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HEMATOLOGY

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1. Iron Deficiency Anemia (IDA)

• Chronic blood loss (most common in adults) - GI bleeding (ulcer, cancer, hookworm), menorrhagia
• Inadequate dietary intake (children, vegetarians)
• Malabsorption - celiac disease, post-gastrectomy
• Increased demand - pregnancy, infancy

• General: fatigue, weakness, pallor, dyspnea
• Specific signs: koilonychia (spoon-shaped nails), glossitis, angular stomatitis, dysphagia (Plummer-Vinson syndrome in severe cases), pica (craving for ice/dirt)
• Infants/children: irritability, poor growth, impaired cognitive development

• Treat underlying cause
• Oral ferrous sulfate 200mg TID for 3-6 months (continue 3 months after Hb normalizes to replenish stores)
• IV iron (ferric carboxymaltose) if oral not tolerated or malabsorption
• Blood transfusion in severe symptomatic anemia

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2. Megaloblastic Anemia

• Vitamin B12 deficiency: Pernicious anemia (anti-intrinsic factor antibodies), strict veganism, gastrectomy, terminal ileum disease (Crohn's), fish tapeworm (Diphyllobothrium)
• Folate deficiency: Poor diet, alcoholism, pregnancy, drugs (methotrexate, trimethoprim, phenytoin), malabsorption

• General: pallor, jaundice (mild, from ineffective erythropoiesis), weakness
• B12-specific: subacute combined degeneration of spinal cord (posterior + lateral columns) → ataxia, loss of vibration/position sense, peripheral neuropathy, dementia. Glossitis ("beefy red tongue")
• Folate: similar hematological picture but NO neurological features

• High MCV (>100 fL) - macrocytic
• Peripheral smear: oval macrocytes, hypersegmented neutrophils (>5 lobes in >5% - pathognomonic)
• Low serum B12 or folate
• Elevated homocysteine (both B12 and folate deficiency)
• Elevated methylmalonic acid (MMA) - specific for B12 deficiency only
• Bone marrow: megaloblasts, giant metamyelocytes

• B12 deficiency: IM hydroxocobalamin or cyanocobalamin (1mg weekly x4, then monthly for life in pernicious anemia); high-dose oral B12 also effective
• Folate deficiency: folic acid 5mg/day orally x 4 months
• Important: Always rule out B12 deficiency before giving folate alone (folate can correct the anemia but worsen neurological damage from B12 deficiency)

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3. Sickle Cell Disease (SCD)

• Hb: 6-9 g/dL; MCV normal or slightly elevated (if concurrent folate deficiency)
• Peripheral smear: sickle cells, target cells, Howell-Jolly bodies (functional asplenia)
• Hb electrophoresis: HbSS (diagnosis)
• Sickling test (sodium metabisulfite): positive
• Reticulocytosis (compensatory)

• Hydroxyurea - increases HbF (fetal Hb does not sickle), reduces frequency of crises
• Folic acid supplementation (for increased erythropoiesis)
• Pain crisis: hydration, analgesia (NSAIDs/opioids), O2
• Prophylactic penicillin (from birth to 5 years) + vaccinations (pneumococcal, meningococcal, Hib)
• Exchange transfusion: for stroke, acute chest syndrome
• Curative: bone marrow transplant

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4. Thalassemia

β-Thalassemia:

• β-thal major (Cooley's anemia): Both β-globin genes absent/severely reduced → severe hemolytic anemia from birth (HbF predominates in fetus, symptoms appear 6 months after birth)
• β-thal intermedia: Milder form
• β-thal minor (trait): One normal gene, usually asymptomatic with mild microcytic anemia

• Severe anemia from 6 months old
• Hepatosplenomegaly (extramedullary hematopoiesis)
• "Chipmunk face" (maxillary overgrowth due to marrow expansion)
• "Hair on end" skull X-ray (marrow hyperplasia)
• Growth retardation, delayed puberty
• Iron overload (from transfusions + increased GI absorption) → cardiomyopathy, cirrhosis, endocrine failure

• HbA2 elevated (>3.5%) in β-thal minor (key diagnostic feature)
• Hb electrophoresis: HbF elevated, HbA absent in major
• Microcytic hypochromic anemia; peripheral smear: target cells, nucleated RBCs, basophilic stippling
• X-ray: "hair on end" skull

• β-thal major: Regular blood transfusions every 3-4 weeks (keep Hb >10)
• Iron chelation: deferoxamine (SC/IV) or deferasirox (oral) to prevent iron overload
• Curative: bone marrow/stem cell transplant
• Splenectomy if hypersplenism

α-Thalassemia:

• 4 α-globin genes (2 per chromosome 16)
• Loss of 1 gene: silent carrier; 2 genes: α-thal trait; 3 genes: HbH disease (moderate hemolysis); 4 genes: Hb Bart's hydrops fetalis (fatal, stillbirth)

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5. Acute Myeloid Leukemia (AML)

• Prior chemotherapy (alkylating agents, topoisomerase II inhibitors)
• Prior radiation
• Myelodysplastic syndrome → secondary AML
• Benzene exposure
• Down syndrome (especially M7 - megakaryoblastic)
• Specific mutations: FLT3, NPM1, CEBPA, IDH1/2

• M0: Minimally differentiated
• M1: Without maturation
• M2: With maturation
• M3: APL (Acute Promyelocytic Leukemia) - PML-RARA fusion - most important
• M4: Myelomonocytic
• M5: Monocytic
• M6: Erythroleukemia
• M7: Megakaryoblastic

• Bone marrow failure syndrome:
  • Anemia: fatigue, pallor
  • Neutropenia: recurrent infections, fever
  • Thrombocytopenia: bleeding, petechiae, ecchymoses
• DIC: especially in APL (M3)
• Tissue infiltration: lymphadenopathy, hepatosplenomegaly, gum hypertrophy (M4/M5), CNS involvement
• Leukostasis: if WBC >100,000 → hyperviscosity → stroke, pulmonary infiltrates

• WBC: variable (high, normal, or low)
• Blasts >20% in bone marrow (WHO criteria)
• Auer rods in cytoplasm of blasts (pathognomonic - especially M2, M3)
• Myeloperoxidase (MPO) positive - differentiates from ALL
• Cytogenetics: t(15;17) in APL, t(8;21), inv(16)

• General AML: induction with "7+3" (cytarabine 7 days + daunorubicin 3 days) → remission → consolidation
• APL (M3): All-trans retinoic acid (ATRA) + arsenic trioxide → differentiation of blasts; excellent prognosis
• Bone marrow transplant in high-risk or relapsed disease

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6. Chronic Myeloid Leukemia (CML)

1. Chronic phase (most common at diagnosis): >3-5 years; symptomatic but manageable
2. Accelerated phase: increasing blasts (10-19%), basophilia
3. Blast crisis: blasts >20% (myeloid or lymphoid) - resembles acute leukemia; poor prognosis

• Often incidental finding on CBC
• Massive splenomegaly (most prominent feature - left-sided heaviness, early satiety)
• Mild hepatomegaly
• Fatigue, weight loss, night sweats, fever
• Rarely: leukostasis, priapism, gout (from high cell turnover)

• WBC dramatically elevated (50,000-500,000/μL) - entire myeloid spectrum present
• Peripheral smear: all stages of myeloid development, increased basophils and eosinophils
• Thrombocytosis (early), thrombocytopenia (late)
• Low leukocyte alkaline phosphatase (LAP) score - differentiates from leukemoid reaction (which has high LAP)
• BCR-ABL1 by FISH or RT-PCR: confirmatory
• Bone marrow: hypercellular, all myeloid lineages

