General Medicine

VIROLOGY & EPIDEMIOLOGY

HCV = single-stranded RNA virus (Flaviviridae) ; 6 genotypes (GT1–6); GT1 most common globally; GT3 most common in India/South Asia. No vaccine available . Transmission: parenteral (#1 — IVDU ), blood transfusion (pre-1992), sexual, vertical (low). Incubation: 2–26 weeks.

NATURAL HISTORY

• Acute HCV: usually asymptomatic (75–80%) ; rarely icteric; acute liver failure very rare
• Chronicity: 70–85% — highest rate of chronicity of all hepatitis viruses
• Of chronic HCV: 20–30% progress to cirrhosis over 20–30 years; cirrhosis → HCC risk 2–5%/year

EVALUATION

• Anti-HCV antibody — screening test; ELISA; positive in chronic HCV + past resolved HCV; turns positive 4–10 weeks after infection
• HCV RNA (PCR) — confirmatory test; quantitative (viral load); also positive in window period when antibody negative; used to monitor treatment response
• HCV Genotype — determines treatment duration and drug selection
• Liver biopsy / FibroScan — staging fibrosis; degree of fibrosis determines urgency of treatment

TREATMENT — DIRECT ACTING ANTIVIRALS (DAAs)

▶ Sofosbuvir (NS5B inhibitor) + Velpatasvir (NS5A inhibitor) — PANGENOTYPIC (Epclusa): 400/100 mg OD × 12 weeks; effective for GT1–6; recommended WHO first-line

▶ Glecaprevir + Pibrentasvir (Mavyret/Maviret) — pangenotypic; 3 tablets OD × 8 weeks (non-cirrhotic); 12 weeks (cirrhosis); pan-genotypic NS3/4A + NS5A inhibitor combination

▶ Sofosbuvir + Ledipasvir (Harvoni) — GT1 and GT4; 400/90 mg OD × 12 weeks

• Monitor: HCV RNA at week 4 (early virological response), end of treatment, and at 12 weeks post-treatment (SVR12 = cure )
• Screen for and treat HCV in HIV co-infection; post-transplant recurrence; compensated cirrhosis

DEFINITION

HRS = functional renal failure (no structural renal damage) occurring in patients with advanced cirrhosis + portal hypertension , characterised by intense renal vasoconstriction (↑ splanchnic vasodilation → compensatory renal vasoconstriction → ↓ GFR).

DIAGNOSIS (Criteria)

• Cirrhosis with ascites + serum Cr > 1.5 mg/dL (AKI criteria in cirrhosis )
• No response to 2 days of diuretic withdrawal + volume expansion (albumin 1 g/kg/day × 2 days) — rules out pre-renal AKI
• Absence of structural renal disease (no proteinuria > 500 mg/day, no haematuria, normal renal USS)

MANAGEMENT

▶ Terlipressin 1–2 mg IV q4–6h (splanchnic vasoconstrictor → ↓ splanchnic blood flow → ↑ renal perfusion) + Albumin 1 g/kg/day IV (plasma expansion) — most effective medical therapy; response in 40–50%

▶ Noradrenaline infusion (ICU setting) — alternative vasoconstrictor; equivalent to terlipressin

• TIPSS — decompresses portal system → ↓ RAAS activation → ↑ renal perfusion; for HRS-2 + refractory ascites
• Liver transplantation — only definitive treatment; renal function usually recovers post-transplant; simultaneous liver-kidney transplant (SLKT) if AKI > 4 weeks

• Patterns of derangement: Hepatocellular (ALT/AST raised >> ALP - viral, toxic, ischaemic hepatitis); Cholestatic (ALP/GGT raised >> ALT - biliary obstruction, PBC, drugs); Mixed; Isolated hyperbilirubinaemia (Gilbert syndrome, haemolysis).
• Synthetic function: Serum albumin - low in chronic liver disease (long half-life ~20 days); Prothrombin time/INR - prolonged in acute synthetic failure (best early marker, factor VII has short half-life); ammonia rises in encephalopathy.
• Other markers: GGT raised alongside ALP confirms a hepatobiliary source; isolated GGT rise with alcohol or enzyme inducers; isolated ALP rise also occurs with bone disease, pregnancy and placenta.

DEFINITION & CLASSIFICATION

Jaundice (Icterus) = yellowish discolouration of skin, sclerae, and mucous membranes due to raised serum bilirubin > 2.5–3 mg/dL (normal < 1 mg/dL). Latent jaundice = bilirubin 1–2.5 mg/dL (clinically inapparent).

Approach to Jaundice — Investigation Algorithm:

• History: Speed of onset; dark urine/pale stool (obstructive); fever + rigors (cholangitis ); recent viral illness; alcohol; drugs; family history
• LFTs: Conjugated vs unconjugated bilirubin (van den Bergh test ); ALT/AST vs ALP/GGT pattern
• USS — first imaging; biliary dilatation = obstruction; gallstones; liver disease; pancreatic mass
• MRCP — non-invasive biliary tract imaging; choledocholithiasis; malignancy; PSC ('beaded' appearance)
• ERCP — diagnostic + therapeutic (stone removal, stenting); only if intervention planned
• Viral markers, autoimmune antibodies, haemolysis screen as indicated by history

HAV Vaccine: Inactivated; 2 doses at 0 and 6–12 months; long-lasting immunity (> 20 years); recommended for travellers, IVDU, MSM, liver disease patients, food handlers.

HBV Vaccine: Recombinant HBsAg; 3 doses at 0, 1, 6 months; > 95% seroconversion; check anti-HBs titre at 4–8 weeks post-vaccination; revaccinate non-responders.

Management of acute hepatitis: Rest; adequate caloric intake; avoid alcohol and hepatotoxic drugs; monitor for signs of fulminant failure (encephalopathy, coagulopathy, hypoglycaemia, ↑ PT). Admit if encephalopathy, PT > 1.5× normal, severe vomiting, or dehydration.

• Serological diagnosis: HAV - anti-HAV IgM (acute), IgG (past/immunity); HBV - HBsAg + IgM anti-HBc (acute), HBeAg/HBV DNA (replication); HCV - anti-HCV antibody then HCV RNA to confirm active infection (antibody cannot separate past from current).
• Clinical course: Prodrome (anorexia, nausea, malaise, RUQ pain) then icteric phase (jaundice, dark urine, pale stools) then recovery; HAV and HEV never become chronic; HBV becomes chronic in 5-10% of adults (up to 90% of neonates); HCV becomes chronic in 70-80%.
• Complications: Fulminant hepatic failure (especially HEV in pregnancy, HBV with HDV co-infection); chronic hepatitis progressing to cirrhosis and hepatocellular carcinoma (HBV/HCV).

