85% Thrombotic thrombocytopenia purpura
o Eye  Occurs more in adults
o Skin: splinter haemorrhages  Clinical manifestation
o Joints: pain o CNS: confusion, coma
o Heart o Myocardial damage
o CNS  Management
 Investigations o Plasma exchange
o ANCA +ve in > 90%  a/w reduction in mortality rate to < 25%
o Anaemia with leukocytosis, thrombocytosis o FFP (interim solution until plasma exchange available)
o CXR: granulomas o No role for steroids/antibiotics/IVIg
o Nasal/URT mucosa biopsy o Platelet transfusion CONTRAINDICATED unless life threatening haemorrhage
o Lung/Renal biopsy  Prognosis
o LFT: raised KCO (pulmonary haemorrhage) o Worse as compared to HUS
 Management
o Steroids Haemolytic uraemic syndrome
o Cyclophosphamide  Usually in childhood or old age
o IVIg in severely ill  Presents with AKI following diarrhoeal illness
o IV rituximab: in patients resistant to treatment o Strong association with verotoxin producing E. coli 0157
o Renal o Shiga toxin producing bacteria – Shigella dysenteria
 Plasama exchange in Cr > 400  Characterized by widespread deposition of loose strands of fibrin in multiple small
 Dialysis blood vessels which damage platelets and RBCS (also seen in TTP)
 Prognosis o Results in microangiopathic haemolytic anaemia, DIC and thrombocytopenia
o Remission in up to 90%  Clinical features
o If untreated, 1 yr mortality 80% o Microangiopathic haemolysis with thrombocytopenia
 Fragmented red cells
Renal vein thrombosis o Acute kidney injury
 Clinical features o Fever
o Silent with gradual worsening renal impairment o CNS: confusion, coma
o Acute renal impairment o Jaundice
 Investigations  Investigations
o Doppler ultrasound of renal veins o Stool culture
o CT o Blood film: fragmented and deformed red cells (acanthocytes, schistocytes,
o MRI burr cells, helmet cells)
o Venography  Monitoring
 Management o LDH can help in monitoring treatment efficacy
o Mobilization  Management
o Avoidance of volume depletion o FFP

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 o Plasma exchange (especially if neurological involvement or oligo-anuric)
o PCT should NOT be transfused if Hb < 6 or Hct < 18% Cardiac amyloidosis
 But to aim HB 8-9 to prevent cardiopulmonary complications 2’  Occurs in light chain (AL) amyloidosis and hereditary amyloidosis, rarely in secondary
high output cardiac failure amyloidosis
o Steroids  Clinical features
 Prognosis o Restrictive CMP
o < 10% mortality with good supportive care  RHF
o Systolic dysfunction in advanced stages
Amyloidosis o Postural hypotension: poor ventricular filling or autonomic neuropathy
 Accumulation in various tissues of deposited insoluble protein that impairs normal  Investigations
function o ECG: low voltage
 Two major types of protein o Echo: thickened ventricular walls, dilatation of atria, thickened interatrial
o Light chain AL in primary amyloidosis and myeloma associated amyloidosis septum, diastolic dysfunction, small volume ventricles
o Non-immunoglobulin protein AA in 2’ amyloidosis (a/w chronic diseases: TB,  Sparkling granular appearance of myocardium
bronchiectasis, OM, RA, FMF, Hodgkin’s disease)
 Associations Familial renal amyloidosis
o Systemic inflammation: RA  Clinical features
o Haematological malignancies: meyloma o Hepatosplenomegaly
 Clinical features o Nephrotic syndrome
o Nephrotic syndrome o Progressive renal failure
o Cardiac: cardiomegaly, arrhythmia, heart failure o Hyperparathyroidism
o Hepatomegaly
o Thyroid Dialysis amyloidosis
o Lung  Due to excess beta2 microglobulin
o GIT  Clinical features
o Adrenal o MSK:
o Lymph nodes  Carpal tunnel syndrome
o Skin  Flexor tenosynovitis
o Autonomic neuropathy: postural HoTN, impotence, decrease sweating,  Scalpulohumeral arthropathy
nocturnal diarrhea, constipation, post prandial dizziness, nocturia, bladder  Subchondral bone cysts
urgency, Horner’s pupil  Pathological fracture
 Management: raise head of bed to increase renin release, decrease o Cardiac
fluid loss, eat less, fluid retaining drugs o GIT
 Investigations  Management
o Rectal biopsy o Symptomatic treatment
o Renal biopsy o Treat each complication
o Skin/nerve/gingival biopsy o Switch to high-flux dialysis membranes consisting of polyacrylonitrile and
o Congo red stain polysulphone membranes -> reduces amyloid deposition
 “Apple green birefringence” under polarized light o Renal transplantation: halts diseases progression
o Subcutaneous fat aspiration
Peritoneal dialysis
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 Complication o Urinary alkalinisation used sometimes
o Pleuroperitoneal fitula o Postassium/calcium abnormalities needs monitoring but no active
 Dialysis fluid is high dextrose solution treatment – will resolve with fluid resuscitation
 Right sided pleural effusions commonly reported
Diabetes Insipidus
Familial Mediterranean Fever (FMF) Nephrogenic
 Inherited condition resulting in repeated episodes of polyserositis mimicking acute  Causes:
abdomen o Drugs: lithium
o Abnormal triggering of inflammatory response -> AA type amyloid  Investigations
deposition -> renal failure o Water deprivation test with ADH administration
 Common in Middle East, TUrkery, Syria, Lebanon, Israel, Egypt
 Investigations Renal artery stenosis
o Gene testing  Major cause of HTN especially in younger adults
o IVU: “cu and spill” calivces (possible analgesic nephropathy)  Atherosclerotic RAS
o Rectal biopsy with polarized light examination: “apple green” birefringence o Management
– confirm amyloidosis  Medical = angioplasty
o Renal biopsy: to be diagnostic for analgesic/amyloid associated nephropathy  Congenital RAS
o Very rare
Anaemia and CKD o Associated with coarctation of aorta
 Target Hb > 11g/dl or Hct > 33% o Others may be related to arteritis or neurofibromatosis
 To reach target within 4 months of commencing Erythropoietin  Transplant RAS
o Ensure ferritin replete before starting EPO o 10% after transplant
o May be due to surgical complication or transplant rejection
Erythropoietin induced epilepsy  Management
 Rare but seen within 90 days of erythropoietin initiation o Optimize blood pressure
 Mechanism unknown but may be related to veno occlusive disease or rise in o Risk factor control: smoking, diabetes, obseity
haemoglobin associated with EPO use o Revascularization: bilateral RAS or stenosis in solitary functioning kidney
 ACE-I result in decrease in efferent renal arteriolar BP and deterioration in serum
Rhabdomyolysis creatinine in RAS
 Investigations o Investigation
o Urine Myoglobinuria (false positive for blood on urine dipstick)  MRA (definitive)
o Hyperkalaemia o Monitoring
o Hypocalcemia  Recheck renal function 1/52 and 1/12 after initiation
o Raised Cr:Ur ratio o Management
o Hyperphosphatemia  Stop ACE-I, and replace with another anti-HTN (CCB)
o Creatine kinase
o Serum myoglobin Fibromuscular hyperplasia
 Management  Investigations
o Fluid resuscitation with urine measurement (rigorous hydration) o Renal angiogram: “strings of beads” appearance
o RRT (if oliguria and hyperK does not improve)  Management