• Tyrosine kinase inhibitors (TKIs): imatinib (Gleevec) 1st line, nilotinib/dasatinib 2nd generation
• TKIs are highly effective - most patients achieve remission
• Bone marrow transplant: now reserved for blast crisis or TKI failure
• No curative medication (except BMT)

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7. ITP (Immune Thrombocytopenic Purpura)

• Primary ITP: No identifiable cause
• Secondary ITP: Associated with SLE, HIV, HCV, H. pylori, drugs, CLL

• Mucocutaneous bleeding: petechiae (small pinpoint hemorrhages), purpura, ecchymoses
• Bleeding from mucous membranes: epistaxis, gingival bleeding, menorrhagia
• NO splenomegaly (important distinguishing feature)
• Intracranial hemorrhage (rare but life-threatening)
• Children: Acute, self-limiting (often post-viral), good prognosis
• Adults: Chronic (>3 months), women predominate

• Isolated thrombocytopenia (platelets <100,000/μL, often <30,000 when symptomatic)
• Normal PT, aPTT (no coagulation factor deficiency)
• Peripheral smear: large platelets (megathrombocytes), absent clumping
• No anemia or neutropenia (bone marrow otherwise normal)
• Bone marrow: increased megakaryocytes (increased production, peripheral destruction)
• Anti-platelet antibody test (not routinely needed for diagnosis)

• Mild (platelets >30,000, no bleeding): Observe
• Moderate-Severe: 1st line = oral prednisolone (1mg/kg/day); IVIG (for rapid response - pre-surgery)
• Refractory/Chronic: Splenectomy (removes main site of destruction), rituximab (anti-CD20), thrombopoietin receptor agonists (romiplostim, eltrombopag)

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8. Von Willebrand Disease (VWD) - Factor

• Type 1 (most common, 70%): Quantitative reduction of normal vWF - autosomal dominant
• Type 2: Qualitative defect in vWF - multiple subtypes (2A, 2B, 2M, 2N)
• Type 3 (most severe, rare): Near-complete absence of vWF - autosomal recessive; resembles hemophilia A

• Mucocutaneous bleeding pattern (like platelet disorders):
  • Easy bruising, epistaxis, menorrhagia, gingival bleeding
  • Excessive bleeding after dental extraction/surgery
• Type 3: more severe; joint bleeds possible (from low Factor VIII)

• Prolonged bleeding time and PFA-100 closure time
• Prolonged aPTT (due to low Factor VIII, which is carried by vWF)
• Normal PT
• Decreased vWF antigen (vWF:Ag)
• Decreased vWF ristocetin cofactor activity (vWF:RCo)
• Ristocetin-induced platelet aggregation (RIPA): absent/reduced (Type 1, 2A, 3) or enhanced at low concentrations (Type 2B)

• Desmopressin (DDAVP): 1st line for Type 1 - releases stored vWF from endothelial cells (Weibel-Palade bodies)
• Factor VIII/vWF concentrate (e.g., Humate-P): for severe types, surgery, Type 2B (DDAVP contraindicated)
• Tranexamic acid: adjunct for mucosal bleeding
• Combined oral contraceptive: for menorrhagia

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9. Hemophilia A

• Hemarthroses (joint bleeds) - most common; knees, ankles, elbows most affected → chronic arthropathy (target joints)
• Deep muscle hematomas - iliopsoas, calf muscles
• Intracranial hemorrhage - after minor head trauma
• Prolonged bleeding after surgery/dental procedures
• NO mucocutaneous bleeding (platelet function normal)
• Family history (maternal) important

• Prolonged aPTT (intrinsic pathway: XII → XI → IX → VIII → X → V → prothrombin)
• Normal PT (extrinsic pathway intact)
• Normal bleeding time and platelet count
• Specific Factor VIII assay: low
• Mixing study: aPTT corrects with normal plasma (factor deficiency, not inhibitor)

• Factor VIII concentrate (recombinant preferred) - on-demand or prophylactic
• Prophylaxis: 3x/week injections to maintain Factor VIII >1% - now standard for severe disease
• Desmopressin (DDAVP): for mild hemophilia A only - releases stored Factor VIII; NOT effective for moderate/severe
• Inhibitor development (anti-Factor VIII antibodies) in 20-30% of severe cases → use bypassing agents (recombinant FVIIa = NovoSeven, FEIBA)
• Novel therapies: emicizumab (bispecific antibody mimicking Factor VIII) - subcutaneous, weekly

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AUTOIMMUNE / RHEUMATOLOGY

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10. Rheumatoid Arthritis (RA)

• Symmetrical, small joint polyarthritis (PIPs, MCPs, wrists) - bilateral
• Morning stiffness >1 hour (hallmark)
• Fusiform (spindle-shaped) swelling of fingers
• Deformities in late disease:
  • Swan-neck deformity (PIP hyperextension + DIP flexion)
  • Boutonnière deformity (PIP flexion + DIP extension)
  • Ulnar deviation of fingers
  • Z-thumb
  • Volar subluxation at MCP joints

• Rheumatoid nodules (subcutaneous, extensor surfaces, elbows) - in RF+ patients
• Eye: keratoconjunctivitis sicca (secondary Sjögren's), scleritis, episcleritis
• Lung: ILD, pleural effusion, pulmonary nodules, bronchiectasis
• Heart: pericarditis
• Skin: vasculitis, pyoderma gangrenosum
• Hematology: anemia of chronic disease, Felty's syndrome (RA + splenomegaly + neutropenia)
• Neurological: carpal tunnel syndrome, atlantoaxial subluxation
• Kidney: AA amyloidosis, drug-induced nephrotoxicity

• RF (Rheumatoid Factor) positive in 70-80% (not specific)
• Anti-CCP (anti-cyclic citrullinated peptide) - most specific (>95%), appears early
• High ESR and CRP (disease activity markers)
• Mild normochromic normocytic anemia (ACD)
• X-ray: periarticular osteoporosis (early) → joint space narrowing → erosions (late)
• Synovial fluid: inflammatory (WBC 2,000-50,000, predominantly neutrophils)

• DMARDs (Disease-Modifying Antirheumatic Drugs) - started EARLY to prevent joint damage:
  • Methotrexate (1st line DMARD)
  • Leflunomide, sulfasalazine, hydroxychloroquine (triple therapy)
• Biologics (for inadequate DMARD response):
  • TNF inhibitors: etanercept, infliximab, adalimumab
  • IL-6 inhibitors: tocilizumab
  • B-cell depletion: rituximab
  • T-cell co-stimulation blockade: abatacept
• JAK inhibitors (oral targeted synthetic DMARDs): tofacitinib, baricitinib
• Steroids: for acute flares/bridging
• NSAIDs: symptom relief only
• Physiotherapy, joint protection, splints

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11. Systemic Lupus Erythematosus (SLE)

• ANA (antinuclear antibody): positive in >95% - most sensitive but not specific
• Anti-dsDNA: most specific for SLE; correlates with disease activity and lupus nephritis
• Anti-Sm (anti-Smith): most specific (90-99%) but less sensitive (25-30%)
• Anti-Ro (SS-A) / Anti-La (SS-B): neonatal lupus, congenital heart block
• Anti-phospholipid antibodies: antiphospholipid syndrome
• Low complement C3, C4 (consumed during active disease)
• High ESR; CRP often NOT elevated (except in serositis) - useful in distinguishing SLE flare from infection
• CBC: pancytopenia
• Urinalysis: proteinuria, RBC casts (lupus nephritis)