DEFINITION

ALF = rapid hepatocellular dysfunction in a person with no pre-existing liver disease , manifesting as coagulopathy (INR ≥ 1.5) + hepatic encephalopathy , occurring within 26 weeks of the initial insult.

CAUSES

• Paracetamol toxicity (#1 in UK/USA) — dose-dependent hepatotoxicity; > 150 mg/kg or 15 g in an adult; metabolite NAPQI depletes glutathione → hepatocyte necrosis
• Viral hepatitis (#1 in India/developing world) — HBV (#1 overall), HAV, HEV (pregnancy — 30% mortality)
• Drug-induced liver injury (DILI) — antitubercular drugs (HRZE), halothane, valproate, isoniazid
• Wilson's disease (young patient + ALF + haemolytic anaemia + normal or low ALP = Wilson's )
• Acute fatty liver of pregnancy (3rd trimester); HELLP syndrome; ischaemic hepatitis ('shock liver')

MANAGEMENT

• N-acetylcysteine (NAC) — replenishes glutathione; works best if given within 8–10 hrs of paracetamol OD but beneficial up to 24 hrs; also used in non-paracetamol ALF (improves transplant-free survival)

▶ Paracetamol OD: NAC 150 mg/kg IV over 1 hr → 50 mg/kg over 4 hrs → 100 mg/kg over 16 hrs

• Hepatic encephalopathy: Lactulose; rifaximin; avoid sedatives; nursing in quiet environment; treat precipitants
• Cerebral oedema (Grade 4 HE): Mannitol 0.5–1 g/kg IV; elevate head of bed 30°; ICP monitoring; target CPP > 60 mmHg; avoid hyperthermia/hyponatraemia
• Coagulopathy: FFP only if active bleeding or before procedures (NOT prophylactic — INR used as prognostic tool); Vitamin K 10 mg IV
• Hypoglycaemia — 50% dextrose + glucose monitoring 1–2 hourly; 10% dextrose maintenance infusion
• Avoid infection: Prophylactic antibiotics (co-amoxiclav) in selected cases; antifungals; surveillance cultures
• Haemodynamic support: Noradrenaline + vasopressin for septic shock; CRRT for AKI

KING'S COLLEGE CRITERIA FOR LIVER TRANSPLANTATION

DEFINITION & SPECTRUM

NAFLD = spectrum of liver disease from simple steatosis (fatty liver) to NASH (Non-Alcoholic SteatoHepatitis) to cirrhosis and HCC, occurring in the absence of significant alcohol use (< 2 drinks/day in women, < 3 drinks/day in men) and without other secondary causes of hepatic steatosis.

New nomenclature (2023): NAFLD → MASLD (Metabolic dysfunction-Associated Steatotic Liver Disease); NASH → MASH (Metabolic dysfunction-Associated SteatoHepatitis).

RISK FACTORS — METABOLIC SYNDROME

• Obesity (#1 risk factor) — especially central/visceral adiposity; BMI > 30
• Type 2 DM — insulin resistance is the core mechanism → ↑ hepatic lipogenesis (de novo) + ↑ free fatty acid flux to liver
• Dyslipidaemia (↑ TG, ↓ HDL); Hypertension; Polycystic ovary syndrome (PCOS)
• Hypothyroidism; sleep apnoea; rapid weight loss; TPN

CLINICAL FEATURES & DIAGNOSIS

• Often asymptomatic — discovered incidentally on USS or by elevated ALT/GGT
• Fatigue; RUQ discomfort; features of metabolic syndrome; hepatomegaly (smooth, non-tender)
• USS — hepatic steatosis (echobright liver, 'bright liver'); first-line imaging
• FibroScan (transient elastography with controlled attenuation parameter — CAP) — measures both steatosis + fibrosis non-invasively; replacing biopsy in many centres
• Liver biopsy — gold standard for NAFLD vs NASH differentiation; required for diagnosis of NASH and fibrosis staging

MANAGEMENT

• Weight loss — even 5–10% weight loss significantly reduces steatosis; > 10% can regress NASH fibrosis; cornerstone of management

▶ Semaglutide (GLP-1 agonist) 2.4 mg SC weekly — NASH resolution in 59% (NASH trial); FDA-approved for obesity; weight loss + direct anti-inflammatory hepatic effects

▶ Pioglitazone (thiazolidinedione) 30–45 mg OD — improves NASH histology even in non-diabetics; increases insulin sensitivity; limited by weight gain + fluid retention

▶ Resmetirom (Rezdiffra) — first FDA-approved drug specifically for NASH with fibrosis (2024); THRβ agonist (thyroid hormone receptor beta); reduces liver fat + fibrosis

• Vitamin E (800 IU/day) — antioxidant; improves NASH in non-diabetics (AGA guideline); avoid in diabetics + prostate cancer risk
• Treat metabolic syndrome: DM control; statins (safe in NAFLD; often avoided incorrectly); hypertension management

SPECTRUM

• Clinical features: Fatty liver - asymptomatic with hepatomegaly; alcoholic hepatitis - jaundice, tender hepatomegaly, fever, anorexia, ascites; cirrhosis - stigmata of chronic liver disease (spider naevi, palmar erythema, gynaecomastia, Dupuytren contracture) and features of decompensation; look for signs of dependence and withdrawal.
• Investigations: AST:ALT > 2:1 (both usually < 300 U/L); raised GGT and macrocytosis (high MCV); low albumin, raised bilirubin and INR in advanced disease; thrombocytopenia; ultrasound/FibroScan; Maddrey discriminant function and MELD score grade severity of alcoholic hepatitis.

MANAGEMENT

• Alcohol abstinence — single most important intervention; improves all stages
• Nutritional support — malnutrition is universal; enteral nutrition (nasogastric if needed); high-calorie, high-protein diet (1.2–1.5 g/kg/day protein)

▶ Prednisolone 40 mg OD × 28 days — for severe alcoholic hepatitis (Maddrey's DF > 32 OR MELD > 20); reduces 28-day mortality; check for infection/GI bleed first (contraindications)

▶ Pentoxifylline 400 mg TDS × 28 days — TNF-α inhibitor; alternative if steroids contraindicated; less evidence than steroids alone

• Manage complications: SBP (prophylactic norfloxacin), ascites (spironolactone + furosemide), HE (lactulose + rifaximin), variceal bleed (propranolol + EVL)
• Thiamine (Vitamin B1) supplementation — prevent/treat Wernicke's encephalopathy; give IV thiamine BEFORE any glucose/dextrose in alcoholics
• Liver transplantation — for end-stage ALD; usually require 6 months abstinence; excellent outcomes in carefully selected patients

DEFINITION & CAUSES

Portal hypertension = portal venous pressure > 10–12 mmHg (normal 5–10 mmHg). HVPG (Hepatic Venous Pressure Gradient) is the gold standard measurement; HVPG > 10 mmHg = clinically significant portal HTN; > 12 mmHg = variceal bleeding risk.

