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🏥 MASTER CLINICAL NOTES: EXAM TRAPS, WARD ERRORS & CLINICAL PEARLS

All Systems | Based on Harrison's, Davidson's, Kumar & Clark, Oxford Handbook, Master the Wards (Fischer)

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SYSTEM 1: RESPIRATORY

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ASTHMA vs COPD

• Asthma: atopy/allergy, occupational triggers, aspirin sensitivity
• COPD: cigarette smoking (>90%), alpha-1 antitrypsin deficiency (young, non-smoker, lower lobe emphysema)

• COPD misdiagnosed as asthma (or vice versa) in smokers over 40 - KEY: only asthma is reversible
• Alpha-1 antitrypsin deficiency labeled as "smoker's COPD" - check AAT levels in any COPD patient under 45 or non-smoker
• Vocal cord dysfunction (VCD) mimics asthma - inspiratory stridor, normal spirometry, normal PEFR between episodes - NOT bronchospasm

• Reversibility test: FEV1 increase >12% AND >200mL post-bronchodilator = asthma. In COPD: fixed obstruction - FEV1/FVC <0.7 POST-bronchodilator (not pre)
• Severity of acute asthma uses PEFR (not spirometry): moderate <50-75%, severe <33-50%, life-threatening <33% predicted
• Silent chest = WORSE prognosis than loud wheeze (no airflow = no wheeze = impending arrest)
• LABA as monotherapy in asthma = INCREASES mortality. Must ALWAYS be combined with ICS

• Prescribing beta-blockers (including topical timolol eye drops) to asthmatics = fatal bronchospasm
• Targeting SpO2 100% in COPD exacerbation = blunts hypoxic drive. Target 88-92%
• Not checking inhaler technique before stepping up therapy
• Giving high-dose nebulized salbutamol without monitoring potassium = hypokalemia

• Samter's triad (Aspirin-exacerbated respiratory disease): asthma + nasal polyps + aspirin/NSAID sensitivity
• Churg-Strauss (EGPA): asthma + eosinophilia + vasculitis + p-ANCA
• Cardiac asthma: nocturnal dyspnea in elderly - actually LVF. Check BNP

• COPD exacerbation treatment: nebulized SABA + SAMA, IV/oral prednisolone 30-40mg x5 days, antibiotics if purulent sputum (amoxicillin or doxycycline), controlled O2 88-92%, consider NIV if pH <7.35
• Step-up in asthma: SABA alone → low-dose ICS → ICS + LABA → medium ICS + LABA → add tiotropium/LTRA/increase ICS → biologic (omalizumab for allergic, mepolizumab for eosinophilic)

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PNEUMONIA

• CAP: Streptococcus pneumoniae (most common all ages)
• Atypical: Mycoplasma pneumoniae (young adults, bilateral patchy, raised cold agglutinins, extrapulmonary features)
• Legionella: Air conditioning/water cooling towers, hyponatremia + diarrhea + elevated LFTs + relative bradycardia. Urinary antigen = KEY test
• HAP/VAP: Gram-negative organisms (Pseudomonas, Klebsiella), MRSA

• Legionella missed because it resembles typical pneumonia but is INTRACELLULAR - does NOT respond to beta-lactams alone
• PCP (Pneumocystis jirovecii) in HIV patient with "bilateral pneumonia" - check CD4 count (<200), raised LDH, bilateral ground-glass

• Legionella = NOT treated with amoxicillin. Use fluoroquinolone (levofloxacin) or clarithromycin
• Klebsiella = alcoholics, diabetics, upper lobe consolidation, "currant jelly" sputum, cavitation
• Aspiration pneumonia (right lower lobe if upright, right upper lobe posterior segment if supine) vs aspiration pneumonitis (chemical, no antibiotics initially)
• CURB-65: Confusion + Urea >7mmol/L + RR >30 + BP <90/60 + Age >65. Score 0-1 = outpatient, 2 = admit, 3+ = consider ICU

• Not getting blood cultures BEFORE antibiotics in hospitalized/severe pneumonia
• Not getting urinary antigen for Legionella and pneumococcus in severe/ICU CAP
• Not covering atypicals in hospitalized CAP (amoxicillin alone is insufficient - add clarithromycin)
• Forgetting PCP in any HIV patient with bilateral pneumonia: treat with high-dose co-trimoxazole; add steroids if PaO2 <70mmHg or A-a gradient >35mmHg

• Pneumococcal pneumonia: rust-colored sputum, lobar consolidation, elderly/asplenic/post-splenectomy patients
• Staphylococcal pneumonia post-influenza: pneumatoceles, rapidly cavitating bilateral infiltrates
• Cavitating upper lobe pneumonia in immunocompromised = think Aspergillus (halo sign on CT)

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PULMONARY EMBOLISM

• DVT (85-90%), lower limbs. Risk factors: immobility, surgery, malignancy, thrombophilia, OCP, pregnancy (Virchow's triad)

• Classic triad (dyspnea + pleuritic chest pain + hemoptysis) occurs in <20% - most PEs present with dyspnea only or look like pneumonia/panic attack
• PE in young woman on OCP presenting with "atypical chest pain" = dismissed as musculoskeletal

• ECG: Most common finding = sinus tachycardia (not S1Q3T3). S1Q3T3 is present in <20% and is nonspecific
• D-dimer: ONLY rules out PE in LOW pre-test probability (Wells score low). A high-probability patient needs CT-PA regardless of D-dimer
• Wells Score: Clinical signs of DVT (+3), PE most likely diagnosis (+3), HR >100 (+1.5), immobilization >3 days (+1.5), prior PE/DVT (+1.5), hemoptysis (+1), malignancy (+1). >4 = high probability
• Normal CXR does NOT exclude PE. Classic findings (Hampton's hump, Westermark sign) are rare

• Not anticoagulating stable submassive PE while waiting for CT - start heparin empirically once decision made
• Stopping anticoagulation after 3 months in UNPROVOKED PE - guidelines recommend indefinite anticoagulation
• Massive PE (systolic BP <90mmHg) without contraindication = systemic thrombolysis (alteplase 100mg over 2h) - do NOT delay
• Using thrombolytics in submassive PE without RV dysfunction evidence

• Saddle PE = straddles bifurcation of main pulmonary artery, acute cor pulmonale, thrombolysis/surgical embolectomy
• Paradoxical embolism through PFO = simultaneous DVT + ischemic stroke

• PESI score for outpatient PE treatment eligibility
• DOAC (rivaroxaban, apixaban) now preferred over LMWH/warfarin in most PE (except antiphospholipid syndrome - use warfarin)
• Cancer-associated PE = LMWH or DOAC (rivaroxaban/edoxaban) preferred over warfarin

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PLEURAL EFFUSION

• Light's criteria (exudate if ANY ONE met): (1) Pleural protein/serum protein >0.5, (2) Pleural LDH/serum LDH >0.6, (3) Pleural LDH >2/3 upper limit of normal for serum LDH
• Students REVERSE the ratio (should be pleural/serum, NOT serum/pleural)
• Transudates: Heart failure (most common), cirrhosis, nephrotic syndrome, hypothyroidism, Meigs syndrome, constrictive pericarditis
• Exudates: Infection/parapneumonic, malignancy, PE, TB, RA (very low glucose), SLE, pancreatitis (raised amylase in pleural fluid)

• Not checking coagulation before thoracocentesis (hold if INR >1.5, platelets <50,000)
• Removing >1.5L in a single session = risk of re-expansion pulmonary edema
• Not sending fluid for pH, glucose, LDH, protein, cytology, culture - incomplete analysis

• Meigs syndrome: Ovarian fibroma + right-sided pleural effusion (transudate) + ascites - resolves with tumor removal
• Chylothorax: Milky fluid, triglycerides >110mg/dL, thoracic duct damage (trauma or lymphoma)
• RA effusion: VERY low glucose (<1.6 mmol/L), low complement, exudate - pathognomonic in right context
• Empyema criteria: pH <7.2, glucose <60mg/dL, LDH >1000, frank pus = needs chest drain (tube thoracostomy)

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TUBERCULOSIS

• Primary TB in children: fever + hilar lymphadenopathy on CXR + Ghon focus = called "pneumonia"
• Miliary TB: Hematogenous spread, millet-seed pattern on CXR, can have NORMAL CXR early, pancytopenia, hepatosplenomegaly, choroidal tubercles on fundoscopy

• RIPE for 2 months (Rifampicin + Isoniazid + Pyrazinamide + Ethambutol), then RI for 4 months = total 6 months pulmonary TB
• Meningeal TB, bone/joint TB, pericardial TB = 9-12 months
• Rifampicin: orange urine/secretions/tears, potent liver enzyme INDUCER (reduces OCP, warfarin, antiretrovirals, phenytoin efficacy)
• Isoniazid: peripheral neuropathy (prevented by pyridoxine B6 - ALWAYS co-prescribe)
• Ethambutol: optic neuritis (check color vision and visual acuity monthly)
• Pyrazinamide: hyperuricemia, hepatotoxicity

• Not giving pyridoxine with isoniazid = peripheral neuropathy
• Not checking baseline LFTs before RIPE (rifampicin and isoniazid are hepatotoxic)
• Treating latent TB with INH alone for 6-9 months (NOT full RIPE - this is correct for latent TB)
• Not isolating smear-positive patient until 2 weeks of treatment completed

• Pott's disease: TB spine, psoas/paraspinal cold abscess, kyphosis ("gibbus"), cord compression
• Addison's disease secondary to TB = most common cause worldwide (adrenal calcification on CT)
• Steroids INDICATED as adjuvant: TB meningitis (reduces mortality/disability) + TB pericarditis (prevents constrictive pericarditis). NOT routine in pulmonary TB

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LUNG CANCER

• Adenocarcinoma: Most common overall, peripheral, non-smokers/women/East Asians, EGFR mutations, BAC (bronchoalveolar) subtype
• Squamous cell: Central, cavitates, hypercalcemia via PTHrP (NOT PTH itself)
• Small cell (SCLC): Central, "oat cells," early metastases, MULTIPLE paraneoplastic syndromes
• Large cell: Peripheral, no specific features

• Pancoast tumor (superior sulcus) presenting as shoulder pain - attributed to rotator cuff or cervical spondylosis for months. Look for ipsilateral Horner's (ptosis + miosis + anhidrosis)
• SCLC presenting with hyponatremia (SIADH) labeled as "pneumonia"

• SCLC paraneoplastics: SIADH (hyponatremia), ectopic ACTH (Cushing's - no response to high-dose dexamethasone suppression), Lambert-Eaton syndrome (proximal weakness IMPROVES with repeated use - OPPOSITE of myasthenia where it worsens)
• Squamous cell = hypercalcemia via PTHrP (not PTH), central location
• Adenocarcinoma = hypertrophic pulmonary osteoarthropathy (HPOA), clubbing, periosteal new bone

• Ordering imaging before tissue biopsy - tissue diagnosis FIRST, then staging
• Starting EGFR inhibitors without confirming EGFR mutation status
• Not screening eligible patients: CT chest for lung cancer screening in 50-80 year-olds, 20+ pack-year history, current smoker or quit within 15 years (USPSTF/NLST criteria)

• SVC syndrome: facial/arm swelling, dilated neck veins, headache worse on bending. Most common cause = SCLC or lymphoma
• Lambert-Eaton = IMPROVES with repeated use. Myasthenia = WORSENS with repeated use
• Molecular targets: EGFR mutation → gefitinib/erlotinib/osimertinib; ALK rearrangement → crizotinib/alectinib; PD-L1 ≥50% → pembrolizumab monotherapy

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INTERSTITIAL LUNG DISEASE / IPF / SARCOIDOSIS

• IPF treatment = pirfenidone or nintedanib (antifibrotics). Steroids WORSEN IPF
• IPF on HRCT = UIP pattern: honeycombing + traction bronchiectasis + bilateral basal subpleural distribution. Ground-glass opacity suggests NSIP (connective tissue disease, better prognosis, steroid-responsive)
• Sarcoidosis staging: Stage I = bilateral hilar lymphadenopathy only (often spontaneously resolves, no treatment). Stage II = BHL + parenchymal. Stage III = parenchymal only. Stage IV = fibrosis
• ACE level is raised in sarcoidosis but has poor sensitivity/specificity - used for monitoring activity, NOT diagnosis

• Giving steroids for IPF = accelerates fibrosis (one of the classic ward errors in respiratory)
• Missing sarcoidosis as a cause of hypercalcemia - macrophages in granulomas produce 1-alpha-hydroxylase → activated vitamin D → hypercalcemia (independent of PTH)

• Sarcoidosis: bilateral hilar lymphadenopathy + erythema nodosum + anterior uveitis + hypercalcemia + non-caseating granulomas
• Löfgren syndrome: BHL + erythema nodosum + ankle periarthritis + fever = good prognosis, often resolves without treatment
• Bird fancier's lung vs farmer's lung: both hypersensitivity pneumonitis. Treat by removing exposure. Steroids for acute/severe episodes
• NSIP: associated with RA, SSc, SLE, polymyositis, Sjögren's - "ground glass" pattern, steroid-responsive

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PNEUMOTHORAX

• Tension pneumothorax = CLINICAL DIAGNOSIS. Tracheal deviation AWAY from affected side + absent breath sounds + hypotension + distended neck veins. Do NOT wait for CXR. Needle decompression IMMEDIATELY at 2nd ICS, MCL
• Primary spontaneous: Tall, thin, young male, subpleural bleb rupture

• Ordering CXR before needle decompression in suspected TENSION pneumothorax = fatal delay
• Inserting chest drain in wrong location (correct = 5th ICS, midaxillary line, within the "safe triangle")
• Not getting follow-up CXR after chest drain removal to confirm resolution

• Small (<2cm rim on CXR) primary spontaneous PTX in well patient = high-flow O2 + observation
• Large or symptomatic = aspiration (first attempt) → chest drain if fails
• Secondary PTX (underlying lung disease) = lower threshold for chest drain regardless of size
• Pneumothorax in ventilated patient = always tension until proven otherwise - immediate needle decompression

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ARDS

• Berlin criteria: bilateral infiltrates + PaO2/FiO2 <300 + NOT explained by cardiac failure/fluid overload. Mild: 201-300; Moderate: 101-200; Severe: ≤100
• ARDS = non-cardiogenic. Cardiogenic pulmonary edema = PCWP >18 (or BNP very elevated). Both have bilateral infiltrates

• High tidal volumes in ARDS = volutrauma/barotrauma. Use 6mL/kg predicted body weight (ARDSNet), plateau pressure <30 cmH2O
• Aggressive fluid resuscitation in ARDS worsens oxygenation - conservative fluid strategy after initial resuscitation
• Not using prone positioning in severe ARDS (PaO2/FiO2 <150) - PROSEVA trial: 16h/day prone reduces mortality significantly
• Routine corticosteroids in early ARDS = no clear benefit (context-dependent)

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SYSTEM 2: GASTROENTEROLOGY & HEPATOLOGY

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PEPTIC ULCER DISEASE

• H. pylori (80% of duodenal ulcers, 60-70% of gastric ulcers). Second = NSAIDs. Rare = Zollinger-Ellison syndrome

• Gastric ulcer vs gastric CANCER: ALWAYS biopsy gastric ulcers at endoscopy. Duodenal ulcers are rarely malignant
• Posterior duodenal ulcer eroding into pancreas = pancreatitis with back pain - missed as musculoskeletal

• Duodenal ulcer pain: relieved by eating (food buffers). Gastric ulcer: pain WORSE with eating (but unreliable clinically)
• H. pylori testing: urea breath test or stool antigen unreliable within 4 weeks of antibiotics or 2 weeks of PPI. Stop both before testing
• Triple therapy: PPI + clarithromycin + amoxicillin (or metronidazole) x 7-14 days (quadruple therapy if clarithromycin resistance high)
• Zollinger-Ellison: multiple/refractory ulcers + diarrhea + fasting gastrin >1000 pg/mL. Part of MEN-1. Gastrinoma in pancreas/duodenum

• Using NSAIDs + aspirin without PPI gastroprotection in high-risk patients (elderly, prior ulcer, on anticoagulants)
• Not repeating endoscopy at 6-8 weeks to confirm healing of gastric ulcers (missed cancer)
• Anterior ulcers PERFORATE (peritonitis). Posterior ulcers BLEED into pancreas or left hepatic artery territory

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GI BLEEDING

• BUN:Creatinine ratio >20 = upper GI source (digested blood absorbed, raises BUN)
• Hematochezia (bright red PR) is USUALLY lower GI, but massive upper GI bleed (with rapid transit) can cause it too
• Melena = upper GI (digested blood - dark, tarry, foul-smelling). Minimum ~50mL blood needed to produce melena
• Glasgow-Blatchford score = used BEFORE endoscopy for risk stratification. Rockall score = includes endoscopic findings

• Upper GI: Peptic ulcer (most common), esophageal varices, Mallory-Weiss tear (vomiting + retching → distal esophageal mucosal tear)
• Lower GI: Diverticulosis (painless, massive, elderly), angiodysplasia, colorectal cancer, colitis

• Not correcting coagulopathy (INR, platelets, fibrinogen) before emergency endoscopy
• Not giving IV PPI infusion (omeprazole 80mg bolus then 8mg/h) before endoscopy in suspected peptic ulcer bleed - reduces re-bleeding
• Not giving IV terlipressin or octreotide EMPIRICALLY if variceal bleed suspected before endoscopy
• Not starting prophylactic antibiotics (IV ceftriaxone 1g daily) in ALL cirrhotics with GI bleed (reduces SBP risk, improves survival)
• Transfusing to Hb >10 in variceal bleed = worsens portal hypertension. Restrictive transfusion strategy (Hb target 7-8 g/dL) is better

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INFLAMMATORY BOWEL DISEASE

• Crohn's ileitis = RLQ pain + fever + raised WCC = operated as appendicitis. Terminal ileum involvement
• C. difficile colitis in IBD patient labeled as IBD flare (ALWAYS check C. diff before escalating IBD treatment)
• Infectious colitis (Campylobacter, Salmonella, E. coli O157) mimicking IBD

• Toxic megacolon = colonic diameter >6cm on AXR + systemic toxicity (fever, tachycardia, WBC >10.5). STOP antidiarrheals + laxatives. IV steroids, bowel rest, NG decompression, surgical consult. No improvement in 48-72h = colectomy
• Primary sclerosing cholangitis (PSC) = strongly associated with UC (NOT Crohn's). 70% of PSC patients have UC
• UC has higher CRC risk than Crohn's colitis (extent + duration). Surveillance colonoscopy from 8-10 years of disease
• Anti-TNF (infliximab): do NOT use in active TB, sepsis, demyelinating disease, decompensated heart failure (EF <35%)

• Antidiarrheals (loperamide) in severe IBD flare = precipitates toxic megacolon
• Not giving VTE prophylaxis in hospitalized IBD patients - IBD is a thrombotic state
• Missing steroid-induced complications: hyperglycemia, osteoporosis (give bisphosphonate + calcium + vit D for long-term steroid use)

• PSC: cholestatic LFTs + "beaded" bile ducts on MRCP. UC association. High risk of cholangiocarcinoma. Ursodeoxycholic acid does NOT prevent cancer
• Pyoderma gangrenosum: typically lower leg, starts as pustule → deep ulcer with violaceous undermined edges. Associated with UC > Crohn's
• Ankylosing spondylitis more with Crohn's. PSC more with UC. Peripheral arthritis and erythema nodosum parallel IBD activity

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CIRRHOSIS AND COMPLICATIONS

• DIAGNOSIS: Ascitic PMN ≥250 cells/mm³ (even without positive culture). Most common organism = E. coli
• EXAM MISTAKE: Threshold is 250 cells/mm³ NOT 500. Treat empirically = do NOT wait for culture result
• TREATMENT: IV ceftriaxone 2g daily x 5 days + IV albumin 1.5g/kg Day 1, then 1g/kg Day 3 (prevents hepatorenal syndrome - reduces mortality)
• WARD ERROR: Not giving albumin with SBP treatment - the albumin is as important as the antibiotic
• PREVENTION: Norfloxacin or ciprofloxacin prophylaxis if: ascitic protein <10g/L, prior SBP, or after variceal bleed

• PRECIPITANTS (must identify and treat): GI bleed, infection, constipation, hypokalemia/hyponatremia, diuretics over-diuresis, sedatives/opioids, porto-systemic shunts, excess dietary protein
• WARD ERROR: Giving morphine, diazepam, or any sedative to encephalopathic patient = worsens it dramatically
• TREATMENT: Lactulose (titrate to 2-3 soft stools/day) + rifaximin (for recurrence prevention) + treat precipitant
• Protein restriction is OUTDATED. Normal protein diet with branched-chain amino acids preferred

• DIAGNOSIS: Rising creatinine in cirrhotic + ascites, no improvement after 2 days of albumin 1.5g/kg + diuretic withdrawal, no other cause of AKI
• TYPE 1: Rapid (Cr doubles to >226 in <2 weeks), very poor prognosis
• TYPE 2: Slower, refractory ascites
• WARD ERROR: Giving NSAIDs or nephrotoxic IV contrast in cirrhotic patient = precipitates HRS
• TREATMENT: Terlipressin + albumin (most evidence). Bridge to TIPS or liver transplant

• PRIMARY PREVENTION (medium/large varices): Non-selective beta-blocker (propranolol or carvedilol)
• EXAM MISTAKE: Selective beta-blockers (atenolol, bisoprolol) do NOT reduce portal pressure adequately
• SECONDARY PREVENTION: Band ligation + non-selective beta-blocker
• ACUTE VARICEAL BLEED: Terlipressin + antibiotics (ceftriaxone) + urgent endoscopy (banding). Sengstaken-Blakemore tube only as bridge to TIPS/endoscopy

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JAUNDICE - DIFFERENTIAL

• Pre-hepatic (hemolysis): Unconjugated bilirubin ↑, LDH ↑, haptoglobin ↓, urine = dark (urobilinogen) but NO bilirubin in urine, normal stools
• Post-hepatic (obstructive): Conjugated bilirubin ↑, ALP + GGT ↑↑ > AST/ALT, pale/clay stools, dark urine (conjugated bili in urine), pruritus
• Hepatic: BOTH fractions raised, AST/ALT ↑↑ > ALP