• Hydroxychloroquine: ALL SLE patients (reduces flares, prevents organ damage, protects against APS)
• NSAIDs: for arthritis and serositis
• Steroids: for flares and organ-threatening disease
• Azathioprine: maintenance for lupus nephritis, skin, hematological disease
• Mycophenolate mofetil (MMF): preferred for lupus nephritis induction/maintenance
• Cyclophosphamide: severe lupus nephritis (Class III/IV), CNS lupus
• Belimumab (anti-BAFF): biologic - reduces flares
• Sunscreen, vitamin D, contraception (avoid estrogen-containing OCP in APS patients)

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12. Gout

• Underexcretion (90%): CKD, drugs (thiazides, low-dose aspirin, pyrazinamide), alcohol, hypertension
• Overproduction (10%): Lesch-Nyhan syndrome (HGPRT deficiency), tumor lysis syndrome, psoriasis, hemolytic anemia
• Diet: red meat, shellfish, beer (purines → xanthine → uric acid)
• Fructose (stimulates purine synthesis)

1. Asymptomatic hyperuricemia
2. Acute gouty arthritis
3. Intercritical gout
4. Chronic tophaceous gout

• Sudden onset, severe, incapacitating joint pain (often wakes from sleep)
• 1st MTP joint (podagra) - most classic (75% of first attacks)
• Also: ankle, knee, wrist
• Redness, warmth, swelling, exquisite tenderness
• Triggers: alcohol, dietary indulgence, surgery, dehydration, infections, starting allopurinol
• Self-limiting (7-14 days)

• Tophi: subcutaneous deposits of urate crystals (helices of ears, extensor tendons, olecranon, first MTP)
• Chronic arthropathy, joint destruction
• Urate nephropathy, urolithiasis (uric acid stones)

• Gold standard: synovial fluid analysis - needle-shaped (negative birefringent) MSU crystals under polarized light (appear yellow when parallel to compensator axis)
• Serum uric acid: elevated (>7 mg/dL in men, >6 mg/dL in women) - but may be normal during acute attack
• X-ray: "rat bite" erosions with overhanging edges (Martel's sign), punched-out lesions - late

• Acute attack: NSAIDs (indomethacin), colchicine (within 12-24h of attack onset), or steroids (if NSAIDs/colchicine contraindicated)
• Urate-lowering therapy (ULT): Target uric acid <6 mg/dL
  • Allopurinol (xanthine oxidase inhibitor) - 1st line; start at low dose (100mg), titrate; do NOT start during acute attack
  • Febuxostat (selective xanthine oxidase inhibitor) - alternative
  • Uricosurics: probenecid (increases renal excretion) - if underexcretor with normal renal function
  • Rasburicase/pegloticase: uricase enzyme - for severe tophaceous gout/tumor lysis
• Lifestyle: avoid triggers, dietary modification, adequate hydration

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HEPATOLOGY

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13. Viral Hepatitis

Hepatitis B - HBsAg Serology:

• Prodrome: nausea, vomiting, RUQ discomfort, fatigue, fever, anorexia
• Icteric phase: jaundice, dark urine (bilirubinuria), pale stools, pruritus
• ALT/AST: markedly elevated (>10x normal)
• Recovery: majority in acute hepatitis

• Fulminant hepatitis (massive necrosis) - rare but fatal without transplant
• Chronic hepatitis → cirrhosis → HCC

• HAV/HEV: supportive
• HBV: entecavir, tenofovir (NRTIs) for chronic hepatitis
• HCV: Direct-acting antivirals (DAAs) - sofosbuvir-based regimens, near 100% cure rate, 8-12 weeks

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14. Cirrhosis

• Chronic alcohol abuse (most common in Western world)
• Chronic viral hepatitis B and C (most common globally)
• NAFLD/NASH (metabolic - increasingly common)
• Autoimmune hepatitis
• Primary biliary cholangitis / PSC
• Hemochromatosis, Wilson's disease
• Drug-induced

• Compensated: no decompensation (Child-Pugh A)
• Decompensated: ascites, variceal bleeding, encephalopathy, jaundice (Child-Pugh B/C)

• Jaundice, spider nevi, palmar erythema, leukonychia, clubbing
• Hepatic encephalopathy (asterixis/"flapping tremor")
• Coagulopathy (low PT/INR - cannot synthesize clotting factors)
• Hypoalbuminemia → edema, ascites
• Gynecomastia, testicular atrophy, loss of body hair (in males from estrogen excess)

• Splenomegaly
• Ascites
• Caput medusae (dilated periumbilical veins)
• Esophageal/gastric varices

• Elevated bilirubin, ALT, AST (AST:ALT >2:1 in alcoholic cirrhosis)
• Low albumin, prolonged PT
• Thrombocytopenia (hypersplenism + decreased thrombopoietin)
• Elevated liver enzymes + low synthetic function

• Ascites (managed with spironolactone ± furosemide, paracentesis)
• Spontaneous bacterial peritonitis (SBP) - ascitic fluid PMN >250/μL; treat with cefotaxime
• Hepatic encephalopathy - precipitated by GI bleed, infection, constipation; treat with lactulose, rifaximin
• Hepatorenal syndrome (HRS)
• Esophageal varices → bleeding (propranolol prophylaxis, endoscopic band ligation)
• HCC (regular surveillance with US + AFP every 6 months)

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15. Portal Hypertension

• Pre-sinusoidal (pre-hepatic): Portal vein thrombosis, splenic vein thrombosis, schistosomiasis
• Sinusoidal (hepatic) - most common: Cirrhosis (any cause), hepatic vein thrombosis (Budd-Chiari syndrome before)
• Post-sinusoidal (post-hepatic): Budd-Chiari syndrome, constrictive pericarditis, right heart failure

1. Left gastric vein → esophageal veins → esophageal varices (most dangerous - can bleed massively)
2. Superior rectal → inferior rectal veins → anorectal varices (not hemorrhoids)
3. Paraumbilical veins → epigastric veins → caput medusae
4. Retroperitoneal collaterals → veins of Retzius

• Splenomegaly → hypersplenism → pancytopenia
• Ascites
• Portosystemic encephalopathy
• Esophageal variceal bleeding (hematemesis, melena) - life-threatening
• Caput medusae

• Primary prevention of variceal bleeding: non-selective beta-blockers (propranolol, carvedilol)
• Acute variceal bleed: IV terlipressin/octreotide + endoscopic variceal band ligation (EVL); Sengstaken-Blakemore tube for refractory
• TIPS (transjugular intrahepatic portosystemic shunt) for refractory ascites or recurrent variceal bleeds
• Treat underlying cause

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16. Amoebic Liver Abscess

• Fever (spiking) - most common
• Right hypochondrial pain/tenderness (pleuritic component - referred to right shoulder)
• Hepatomegaly (tender)
• Intercostal tenderness
• Only 10-30% have concurrent diarrhea/dysentery
• Men aged 20-40 most affected
• Complications: rupture into pleura (most common), pericardium (most serious), peritoneum

• WBC markedly elevated (neutrophilia)
• Elevated ALP (most consistently elevated LFT)
• Stool: trophozoites/cysts (often negative)
• Serology: indirect hemagglutination antibody test or ELISA - positive in >90%
• Ultrasound (investigation of choice): single, hypoechoic lesion, right lobe (>80%), "anchovy paste" pus
• Aspiration: chocolate brown/anchovy sauce pus (lytic necrosis of tissue)