COMPLICATIONS OF PORTAL HYPERTENSION

• Oesophageal varices — gastro-oesophageal junction submucosa; rupture → massive haematemesis
• Gastric varices — cardiofundal varices; bleed less commonly but more severely
• Splenomegaly + Hypersplenism — thrombocytopenia (→ ↑ bruising/bleeding risk) + leucopenia + anaemia
• Ascites — see SN12; Na retention + hypoalbuminaemia + lymphatic overflow
• Hepatic encephalopathy ; Hepatorenal syndrome; Portopulmonary hypertension; Hepatopulmonary syndrome (HPS)
• Caput medusae — dilated periumbilical collateral veins; flow is centrifugal (outward from umbilicus); venous hum at umbilicus (Cruveilhier-Baumgarten murmur)

VARICEAL MANAGEMENT

• Primary prophylaxis (prevent 1st bleed): Screen all cirrhotics with OGD at diagnosis; small varices → propranolol (non-selective beta-blocker); medium/large varices → propranolol OR EVL (band ligation)
• Acute variceal bleed: Terlipressin + antibiotics + urgent endoscopy (EVL) within 12 hrs
• Secondary prophylaxis: EVL + propranolol (combination); TIPSS for those who fail endoscopic/pharmacological therapy

DEFINITION & PATHOGENESIS

HE = neuropsychiatric dysfunction caused by hepatic failure (inadequate detoxification → accumulation of neurotoxins — primarily ammonia — reaching the brain). Additional factors: false neurotransmitters, GABA receptor sensitisation, neuroinflammation.

WEST HAVEN GRADING

Asterixis (liver flap) = non-rhythmic lapse in sustained posture; best elicited with hands extended dorsally — hands flap at wrist. Also in uraemia, CO₂ retention (not specific to HE). Pathognomonic of metabolic encephalopathy.

PRECIPITANTS — FIND AND TREAT FIRST

MANAGEMENT

• Identify and treat precipitant (most important step — e.g., antibiotics for SBP, PRBC for GI bleed)

▶ Lactulose 30–60 mL TDS (non-absorbable disaccharide) — acidifies colon → NH₃ → NH₄⁺ (trapped) → expelled; target 2–3 soft stools/day; rectal lactulose if cannot swallow

▶ Rifaximin 550 mg BD — non-absorbable antibiotic; reduces urease-producing bacteria; prevents recurrence; better tolerated than lactulose

• Protein restriction: historically recommended; current guideline — maintain normal protein intake (1.2–1.5 g/kg/day) with vegetable/BCAA protein preferred over animal protein
• Correct electrolytes: Hypokalaemia (↑ NH₃ production in kidney) + hyponatraemia (worsens HE)
• Zinc supplementation (50 mg/day) — zinc is cofactor in urea cycle; often deficient in cirrhosis

DEFINITION & PATHOGENESIS

SBP = bacterial infection of ascitic fluid without an evident intra-abdominal surgically treatable source . Occurs in 10–30% of hospitalised cirrhotic patients. Pathogenesis: bacterial translocation from gut → mesenteric lymph nodes → systemic circulation → seeding of ascitic fluid (low opsonic activity — ↓ complement proteins → impaired bacterial clearance).

ORGANISMS

• E. coli (#1) — most common overall
• Klebsiella pneumoniae (#2)
• Streptococcus pneumoniae (#3 — Gram positive)
• Usually monomicrobial — polymicrobial suggests secondary peritonitis (perforated viscus — surgical emergency)

DIAGNOSIS

• Diagnostic paracentesis (mandatory in all cirrhotics admitted to hospital or with clinical deterioration)
• Ascitic fluid PMN count > 250 cells/mm³ = SBP (regardless of culture result — culture negative SBP = CNNA is common)
• Ascitic fluid culture — inoculate directly into blood culture bottles at bedside (↑ sensitivity); positive in only 40–50%
• Clinical features: fever (± rigors), abdominal pain/tenderness (may be subtle in cirrhosis!), worsening HE, deteriorating renal function

TREATMENT & PROPHYLAXIS

▶ Cefotaxime 2 g IV q8h × 5 days — first-line; OR Ceftriaxone 1 g IV OD × 5 days (alternative)

▶ IV Albumin: 1.5 g/kg on Day 1 + 1 g/kg on Day 3 — prevents HRS type 1 (reduces renal impairment from 33% to 10%); MANDATORY in SBP

SBP Prophylaxis:

▶ Primary prophylaxis: Norfloxacin 400 mg OD — for cirrhosis + ascitic protein < 15 g/L + Child C or Cr > 1.2 OR Na < 130

▶ Secondary prophylaxis (after any SBP episode): Norfloxacin 400 mg OD lifelong OR co-trimoxazole; reduces recurrence from 70% to 20%

• Pathogenesis: bacterial translocation from congested gut mucosa in cirrhosis; organisms seed the low-protein ascitic fluid which has poor opsonic activity; E. coli is the most common organism, followed by Klebsiella and Streptococcus pneumoniae; polymicrobial cultures suggest secondary peritonitis from a perforated viscus.
• Diagnosis: ascitic fluid PMN count >= 250 cells/mm3 is diagnostic regardless of culture result; inoculate blood culture bottles at the bedside for best yield; ascitic protein, LDH, and glucose help exclude secondary peritonitis; treatment should start while awaiting culture results.
• IV albumin: given alongside antibiotics prevents type 1 hepatorenal syndrome (rises in creatinine) and reduces mortality; the mechanism is maintenance of effective circulating volume and attenuation of the systemic inflammatory response.

DEFINITION & SAAG

Ascites = abnormal accumulation of fluid in the peritoneal cavity (> 150 mL detectable on USS). SAAG (Serum-Ascites Albumin Gradient) = serum albumin − ascites albumin; measured at the same time.