• Courvoisier's law: Palpable gallbladder + jaundice = NOT gallstones (fibrosed, non-distensible GB). Think pancreatic cancer or cholangiocarcinoma
• Gilbert's syndrome: Benign unconjugated hyperbilirubinemia, precipitated by fasting/illness/stress. Normal LFTs, normal blood film. No treatment needed. UGT1A1 gene mutation
• Hepatitis E in pregnancy: HIGH mortality (20% in third trimester). Fecal-oral, developing countries

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HEPATITIS B vs C

• HBsAg = active infection (acute or chronic)
• Anti-HBs = immunity (vaccination OR resolved infection)
• Anti-HBc IgM = ACUTE infection
• Anti-HBc IgG = past/resolved OR chronic (background antibody)
• HBeAg = high replication/infectivity; Anti-HBe = low replication
• WINDOW PERIOD: HBsAg cleared but Anti-HBs not yet detectable - ONLY Anti-HBc IgM positive
• WARD ERROR: Not screening for HBsAg before starting immunosuppression/chemotherapy/rituximab = HBV reactivation (can be fatal). Give prophylactic entecavir or tenofovir

• Anti-HCV = exposure/past. CONFIRM active infection with HCV RNA (PCR)
• Treatment: DAA (direct-acting antivirals) - sofosbuvir + ledipasvir/velpatasvir >95% SVR (cure). Pangenotypic regimens now standard
• WARD ERROR: Still using pegylated interferon + ribavirin = obsolete, inferior, more toxic

• Tenofovir or entecavir (preferred). Avoid lamivudine alone (high resistance)
• EXAM MISTAKE: HBV DNA monitoring determines treatment response; HBsAg loss = functional cure (rare)

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PANCREATITIS

• Gallstones (40%) > Alcohol (35%). Mnemonic GET SMASHED: Gallstones, Ethanol, Trauma, Steroids, Mumps, Autoimmune, Scorpion sting, Hyperlipidemia/Hypercalcemia, ERCP/Emboli, Drugs (azathioprine, thiazides, valproate, tetracycline, pentamidine)

• AT ADMISSION: Age >55, WBC >16,000, Glucose >200mg/dL, LDH >350 IU/L, AST >250 IU/L
• AT 48H: Ca <8mg/dL, PaO2 <60, Base deficit >4, BUN rise >5mg/dL, Fluid sequestration >6L, Hct fall >10%
• Score ≥3 = severe pancreatitis
• EXAM MISTAKE: Lipase is MORE SPECIFIC and stays elevated LONGER than amylase. Amylase can be normal in chronic pancreatitis
• EXAM MISTAKE: Amylase is also raised in: salivary gland disease, perforated viscus, bowel infarction, renal failure - not specific

• Prolonged fasting beyond 48h in mild acute pancreatitis = unnecessary. Early enteral feeding (NG tube) preferred in severe pancreatitis (maintains gut barrier, prevents bacterial translocation)
• Routine prophylactic antibiotics in acute pancreatitis = NOT indicated even with necrosis (UNLESS infected necrosis confirmed by CT/aspiration)
• Not recognizing pancreatic duct leak in severe pancreatitis (pseudocyst, Wirsung duct disruption)

• Cullen's sign (periumbilical bruising) + Grey Turner's sign (flank bruising) = hemorrhagic pancreatitis
• Chronic pancreatitis: steatorrhea + diabetes mellitus + calcifications on AXR/CT. Treat with pancreatic enzyme replacement (creon) with meals

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CELIAC DISEASE vs IBS vs IBD

• Anti-tTG IgA = most sensitive/specific. MUST be eating gluten at time of testing
• IgA deficiency = FALSE NEGATIVE anti-tTG IgA - always check total IgA first. If deficient, use anti-tTG IgG or anti-DGP antibodies
• Confirm with duodenal biopsy: villous atrophy + crypt hyperplasia + increased intraepithelial lymphocytes
• IBS = DIAGNOSIS OF EXCLUSION. Must rule out celiac, IBD, thyroid disease, colorectal cancer, and microscopic colitis first

• Dermatitis herpetiformis: IgA deposits at dermal-epidermal junction, extremely itchy vesicles on extensor surfaces (elbows, knees, scalp) = celiac skin manifestation
• Celiac associations: Type 1 DM, autoimmune thyroid disease, IgA deficiency, Down syndrome, Turner syndrome
• Rome IV criteria for IBS: abdominal pain ≥1 day/week for 3 months + associated with defecation or change in stool frequency/form

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ASCITES MANAGEMENT

• Large-volume paracentesis (>5L) WITHOUT albumin = post-paracentesis circulatory dysfunction. Give albumin 8g per litre removed (>5L)
• Wrong diuretic ratio: Start spironolactone 100mg + furosemide 40mg (5:2 ratio) to maintain normokalemia. Do NOT titrate furosemide alone
• Not doing diagnostic paracentesis on ALL new-onset ascites (exclude malignancy, TB, SBP)

• SAAG (Serum-Ascites Albumin Gradient) = serum albumin MINUS ascites albumin: ≥1.1 g/dL = portal hypertension (liver, RHF, constrictive pericarditis). <1.1 = non-portal (malignancy, TB peritonitis, pancreatitis)
• SAAG has REPLACED Light's criteria for ascites (Light's is for pleural effusion)

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GALLSTONE DISEASE

• Charcot's triad = RUQ pain + fever + jaundice = acute cholangitis = MEDICAL EMERGENCY
• Reynold's pentad = Charcot's triad + confusion + shock = suppurative cholangitis
• EXAM MISTAKE: Choledocholithiasis treated by ERCP (stone removal), not cholecystectomy alone (need both in sequence)
• WARD ERROR: Not covering with antibiotics before ERCP in cholangitis
• Acalculous cholecystitis: no gallstones, occurs in critically ill ICU patients, high mortality, US or HIDA scan for diagnosis

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SYSTEM 3: ENDOCRINOLOGY

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DIABETES - DKA vs HHS

• Most common precipitant: INFECTION (most common), missed insulin, new-onset T1DM
• Diagnosis: Glucose >11 + pH <7.3 + HCO3 <15 + ketones >3 mmol/L or ++ on urine. Anion gap metabolic acidosis (AG = Na - (Cl + HCO3), normal 8-12)

• Pseudohyponatremia in DKA: glucose dilutes sodium. Corrected Na = measured Na + 2.4 per 10mmol/L glucose above 5. Actual sodium is higher than measured
• Cerebral edema: more common in children with DKA from rapid fluid replacement. Use 0.9% NaCl initially (not hypotonic)
• "RESOLVING DKA" = anion gap closed + HCO3 normalized + pH >7.3 - NOT just when glucose normalizes

• Stopping insulin infusion when glucose normalizes = DKA NOT resolved. Continue insulin, start 5% dextrose alongside to prevent hypoglycemia while completing DKA resolution
• Not checking/replacing potassium: insulin drives K+ into cells. DO NOT start insulin if K+ <3.5 mmol/L - replace K+ first. Monitor K+ every hour
• Giving sodium bicarbonate routinely = NOT indicated unless pH <6.9 (paradoxically worsens CNS acidosis)
• Not identifying and treating precipitating cause (infection, etc.)

• Glucose typically >33 mmol/L, osmolality >320 mOsm/kg, no significant ketosis
• Typically elderly T2DM patient, very high DVT risk
• WARD ERROR: Rehydrating too rapidly = cerebral edema. Replace fluid deficit over 24-48h with 0.9% NaCl
• WARD ERROR: Starting insulin immediately in HHS - fluids alone often reduce glucose significantly. Introduce low-dose insulin carefully after initial fluid resuscitation
• Always give LMWH prophylaxis (high thrombosis risk)

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THYROID DISORDERS

• Most common cause: Hashimoto's thyroiditis (anti-TPO antibodies, goiter, lymphocytic infiltration)
• Most common misdiagnosis: Depression, fatigue syndrome, weight gain labeled as lifestyle issues. Always check TSH
• TSH raised + free T4 low = PRIMARY. TSH low + free T4 low = SECONDARY (pituitary/hypothalamic)
• WARD ERROR: Starting full-dose levothyroxine in elderly or cardiac patients = can precipitate angina/MI or AF. Start 25-50mcg, titrate slowly over weeks
• Subclinical hypothyroidism: TSH raised, T4 normal. Treat if TSH >10 mU/L or symptomatic or pregnant

• Most common cause: Graves' disease (anti-TSH receptor antibodies, diffuse goiter, exophthalmos, pretibial myxedema)
• Exam mistake: Toxic multinodular goiter in elderly = AF + weight loss + NO exophthalmos
• WARD ERROR: Not giving beta-blocker (propranolol) FIRST to control symptoms while waiting for antithyroid drugs to take effect (2-4 weeks onset)
• WARD ERROR: Radioiodine in pregnancy = ABSOLUTE CONTRAINDICATION
• Antithyroid drugs: Carbimazole (UK, standard). PTU = preferred in first trimester (carbimazole is teratogenic - aplasia cutis). PTU ALSO blocks peripheral T4→T3 conversion (hence preferred in thyroid storm)

• Precipitants: surgery, infection, trauma, radioiodine in undertreated patient
• Treatment sequence (critical exam order):
  1. PTU 500-1000mg loading (blocks synthesis + peripheral conversion)
  2. Lugol's iodine 1 HOUR AFTER PTU (blocks hormone release from gland)
  3. Propranolol (controls HR, blocks peripheral conversion)
  4. Hydrocortisone (blocks T4→T3 conversion, treats relative adrenal insufficiency)
  5. Treat precipitant
• EXAM TRAP: Iodine BEFORE PTU = Jod-Basedow effect (iodine used as substrate → MORE thyroid hormone synthesis)

• Hypothermia + bradycardia + hypotension + hypoventilation + coma
• WARD ERROR: Active external rewarming = causes vasodilation, cardiovascular collapse. Use passive rewarming
• TREATMENT: IV liothyronine (T3) or levothyroxine + IV hydrocortisone (adrenal insufficiency often coexists) + treat precipitant

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ADRENAL DISORDERS

• Most common cause in developed world: Autoimmune (anti-21-hydroxylase antibodies)
• Most common cause worldwide: Tuberculosis (adrenal calcification on CT)
• Features: HYPERPIGMENTATION (↑ACTH → stimulates MSH receptor) + hyponatremia + HYPERKALEMIA + hypotension + hypoglycemia + eosinophilia
• Primary: low cortisol + HIGH ACTH. Secondary (pituitary): low cortisol + LOW ACTH, NO hyperpigmentation, NO hyperkalemia (aldosterone preserved in secondary)
• MOST COMMON MISDIAGNOSIS: Depression, anorexia, IBD, chronic fatigue syndrome - the fatigue + weight loss + GI symptoms are non-specific. Check for hyperpigmentation (buccal mucosa, palmar creases, scars, pressure areas)

• Trigger: intercurrent illness, surgery, missed hydrocortisone
• EXAM MISTAKE: Synacthen test confirms Addison's: primary = NO rise in cortisol after ACTH injection. Secondary = delayed but eventual cortisol rise
• WARD ERROR: Giving IV saline alone without hydrocortisone = dangerously ineffective
• TREATMENT: Hydrocortisone 100mg IV STAT, then 50mg every 6-8h, IV saline 0.9%, IV glucose if hypoglycemic
• Never investigate (synacthen test) DURING crisis - treat first, investigate later

• Most common cause OVERALL: Exogenous corticosteroids (iatrogenic - the most important to recognize)
• Most common ENDOGENOUS cause: Cushing's DISEASE (pituitary ACTH-secreting adenoma, 70%)
• Diagnosis sequence (CRITICAL exam question):
  1. CONFIRM hypercortisolism: 24h urinary free cortisol OR overnight 1mg dexamethasone suppression test (failure to suppress = cortisol >50 nmol/L)
  2. ACTH level: if raised = ACTH-dependent (pituitary or ectopic). If suppressed = ACTH-independent (adrenal adenoma/carcinoma)
  3. If ACTH-dependent: High-dose dexamethasone test (8mg overnight): Cushing's disease (pituitary) = suppresses >50%. Ectopic ACTH (SCLC) = does NOT suppress
  4. Then MRI pituitary
• EXAM MISTAKE: Students jump to MRI pituitary before biochemical confirmation

• Stopping long-term corticosteroids ABRUPTLY = Addisonian crisis (HPA axis suppressed). Always taper

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CONN'S SYNDROME (PRIMARY HYPERALDOSTERONISM)

• Most common CURABLE hypertension - frequently missed
• Screen in: hypokalemia + hypertension (even on K-sparing drugs), resistant HTN (≥3 drugs), adrenal incidentaloma + HTN, HTN onset <30
• Diagnosis: Aldosterone-to-renin ratio (ARR). Aldosterone HIGH, renin LOW (autonomous aldosterone suppresses renin)
• EXAM MISTAKE: Renin is LOW (not high) - opposite of renovascular HTN where renin is HIGH
• Confirm with salt loading or fludrocortisone suppression test
• Treatment: Adenoma = laparoscopic adrenalectomy. Bilateral hyperplasia = spironolactone (or eplerenone)

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PHEOCHROMOCYTOMA

• Rule of 10s: 10% malignant, 10% bilateral, 10% extraadrenal (paraganglioma), 10% in children, 10% familial (MEN2, VHL, NF1, SDH mutations)
• Diagnosis: Plasma free metanephrines (most sensitive) or 24h urinary metanephrines/catecholamines

1. Alpha-blockade FIRST (phenoxybenzamine or doxazosin) x minimum 10-14 days
2. THEN beta-blockade (to control reflex tachycardia from alpha-blockade)
3. THEN surgical resection

• WARD ERROR: Beta-blocker BEFORE alpha-blocker = unopposed alpha stimulation = severe hypertensive crisis (can be fatal)
• WARD ERROR: Biopsy or manipulation without alpha-blockade = hypertensive crisis
• WARD ERROR: Not maintaining high fluid/salt intake before surgery = severe hypotension post-resection (from sudden loss of catecholamine-driven vasoconstriction)

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HYPERCALCEMIA

• Most common cause OVERALL (outpatient): Primary hyperparathyroidism (parathyroid adenoma, 80%)
• Most common cause in HOSPITAL (inpatient): Malignancy (PTHrP or osteolytic metastases)
• PTH raised = hyperparathyroidism. PTH suppressed = malignancy
• Symptoms: "Bones, Stones, Groans, Psychic Moans" (osteitis fibrosa cystica, kidney stones, constipation/nausea, depression/confusion)
• ECG: Short QT interval
• EXAM MISTAKE: Thiazide diuretics RAISE calcium (reduce renal excretion). Loop diuretics LOWER calcium
• Treatment sequence: IV fluids (0.9% NaCl, FIRST) → loop diuretics only if fluid overloaded → IV bisphosphonate (zoledronic acid, takes 2-4 days) → calcitonin (fastest, but tachyphylaxis in 48h) → steroids (for sarcoidosis/vitamin D toxicity/myeloma)
• WARD ERROR: Giving bisphosphonate before adequate hydration = renal toxicity

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HYPONATREMIA - SIADH

• SIADH causes: CNS disease (SAH, meningitis), malignancy (SCLC #1), drugs (carbamazepine, SSRIs, thiazides, cyclophosphamide, oxytocin), pulmonary (pneumonia, TB, abscess), post-surgery
• Diagnostic criteria: Hyponatremia + low plasma osmolality + high urine osmolality (>100 mOsm/kg) + high urine Na (>40) + euvolemic
• Treatment: Fluid restriction (first line). Demeclocycline or tolvaptan if refractory
• EXAM MISTAKE: Thiazide diuretics can cause both hyponatremia (SIADH-like) AND hypercalcemia - frequently tested
• WARD ERROR: Correcting hyponatremia too rapidly = OSMOTIC DEMYELINATION SYNDROME (central pontine myelinolysis). Correct no faster than 8-10 mmol/L per 24 hours. In severe symptomatic hyponatremia = 3% NaCl 1-2 mL/kg/h, max 100-150mL, only enough to raise by 4-6 mmol/L then STOP

• Central DI: responds to DDAVP (desmopressin). Cause = pituitary surgery, trauma, granuloma
• Nephrogenic DI: does NOT respond to DDAVP. Causes = lithium (most common drug cause), hypercalcemia, hypokalemia
• Treatment nephrogenic DI from lithium: thiazide + low-sodium diet + amiloride (reduces lithium entry into collecting duct)

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MEN SYNDROMES (Classic Exam Topic)

• MEN 1 (3 P's - Wermer syndrome): Pituitary (prolactinoma most common) + Parathyroid (hyperparathyroidism = most common component overall) + Pancreas (gastrinoma/Zollinger-Ellison most common, insulinoma, VIPoma). MEN1 gene (chromosome 11)
• MEN 2A (Sipple): Medullary thyroid carcinoma (MTC) + Pheochromocytoma + Parathyroid hyperplasia. RET proto-oncogene
• MEN 2B: MTC + Pheo + Marfanoid habitus + Mucosal neuromas (tongue, lips, eyelids) + NO parathyroid. Most aggressive MTC
• EXAM TRAP IN MEN 2: ALWAYS treat pheochromocytoma FIRST (alpha-blockade then surgery) before thyroidectomy
• Prophylactic thyroidectomy timing based on RET mutation codon (codon 918 = earliest, in infancy)
• Calcitonin = tumor marker for medullary thyroid carcinoma (MTC)

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SYSTEM 4: NEUROLOGY

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STROKE

• BP >185/110 (must be controlled BEFORE giving tPA)
• Platelet <100,000; INR >1.7; on direct thrombin inhibitor/Xa inhibitors with elevated coagulation tests
• Blood glucose <2.7 or >22.2 mmol/L
• Prior intracranial hemorrhage; stroke or serious head trauma within 3 months; intracranial neoplasm/AVM/aneurysm
• Active internal bleeding (not menstruation); arterial puncture at non-compressible site within 7 days
• Recent intracranial/spinal surgery within 3 months

• tPA (alteplase): up to 4.5 hours from CLEAR onset. For wake-up stroke: use DWI-FLAIR mismatch on MRI
• Thrombectomy: up to 24 hours in selected patients with salvageable penumbra (DAWN/DEFUSE-3 trials)

• Giving aspirin within 24h of tPA = hemorrhagic transformation risk. Wait 24h after tPA before starting antiplatelet
• Aggressively lowering BP in acute ischemic stroke (unless >220/120 in patients NOT receiving tPA, or >185/110 for tPA candidates) = reduces perfusion to penumbra
• Not initiating secondary prevention: aspirin/clopidogrel (POINT/CHANCE trial - dual antiplatelet for 21 days in minor stroke/TIA, then single), statin, antihypertensive

• Posterior circulation stroke: vertigo + vomiting + ataxia + diplopia + dysarthria + crossed signs (ipsilateral face + contralateral body)
• Wallenberg syndrome (lateral medullary): ipsilateral Horner's + ipsilateral facial sensory loss + contralateral body pain/temp loss + dysphagia + vertigo + ataxia
• Lacunar infarcts: pure motor, pure sensory, ataxic hemiparesis, dysarthria-clumsy hand. Small vessel disease. NO cortical signs
• PACS/TACS/LACS/POCS (Bamford classification) - TACS = all 3: motor/sensory deficit + hemianopia + cortical sign (dysphasia/neglect) = worst prognosis

• Hypertension = most common cause. Sites: putamen (most common) > thalamus > cerebellum > pons
• Cerebellar hematoma >3cm = surgical emergency (can cause acute hydrocephalus + herniation)
• NOT a candidate for tPA (absolute contraindication)

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TIA

• ABCD2 score: Age ≥60 (+1), BP ≥140/90 (+1), Clinical features: unilateral weakness (+2) or speech only (+1), Duration: ≥60min (+2), 10-59min (+1), Diabetes (+1)
• Score 0-3 = low risk. 4-5 = moderate. 6-7 = high risk of stroke within 48h
• Most common misdiagnosis: Migraine with aura, focal seizure (Todd's paralysis), hypoglycemia, complex migraine, MS relapse
• WARD ERROR: Discharging TIA patient without urgent workup (MRI brain, carotid Doppler, ECG + 24h Holter monitor for AF, echo) within 24h for high-risk
• Dual antiplatelet therapy (aspirin + clopidogrel) for 21 days then single antiplatelet (POINT trial)
• Carotid stenosis >70% ipsilateral to symptoms = carotid endarterectomy (CEA) within 2 weeks (65% RRR for ipsilateral stroke)

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MENINGITIS

• Most common organisms: Adults = N. meningitidis (young adults, petechial/purpuric rash = non-blanching), S. pneumoniae (all ages). Elderly/immunocompromised/neonates = Listeria monocytogenes (must cover with ampicillin)
• Empiric treatment: Ceftriaxone 2g IV 12-hourly + ampicillin 2g IV 4-hourly (for Listeria) + dexamethasone 0.15mg/kg QDS (give WITH or BEFORE first antibiotic dose)
• WARD ERROR: Delaying antibiotics for CT/LP = FATAL. Give antibiotics IMMEDIATELY if LP will be delayed. LP can occur after antibiotics but reduces yield
• WARD ERROR: Not giving dexamethasone before/with first antibiotic dose = loss of benefit. It only helps if given first
• CSF findings: bacterial = cloudy, WBC ↑↑ (neutrophils), protein ↑↑, glucose very low (<50% of blood glucose)

• HSV encephalitis: temporal lobe involvement, personality change, bizarre behavior, seizures, temporal lobe changes on MRI, RBC + lymphocytes in CSF
• TREATMENT: Acyclovir 10mg/kg IV TDS EMPIRICALLY. Do NOT wait for PCR results. Early acyclovir is life-saving
• Anti-NMDA receptor encephalitis: young woman, psychiatric features + seizures + autonomic instability + decreased consciousness. Check for ovarian teratoma (remove it). Anti-NMDAR antibodies in CSF/serum. Treat with immunotherapy (steroids, IVIG, plasma exchange)

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EPILEPSY / SEIZURES

1. 0-5 min: Secure airway, O2, glucose (after thiamine), IV access
2. 5-10 min: Lorazepam 0.1mg/kg IV (or diazepam 10mg PR/IV if no IV)
3. 10-20 min (if persisting): Levetiracetam 60mg/kg IV over 10 min, OR valproate 40mg/kg IV, OR phenytoin 20mg/kg IV (fosphenytoin preferred)
4. 30-60 min (refractory): Phenobarbital 20mg/kg, then RSI + anesthesia (propofol, thiopental, midazolam infusion) with EEG monitoring