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 o Angioplasty (superior outcomes with respect to BP control and long term  S/E: hypotension, tachycardia, insomnia, depression, anorexia,
sequelae) decreased libodo, ejaculation disorders, decreased volume of
ejaculate
Polyarteritis nodosa o 5-alphage reductase inhibitor: reduce prostatic hypertrophy
 Clinical features
o Associated with hepatitis B Iron deficiency in dialysis patients
 Investigations  Management
o pANCA +ve o Ferritin < 100mcg/L or <200mcg/L + transferrin sats < 20%
o Angio: small-medium sized artery renal aneurysms (typical picture!!)  IV iron replacement
o Histo: microscopic polyangitis (similar to Wegener’s) o Poor GI absorption of iron in renal impairment
 Management o Erythropoietin
o Corticosteroids  Only considered when ferritin > 100 or > 100 with transferrin
o Cyclophosphamide saturation > 20%

Pre-eclampsia RENAL GRAFTS

 Clinical features Graft dysfunction (up to 4/12 post transplant)
o Triad: epigastric pain, HTN, proteinuria  Acute rejection
 Manangement o Greater up to 2/52 post op
o IV labetalol o 30-50% of all transplants
o Delivery of baby is the definitive treatment  Ciclosporin toxicity
o In acute or chronic but well patients
Ureteric stones o Avoid erythromycin/clarithromycin (CYP3A4 inhibitoris), Diltiazem: can
 Types result in ciclosporin toxicity -> renal toxicity
o Calcium oxalate: ~60% of all stones o Symptoms
 Radio-opaque  Tremor
 Short bowel syndrome  Headache
o Cysteine stones – in cysteinuria  Nausea/vomiting
 Inherited AR of renal tubular absorption of increased amino acids  Abdominal
 Inherited increased urinary cysteine excretion  Raised creatinine, anaemia, thrombocytopaenia
o Uric acid  Acute tubular necrosis of graft
 Not radio-opaque (cannot be seen on XR)  Vascular thrombosis
 Gout  Ureteric leakage from anastomosis
o Mg-NH3-PO4 stones/Struvite stones
 Usually infectious Post transplant lymphoproliferative disorder (PTLD)
 Organisms: proteus, klebsiella, pseudomonas  Seen on average 18 months post transplant
 Caused by EBV
Benign prostatic hypertrophy o Initial stages: benign polyclonal proliferation of lymphocytes in response to
 Management rising tires of EBV
o Alpha-blockade: promotes smooth muscle relaxation improving urinary flow o Later stages: monoclonal proliferation
and reducing problem of residual urine in bladder post voiding o Follows lymphoma type pattern
 Clinical features
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 o Fatigue with night sweats
o Gradual weight loss
o Generalized lymphadenopathy
 Investigations
o CXR: hilar lymphadenopathy
o Marked elevation in EBV viral load
 Management
o Reduction in immunosuppression
o Anti-CD20 based intervention: Rituximab

CMV post transplant infection

 Generally presents in first few months after solid organ transplant
 Clinical features
o Hepatitis
o Pneumonitis
o Meningoencephalitis

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HAEMATOLOGY & IMMUNOLOGY  High WBC
 CXR infiltrate which may extend rapidly, involving lobes and pleura
o Management
Henoch-Schonlein purpura (HSP)  Hydroxyurea: increase production of fetal Hb(less likely to sickle)
 IgA mediated small vessel vasculitis (secondary to hypersensitivity)  Reduced acute chest syndrome and need for blood
o IgA dominant immune complexes present in venules, capillaries, arteriole transfusion for mean of 21 months
 Affects predominantly children  No difference in stroke, hepatic sequestration and
o 75% in 2-11yo mortality
o Males 2x more  S/E: BM toxicity, GI disturbances, skin rashes
 Clinical features  Pain management
o Purpura  Strong opiate for severe pain
o Arthritis  Avoid pethidine
o Abdominal pain o Spasm of gallbladder
o Haematuria
 Complications Haemolytic ureamic syndrome
o Renal: proteinuria, nephritis, nephritic syndrome  Clinical features: triad
o GIT: Hepatosplenmegaly, abdo surgery, intussusception, GI bleed, bowel o Microangiopathic haemolytic anaemia, thrombocytopaenic, acute renal
infarct failure
o CVS: MI  Investigations
o CNS: nervous system vasculitic o PBF: schiostocytes, burr cells
o Lung: Pulmonary haemorrhage, pleural effusion  Two types
o Typical: occurs after prodrome of diarrhea
G6PD o Atypical: not associated with diarrhea
 Drugs to avoid  Causes
o Antimalarial: Primaquine o Adults:
 SAFE: atovaquone, doxycycline, mefloquine, proquanil  Enterohaemorrhagic serotypes of E. Coli O157:H7
 Contaminated beef, poultry, cider
Sickle cell disease  Faecal to hand transmission
 Acute chest syndrome o Also associated with malignant HTN, infection, vasculitis, radiation nephritis,
o CXR: Appearance of new pulmonary infiltrate collagen vascular disease, cryoglobulinaemia, malignancy (adenocarcinoma),
o Causes: infection, infarction drugs (OCP, chemo, cyclosporine), eclampsia, post partum AKI, bone
 Usual organisms: pneumococcus, mycoplasma and chlamydia marrow transplantation
o Clinical features  Management
 Accompanied or preceded by pain in chest/extremities o Plasmapheresis with FFP
 Fever o RRT
 Respiratory distress
 Low oxygen saturations Primary polycythaemia
o Investigations  JAK2

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 Minor criteria o Venesection
o BM biopsy: hypercellularity with prominent erythroid, granulocytic and o Hydroxyurea
megakaryocytic proliferation o Allopurinol
o Serum erythropoietin level before normal  Other types
o Endogenous erythroid colony formation in vitro o Gaisbock’s syndrome: relative polycythaemia with reduced plasma volume
 Hypertensive, smokers
Polycythaemia rubra vera o Chuvash polycythaemia: congenital polycythaemia
 Malignant disorder of stem cell, characterized by overproliferation in BM of  Russian
erythroid, myeloid and megakaryocytic elements  Does not affect WBC or platelets counts
o Increase in production of RBC, WBC and platelets
 Clinical features Acute myeloid leukaemia
o Asymptomatic  Malignant disease of bone marrow in which blast cells derived from myeloid marrow
o Headache elements undergo neoplastic proliferation
o Tinnitus  More common in men, prevalence increases with age but can affect all age groups
o Visual disturbances  Increasingly common as long term complication of chemotherapy
o Pruritus  Clinical features
o Plethora o Marrow failure: anaemia, infections, bleeding
o Cyanosis o Organ infiltration with leukaemic cells: bone pain, hepatosplenogemaly,
o Splenomegaly gum hypertrophy, proptosis, lymphadenopathy
o Hepatomegaly o Constitutional symptoms: weakness, fever, lethargy
 Complications  Investigations
o Arterial/venous thrombosis o >20% blasts in blood and/or bone marrow
 Budd-Chiari syndrome  Monocytoid blasts
o Gout o Raised serum lysozyme
o Peptic ulcer o Auer rods: eosinophilic needle-like cytoplasmic inclusions in blast cells
o Worsening of angina (pathognomonic of AML)
o Intermittent claudication  Differentiate from ALL
o Leukaemic transformation  Management
o Neurological: TIA, CVA, fluctuating dementia o Induction
 Investigations o Post remission consolidation (intensification)
o Increase Hb, HCT o Arabinosylcytosine, motoxantrone, daunorubicin
o Increase WBC, platelet counts o In anaemia picture, watch for hyperviscosity/leucostasis (e.g. high WCC<
o Elevated LAP: leucocyte alkaline phosphatase drowsiness, retinal vein dilation)
o Elevated vitamin B 12  Avoid blood transfusion or given during therapeutic apheresis
o Increased red cell mass  Irradiated blood products: prevent transfusion GvHD
o Low erythropoietin levels  Prognosis
o Increased or normal plasma volume o Depends on cytogenetics
o BM: hypercellularity with clustered mature megakaryocytes and formation  Worse with deletion of parts of chromosome 5 or 7, increasing age,
of eythroid colonies without exogenous EPO history or prior preleukaemic condition
 Better with translocation between chromosome 8 and 21 t(8:21)
 Management