PATHOGENESIS OF CIRRHOTIC ASCITES

• Portal hypertension → sinusoidal hypertension → ↑ hydrostatic pressure → capillary leak into peritoneum
• Splanchnic arterial vasodilation (↑ NO, prostacyclin) → ↓ effective arterial blood volume → baroreceptor activation
• RAAS activation → ↑ aldosterone → Na/water retention → ↑ plasma volume → further portal pressure → ascites (vicious cycle)
• ADH release → water retention → dilutional hyponatraemia
• ↓ Serum albumin (↓ hepatic synthesis) → ↓ oncotic pressure → further fluid leakage

MANAGEMENT

• Salt restriction < 2 g/day (88 mmol/day) — cornerstone; most important non-pharmacological measure

▶ Spironolactone 100 mg OD + Furosemide 40 mg OD — maintain 100:40 ratio; titrate weekly; maximum: spironolactone 400 mg + furosemide 160 mg OD

• Target weight loss: 500 g/day (no peripheral oedema); 1 kg/day (with peripheral oedema) — faster diuresis causes AKI
• Large-volume paracentesis (LVP) — for tense/refractory ascites; drain ≤ 5 L; albumin 8 g/L removed (prevents PPCD)
• Refractory ascites: Monthly LVP; TIPSS (if no contraindication); liver transplantation

Hepatosplenomegaly causes: Cirrhosis + portal HTN; Chronic viral hepatitis (B/C); Lymphoma; CML; Kala-azar; Schistosomiasis; Storage diseases; Sarcoidosis.

Massive splenomegaly causes (tip reaches below umbilicus, crosses midline):

• Approach and investigations: History (fever, weight loss, alcohol, travel) and examination (characterise the liver edge - smooth/craggy/pulsatile; feel for a splenic notch); FBC and blood film, LFTs, viral serology, ultrasound abdomen (size, texture, portal vein); further tests (bone marrow, blood cultures, autoimmune screen) guided by the suspected cause.

DEFINITION & PATHOGENESIS

Amoebic liver abscess (ALA) = the most common extraintestinal complication of *Entamoeba histolytica* infection . Ingestion of cysts → trophozoites in colon → invade colonic mucosa → portal circulation → hepatic parenchyma → flask-shaped ulcers in colon and abscess formation in liver (right lobe — 80%; due to right portal vein draining most of colon).

CLINICAL FEATURES

• Fever — high-grade, remittent, with rigors
• RUQ pain — dull, constant; worse on movement; radiates to right shoulder (diaphragmatic irritation)
• Tender hepatomegaly — most important sign; often with intercostal tenderness
• Diaphragmatic irritation signs: Right basal crackles, dullness, reduced breath sounds (sympathetic effusion); hiccups; right shoulder tip pain
• Jaundice is unusual in uncomplicated ALA (< 20%); suggests biliary compression or large abscess
• Dysentery may be absent (concurrent colonic amoebiasis in only 30–40%)

INVESTIGATIONS

• USS — single (right lobe ), round/oval, hypoechoic abscess with well-defined border; first-line imaging
• Serology — amoebic IgG antibody (ELISA) — sensitivity > 95%; highly positive in ALA; also positive in previous infection (remains positive for years)
• Stool examination — *E. histolytica* cysts or trophozoites (present in only 30–40% of ALA)
• LFTs: ↑ ALP (most commonly elevated), ↑ ESR; leucocytosis; ↑ LDH
• Aspiration — 'anchovy sauce' / 'chocolate sauce' pus (sterile, brown/red, necrotic fluid; amoebae at abscess wall, not in pus center); culture negative

MANAGEMENT

▶ Metronidazole 400–800 mg TDS × 7–10 days (IV if severe, oral if mild) — drug of choice; tissue amoebicide; kills trophozoites in liver + gut wall

▶ Luminal amoebicide (after metronidazole) — Diloxanide furoate 500 mg TDS × 10 days — eliminates cysts from colon (prevents relapse and transmission); mandatory

• Percutaneous needle aspiration — indications: large abscess (> 5–10 cm ), imminent rupture, failure to respond to metronidazole in 72 hours, left lobe abscess (rupture risk into pericardium)
• Surgical drainage — rarely needed; for ruptured abscess with peritonitis

VIROLOGY & SPECIAL FEATURES

HDV (Hepatitis D virus) = defective RNA virus (virusoid) that can only infect patients who are simultaneously infected with HBV (requires HBsAg to form its envelope — cannot complete its life cycle without HBV). Single-stranded circular RNA; 35 nm particle; 1 genotype with 8 subtypes.

• Clinical patterns: co-infection (simultaneous HBV + HDV) usually causes acute hepatitis that resolves, with fulminant hepatitis in 5%; superinfection (HDV in a chronic HBV carrier) causes a more severe and often progressive disease with higher risk of cirrhosis and fulminant hepatic failure.
• Investigations: HBsAg positive (HDV requires HBV for replication); anti-HDV IgM (acute), anti-HDV IgG (past or chronic); HDV RNA by PCR confirms active replication; liver biopsy shows more severe necroinflammation than HBV alone.
• Treatment and prevention: no licensed anti-HDV treatment with high efficacy; bulevirtide (entry inhibitor) has recent European approval; pegylated interferon suppresses but rarely clears HDV; HBV vaccination prevents HDV co-infection (HDV cannot exist without HBV).

DIAGNOSIS

• Anti-HDV IgM — acute marker; elevated in co-infection and super-infection; distinguishes from isolated HBV
• Anti-HDV IgG — past or chronic HDV infection; persists lifelong
• HDV RNA (PCR) — quantitative; confirms active replication; used to monitor treatment
• HBsAg must be positive — HDV cannot exist without HBV; if HBsAg negative, HDV not possible

TREATMENT & PREVENTION

▶ Pegylated Interferon-α — only proven treatment for chronic HDV; × 48 weeks; achieved HDV RNA suppression in ~25% (poor response)

▶ Bulevirtide (Hepcludex) — 2 mg SC daily; entry inhibitor (blocks NTCP receptor used by HBV + HDV); first specifically approved drug for chronic HDV (EMA approved 2020); significantly reduces HDV RNA

• Prevention: HBV vaccination protects against HDV (cannot infect without HBV) → vaccinating against HBV = vaccinating against HDV
• No specific HDV vaccine exists; HBV vaccine + HBIG prevents co-infection

WILSON'S DISEASE

Wilson's disease = autosomal recessive disorder of copper metabolism (ATP7B gene mutation on chromosome 13) → defective hepatic copper excretion into bile → copper accumulation in liver, brain, eyes, kidneys, and joints.

