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Clinical Learning Notes: Gastroenterology & Hepatology

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1. DIARRHOEA DISEASES

Definition & Classification

• Secretory - active ion secretion (cholera, VIPoma). Does NOT resolve with fasting.
• Osmotic - unabsorbed solutes draw water (lactase deficiency, lactulose). DOES resolve with fasting.
• Inflammatory/Exudative - mucosal damage with blood/pus (IBD, invasive infections)
• Motility-related - accelerated transit (IBS-D, post-vagotomy)
• Malabsorptive - defective absorption (coeliac, pancreatic exocrine insufficiency)

Pathophysiology

• Infectious diarrhoea: pathogens disrupt normal mucosal function via toxin production, mucosal invasion, or alteration of fluid/ion transport
• Early rapid transit through the ascending and transverse colon is a dominant feature on scintigraphic studies. A relative lack of distal colonic segmenting activity combined with increased proximal colonic propagating pressure waves accelerates transit.
• In HIV/AIDS: CD4+ T cell depletion throughout the GI tract leads to enteropathy with increased lamina propria inflammation, damaged epithelium, and microbial translocation. Cryptosporidium parvum is the most frequent protozoon identified; it causes self-limited diarrhoea in immunocompetent hosts but chronic, refractory disease in AIDS.

Causes by Category

• Bacteria: Salmonella, Shigella, Campylobacter, E. coli (ETEC, EHEC), C. difficile, Vibrio cholerae
• Viruses: Rotavirus (commonest in children), Norovirus, Adenovirus
• Protozoa: Giardia lamblia, Entamoeba histolytica, Cryptosporidium

• IBD (Crohn's, Ulcerative Colitis)
• Malabsorption syndromes (coeliac disease, short bowel)
• Functional (IBS-D)
• Drug-induced (antibiotics, NSAIDs, metformin, laxative abuse)
• Endocrine (hyperthyroidism, Addison's, carcinoid, VIPoma)
• Microscopic colitis

Clinical Assessment

• Weight loss (unintentional)
• Age > 50 (new onset)
• Nocturnal diarrhoea
• Documented blood in stool
• Anaemia or family history of colorectal cancer

• Stool microscopy, culture, and sensitivity (MC&S); O&P (ova and parasites)
• C. difficile toxin PCR
• FBC (anaemia, eosinophilia), CRP, ESR
• LFTs, TFTs, coeliac screen (tTG-IgA)
• Faecal calprotectin (distinguishes IBD from IBS)
• Colonoscopy with biopsy if chronic/bloody

Management

Antidiarrhoeal agents (loperamide) are contraindicated in dysentery (bloody diarrhoea) and suspected C. difficile infection.

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2. CHRONIC LIVER DISEASE (CLD) / CIRRHOSIS

Definition

• Compensated cirrhosis: asymptomatic, no major complications
• Decompensated cirrhosis: defined by the presence of ascites, variceal bleeding, encephalopathy, or jaundice

Aetiology

Pathobiology

1. Fixed component - fibrous tissue and regenerative nodule compression
2. Functional component - active vasoconstriction from deficiency of intrahepatic nitric oxide (NO)

Clinical Features

Complications

• Varices - form when HVPG >10-12 mmHg; rupture risk increases with size and pressure. Variceal haemorrhage has a 20-30% mortality per episode.
• Ascites - sinusoidal hypertension + aldosterone activation + decreased oncotic pressure. Managed with salt restriction, spironolactone, furosemide, large-volume paracentesis (with albumin cover)
• Spontaneous bacterial peritonitis (SBP) - ascitic fluid infection (PMN >250 cells/mm3). Treat with cefotaxime IV; prophylax with norfloxacin in high-risk
• Hepatorenal syndrome (HRS) - functional renal failure; Type 1 is acute/severe, Type 2 is chronic