• Metronidazole 400-800mg TID x 7-10 days (drug of choice - kills trophozoites)
• Followed by luminal agent: diloxanide furoate (500mg TID x 10 days) to eliminate intraluminal cysts
• Aspiration: indicated if: large abscess (>5cm), left lobe (risk of pericardial rupture), no response to metronidazole after 72h, diagnosis uncertain
• Surgery: rarely needed (rupture with peritonitis)

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INFECTIOUS DISEASES

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17. Enteric Fever (Typhoid Fever)

• Intestinal perforation (ileum, at Peyer's patches) - peritonitis - most dreaded
• Intestinal hemorrhage
• Typhoid hepatitis, cholecystitis
• Myocarditis, encephalopathy ("typhoid state")
• 5-10% become chronic carriers (gallbladder reservoir)

• Gold standard: Blood culture (1st week) - 80-90% positive
• Bone marrow culture: most sensitive (remains positive even after antibiotics started)
• Stool culture (2nd-3rd week)
• Widal test: agglutination test (TO and TH antigens) - O titer >1:160, H titer >1:160 significant; but false positives common (low specificity)
• Typhidot/Typhidot-M: rapid IgM detection - more specific

• Fluoroquinolones (ciprofloxacin): traditional 1st line, now resistance common in South Asia
• Ceftriaxone/cefixime: for fluoroquinolone-resistant strains (common in Indian subcontinent)
• Azithromycin: for uncomplicated typhoid, especially in South Asia
• Duration: 7-14 days
• Dexamethasone: for severe typhoid with altered consciousness
• Cholecystectomy: for chronic carriers

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18. Dengue

1. Dengue without warning signs
2. Dengue with warning signs (abdominal pain, persistent vomiting, fluid accumulation, mucosal bleed, lethargy, liver enlargement >2cm, platelet rapidly dropping)
3. Severe dengue: severe plasma leakage (shock), severe bleeding, severe organ impairment

• Febrile phase (Days 1-3): High fever (39-40°C), "breakbone fever" - severe myalgia, arthralgia, headache, retro-orbital pain; macular rash; facial flushing; relative bradycardia
• Critical phase (Days 4-6): Defervescence (fever drops) - plasma leakage → dengue shock syndrome (DSS); thrombocytopenia nadir; ascites, pleural effusion; bleeding
• Recovery phase (Days 7+): Reabsorption of leaked fluids - risk of fluid overload; bradycardia; convalescent rash (isles of white in sea of red)

• WBC: leukopenia (hallmark)
• Platelets: thrombocytopenia (often <100,000; <20,000 in severe)
• Hematocrit: elevated (hemoconcentration from plasma leakage)
• NS1 antigen: positive Day 1-5 (best early test)
• IgM antibody: positive from Day 5-6 (primary) or earlier (secondary)
• PCR: gold standard for definitive diagnosis

• No specific antiviral
• Supportive: oral hydration (dengue without warning signs)
• IV crystalloids (dengue with warning signs or severe dengue) - careful fluid management
• Platelet transfusion: only for active bleeding + platelets <20,000 (NOT prophylactic)
• Aspirin/NSAIDs/steroids: CONTRAINDICATED (risk of bleeding)
• Paracetamol for fever

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19. Malaria

• P. falciparum - most dangerous, cerebral malaria, most deaths
• P. vivax - most common; causes relapse (hypnozoites in liver)
• P. malariae - quartan malaria (72h cycle); causes nephrotic syndrome
• P. ovale - rare; relapse (hypnozoites)
• P. knowlesi - zoonotic (macaques), Southeast Asia

• Sporozoites (mosquito saliva) → liver (exoerythrocytic schizogony) → merozoites → RBCs (erythrocytic schizogony) → ring forms → trophozoites → schizonts → merozoites (released → fever cycle) → gametocytes (taken up by mosquito).
• P. vivax/ovale: dormant hypnozoites in liver → relapse months/years later.

• Classic malarial paroxysm: cold stage (rigors) → hot stage (high fever, 40-41°C) → sweating stage (profuse sweating, defervescence)
• Fever periodicity: 48h (tertian - P. vivax, P. ovale, P. falciparum); 72h (quartan - P. malariae)
• Anemia, splenomegaly (chronic)
• Headache, myalgia, nausea, vomiting

• Cerebral malaria: altered consciousness, seizures, coma - rosetting and sequestration of infected RBCs in brain capillaries
• Severe anemia (Hb <7)
• Respiratory distress (ARDS)
• Hypoglycemia (quinine-induced or from parasite consumption)
• Renal failure (blackwater fever - massive hemolysis, hemoglobinuria)
• Hyperparasitemia (>5%)
• Algid malaria: septicemic shock
• Splenic rupture

• Thick blood film (most sensitive - screening)
• Thin blood film (species identification and parasite density)
• Rapid Diagnostic Tests (RDTs): HRP2 antigen (P. falciparum), pLDH
• PCR: most sensitive and specific

• P. vivax/ovale: Chloroquine (blood stage) + Primaquine (liver hypnozoites - prevents relapse; check G6PD first)
• P. falciparum (uncomplicated): Artemisinin-based combination therapy (ACT) - artemether-lumefantrine or artesunate-amodiaquine
• Severe malaria: IV artesunate (preferred) or IV quinine + doxycycline; supportive ICU care

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20. Tuberculosis (TB)

• Usually asymptomatic or mild (children, immunocompromised may develop symptomatic primary)
• Ghon focus (mid-lung) + hilar lymphadenopathy = Ranke complex on CXR

• Occurs in upper lobes (high O2 tension)
• Cavity formation (cheesy/caseous necrosis)

• Constitutional: fever (low-grade, evening rise), night sweats, weight loss, fatigue, anorexia
• Respiratory: chronic cough (>2-3 weeks), hemoptysis, pleuritic chest pain
• Massive hemoptysis (Rasmussen aneurysm - erosion of pulmonary artery)

• Lymphadenitis (most common in India/developing countries) - cervical nodes, matted, may become collar-stud abscess
• Pleural TB: pleural effusion (lymphocytic exudate)
• CNS: tuberculous meningitis (neck stiffness, CSF: lymphocytes, high protein, low glucose, India-ink negative), tuberculoma
• Bone: Pott's disease (vertebral TB - D10-L1), cold abscess (psoas abscess), Pott's paraplegia
• GI: ileocaecal TB (commonest site), strictures
• Genitourinary: "sterile pyuria" (WBCs in urine, culture negative on routine media)
• Adrenal (Addison's disease)
• Miliary TB: hematogenous spread → seed-like 2mm lesions throughout body; millet seed shadows on CXR; highest risk in immunocompromised

• AFB smear (sputum): cheap, quick; 3 sputum samples (2 early morning, 1 spot)
• Culture (Lowenstein-Jensen medium): gold standard; slow (6-8 weeks)
• CBNAAT/GeneXpert MTB/RIF: rapid molecular diagnosis + rifampicin resistance in 2 hours - now recommended as first-line in India
• Mantoux/TST: positive (≥10mm in immunocompetent) = past exposure or latent TB; ≥5mm in HIV/immunocompromised
• IGRA (interferon-gamma release assay): QuantiFERON-TB Gold - better than TST, not affected by BCG
• CXR: apical infiltrates, cavitation, calcification, hilar adenopathy
• Adenosine deaminase (ADA): elevated in pleural/CSF TB