Clinical features:

• Kayser-Fleischer (KF) rings — golden-brown rings at the periphery of cornea (Descemet membrane); seen by slit-lamp examination; present in > 95% with neurological Wilson's; may be absent in pure hepatic presentation
• Liver — acute hepatitis (can mimic viral hepatitis) → fulminant hepatic failure (young patient + ALF + haemolytic anaemia + low/normal ALP = Wilson's until proven otherwise) → cirrhosis
• Neuropsychiatric — dysarthria, tremor (wing-beating ), dystonia, psychiatric symptoms (personality change, psychosis)
• Haematological — Coombs-negative haemolytic anaemia (direct copper toxicity to RBC membrane)

Investigations:

• ↓ Serum caeruloplasmin (< 20 mg/dL); ↑ 24-hr urine copper (> 100 μg/day); ↑ serum free copper
• Slit-lamp examination for KF rings ; liver biopsy (copper stain — rhodanine/rubeanic acid) if diagnosis uncertain

▶ D-penicillamine — copper chelator; 250 mg QDS; first-line; lifelong; side effects: rash, nephrotic syndrome, SLE-like, worsening of neurological symptoms initially

▶ Trientine — alternative chelator; less side effects; preferred if penicillamine intolerant

▶ Zinc acetate — maintenance therapy; blocks intestinal copper absorption; safe in pregnancy; first-line for asymptomatic patients and maintenance

GAUCHER'S DISEASE

Gaucher's disease = most common lysosomal storage disorder worldwide; autosomal recessive (GBA gene mutation); deficiency of glucocerebrosidase (acid beta-glucosidase) → glucocerebroside accumulates in macrophages (Gaucher cells — 'crumpled tissue paper' cytoplasm on PAS stain ).

• Type 1 (Non-neuropathic ) — most common; massive splenomegaly (#1 symptom); hepatomegaly; bone disease (Erlenmeyer flask deformity ); pancytopenia; NO CNS involvement
• Types 2 & 3 — neuropathic; horizontal gaze palsy; fatal in childhood (Type 2)

▶ Enzyme Replacement Therapy (ERT): Imiglucerase (Cerezyme) IV biweekly — treats Type 1 and Type 3; dramatically reduces splenomegaly and improves haematological parameters; lifelong

▶ Substrate Reduction Therapy (SRT): Eliglustat / Miglustat — oral; inhibits glucosylceramide synthase → reduces substrate

HELICOBACTER PYLORI

*H. pylori* = gram-negative, microaerophilic, spiral bacillus that colonises the gastric antrum. Present in 50% of world population . Causes: peptic ulcer disease (duodenal > gastric), gastric adenocarcinoma (6× risk ), MALT lymphoma. Classified by WHO as Group 1 carcinogen.

Diagnosis:

• Urea breath test (UBT) — most accurate non-invasive test; patient drinks ¹³C-urea → H. pylori urease converts to ¹³CO₂ → detected in breath; avoidPPI × 2 weeks + antibiotics × 4 weeks before test
• H. pylori stool antigen — accurate; cheap; used for diagnosis + post-treatment test of cure
• Rapid urease test (CLO test) — from endoscopic biopsy (antrum); quick, cheap; 95% sensitivity; affected by PPI/antibiotics
• Serology (IgG) — cannot distinguish current vs past infection; NOT recommended for diagnosis/cure

H. PYLORI ERADICATION — TRIPLE THERAPY

▶ Standard Triple Therapy (14 days preferred over 7 days):
Omeprazole 20 mg BD + Amoxicillin 1 g BD + Clarithromycin 500 mg BD × 14 days
Eradication rate: ~80% (reduced due to clarithromycin resistance)

▶ Bismuth Quadruple Therapy (preferred if clarithromycin resistance > 20%):
Omeprazole 20 mg BD + Bismuth subcitrate 120 mg QDS + Tetracycline 500 mg QDS + Metronidazole 400 mg TDS × 14 days
Eradication rate: ~90%

▶ Concomitant Therapy (PCAM):
PPI + Clarithromycin + Amoxicillin + Metronidazole × 14 days — 90% eradication

• Test of cure — UBT or stool antigen 4–8 weeks after completion of therapy (not during treatment; avoid PPI × 2 weeks before test)

PEPTIC ULCER DISEASE

Duodenal ulcer (DU) ): Posterior wall D1 (erodes gastroduodenal artery → haemorrhage ); pain relieved by food , occurs 2–3 hrs after meals and at night (midnight hunger); excess acid; H. pylori in 90–95%. Gastric ulcer (GU) ): Lesser curvature antrum; pain worsened by food ; H. pylori 70–80%; NSAID association stronger.

▶ PPI (Omeprazole 20 mg BD × 4 weeks for DU; × 8 weeks for GU) — heals > 90% of ulcers; combine with H. pylori eradication if Hp-positive

• NSAID-induced ulcers: Stop NSAID if possible; PPI healing + maintenance; misoprostol (prostaglandin) for prevention if NSAID cannot be stopped

DEFINITION & CLASSIFICATION

Chronic diarrhoea = > 3 loose/watery stools/day persisting > 4 weeks (or stool weight > 200 g/day consistently). Classified by mechanism:

APPROACH TO DIAGNOSIS

• Stool studies: Consistency + volume + blood/fat/pus; stool culture + sensitivity + OPE; stool calprotectin (↑ in inflammatory ); stool fat (72-hr collection > 6 g/day = steatorrhoea)
• Investigations: CBC (anaemia, eosinophilia for parasite), TFT, anti-tTG IgA (coeliac), colonoscopy + biopsy (IBD, microscopic colitis), CT abdomen (Crohn's, pancreatic disease)
• D-xylose test — absorptive capacity of small intestine; low D-xylose in urine = mucosal disease (coeliac); normal = pancreatic insufficiency

Management:

• Treat underlying cause; oral rehydration + electrolyte replacement for all; nutritional support

▶ Coeliac disease: Strict gluten-free diet lifelong — resolution of symptoms within weeks

▶ IBD: Mesalazine (UC ); azathioprine/anti-TNF (Crohn's ); steroids for acute flares

▶ Bile acid malabsorption: Cholestyramine (bile acid sequestrant)

▶ Antimotility: Loperamide (peripheral opioid agonist) — reduces stool frequency; NOT for bloody diarrhoea (exacerbates inflammatory)

COELIAC DISEASE

Coeliac disease (gluten-sensitive enteropathy) = immune-mediated small intestinal injury triggered by dietary gluten (gliadin fraction) (wheat, barley, rye) in genetically susceptible individuals (HLA-DQ2 [95%] + HLA-DQ8 [5%] ). Results in villous atrophy and malabsorption.