• Hepatic encephalopathy - ammonia accumulation; graded I-IV. Treat with lactulose, rifaximin, protein restriction (controversial)
• Jaundice - impaired conjugation and excretion
• Coagulopathy - reduced synthesis of clotting factors (II, VII, IX, X); reduced platelet count from splenomegaly
• Hepatocellular carcinoma (HCC) - 1-5% annual risk in cirrhosis; screen with USS + AFP every 6 months

Scoring Systems

• Class A (5-6): Well compensated, 1-year survival ~100%
• Class B (7-9): Significant compromise
• Class C (10-15): Decompensated, 1-year survival ~45%

Investigations

• FBC (low platelets, anaemia), LFTs (raised bilirubin, low albumin, raised GGT/ALP), PT/INR
• Hepatitis B/C serology, ANA, ASMA, AMA, serum ferritin, copper, caeruloplasmin
• USS abdomen (liver texture, splenomegaly, ascites, portal vein flow)
• Upper GI endoscopy (oesophageal varices)
• Liver biopsy (gold standard for staging); FibroScan (transient elastography) as non-invasive alternative

Management

• Treat underlying cause (antivirals for HBV/HCV, abstinence for alcohol, immunosuppression for AIH)
• Non-selective beta-blockers (propranolol, carvedilol) for primary/secondary variceal prophylaxis
• TIPS (Transjugular Intrahepatic Portosystemic Shunt) for refractory variceal bleeding/ascites
• Liver transplantation - definitive treatment for decompensated cirrhosis

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3. ACUTE HEPATITIS

Definition

• Direct (acetaminophen overdose, ischaemia): rapid rise then rapid fall of enzymes
• Immunologically mediated (viral hepatitis, most drugs, alcohol): gradual rise, plateau phase, gradual resolution

Causes

Laboratory Features

Clinical Features

• Jaundice occurs in ~70% of HAV, ~33% of HCV, variable in HBV
• Frank jaundice occurs when bilirubin >35-40 μmol/L (2-3 mg/dL)

Viral Hepatitis Serology Summary

Complications

• Acute (fulminant) liver failure - in <1% of viral hepatitis cases but high mortality; liver transplant may be needed
• Chronic hepatitis - HBV (5-10%), HCV (75-85%); progresses to cirrhosis over years
• Cholestatic hepatitis - prolonged jaundice with marked ALP rise
• Aplastic anaemia - rare complication of hepatitis (particularly non-A-E)

Management

• Rest, adequate nutrition, avoid alcohol and hepatotoxic drugs
• Monitor LFTs, PT/INR; admit if PT/INR rising (signs of liver failure)
• Notify public health (notifiable disease - HAV, HBV)

• Paracetamol overdose: N-acetylcysteine (NAC) ASAP; refer liver unit if criteria met (King's College Criteria)
• HAV: Supportive; immunoglobulin + vaccine for contacts
• HBV: Tenofovir or entecavir for severe acute or HBeAg-positive; pegylated interferon
• HCV: Direct-acting antivirals (DAAs) - sofosbuvir-based regimens; >95% cure

• Paracetamol: pH <7.3 after resuscitation, OR PT >100s + creatinine >300 μmol/L + grade III/IV encephalopathy
• Non-paracetamol: PT >100s, OR any 3 of: aetiology (drug/indeterminate), age <10 or >40, jaundice >7 days before encephalopathy, bilirubin >300 μmol/L, PT >50s

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4. FATTY LIVER DISEASE

Classification

Fatty Liver Disease
├── NAFLD (Non-Alcoholic Fatty Liver Disease) / MAFLD
│   ├── Simple steatosis (benign)
│   └── NASH (Non-Alcoholic SteatoHepatitis) - active injury
│       └── → Fibrosis → Cirrhosis → HCC
└── AFLD (Alcohol-related Fatty Liver Disease)
    ├── Simple steatosis
    ├── Alcoholic hepatitis
    └── Cirrhosis

The term MAFLD (Metabolic-Associated Fatty Liver Disease) has been proposed as a replacement for NAFLD to better reflect the underlying systemic metabolic dysfunction.