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Chronic myeloid leukaemia  Corticosteroids or Rituximab – rescue therapy
 Myeloproliferative disorder characterized by uncontrolled proliferation of precursors
for WBC/myeloid cells Myelofibrosis
o Precursors retain ability to differentiate  Clinical features
 Acquired abnormality involving haematopoietic stem cell and reciprocal o Hepatosplenogemaly: extramedullary haematopoiesis
chromosomal translocation -> Philadelphia chromosome – abnormally small  Investigations
chromosome 22 (present in granulocyte, RBC, platelet precursor in > 95%) o JAK2 positive
 Clinical features o Pancytopenia
o Chronic o BMA: dry tap
o Progressive cytopenia in presence of hypercellular bone marrow and usually  Management
involves all 3 cell lines o Hydroxyurea
o Marked splenomegaly
 Investigations Lymphoma
o Increased ++ WBC  Relapse of CNS lymphoma in high grade lymphoma not uncommon
o Low/normal Hb (mild)  Risk factors
o Variable platelet count (can manifests with thrombocytosis at presentation o >1 site of extranodal disease
usually with raised WBC with gross left shifts) o High LDH
o Basophil count often increase in myeloprolferative iang o Bone marrow/sinus involvement
o PBF: leukoerythroblastic picture (immaure cells: myelocytes and  Clinical features
normoblasts) o Complicated by reflexes suppressed from vincristine exposure
 Investigations
Acute lymphoblastic leukaemia o Imaging: no lesion demonstrated initially
 Management o LP: several times may be required
o Dexamethasone and vincristine to induce remission  Management
 Management o Induce remission with high dose cytosine arabinoside/methotrexate with
o Dexamethasone and vincristine to induce remission folinic acid rescue
o Then autologous tem cell transplantation/cranial radiotherapy
Chronic myelomonocytic leukemia  Prognosis
 Progressive cytopenia in presence of hypercellular bone marrow o Grave
 Usually involves all 3 cell lines
o Myeloid/monocyte Hodgkin’s lymphoma
o Erythroid  Malignant proliferation of lymphocytes
o Megakaryocyte  Clinical features
o Constitutional upset: night sweats, weight loss, fever, pruritus, lethargy
Chronic lymphocytic leukaemia o Alcohol induced pain or features due to mass effects of nodes
 Clinical features o Can have subacute motor neuronopathy (also seen in non-Hodgkin’s)
o Autoimmune haemolytic anaemia: Due to autoreactive T cells induction for  Asymmetric, subacute LMN weakness: atrophy, fasciculations,
rhesus family antigens -> drive B cell antibody production areflexia
 Management: Only If active/symptomatic (LOW>10%, fatigue, fever, night sweats,  Predominantly LL
marrow failure, AI anaemia, refractory thrombocytopenia, massive LAD,  Sparing bulbar muscles
lymphocytosis: increase > 50% or double in < 6/12
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 Investigations
o BM biopsy may be unrevealing as Hodgkin disease results in patchy BM Multiple Myeloma
infiltration  Clinical features
 More useful for staging of advanced disease o Back pain, headache, lethargy
o LN biopsy: more likely to be positive, less invasive than mediastinal biopsy  Investigations
 Reed-Sternberg cell o Elevated calcium
 Management o Decreased albumin
o Multi-agent chemotherapy o Elevated total protein
 Complications o Proteinuria
 Sarcoidosis (begin ~ 18/12 after completion of treatment) o Serum electrophoresis: paraprotein band
 Prognosis o P-ANCA +ve
o Good overall but depends on classification and staging  Diagnostic criteria for symptomatic MM
o Monoclonal protein in serum/urine
Non-Hodgkin’s lymphoma o Bone marrow plasma cells or biopsy proven plasmacytoma
 Low grade lymphoma o Myeloma related organ or tissue impairment
o Predominantly disease of older people
o More likely to have bone marrow infiltration Waldenstrom’s macroglobulinaemia
 Clinical features  Type of lymphoplasmacytoid lymphoma
o Low grade anaemia  Tender to occur in older men and present with peripheral LN enlargement and
o Intra-abdominal/pelvic LN enlargement -> compressive symptoms symptoms due to bone marrow infiltration
 Ureteric obstruction -> renal impairment  Associated with paraprotein IgM responsible for symptoms of hyperviscosity
 Management  Clinical features
o Chemotherapy o Anaemia, low WCC/platelet counts
 Risk of leukaemia (peaks 5 years after treatment) o Raised ESR
o Plasma cell infiltration of BM
Hairy cell leukaemia o IgM paraprotein
 B-lymphocyte disorder o Hyperviscosity: headache, visual disturbance
o Abnormal cell has hair like cytoplasmic projections o General malaise
 Clinical features o Weight loss
o Infiltration of bone marrow leads to pancytopaenia o LAD
o Hepatosplenomegaly o Bleeding tendencies
 Investigations  Investigations
o Abnormal cells are strongly positive for tartrate resistant acid phosphatase o Low/normal Hb/WCC/Plt
stain (TRAP) o Elevated ESR
o BMA: dry tap o PBF: rouleaux formation
o BM biopsy: cells to have characteristic fried egg appearance o BMA: lymphoplasmacytoid cells
 Management o Protein electrophoresis: IgM paraprotein >20g/L
o Purine analogues  Management
o Interferon o Chemotherapy:
o Splenectomy  Elder patients: alkylating agents

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  Younger patients: doxorubicin regimens  Cyclosporine, tacrolimus, antithymocyte globulin,
o Plasmapheresis for hyperviscosity mycophenolate mofetil
 Prognosis
o Recurrence inevitable Iron overload 2’ chronic blood transfusion
o Death due to CVS events due to increased viscosity/increased BM  Clinical features
infiltration leading to suppressed response to infection o Grey skin
o Early heart failure
Labs stains o Diabetes
 TRAP: hairy cell leukaemia  Management
 Sudan black B stain and myeloperoxidase: acute myeloblastic leukaemia o Chelation: Desferrioxamine
 Terminal deoxynucleotidyl transferase stain (TDT): acute lymphoblastic leukaemia  Binds iron, needs to be given 8-12 hours a day for 5-7 days per
 LAP: elevated in polycythemia rubra vera, myelofibrosis, low in chronic myeloid week
leukaemia  S/E: HF deafness, retinopathy, Yersinia infection