CLINICAL FEATURES

• Classical: Chronic diarrhoea; steatorrhoea (pale, bulky, offensive, floating stools); weight loss; bloating; failure to thrive (children)
• Nutritional deficiencies: Iron deficiency anaemia (most common; duodenal Fe absorption); folate deficiency; Vitamin B12 deficiency; Vitamin D/Ca → osteoporosis; Vitamin K → coagulopathy
• Dermatitis herpetiformis — itchy blistering rash on elbows, knees, buttocks; pathognomonic skin manifestation of coeliac ; IgA deposits in skin
• Atypical/Silent — iron deficiency anaemia alone; infertility; arthritis; peripheral neuropathy; epilepsy; dental enamel defects

DIAGNOSIS

• Anti-tTG IgA antibody (anti-tissue transglutaminase) — best screening test; sensitivity + specificity > 90%; check with total IgA (10% of coeliac have selective IgA deficiency → false negative; use anti-tTG IgG or anti-DGP IgG if IgA deficient)
• Anti-endomysial antibody (EMA) IgA — highly specific (> 99%) but less sensitive; expensive
• Upper GI endoscopy + duodenal biopsy (Gold Standard) — while on gluten-containing diet; Marsh classification: Type 0 (normal) → Type IIIC (total villous atrophy )
• Histology: Villous atrophy + crypt hyperplasia + ↑ intraepithelial lymphocytes (> 30/100 enterocytes)
• HLA typing — negative HLA-DQ2/DQ8 excludes coeliac (NPV 99%)

MANAGEMENT

• Strict gluten-free diet (GFD) lifelong — remove wheat, barley, rye; rice, corn, potatoes, oats (pure) allowed; improvement in symptoms within 2 weeks; mucosal healing 1–2 years
• Nutritional supplements: Iron + folic acid + Vitamin B12 + Vitamin D + Ca + Vitamin K as needed; dietitian referral
• Monitor with anti-tTG IgA (should fall to normal on GFD); repeat endoscopy if no response
• Refractory coeliac disease: Not responding to strict GFD; rule out dietary non-compliance first; then steroids/immunosuppression; risk of enteropathy-associated T-cell lymphoma (EATL)

OVERVIEW

Extraintestinal manifestations (both IBD types):

MANAGEMENT

Ulcerative Colitis:

▶ Mild-Moderate UC: 5-ASA (Mesalazine ) oral + topical (enema/suppository) — for proctitis and left-sided UC; maintenance therapy lifelong

▶ Moderate-Severe UC: Oral prednisolone 40 mg OD + Azathioprine 2 mg/kg/day (steroid-sparing/maintenance)

▶ Acute severe UC (ASUC) — Truelove & Witts criteria: Bloody diarrhoea > 6/day + systemic features → Hospitalise; IV methylprednisolone 60 mg/day × 5 days; if no response at 72–96 hrs → IV Ciclosporin (2 mg/kg/day) OR Infliximab 5 mg/kg IV

• Colectomy — for refractory ASUC (toxic megacolon, perforation, failed medical treatment); curative in UC

Crohn's Disease:

▶ Mild flare: Prednisolone 40 mg OD × 8 weeks; Budesonide (ileal-release) for terminal ileal CD

▶ Moderate-Severe CD: Azathioprine / 6-mercaptopurine (maintenance); Methotrexate

▶ Biologic therapy (if steroid-dependent/refractory): Infliximab (anti-TNF-α) 5 mg/kg IV at 0, 2, 6 weeks then 8-weekly; Adalimumab SC; Vedolizumab (anti-α4β7 integrin ); Ustekinumab (anti-IL-12/23 )

DEFINITION & CAUSES

LGIB = bleeding from the GI tract distal to the ligament of Treitz (jejunum, ileum, colon, rectum, anus). Presents as haematochezia (fresh red blood per rectum) or dark maroon stools.

• Causes of lower GI bleed: haemorrhoids (#1 cause in young), diverticular disease (#1 cause of significant LGIB in adults > 60), angiodysplasia (elderly, aortic stenosis - Heyde syndrome), colorectal carcinoma, IBD (Crohn/UC), ischaemic colitis, radiation proctitis, anal fissure, and small bowel sources (Meckel diverticulum in children).
• Investigations: digital rectal examination; proctoscopy/sigmoidoscopy for anorectal bleeding; colonoscopy (gold standard for LGIB evaluation); CT angiography for massive ongoing haemorrhage; Meckel scan (99Tc pertechnetate) for children with unexplained LGIB.
• Management: resuscitate with IV fluids and blood transfusion; most LGIB stops spontaneously; colonoscopic haemostasis (adrenaline, clips, APC); interventional radiology (embolisation) for massive bleeding; surgery as a last resort.

MANAGEMENT

• Resuscitate + crossmatch; digital rectal examination; rigid sigmoidoscopy
• Colonoscopy — gold standard investigation; allows haemostasis (APC, clipping, injection)
• CT angiography — if active brisk bleeding; identifies bleeding site; allows angiographic embolisation
• Tagged RBC scan (Tc-99m-labelled RBC) — sensitive for slow bleeds (0.1–0.5 mL/min); non-specific location
• Surgical resection — for massive refractory bleeding; Meckel's diverticulectomy

DEFINITION & ORGANISMS

Bacillary dysentery (Shigellosis) = acute inflammatory colitis caused by *Shigella* spp. (S. dysenteriae most severe; S. flexneri most common worldwide; S. sonnei mild). Faeco-oral transmission; very low infectious dose (10–100 organisms ); invades colonic mucosa.

CLINICAL FEATURES

• Classic triad: Bloody diarrhoea (mucus + pus + blood ) + Abdominal cramps + Tenesmus (painful urge to defecate with little passed )
• High-grade fever; malaise; incubation 1–4 days; symptoms 4–7 days
• Investigations: Stool microscopy (numerous pus cells and RBCs, no trophozoites - distinguishes from amoebic dysentery); stool culture confirms Shigella and gives sensitivity; FBC (leucocytosis); U&E for dehydration; in suspected HUS - FBC (anaemia, thrombocytopenia, fragmented cells), creatinine and LDH.
• Complications: HUS (especially S. dysenteriae type 1 — Shiga toxin; D+ HUS); toxic megacolon; intestinal perforation; reactive arthritis (Reiter's syndrome — arthritis + urethritis + conjunctivitis — HLA-B27 ); seizures (Ekiri syndrome in children)

TREATMENT

• ORS + IV fluids — maintain hydration; correct electrolytes

▶ Ciprofloxacin 500 mg BD × 3–5 days — first-line (fluoroquinolone); reduces severity + duration; shortens excretion

▶ Azithromycin 500 mg OD × 3 days — for ciprofloxacin-resistant Shigella; preferred in children (500 mg/day); pregnancy

▶ Ceftriaxone 2 g IV OD — for severe/hospitalised cases; resistant organisms

• DO NOT use: Anti-motility agents (loperamide) — CONTRAINDICATED in bloody diarrhoea (↑ risk of toxic megacolon + prolongs excretion)
• HUS management: Supportive; IV fluids; avoid antibiotics in E. coli O157:H7 HUS (may worsen toxin release ); dialysis for severe AKI; platelet transfusion only if life-threatening bleeding

DEFINITION & PATHOPHYSIOLOGY

GERD (Gastro-Oesophageal Reflux Disease) = symptoms or mucosal damage caused by abnormal reflux of gastric contents into the oesophagus , resulting from failure of the anti-reflux barrier (predominantly the lower oesophageal sphincter — LOS ).