NAFLD/MAFLD

• Obesity (especially central/visceral)
• Type 2 diabetes (or family history)
• Dyslipidaemia (high TG, low HDL, high LDL)
• Hypertension
• Metabolic syndrome

1. Insulin resistance → increased release of free fatty acids from adipocytes (lipoprotein lipase overactivity) + reduced adiponectin → increased FFA uptake into hepatocytes → triglyceride accumulation (steatosis)
2. Second hits driving progression to NASH:
   • Inflammasome activation → IL-1 release
   • Reactive oxygen species (ROS) overproduction
   • ER stress and mitochondrial dysfunction
   • Gut microbiome dysbiosis → increased gut-derived endotoxin
   • Stellate cell activation → fibrosis

• Simple steatosis: >5% of hepatocytes with macrovesicular fat; no inflammation
• NASH: steatosis + lobular inflammation + hepatocyte ballooning (injury); may have Mallory-Denk bodies
• NAFLD Activity Score (NAS): steatosis (0-3) + lobular inflammation (0-3) + ballooning (0-2); NAS ≥5 = NASH

Clinical Features

• Usually asymptomatic - often incidentally found on USS or liver enzyme screen
• May have fatigue, malaise, or RUQ discomfort
• Hepatomegaly on examination
• Signs of metabolic syndrome (central obesity, hypertension, acanthosis nigricans)
• In advanced disease: features of cirrhosis

• AST:ALT ratio < 1 in NAFLD (opposite to alcoholic liver disease where >2:1)
• GGT may be mildly elevated
• ALP mild-moderate elevation
• Normal or slightly elevated bilirubin
• Lipid profile, HbA1c, fasting glucose

Investigations

• USS abdomen: echobright/hyperechoic liver (>30% steatosis)
• FibroScan / MRI elastography: non-invasive fibrosis staging
• Liver biopsy: gold standard to distinguish simple steatosis from NASH and grade fibrosis; essential for guiding management
• FIB-4 score (age x AST / platelet count x √ALT): non-invasive fibrosis index

Complications

• Progression to cirrhosis in ~20% of NASH
• HCC can develop even before cirrhosis in NASH (important - unlike most other causes)
• Increased cardiovascular disease risk (shared risk factors)
• Paediatric NAFLD: pattern differs - portal tract inflammation and mononuclear (not neutrophilic) infiltrates more prominent

Management

There are no drugs currently approved for NAFLD with simple steatosis. Liver transplant for end-stage NASH cirrhosis.

Alcoholic Fatty Liver Disease

• Steatosis: reversible with abstinence (within days-weeks)
• Alcoholic hepatitis: fever, jaundice, tender hepatomegaly, neutrophilia, AST:ALT >2; Maddrey's Discriminant Function (MDF) >32 = severe; treat with prednisolone 40 mg/day x 28 days
• Mallory-Denk bodies (eosinophilic intracytoplasmic inclusions) on histology
• Cirrhosis: irreversible; abstinence can still reduce portal pressure and improve survival

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5. IRRITABLE BOWEL SYNDROME (IBS)

Definition

Epidemiology

• Global prevalence: ~4.1% using Rome IV criteria (more common in women: 5.2% vs 2.9% in men)
• Estimated incidence: ~38 per 10,000 person-years
• Onset typically in young adults (20-40 years)
• Up to 50% do not seek healthcare

Subtypes (Rome IV)

Rome IV Diagnostic Criteria

1. Related to defecation
2. Associated with a change in frequency of stool
3. Associated with a change in form (appearance) of stool