• Giving phenytoin IV too fast = cardiac arrhythmias (max rate 50mg/min IV). Fosphenytoin is safer
• Giving phenytoin in eclampsia = magnesium sulfate is correct for eclampsia (NOT phenytoin)
• Not giving glucose/thiamine in ALL seizing patients with unknown history

• Carbamazepine: CYP450 INDUCER (reduces OCP, warfarin, other AEDs). Also causes SIADH (hyponatremia)
• Valproate: CYP450 INHIBITOR, teratogenic (neural tube defects, autism, fetal valproate syndrome). Avoid in women of childbearing potential. If used, folic acid 5mg/day
• Lamotrigine: reduce dose by 50% when adding valproate (valproate doubles lamotrigine level). SJS risk with rapid titration
• Phenytoin: zero-order kinetics (small dose increase → disproportionate rise in levels). Gingival hyperplasia, hirsutism, coarse facies, teratogenic. Avoid in focal cortical dysplasia
• Levetiracetam: safe in renal impairment? No - dose adjust in CKD. Can cause behavioral side effects (irritability, aggression)

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MULTIPLE SCLEROSIS

• McDonald criteria (2019): Dissemination in SPACE (different CNS locations) AND TIME (different attacks). CSF oligoclonal bands (IgG) present in >95% - support but not required
• Common presentations: Optic neuritis (unilateral painful vision loss, afferent pupillary defect, disc pallor), internuclear ophthalmoplegia (MLF lesion - adduction deficit ipsilateral + nystagmus contralateral), Lhermitte's sign (electric shock sensation down spine on neck flexion = cervical cord lesion), Uhthoff's phenomenon (worsening with heat - does NOT mean new relapse, no steroids)
• RELAPSE TREATMENT: IV methylprednisolone 1g daily x 3-5 days - SPEEDS recovery, does NOT change long-term outcome or disability
• DISEASE MODIFYING: interferon-beta, glatiramer (first line), natalizumab (risk of PML - check JCV antibodies), fingolimod (bradycardia on first dose - monitor), alemtuzumab, ocrelizumab (first for primary progressive MS)
• WARD ERROR: Treating Uhthoff's phenomenon as a relapse = steroids not needed

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PARKINSON'S DISEASE

• Drug-induced Parkinsonism: metoclopramide, prochlorperazine, haloperidol, risperidone (D2 blockers) = symmetric resting tremor, NO response to levodopa. STOP the drug
• Essential tremor: ACTION tremor (not resting), improves with alcohol, family history. No rigidity or bradykinesia
• Progressive supranuclear palsy (PSP): falls BACKWARD, downward gaze palsy, symmetric Parkinsonism, no tremor, axial rigidity, poor response to levodopa
• MSA: Parkinsonism + autonomic failure (orthostatic hypotension, urinary incontinence) + cerebellar signs

• Abruptly stopping levodopa/dopamine agonists = dopaminergic crisis (hyperthermia, rigidity, rhabdomyolysis, similar to NMS). NEVER stop Parkinson's medications perioperatively without replacement
• Giving antipsychotics (haloperidol, metoclopramide) for PD hallucinations = worsens Parkinsonism. Use quetiapine (lowest D2 blockade) or clozapine
• Not adjusting levodopa around meals: high-protein meals compete with levodopa absorption at gut and BBB

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MYASTHENIA GRAVIS

• Anti-AChR antibodies (85%). Anti-MuSK (10% of seronegative). Thymic abnormality in 75% (15% thymoma, 60% hyperplasia)
• Repetitive nerve stimulation: DECREMENT at 3Hz = MG (contrast: Lambert-Eaton = INCREMENT at rapid rates)
• Tensilon (edrophonium) test: improvement = myasthenic crisis. Worsening = cholinergic crisis

• Myasthenic crisis: Under-treated. Worsening weakness, respiratory failure. Treat with IVIG/plasmapheresis + increase pyridostigmine
• Cholinergic crisis: Over-treated (too much anticholinesterase). SLUDGE (Salivation, Lacrimation, Urination, Defecation, GI cramps, Emesis) + weakness + miosis. STOP pyridostigmine

• Drugs worsening MG: aminoglycosides, fluoroquinolones, beta-blockers, CCBs, magnesium, D-penicillamine, procainamide, chloroquine
• Not monitoring FVC - respiratory involvement can be subtle until critical. Intubate if FVC <1L or <15-20mL/kg
• Not doing CT chest to screen for thymoma in ALL newly diagnosed MG

• CRITICAL EXAM TRAP: Do NOT give steroids - worsen outcome. Use IVIG or plasmapheresis (equivalent efficacy)
• Most common preceding infection: Campylobacter jejuni (anti-GM1 antibodies). Also EBV, CMV, Zika, COVID-19, post-vaccination
• Spirometry monitoring: "20-30-40 rule": FVC <20mL/kg, MIP <30 cmH2O, MEP <40 cmH2O = intubate. Do NOT rely on SpO2 (drops late)
• Miller-Fisher variant: ophthalmoplegia + ataxia + areflexia. Anti-GQ1b antibodies
• Autonomic dysfunction: cardiac monitoring for arrhythmias, BP lability. DVT prophylaxis essential

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HEADACHE

• "Worst headache of life" / "thunderclap headache" = SAH until proven otherwise
• CT head within 6h: >98% sensitive. If negative = LP at 12h for xanthochromia (yellow CSF from bilirubin)
• WARD ERROR: Normal CT + no LP = MISSED SAH. LP at 12h is mandatory if CT negative
• Most common cause: Berry aneurysm rupture at anterior communicating artery junction (most common site)
• Treat with nimodipine (CCB, reduces cerebral vasospasm = delayed ischemia)

• Migraine: unilateral, pulsating, nausea/vomiting, photophobia/phonophobia, 4-72h. Acute = sumatriptan (oral/SC). Prophylaxis = propranolol (first line), topiramate, amitriptyline, CGRP antagonists (rimegepant, erenumab)
• Cluster: Severe unilateral periorbital/orbital, autonomic features (lacrimation, rhinorrhea, miosis/ptosis, conjunctival injection), MALE, episodic (1-8/day for weeks then remission). Acute = 100% O2 (15L/min, 15-20 min) + sumatriptan SC. Prophylaxis = verapamil
• EXAM MISTAKE: Triptans CONTRAINDICATED in hemiplegic migraine, basilar migraine, ischemic heart disease, uncontrolled hypertension

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SUBHD HEMATOMA vs EPIDURAL HEMATOMA

• EXAM MISTAKE: Chronic subdural in elderly = "dementia" - ALWAYS CT in new-onset cognitive change + history of falls
• WARD ERROR: Not reversing anticoagulation (warfarin: Vit K + PCC; DOAC: specific reversal agents) immediately in traumatic intracranial hemorrhage

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BELL'S PALSY vs CENTRAL VII

• Bell's palsy (LMN lesion): ENTIRE face involved INCLUDING forehead - cannot raise eyebrow, cannot close eye (risk of corneal exposure - eye care essential)
• Central VII (UMN lesion = stroke): Forehead SPARED (bilateral cortical representation) - only lower face weakness contralateral to lesion
• EXAM TRICK: Bell's = forehead NOT spared. Central = forehead spared
• Treatment: Prednisolone within 72h of onset improves recovery. Add acyclovir in severe Bell's (HSV-1 reactivation). Eye patch + lubricating drops to prevent corneal damage

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WERNICKE'S ENCEPHALOPATHY

• Classic triad: Confusion + Ophthalmoplegia (lateral gaze palsy, nystagmus) + Ataxia. Only 10% have all three - most have 1 or 2 features only
• Causes: Thiamine deficiency - alcoholism, prolonged vomiting, malnutrition, hyperemesis gravidarum, post-bariatric surgery, PPN without thiamine supplementation
• WARD ERROR: IV glucose BEFORE thiamine = precipitates or worsens Wernicke's (glucose depletes last remaining thiamine)
• TREATMENT: IV thiamine (Pabrinex 2 ampoules TDS) BEFORE any glucose in any confused/at-risk patient
• Korsakoff's psychosis = chronic irreversible sequel: anterograde > retrograde amnesia, confabulation, preserved intelligence, relatively alert = PERMANENT damage (thiamine resistant)

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NORMAL PRESSURE HYDROCEPHALUS

• Classic triad: "Wet, Wobbly, Wacky" = Urinary incontinence + Gait apraxia (magnetic gait, wide-based, shuffling, feet stuck to floor) + Cognitive decline. Gait comes FIRST, dementia last
• CT/MRI: dilated ventricles disproportionate to sulcal atrophy (Evans' index >0.3)
• Diagnostic test: Large-volume LP (30-50mL removal) → improvement in gait = diagnostic and therapeutic
• MISDIAGNOSIS: Most commonly mistaken for Parkinson's disease (gait) or Alzheimer's disease (memory)
• Treatment: Ventriculoperitoneal shunt. Gait improves most. Incontinence next. Dementia improves least

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SYSTEM 5: CARDIOLOGY

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ACUTE CORONARY SYNDROME

• STEMI = ST elevation ≥1mm in 2+ contiguous limb leads, or ≥2mm in 2+ contiguous precordial leads, OR new LBBB with Sgarbossa criteria
• Posterior STEMI: ST DEPRESSION in V1-V4 + dominant R in V1 = place posterior leads (V7-V9) to see ST elevation
• RV infarction (inferior STEMI): hypotension + clear lungs + raised JVP = PRELOAD DEPENDENT
• EXAM TRAP: Do NOT give nitrates or diuretics in RV infarction = severe hypotension. Give IV fluids to maintain preload

• Women, diabetics, elderly = atypical: fatigue, nausea, jaw pain, epigastric pain, dyspnea without chest pain
• Posterior MI missed: ST depression anteriorly mistaken for "NSTEMI" - check posterior leads

• Not giving dual antiplatelet therapy (aspirin 300mg + ticagrelor 180mg or prasugrel 60mg, then 90mg BD or 10mg OD) - prasugrel CONTRAINDICATED in prior stroke/TIA, age >75, weight <60kg
• Stopping ACEi/beta-blocker/statin after MI = significantly worsens outcome
• Not achieving door-to-balloon time <90min for primary PCI (STEMI). If PCI not available within 120min = thrombolyse
• Not monitoring for mechanical complications post-MI: ventricular septal defect (new harsh pansystolic murmur + RHF), papillary muscle rupture (acute MR + pulmonary edema), free wall rupture (sudden hemodynamic collapse)

• Wellens syndrome: biphasic or deeply inverted T waves in V2-V3 in pain-FREE interval = critical LAD stenosis. HIGH RISK of anterior STEMI. Do NOT exercise test - catheterize urgently
• Dressler's syndrome: fever + pleuritic chest pain + pericardial rub 2-10 weeks post-MI = autoimmune pericarditis. Treat with aspirin + colchicine
• De Winter T-waves: upsloping ST depression + tall peaked T-waves in precordial leads = LAD occlusion (equivalent to anterior STEMI - activate cath lab)

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HEART FAILURE

• "The Fantastic Four" (all proven mortality benefit):
  1. ACEi (ramipril) or ARB or ARNI (sacubitril/valsartan - superior to ACEi in stable HFrEF)
  2. Beta-blocker (bisoprolol, carvedilol, metoprolol succinate - must be EVIDENCE-BASED beta-blockers)
  3. MRA = mineralocorticoid receptor antagonist (spironolactone or eplerenone)
  4. SGLT2 inhibitor (dapagliflozin or empagliflozin - DAPA-HF/EMPEROR-Reduced trials)
• If ACEi/ARB intolerant (cough/angioedema): hydralazine + isosorbide dinitrate (particularly beneficial in Black patients - A-HeFT trial)
• CRT (cardiac resynchronization therapy): HFrEF + LBBB + QRS >150ms + NYHA class III-IV on optimal therapy
• ICD: primary prevention if EF <35% on optimal therapy despite ≥3 months treatment

• Only SGLT2 inhibitors (empagliflozin - EMPEROR-Preserved trial) have shown benefit in HFpEF
• Symptom management: diuretics for congestion, rate-control for AF
• EXAM MISTAKE: Digoxin reduces hospitalizations in HFrEF but does NOT reduce mortality. Not for HFpEF

• Starting beta-blocker in ACUTELY decompensated HF = worsens decompensation. Stabilize with diuretics first
• NSAIDs in HF = cause sodium/water retention, reduce diuretic response, worsen renal function = AVOID in HF
• Aggressive diuresis without monitoring renal function and electrolytes
• Not using sacubitril/valsartan (ARNI) instead of ACEi when eligible (HFrEF, symptomatic, tolerating ACEi, EF <40% - PARADIGM-HF)

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ATRIAL FIBRILLATION

• CHF(1) + Hypertension(1) + Age ≥75(2) + Diabetes(1) + Stroke/TIA/TE(2) + Vascular disease(1) + Age 65-74(1) + Sex female(1)
• Score ≥2 (men) or ≥3 (women) = anticoagulate. Women get +1 only if another risk factor present

• Aspirin has NO significant benefit for stroke prevention in AF - do NOT substitute aspirin for anticoagulation
• DOAC preferred over warfarin for non-valvular AF (exceptions: mechanical heart valves, significant mitral stenosis = use warfarin)
• Rate control with digoxin: only controls rate at REST (vagotonic) - useless during exercise. Use beta-blocker or rate-limiting CCB (diltiazem/verapamil) as first line

• Cardioverting AF of unknown duration (>48h) without anticoagulation for 3 weeks beforehand OR transesophageal echo (TOE) first = risk of embolizing LA thrombus
• WPW + AF = CRITICAL DANGER. Accessory pathway conducts all impulses rapidly → VF. DO NOT give digoxin, adenosine, beta-blockers, or verapamil. Use DC cardioversion or procainamide/flecainide
• Not anticoagulating before cardioversion or rate/rhythm control in patients not already anticoagulated

• Polymorphic VT, long QT (>500ms), twists around baseline
• Causes: hypokalemia, hypomagnesemia, drugs (quinidine, sotalol, haloperidol, clarithromycin, ondansetron, TCAs, methadone)
• Treatment: IV magnesium sulfate 2g over 10-15 min + remove causative drug + correct electrolytes. Temporary pacing if recurrent (increases HR, shortens QT)

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VALVULAR HEART DISEASE

• Symptoms = SAD: Syncope → Angina → Dyspnea (HF). Median survival once symptomatic: Angina 5yr, Syncope 3yr, Dyspnea 2yr
• Severe AS: valve area <1cm², mean gradient >40mmHg, peak velocity >4m/s
• WARD ERROR: Giving nitrates, ACEi, or vasodilators in severe AS = dangerous hypotension (fixed cardiac output, preload-dependent)
• Treatment: TAVR for high surgical risk. Surgical AVR for standard risk. NO medical therapy delays surgery in symptomatic severe AS

• Most common cause: Rheumatic heart disease (worldwide)
• EXAM TRICK: Opening snap (OS) - CLOSER to S2 = MORE severe MS (high LA pressure opens valve earlier in diastole). LONGER diastolic murmur rumble = more severe
• MS + AF = high stroke risk = anticoagulate with warfarin (not DOAC for this indication)
• Pregnancy worsens MS: increased blood volume + HR raises LA pressure → acute pulmonary edema in previously compensated patients

• Acute MR (papillary muscle rupture 2-7 days post-inferior MI, or chordal rupture): surgical emergency. Soft murmur (equalization of LA and LV pressures), flash pulmonary edema, NO cardiomegaly on CXR (no time for remodeling)
• MVP: mid-systolic click + late systolic murmur. Murmur MOVES EARLIER with standing (reduced LV volume) = Barlow's sign

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PERICARDITIS AND TAMPONADE

• Most common cause: Viral/idiopathic
• ECG: saddle-shaped ST elevation in ALL leads EXCEPT aVR and V1 (diffuse, not localized like MI) + PR DEPRESSION (highly specific, often missed)
• Treatment: NSAIDs (ibuprofen 600mg TDS) + colchicine 0.5mg BD for 3 months (halves recurrence rate). Avoid exercise. Steroids only if autoimmune cause or NSAIDs contraindicated

• Beck's triad: Hypotension + distended neck veins (raised JVP) + muffled heart sounds
• Pulsus paradoxus: >10mmHg drop in systolic BP on inspiration (check with sphygmomanometer)
• ECG: electrical alternans (alternating QRS axis) = highly specific for large effusion
• WARD ERROR: Giving diuretics or nitrates in tamponade = worsens hemodynamics (preload-dependent). Emergency pericardiocentesis is treatment

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HYPERTROPHIC CARDIOMYOPATHY (HCM)

• Most common cause of SUDDEN CARDIAC DEATH in young athletes
• Murmur increases with STANDING or VALSALVA (reduces preload → worsens outflow obstruction) - OPPOSITE of aortic stenosis
• Murmur DECREASES with SQUATTING or PASSIVE LEG RAISE (increases preload → reduces obstruction)
• WARD ERROR: Digoxin, nitrates, diuretics, vasodilators = worsen outflow obstruction. AVOID
• Treatment: Beta-blockers (first line), non-dihydropyridine CCB (verapamil). ICD for SCD prevention if risk factors (VT, syncope, family history SCD, LVWT >30mm, abnormal BP response to exercise)
• Septal myectomy or alcohol septal ablation for refractory symptomatic obstruction

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INFECTIVE ENDOCARDITIS

• Most common organism: S. viridans (native valve, dental procedures). S. aureus (IVDU, prosthetic valves, most aggressive, tricuspid valve in IVDU)
• Duke criteria: 2 major OR 1 major + 3 minor OR 5 minor = definite IE
• WARD ERROR: Only 1 set of blood cultures before antibiotics = inadequate. Need 3 sets from different venipuncture sites
• WARD ERROR: Empiric single-antibiotic therapy. Standard: penicillin/amoxicillin + gentamicin (streptococcal). Vancomycin + gentamicin (MRSA/prosthetic valve)
• Right-sided IE (IVDU): Tricuspid valve. Septic pulmonary emboli = bilateral cavitating nodules on CXR. Peripheral stigmata often ABSENT
• Peripheral features: Osler's nodes (tender, fingers/toes, immune complex) vs Janeway lesions (painless, palms/soles, septic emboli). Roth spots (retinal hemorrhages with pale center). Splinter hemorrhages
• Indications for surgery: refractory HF from valvular damage, persistent bacteremia/sepsis, abscess formation, prosthetic valve involvement, fungal endocarditis, recurrent emboli on antibiotics

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SYSTEM 6: RHEUMATOLOGY

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RHEUMATOID ARTHRITIS

• Anti-CCP (anti-cyclic citrullinated peptide): more SPECIFIC than RF for RA, predicts erosive/severe disease. RF also positive in: SLE, Sjögren's, SBE, hepatitis, elderly, cryoglobulinemia
• Extra-articular: Rheumatoid nodules (extensor surfaces), pleuritis/pleural effusion (very LOW glucose), ILD (NSIP pattern), vasculitis, pericarditis, Felty's syndrome (RA + splenomegaly + neutropenia), scleritis, atlantoaxial subluxation

• Anti-TNF without TB screening (CXR + IGRA/Mantoux): reactivation of latent TB can be fatal
• Methotrexate WITHOUT folic acid (5mg weekly, not same day as MTX) = mucositis, hepatotoxicity, cytopenias
• Not monitoring FBC and LFTs on methotrexate
• Not checking for atlantoaxial subluxation before general anesthesia in severe RA (C-spine flexion-extension X-rays required preoperatively)

• NSAIDs (symptom relief) → MTX (first-line DMARD) → add leflunomide or hydroxychloroquine → biologics (anti-TNF: etanercept, adalimumab, certolizumab) → JAK inhibitors (baricitinib, tofacitinib, upadacitinib) if anti-TNF fails

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SLE

• Demographics: Young women, Afro-Caribbean most severely affected
• ANA: >95% sensitive but NOT specific. Anti-dsDNA = correlates with disease activity, elevated in nephritis. Anti-Smith (Sm) = most SPECIFIC for SLE. Anti-Ro (SSA)/Anti-La (SSB) = neonatal lupus + congenital heart block (from maternal antibodies)
• Anti-phospholipid antibodies (anticardiolipin, lupus anticoagulant, anti-beta2-glycoprotein I): APS = recurrent thrombosis + pregnancy loss + thrombocytopenia. Treat with long-term warfarin (NOT DOAC for APS - inferior)

• Complement C3 + C4 both LOW in active SLE nephritis (classical pathway activation by immune complexes)
• Lupus nephritis class IV (diffuse proliferative) = worst, treat with cyclophosphamide (or mycophenolate mofetil = equally effective, better tolerated) + high-dose steroids
• Libman-Sacks endocarditis: sterile vegetations on BOTH sides of mitral valve leaflets (compare to infective: usually one side, typically on low-pressure side)

• NSAIDs in lupus nephritis = worsen renal function
• Not monitoring urine PCR regularly in all SLE patients (early nephritis often asymptomatic)
• Not giving hydroxychloroquine to ALL SLE patients (reduces flares, protects kidneys, improves survival, safe in pregnancy)

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CRYSTAL ARTHROPATHIES

• Urate crystals: needle-shaped, NEGATIVELY birefringent (yellow when parallel to compensator, blue when perpendicular)
• Most common site: First MTP (podagra). Also ankle, knee, wrist
• WARD ERROR: Starting allopurinol DURING acute attack = prolongs and worsens it. Start 2-4 weeks AFTER resolution
• WARD ERROR: Not giving colchicine prophylaxis for 3-6 months when initiating urate-lowering therapy
• Treat acute attack: NSAIDs (indomethacin), colchicine (1mg then 0.5mg 1h later), or corticosteroids (if NSAIDs/colchicine contraindicated)
• DANGEROUS DRUG INTERACTION: Allopurinol + azathioprine = azathioprine toxicity (bone marrow suppression) because allopurinol inhibits xanthine oxidase (azathioprine metabolism). Reduce azathioprine dose by 75%, or use febuxostat instead

• Calcium pyrophosphate crystals: rhomboid, POSITIVELY birefringent (blue when parallel)
• Knee and wrist most common
• Associated metabolic causes: Hyperparathyroidism, hemochromatosis, hypercalcemia, hypothyroidism, hypomagnesemia, Wilson's disease
• Chondrocalcinosis on X-ray (calcification in cartilage)

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SYSTEMIC SCLEROSIS (SCLERODERMA)

• Limited (CREST): Anti-centromere antibodies. Late complication = pulmonary arterial HYPERTENSION (PAH)
• Diffuse: Anti-Scl-70 (anti-topoisomerase I) antibodies. EARLY complication = scleroderma renal crisis