Acute graft-versus-host disease Acquired factor VIII deficiency

 Presents within 100 days of an allogenic bone marrow transplant with skin rash  Risk factors
 Clinical feature o Elderly
o Erythroderma o Pregnancy
o Cholestatic liver dysfunction o Concurrent autoimmune disease (RA/IBD) or malignancy
o Diarrhea +- bloody  Causes
 Management o Antibody to coagulation factor, most commonly factor VIII
o Aggressive IV corticosteroids treatment  Investigations
o TPN: nutrition if significant bowel involvement and diarrhea and vomiting o APTT prolonged
 Liver acute GvHD: 2nd most commonly organ involved  Mixing studies: acquired inhibitor will not correct with mixing
o 15 days from transplantation as marrow engulfment appears o Decreased factor VIII levels
o Clinical features o PT, bleeding time, platelet count all normal
 Jaundice o Bethesda assay: to measure inhibitor
 Hepatomegaly with abnormal LFTs (earliest & common: elevated  Management
conjugated bilirubin & ALP) o Aggressive treatment of underlying condition
 Damage to bile canaculi leading to cholestasis o Factor VIII: ineffective as inhibitor has rapid activity
 Abnormal hepatic US and Doppler flow o Recombinant activated factor VII or factor eight bypassing agent (FEIBA)
o Investigations  Latter is pooled donor product and is prothrombotic
 Biopsy: definite histological diagnosis but not feasible (acute  Risk of MI, DIC
bleeding due to severe thrombocytopenia)  rFVIIa: binds to surface of activated platelets, where it supports
 Extensive bile duct damage, bile duct atypia and thrombin generation and bypasses the need for VIII
degeneration, epithelial cell droupout, lymphocytic o Severe bleeding
infiltration of small bile ducts  Recombinant factor VIIIa
o Management  Activated prothrombin complex concentrate
 Corticosteroids: IV methylpred o Desmopressin: if low inhibitor titres with residual FVIII activity
 If not successful by 3-5 days: 2nd line less successful o Immunosuppression (successful in half) to remove auto-antibody

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  Methylpred/prednisolone o Methylene blue
 Cyclosporine  2nd line: IV ascorbic acid if fail (potentially useful in G6PD
 Rituximab in resistant cases or intolerant to above therapies deficiency)
o Exchange transfusion if refractory
Von Willebrand Disease
 Common, inherited, genetically and clinically heterogenous haemorrhagic disorder Carbon monoxide poisoning
caused by a deficiency or dysfunction of protein  Clinical features
 vWF is a large multimeric glycoprotein which functions as carrier protein for factor o Cherry red skin colouration
VIII by binding and stabilizing factor
o Mediates adhesion of platelets to sites of vascular injury Thrombotic thrombocytopenic purpurae
 vWF gene near tip of short arm of chromosome 12  Acquired autoantibody to metalloproteinase ADAMTS13
 3 major categories o Function to control size of vWB factor multimers -> ultra large vWB factor
o Partial quantitative deficiency type 1 multimers with enhanced activity accumulate and cause increased binding
o Qualitative deficiency type 2 of platelets to small blood vessels
o Total deficiency type 3 o Platelet counts fall and red cells damaged when passed through narrow
 Investigations vessel
o Screening:  Investigations
 Prothrombin time – normal o Anaemia with raised reticulocyte
 Activated partial thromboplastin time – prolonged o Lactate dehydrogenase (haemolysis)
 Factor VIII activity – variably decreased  Schistocytes: compatible with microangiopathic mechanism
 vWF activity and vWF antigen level determination o Low platelets
 Management  Management
o Ristocetin: antibiotic that causes plasma vWF to bind and active platelets o Urgent plasmapheresis with FFP or cryosupernate
 Reduce mortality
Methaemoglobinaemia o Aspirin: only started when platelet count at safe level
 Hb carries iron in ferrous form (Fe2+), when converted to ferric (Fe3+) o Rituximab: reduced relapse rates
methaemoglobin created, reducing red cell’s ability to carry oxygen o Platelet transfusion NEGATIVE IMPACT on prognosis
o NADPH reduced Fe3+ to Fe2+
 Drugs that provide oxidative stress: Hereditary haemorrhoagic telangiectasis/Osler-Weber-Rendu disease
o LA (esp. on mucosa)  AD disorder
o Sulphonamides o HHT1 (Chromosome 9) and HHT2 (chromosome 12)
o Nitrates (amyl nitrite)  Clinical features
 Clinical features o Telangiectases of skin and mucous membranes a/w bleeding tendency
o Headache, Confusion  Can affect naspharynx, CNS, lung, liver, spleen, GIT, GUT
o SOB, Chest pain o AVM: source of morbidity and mortality
o Cyanosed with no obvious cardiorespiratory cause despite increased oxygen  HHT1: pulmonary and cerebral AVMs
delivery, O2 sats remain low
o Blood: chocolate brown in colour Paroxysmal nocturnal haemoglobinuria
 Investigations  Acquired clonal disorder of haematopoietic stem cells, characterized by
o Methaemoglobin levels o Intravascular haemolysis
 Management o Thrombosis
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 o BM failures
 Mutation in phosphatidylinositol glycan A (PIG-A) on X chromosome -> deficiency of Post transfusion purpura (PTP)
several glycosyl-phosphatidylinositol (GPI) linked molecules (e.g. decay accelerating  Most commonly implicated antigen: human platelet antigen 1a (HPA-1a)
factor DAF, CD55, membrane inhibitor of reactive lysis MIRL, CD 59) -> increases  Management
complement mediated lysis of blood cells o High dose IVIg
 Investigations o Exchange transfusion and high dose corticosteroids have been used but
o Flow cytometry: CD55 and CD59 deficiencies and other GPI linked proteins effect slower
 Management
o Eculizumab: binds and prevents activation of C5 and subsequent formation
of cytolytic membrane attack complex of complement
 Reduces IV haemolysis and haemoglobinuria
 Staibilises Hb and reduces need for transfusion

Warfarin reversal
 Minor bleeding & INR > 8
o Low dose vitamin K
o Warfarin cessation
 Major bleeding
o Prothrombin complex concentrate: factors 2, 7, 9, 10, protein C and S
 Targeted reversal agent for increased INR a/w warfarin
o Vitamin K
 If no bleed, INR exceeds therapeutic but less than 6
o Reduce warfarin dose
o Might not have to stop warfarin