• Intensive phase (2 months): HRZE - Isoniazid (H) + Rifampicin (R) + Pyrazinamide (Z) + Ethambutol (E)
• Continuation phase (4 months): HR - Isoniazid + Rifampicin
• Total: 6 months (new cases)
• Key side effects:
  • Isoniazid: peripheral neuropathy (give pyridoxine/B6), hepatotoxicity, lupus-like syndrome
  • Rifampicin: hepatotoxicity, orange discoloration of urine/secretions, enzyme inducer (reduces OCP, warfarin efficacy)
  • Pyrazinamide: hepatotoxicity, hyperuricemia/gout
  • Ethambutol: optic neuritis (color vision - red-green discrimination; baseline visual acuity)
• MDR-TB: resistant to H+R → 18-24 months treatment with second-line agents

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NEUROLOGY

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21. Headache

• Primary headaches (no structural cause): Tension-type, Migraine, Cluster
• Secondary headaches (underlying pathology): SAH, meningitis, raised ICP, hypertension, GCA

Tension-Type Headache (TTH) - Most Common:

• Bilateral, "band-like" pressure/tightening, mild-moderate intensity
• NOT aggravated by physical activity; NO nausea/vomiting, NO photophobia/phonophobia (or only one)
• Episodic (<15 days/month) or chronic (>15 days/month for >3 months)
• Treatment: Paracetamol, aspirin, NSAIDs; preventive: amitriptyline

Migraine:

• Unilateral (but can be bilateral), pulsating/throbbing, moderate-severe
• Aggravated by physical activity
• Nausea ± vomiting; photophobia + phonophobia
• Duration 4-72 hours
• Aura (in ~30%): fully reversible neurological symptoms preceding/accompanying headache - visual (zig-zag fortification spectra/scotoma), sensory, speech
• Triggers: stress, hormonal changes (menstruation), lack of sleep, certain foods (cheese, chocolate, red wine), bright lights
• Pathophysiology: cortical spreading depression → trigeminal activation → neurogenic inflammation
• Treatment - Acute: triptans (sumatriptan) - 5-HT1B/D agonists; NSAIDs; antiemetics; ergotamine
• Preventive (if ≥4 attacks/month): propranolol, amitriptyline, valproate, topiramate, CGRP antagonists (erenumab)

Cluster Headache:

• Most severe headache - "suicide headache"
• Strictly unilateral, orbital/periorbital, excruciating (9-10/10)
• Duration 15-180 minutes
• Autonomic features: ipsilateral lacrimation, conjunctival injection, nasal congestion, ptosis, miosis (Horner's)
• Occurs in clusters (weeks) with remission periods
• 90% male
• Treatment - Acute: high-flow O2 (100%, 10-15L/min), sumatriptan SC; Preventive: verapamil, lithium, corticosteroids

Subarachnoid Hemorrhage (SAH):

• "Thunderclap" headache - "worst headache of my life," sudden onset
• Stiff neck, photophobia
• CT head (non-contrast) - 1st investigation
• LP if CT negative: xanthochromia (yellow CSF)
• Cause: ruptured berry aneurysm (80%)

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22. Stroke

• Ischemic stroke (85%): Thrombotic or embolic occlusion of cerebral artery
• Hemorrhagic stroke (15%): Intracerebral hemorrhage (10%) + Subarachnoid hemorrhage (5%)

• Large artery atherosclerosis (carotid, MCA, vertebrobasilar)
• Cardioembolic: AF (most common cardiac cause), recent MI, valvular heart disease, patent foramen ovale
• Small vessel disease (lacunar): hypertension, diabetes
• Other: dissection, vasculitis, hypercoagulable state, sickle cell

• CT head (non-contrast): 1st line - to exclude hemorrhage (appears white/hyperdense in hemorrhagic stroke)
• CT/MRI angiography: identifies vessel occlusion
• MRI DWI: most sensitive for early ischemia (within hours)
• ECG: AF, MI
• Echo: cardiac source
• Carotid Doppler: stenosis

• Time is brain (1.9 million neurons die per minute during ischemic stroke)
• IV thrombolysis: rt-PA (alteplase) within 4.5 hours of onset (if no contraindications: no hemorrhage, no recent surgery, BP <185/110)
• Mechanical thrombectomy: within 6-24 hours for large vessel occlusion (MCA, basilar) - superior to thrombolysis
• Aspirin 300mg within 48h (if thrombolysis not given)
• Blood pressure: do NOT aggressively lower in acute ischemic stroke (permissive hypertension)

• Antiplatelets (aspirin + clopidogrel for 21 days, then single agent) or anticoagulation (AF)
• Statin therapy
• BP control (ACEI/ARB)
• Carotid endarterectomy (if >70% symptomatic stenosis)

• Stop anticoagulants (reversal agents)
• BP control: target <140 systolic
• Neurosurgical evaluation (large hematoma with mass effect, cerebellar hemorrhage)
• NO thrombolysis

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RESPIRATORY MEDICINE

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23. Asthma

• Episodic wheezing, dyspnea, chest tightness
• Cough (especially nocturnal/early morning - characteristic)
• Symptoms worse at night and early morning
• Diffuse expiratory wheeze on auscultation
• Hyperinflated chest (in chronic/severe disease)
• Prolonged expiratory phase
• Features of allergic disease: eczema, rhinitis, conjunctivitis (atopic triad)

• FEV1/FVC ratio: <0.7 (obstructive pattern)
• FEV1: reduced
• FVC: normal or mildly reduced
• Reversibility: FEV1 improvement ≥12% AND ≥200mL after bronchodilator (salbutamol 400mcg) - diagnostic
• Peak Flow: diurnal variation >20% (morning dip)
• Bronchial provocation (methacholine challenge): hyperresponsiveness

• Acute severe asthma: SABA nebulized (salbutamol), ipratropium (anticholinergic), systemic steroids (IV hydrocortisone/oral prednisolone), O2, IV magnesium sulphate
• Life-threatening asthma: Silent chest, bradycardia, exhaustion, PaO2 <8kPa → ICU + intubation

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24. Chronic Bronchitis

• Predominantly bronchitis component of COPD
• Overweight, cyanosed (hypoxemia)
• Oedematous (cor pulmonale → right heart failure)
• Productive cough (chronic sputum)
• Recurrent respiratory infections
• Hypoxic + Hypercapnic (PaO2↓, PaCO2↑)
• Hematocrit elevated (secondary polycythemia)

• Thin, breathless (SOB dominant)
• Barrel chest, hyperinflation
• Pursed-lip breathing
• PaO2 relatively preserved, PaCO2 low/normal

• Spirometry: FEV1/FVC <0.7 post-bronchodilator (COPD confirmation); FEV1% for severity (GOLD classification)
• CXR: increased bronchial markings, hyperinflation, cardiomegaly (cor pulmonale)
• HRCT: airway wall thickening, mucus plugging
• ABG: hypoxemia, hypercapnia (type 2 respiratory failure)
• Sputum culture: Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis (common exacerbating organisms)

• Smoking cessation (most important intervention - slows FEV1 decline)
• Bronchodilators: SABA (salbutamol), LABA (salmeterol), LAMA (tiotropium)
• ICS: in high-risk patients (eosinophilia) - add to LABA
• Mucolytics: N-acetylcysteine, carbocisteine
• Pulmonary rehabilitation
• Vaccinations: annual influenza, pneumococcal
• Long-term O2 therapy (LTOT): if PaO2 <7.3kPa (55 mmHg) at rest → improves survival in severe COPD
• Acute exacerbation: bronchodilators (nebs), steroids (prednisolone 40mg x 5d), antibiotics (amoxicillin/doxycycline), controlled O2, NIV (BiPAP for hypercapnic failure)