• Sudden severe hypertension + acute AKI in diffuse SSc patient
• CRITICAL EXAM TRAP: ACEi (captopril) is LIFESAVING. Start immediately even if creatinine rising. This is one situation where ACEi is used DESPITE AKI
• WARD ERROR: Withholding ACEi because of rising creatinine = fatal mistake in this context

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VASCULITIS

• Patient >50, female, severe headache, temporal artery tenderness, jaw claudication, scalp tenderness, visual symptoms
• CRITICAL: Visual loss = PERMANENT if steroids delayed (ischemic optic neuropathy)
• WARD ERROR: Waiting for biopsy results before starting steroids = NEVER acceptable. Start prednisolone 40-60mg immediately, then biopsy within 2 weeks (granuloma persists for weeks on steroids)
• Associated with PMR in 50%: bilateral shoulder/hip girdle stiffness + elevated ESR/CRP, responds dramatically to low-dose prednisolone

• Upper respiratory (sinusitis, epistaxis, saddle-nose) + Lower respiratory (cavitating nodules, hemorrhage) + Renal (rapidly progressive GN = pauci-immune on IF)
• c-ANCA (anti-PR3) = GPA. p-ANCA (anti-MPO) = MPA (microscopic polyangiitis, no upper respiratory)
• Treatment: Rituximab + high-dose steroids (induction). Azathioprine or rituximab (maintenance)

• Children <5, fever >5 days + 4/5: conjunctival injection, oral changes (strawberry tongue, cracked dry lips), polymorphic rash, extremity changes (red palms/soles → desquamation), cervical lymphadenopathy
• TREATMENT: IVIG single dose + aspirin (high dose in acute phase, then low dose). IVIG reduces coronary artery aneurysm risk
• EXAM TRAP: Aspirin is INDICATED in Kawasaki (exception to Reye's syndrome rule)

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ANKYLOSING SPONDYLITIS

• HLA-B27 (90%). Young male. Inflammatory back pain: WORSE at rest/night/morning, IMPROVES with exercise (opposite of mechanical back pain)
• WARD ERROR: Avoiding NSAIDs because of "GI risk" - NSAIDs are first-line in AS and may slow radiographic progression. Use them continuously, add PPI gastroprotection
• EXAM MISTAKE: DMARDs (methotrexate, sulfasalazine) do NOT work for AXIAL disease in AS - only help peripheral arthritis
• Treatment: NSAIDs (first line) → anti-TNF (etanercept, adalimumab) → IL-17A inhibitors (secukinumab, ixekizumab) if anti-TNF fails
• Complications: anterior uveitis (most common extraarticular - acute, painful, unilateral red eye), aortic regurgitation, cardiac conduction defects, apical lung fibrosis (upper lobe - unusual pattern)

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SYSTEM 7: NEPHROLOGY

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ACUTE KIDNEY INJURY

• Pre-renal (60%): dehydration, sepsis, cardiac failure, hepatorenal syndrome. Renal (30%): ATN, interstitial nephritis, GN. Post-renal (10%): obstruction (BPH, stones, cervical cancer)

• FeNa <1% = pre-renal (kidneys avidly retaining sodium)
• FeNa >2% = ATN (tubular damage, cannot reabsorb sodium)
• UNRELIABLE if: diuretics given, contrast nephropathy, myoglobinuria, early obstruction

• Continuing ACEi/ARB + NSAIDs in AKI = compounds renal ischemia
• NOT catheterizing to exclude post-renal obstruction = missed diagnosis (simple relief may recover renal function)
• Using nephrotoxic contrast without pre-hydration or without deferring it
• Not dose-adjusting medications in AKI: metformin (lactic acidosis), methotrexate, aminoglycosides, lithium, digoxin, NSAIDs, direct oral anticoagulants

• Contrast-induced nephropathy: creatinine rises 24-48h after contrast, peaks 3-5 days, usually recovers. Prevention: IV hydration pre and post contrast
• AIN (acute interstitial nephritis): drugs (NSAIDs, PPIs, antibiotics - penicillins, rifampicin), eosinophilia, eosinophiluria, rash, fever, AKI. Treatment: stop offending drug + steroids if severe/not recovering

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GLOMERULONEPHRITIS

• IgA nephropathy (Berger's): Most common GN worldwide. Hematuria within 24-48h of URTI (synpharyngitic). Vs post-streptococcal GN = 2-3 weeks AFTER strep throat/skin infection (latent period), low C3, raised ASO titre
• Minimal change disease: Most common nephrotic syndrome in CHILDREN. Responds to steroids. Associated with Hodgkin's lymphoma in adults
• Membranous nephropathy: Most common adult-onset nephrotic syndrome. PLA2R antibodies (primary). Secondary = malignancy, HBV, SLE, drugs (NSAIDs, gold, penicillamine). HIGH thrombosis risk (renal vein thrombosis)
• FSGS: Most common nephrotic in African-Americans. HIV-associated (collapsing variant). Obesity-related
• Goodpasture's syndrome: anti-GBM antibodies. Linear IgG on immunofluorescence. Hemoptysis + nephritis = pulmonary-renal syndrome
• Post-streptococcal GN: LOW C3 (consumed via alternative pathway). Resolves spontaneously in children
• SLE nephritis: LOW C3 AND C4 (classical pathway). Class IV = worst, treat with MMF or cyclophosphamide

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CHRONIC KIDNEY DISEASE

• G1: eGFR ≥90, G2: 60-89, G3a: 45-59, G3b: 30-44, G4: 15-29, G5: <15 or dialysis
• Always combine with albuminuria category (A1/A2/A3) for risk stratification

• Not adjusting drug doses in CKD: metformin (stop if eGFR <30, hold before contrast if eGFR <45), low MW heparin, aminoglycosides, digoxin, NSAIDs, antibiotics
• ACEi/ARB causing creatinine rise ≤30% = ACCEPTABLE (efferent dilation). Rise >30% = renovascular disease or volume depletion

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DIALYSIS INDICATIONS (AEIOU)

• A = Acidosis (pH <7.1 or refractory to bicarbonate)
• E = Electrolytes (life-threatening hyperkalemia refractory to medical management)
• I = Intoxication (lithium, salicylate, methanol, ethylene glycol, metformin lactic acidosis)
• O = Overload (fluid overload refractory to IV diuretics)
• U = Uremia (symptomatic: pericarditis, encephalopathy, uremic bleeding, intractable nausea/vomiting)

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RENAL TUBULAR ACIDOSIS (RTA)

• Type 4 RTA = hyperkalemia + non-anion gap metabolic acidosis in T2DM = frequently missed, frequently tested

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NEPHROLITHIASIS

• WARD ERROR: Not sending stone for analysis = missed metabolic cause
• EXAM MISTAKE: Stones <5mm = 80% pass spontaneously. Indications for intervention: obstruction + sepsis (urological emergency), pain not controlled, failure to pass, solitary kidney obstruction

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POLYCYSTIC KIDNEY DISEASE (ADPKD)

• PKD1 gene (chr 16, 85%) > PKD2 (chr 4, 15%). Autosomal dominant
• Extrarenal manifestations: Berry aneurysms (Circle of Willis), hepatic cysts, splenic cysts, MVP, colonic diverticula, inguinal hernias
• EXAM MISTAKE: Annual screening for intracranial aneurysms by MRA in ADPKD patients with family history of SAH or aneurysm
• Tolvaptan (V2 receptor antagonist): slows cyst growth and GFR decline. Hepatotoxicity monitoring required

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RENAL ARTERY STENOSIS

• Atherosclerosis (elderly, smoker, diabetes) vs fibromuscular dysplasia (young woman, "beaded string" appearance on angiography)
• EXAM TRAP: Bilateral RAS or RAS in solitary kidney + ACEi/ARB = acute AKI (efferent arteriole dilation drops GFR). Always monitor creatinine within 1-2 weeks of starting ACEi in any suspected renovascular disease
• Flash pulmonary edema (recurrent bilateral) + refractory hypertension in elderly = think bilateral RAS

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SYSTEM 8: PSYCHIATRY

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DEPRESSION

• Hypothyroidism mimics depression EXACTLY: fatigue + low mood + weight gain + constipation + cognitive slowing. Always check TSH in new-onset depression
• Also check: FBC (anemia), fasting glucose (diabetes), calcium, B12/folate
• Parkinson's disease: depression precedes motor symptoms by years in 50%

• SSRIs take 4-6 WEEKS for FULL therapeutic effect. Do NOT stop after 2 weeks of "no response"
• Continue antidepressants for at least 6 months after full remission (reduces relapse risk by 70%). Second episode = 1-2 years. Third+ episode = lifelong treatment
• Treatment-resistant depression = failure of 2+ adequate trials (correct dose, correct duration). Consider lithium augmentation, atypical antipsychotic augmentation, or ECT

• Not assessing suicidal ideation in every depressed patient = standard of care. Ask directly - it does NOT increase suicide risk
• Stopping antidepressants suddenly = discontinuation syndrome (FINISH mnemonic: Flu-like symptoms, Insomnia, Nausea, Imbalance, Sensory disturbances, Hyperarousal)
• Not recognizing masked/somatic depression presenting as chronic pain, fatigue, or multiple medically unexplained symptoms

• Serotonin syndrome: SSRIs + MAOIs/triptans/tramadol/fentanyl/linezolid/St John's Wort. Features: Hyperthermia + CLONUS (pathognomonic) + myoclonus + agitation + diarrhea + autonomic instability. Treatment: cyproheptadine (5-HT antagonist) + supportive care. DISTINGUISH from NMS: serotonin syndrome = clonus + hyperreflexia + rapid onset (<24h). NMS = lead-pipe rigidity + hyporeflexia + slower onset + high CK
• Seasonal affective disorder: autumn/winter depression + hypersomnia + carbohydrate craving + weight gain. Treat with light therapy (10,000 lux, 30 min morning) + SSRI

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BIPOLAR DISORDER

• Bipolar I: at least ONE full manic episode (>7 days or hospitalized). Bipolar II: hypomania (4-6 days, NO functional impairment, NOT hospitalized) + major depressive episodes
• Hyperthyroidism can mimic mania. Check TFTs before diagnosing new mania
• Most common misdiagnosis: Unipolar depression (depressive phases predominate in bipolar II). Treating with SSRI alone can trigger MANIC SWITCH

• SSRI monotherapy in bipolar = precipitates hypomania/mania. Always add mood stabilizer
• Lithium monitoring: therapeutic range 0.6-1.0 mmol/L (maintenance), 0.8-1.2 (acute mania). Toxicity at >1.5 mmol/L
  • Toxicity signs: coarse tremor (fine tremor is normal with lithium), dysarthria, ataxia, confusion, nausea/vomiting, cardiac arrhythmias, seizures
  • Drug interactions that RAISE lithium levels: NSAIDs, thiazide diuretics, ACEi/ARBs, metronidazole, dehydration. All reduce renal lithium clearance
  • Long-term monitoring: TFTs 6-monthly (lithium causes hypothyroidism), U&E (nephrogenic DI, CKD), calcium (hypercalcemia/hyperparathyroidism)
• Not switching from lithium in pregnancy planning: lithium teratogenic (Ebstein's anomaly - tricuspid valve malformation). Consider lamotrigine or quetiapine if needed

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SCHIZOPHRENIA / PSYCHOSIS

• Duration distinction: Schizophrenia = symptoms >6 months. Schizophreniform = 1-6 months. Brief psychotic disorder = <1 month
• Positive symptoms (hallucinations, delusions, thought disorder) vs negative (flat affect, alogia, avolition, anhedonia, asociality)
• First-episode psychosis: ALWAYS exclude organic causes: substance-induced (cannabis, amphetamines, PCP), anti-NMDAR encephalitis (must check antibodies in young person with new psychosis + seizures + movement disorder), Wilson's disease, thyroid, metabolic

• High-dose typical antipsychotics in elderly = extrapyramidal effects, falls, QTc prolongation
• Clozapine: most effective for treatment-resistant schizophrenia (failure of ≥2 adequate trials). Requires weekly FBC for 18 weeks, then fortnightly (agranulocytosis risk 1-2%). ABSOLUTE CONTRAINDICATION: combine with carbamazepine (both myelosuppressive - additive risk of agranulocytosis)
• Not getting baseline ECG before starting antipsychotic (all prolong QTc to varying degrees - ziprasidone, IV haloperidol, thioridazine = highest risk)

• Neuroleptic malignant syndrome (NMS): hyperthermia + "lead-pipe" rigidity + autonomic instability (BP lability, tachycardia, diaphoresis) + altered consciousness + raised CK (>1000). Caused by dopamine blockade (antipsychotics, metoclopramide, withdrawal of dopamine agonists)
  • Treatment: STOP antipsychotic immediately, IV fluids, cooling, dantrolene (muscle relaxant), bromocriptine (DA agonist), lorazepam for agitation. Mortality 10-20% if not treated

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DEMENTIA

• Haloperidol in LEWY BODY DEMENTIA = severe neuroleptic sensitivity reaction (rigidity, falls, accelerated decline, death). Use quetiapine at lowest effective dose if antipsychotic absolutely necessary
• Not assessing for REVERSIBLE causes: hypothyroidism, B12/folate deficiency, normal pressure hydrocephalus, neurosyphilis, subdural hematoma, depression (pseudodementia)
• Pseudodementia (depressive pseudodementia): gradual onset, patient COMPLAINS of memory problems (in true dementia they often minimize), improves with antidepressant treatment. Distinguish with neuropsychological testing

• CAM (Confusion Assessment Method): (1) Acute onset + fluctuating + (2) inattention + (3) disorganized thinking OR (4) altered consciousness = positive if 1+2 and either 3 or 4
• Hypoactive delirium: quiet, withdrawn, somnolent = MOST commonly missed type (mistaken for depression)

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ALCOHOL DISORDERS

• 6-24h: Tremors, diaphoresis, anxiety, tachycardia
• 12-48h: Auditory/visual/tactile HALLUCINATIONS (but oriented - different from DT)
• 12-48h: SEIZURES (generalized tonic-clonic)
• 48-72h (up to 5 days): Delirium Tremens (disorientation + autonomic hyperactivity + hallucinations). MORTALITY 5-15% if untreated

• Under-dosing benzodiazepines in alcohol withdrawal = seizures. Use CIWA-Ar protocol (Clinical Institute Withdrawal Assessment). Diazepam or chlordiazepoxide preferred (long-acting). If liver failure = lorazepam (no active metabolites)
• IV glucose WITHOUT thiamine = precipitates Wernicke's
• Using phenytoin for alcohol withdrawal seizures = NOT effective. Use benzodiazepines

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EATING DISORDERS

• BMI <17.5, distorted body image, intense fear of weight gain, amenorrhea
• Medically most dangerous psychiatric disorder (highest mortality rate ~5-10% per decade)
• Physical complications: electrolyte abnormalities (hypokalemia, hypophosphatemia, hypomagnesemia), bradycardia, QTc prolongation, osteoporosis, lanugo hair, hypotension

• Hypophosphatemia (most dangerous - cardiac arrhythmias, respiratory failure, cardiac failure, hemolysis) + hypokalemia + hypomagnesemia + thiamine depletion
• Occurs when refeeding begins after prolonged starvation (insulin release drives phosphate + K + Mg intracellularly)
• Prevention: CHECK phosphate, K, Mg before and during refeeding. Give thiamine before feeding. Introduce feeding SLOWLY (NICE guideline: start at 5-10 kcal/kg/day, increase over 4-7 days)
• WARD ERROR: Starting aggressive enteral/parenteral nutrition without monitoring electrolytes = potentially fatal

• Binge-purge cycles, normal or overweight BMI, dental erosions (enamel loss on lingual surface), parotid gland hypertrophy, Russell's sign (dorsal hand calluses)
• Purging (vomiting): hypokalemia + metabolic ALKALOSIS (loss of HCl)
• Laxative abuse: metabolic ACIDOSIS + hypokalemia

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OVERDOSE / TOXICOLOGY

• Use Rumack-Matthew nomogram (time from ingestion vs plasma level) to determine if NAC needed
• WARD ERROR: Waiting for "elevated LFTs" before starting NAC = delay. In significant overdose, start NAC promptly
• NAC regimen: 150mg/kg IV over 1h, then 50mg/kg over 4h, then 100mg/kg over 16h
• Risk factors for hepatotoxicity at lower paracetamol levels: malnutrition, alcoholism, enzyme-inducing drugs (rifampicin, carbamazepine = increase toxic NAPQI production)

• Features: Anticholinergic (dry mouth, urinary retention, dilated pupils, tachycardia, fever) + QRS widening (>100ms = significant, >160ms = high arrhythmia risk) + seizures + hypotension
• Treatment: IV sodium bicarbonate (alkalinizes plasma, reduces TCA binding to cardiac Na channels, narrows QRS). Target serum pH 7.45-7.55
• WARD ERROR: Giving flumazenil in mixed benzodiazepine + TCA overdose = precipitates unmasked TCA-driven seizures. NEVER use flumazenil if TCA ingestion possible
• WARD ERROR: Physostigmine for TCA = CAN cause seizures and cardiac arrest

• Flumazenil = antidote BUT: precipitates withdrawal seizures in chronic users, short duration (re-sedation occurs). Only use in iatrogenic/procedural over-sedation in benzo-naive patient

• Triad: Miosis (pinpoint) + respiratory depression + decreased consciousness
• Naloxone: 0.4-2mg IV/IM/IN. Short acting (45-90min). Repeat doses often needed for long-acting opioids (methadone, sustained-release morphine). Consider infusion

• NOT life-threatening (unlike alcohol/benzo withdrawal which CAN be fatal)
• Symptoms: lacrimation, rhinorrhea, yawning, piloerection ("cold turkey"), diarrhea, muscle cramps, insomnia, anxiety. NO seizures, NO delirium
• Treatment: Methadone (long-acting opioid substitution) or buprenorphine/naloxone (Suboxone)

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CROSS-SYSTEM EXAM TRAPS (Multi-System Pearls)

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• Beta-blockers → worsen asthma (avoid), peripheral arterial disease (caution), COPD (use cardioselective with caution), HCM (beneficial), MG (worsen)
• NSAIDs → worsen: HF, AKI, cirrhosis/HRS, hypertension, peptic ulcers, asthma (in aspirin-sensitive)
• Thiazides → worsen: gout (raise urate), hyponatremia, hypercalcemia (raise calcium), hypokalemia. IMPROVE: nephrolithiasis (calcium stones - reduces urinary calcium excretion)
• ACEi → worsen: bilateral RAS, hyperkalemia in CKD/AKI, angioedema. AVOID in pregnancy (teratogenic) and scleroderma renal crisis (GIVE in SSc renal crisis)
• Metoclopramide → worsens: Parkinson's disease, MG, precipitates NMS

1. Never give nitrates in RV infarction = fatal hypotension
2. Never give beta-blocker before alpha-blocker in pheochromocytoma = hypertensive crisis
3. Never give iodine before PTU in thyroid storm = Jod-Basedow
4. Never give glucose before thiamine in at-risk patient = precipitates Wernicke's
5. Never give steroids for GBS = worsen outcome
6. Never give haloperidol in Lewy body dementia = neuroleptic sensitivity reaction
7. Never perform needle biopsy of pheo without alpha-blockade = crisis
8. Never give allopurinol in acute gout attack = prolongs it
9. Never give SSRI alone in bipolar disorder = triggers mania
10. Never cardiovert AF >48h duration without anticoagulation or TOE = embolism risk
11. Never allow LP to delay antibiotics in bacterial meningitis = fatal
12. Never give digoxin/beta-blocker/verapamil in WPW + AF = VF risk
13. Never lower BP aggressively in acute ischemic stroke (unless >220/120 or pre-tPA) = extends infarct
14. Never give high-dose oxygen to COPD patients targeting SpO2 >92% = blunts hypoxic drive
15. Never correct hyponatremia faster than 8-10 mmol/L in 24h = osmotic demyelination syndrome

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• Anti-dsDNA + active nephritis = SLE
• Anti-Sm = most specific for SLE
• Anti-Ro (SSA) = Sjögren's, neonatal lupus + congenital heart block
• Anti-CCP = RA (specific, predicts erosive disease)
• Anti-centromere = limited SSc (CREST)
• Anti-Scl-70 (anti-topoisomerase I) = diffuse SSc
• Anti-Jo-1 (anti-synthetase) = polymyositis/dermatomyositis + ILD + mechanic's hands + Raynaud's
• Anti-GBM = Goodpasture's
• c-ANCA (anti-PR3) = GPA (Wegener's)
• p-ANCA (anti-MPO) = MPA, eosinophilic GPA (EGPA/Churg-Strauss)
• Anti-AChR = myasthenia gravis
• Anti-MuSK = seronegative MG
• Anti-GQ1b = Miller-Fisher variant of GBS
• Anti-TPO = Hashimoto's thyroiditis
• Anti-TSH receptor = Graves' disease
• Anti-21-hydroxylase = Addison's disease (autoimmune)
• PLA2R antibody = primary membranous nephropathy

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• SCLC: SIADH (hyponatremia), Cushing's (ectopic ACTH - no dexamethasone suppression), Lambert-Eaton (proximal weakness improves with use), peripheral neuropathy, cerebellar degeneration (anti-Hu)
• Squamous cell lung: Hypercalcemia (PTHrP), hypertrophic osteoarthropathy
• Thymoma: Myasthenia gravis, pure red cell aplasia, hypogammaglobulinemia
• Renal cell carcinoma: Polycythemia (ectopic EPO), hypercalcemia
• Hepatocellular carcinoma: Hypoglycemia (ectopic insulin-like), polycythemia
• Ovarian teratoma: Anti-NMDAR encephalitis

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How to Use These Notes

• Focus on the "Classic Exam Mistakes" and "Eye-Catchers" sections under each topic - these are the highest-yield items that distinguish pass from fail
• The cross-system section at the end (15 "Never Do" errors + antibody table + paraneoplastic syndromes + scoring systems) is particularly dense exam material

• The "Ward Errors" sections are drawn directly from common clinical mistakes documented in Harrison's, Davidson's, and Fischer's Master the Wards
• The comparison tables (nephritic vs nephrotic, delirium vs dementia, cholecystitis vs cholangitis, etc.) are for rapid bedside decision-making