Pathophysiology: ↓ LOS tone (normal 15–35 mmHg) → Transient Lower Oesophageal Sphincter Relaxations (TLESRs) — the primary mechanism (not simply low basal LOS pressure); vagally mediated; triggered by gastric distension. Additional factors: hiatus hernia (reduces LOS length/pressure), delayed gastric emptying, ↓ oesophageal clearance, ↑ acid secretion.

CLINICAL FEATURES

• Heartburn (pyrosis) — retrosternal burning sensation; worse after meals, lying down, bending forward; relieved by antacids
• Regurgitation — effortless return of gastric contents to mouth; 'water brash' (sudden mouth-filling with saliva)
• Dysphagia (if oesophagitis or stricture); odynophagia (painful swallowing — indicates oesophagitis)
• Atypical (extra-oesophageal) symptoms: Chronic cough (acid micro-aspiration); hoarseness; laryngitis; asthma exacerbation; dental erosion; non-cardiac chest pain
• Complications: Barrett's oesophagus (columnar metaplasia → intestinal metaplasia; precancerous; gastric-type mucosa in lower oesophagus ) → Oesophageal adenocarcinoma ; oesophageal stricture; ulcer

MANAGEMENT

• Lifestyle measures: Head-of-bed elevation (30 cm); avoid lying down within 2–3 hrs of eating; weight loss; small frequent meals; avoid coffee, chocolate, alcohol, fatty/spicy foods, smoking; avoid tight clothing

▶ PPI (Proton Pump Inhibitors) — first-line pharmacotherapy:
Omeprazole 20 mg OD/BD × 4–8 weeks; Esomeprazole 40 mg OD; Pantoprazole 40 mg OD
Take 30–60 min BEFORE meals (H⁺/K⁺-ATPase most active when stimulated by food)
Highest acid suppression; heals oesophagitis in > 90% within 8 weeks

▶ H2 receptor antagonists (Ranitidine/Famotidine) — for mild/intermittent symptoms; less potent than PPI

▶ Antacids (Mg hydroxide/Al hydroxide) — immediate symptom relief; short duration; adjunct

▶ Prokinetics (Metoclopramide/Domperidone) — for gastroparesis + GERD; enhances LOS tone + gastric emptying; limited long-term use (tardive dyskinesia risk for metoclopramide)

• Surgical (Nissen's fundoplication): Laparoscopic; 360° wrap of gastric fundus around LOS; for GERD refractory to medical treatment; persistent regurgitation despite PPI; young patients wanting to avoid lifelong medication
• Barrett's oesophagus surveillance: Endoscopy every 3–5 years (no dysplasia); radiofrequency ablation (RFA ) or endoscopic mucosal resection (EMR) for high-grade dysplasia

ZOLLINGER-ELLISON SYNDROME (ZES)

ZES = gastrinoma (gastrin-secreting neuroendocrine tumour) of the pancreas or duodenum → massive ↑ gastrin → maximal acid secretion → multiple severe peptic ulcers (especially in unusual locations: D2, jejunum) + chronic diarrhoea from acid inactivating pancreatic enzymes + malabsorption.

• 25% associated with MEN-1 (multiple endocrine neoplasia type 1 — parathyroid + pituitary + pancreatic tumours)
• Clinical features: Multiple/recurrent PUD (atypical sites — D2/jejunum ); refractory to standard PPI; diarrhoea (acid inactivates lipase → steatorrhoea); weight loss
• Diagnosis: Fasting serum gastrin > 1000 pg/mL (strongly suggestive; normal < 100 pg/mL); Secretin stimulation test — IV secretin → paradoxical ↑ gastrin > 200 pg/mL (confirms ZES; in normal subjects secretin suppresses gastrin); tumour localisation by CT/MRI + EUS (endoscopic USS) + octreotide scan (SRS — somatostatin receptor scintigraphy )

▶ High-dose PPI (omeprazole 60–120 mg/day in divided doses) — acid suppression first priority; then surgical resection of tumour if localised and non-metastatic

ZENKER'S DIVERTICULUM

Zenker's diverticulum (pharyngo-oesophageal/posterior pulsion diverticulum) = herniation of pharyngeal mucosa through Killian's triangle (Killian's dehiscence ) — an area of weakness between the oblique (thyropharyngeus) and horizontal (cricopharyngeus) fibres of the inferior pharyngeal constrictor. Pulsion type (pushed out by ↑ intraluminal pressure from cricopharyngeal dysfunction).

• Clinical features: Elderly males; dysphagia (oesophageal compression by pouch); regurgitation of undigested food (sometimes hours after eating — 'gurgling sound in neck '); halitosis (decomposing food); aspiration pneumonia; palpable neck swelling (when large)
• Diagnosis: Barium swallow — shows the posterior diverticulum clearly (do NOT scope without X-ray — risk of perforation); CT neck/oesophagus
• Treatment: Symptomatic or large pouches — endoscopic stapling (Dohlman's procedure) (divides the cricopharyngeal bar between pouch and oesophagus — preferred) OR open surgical diverticulectomy + cricopharyngeal myotomy

AETIOLOGY & PATHOGENESIS

*Entamoeba histolytica* — intestinal protozoan; faeco-oral transmission (contaminated water/food); worldwide but endemic in India, Africa, Latin America. Cysts (infective form; 4-nucleated ) → swallowed → excystation in ileum → trophozoites in colon → invade mucosa → flask-shaped ulcers → bloody dysentery; trophozoites may enter portal circulation → liver abscess.