Pathobiology

• Visceral hypersensitivity - lowered pain threshold in the gut; exaggerated responses to normal luminal stimuli
• Altered motility - accelerated transit (IBS-D), delayed transit (IBS-C)
• Gut microbiome dysbiosis - altered composition following gastroenteritis (post-infectious IBS in ~10%)
• Mucosal immune activation - increased mast cells, cytokines
• Psychological factors - anxiety, depression, adverse childhood experiences
• Genetic predisposition - IBS clusters in families (OR 1.75-2.75x vs unaffected relatives)
• Serotonin (5-HT) dysregulation - altered 5-HT signalling in the enteric nervous system

Clinical Features

• Abdominal pain or discomfort - typically cramping, relieved by defecation
• Bloating / abdominal distension
• Altered bowel habit (diarrhoea, constipation, or alternating)
• Mucus in stools (no blood)
• Symptoms worse with stress, meals, menstruation

Alarm Features (Red Flags - EXCLUDE IBS)

• New onset age ≥ 50 years
• Unintentional weight loss
• Rectal bleeding or haematochezia/melaena
• Nocturnal diarrhoea
• Anaemia
• Palpable abdominal mass or lymphadenopathy
• Family history of colorectal cancer, IBD, or coeliac disease

Investigations

Management

• Regular meals, no skipping
• Limit gas-producing foods (beans, lentils, carbonated drinks)
• Low FODMAP diet (fermentable oligosaccharides, disaccharides, monosaccharides, polyols) - effective in ~50% of IBS patients
• Adequate fluid and fibre intake

• Cognitive-behavioural therapy (CBT) - strong evidence
• Gut-directed hypnotherapy
• Mindfulness-based therapy

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6. GALLSTONE DISEASE (CHOLELITHIASIS)

Types of Gallstones

• Bile supersaturation with cholesterol (increased hepatic cholesterol secretion)
• Gallbladder hypomotility (bile stasis)
• Nucleation factors accelerating crystal formation

Clinical Presentations

Murphy's Sign

Tokyo Guidelines Diagnostic Criteria (Acute Cholecystitis)

• Suspected diagnosis: 1 item from A (Murphy's sign OR RUQ pain/tenderness/mass) + 1 item from B (fever OR raised CRP OR raised WBC)
• Definite diagnosis: A + B + C (imaging findings)

Investigations

• USS abdomen: first-line investigation; >95% sensitivity for gallstones; shows thickened GB wall, pericholecystic fluid in cholecystitis
• CT abdomen: superior for complications (perforation, abscess), gallstone ileus (sensitivity ~93%)
• MRCP (Magnetic Resonance Cholangiopancreatography): non-invasive imaging of biliary tree; best for CBD stones
• ERCP: both diagnostic and therapeutic; stone extraction, stenting
• Blood tests: FBC (raised WBC), LFTs (raised ALP, GGT, bilirubin with CBD stone), amylase/lipase (if pancreatitis)

Management

• Stones >3 cm
• Choledocholithiasis
• Chronic haemolytic conditions
• Gallbladder polyps >1 cm
• Porcelain gallbladder
• High-risk ethnic groups (e.g., Native Americans, northern India)
• Transplant patients, bariatric surgery patients

1. Nil by mouth + IV fluids
2. Analgesia
3. IV antibiotics (cefazolin; add metronidazole for Gram-negative cover)
4. Early laparoscopic cholecystectomy (within 72 hours - best outcomes)

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7. LIVER ABSCESS

Types

Pathogenesis

1. Biliary tract disease (35%) - cholangitis, biliary obstruction
2. Portal spread (20%) - from diverticulitis, appendicitis, Crohn's
3. Bacteraemia - systemic sepsis, trauma, infected cysts
4. Contiguous spread - subphrenic abscess, intra-abdominal collections
5. Cryptogenic (10%) - no identifiable source

Clinical Features

• Fever (most common), rigors, sweats
• Anorexia, weight loss, malaise
• Right upper quadrant pain and tenderness
• Hepatomegaly
• Jaundice (if biliary obstruction)
• Referred right shoulder pain (diaphragmatic irritation)
• Rarely: pleuritic chest pain (if right diaphragm involved)