1. Sequence matters - pheo (alpha before beta), thyroid storm (PTU before iodine), thyamine before glucose, antibiotics before CT in meningitis
2. What to avoid - steroids in IPF/GBS, digoxin/adenosine in WPW+AF, ACEi in bilateral RAS, haloperidol in Lewy body, SSRI alone in bipolar
3. Don't correct too fast - hyponatremia (osmotic demyelination), DKA (cerebral edema in children), HHS (cerebral edema)
4. Screen before you treat - TB screening before anti-TNF, HBsAg before immunosuppression, tissue diagnosis before staging in cancer

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🏥 MASTER CLINICAL NOTES — COMPLETE EDITION

Exam Traps | Ward Errors | Misdiagnosis | Clinical Pearls | Mnemonics

All 8 Systems | Harrison's | Davidson's | Kumar & Clark | Oxford | Master the Wards (Fischer)

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SYSTEM 1: RESPIRATORY

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ASTHMA vs COPD

• Cigarettes (primary cause)
• Obstruction fixed (post-bronchodilator FEV1/FVC <0.7)
• Pink puffer (emphysema) / Blue bloater (chronic bronchitis)
• Dyspnea progressive
• FEV1 determines severity
• Alpha-1 antitrypsin in young/non-smoker
• Chest hyperinflation
• Target O2 88-92%
• Sputum purulent = antibiotics in exacerbation

• Asthma: atopy, occupational triggers, aspirin/NSAID sensitivity (Samter's triad)
• COPD: smoking (>90%). Alpha-1 antitrypsin deficiency (AAT) = young, non-smoker, LOWER lobe emphysema (not upper - upper = smoking). Check in any COPD patient under 45 or non-smoker
• Vocal cord dysfunction (VCD) = inspiratory stridor, normal PEFR, normal spirometry between attacks - mimics asthma perfectly

• Reversibility: FEV1 increase >12% AND >200mL = asthma. COPD = fixed obstruction post-bronchodilator
• Acute asthma severity uses PEFR, NOT spirometry: Moderate <75%, Severe <50%, Life-threatening <33%
• Silent chest in acute asthma = WORSE than loud wheeze (no airflow = no sound = impending arrest)
• LABA as monotherapy in asthma = INCREASES mortality. Must ALWAYS be with ICS

• Beta-blockers (even topical timolol eye drops) in asthmatic = fatal bronchospasm
• SpO2 100% in COPD exacerbation = blunts hypoxic drive. Target 88-92%
• Nebulized salbutamol without K+ monitoring = hypokalemia

• Samter's triad: asthma + nasal polyps + aspirin sensitivity
• Churg-Strauss (EGPA): asthma + eosinophilia + p-ANCA vasculitis
• Cardiac asthma: nocturnal wheeze in elderly = LVF. Check BNP

• Salbutamol + ipratropium nebulizers
• Oxygen controlled (88-92%)
• Antibiotics if purulent sputum
• Prednisolone 30-40mg x5 days
• Bronchodilators regular
• Assess for NIV if pH <7.35
• Nasal high-flow if NIV fails

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PNEUMONIA

• Mycoplasma (young adults, cold agglutinins, bilateral patchy)
• Legionella (AC systems, hyponatremia + diarrhea + raised LFTs + relative bradycardia)
• Chlamydophila pneumoniae/psittaci
• Whooping cough (Bordetella pertussis)

• Legionella looks like typical pneumonia but is intracellular - urinary antigen is the KEY test, NOT culture
• PCP in HIV: bilateral ground-glass, CD4 <200, raised LDH, dry non-productive cough

• Legionella = NOT treated with beta-lactams. Use levofloxacin or clarithromycin
• Klebsiella = alcoholics + diabetics + upper lobe + "currant jelly" sputum + cavitation
• Aspiration pneumonia: right lower lobe (upright), right upper lobe posterior segment (supine/recumbent)

• Confusion
• Urea >7 mmol/L
• Respiratory rate >30
• BP <90/60
• 65 = Age >65
• Score 0-1 = outpatient, 2 = admit, 3+ = HDU/ICU

• Blood cultures BEFORE antibiotics in hospitalized pneumonia
• Not getting urinary antigen for Legionella + pneumococcus in severe/ICU CAP
• Amoxicillin alone for CAP = misses atypicals. Add clarithromycin
• PCP: co-trimoxazole high dose. Add steroids if PaO2 <70mmHg

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PULMONARY EMBOLISM

• Clinical signs of DVT: +3
• PE most likely diagnosis: +3
• Immobilization/surgery >3 days: +1.5
• Malignancy: +1
• Hemoptysis: +1
• HR >100: +1.5
• Medical history of prior PE/DVT: +1.5

• 4 = high probability

• "Classic triad" (dyspnea + pleuritic pain + hemoptysis) in <20% of cases
• ECG most common finding = SINUS TACHYCARDIA (not S1Q3T3 which is present in <20%)
• D-dimer only rules out PE in LOW pre-test probability
• Hampton's hump (wedge-shaped infarct) and Westermark sign (oligemia) = classic but rare CXR findings

• Unprovoked PE: indefinite anticoagulation (not just 3 months)
• Massive PE (SBP <90) = thrombolysis (alteplase 100mg over 2h). Do NOT delay
• DOAC preferred over LMWH/warfarin except: antiphospholipid syndrome = warfarin; cancer = DOAC (rivaroxaban or edoxaban) or LMWH

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PLEURAL EFFUSION

• Pleural protein / serum protein > 0.5
• Pleural LDH / serum LDH > 0.6
• LDH pleural > 2/3 upper limit serum normal

• Cardiac failure (most common)
• Hypoalbuminemia (cirrhosis, nephrotic)
• Ascites with pleuroperitoneal communication
• Nephrotic syndrome
• Thyroid (hypothyroidism)
• Meigs syndrome (ovarian fibroma + right effusion + ascites)

• RA effusion = VERY low glucose (<1.6 mmol/L), low complement
• Chylothorax: triglycerides >110 mg/dL, milky fluid, thoracic duct damage (trauma or lymphoma)
• Empyema: pH <7.2 + glucose <60 + LDH >1000 = chest drain mandatory

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TUBERCULOSIS

• Rifampicin = Red/orange secretions, enzyme inducer (↓OCP, warfarin), hepatitis
• Isoniazid = peripheral neuropathy (give pyridoxine B6), hepatitis, SLE-like reaction
• Pyrazinamide = gout (hyperuricemia), hepatitis
• Ethambutol = optic neuritis (check color vision monthly)

• Duration: pulmonary TB = 6 months (2 RIPE + 4 RI). Meningeal/spinal/pericardial TB = 9-12 months
• Steroids INDICATED for: TB meningitis + TB pericarditis (reduces mortality). NOT routine in pulmonary
• Latent TB = INH alone x 6-9 months (NOT full RIPE)
• Rifampicin enzyme induction: reduces OCP, warfarin, phenytoin, antiretrovirals - always warn

• Pott's disease: cold abscess + gibbus deformity + cord compression
• Miliary TB: millet-seed CXR, pancytopenia, choroidal tubercles (fundoscopy), can have NORMAL CXR early
• Addison's worldwide most common cause = TB (adrenal calcification on CT)

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LUNG CANCER

• SIADH (hyponatremia)
• Cushing's (ectopic ACTH - no dexamethasone suppression)
• Lambert-Eaton (proximal weakness IMPROVES with repeated use)
• Cerebellar degeneration (anti-Hu)
• Encephalomyelitis
• Anti-neuronal antibodies
• Thromboembolism

• Squamous cell = hypercalcemia (PTHrP, NOT PTH) + central + cavitates
• Lambert-Eaton IMPROVES with use vs Myasthenia WORSENS with use
• Adenocarcinoma = HPOA + clubbing + peripheral + non-smoker/female/East Asian
• Molecular targets: EGFR → osimertinib; ALK → alectinib; PD-L1 >50% → pembrolizumab

• Pancoast tumor: shoulder pain + Horner's (ptosis + miosis + anhidrosis) = apex lung
• SVC syndrome: facial/arm swelling + dilated neck veins + headache worse on bending = SCLC/lymphoma
• Wellens syndrome: biphasic T waves V2-V3 (pain-free) = critical LAD stenosis (NOT lung cancer but common exam trap in cardio section)

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INTERSTITIAL LUNG DISEASE

• Sarcoidosis: non-caseating granulomas, BHL, hypercalcemia, ACE level
• NSIP: connective tissue disease (RA, SSc, SLE), ground-glass, steroid-responsive
• Asbestosis: lower lobe, pleural plaques, mesothelioma risk, parietal pleural calcification
• Pulmonary fibrosis (IPF): UIP pattern, honeycombing + traction bronchiectasis, Velcro crackles, NO steroids

• IPF = pirfenidone or nintedanib (antifibrotics). Steroids WORSEN IPF
• NSIP = ground-glass pattern, steroid-RESPONSIVE (associated with CTD)
• Sarcoidosis Stage I = BHL alone (often resolves spontaneously, no treatment). Stage IV = fibrosis

• Löfgren syndrome: BHL + erythema nodosum + ankle periarthritis + fever = good prognosis
• Hypersensitivity pneumonitis: bird fancier's lung (pigeon proteins), farmer's lung (Thermophilic actinomyces)
• Sarcoidosis hypercalcemia: macrophages → 1-alpha-hydroxylase → activated vitamin D → hypercalcemia (independent of PTH). Thiazides worsen it

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ARDS

• Mild: PaO2/FiO2 201-300
• Moderate: 101-200
• Severe: ≤100

• ARDS = non-cardiogenic (PCWP <18, BNP normal/low-normal). Cardiogenic pulmonary edema = PCWP >18
• Bilateral infiltrates required: if unilateral = consider pneumonia/contusion

• High tidal volumes = volutrauma. Use 6mL/kg predicted body weight (ARDSNet), plateau pressure <30 cmH2O
• Not using prone positioning in severe ARDS (PF ratio <150) = proven mortality benefit (PROSEVA trial, 16h/day)
• Aggressive fluids after initial resuscitation worsens oxygenation - conservative fluid strategy

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SYSTEM 2: GASTROENTEROLOGY & HEPATOLOGY

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PEPTIC ULCER DISEASE

• Anterior duodenal ulcer = PERFORATES → peritonitis
• Posterior duodenal ulcer = PENETRATES into pancreas → pancreatitis or into left hepatic artery → hemorrhage

• ALWAYS biopsy gastric ulcers (malignancy). Duodenal ulcers rarely malignant
• H. pylori testing: stop antibiotics for 4 weeks and PPIs for 2 weeks before urea breath test or stool antigen
• Zollinger-Ellison: fasting gastrin >1000 pg/mL + refractory ulcers + diarrhea. Part of MEN-1

• NSAIDs + aspirin without PPI = GI bleed risk
• Not repeating endoscopy at 6-8 weeks for gastric ulcer healing confirmation

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GI BLEEDING

• Melena = upper GI (digested blood, dark tarry)
• Upper = BUN:Cr ratio >20 (digested protein absorbed)
• Diarrhea with blood = lower GI or infective

• Upper: Peptic ulcer > varices > Mallory-Weiss tear
• Lower: Diverticulosis > angiodysplasia > colorectal cancer

• Blood products (restrictive transfusion - Hb target 7-8)
• Octreotide/Terlipressin (reduce portal pressure)
• Antibiotics (IV ceftriaxone 1g - SBP prevention, improves survival)
• Tight banding (urgent endoscopy + band ligation)

• Mallory-Weiss = distal esophageal mucosal tear from retching/vomiting (think alcoholic after binge)
• Dieulafoy lesion = large tortuous submucosal artery, massive bleed, no ulcer - very hard to find endoscopically
• Hematochezia (bright red PR) = usually lower GI, but MASSIVE upper GI bleed (rapid transit) can also present as hematochezia

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INFLAMMATORY BOWEL DISEASE

• Fistulas (enterocutaneous, rectovaginal, enterovesical)
• Abscesses
• Strictures (obstructive symptoms)
• Small bowel malabsorption (terminal ileum = B12, fat-soluble vitamins)

• Toxic megacolon: colon >6cm + systemic toxicity → stop antidiarrheals, IV steroids, surgical consult within 48-72h
• C. diff before escalating IBD treatment (both can coexist)
• PSC = "beaded" MRCP, cholangio carcinoma risk. Ursodeoxycholic acid does NOT prevent cancer

• Antidiarrheals (loperamide) in severe flare = precipitates toxic megacolon
• Anti-TNF without TB screening (CXR + IGRA) = fatal reactivation
• Not giving VTE prophylaxis in hospitalized IBD = IBD is highly thrombogenic

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CIRRHOSIS COMPLICATIONS

• Ascitic PMN ≥250 cells/mm³ = SBP (do NOT wait for culture)
• IV ceftriaxone 2g daily + IV albumin 1.5g/kg Day 1, then 1g/kg Day 3
• WARD ERROR: Not giving albumin = misses the protective hepatorenal syndrome prevention

• GI bleed
• Infection
• Drugs (opioids, benzodiazepines)
• Glucose/electrolyte imbalance (hypokalemia, hyponatremia)
• Excessive dietary protein
• Transjugular shunt (portosystemic)

• PRopranolol (non-selective beta-blocker = PRIMARY prevention of variceal bleeding)
• Oesophageal band ligation (secondary prevention)
• Primary: medium/large varices → propranolol/carvedilol
• Selective beta-blockers (atenolol) = DO NOT reduce portal pressure adequately

• NSAIDs or IV contrast in cirrhotic = precipitates hepatorenal syndrome
• Morphine/benzodiazepines in hepatic encephalopathy = fatal
• Lactulose: titrate to 2-3 soft stools/day. Rifaximin for secondary prevention of HE recurrence

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JAUNDICE

• Pre-hepatic (hemolysis): unconjugated bilirubin ↑, LDH ↑, haptoglobin ↓, NO bilirubin in urine
• Active hepatic (hepatocellular): BOTH fractions ↑, AST/ALT ↑↑ > ALP
• Hepatic obstruction (post-hepatic): conjugated ↑, ALP/GGT ↑↑ > AST/ALT, pale stools, dark urine, pruritus

• Courvoisier's law: palpable GB + jaundice ≠ gallstones = pancreatic cancer/cholangiocarcinoma
• Gilbert's syndrome: benign unconjugated hyperbilirubinemia, fasting/illness precipitates, no treatment
• Hepatitis E in pregnancy: 20% mortality in third trimester

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HEPATITIS B SEROLOGY

• Window period = HBsAg cleared, anti-HBs not yet present → ONLY anti-HBc IgM positive
• WARD ERROR: Not screening HBsAg before immunosuppression = fatal reactivation. Give prophylactic entecavir/tenofovir

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PANCREATITIS

• Gallstones (40%)
• Ethanol (35%)
• Trauma
• Steroids
• Mumps (viral)
• Autoimmune
• Scorpion sting
• Hyperlipidemia / Hypercalcemia
• ERCP / Emboli
• Drugs (azathioprine, thiazides, valproate, tetracycline, pentamidine)

• Glucose >200 mg/dL
• Age >55
• LDH >350 IU/L
• Blood WBC >16,000
• AST >250

• Calcium <8 mg/dL
• Hematocrit fall >10%
• Oxygen PaO2 <60
• BUN rise >5 mg/dL
• Fluid sequestration >6L + Base deficit >4

• Prolonged fasting: early enteral nutrition preferred in severe pancreatitis
• Prophylactic antibiotics: NOT indicated even in necrosis unless infection confirmed
• Cullen's + Grey Turner's signs = hemorrhagic pancreatitis = severe disease

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GALLSTONE DISEASE

• Fat
• Female
• Forty
• Fertile

• Charcot's TRIAD = RUQ pain + fever + jaundice
• Reynolds PENTAD = Charcot's triad + confusion + shock = suppurative cholangitis = emergency

• Choledocholithiasis = ERCP (stone removal) + then cholecystectomy
• Acalculous cholecystitis = no stones, ICU patients, high mortality
• Murphy's sign = inspiratory arrest with deep palpation RUQ = acute cholecystitis

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CELIAC DISEASE

• Check total IgA first (IgA deficiency = false negative anti-tTG IgA)
• Anti-tTG IgA = most sensitive/specific
• Villous atrophy on duodenal biopsy (must be eating GLUTEN at time of testing)
• Extra-intestinal: DH (dermatitis herpetiformis), T1DM, autoimmune thyroid, osteoporosis
• Dermatitis herpetiformis = IgA at dermal-epidermal junction, extensor surfaces, pathognomonic for celiac

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SYSTEM 3: ENDOCRINOLOGY

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DKA vs HHS

• Kussmaul breathing (deep, rapid = respiratory compensation for metabolic acidosis)
• Glucose >11 + pH <7.3 + HCO3 <15 + ketones >3 mmol/L
• Anion gap = Na - (Cl + HCO3). Normal 8-12. Raised = DKA

• Fluids (0.9% NaCl first - not hypotonic)
• Insulin (0.1 units/kg/h - only start if K+ >3.5)
• Investigate/treat precipitant (infection most common)
• Correct potassium (insulin drives K+ in - monitor hourly)
• Ketones + anion gap = resolution criteria (NOT just glucose)

• Stop insulin when glucose normalizes = WRONG. Glucose normalizes before ketoacidosis resolves. Continue insulin + start 5% dextrose
• Give insulin if K+ <3.5 = WRONG. Replace K+ first
• Sodium bicarbonate routinely = NOT indicated unless pH <6.9
• Pseudohyponatremia: corrected Na = measured Na + 2.4 per 10 mmol/L glucose above 5

• Hyperosmolar (osmolality >320 mOsm/kg)
• Old patient, T2DM
• Thrombus risk = LMWH mandatory

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THYROID DISORDERS

• Hashimoto's (most common developed world)
• Amiodarone
• Subacute thyroiditis (de Quervain's - viral, self-limiting)
• Hypopituitarism (secondary - TSH low + T4 low)
• Drugs (lithium, carbimazole, PTU)
• Iodine deficiency (most common worldwide)
• De Quervain's (transient)
• Iatrogen (post-radioiodine, post-surgery)
• TSH raised + T4 low = primary; TSH low + T4 low = secondary (pituitary)

• Full-dose levothyroxine in elderly/cardiac patient = angina/MI/AF. Start 25-50mcg, titrate slowly
• Subclinical hypothyroidism: treat if TSH >10 mU/L OR symptomatic OR pregnant

1. PTU (blocks synthesis + conversion) - FIRST
2. Iodine (Lugol's) - 1 HOUR AFTER PTU
3. Beta-blocker (propranolol - controls HR + peripheral conversion)
4. Hydrocortisone (blocks T4→T3 conversion + adrenal support)
5. Cure precipitant (infection, surgery, trauma)

• Cold (hypothermia)
• Obtundation
• Low BP/HR
• Drug precipitants (sedatives, amiodarone)
• Cortisol IV (adrenal insufficiency coexists)
• Oxygen support/ventilate
• Magnesium-like passive rewarming only (no active = vasodilation + collapse)
• Active IV levothyroxine (T3 preferred for faster onset)

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ADRENAL DISORDERS

• Sodium low (hyponatremia)
• ACTH high → pigmentation (buccal mucosa, palmar creases, scars)
• Low blood pressure (postural hypotension)
• Tired (profound fatigue, weight loss)
• Eosinophilia
• Dextrose low (hypoglycemia)

• Primary (Addison's): low cortisol + HIGH ACTH + HYPERPIGMENTATION + HYPERKALEMIA (aldosterone also low)
• Secondary (pituitary): low cortisol + LOW ACTH + NO pigmentation + NO hyperkalemia (aldosterone preserved)

• Hydrocortisone 100mg IV STAT, then 50mg every 6-8h
• IV 0.9% NaCl
• IV glucose if hypoglycemic
• NEVER investigate during crisis - treat first

1. Confirm hypercortisolism: overnight 1mg dexamethasone suppression test (failure to suppress) OR 24h urinary free cortisol
2. ACTH: raised = dependent (pituitary or ectopic). Suppressed = independent (adrenal)
3. Source: High-dose dexamethasone (8mg): Cushing's disease (pituitary) = suppresses >50%. Ectopic ACTH = does NOT suppress. Then MRI pituitary

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CONN'S SYNDROME

• Renovascular HTN = high renin + high aldo (secondary)
• Conn's (primary) = high aldo + LOW renin (autonomous production suppresses renin)
• Screen: any hypertensive with hypokalemia, resistant HTN (≥3 drugs), adrenal incidentaloma + HTN
• Aldosterone:renin ratio >30-50 = positive screen. Confirm with salt loading
• Treatment: adenoma = laparoscopic adrenalectomy. Bilateral hyperplasia = spironolactone/eplerenone

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PHEOCHROMOCYTOMA

• 10% malignant
• 10% bilateral
• 10% extraadrenal (paraganglioma)
• 10% in children
• 10% familial (MEN2, VHL, NF1, SDH mutations)

1. Alpha-blockade FIRST (phenoxybenzamine or doxazosin) x 10-14 days minimum
2. THEN beta-blockade (controls reflex tachycardia)
3. THEN surgery

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HYPERCALCEMIA

• Bones: osteitis fibrosa cystica
• Stones: nephrolithiasis (calcium oxalate)
• Groans: constipation, nausea, peptic ulcer
• Psychic moans: depression, confusion, cognitive impairment

• Primary hyperparathyroidism (most common outpatient)
• Thyroid medications (thiazides raise calcium, loop diuretics lower it)
• Hyperparathyroidism secondary/tertiary (CKD)
• Williams syndrome (neonates)
• Hematological malignancy (myeloma, lymphoma)
• Adenocarcinoma/other malignancy (PTHrP, most common inpatient)
• Thiazide diuretics + Vitamin D toxicity + sarcoidosis/granulomas

• Fluids (IV 0.9% NaCl - FIRST, always)
• Inhibit (bisphosphonate - zoledronic acid, takes 2-4 days)
• Salt diuresis (furosemide only if fluid overloaded)
• Hormon - calcitonin (fastest acting, tachyphylaxis at 48h)
• Bisphosphonate (above)
• Corticosteroids (for sarcoidosis, myeloma, vitamin D toxicity)

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HYPONATREMIA - SIADH

• CNS disease (SAH, meningitis, stroke, encephalitis)
• Malignancy (SCLC #1 - think "lung cancer with hyponatremia")
• Pulmonary (pneumonia, TB, abscess, IPPV)
• Drugs (carbamazepine, SSRIs, thiazides, cyclophosphamide, chlorpropamide, opioids, oxytocin)