**BLOOD TRANSFUSION RELATED ADVERSE EVENTS**

Transfusion related lung injury (TRALI)
 Relate to anti-HLA or anti-granulocytes antibodies in donor blood
 More often in blood from multiparous women
o Generation of antibodies to HLA antigens through multiple exposures to
fetal blood
 Can develop within 6 hours of blood transfusion due to anti-HLA or anti-neutrophil
antibodies
 Risk factors
o Multiparous
 Investigations
o Anti-HLA/anti-neutrophil antibodies
 Management
o Full respiratory support
o Male donors for transfusion to reduce risk for subsequent attacks (lower
rate of carriage anti-HLA/neutrophil – 1-5%, 20% in women)
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ONCOLOGY & PALLIATIVE Surgery
 Contraindications
o Involvement of SVC
HEAD AND NECK o Presence of tumour within 2cm of either main bronchus (insufficienct
Glomus jugulare tumour resection margins)
 Vascular slow growing tumour, o Age over 65yo (relative contraindication)
o Rare but one of most frequent middle ear tumour
o More common in weomen, around 40-70yo GUT
 Clinical features Renal Cell Carcinoma
o Jugular foramen syndrome: CN 9, 10,11  Metastasis
o Onset of conductive hearing loss, pulsatile tinnitus 1 year before onset of o Lung: Most commonest cause of solitary round shadow of CXR
other CN  Management
o
BREAST o Nephrectomy unless (then partial nephrectomy)
Tamoxifen  Bilateral tumours
 Estrogen receptor antagonist for ER+ve breast cancer  Contralateral kidney poor function
 Taken orally once a day up to 5 years  Still first line even if mets are present: regression of mets after
o Can be longer in patients with metastatic disease removal of main tumour and relieve local symptoms
 Also effective in women with no personal history but at increased risk of breast o Sunitinib (TKI): for metastatic renal carcinoma with good functional status
cancer for cytokine therapy
 Reduces risk of developring cancer in the other breast o Pazopanib: alternative if not suitable for cytokine therapy
 S/E o Il-2: upregulate T cell immune response
o Increases risk of endometrial carcinoma and uterine sarcoma  Prognosis
o Related to presence of metastases
LUNG  5year survival 10% in distant mets
Asbestos & Mesothelioma  90% in early renal cancer
 3 types of asbestos: blue, brown and white
o Mesothelioma: blue and brown Bladder cancer
 Occurs >10-60 years after asbestos exposure  Risk factors
 Exposure to radiation in rare cases has also been linked to mesothelioma o Cyclophosphamide
 Risk can still be present even if exposure was many years
Bronchial carcinoma
 Smoker ADRENAL
 Clinical features Adrenal cortical adenocarcinomas
o Ipsilateral hilar LN involvement  Functioning or non-functioning
 Investigations  Management
o CXR: fluffy or spiked appearance of tumour edges o Mitotane (adrenal cortical cytotoxic agent)

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GASTROINTESTINAL o Necrolytic erythema migrans
Gastric cancer o Psychiatric disturbances
 Involves mediastinal glands and spreads along lymphatics of both lungs o Anaemia
o Thromboembolic disease with venous thrombosis or PE
Colorectcal carcinoma Pancreatic Polypeptidoma
 Dukes staging  Clnical features
o A: tumour confined to bowel wall o Watery diarrhea
o B: invades through muscle wall o Chronic duodenal ulcers
o C: involves LN o Multiple endocrine tumours
o Metasatic disease
 Prognosis CERVICAL
o Regional LN involvement and number of involved nodes PAP smear
o Favourable when 1-4 LN involved  Recommendations
o First screening at 25 years then 3 yearly until 49yo
Insulinoma o 50-64yos: five yearly screening
 Most common pancreatic endocrine tumour o 65 and above: not needed unless recent cervical changes
o 50% of islet cell tumours are insulinomas  Results
 Clinical features o Mlld dyskaryosis or CIN 1: repeat smear in 6 months
o Symptoms tend to occur at night or early in the morning  If next smear still abnormal -> colposcopy
o Hypoglycemia episodes o Moderate or severe dyskaryosis: colposcopy
o Neurological  3 negative 6/12ly smear before back to regular screening
o Psychiatric disturbances
 Investigations TESTICULAR
o Chromogranin A and synptophysin (useful markers of neuroendocrine Seminoma
differentiation of neoplasms)  Germ cell tumour
o Inappropriately high levels of both insulin and C-peptide  Rare but most common malignancy in men 15-35yo
o Provocative testing: 48h fast  Clinical presentation
 Low value H/C: serum for insulin and C-peptide o Painless testicular lump present
o Pulmonary metastases
Somatostinoma  Investigations
 Clinical features o B-hCG most specific for testicular seminoma (secreted by
o Diabetes mellitus syncytiotrophoblast cells within GCTs)
o Cholelithiasis  Only elevated in 5-10% of patients
o Diarrhea, steotorrhea
o Hypochlorhydria Choriocarcinoma
o Anaemia  Clinical features
o Weight loss o Small testi
o Early mestatasis
Glucagonoma o Gynaecomastia
 Clinical features o Increased skin pigmentation (related to elevated BhCG)

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 Investigations  Male
o Metastatic diseases  Age >12yo
 Abnormal LFTs  Elevated LDH
 Abnormal CXR  Anaemia
o Elevated BhCG  Poor response to chemotherapy
 Management
o Very treatable, including advanced disease CHEMOTHERAPY
o 80% responded to cisplatin based chemotherapy Bleomycin
 Used in haematological malignancies
PROSTATE  S/E: pulmonary fibrosis/interstitial pneumonia (10%)
Disseminated prostatic cancer
 Management Anastrazole
o IV Zolendronate: reduce skeletal relvant events and bone pain  Potent and highly selective nonsteroidla aromatase inhibitor
 Dose reduction for patient with eGFR < 60ml/min o Daily dose of 1 mg proceeded estradiol suppression at greater than 80%
 Infusion given at least over 15 mins  S/E: venous thromboembolism
 Impact can be seen in days while oral formulation such as
alendronate will need prolonged dosing Epirubucin
o Goserelin (GnRH agonist)  S/E: cardiac dysfunction, bone marrow suppression
 Suppress testosterone production but initial flare occurs leading to
increased testosterone Traztuzumab
 Prevented by 1/52 pre treatement with anti-androgen:  S/E: dilated cardiomyopathy
cyproterone o Discontinued when 10% or worse deterioration in EF or below 50%
 Otherwise: increase in PSA -> worsening of obstruction  Repeat LVEF in about 3/52: if no improvement of further
and renal function deterioration: discontinuation unless benefit outweigh risk

Tumour markers Atezolizumab

 aFP: yolk sac elements  PD-L! inhibitor: upregulate T cell activity and thus improve recognition of tumour
 LDH: overall tumour burder (less specific for GCTs) cells
 ALP: seminoma especially with increasing tumour burden  S/E: associated with increased risk of T1DM and autoimmune thyroid disease
o Also may be elevated with smoking
Paclitaxel
BONE  S/E: myelosuppresion
Ewing’s sarcoma
 Most lethal malignant primary bone tumour from red bone marrow Lapatinib
 Most common in children and adolescents, rare after 30yo  Advanced breast cancer
 Male: female = 3:2  S/E: LV failure
 Clinical features
o Bone pain (intermittent but increasingly intense) Cisplastin
o Large palpable rapidly growing mass: tense and tender  S/E: neurotoxicity
 Prognosis
o Poor Rituximab
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 Common side effects  Used in treatment of osteoporosis but reduces long term risk of breast cancer
o Flu like symptoms during infusion
 Fever, chills, weakness, myalgia, tiredness, dizziness, headaches OTHERS
o Hypotension during infusion Superior vena cava obstruction
o Nausea and vomiting  Due to external pressure from tumour on vessel
o Tumour pain  Management
o Allergic reactions: rashes & pruritus, swelling of tongue/throat, irritation of o Acute: IV dexamethasone and LMWH
nasal passages, wheeze, cough and SOB o Radiotherapy (effects not quick enough)
o Facial flushing during infusion o Stenting
o Surgery: high morbidity and mortality risk
Leuprolide
 Advanced prostatic cancer with metastases Tumour lysis syndrome
 Clinical feature
RFBC based chemo: rituximab/fludarabine/cyclophosphamide o Pulmonary edema
 Result in significant increase in susceptibility to opportunistic bacterial and viral o Haematuria
infections o Deteriorating creatinin
 Management o Hyoeruricaemia
o PCP prophylaxis o Hyperphosphatemia
o Oral valciclovir  Management
o Adequate rehydration
RADIOTHERAPY o Pre-treatment with allopurinol
Post-cranial irradiation somnolence syndrome o Recombinant urate oxidate
 Clinical features
o Excessive somnolence
o Lethargy
o Clumsiness
o Occur around 11-21 or 31-35 days after high dose craial RT
 Cause: ?post irradiation demyelination
 Management
o No specific therapy
o KIV steroids but no firm evidence