CLINICAL FORMS

• Asymptomatic cyst passer (90%) — most common; carrier; source of transmission; treat with luminal amoebicide
• Acute amoebic dysentery — bloody diarrhoea + crampy abdominal pain + tenesmus; stool shows RBCs + Charcot-Leyden crystals + trophozoites with ingested RBCs (haematophagous trophozoites — pathognomonic )
• Amoeboma — chronic inflammatory mass in caecum/ascending colon; mimics colonic carcinoma
• Amoebic liver abscess — see SN14

INVESTIGATIONS

• Stool microscopy — trophozoites with ingested RBCs; 4-nucleated cysts; at least 3 stool examinations
• Stool antigen ELISA — specific for *E. histolytica* (vs non-pathogenic *E. dispar*)
• Amoebic serology (IgG) — positive in invasive disease; elevated in ALA; may be negative in acute colitis
• Sigmoidoscopy — discrete flask-shaped ulcers separated by normal mucosa; biopsy from ulcer edge

TREATMENT

▶ Metronidazole 400–800 mg TDS × 5–10 days — tissue amoebicide; kills invasive trophozoites

▶ Diloxanide furoate 500 mg TDS × 10 days — luminal amoebicide; eliminates cysts from colon; given AFTER metronidazole (or alone for asymptomatic cyst passers); prevents relapse and transmission

• Clinical features: invasive colitis - bloody diarrhoea with mucus and tenesmus, right iliac fossa pain mimicking appendicitis; amoebic liver abscess - fever, right upper quadrant pain, hepatomegaly, hepatic tenderness, referred right shoulder tip pain; abscess usually single and in the right lobe.
• Investigations: stool microscopy for motile trophozoites with ingested RBCs (pathognomonic of E. histolytica); stool antigen test or PCR (more sensitive than microscopy); serology (anti-amoebic IgG) is useful for liver abscess; ultrasound of the liver for abscess characterisation.
• Complications: rupture of liver abscess into the pleural space, pericardium, or peritoneum; amoeboma (inflammatory mass mimicking carcinoma); toxic megacolon; rectal stricture in chronic disease.

CLASSIFICATION

CLINICAL FEATURES — SECONDARY PERITONITIS

• Sudden severe abdominal pain (perforation → 'board-like rigidity ')
• Guarding + Rigidity (involuntary muscular contraction — the cardinal signs)
• Rebound tenderness (Blumberg's sign) — pain on rapid release of pressure
• Absent bowel sounds (paralytic ileus from peritoneal inflammation)
• Fever, tachycardia, hypotension → septic shock ; pallor; toxic facies
• Obliteration of liver dullness (on percussion) — free air under diaphragm in perforation

INVESTIGATIONS

• Erect CXR/AXR — free gas under right dome of diaphragm (pneumoperitoneum = perforation); confirms perforated hollow viscus
• CT abdomen (gold standard) — identifies source; free fluid; free gas; bowel thickening
• CBC — leucocytosis; LFTs; serum amylase (pancreatitis); blood cultures × 2 (before antibiotics)
• Diagnostic peritoneal lavage — if diagnosis uncertain; peritoneal fluid: WBC > 500/mm³ = peritonitis

MANAGEMENT

• Resuscitation: IV fluids + O2 + urinary catheter; correct coagulopathy; blood cultures BEFORE antibiotics
• Broad-spectrum antibiotics: Piperacillin-tazobactam 4.5 g IV TDS (excellent empirical coverage) OR Ceftriaxone + Metronidazole; narrowed by culture results
• Emergency laparotomy — for secondary peritonitis from perforation; repair/resection of source; peritoneal lavage; drain placement
• Nasogastric tube — decompression; nil by mouth
• ICU care — for septic shock; vasopressors; mechanical ventilation if needed

DEFINITION & INDICATIONS

TPN (Total Parenteral Nutrition) = IV delivery of all nutritional requirements (carbohydrates, proteins as amino acids, lipids, electrolytes, vitamins, trace elements) bypassing the GI tract. Only indicated when the GI tract cannot be used (enteral route always preferred).

COMPLICATIONS

• Enteral nutrition - routes and monitoring: nasogastric tube for short-term; nasojejunal or PEG/PEJ for longer-term or gastroparesis; check residual volumes (> 250 mL hold and reassess); monitor electrolytes (especially phosphate, potassium, magnesium), glucose, liver enzymes and fluid balance daily.
• Vitamin D: synthesised in skin (cholecalciferol, D3) then hepatic 25-hydroxylation, then renal 1-alpha-hydroxylation (activated by PTH); functions - intestinal calcium and phosphate absorption, bone mineralisation, immune modulation; deficiency causes rickets (children) and osteomalacia (adults).

AETIOLOGY & PATHOGENESIS

*Vibrio cholerae* (serogroup O1 or O139) — gram-negative curved rod; produces cholera toxin (CT) (ADP-ribosylation of Gsα → permanently activates adenylate cyclase → ↑↑ cAMP → opens CFTR chloride channels → massive Cl⁻ + water secretion into gut lumen → rice-water diarrhoea ). Faeco-oral; contaminated water; epidemic/pandemic disease.

CLINICAL FEATURES

• 'Rice-water' stools — watery, colourless, with flecks of mucus; no blood; no pus; odourless; copious (10–20 L/day in severe cases)
• Profound dehydration — skin turgor ↓ (skin tenting ); sunken eyes; dry mucous membranes; thready pulse; 'washerwoman's hands' (wrinkled skin from dehydration)
• Hypovolaemic shock — tachycardia, hypotension; impaired consciousness in severe dehydration
• Muscle cramps — hypokalaemia + hyponatraemia from massive electrolyte losses
• Afebrile (no fever) — cholera toxin is purely secretory; no mucosal invasion; no inflammation → no fever (distinguishes from Shigella/Salmonella)

TREATMENT — CORNERSTONE: ORAL REHYDRATION

▶ ORS (Oral Rehydration Salts) — WHO ORS: Glucose 13.5 g + NaCl 2.6 g + KCl 1.5 g + trisodium citrate 2.9 g per litre of water = 245 mOsm/L (low-osmolarity ORS); FIRST-LINE for mild-moderate dehydration; restores using sodium-glucose co-transporter (SGLT1) which is NOT affected by CT

▶ IV Ringer's Lactate (Hartmann's) — preferred for severe dehydration/shock; 100 mL/kg over 3 hours (child) or 2 hours (adult); replace deficit rapidly; monitor for hypokalaemia

▶ Doxycycline 300 mg single dose (adults) — single most effective antibiotic; reduces duration + stool volume + carriage; first-line for cholera in adults
Azithromycin 1 g single dose — preferred in children (< 8 yrs) and pregnancy; fewer side effects
Ciprofloxacin 1 g single dose — alternative if above unavailable

• Antibiotics reduce severity and duration by ~50% and eliminate vibrio from stool; ORS remains the cornerstone — antibiotics are adjuncts
• Zinc supplementation (20 mg/day × 10–14 days) — recommended by WHO for children with cholera/acute diarrhoea; reduces duration + severity; prevents recurrence