• Hypotonic (plasma osmolality <280)
• Osmolality urine >100 mOsm/kg (concentrated urine despite low plasma osmolality)
• Low sodium (<130 symptomatic)
• Euvolemic (not hypo or hypervolemic)
• Sodium in urine >40 mmol/L (kidneys wasting sodium)

• Acute symptomatic hyponatremia: 3% NaCl 1-2 mL/kg/h, raise by 4-6 mmol/L then STOP until reassessment

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MEN SYNDROMES

• Pituitary (prolactinoma = most common)
• Parathyroid (hyperparathyroidism = most common overall component)
• Pancreas (gastrinoma/ZES most common, insulinoma)
• Gene = MEN1, chromosome 11 ("1 on 11")

• Medullary thyroid carcinoma (MTC)
• Pheochromocytoma
• Parathyroid hyperplasia
• Gene = RET proto-oncogene

• MTC + Pheo + Marfanoid habitus + Mucosal neuromas (tongue, lips, eyelids)
• NO parathyroid disease in MEN 2B
• Most aggressive MTC (treat earliest)

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SYSTEM 4: NEUROLOGY

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STROKE

• Bleeding active or coagulopathy (INR >1.7, platelets <100,000)
• Aneurysm/AVM/brain tumor intracranial
• Stroke or serious head trauma within 3 months
• Hypertension BP >185/110 (must control first)
• Hemorrhagic stroke (obvious - also prior intracranial bleed)
• Insulin: glucose <2.7 or >22.2
• Patency: recent non-compressible arterial puncture within 7 days; recent surgery within 3 months

• Lower BP aggressively in acute ischemic stroke = reduces perfusion to penumbra. Only lower if >220/120 (no tPA) or >185/110 (for tPA)
• Aspirin within 24h of tPA = hemorrhagic transformation risk
• Not starting secondary prevention (antiplatelet + statin + antihypertensive)

• Wallenberg (lateral medullary): Dysphagia + Ataxia + ipsilateral Horner's + ipsilateral facial sensory loss + contralateral body pain/temp loss + vertigo/nystagmus

• Pure motor hemiplegia (posterior limb internal capsule)
• Ataxic hemiparesis
• Pure sensory stroke
• Sensorimotor stroke + dysarthria-clumsy hand

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TIA

• Age ≥60 = 1
• BP ≥140/90 = 1
• Clinical: unilateral weakness = 2, speech only = 1
• Duration: ≥60 min = 2, 10-59 min = 1
• Diabetes = 1
• Score ≥4 = high risk of stroke within 48h = urgent investigation

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MENINGITIS

• Ceftriaxone 2g IV 12-hourly (covers N. meningitidis + S. pneumoniae)
• Ampicillin 2g IV 4-hourly (covers Listeria in elderly/immunocompromised)
• Dexamethasone 0.15mg/kg QDS - WITH or BEFORE first antibiotic dose

• Acyclovir 10mg/kg IV TDS empirically = do NOT wait for PCR results

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SEIZURES / STATUS EPILEPTICUS

• Lorazepam IV 0.1mg/kg (first line, 0-10 min)
• Another benzo if no IV (diazepam PR 10-20mg)
• Valproate IV / Levetiracetam IV / phenytoin IV (10-30 min, if not broken)
• Anesthesia (propofol/thiopental) + RSI if refractory (>30-60 min)

• Phenytoin: zero-order kinetics (small increase = huge level rise), enzyme INDUCER, gingival hyperplasia, teratogenic
• AEDDs + enzyme inducers (carbamazepine, phenytoin, phenobarbital) = reduce OCP, warfarin, other AEDs
• Valproate: enzyme INHIBITOR (raises lamotrigine levels - HALVE lamotrigine dose when adding valproate), teratogenic (neural tube defects + fetal valproate syndrome)
• Eclampsia = magnesium sulfate (NOT phenytoin)

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MULTIPLE SCLEROSIS

• Lhermitte's sign (electric shock on neck flexion = cervical cord)
• Internuclear ophthalmoplegia (MLF lesion = adduction deficit + contralateral nystagmus)
• Optic neuritis (painful vision loss, afferent pupillary defect, disc pallor)
• Neurogenic bladder + fatigue + heat sensitivity (Uhthoff's)

• Relapse: IV methylprednisolone 1g x 3-5 days (speeds recovery, does NOT change long-term disability)
• Disease modification: interferon-beta/glatiramer → natalizumab → alemtuzumab/ocrelizumab

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PARKINSON'S DISEASE

• Tremor (resting, pill-rolling, 4-6 Hz)
• Rigidity (cogwheel, lead-pipe)
• Akinesia/Bradykinesia (reduced speed)
• Postural instability

• Metoclopramide
• Evening primrose (uncommon)
• Prochlorperazine
• Sulpiride / risperidone / haloperidol

• Abruptly stopping dopaminergic drugs = dopaminergic crisis/NMS-like (hyperthermia, rigidity, rhabdomyolysis)
• Antipsychotics for PD psychosis = use quetiapine (lowest D2 blockade) or clozapine only
• High-protein meals compete with levodopa absorption at gut and BBB

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MYASTHENIA GRAVIS

• Myasthenic crisis: under-treated → SLUDGE absent, worsening weakness. Edrophonium test IMPROVES
• Cholinergic crisis: over-treated (too much pyridostigmine) → SLUDGE (Salivation, Lacrimation, Urination, Defecation, GI cramps, Emesis) + miosis. Edrophonium test WORSENS

• Aminoglycosides
• Beta-blockers
• Calcium channel blockers
• Magnesium
• Macrolides / fluoroquinolones / D-penicillamine

• Steroids = CONTRAINDICATED in GBS (worsen outcome)
• Most common preceding infection = Campylobacter jejuni
• 20-30-40 rule for intubation: FVC <20mL/kg, MIP <30, MEP <40
• SpO2 drops LATE in GBS - monitor FVC serially, not saturation

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HEADACHE

• Worst headache of life
• Wake-up/exertional precipitant (weight lifting, sex, straining)
• Well initially then deteriorates (sentinel bleed)
• Warning signs: stiff neck, photophobia, vomiting
• Write off? NO. CT within 6h. If negative → LP at 12h for XANTHOCHROMIA

• Migraine: Unilateral, pulsating, nausea, photo/phonophobia, 4-72h. Acute = triptan. Prophylaxis = propranolol/topiramate/CGRP antagonist
• Tension: Bilateral, band-like, NO nausea/vomiting/photophobia. Paracetamol/NSAIDs
• Cluster: Severe unilateral periorbital, AUTONOMIC features (lacrimation, rhinorrhea, Horner's). Male. Acute = 100% O2 + SC sumatriptan. Prophylaxis = verapamil

• Coronary artery disease / ischemic heart disease
• Hemiplegic migraine
• Ischaemic stroke / TIA
• Vasospasm (basilar migraine, Prinzmetal angina)

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BELL'S PALSY vs CENTRAL VII

• Bell's (LMN): ENTIRE face including forehead affected - cannot raise eyebrow
• Central (UMN): forehead SPARED - upper face bilateral cortical representation

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WERNICKE'S ENCEPHALOPATHY

• Only 10% have all three. Most have 1 or 2 features. Give thiamine empirically in ANY confused at-risk patient

• IV thiamine (Pabrinex 2 ampoules TDS) BEFORE any glucose. ALWAYS.

• Confabulation
• Onwards amnesia (anterograde >> retrograde)
• No new memories
• Fair intelligence preserved
• Alert/awake
• Brain mammillary body damage (thiamine-resistant)

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HORNER'S SYNDROME

• Ptosis (partial, superior tarsal muscle)
• Anhidrosis (same side)
• Miosis (small pupil)

• Enophthalmos (apparent, not real)

• Central (hypothalamus → T1): MS, Wallenberg syndrome, syringomyelia, pontine glioma
• Preganglionic (T1 → superior cervical ganglion): Pancoast tumor (lung apex), cervical rib, thyroid tumor, neck dissection
• Postganglionic (superior cervical ganglion → eye): ICA dissection (neck pain + Horner's in young = URGENT), cluster headache, cavernous sinus pathology

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SYSTEM 5: CARDIOLOGY

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ACUTE CORONARY SYNDROME

• Posterior STEMI = ST depression V1-V4 + dominant R in V1 (put posterior leads V7-V9)
• Right ventricle infarction = inferior STEMI + hypotension + clear lungs + raised JVP. NO NITRATES
• Aspirin 300mg + ticagrelor 180mg (or prasugrel - AVOID if prior stroke/TIA, age >75, weight <60kg)
• Wellens syndrome = biphasic/deep T-wave inversion V2-V3 (pain-free) = critical LAD = do NOT exercise test
• Not giving dual antiplatelet = increases reinfarction risk

• VSR (ventricular septal rupture): day 3-5, harsh pansystolic murmur + RHF
• Papillary muscle rupture: day 2-7, acute MR + flash pulmonary edema (soft murmur)
• Pericarditis (Dressler's): week 2-10, autoimmune, fever + pleuritic pain + raised ESR

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HEART FAILURE

• Beta-blocker (bisoprolol, carvedilol, metoprolol succinate)
• ACEi/ARB/ARNI (sacubitril-valsartan preferred if eligible - PARADIGM-HF)
• MRA (spironolactone or eplerenone)
• SGLT2 inhibitor (dapagliflozin or empagliflozin - DAPA-HF/EMPEROR-Reduced)

• Beta-blocker in ACUTELY decompensated HF = worsens decompensation. Stabilize first
• NSAIDs in HF = fluid retention, diuretic resistance, worsened renal function. AVOID absolutely
• Digoxin = reduces hospitalizations (NOT mortality) in HFrEF. Not for HFpEF

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ATRIAL FIBRILLATION

• Congestive HF = 1
• Hypertension = 1
• Age ≥75 = 2
• Diabetes = 1
• Stroke/TIA/TE = 2
• Vascular disease (prior MI, PAD, aortic plaque) = 1
• Age 65-74 = 1
• Sex female = 1 (only if another risk factor present)
• Score ≥2 (men) or ≥3 (women) = anticoagulate

• Don't give: Adenosine, Beta-blockers, Amiodarone (IV), Digoxin/diltiazem/verapamil
• All can enhance accessory pathway conduction → VF
• USE: DC cardioversion (first line if unstable) or procainamide/flecainide (if stable)

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VALVULAR DISEASE

• Syncope = 3 years median survival
• Angina = 5 years median survival
• Dyspnea (heart failure) = 2 years median survival
• Do NOT give vasodilators (nitrates, ACEi) in severe AS = dangerous hypotension

• OS closer to S2 = higher LA pressure = more severe MS
• Longer diastolic murmur = more severe
• MS + AF = anticoagulate with WARFARIN (not DOAC for significant MS with AF)

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PERICARDITIS & TAMPONADE

• Beck's triad: Hypotension + raised JVP + Muffled heart sounds
• Pulsus paradoxus: >10mmHg drop in systolic on INSPIRATION
• Electrical alternans on ECG = large pericardial effusion (pathognomonic)
• TREATMENT = pericardiocentesis. NOT diuretics (preload-dependent)

• Saddle-shaped ST elevation in ALL leads except aVR and V1
• PR DEPRESSION (highly specific, commonly missed)
• Treatment: ibuprofen + colchicine 3 months (halves recurrence)

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HCM

• Murmur LOUDER with standing/Valsalva (reduces preload → worse outflow obstruction)
• Murmur SOFTER with squatting/leg raise (increases preload → less obstruction)
• OPPOSITE of AS (which decreases with Valsalva)
• Most common cause of sudden cardiac death in young athletes

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INFECTIVE ENDOCARDITIS

• Janeway lesions (painless - septic emboli, palms/soles)
• Osler's nodes (painful - immune complex, finger/toe pads)
• Nail splinter hemorrhages
• Eye (Roth spots - retinal hemorrhage with pale center)
• Splenomegaly
• Roth spots (above)

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SYSTEM 6: RHEUMATOLOGY

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RHEUMATOID ARTHRITIS

• MCP + PIP + wrists (symmetric). DIP spared (DIP = OA/psoriatic)
• Heberden's nodes (DIP) = OA. Bouchard's nodes (PIP) = RA or OA

• Splenomegaly
• Severe RA
• Suppressed neutrophils (neutropenia = infection risk)

• NSAIDs (symptom relief only)
• MTX first-line DMARD (ALWAYS with folic acid 5mg weekly, NOT same day)
• Biologics: anti-TNF (etanercept, adalimumab, certolizumab) - screen for TB first
• JAK inhibitors: baricitinib, tofacitinib (if anti-TNF fails, but VTE/cardiac risk monitoring)

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SLE

• Serositis
• Oral ulcers
• Arthritis
• Photosensitivity
• Blood disorders (cytopenias)
• Renal involvement
• ANA positive
• Immunological (anti-dsDNA, anti-Sm)
• Neurological (seizures, psychosis)
• Malar rash
• Discoid rash

• ANA = 95% sensitive but NOT specific
• Anti-dsDNA = disease activity + nephritis marker
• Anti-Sm = MOST SPECIFIC for SLE

• Miscarriages (recurrent pregnancy loss)
• Microcirculation (livedo reticularis, skin)
• Major thrombosis (arterial AND venous)
• Treatment = WARFARIN (not DOAC - APS trials showed inferiority of DOACs in APS)

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CRYSTAL ARTHROPATHIES

• Gout = NEGATIVELY birefringent (yellow when parallel to compensator axis)
• Pseudogout = POSITIVELY birefringent (blue when parallel) + RHOMBOID crystals

• Acute attack: NSAIDs (indomethacin) OR colchicine OR corticosteroids
• Start allopurinol 2-4 weeks AFTER attack resolves, WITH colchicine prophylaxis x 3-6 months

• Calcium (hypercalcemia)
• Hemochromatosis
• Hyperparathyroidism
• Magnesium low (hypomagnesemia)
• Hypothyroidism
• Wilson's disease

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SYSTEMIC SCLEROSIS

• CREST (Limited SSc): Calcinosis + Raynaud's + Esophageal dysmotility + Sclerodactyly + Telangiectasia. Anti-centromere antibodies. Late complication = PAH
• Diffuse SSc: Anti-Scl-70 (anti-topoisomerase I). Early complication = scleroderma renal crisis

• Sudden severe hypertension + AKI in diffuse SSc
• ACEi (captopril) = LIFESAVING. Use even if creatinine rising
• This is THE exception where ACEi is GIVEN despite AKI (not withheld)

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VASCULITIS

• Visual loss = PERMANENT if steroids delayed
• Start prednisolone 40-60mg immediately. Biopsy within 2 weeks (granulomas persist weeks on steroids)
• Skip lesions = biopsy must be >2cm length
• PMR in 50%: bilateral shoulder/hip girdle stiffness + ESR/CRP raised (responds dramatically to LOW-dose prednisolone)

• Upper airways (sinusitis, saddle nose) → Lungs (cavitating nodules) → Kidneys (rapidly progressive GN, pauci-immune)
• c-ANCA (anti-PR3) = GPA. p-ANCA (anti-MPO) = MPA (no upper respiratory)
• Treatment: Rituximab + steroids (induction), then rituximab/azathioprine (maintenance)

• Conjunctival injection (bilateral, non-purulent)
• Rash (polymorphic)
• Adenopathy (cervical, unilateral)
• Strawberry tongue + cracked lips
• Hands/feet desquamation
• Fever >5 days + 4/5 above features
• Treatment: IVIG + aspirin (Aspirin IS indicated here - exception to Reye's rule)

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ANKYLOSING SPONDYLITIS

• Worse at rest/night/morning. IMPROVES with exercise. HLA-B27 (90%)
• Opposite of mechanical back pain (worse with activity)

• Anterior uveitis (most common, acute painful unilateral red eye)
• Aortic regurgitation
• Apical lung fibrosis (unusual upper lobe)
• Block (cardiac conduction defect)

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SYSTEM 7: NEPHROLOGY

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ACUTE KIDNEY INJURY

• Volume depletion, sepsis, cardiac failure, HRS, NSAIDs/ACEi

• ATN (most common intrinsic), GN, AIN (drugs - PPIs, antibiotics, NSAIDs), rhabdomyolysis

• BPH, stones, cervical cancer, retroperitoneal fibrosis, bladder clot

• Contrast without pre-hydration
• ACEi/ARB + NSAIDs - continue during AKI
• Not catheterizing (misses obstructive uropathy)
• Stop nephrotoxic drugs immediately (aminoglycosides, metformin, lithium)

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GLOMERULONEPHRITIS

• Nephritic: RBC casts (pathognomonic), hematuria, hypertension, oliguria
• Nephrotic: fatty casts + oval fat bodies, heavy proteinuria >3.5g/day, edema, hypoalbuminemia, hyperlipidemia, thrombosis

• IgA nephropathy (Berger's): hematuria 24-48h after URTI = synpharyngitic
• Post-streptococcal GN: 2-3 weeks LATENT PERIOD after throat/skin infection, LOW C3, raised ASO

• Linear IgG = Goodpasture's (anti-GBM)
• Immune complex (granular) = Post-strep GN, SLE, membranous
• No/pauci immune = ANCA vasculitis (GPA, MPA)
• Granular mesangial IgA = IgA nephropathy

• Low C3 only: post-streptococcal GN, alternative pathway activation
• Low C3 AND C4: SLE, cryoglobulinemia (classical pathway activation)
• Normal complement: IgA nephropathy, Goodpasture's, ANCA vasculitis

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CHRONIC KIDNEY DISEASE

• Anemia (normochromic normocytic, ↓EPO → ESA + IV iron, target Hb 100-120)
• Bone disease (renal osteodystrophy: ↓vit D, ↑PO4, ↑PTH → alfacalcidol + phosphate binders)
• Cardiovascular risk (#1 cause of death in CKD)
• Drugs - dose adjust or avoid (metformin, NSAIDs, aminoglycosides, LMWH, digoxin)
• Electrolytes (hyperkalemia, metabolic acidosis → sodium bicarbonate supplementation)

• G1 ≥90, G2 60-89, G3a 45-59, G3b 30-44, G4 15-29, G5 <15 (dialysis)

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DIALYSIS INDICATIONS

• Acidosis (pH <7.1 or refractory)
• Electrolytes (severe hyperkalemia refractory to medical management)
• Intoxication (lithium, salicylate, methanol, ethylene glycol, metformin lactic acidosis)
• Overload (fluid overload refractory to IV diuretics)
• Uremia (symptomatic: pericarditis, encephalopathy, uremic bleeding, platelet dysfunction)

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RENAL TUBULAR ACIDOSIS

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NEPHROLITHIASIS

• Calcium oxalate (80%) - radiopaque, most common
• Uric acid - RADIOLUCENT (invisible on plain XR), gout/hyperuricemia → alkalinize urine
• Struvite - "Staghorn" calculi, urease-producing organisms (Proteus, Klebsiella), female > male
• Cystine - hexagonal crystals on urine microscopy, autosomal recessive

• Stone <5mm = ~80% pass spontaneously
• Indications for intervention: Sepsis + obstruction (urological emergency), Size >10mm, uncontrolled Pain, Single kidney obstructed, Stagnant (failure to progress)

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POLYCYSTIC KIDNEY DISEASE (ADPKD)

• Berry aneurysms (Circle of Willis - SAH risk - screen with MRA if family history SAH)
• Bileduct/hepatic cysts (most common extrarenal finding)
• BP elevation (hypertension - ACEi/ARB first line)
• PKD1 (chr 16) = 85%, PKD2 (chr 4) = 15%. PKD1 = more severe, earlier ESRD
• Tolvaptan = slows cyst growth (V2 receptor antagonist). Monitor for hepatotoxicity

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SYSTEM 8: PSYCHIATRY

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DEPRESSION

• Sleep disturbance
• Interest loss (anhedonia)
• Guilt / worthlessness
• Energy low
• Concentration impaired
• Appetite change (usually decreased)
• Psychomotor changes (agitation or retardation)
• Suicidal ideation

• SSRIs take 4-6 WEEKS for full effect. Do NOT stop before 4-6 weeks
• Continue for 6 months minimum after FULL remission. Second episode = 1-2 years. Third+ = lifelong
• Always check TSH, FBC, B12/folate, glucose in new-onset depression (exclude organic causes)

• SSRIs/SNRIs
• MAOIs (including linezolid, methylene blue)
• Anti-migraine triptans
• Lithium
• Tramadol/Tapentadol/fentanyl + St. John's Wort + TCAs

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BIPOLAR DISORDER

• Bipolar I = full manic episode (>7 days or hospitalized, IMPAIRS functioning)
• Bipolar II = hypomanic episodes (4-6 days, does NOT impair functioning) + major depressive episodes

• Coarse tremor (fine tremor = normal at therapeutic levels)
• Ataxia + dysarthria
• Twitching (myoclonus) + GI upset (nausea, diarrhea)
• Seizures + confusion + cardiac arrhythmias (at toxic levels >1.5 mmol/L)

• TFTs every 6 months (hypothyroidism)
• U&E every 6 months (CKD, nephrogenic DI)
• Calcium annually (hypercalcemia/hyperparathyroidism)

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SCHIZOPHRENIA

• Brief psychotic disorder = <1 month
• schizoAffective = concurrent mood disorder
• Schizophreniform = 1-6 months
• Schizophrenia = >6 months

• Most EFFECTIVE for treatment-resistant schizophrenia (failure of ≥2 adequate antipsychotics)
• Granulocyte monitoring = weekly FBC for 18 weeks, then fortnightly
• Restricted prescription
• Effective where others fail
• Agranulocytosis (1-2% risk = potentially fatal)
• Titrate slowly
• ABSOLUTE CONTRAINDICATION: Carbamazepine (both myelosuppressive) + previous clozapine-induced agranulocytosis

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DEMENTIA

• Dell hallucinations (visual, well-formed)
• Instable fluctuating cognition
• Voluntary movement = Parkinsonism
• Autonomic dysfunction (orthostatic hypotension) + REM sleep behavior disorder

• Use quetiapine only if antipsychotic absolutely necessary

• Subdural hematoma
• Metabolic (hypothyroidism, B12/folate deficiency, thiamine)
• Infection (neurosyphilis, HIV dementia, prion - rare)
• Tumor + normal pressure Hydrocephalus
• Hydrocephalus (NPH = wet + wobbly + wacky)