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25. Pleural Effusion

1. Pleural protein/serum protein ratio >0.5
2. Pleural LDH/serum LDH ratio >0.6
3. Pleural LDH >2/3 of upper normal serum LDH

• Small effusion: may be asymptomatic
• Moderate-large: dyspnea, chest discomfort, non-productive cough
• Examination: reduced chest expansion, stony dull percussion (most prominent), reduced/absent breath sounds, reduced VF/VR, tracheal deviation away from effusion (large effusion)

• CXR: >300mL needed to blunt costophrenic angle; meniscus sign; tracheal shift
• Ultrasound: most sensitive (detects even small effusions); guides aspiration
• CT chest: for underlying cause (malignancy, empyema)
• Diagnostic thoracocentesis (pleural tap): send for protein, LDH, glucose, pH, cytology, culture, adenosine deaminase (ADA - for TB)
• Pleural fluid pH <7.2: empyema/complicated parapneumonic → chest drain required
• ADA >40 U/L: TB pleuritis (highly sensitive + specific)

• Treat underlying cause
• Therapeutic drainage if symptomatic (large effusion)
• Empyema: antibiotics + chest drain; surgery (VATS) if loculated
• Malignant effusion: talc pleurodesis or indwelling pleural catheter (IPC)

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26. Pneumothorax

• Primary Spontaneous Pneumothorax (PSP): No underlying lung disease; tall, thin young men; subpleural bleb rupture
• Secondary Spontaneous Pneumothorax (SSP): Complicating existing lung disease (COPD, asthma, cystic fibrosis, TB, Pneumocystis)
• Traumatic: Rib fractures, penetrating chest wound, iatrogenic (after subclavian line, mechanical ventilation)
• Tension Pneumothorax: Air enters but cannot escape (one-way valve) → progressive mediastinal shift → compresses opposite lung and heart → cardiorespiratory collapse - MEDICAL EMERGENCY

• Sudden onset sharp pleuritic chest pain (ipsilateral)
• Dyspnea
• Tachycardia
• Examination: reduced chest expansion, hyperresonant percussion (air-filled), absent/reduced breath sounds, reduced VF/VR, tracheal deviation away (tension)

• Severe hypotension, tachycardia, JVP raised, tracheal deviation away, absent breath sounds
• Treat IMMEDIATELY - clinical diagnosis; don't wait for CXR
• Needle decompression: 2nd intercostal space, midclavicular line → converts tension to simple pneumothorax → definitive chest drain

• CXR: visible lung edge with absent lung markings beyond; deep sulcus sign (supine)
• CT chest: if doubt, or SSP (better defines underlying disease)

• Small PSP (<2cm) + no SOB: observe (spontaneous reabsorption at 1.25% per day; high-flow O2 speeds reabsorption)
• Large PSP (≥2cm) or SOB: aspiration (1st line in BTS guidelines) → intercostal drain if fails
• SSP: intercostal chest drain (underlying lung disease means less tolerance)
• Recurrent PSP: surgical pleurodesis (VATS) or talc pleurodesis
• Intercostal drain: 5th ICS, anterior axillary line (safe triangle)

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27. Pneumonia

• Fever, rigors
• Productive cough (purulent sputum; rusty/red = pneumococcal)
• Pleuritic chest pain (sharp, worse with inspiration)
• Dyspnea
• Examination: reduced expansion, dull percussion, bronchial breathing (harsh, >2kHz sound over consolidation), increased tactile vocal fremitus, crackles (fine to coarse), whispering pectoriloquy (sound enhanced over consolidation)

• 0-1: Mild (outpatient)
• 2: Moderate (hospital admission)
• 3-5: Severe (ICU consideration)

• CXR: consolidation (opacification with air bronchograms - pathognomonic)
• CBC: leukocytosis (neutrophilia in bacterial; lymphocytosis in viral/atypical)
• CRP, procalcitonin (elevated)
• Sputum Gram stain and culture
• Blood cultures (2 sets)
• ABG (severe)
• Urinary antigen test: Legionella urinary antigen, Pneumococcal urinary antigen (rapid, specific)
• Atypical serology: Mycoplasma IgM, cold agglutinins

• Mild (outpatient): amoxicillin 500mg TID x 5 days; if penicillin allergic: doxycycline or clarithromycin
• Moderate-Severe (inpatient): IV co-amoxiclav + clarithromycin (or azithromycin)
• Severe/ICU: IV piperacillin-tazobactam + clarithromycin ± oseltamivir (if influenza)
• Legionella: fluoroquinolone (levofloxacin) or clarithromycin

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28. Coal Worker's Pneumoconiosis (CWP)

1. Simple CWP: Coal macules (1-2mm) and nodules (>7mm) in upper lobes; relatively benign; FVC/FEV1 may be normal; asymptomatic or mild symptoms
2. Progressive Massive Fibrosis (PMF): Large, bilateral, upper lobe opacities >10mm; severe disease; restriction + obstruction; massive central necrosis (melanoptysis - coughing black sputum)

• Duration and intensity of exposure
• Small particle size (1-5 μm - reaches alveoli)
• Co-exposure to silica (increases fibrogenic potential)

• Dyspnea (progressive)
• Productive cough
• Black/dark sputum (anthracosis)
• Advanced: severe restrictive/combined defect, cor pulmonale, respiratory failure

• CXR: upper lobe opacities (coal dust: 0/0 to 3/3 ILO profusion score); PMF: large bilateral perihilar masses
• HRCT: more sensitive, better characterization
• PFTs: restrictive or mixed pattern in PMF

• No specific treatment - preventive/supportive
• Dust control (most important) - dust suppression at workplace
• Surveillance programs for coal workers
• Smoking cessation
• Treat complications: inhaled bronchodilators, O2, pulmonary rehabilitation
• Compensation programs (industrial disease)

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CARDIOLOGY

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29. Angina Pectoris

• Retrosternal chest pain/pressure/heaviness/"elephant on chest"
• Radiation to left arm (C8-T1 dermatome), jaw, neck, epigastrium
• Triggered by exertion, cold, emotion, large meals (increased demand)
• Relieved by rest and GTN (glyceryl trinitrate)
• Duration 2-10 minutes (>20 min suggests MI)
• Dyspnea often accompanies

• ECG: may be normal at rest; ST depression + T-wave inversion during pain/exercise
• Exercise ECG (ETT): ST depression ≥1mm horizontal/downsloping = positive test; used for diagnosis and risk stratification
• Echocardiography: wall motion abnormalities, LV function
• Coronary CT angiography (CTCA): non-invasive assessment of coronary anatomy
• Nuclear imaging/stress perfusion imaging (SPECT, cardiac PET)
• Coronary angiography (gold standard): defines anatomy, guides revascularization

• Lifestyle: stop smoking, weight loss, exercise, Mediterranean diet
• Anti-anginal drugs:
  • Short-acting nitrates (GTN sublingual/spray) - for acute attacks
  • Beta-blockers (atenolol, bisoprolol) - 1st line for stable angina (reduces HR and contractility)
  • Calcium channel blockers (amlodipine, diltiazem) - if beta-blockers contraindicated
  • Long-acting nitrates (isosorbide mononitrate) - 2nd line
  • Ivabradine (If channel inhibitor) - rate control
  • Ranolazine: for refractory angina
• Secondary prevention:
  • Aspirin 75mg daily (antiplatelet)
  • Statin (atorvastatin 80mg)
  • ACEI/ARB (especially if LV dysfunction or diabetes)
• Revascularization:
  • PCI (percutaneous coronary intervention/angioplasty + stent)
  • CABG (coronary artery bypass grafting) - preferred for left main, 3-vessel disease, diabetics