HORMONAL THERAPY
Anastrozole
 Lower risk of recurrence for hormone receptor positive breast cancer
o Lower risk of venous thrombosis as compared to tamoxifen
o S/E: greater hormonal suppression -> greater risk of osteoporotic fracture

Raloxifene
 Selective estrogen receptor modulator

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DERMATOLOGY o Dry skin
o Erythema
o Telangiectasias
Erythema multiforme o Rhinophyma
 Acute self limiting illness, causes erythematous macules, papules, target lesions on
 Management
palms and soles
o Doxycycline 4-6/52
 Triggered by:
 Could be extended up to 3/12 if slow to response
o Infections: HSV, CVM, HBV, HIV, EBV, mumps, orf, mycoplasma, psittacosis,
o Oral isotretinoin if resistant
rickettsiae, streptococcus, typhoid, diphtheria
o Sunblock: present worsening of symptoms
o Drugs: penicillin, sulphonamides, phenytoin, barbiturates
o Topical metronidazole & bromidine: for limited disease
o CTD: SLE, RA
 Brimonidine gel: used when episodes of facial flushing
o Vasculitis: PAN, granulomastosis with polyangiitits
o Underlying malignancy Actinic keratosis
o Sarcoidosis  Occurs due to prolonged sun exposure
o Ulcerative colitis  Management
 Clinical criteria for diagnosis o Cryotherapy
o Acute self limiting (<4/52) o Curettage: greater potential for scarring vs cryotherapy
o Symmetrical, discrete, round, red papules that persist at same site for at o Topical 5FU: takes number of applications for healing
least 7 days
o Some papules evolve into target lesions Bullous pemphigoid
o No mucosal involvement (or limited to one mucosal surface, usually oral)  Causes
o Drugs: frusemide, NSAIDS, captopril, penicillamine, BPP IV inhibitors,
Calciphylaxis antibiotics
 Life threatening disorder, most common seen in ESRF on dialysis
 Calcium deposits in cutaneous arteries -> thrombosis, isachemia necrosis Gravitational eczema
 Refractory ulcers in LL, abdomen, buttocks  Clinical features
 Risk factors o Haemosiderin deposition
o Elevated calcium-phosphate product o Thickened erythematous areas of skin below knee
o Hyperparathyroidism – primary and secondary o Venous ulceration
o Female sex o Previous history of varicose vein -> venous hypertension
o Obesity  Management
o Diabetes o Regular emollients
o Warfarin o Compression stockings (assess ABPI before 3 layer bandage)
Drugs and rashes
Rosacea  Beta blockers
 3x more common in women than men o Hypersensitivity reactions
 peak onset 30-60 years o Worsen psoriasis
 Clinical features  Amlodipine/CCD
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 o Purpura o Hyponatraemia 2’ SIADH
o Photosensitive dermatitis  Management
 Atorvastatin o Carbohydrate loading
o Urticaria o IV haem infusion
o Skin rashes o Opiate analgesia
o Alopecia o Avoid hypotonic fluids
 Dapagliflozin/SGLT 2 inhibitors
 Increased risk of skin infection (e.g. candidiasis) Atopic eczema
 Management
Lentigo maligna o Topical steroids
 Clinical features o Topical calcineurin inhibitors (Tacrolimus/Pimecrolimus) as steroids
o Area of darker skin with 4 irrefular deeply pigmented lesions alternative
 Investigations
o Biopsy: neoplastic melanocytes along epidermis border and dermis arranged Toxic epidermal necrolysis
in lentinigous pattern  Mediated by an early cytotoxic T cell response followed by Fas ligand binding to Fas
 Management (death receptors) on keratinocytes which trigger apoptosis
o Surgical exicison with 5-10mm margins  Other reactions
o Drug antibody immune complex: type 3 allergic reaction
Porphyria cutanea tarda  E.g. serum sickness
 Acquired and due to defieincy of uroporphyrinogen decarboxylase o Cytotoxic IgG or IgM antibodies: type 2 allergic reaction
 Risk factors  E.g. allergic thrombocytopenic purpura
o Alcohol exposure o IgE mediated reaction: type 1 allergic reaction
o Sun exposure  Release of histamine from mast cells
 Clinical features
o Fragility and blistering of exposed skin Pyogenic granuloma
o Scarring alopecia following resolution of scalp bullae  Vascular tumour which commonly presents at site of penetrating injury
o Hypertrichosis  Risk factor
o Hyperpigmentation o Pregnancy
 Clinical features
Acute intermittent porphyria o Rapid growth on previously normal skin
 Clinical features o Vascular, bleeds easily
o Confusion  History of mole at site where lesion occurs: alert to possibility of amelanotic
o Abdominal pain malignant melanoma
o HTN, tachycardia
o Peripheral neuropathy: cannot be reversed by treatment
 Provoking medications
o Antihistamines
 Investigations
o Increased urinary excretion of haem precursor prophobilinogen (PBG)
o Increased activity of hepatic 5-aminolevulinate (ALA) synthase