• Wet (urinary incontinence) - appears first
• Wobbly (magnetic gait - feet stuck to floor) - appears first
• Wacky (cognitive impairment) - appears LAST
• Treatment: ventriculoperitoneal shunt. Gait improves most, dementia least

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ALCOHOL DISORDERS

• Tremors + autonomic (6-24h)
• Hallucinations (auditory/visual, 24-48h, but ORIENTED)
• Seizures (12-48h)
• Delirium tremens (48-72h to 5 days) - mortality 5-15% untreated

• Diazepam or chlordiazepoxide (long-acting) - CIWA-Ar guided dosing
• Liver failure = lorazepam (short-acting, no hepatic metabolism)
• ALWAYS thiamine BEFORE glucose

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EATING DISORDERS

• Phosphate (most dangerous - cardiac arrhythmias, respiratory failure)
• Kalium (potassium) - hypokalemia
• Magnesium - hypomagnesemia
• Thiamine depletion (Wernicke's risk)

• Parotid hypertrophy (bilateral)
• Acidosis/Alkalosis (vomiting = metabolic alkalosis; laxatives = acidosis)
• Russell's sign (dorsal hand calluses)
• Enamel erosion (dental, lingual surface)
• Dental caries + hypokalemia

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OVERDOSE / TOXICOLOGY

• QRS >100ms = significant; >160ms = arrhythmia risk
• Anticholinergic: dry, hot, mad, red (dry mouth, urinary retention, confusion, flushed)
• Treatment: IV SODIUM BICARBONATE (alkalinizes plasma, narrows QRS, stabilizes myocardium)
• WARD ERROR: Flumazenil in mixed TCA/benzo overdose = precipitates seizures

• Miosis (pinpoint pupils)
• Mute (depressed consciousness)
• Minimal respiration (respiratory depression)
• Treatment: Naloxone 0.4-2mg IV. Short-acting - repeat doses needed for long-acting opioids

• Opioid withdrawal = very uncomfortable, NOT life-threatening (no seizures, no DTs)
• Alcohol/benzodiazepine withdrawal = CAN be fatal (seizures + delirium tremens)

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CROSS-SYSTEM MASTER REFERENCE

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THE "NEVER DO" LIST (15 Cardinal Errors)

1. Nitrates in RV infarction = hypotension
2. Every TB drug without pyridoxine alongside INH
3. Vasodilators (ACEi/nitrates) in severe aortic stenosis
4. Exercise test in Wellens syndrome = LAD → STEMI
5. Rapid hyponatremia correction (>10 mmol/24h) = osmotic demyelination
6. Beta-blocker before alpha-blocker in pheo = crisis
7. Iodine before PTU in thyroid storm = Jod-Basedow
8. Glucose before thiamine in Wernicke's = precipitates encephalopathy
9. ASP (aspirin) within 24h of tPA in ischemic stroke = hemorrhage
10. LP before antibiotics in suspected bacterial meningitis = fatal delay
11. PH assay (waiting) before CT-PA in massive PE = delay thrombolysis
12. Haloperidol in Lewy body dementia = neuroleptic sensitivity reaction
13. Allopurinol during acute gout attack = prolongs it
14. Full SSRI monotherapy in bipolar = triggers mania
15. Anticoagulate inadequately before cardioversion in AF >48h = embolism
16. Steroids for GBS = worsen outcome
17. Thalidomide... → replace with: NOT stopping metoclopramide in Parkinson's = worsens motor function

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HIGH-YIELD ANTIBODY REFERENCE TABLE

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PARANEOPLASTIC SYNDROMES REFERENCE

• SIADH (hyponatremia)
• Cushing's (ectopic ACTH, no suppression)
• Lambert-Eaton (proximal weakness IMPROVES with repeated use)
• Cerebellar degeneration (anti-Hu)
• Encephalomyelitis
• Anti-neuronal antibodies
• Thromboembolism

• Squamous cell lung: PTHrP → hypercalcemia
• Adenocarcinoma lung: HPOA → clubbing, periosteal new bone
• Thymoma: Myasthenia gravis + pure red cell aplasia + hypogammaglobulinemia
• RCC: ectopic EPO → polycythemia
• HCC: ectopic IGF-2 → hypoglycemia
• Ovarian teratoma: anti-NMDAR encephalitis

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KEY SCORING SYSTEMS SUMMARY

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DRUGS THAT WORSEN SPECIFIC CONDITIONS

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ADRENAL CRISIS vs ANAPHYLAXIS vs SEPTIC SHOCK (DIFFERENTIATING THE COLLAPSED PATIENT)

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FINAL HIGH-YIELD EXAM PEARLS (Commonly Missed)

1. Carcinoid syndrome: flushing + diarrhea + right-sided valvular disease + wheeze. 5-HIAA in urine. Octreotide for symptoms. Carcinoid heart disease = tricuspid + pulmonary valve (right-sided) because serotonin deactivated in lungs before reaching left side
2. Addison's + hyponatremia: the only case of hyponatremia where SALT is the answer (not just fluid restriction)
3. Polycythemia vera: raised Hb + splenomegaly + aquagenic pruritus (itch after hot bath) + raised WBC + raised platelets + low EPO. JAK2 mutation. Treat with venesection + hydroxycarbamide
4. Hemochromatosis: "Bronze diabetes" = bronze skin + diabetes + cirrhosis + cardiomyopathy + arthropathy (2nd/3rd MCP joints, calcium pyrophosphate crystals). Raised ferritin + transferrin saturation >45%. HFE gene mutation (C282Y). Treat with phlebotomy
5. Porphyria (AIP): dark urine (porphobilinogen) + abdominal pain + neuropsychiatric symptoms + autonomic dysfunction. Precipitated by: alcohol, drugs (carbamazepine, valproate, sulfonamides, rifampicin), fasting, hormones. Treat: high carbohydrate diet, haem arginate (IV), avoid triggers
6. Wilson's disease: Kayser-Fleischer rings + liver disease + neuropsychiatric symptoms + Coombs-negative hemolytic anemia. Low ceruloplasmin + raised urinary copper. Treatment: D-penicillamine or trientine (copper chelator), then zinc maintenance
7. Acromegaly: enlarged jaw + hands + feet + coarse facies + macrognathia + carpal tunnel + sleep apnea + diabetes + hypertension. Raised IGF-1. Confirm: failure of GH suppression after oral glucose. GH normally falls to <1 mcg/L in normal. Treatment: transsphenoidal surgery
8. SIADH from carbamazepine: student in clinic with epilepsy + hyponatremia = ALWAYS check carbamazepine as cause (enzyme inducer AND causes SIADH - both effects)
9. Osler-Weber-Rendu (HHT): hereditary hemorrhagic telangiectasia. Telangiectasias (lips, tongue, fingertips) + recurrent epistaxis + arteriovenous malformations (lung = platypnea/orthodeoxia). Autosomal dominant
10. Myxoma: left atrial myxoma = constitutional symptoms (fever, weight loss, raised ESR) + obstructive symptoms (syncopal attacks on bending, positional dyspnea) + embolic events. "Tumor plop" on auscultation. Echo is diagnostic. Surgical excision

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• System 1: Respiratory (Asthma/COPD, Pneumonia, PE, Pleural effusion, TB, Lung Ca, ILD, ARDS)
• System 2: GI/Hepatology (PUD, GI bleed, IBD, Cirrhosis, Jaundice, Hepatitis, Pancreatitis, Celiac, Gallstones)
• System 3: Endocrinology (DKA/HHS, Thyroid, Adrenal, Cushing's, Conn's, Pheo, Hypercalcemia, Hyponatremia, MEN)
• System 4: Neurology (Stroke, TIA, Meningitis, Seizures, MS, PD, MG, GBS, Headache, Hematoma, Bell's, Wernicke's, NPH, Horner's)
• System 5: Cardiology (ACS, HF, AF, Valvular, Pericarditis/Tamponade, HCM, IE)
• System 6: Rheumatology (RA, SLE, Gout/Pseudogout, SSc, Vasculitis, AS)
• System 7: Nephrology (AKI, GN, CKD, Dialysis, RTA, Stones, PKD, RAS)
• System 8: Psychiatry (Depression, Bipolar, Schizophrenia, Dementia, Alcohol, Eating disorders, Overdose)

🩸 SYSTEM 9: HEMATOLOGY & ONCOLOGY

Exam Traps | Ward Errors | Misdiagnosis | Clinical Pearls | Mnemonics

Based on Harrison's | Davidson's | Kumar & Clark | Oxford Handbook | Master the Wards (Fischer)

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PART A: HEMATOLOGY

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ANEMIA - OVERVIEW & CLASSIFICATION

• Thalassemia
• Anemia of chronic disease (can be micro OR normo)
• Iron deficiency anemia (most common cause worldwide)
• Lead poisoning (sideroblastic)
• Sideroblastic anemia (congenital or acquired)

• Megaloblastic: B12 deficiency / folate deficiency
• Alcohol (direct marrow toxicity)
• Liver disease
• Thyroid (hypothyroidism)
• Bone marrow failure / myelodysplasia
• Antifolates (methotrexate, trimethoprim, hydroxyurea)
• Reticulocytosis (raised MCV from large reticulocytes - hemolysis, post-hemorrhage)

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IRON DEFICIENCY ANEMIA (IDA)

• Women of reproductive age: menorrhagia (most common)
• Men and post-menopausal women: GI blood loss until proven otherwise (colonoscopy mandatory)
• Worldwide: dietary deficiency + hookworm infection

• Ferritin is an ACUTE PHASE REACTANT - can be falsely NORMAL or HIGH in IDA if concurrent infection/inflammation. Check transferrin saturation (low in IDA) if ferritin equivocal
• IDA indices: ↓Hb + ↓MCV + ↓MCH + ↓ferritin + ↓serum iron + ↑TIBC (total iron binding capacity raised = body craving iron)
• Anemia of chronic disease (ACD): ↓ferritin NORMAL or HIGH + ↓serum iron + ↓TIBC (body locks iron away from bacteria/inflammation). KEY: TIBC differentiates IDA (high TIBC) from ACD (low/normal TIBC)

• Not investigating the CAUSE of IDA before just treating with iron supplements - GI malignancy missed
• Giving IV iron without checking for active infection (iron feeds bacteria)
• Not rechecking Hb + ferritin after 4-6 weeks of treatment to confirm response

• Plummer-Vinson syndrome (Patterson-Kelly): IDA + dysphagia (esophageal web) + koilonychia (spoon nails). Premalignant (squamous cell carcinoma of esophagus/pharynx risk). Middle-aged women
• Pica: craving for non-food items (ice = pagophagia, clay = geophagia, dirt) = classic IDA symptom
• Koilonychia (spoon nails), angular stomatitis, glossitis = classic IDA signs

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B12 AND FOLATE DEFICIENCY

• Pernicious anemia (autoimmune - anti-intrinsic factor antibodies = most common cause in developed world)
• Absorption failure (terminal ileum disease - Crohn's, surgical resection)
• Surgery (gastrectomy, bariatric)
• Tapeworm (Diphyllobothrium latum - eats B12)
• Vegan diet (no animal products)

• B12 deficiency = megaloblastic anemia + NEUROLOGICAL manifestations (subacute combined degeneration of spinal cord = dorsal columns + lateral corticospinal tracts = loss of proprioception/vibration + upper motor neuron signs). Folate deficiency = NO neurological features
• Folate deficiency treated with folic acid ALONE in suspected B12 deficiency = corrects anemia but allows neurological damage to PROGRESS (subacute combined degeneration) = DANGEROUS
• Always check B12 before treating with folate alone

• Proprioception lost (dorsal columns)
• Inability to walk straight (sensory ataxia)
• Leg weakness + hyperreflexia (corticospinal)
• Spastic weakness (upper motor neuron)

• Giving folic acid alone in B12 deficiency = neurological deterioration
• Not supplementing B12 lifelong in pernicious anemia and gastrectomy patients
• Pernicious anemia = increased risk of gastric cancer and gastric carcinoid - regular surveillance

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HEMOLYTIC ANEMIA

• Coombs test (direct antiglobulin test) - positive = immune-mediated hemolysis
• Anemia (normochromic, normocytic usually, raised reticulocytes)
• Raised LDH + unconjugated bilirubin + reduced haptoglobin
• Spherocytes on blood film (hereditary spherocytosis or autoimmune hemolytic anemia)

• Hemolytic transfusion reaction
• AANCA/TTP/HUS (microangiopathic)
• Serpent venom + malaria

• Hereditary spherocytosis
• Immune hemolytic anemia (warm/cold autoimmune)
• Thalassemia/sickle cell (structural defects)

• X-linked recessive (males affected). Heinz bodies (denatured Hb) + bite cells on blood film
• Triggers Mnemonic: "DAMP"
  • Drugs: dapsone, primaquine, nitrofurantoin, rasburicase, quinolones, sulfamethoxazole
  • Acid (metabolic - infections are major trigger)
  • Malaria (infection triggers)
  • Peas (fava beans = favism)
• WARD ERROR: Giving primaquine for malaria prophylaxis to G6PD-deficient patient = hemolytic crisis

• Autosomal dominant. Anemia + jaundice + splenomegaly. Spherocytes on film. Osmotic fragility test positive. MCHC raised (dense cells)
• Treatment: folic acid supplements. Splenectomy if severe (after age 6-7, with vaccinations)
• EXAM TRAP: Splenectomy before vaccinations = risk of overwhelming post-splenectomy infection (OPSI)

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SICKLE CELL DISEASE

• Sickle-shaped RBCs (HbS = glutamate→valine substitution at position 6 of beta-globin)
• Infarcts (vaso-occlusive crises = most common crisis type)
• Chronic hemolysis (unconjugated bilirubin → gallstones)
• Kidney (renal papillary necrosis, isosthenuria = fixed dilute urine)
• Lung (acute chest syndrome = fever + chest pain + new CXR infiltrate + hypoxia)
• Eye (proliferative retinopathy)
• Splenic sequestration (ACUTE, especially children - spleen suddenly fills with blood → circulatory collapse)
• Painful crises (bones, abdomen, chest)
• Encephalopathy/Stroke (especially children - large vessel disease)
• Leg ulcers (chronic ischemia)
• Liver (hepatic sequestration)
• Salmonella (most common cause of osteomyelitis in SCD - not Staphylococcus as in normal population)

• Most common overall cause of osteomyelitis in sickle cell = Salmonella (exam reversal trap - Staph is most common in general population)
• Acute chest syndrome = sickle cell emergency. Treatment: exchange transfusion + analgesia + antibiotics + O2. Hydroxyurea PREVENTS recurrence (raises fetal HbF)
• Functional asplenia by age 5 → prophylactic penicillin V lifelong + vaccinations (pneumococcus, meningococcus, Hib)

• Over-sedation with opioids in painful crises = respiratory depression + risk of acute chest syndrome
• Not giving IV fluids adequately during crisis (dehydration worsens sickling)
• Giving iron supplements without evidence of iron deficiency = iron overload (already iron-overloaded from hemolysis + transfusions)

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THALASSEMIA

• Alpha thalassemia: gene deletions (HBA1/HBA2). Common in Southeast Asia, Africa
  • 1 gene deleted = silent carrier. 2 = alpha thal trait (mild microcytic anemia). 3 = HbH disease (moderate). 4 = Hb Barts hydrops fetalis (incompatible with life - 4 alpha chain deletions, no adult or fetal alpha globin)
• Beta thalassemia: reduced/absent beta chain synthesis. Mediterranean, Middle East, South Asia
  • Thal minor (trait) = mild microcytic anemia, raised HbA2 (>3.5%)
  • Thal major (Cooley's anemia) = severe transfusion-dependent anemia, skeletal deformities ("chipmunk" facies = frontal bossing + maxillary overgrowth), hepatosplenomegaly, extramedullary hematopoiesis

• Beta thalassemia trait vs IDA: BOTH have microcytic anemia. BUT in beta thal = RBC count HIGH (not low), Mentzer index <13 (RBC count high relative to MCV). In IDA = Mentzer index >13 (MCV low, RBC count low)
• Mentzer index = MCV/RBC count. <13 = thalassemia. >13 = IDA
• WARD ERROR: Giving iron to thalassemia patient without confirmed iron deficiency = iron overload

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COAGULATION DISORDERS

• PT (prothrombin time) / INR = tests EXTRINSIC + COMMON pathway (factors VII, X, V, II, I). Prolonged in: warfarin, vitamin K deficiency, liver disease (factor VII shortest half-life - earliest marker of liver synthetic function)
• aPTT (activated partial thromboplastin time) = tests INTRINSIC + COMMON pathway (factors XII, XI, IX, VIII, X, V, II, I). Prolonged in: heparin, hemophilia A (VIII) and B (IX), lupus anticoagulant (paradoxically THROMBOTIC not bleeding)

• Hemophilia A: Factor VIII deficiency. X-linked recessive
• Hemophilia B (Christmas disease): Factor IX deficiency. X-linked recessive
• Both: prolonged aPTT, normal PT, normal bleeding time
• Treatment: Factor VIII concentrate (A) or Factor IX concentrate (B). rFVIIa for inhibitor patients

• Most common inherited bleeding disorder
• Features: mucocutaneous bleeding (epistaxis, menorrhagia, easy bruising)
• Type 1 (most common, 70%): quantitative deficiency of vWF. Treat with DDAVP (desmopressin - releases stored vWF)
• Type 3: severe, absent vWF + low Factor VIII
• Lab: prolonged bleeding time + aPTT, normal PT, low vWF antigen, reduced Factor VIII

• Mnemonic: "DIC = Everything is Used UP"
• ↓Platelets + ↓fibrinogen + ↑PT + ↑aPTT + ↑D-dimer + ↑FDPs (fibrin degradation products) + microangiopathic hemolytic anemia (schistocytes on film)

• Sepsis (most common - Gram-negative especially)
• Trauma (massive)
• Obstetric (abruption, HELLP, amniotic fluid embolism)
• Promyelocytic leukemia (AML M3 - most famous for DIC)
• Malignancy (mucin-secreting adenocarcinomas)

• Giving platelets/FFP without treating underlying cause = pouring fuel on the fire
• Not recognizing AML-M3 (APL) presenting with DIC = all-trans retinoic acid (ATRA) is specific treatment (differentiates APL from other AML)
• Heparin in DIC = controversial, generally only in thrombosis-dominant DIC

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THROMBOCYTOPENIA

• Platelet destruction (immune): ITP, HIT, TTP, SLE, drug-induced
• Liver disease (splenic sequestration + reduced TPO)
• Applastic anemia/bone marrow failure
• Transfusion-related
• Excess consumption: DIC, TTP, HUS
• Leukemia (infiltrating marrow)
• Edge: sepsis, malaria, viral (HIV, EBV, CMV)
• Therapeutic drugs (chemotherapy, heparin = HIT, valproate, quinidine, sulfonamides)

• Immune-mediated platelet destruction (anti-GPIIb/IIIa antibodies). Platelets <100,000
• Acute ITP (children): post-viral, self-limiting, rarely needs treatment
• Chronic ITP (adults): women > men, insidious onset
• EXAM MISTAKE: No splenomegaly in ITP (if splenomegaly present = think another cause: lymphoma, CML, portal hypertension)
• Treatment: Observe if platelet >30,000 and no bleeding. Prednisolone (first line). IVIg (rapid rise needed - pre-surgery, bleeding). Splenectomy (second line). Rituximab or TPO receptor agonists (romiplostim, eltrombopag) for refractory

• Mnemonic: "HIT = Heparin + Thrombosis (not just thrombocytopenia)"
• Type 1: benign, mild, non-immune, resolves despite continued heparin
• Type 2 (dangerous): immune-mediated (anti-PF4-heparin antibody), platelets fall 5-10 days after heparin (or sooner if prior exposure). Paradoxically THROMBOTIC (arterial + venous)
• 4T Score: Thrombocytopenia extent + Timing + Thrombosis + other cause (oTher)
• WARD ERRORS:
  • Stopping heparin but giving platelets = wrong. Platelets are CONTRAINDICATED (add fuel to thrombosis)
  • Not starting alternative anticoagulant: argatroban or fondaparinux or danaparoid (NOT warfarin immediately - can cause limb gangrene via initial protein C drop)
  • Using LMWH instead of unfractionated heparin thinking it's safer: both can cause HIT (LMWH slightly less risk)

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LEUKEMIA

ACUTE LEUKEMIA

• ALL (Acute Lymphoblastic Leukemia): peaks at age 3-5 (children, most common childhood cancer). Adults have worse prognosis
• AML (Acute Myeloid Leukemia): adults, median age 65-70

• T21 (Down syndrome - 20-30x risk ALL)
• Atlantoaxial subluxation (pre-treatment workup in Down's)
• Lymphadenopathy + hepatosplenomegaly
• Leukaemia: CNS involvement common (CSF involvement, give intrathecal methotrexate)

• AML M3 (APL = acute promyelocytic leukemia): t(15;17) translocation → PML-RARα fusion. Presents with DIC. Treatment = ATRA (all-trans retinoic acid) + arsenic trioxide. ATRA differentiates blasts → myelocytes, resolving DIC
• EXAM TRAP: AML-M3 = DIC + Auer rods (pink needle-like cytoplasmic inclusions in myeloblasts) = ATRA urgently

• Auer rods = pathognomonic for AML (not ALL). Myeloblasts on blood film
• AML blast crisis threshold: ≥20% blasts in marrow (WHO) or >30% (FAB)
• t(8;21) = AML M2 (good prognosis). t(15;17) = AML M3 (ATRA). inv(16) = AML M4Eo (good prognosis). Complex karyotype = poor prognosis

CHRONIC LEUKEMIA

• Philadelphia chromosome: t(9;22) → BCR-ABL fusion gene → constitutively active tyrosine kinase
• Features: massive splenomegaly + raised WBC (all stages of myeloid development) + basophilia
• Mnemonic: "CML = BCR-ABL = iMATINIB (Gleevec) = MIRACLE DRUG"
• Treatment: imatinib (TKI - tyrosine kinase inhibitor), then dasatinib/nilotinib if resistance
• EXAM TRAP: Blast crisis = transformation to AML or ALL (>20% blasts). Philadelphia chromosome also found in 25% of adult ALL (poor prognosis in ALL)