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30. Myocardial Infarction (MI)

• STEMI (ST-Elevation MI): Complete occlusion → transmural infarction → ST elevation + LBBB
• NSTEMI (Non-ST Elevation MI): Partial occlusion → ST depression, T-wave changes + POSITIVE TROPONIN
• Unstable Angina: Like NSTEMI but NEGATIVE troponin (no necrosis)

• Severe crushing/squeezing chest pain - "worst pain of my life"
• Onset usually at rest or minimal exertion (unlike stable angina)
• NOT relieved by GTN
• Radiation to left arm, jaw, neck
• Sweating (diaphoresis), pallor, nausea, vomiting
• Fear of death (angor animi)
• Duration >30 minutes
• Silent MI (no pain): in diabetics (autonomic neuropathy), elderly, women

• Troponin I or T: most specific/sensitive; rises at 3-6h, peaks 12-24h, remains elevated 7-14 days
• CK-MB: rises 4-6h, peaks 12-24h, normalizes in 48-72h (useful for re-infarction)
• LDH: rises 24-48h, peaks 3-5 days, normalizes in 7-14 days (if presenting late)
• Myoglobin: earliest marker (1-4h) but not cardiac specific

• Immediate (minutes-hours): ventricular fibrillation (most common cause of early death), sinus bradycardia/heart block (inferior MI - RCA supplies SA/AV node)
• Early (hours-days): cardiogenic shock, acute MR (papillary muscle rupture), VSD, free wall rupture → cardiac tamponade
• Late (weeks): Dressler's syndrome (pericarditis at 2-10 weeks, autoimmune), LV aneurysm, heart failure, mural thrombus → embolism

• MONA (Morphine, Oxygen, Nitrates, Aspirin) - though O2 only if hypoxic; morphine may delay clopidogrel absorption
• Dual antiplatelet: Aspirin 300mg + Ticagrelor 180mg (or Prasugrel or Clopidogrel 600mg)
• Anticoagulation: Unfractionated heparin or fondaparinux
• Primary PCI (preferred reperfusion) - within 90 minutes of first medical contact (door-to-balloon time)
• Thrombolysis (streptokinase, alteplase) - if PCI not available within 120 minutes; door-to-needle within 30 minutes
• Beta-blocker (if no cardiogenic shock)
• ACE inhibitor/ARB (reduces LV remodeling)
• Statin (high-intensity)

• Aspirin + P2Y12 inhibitor (12 months)
• Beta-blocker (especially if EF <40%)
• ACEI/ARB + Aldosterone antagonist (eplerenone if EF <35%)
• Statin (atorvastatin 80mg)

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31. Acute Rheumatic Fever (ARF)

• J - Joint involvement: Migratory polyarthritis (most common, >75%) - large joints (knees, ankles, elbows, wrists); painful, fleeting, responds dramatically to aspirin
• O - ♥ Carditis: Pancarditis (endo + myo + pericarditis); mitral regurgitation most common valve lesion; leads to Rheumatic Heart Disease (RHD)
• N - Nodules: Subcutaneous nodules (firm, painless, over bony prominences)
• E - Erythema marginatum: Pink/red rash with pale center, margin moves outward; trunk > limbs
• S - Sydenham's chorea (St. Vitus dance): Irregular, involuntary, purposeless movements of face and limbs; delayed manifestation (weeks-months); associated with emotional lability

• Fever (>38.5°C)
• Elevated ESR/CRP
• Prolonged PR interval on ECG
• Arthralgia (only if arthritis not used as major criterion)

• Positive throat culture or rapid strep test
• Elevated/rising ASO (anti-streptolysin O) titer (>200 IU in adults, >333 IU in children)
• Anti-DNase B (more sensitive than ASO for skin infection)

• Eradicate streptococcus: benzylpenicillin (single IM dose of 1.2 million units) OR oral phenoxymethylpenicillin x 10 days
• Anti-inflammatory:
  • Arthritis + carditis (mild): Aspirin 4-8g/day (salicylates in divided doses)
  • Severe carditis (cardiomegaly, heart failure): Corticosteroids (prednisolone)
• Chorea: valproate or carbamazepine; diazepam for severe

• Benzathine penicillin G 1.2 million units IM every 3-4 weeks
• Duration: 10 years or until age 21 (no carditis); 10 years or age 25 (mild carditis); lifelong if severe RHD

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32. Hypertension

• Primary (essential) hypertension: 95% - no identifiable cause; multifactorial (genetics, obesity, salt intake, alcohol, stress, renal)
• Secondary hypertension: 5% - identifiable cause:
  • Renal: CKD, renovascular (renal artery stenosis - "2-3% of hypertension")
  • Endocrine: Primary aldosteronism (Conn's), Cushing's, Phaeochromocytoma, Acromegaly, Hypothyroidism
  • Coarctation of aorta
  • Drugs: OCP, steroids, NSAIDs, cocaine

• Heart: LVH → diastolic dysfunction → HFpEF; CAD, MI; HF
• Brain: stroke (ischemic and hemorrhagic), hypertensive encephalopathy, vascular dementia
• Kidneys: hypertensive nephropathy → CKD
• Eyes: hypertensive retinopathy (Keith-Wagener grades I-IV): Grade I (arteriolar narrowing), II (AV nipping), III (flame hemorrhages, cotton-wool spots), Grade IV (papilledema) = malignant hypertension
• Vessels: peripheral vascular disease, aortic aneurysm, aortic dissection

• Urine: dipstick (protein, blood), ACR (albumin:creatinine ratio)
• Bloods: U&E, creatinine, glucose, lipids, FBC
• ECG: LVH (Sokolov-Lyon criteria: S in V1 + R in V5/V6 >35mm)
• Echo: for LVH, diastolic function
• Renal US, aldosterone:renin ratio, 24h urinary catecholamines (if secondary cause suspected)
• Fundoscopy

• Lifestyle modifications: salt restriction (<6g/day), weight loss, regular exercise, DASH diet, alcohol limit, smoking cessation
• Drug therapy (NICE step approach):
  • Step 1: ACE inhibitor (or ARB if ACE intolerant) for <55y or diabetics; CCB (amlodipine) for >55y and black patients
  • Step 2: ACE/ARB + CCB
  • Step 3: ACE/ARB + CCB + thiazide diuretic (chlorthalidone/indapamide)
  • Step 4 (resistant): add spironolactone 25-50mg (potassium check first) or alpha-blocker/beta-blocker
• Hypertensive emergency: IV labetalol, IV sodium nitroprusside, IV nicardipine; reduce MAP by 25% in first hour (not more - risk of ischemia)

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33. Aortic Stenosis

• Senile calcific (most common in >65 years): Calcium deposits on normal tricuspid valve
• Congenital bicuspid aortic valve (most common cause in <65 years): Abnormal 2-leaflet valve → earlier calcification (by 4th-5th decade)
• Rheumatic heart disease (also causes MR and AR; pure AS rare from RHD)

1. Syncope (exertional) - vasodilatory reflex or arrhythmia; 3-year survival if untreated
2. Angina (exertional) - subendocardial ischemia due to increased O2 demand; 5-year survival if untreated
3. Dyspnea (heart failure) - worst prognosis; 1-2 year survival if untreated