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THERAPEUTICS & TOXICOLOGY o Penicillins
o Cephalosporins
o Vancomycin
P450 Inhibitors – SICKFACES.COM Group
 Inhibitors of bacterial folate synthesis
Sodium valproate
o Sulphonamides
Isoniazid
o Trimethoprim
Cimetidine
 30S ribosomes: inhibitor of protein synthesis
Ketoconazole (inhibit conversion of lanosterol to ergosterol – a step in fungal cell
o Tetracycline
membrance synthesis)
Fluconazole
Drugs that cause gynaecomastia
Alcohol (binge)
Chloramphenicol  Estrogen and estrogen-like
Erythromycin o Diethylstilbestrol
Sulfonamides o Digoxin
o Cosmetics
Ciprofloxacin o Food contaminated (cows injected with diehylstilboestrol)
Omeprazole o Partners using estrogen vaginal creams
Metronidazole  Enhance estrogen formation
o Gonadotrophins
Grapefruit juice o Clomiphene
 Inhibit testosterone synthesis/action
P450 Inducers – CRAP GPS o Ketoconazole
Cabamazepines o Alkylating agents
Rifampicin o Spironolactone
Alcohol (chronic) o Cimetidine
Phenytoin  Unknown mechanism
o TCA
Griseofulvin (inhibit mitotic spindle of fungus, used to tx dermatophytes) o Heroin/marijuana
Phenobarbitone o Methyldopa
Sulphonylureas o Dusulphan
o Captopril
Antibiotics o CCB (long term use of verapamil)
 DNA gyrase inhibitors o Isoniazid
o Quinolones o Simvastatin
 Inhibitors of bacterial ribosome function
o Aminoglycosides Cinchonism
o Erythromycin  Brought on by both acute and chronic treatment with quinidine and quinine
o Tetracyclines o Quinidine: used for treatment of atrial and ventricular arrhythmias
 Inhibitors of bacterial cell wall synthesis  Clinical features
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 o Prolonged QT interval on ECG o Euphoria, drowsiness
o Cheyne-Stokes respiration
Antiarrhythmic drugs o Coma
 1: sodium channel blocks  Investigations
 2: beta-blockers o Metabolic acidosis
 3: potassium channel blockers, prolong action potential o Hyperglycaemia
 4: calcium channel blockers o Hyperkalaemia
o Hypernatraemia
Amphetamine abuse  Recover quickly within 1-2hours with rapid coma reversal
 Clinical features  Management
o Psychosis o Activated charcoal up to 1hr after ingestion
o Hypertensive o Monitoring of vitals
o High doses: can be indistinguishable from paranoid schiozophrenia o Diazepam: convulsions
o Vasculities
o ICH/SAH Cocaine overdose
o Withdrawal: prolonged sleep, muscle pain, profound fatigue, depression  Psychomimetic drugs
 Management  Cocaine can be snorted, smoked, IV or IM
o Discontinuation of amphetamine  Creates a sense of wellbeing, euphoria, loquacity, restlessness
o Antipsychotics  Blocks presynaptic uptake of biogenic amines
o Forced diuresis with ammonium chloride  Clinical features
o Vasoconstriction & Hypertension
Tricyclic antidepressants  White matter damage and posterior leukoencephalopathy
 E.g. dothiepin, amitriptyline o Tachycardia
 Clinical features o Generalized tremors
o Anticholinergic effects o Myoclonus
 Confusion o Seizures
 Dry mouth, mydriasis o Coma and death
 Constipation, urinary retention o SAH or ICH or ischaemic stroke can follow snorting or smoking
 Seizures
 QT prolongation and Torsades de pointes NSAIDs (Mefanamic acid) overdose
 Increased QRS -> ventricular arrhythmia  Generally safe but these can occur
o Management o Renal failure
 IV sodium bicarbonate o Acute GI bleed
 IV magnesium sulphate o Seizures (especially in mefenamic acid)
 Haemodialysis/haemoperfusion NOT effective
Atropine
Gammahydroxybutric acid overdose  Antimuscarinic drug
 Used illegally for bodybuilding and weight loss (replacement for L-tryptophan) o Effect on eye: mydriasis and cycloplegia of ciliary body
 Taste similar to seaweed (Liquid X, Cherry Meth, Easy Lay, Scoop, GBH)  Increased risk of glaucoma (localized frontal headache, BOV,
 Clinical features nausea, vomiting)
o GI effects, decreased cardiac output, severe respiratory depression
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  Fixed dilated pupil with corneal edema and pericorneal  Haemodynamic compromise
cilary injection  Prognosis
o E.g. given during bradycardia or heart block resuscitation -> precipitate o Digoxin levels > 15ng/ml
glaucoma (localized frontal headache, BOV, nausea and vomiting) o Serum potassium > 5mmol/l
 Management o Susceptibility
 Topical b-blockers  Renal failure
 Acetazolamide  Hypothyroidism
 Topical pilocarpine  Hypomagneasemia

Ethylene glycol poisoning Lithium toxicity

 Clinical features  Clinical features
o High anion gap metabolic acidosis o Nausea, vomiting, increasing drowsiness
o Hyperventilation o Confusion, erratic
o Decreased conscious level o Ataxia, irregular coarse tremors, myoclonic jerks
o Multi-organ failure: renal, respiratory, cardiac failure  Management
 Widespread deposition of calcium oxalate crystals 12 hrs after o Symptomatic with levels > 2.5mmol/L: DIALYSIS
initial insult
o Coma Theophylline overdose
o Renal failure  Causes
o Death o Increase in plasma levels
 Management  Macrolide, quinolone
o Sedation  Drugs that cause decrease in plasma levels
o Infusion of ethanol (competitive inhibitor of alcohol dehydrogenase) o Rifampicin
o Fomepizole: inhibit enzyme directly  Clinical features
o High dose thiamine and pyridoxine: reduces formation of oxalate from o GIT
glyxoylic acid o Agitation
o Haemodialysis o Thirst
o Polyuria
Digoxin toxicity o Seizures
 Clinical features o Metabolic acidosis, hypokalaemia
o Symptomatic bradycardia, hypotension o Tachycardia, cardiac arrhythmias, hypotension
o Arrhythmia: VT, VF, asystole, complete heart block, Mobitz type II  Management
o Hyperkaelamia o Urgent gastric lavage with activated charcoal
o End-organ dysfunction from hypoperfusion o Cardiac monitoring
 Management o Correction of hypokalemia
o VT: IV phenytoin o IV diazepam for seizures
 IV lidocaine as alternative  Mortality up to 30%
 If haemodynamic compromised: DC cardioversion o Haemoperfusion in severe poisoning (levels > 60mg/L)
o Digibind in severe cases (digoxin-binding antibody fragments)
 Significant arrhythmia Tacrolimus toxicity

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 Clinical features o Charcoal
o Hypertension o Gastric lavage if within 1st hour post ingestion
o Worsening of related tremor o Lorazepam (for seizures)
o Rise in creatinine
 Subject to CYP 3A4 metabolism Phenobarbital toxicity
o Potent inhibitor of CYP 3A4: erythromycin  Inducers of hepatic enzymes
 Clinical features
Methotrexate overdose o Drowsiness
 Dihydrofolate reductase inhibitors: convert dihydrofolate to tetrahydrofolate o Respiratory depression
 Clinical features o Impaired coordination
o Nausea, vomiting o Coma
o Stomatitis  Management
o Skin rashes o Sodium bicarbonate
o GI bleed  Acidic drug and eliminated through kidneys (aided by forced
 Management alkaline diuresis with sodium bicarbonate)
o Calcium folinate (leucoorin): derivative of tetrahydrofolate: bypasess o Charcoal
folate step blocked by methotrexate o Haemodialysis
 IV infusion up to 75mg in first 12 hours
 Then 6-12mg every 4hrs Colchicine toxicity
o Blood transfusion  Mechanism
o Massive overdose o Not fully understood
 Hydration o Attributable to probable interference of drug with tubulin – protein required
 Urinary alkalinisation for polymerization of microtubules in muscle and nerve
o High flux dialysis o Weakness resolves when drug discontinued but neuropathic features
remain
Beta-blocker overdose  Clinical features
 Management o Myoneuropathy and can lead to acute necrotizing myopathy
o IV glucagon o Proximal muscles weakness
 Exerts inotropic effect independent of beta-receptor activation by  Investigations
raising myocardial cAMP levels o Creatine phosphokinanse normal or elevated
 50-150ug/kg bolus then infusion at 1-5mg/h o Muscle biopsy: both myopathic and neuropathic disease
o NOT for IV adrenaline o Histo: rimmed vacuoles in muscle fibers on Gomori stain
 Risk of precipitating VT
o Salbutamol nebulisers if bronchospasm Ecstasy toxicity
o Hourly hypocount  Poor prognostic indicators
 Dextrose 50% bolus then infusion o Hyperpyrexia > 42 degree celcius
o Rhabdomyolysis
Carbamazepine toxicity o Renal failure
 Management o Liver failure
o Hydration  Deaths usually due to