• Most common leukemia in adults in Western world. Elderly, often incidental finding
• B-lymphocytes (CD5+, CD19+, CD23+). "Smear/smudge cells" on blood film (fragile lymphocytes squashed by coverslip)
• Complications Mnemonic: "CHAP"
  • Coomb's positive autoimmune hemolytic anemia (warm AIHA)
  • Hypogammaglobulinemia (recurrent infections)
  • Aggressive transformation: Richter's transformation → diffuse large B-cell lymphoma (sudden rapid enlargement of one node + systemic symptoms)
  • Pure red cell aplasia
• EXAM TRAP: Rai and Binet staging. Treatment only if symptomatic (Rai stage III-IV / Binet C) or Binet A/B with symptoms. Watch and wait for early asymptomatic CLL
• First-line treatment: ibrutinib (BTK inhibitor) or FCR (fludarabine + cyclophosphamide + rituximab)

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LYMPHOMA

HODGKIN LYMPHOMA

• Binucleated giant Reed-Sternberg cells with large eosinophilic nucleoli = "owl eyes" on histology
• Origin: B cells (CD15+, CD30+, CD45-)

• Hilum enlarged (mediastinal widening on CXR - anterior mediastinal mass - HL #1 cause in young)
• Alcohol-induced pain (in involved lymph nodes - classic HL symptom, pathognomonic)
• Lymphadenopathy (rubbery, non-tender, painless cervical nodes most common)
• Extranodal spread (rare in HL vs NHL)
• Pruritus (without rash), Pel-Ebstein fever (cyclical)

• Fever >38°C
• Night sweats (drenching)
• Slim (weight loss >10% in 6 months)
• B symptoms = worse prognosis, need more aggressive treatment

• HL spreads in contiguous nodal fashion (predictable, treated with field radiation)
• Ann Arbor staging: I = single node region, II = 2+ regions same side of diaphragm, III = both sides, IV = extranodal organ involvement
• ABVD (Adriamycin + Bleomycin + Vinblastine + Dacarbazine) = standard first-line for HL
• Alcohol-induced pain in HL nodes = PATHOGNOMONIC for HL (no other lymphoma does this)

• Not screening for bleomycin lung toxicity (pulmonary fibrosis) - baseline PFTs + CXR before and during treatment
• Not considering HL in young person with anterior mediastinal mass + alcohol-induced pain + night sweats

NON-HODGKIN LYMPHOMA

• Spreads non-contiguously (unlike HL)
• Higher rate of extranodal involvement (GI, CNS, bone marrow)

• High-grade (aggressive): DLBCL (most common NHL overall), Burkitt's lymphoma. Fast-growing, but POTENTIALLY CURABLE with chemotherapy
• Low-grade (indolent): Follicular lymphoma (most common low-grade), CLL/SLL, marginal zone lymphoma. Slow-growing, INCURABLE with standard chemo (but watch and wait acceptable)

• Endemic (African): EBV-associated, jaw/facial tumor in children
• Sporadic: abdominal mass (ileum/cecum), children in developed world
• AIDS-related: B-cell immunodeficiency
• t(8;14) = c-myc oncogene rearrangement. "Starry sky" pattern on histology (macrophages engulfing apoptotic cells = stars)
• Fastest growing human tumor (doubling time 24-48h)
• Treatment: intensive chemotherapy with CNS prophylaxis. Tumor lysis syndrome risk very HIGH - prophylax with allopurinol/rasburicase + IV fluids

• Most common NHL. Aggressive, rapidly enlarging lymph nodes
• Treatment: R-CHOP (Rituximab + Cyclophosphamide + Hydroxydaunorubicin + Oncovin/vincristine + Prednisolone)
• R-CHOP mnemonic: "Really Cool Hematologists Overcoming Pathology"

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MULTIPLE MYELOMA

• Calcium elevated (hypercalcemia from osteoclast activation)
• Renal impairment (Bence Jones proteinuria, cast nephropathy, amyloidosis)
• Anemia (normochromic normocytic, rouleaux formation on blood film)
• Bone lesions (lytic "punched-out" lesions, NOT osteosclerotic - NO uptake on bone scan - use skeletal survey or PET/CT)

• Bone scan is NORMAL or NEGATIVE in myeloma (lesions are purely lytic with no osteoblastic activity = no uptake). Use skeletal survey (plain X-rays) or whole-body MRI/PET
• Rouleaux formation on blood film (RBCs stack like coins due to high immunoglobulin) + high ESR + normal CRP (ESR raised by paraprotein, CRP doesn't reflect it)
• Bence Jones protein = free light chains (kappa or lambda) in URINE. Standard urine dipstick does NOT detect Bence Jones protein (it detects albumin, not light chains). Need urine protein electrophoresis

• M protein (paraprotein) on serum electrophoresis = monoclonal spike
• Hyperviscosity syndrome: headache, blurred vision, bleeding, confusion = urgent plasmapheresis
• Infections: hypogammaglobulinemia (normal antibodies suppressed) → Streptococcus pneumoniae most common infectious cause of death

• IV contrast in myeloma without pre-hydration = precipitates acute renal failure (Bence Jones + contrast = tubular obstruction)
• Not giving bisphosphonates (zoledronic acid) to ALL myeloma patients = reduces skeletal events
• Not considering myeloma in elderly patient with back pain + hypercalcemia + anemia + raised ESR

• M protein <30g/L + plasma cells <10% + NO CRAB = benign. 1% per year risk of progression to myeloma
• EXAM TRAP: MGUS does NOT need treatment. Annual monitoring only

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MYELOPROLIFERATIVE NEOPLASMS

• JAK2 V617F mutation (>95%)
• Features: raised Hb + raised RBC mass + raised WBC + raised platelets + SPLENOMEGALY + AQUAGENIC PRURITUS (itch after hot bath = pathognomonic) + plethoric facies + hypertension + thrombotic events
• EXAM MISTAKE: Aquagenic pruritus = PV until proven otherwise
• Serum EPO = LOW (autonomous RBC production suppresses EPO). Secondary polycythemia = EPO HIGH
• Treatment: venesection (phlebotomy) + low-dose aspirin. Hydroxycarbamide if high-risk (age >60, thrombosis history)

• JAK2 (50%), CALR (25%), MPL (5%) mutations
• Platelets >450 x 10⁹/L. Thrombosis AND paradoxically bleeding (platelet dysfunction at very high counts)
• EXAM MISTAKE: Very high platelets (>1000 x 10⁹/L) = acquired vWD + bleeding risk. Avoid aspirin if vWF levels low
• Treatment: aspirin (low-risk), hydroxycarbamide + aspirin (high-risk), anagrelide

• JAK2 or CALR mutations. Fibrosis of bone marrow
• Blood film: LEUKOERYTHROBLASTIC picture (immature white cells + nucleated red cells) + TEAR-DROP POIKILOCYTES (dacrocytes) = pathognomonic
• Massive splenomegaly (extramedullary hematopoiesis)
• Treatment: ruxolitinib (JAK1/2 inhibitor) for symptoms. Allogeneic SCT (only potentially curative)
• EXAM MISTAKE: Dry tap on bone marrow aspiration (cannot aspirate marrow = fibrosis). Trephine biopsy needed instead

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MYELODYSPLASTIC SYNDROME (MDS)

• Clonal stem cell disorder: dysplastic (abnormal-looking) blood cells that don't function normally
• Features: cytopenias (anemia + neutropenia + thrombocytopenia) despite HYPERCELLULAR or normocellular marrow. Macrocytic anemia common
• Ringed sideroblasts = mitochondrial iron deposits around nucleus on Prussian blue stain = MDS-RS (MDS with ring sideroblasts)
• Risk of transformation to AML (~30% over time)
• Treatment: low-risk = supportive (ESA, transfusions, G-CSF). High-risk = azacitidine (hypomethylating agent) or allogeneic SCT

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APLASTIC ANEMIA

• Failure of bone marrow stem cells → pancytopenia (all cell lines reduced)
• Causes: autoimmune (most common, T-cell mediated destruction of HSCs), drugs (chloramphenicol, carbamazepine, NSAIDs, gold), viral (EBV, CMV, hepatitis), radiation, PNH (paroxysmal nocturnal hemoglobinuria)
• Blood film: pancytopenia, no blasts (unlike leukemia). Bone marrow biopsy: HYPOCELLULAR ("empty" marrow)
• Treatment: young patient + matched sibling donor = allogeneic SCT (curative). No donor/older patient = ATG + cyclosporine (immunosuppression)

• Mnemonic: "PNH = Dark urine in MORNING (hemoglobin in overnight urine) + Thrombosis in unusual sites"
• Clonal disorder: GPI anchor deficiency (complement attacks RBCs overnight when CO2 builds up, pH drops)
• Features: intravascular hemolysis (raised LDH, dark morning urine) + thrombosis in unusual sites (hepatic vein = Budd-Chiari, cerebral veins, mesenteric veins) + cytopenias
• Diagnosis: flow cytometry (loss of CD55 and CD59 on RBCs)
• Treatment: eculizumab (anti-C5 complement inhibitor) = blocks hemolysis + reduces thrombosis

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ANTICOAGULATION

• Metronidazole / Amiodarone / Clarithromycin / Ciprofloxacin / Alcohol (acute) / Miconazole

• Phenytoin / Carbamazepine / Rifampicin / Alcohol (chronic) / Barbiturates / St John's Wort

• INR 5-8, no bleeding: withhold warfarin + monitor
• INR >8, no bleeding: stop warfarin + oral vitamin K 1-2mg
• Any serious bleeding: PCC (prothrombin complex concentrate = factors II, VII, IX, X) + IV vitamin K 5mg
• WARD ERROR: Using FFP for urgent warfarin reversal = large volumes needed, slow, incomplete reversal. PCC is FASTER and more effective

• Dabigatran (direct thrombin inhibitor): idarucizumab (Praxbind) = specific antidote
• Rivaroxaban/Apixaban/Edoxaban (Factor Xa inhibitors): andexanet alfa = specific antidote (or PCC if unavailable)

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TRANSFUSION MEDICINE

• TRALI: non-cardiogenic, antibodies in donor plasma attack recipient neutrophils in pulmonary vasculature. BNP normal, JVP not raised. NO diuretics
• TACO: cardiogenic fluid overload. BNP raised, JVP raised. GIVE diuretics

• Giving blood to wrong patient = most common serious transfusion error (ABO incompatibility)
• Transfusing too fast in elderly/cardiac/renal patients = TACO
• Removing unit from fridge >30 min before administration = bacterial contamination risk (Yersinia enterocolitica in stored blood)
• Not using CMV-negative blood for CMV-negative immunocompromised recipients

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PART B: ONCOLOGY

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ONCOLOGY EMERGENCIES

• Spinal cord compression
• Obstruction (SVC syndrome)
• Septic neutropenia (febrile neutropenia)
• Calcium (hypercalcemia of malignancy)
• Anaphylaxis (chemotherapy - platinum compounds especially)
• Metabolic: SIADH, tumor lysis syndrome
• Pericardial tamponade (malignant effusion)

FEBRILE NEUTROPENIA

• Port culture (blood cultures x2 - peripheral + central line)
• Risk stratify (MASCC score - low risk = oral antibiotics outpatient)
• Intravenous antibiotics immediately (within 1 hour of presentation). Do NOT wait for culture results
• No clear source usually - empiric broad-spectrum
• Tazocin (piperacillin-tazobactam) = standard empiric monotherapy. Add vancomycin if: CVAD infection, pneumonia, hemodynamic instability, MRSA risk. Add antifungal if >5 days fever despite antibiotics (think Candida/Aspergillus)

• Delaying antibiotics >1h in febrile neutropenia = mortality rises per hour of delay
• Stopping antibiotics if cultures negative = cultures often negative in neutropenic patients
• Not escalating to antifungal after 5 days of persistent fever despite antibiotics

TUMOR LYSIS SYNDROME (TLS)

• Hyperkalemia (cardiac arrhythmias = most immediately dangerous)
• Hyperphosphatemia
• Hypocalcemia (secondary to hyperphosphatemia)
• Hyperuricemia (uric acid crystals → AKI)
• AKI + lactic acidosis

SPINAL CORD COMPRESSION (MSCC)

• New back pain in cancer patient + neurological symptoms (limb weakness, sensory level, bladder/bowel dysfunction) = EMERGENCY
• Most common malignant cause: breast, prostate, lung, myeloma, renal cell carcinoma
• Most common site: thoracic spine (70%)

• Delay in MRI whole spine = irreversible paralysis. MRI within 24h (same day if neurological deficit)
• Not giving dexamethasone 16mg IV immediately (reduces edema, buys time)
• Not catheterizing if bladder dysfunction present
• Treatment: dexamethasone + urgent radiotherapy or surgical decompression (surgery if single level, reasonable prognosis, able to tolerate)

SVC SYNDROME

• Features: facial swelling + arm edema + dilated neck/chest veins + headache (worse bending forward/lying down)
• Causes: SCLC (most common, 70-80%), lymphoma, other malignancies, thrombosis around central line
• EXAM MISTAKE: Do NOT perform biopsy via neck veins in SVC syndrome - risk of bleeding. Get tissue from peripheral site or CT-guided biopsy of primary tumor
• Treatment: dexamethasone + radiotherapy (SCLC = radiosensitive) or chemotherapy + stenting for rapid relief

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CANCER TREATMENT - CHEMOTHERAPY TOXICITIES

• Monitor with serial echos or MUGA scans. Baseline EF must be >50% before starting
• WARD ERROR: Exceeding cumulative doxorubicin dose without cardiac monitoring = dilated cardiomyopathy

• Acrolein metabolite damages bladder wall
• Prevention: MESNA (2-mercaptoethane sulfonate sodium) given with each dose + aggressive IV hydration
• WARD ERROR: Giving cyclophosphamide without mesna = preventable hemorrhagic cystitis

• PD-1 inhibitors (pembrolizumab, nivolumab) + CTLA-4 (ipilimumab) can cause:
  • Pneumonitis (most dangerous - shortness of breath + infiltrates on CT)
  • Colitis (diarrhea + blood - like IBD)
  • Hepatitis (raised LFTs)
  • Endocrinopathies (thyroiditis → hypothyroidism, adrenalitis → Addison's, hypophysitis → panhypopituitarism)
  • Nephritis
  • Dermatitis
• Treatment of immune-related adverse events (irAE): STOP checkpoint inhibitor + HIGH-DOSE STEROIDS (prednisolone 1-2mg/kg/day)
• WARD ERROR: Not recognizing irAE as drug-related (mistaken for infection, IBD flare, other endocrine disease)

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RADIATION THERAPY COMPLICATIONS

• Skin: erythema, desquamation
• GI: mucositis, nausea, diarrhea
• Bone marrow: cytopenias (if field includes marrow)

• Pulmonary fibrosis (chest RT)
• Cardiac disease (pericarditis, coronary artery disease - left-sided breast RT, HL mediastinal RT)
• Hypothyroidism (neck RT)
• Bowel strictures/fistulas (pelvic RT)
• Lymphedema
• Secondary malignancies (most feared long-term complication - leukemia, solid tumors in radiation field)
• Spinal cord (myelopathy if cord in field)

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TARGETED THERAPY & KEY MOLECULAR MARKERS

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CANCER SCREENING (Exam-Relevant)

• Servical: HPV-based cervical smear (age 25-64, every 3-5 years)
• Colorectal: FOBT/FIT annually OR colonoscopy every 10 years (age 45-75)
• RRR = Breast: mammography every 2 years (age 50-74; 40-74 in some guidelines)
• Endometrium: no population screening (Lynch syndrome = annual uterine sampling)
• ERCC = (not screened routinely)
• Neck (thyroid): no population screening
• Esophagus: Barrett's surveillance
• Derm (melanoma): dermoscopy surveillance in high-risk

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TUMOR MARKERS (Classic Exam Associations)

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ONCOLOGY GENETICS / HEREDITARY CANCER SYNDROMES

• MLH1/MSH2 etc. = mismatch repair genes defective → microsatellite instability (MSI-H)
• MSI-H tumors respond to pembrolizumab (PD-1 inhibitor) = FIRST use of immunotherapy based on molecular feature rather than tumor type

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SOLID TUMORS - EXAM PEARLS

COLORECTAL CANCER

• Right colon (cecum, ascending): iron deficiency anemia, weight loss, occult blood, mass. No obstructive symptoms (wide lumen)
• Left colon (descending, sigmoid, rectum): change in bowel habit, rectal bleeding, obstruction (narrow lumen)
• Rectal cancer: tenesmus (feeling of incomplete emptying), fresh rectal bleeding

• Duke's A = T1/T2, N0, M0 (confined to bowel wall) = 90% 5-yr survival
• Duke's B = T3/T4, N0, M0 (through wall, no nodes) = 65-70%
• Duke's C = any T, N1-2, M0 (node positive) = 30-40%
• Duke's D = any M1 (metastases) = <5%

• Missing right-sided colon cancer in young patient with iron deficiency anemia = colonoscopy, not just iron supplementation
• Assuming rectal bleeding = hemorrhoids without appropriate investigation in >45 years

PANCREATIC CANCER

• Courvoisier's law: palpable gallbladder + jaundice ≠ gallstones = periampullary/pancreatic malignancy
• CA 19-9 elevated (but 10% of population Lewis antigen negative = always normal CA 19-9)
• Trousseau's syndrome: migratory superficial thrombophlebitis = paraneoplastic (mucin-producing tumors)
• 5-year survival <10% (most diagnosed at late stage)
• Whipple's procedure (pancreaticoduodenectomy) = only curative option (only 15-20% resectable at presentation)

BREAST CANCER

• Family history (BRCA1/2, first-degree relative)
• Age >50 (main risk factor)
• Late menopause (>55) + Late first pregnancy
• Combined OCP/HRT (modest increase)
• Obesity (post-menopausal - adipose tissue aromatase)
• Nulliparity
• Early menarche (<12)
• Radiation (prior chest RT - e.g., HL treatment)

• Inflammatory breast cancer (peau d'orange skin, erythema, NO discrete lump) = NOT mastitis. HIGH clinical suspicion → immediate biopsy. Often no mass on imaging. Treat as T4d regardless of nodes
• Paget's disease of breast = nipple eczema + underlying DCIS or invasive cancer. Always biopsy nipple changes in older women that fail to respond to topical steroids
• Triple negative breast cancer (ER-PR-HER2 negative) = worst prognosis, no targeted therapy, but now pembrolizumab approved + olaparib for BRCA-mutant

• Treating "breast abscess" with antibiotics alone in older woman = could be inflammatory carcinoma
• Not completing 5-10 years of adjuvant hormonal therapy (tamoxifen/aromatase inhibitor) due to side effects = high recurrence risk

PROSTATE CANCER

• Osteosclerotic (blastic) bone metastases = raised alkaline phosphatase + positive bone scan (OPPOSITE of myeloma which is lytic and bone scan negative)
• PSA: >4 = investigate. PSA velocity (rapid rise) and PSA density (PSA/prostate volume) help stratify
• EXAM TRAP: Finasteride and dutasteride (5-alpha reductase inhibitors) HALVE PSA levels - adjust interpretation (double the PSA for accurate interpretation)
• Bone pain + raised ALP + raised PSA in elderly male = prostate cancer bone metastases

• Localized: active surveillance (low-risk), radical prostatectomy or radiotherapy (intermediate/high-risk)
• Metastatic: ADT (androgen deprivation therapy) = LHRH agonist (goserelin, leuprorelin) ± anti-androgen (bicalutamide) + docetaxel or abiraterone/enzalutamide
• WARD ERROR: Starting LHRH agonist in metastatic prostate cancer without anti-androgen cover first = testosterone FLARE (initial rise before castration) → vertebral collapse, spinal cord compression. Cover with anti-androgen for first 2-4 weeks

OVARIAN CANCER

• Symptoms: abdominal bloating, pelvic pain, urinary symptoms, early satiety = often ignored for months
• CA-125 + pelvic ultrasound = initial investigation
• Most common histology: high-grade serous carcinoma (TP53 mutation, BRCA1/2 association)
• FIGO staging: I = ovary only, II = pelvis, III = abdomen/lymph nodes, IV = distant metastases
• Treatment: optimal cytoreductive surgery + platinum-taxane chemotherapy + maintenance olaparib (BRCA mutant) or bevacizumab

TESTICULAR CANCER

• Most common solid malignancy in men aged 15-35
• Types: Seminoma (radiosensitive, slower, AFP normal) vs Non-seminomatous GCT (NSGCT: teratoma, yolk sac, choriocarcinoma, embryonal - AFP/hCG raised)
• EXAM TRAP: Never biopsy testicular mass through the scrotum = risk of scrotal lymphatic spread (changes lymph node drainage from para-aortic to inguinal). ALWAYS orchidectomy via inguinal approach
• Seminoma = very radiosensitive. NSGCT = chemotherapy (BEP: Bleomycin + Etoposide + Cisplatin)
• Most curable solid malignancy even at advanced stage (>90% 5-year survival with treatment)

• Trans-scrotal biopsy or orchiectomy via scrotal approach = WRONG. Must be inguinal approach to avoid altering lymphatic drainage

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PALLIATIVE CARE / SYMPTOM CONTROL (Exam-Relevant)

• Step 1: Non-opioid (paracetamol + NSAID)
• Step 2: Weak opioid (codeine, tramadol, low-dose oxycodone)
• Step 3: Strong opioid (morphine, oxycodone, fentanyl, hydromorphone)
• Adjuvants at any step: neuropathic pain (amitriptyline, gabapentin, pregabalin), bone pain (NSAIDs, bisphosphonates, steroids), visceral pain (antispasmodics)

• Oral morphine 30mg/day → SC morphine 10mg/day (syringe driver)
• Oral morphine 60mg/day → fentanyl 25 mcg/h patch

• Not prescribing breakthrough analgesia alongside regular opioids (breakthrough = 1/6th of total daily dose)
• Starting strong opioid without prescribing laxative (all opioids cause constipation - prophylactic senna + osmotic agent)
• Not anticipating and prescribing PRN medications for end-of-life (pain = morphine, secretions = hyoscine, agitation = midazolam, nausea = haloperidol or levomepromazine) - "Just in Case" box
• Continuing futile investigations or treatments when comfort is the goal

• Urgent management: IV 0.9% NaCl + zoledronic acid 4mg IV (most potent bisphosphonate)
• Onset of bisphosphonate: 48-72h. Use calcitonin (faster onset, tachyphylaxis) while waiting
• Denosumab for bisphosphonate-resistant or renal impairment

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CROSS-REFERENCE: HEMATOLOGY/ONCOLOGY HIGH-YIELD TABLE

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KEY MNEMONICS SUMMARY - HEMATOLOGY & ONCOLOGY

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