• Pulse: slow-rising, plateau, low-volume (pulsus parvus et tardus)
• Apex: sustained, heaving (LVH)
• Aortic area (right 2nd ICS): harsh ejection systolic murmur (ESM), grade 3-5
• Radiation to carotid arteries (neck) and right clavicle
• Soft/absent A2 (aortic component of S2) with an ejection click (in bicuspid valve, absent in calcified valve)
• Paradoxical splitting of S2 (severe AS)
• S4 gallop (stiff ventricle)

• ECG: LVH (strain pattern - ST depression + T-wave inversion in V5-V6)
• CXR: cardiomegaly, post-stenotic dilation of ascending aorta, calcification of aortic valve
• Echo (Doppler): key diagnostic test - valve area, gradient, LV function
• Cardiac catheterization: direct pressure measurement if echo inconclusive or pre-surgical

• Mild/moderate with no symptoms: surveillance (annual echo for severe)
• Severe AS with symptoms: Valve replacement (indication: survival benefit)
  • SAVR (Surgical Aortic Valve Replacement) - for lower surgical risk (<75y)
  • TAVI/TAVR (Transcatheter Aortic Valve Implantation) - for high/prohibitive surgical risk or age >75y
• Medical: No drugs have proven benefit in slowing progression; manage symptoms (diuretics cautiously for HF); statins have NOT proven to slow progression
• Vasodilators (nitrates, ACEI) used cautiously - risk of hypotension in severe AS

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34. Mitral Stenosis (MS)

• Dyspnea on exertion (earliest symptom) → orthopnoea, PND
• Hemoptysis (pulmonary venous hypertension → rupture of pulmonary veins; frothy blood-stained sputum)
• Palpitations (due to AF)
• Right heart failure (if severe): edema, hepatomegaly, ascites
• Systemic embolism from LA thrombus (especially in AF) → stroke (most feared)
• Hoarseness: Ortner's syndrome (dilated LA compresses left recurrent laryngeal nerve)

• Malar flush: rosy cyanotic cheeks (low CO + vasoconstriction)
• Pulse: irregularly irregular (AF); small volume
• Apex: tapping, non-displaced (in the absence of MR/LVH) - palpable S1
• Loud S1 (pliable mitral valve leaflets, not yet calcified)
• Opening snap (OS) after S2 (passive opening of high-pressure LA) - closer to S2 = more severe
• Mid-diastolic rumbling murmur (MDM) - low-pitched, at apex; heard best in left lateral position with bell; pre-systolic accentuation (in sinus rhythm)
• Pulmonary hypertension signs: loud P2, RV heave, tricuspid regurgitation murmur

• Mild: >1.5 cm²
• Moderate: 1.0-1.5 cm²
• Severe: <1.0 cm²; pressure gradient >10 mmHg

• ECG: P-mitrale (broad, bifid P waves in lead II - LA enlargement), AF (in advanced), RVH (P pulmonale if PAH)
• CXR: LA enlargement (double shadow on right cardiac border, elevated left main bronchus, posterior displacement of oesophagus on barium swallow), Kerley B lines (pulmonary venous hypertension), upper lobe blood diversion
• Echo (Doppler): essential - MVA, gradient, valve morphology (Wilkins score for commissurotomy suitability)

• Medical:
  • Diuretics (for pulmonary congestion)
  • Beta-blockers or digoxin (rate control in AF)
  • Anticoagulation (warfarin) for AF or LA thrombus (dabigatran/NOACs less established in RHD-AF)
  • Antibiotic prophylaxis against streptococcal infection (benzathine penicillin - secondary prevention)
• Interventional (definitive for moderate-severe symptomatic MS):
  • PTMC (Percutaneous Transseptal Mitral Commissurotomy) = PBMC/BMV - 1st choice if valve morphology favorable (Wilkins score ≤8, pliable, no calcium, no significant MR)
  • Surgical: Open mitral commissurotomy or Mitral valve replacement (MVR) - if unfavorable anatomy or significant MR/thrombus

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35. Congenital Heart Disease (CHD)

ACYANOTIC (Left-to-Right Shunts - initially):

• Defect in interventricular septum → LV to RV shunt
• Clinical: pansystolic murmur at left sternal border; small = loud murmur (maladie de Roger); large = soft murmur + features of heart failure
• Complication: Eisenmenger's syndrome (reversal of shunt - right to left - with pulmonary hypertension → cyanosis)
• Management: small may close spontaneously; large → surgical or catheter closure

• Defect in interatrial septum → LA to RA shunt
• Types: Ostium secundum (most common), Ostium primum (associated with AV canal defect + Down syndrome), Sinus venosus
• Clinical: fixed wide splitting of S2 (pathognomonic); flow murmur at pulmonary area; RV heave
• Complications: AF, Eisenmenger's, paradoxical embolism
• ECG: RBBB, right axis deviation (secundum); left axis deviation (primum)
• Management: catheter closure (secundum) or surgery

• Failure of ductus arteriosus to close → continuous aorta-to-pulmonary artery shunt
• Common in premature infants; associated with maternal rubella
• Clinical: continuous "machinery" murmur under left clavicle; bounding/water-hammer pulse; widened pulse pressure
• Management: Indomethacin (NSAIDs close PDA by reducing prostaglandin); surgical ligation or catheter device closure
• Beware: in duct-dependent CHD (e.g., pulmonary atresia), keep PDA open with PGE1 (alprostadil)

• Narrowing of descending aorta (usually just distal to ductus arteriosus, opposite left subclavian artery)
• Clinical: hypertension in upper limbs; reduced/absent femoral pulses; radiofemoral delay; systolic murmur (interscapular)
• CXR: "3 sign" (aortic kink), rib notching (intercostal collaterals)
• Association: bicuspid aortic valve, Turner syndrome (45,X)
• Management: balloon angioplasty or surgical resection

CYANOTIC (Right-to-Left Shunts - from birth):

1. Pulmonary stenosis (right ventricular outflow obstruction - key determinant of severity)
2. Right ventricular hypertrophy
3. Overiding aorta (aorta straddles the VSD)
4. Ventricular septal defect

• Clinical: cyanosis from birth or first weeks; "Tet spells" (hypercyanotic episodes - squatting relieves by increasing SVR, reversing shunt); clubbing; polycythemia
• CXR: "Boot-shaped heart" (coeur en sabot) - RV hypertrophy + small pulmonary artery
• ECG: RVH (right axis deviation, R in V1)
• Management: Tet spells - knee-chest position, morphine, propranolol, O2, phenylephrine; Definitive: complete surgical repair

• Aorta arises from RV; Pulmonary artery from LV → two parallel circulations (not compatible with life unless mixing present - ASD, VSD, PDA)
• Clinical: severe cyanosis from birth; no murmur; egg-on-side heart (CXR)
• Management emergency: PGE1 (keep PDA open), balloon atrial septostomy (Rashkind procedure) → Definitive: arterial switch operation (Jatene procedure) - within first 2 weeks of life

• Echocardiography: diagnosis of choice
• Cardiac catheterization: pre-surgical anatomy
• Prophylaxis against infective endocarditis
• Genetic syndromes: Down syndrome (AV canal, VSD, ASD), Turner syndrome (coarctation, bicuspid AV), DiGeorge (conotruncal defects - TOF, truncus arteriosus), Marfan (aortic root dilation, AR)

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