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 o Hyperthermia  Indications
o Complications of HTN and DIC  Systemic envenomation: persistent HTN, ECG
 Cerebral infarction abnormalities, vomiting, haemostatic abnormalities, WBC
 Haemorrhage > 20 and severe localizing limb swelling extending
 Management proximally within 2-4hrs after the bite
o Rapid convection cooling
o IV benzodiazepines Organophosphate poisoning
o IV rehydration  Strong cholinesterase inhibitors
o BP control  Clinical features
o Muscarinic and nicotinic over-stimulation
Sumatriptan o Miosis
 Can cause chest pain, 2’ ?vasospam o Hypersalivation
 Associated with myocardial infarctions o Chest tightness
 CI in people with known IHD o Sweating
o Nausea/vomiting/diarrhea
Oculo-gyric crisis/acute dystonias o Nicotinic effects
 Acute dystonic reaction 2’ dopaminergic blockade at basal ganglia  Muscle fasciculation
o Usually in young women  Flaccid weakness of limbs & respiratory muscles
 Opsithotonus: acute generalized dystonic reaction  Respiratory failure exacerbated by pulmonary edema
o Arching of back o Coma and convulsions
o Forced extension of neck o Glycosuria and hyperglycemia (usually no ketonuria)
o Internal rotation of arms  Investigations
o Extension of elbows and wrists o Reduced plasma/red cell cholinesterase activity
 Causes  Management
o Drugs: o Decontamination before arrival to hospital
 Neuroleptics:phenothiazines, butyrophenones o Clear airway and removal of respiratory secretions and correction of
 Atypical antipysychotic agents: olanzapine hypoxia are essential
 Metoclopramide, prochlorperazine  ETT intubation and mechanical ventilation
 5-HT3 receptor antagonist (but also possesses 5-HT4 o Atropine: muscarinic receptor antagonist
receptor and dopamine receptor antagonist: increases the  2mg every 10-30min until signs of atropinisation
risk of oculogyric crisis and acute dystonia) o Pralidoxime: cholinesterase activator
 Management  Should be given to all symptomatic patients with atropine
o Withdrawal of offending agent
o Administration of antimuscarinic drugs Cyanide Poisoning
 Procyclidine hydrochroride  Causes
 Trihexyphenidyl hydrochloride (benzhexol) o Nitroprusside: If improperly stored or exposed to sunlight -> degradation ->
formation of sodium cyanide
Adder (VIpera berus) o Burning polyurethane foams
 Available antivenom but with 1% chance of anaphylactic reaction  Irreversibly blocks mitochondrial electron transport
o To give with adrenaline  Clinical features of Cyanide poisoning
o Early: dizziness, chest tightness, confusion
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 o Pulmonary edema o Tinnitus
o HTN and bradycardia -> hypotension and coma o Visual blurring
o AMI, cardiovascular collapse, apnea, paralysis o Repeated vomiting
o Abdominal pain o Respiratory alkalosis -> severe metabolic acidosis w increased anion gap
o SOB  Management
o Death can occur in minutes o Activated charcoal for aspirin overdose
 Investigations  Levels of glucose may not represent intracellular glucose stores:
o Marked lactate elevation low threshold to start IV glucose
 Management  IV fluids and aggressive rehydration
o Intubated and ventilated o Urinary alkalinisation
o Sodium thiosulphite o Haemodialysis
o Dicobalt edetate: 300mg IV bolus (repeated up to 3x)  In severe cases, plasma concentration >700mg/L
 Initially can worsen hypotension and vomiting but recovers over  Renal failure/CCF/pulmonary edema/coma//convulsions/pH <
few minutes 7.2/CNS effects not resolved by acidosis correction/persistently
o Sodium nitrite high salicylate concentrations unresponsive to urinary alkalinisation

Sodium nitroprusside Lead poisoning

 Potent short acting vasodilator: acts via nitric oxide pathway to increase cGMP within  Lead inhibits conversion of delta-aminolevulinic acid dehydrase and ferrochelatase,
smooth muscle cells delta-aminolevulinic acid cannot be converted to porphobilinogen and iron not
 S/E: nausea, sweating, headache, twitching incorporated into protoporphyrin
 Overdose: cyanide toxicity o Erythrocyte protoporphyrin elevated to > 35mcg/dL
o Cobalamin plays a role in cyanide metabolism, B12 level fals and cyanide  Clinical features
levels rise o GI symptoms
o Thus do NOT use in B12 deficiency state o Pure motor polyneuropathy
 Rapid hypotensive effect: within 30-60s of commencing infusion  Predominantly bilateral wrist drop
 Indications  Investigations
o HTN emergencies o Microcytic anaemia
o Dissecting aortic aneurysm o Basophilic stippling
o Acute cardiac failure o Proximal renal tubular acidosis
o Acute VSD o Serum lead levels
o MR  Management
 Contraindications o Remove source of lead poisoning
o Leber’s optic atrophy (B12 can lead to blindness, nitroprusidde not used due o Chelation with oral DMSA (2,3 –dimercaptosuccinic acid) or IV EDTA (sodium
to increased risk of optic nerve ischaemia) calcium edetate)
o Severe liver disease
o B12 deficiency Methanol poisoning
 Used sometime as substitute for ethanol by alcoholics
Salicylate poisoning  Clinical features
 Clinical features o First few hours
o Bilateral deafness  Inebriation
 Gastritis
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 o After latent period of 6-30 hours  Management
 Metabolic acidosis: by both formate and lactate o Laxative administration
 Visual disturbances & Blindness o Surgery if intestinal obstruction or intoxication
 Seizures
 Coma Drug studies
 Death  Phase 1: establish initial safety and toxicity date
o Fundoscopy o In very small numbers of healthy humans
 Disc hyperaemia  Phase 2: evaluate safety and toxicity and effective dose range
 Venous engorgement o Monitor pharmacokinetic and pharmacodynamics effects
 Papilloedema o Around 500 patients
 Slowly metabolized by alcohol dehydrogenase to formaldehyde then by aldehyde  Phase 3: establish efficacy in wider patient population
dehydrogenase to formic acid o Around 1000-2000 patients
 Management  Phase 4: post marketing surveillance studies
o IV sodium bicarbonate to correct acidosis
o IV ethanol/fomepizole HLA Types
 Compete for enzyme alcohol dehydrogenase and block metabolism  B1502: SJS in phenytoin in Chinese patients
of methanol to toxic metabolites  B5701: Abacavir hypersensitivity
o Haemodialysis for rapid removal of toxic products  A3101: SJS in carbamazepine European or Japanese patients
 B5801: allopurinol hypersensitivity
Antibiotics & tendon rupture  DQ2: dermatitis herpertiformis
 Quinolones
o Avoid use in children or pregnant women

Amiodarone and digoxin

 Amiodarone leads to decrease in renal and non-renal clearance of digoxin,
prolonging half life and increase in absorption
o Digoxin needs to be reduced 33-50% when taken with amiodarone
 Acarbose/sodium alginate decrease absorption of digoxn

Tocolysis associated pulmonary edema

 Can occur in up to 5-15% of cases
 And usually 24 hours after administration
o Concomitant corticosteroids are risk factors
 Investigations
o CXR: pulmonary infiltrates and normal heart size
 Management
o Stopping tocolytics
o Oxygen
o Careful volume control

Body packers
111