• FBC: neutrophilia (leukocytosis); elevated CRP, ESR
• LFTs: raised ALP, GGT, bilirubin, mildly elevated transaminases
• Blood cultures (positive in ~50% of pyogenic)
• USS abdomen: multiloculated cystic mass (first-line)
• CT abdomen: confirms diagnosis; shows rim enhancement + air-fluid level; sensitivity 95%+
• Aspiration: Gram stain, MC&S, Ziehl-Neelsen for TB, fungal culture
• Amoebic serology (ELISA >95% sensitive for amoebic abscess)

Management

1. Identify and treat the source
2. Aspirate for microbiology (may require repeated aspiration)
3. Antimicrobial therapy

• IV antibiotics (combination):
  • Metronidazole + clindamycin (anaerobic coverage, excellent cavity penetration)
  • Third-generation cephalosporin or aminoglycoside (Gram-negative cover)
  • Total duration: 4-6 weeks
• Percutaneous needle aspiration or catheter drainage (preferred for large/multiloculated)
• Treat underlying cause (e.g., ERCP for biliary source)

• Metronidazole 400-800 mg TDS x 10 days (drug of choice)
• Diloxanide furoate 500 mg TDS x 10 days (to eradicate intestinal carriage)
• Aspiration only if: no response to metronidazole after 72 hours, large abscess at risk of rupture, left lobe abscess (risk of peritoneal rupture)

• Re-aspirate or insert drain
• Repeat microbiology
• Surgery (laparoscopy or open) if drainage and antibiotics fail

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QUICK REVISION SUMMARY TABLE

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• Goldman-Cecil Medicine International Edition (Elsevier)
• Bailey and Love's Short Practice of Surgery, 28th Edition
• Tietz Textbook of Laboratory Medicine, 7th Edition
• Robbins & Kumar Basic Pathology
• Sleisenger and Fordtran's Gastrointestinal and Liver Disease
• Yamada's Textbook of Gastroenterology, 7th Edition
• Harrison's Principles of Internal Medicine, 22nd Edition (2025)
• Medical Microbiology, 9th EditionAll 7 topics are now covered with detailed, exam-ready clinical notes. Here is a summary of what is included in each section:

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What's Covered

• Mechanistic classification (secretory vs osmotic vs inflammatory vs motility)
• Acute vs chronic causes, red flags, investigations, and management including ORT principles and specific antibiotic therapy

• Full pathobiology of hepatic stellate cell activation and portal hypertension (the NO paradox)
• All complications (varices, ascites, SBP, HRS, hepatic encephalopathy, HCC) with management
• Child-Pugh and MELD scoring, transplant criteria

• Direct vs immunologically-mediated injury distinction
• Full serology table for HAV/HBV/HCV
• Laboratory features table with AST:ALT ratios for each type
• King's College Criteria for liver transplant referral

• NAFLD/MAFLD/NASH spectrum with complete pathogenesis (insulin resistance, two-hit model)
• Histological grading (NAS score)
• Key differentiator: AST:ALT <1 in NAFLD vs >2 in alcoholic liver disease
• Updated 2024 therapy options including resmetirom

• Full Rome IV diagnostic criteria with all subtypes
• Gut-brain interaction model, visceral hypersensitivity, post-infectious IBS
• Low FODMAP diet, stepwise pharmacotherapy by subtype

• Stone types and risk factors, "5 Fs"
• Full clinical spectrum from biliary colic → acute cholecystitis → Charcot's triad → Rigler's triad
• Tokyo Guidelines diagnostic criteria for cholecystitis, management algorithms

• Pyogenic vs amoebic comparison table (including "anchovy sauce" aspirate for amoebic)
• CT image included
• Management: antibiotic combinations, drainage indications, amoebic treatment protocol