TextbookClinical SciencesGastrointestinal Physiology

Gastrointestinal Physiology

GI physiology encompasses motility, secretion, digestion, and absorption throughout the alimentary tract, along with hepatobiliary and pancreatic function.

Key Facts

Gastric acid (HCl) is secreted by parietal cells via H⁺/K⁺ ATPase; stimulated by histamine (H2), acetylcholine (M3), and gastrin (CCK-B) Intrinsic factor (parietal cells) is essential for vitamin B12 absorption in the terminal ileum Bile salts are synthesised from cholesterol in hepatocytes, conjugated, and secreted; critical for fat-soluble vitamin absorption (A, D, E, K) Pancreatic enzymes: Lipase, amylase, trypsin (secreted as trypsinogen, activated by enterokinase); secretion stimulated by CCK and secretin Iron is absorbed in the duodenum (Fe²⁺ form); regulated by hepcidin (inhibits ferroportin) Folate is absorbed in the jejunum; vitamin B12 in the terminal ileum The migrating motor complex (MMC) sweeps debris during fasting — disrupted in SIBO Enterohepatic circulation recycles ~95% of bile salts; disruption (e.g., ileal resection) causes bile salt malabsorption and diarrhoea

Overview

Key Facts

The GI tract processes approximately 9L of fluid daily (2L ingested + 7L secretions); only ~100mL is excreted in faeces. Each region has specialised functions in digestion and absorption.

Epidemiology

GI diseases are extremely common in UK clinical practice. Coeliac disease affects approximately 1% of the population (many undiagnosed). IBS affects 10-20% of the population. Peptic ulcer disease affects ~5-10% lifetime risk.

Aetiology

GI function depends on:

  • Motility: Coordinated smooth muscle contraction (enteric nervous system — "second brain")
  • Secretion: Acid, enzymes, bile, mucus, bicarbonate
  • Digestion: Mechanical and chemical breakdown of macronutrients
  • Absorption: Specific transport mechanisms for nutrients, electrolytes, water
  • Neuroendocrine regulation: Vagus nerve, hormones (gastrin, CCK, secretin, GIP, motilin)

Pathophysiology

Gastric acid secretion has three phases:

  1. Cephalic phase (30%): Vagal stimulation — sight, smell, taste of food
  2. Gastric phase (60%): Gastric distension, peptides → gastrin release → acid secretion
  3. Intestinal phase (10%): Initially stimulatory, then inhibitory (secretin, GIP)

Defence mechanisms against acid: Mucus-bicarbonate barrier, prostaglandins (PGE2 promotes mucus/HCO3⁻ secretion, mucosal blood flow), epithelial cell turnover (3-5 days)

Hepatic function: Metabolism (drugs, bilirubin, ammonia), synthesis (albumin, clotting factors, bile), storage (glycogen, vitamins, iron), detoxification

Clinical Presentation

Malabsorption Syndromes

  • Diarrhoea, steatorrhoea, weight loss, nutritional deficiencies
  • Iron deficiency (duodenal disease — coeliac)
  • B12 deficiency (ileal disease — Crohn's, pernicious anaemia)
  • Fat-soluble vitamin deficiency (A, D, E, K) — pancreatic insufficiency, biliary obstruction

Dyspepsia and Acid-Related Disease

  • Epigastric pain, heartburn, early satiety, nausea
  • Duodenal ulcer pain: Relieved by eating, worse at night
  • Gastric ulcer pain: Worse with eating

Hepatobiliary Disease

  • Jaundice (bilirubin >35 µmol/L), pruritus, pale stools, dark urine (obstructive)
  • Coagulopathy (reduced synthesis of factors II, VII, IX, X)
  • Ascites, encephalopathy (decompensated liver disease)

Red Flags

  • Dysphagia — urgent 2-week-wait OGD referral
  • Unexplained weight loss with GI symptoms — malignancy screen
  • Haematemesis or melaena — upper GI bleeding
  • Iron deficiency anaemia in men or post-menopausal women — investigate GI tract

Differential Diagnosis

DiagnosisKey FeaturesInvestigation
Coeliac diseaseDiarrhoea, iron/folate deficiency, dermatitis herpetiformistTG-IgA antibodies, duodenal biopsy
Chronic pancreatitisSteatorrhoea, epigastric pain, diabetesFaecal elastase, CT pancreas
Bile salt malabsorptionWatery diarrhoea, post-cholecystectomy or ileal resectionSeHCAT scan (retention <15%)
Small intestinal bacterial overgrowthBloating, diarrhoea, B12 deficiencyGlucose hydrogen breath test
Peptic ulcer diseaseEpigastric pain, H. pylori associationOGD, H. pylori testing
Pernicious anaemiaB12 deficiency, macrocytic anaemia, glossitisB12, intrinsic factor antibodies, parietal cell antibodies

Diagnosis / Investigation

Bedside

  • Stool analysis: MC&S, faecal calprotectin (>100 µg/g suggests IBD), faecal elastase (<200 = pancreatic insufficiency)
  • Urea breath test: H. pylori (stop PPI 2 weeks before)

Bloods

  • FBC: Microcytic (iron), macrocytic (B12/folate) anaemia
  • Iron studies, B12, folate: Malabsorption screen
  • LFTs: Bilirubin, ALT, ALP, GGT, albumin
  • tTG-IgA + total IgA: Coeliac disease screening
  • Clotting: PT prolonged in liver disease/vitamin K deficiency

Imaging

  • OGD: Upper GI pathology, duodenal biopsy (coeliac)
  • Colonoscopy: Lower GI pathology, IBD assessment
  • USS abdomen: Gallstones, liver assessment
  • MRCP: Biliary tree, pancreatic duct assessment

Special Tests

  • SeHCAT scan: Bile salt malabsorption
  • Hydrogen breath test: SIBO, lactose intolerance
  • Capsule endoscopy: Small bowel pathology

Management

Non-pharmacological

  • Gluten-free diet: Coeliac disease — lifelong, with dietitian support
  • Low FODMAP diet: IBS symptom management
  • Pancreatic enzyme replacement: Creon 25,000-50,000 units with meals for exocrine pancreatic insufficiency

Pharmacological

  • PPI: Omeprazole 20mg OD for acid-related disease (NICE NG12)
  • H. pylori triple therapy: PPI + amoxicillin 1g BD + clarithromycin 500mg BD for 7 days
  • Loperamide: 2-4mg PRN for symptomatic diarrhoea (max 16mg/day)
  • Bile acid sequestrants: Colestyramine 4g OD-QDS for bile salt malabsorption
  • B12 replacement: Hydroxocobalamin 1mg IM on alternate days × 2 weeks, then every 3 months
  • Iron replacement: Ferrous sulphate 200mg BD-TDS (65mg elemental iron per tablet)

Referral Criteria

  • Red flag symptoms — urgent 2-week-wait referral
  • Positive coeliac serology — gastroenterology for biopsy
  • Suspected IBD (raised calprotectin) — gastroenterology
  • Deranged LFTs >3 months — hepatology

Prognosis

  • Coeliac disease: Excellent prognosis with strict GFD; small increased risk of enteropathy-associated T-cell lymphoma (~6-9× relative risk)
  • Peptic ulcer disease: >95% cure rate with H. pylori eradication and PPI
  • Chronic pancreatitis: 10-year survival ~70%; pancreatic cancer risk approximately 4%
  • Pernicious anaemia: Lifelong B12 replacement required; ~5% risk of gastric carcinoma
  • Untreated coeliac disease associated with osteoporosis, infertility, and neurological complications

Other Relevant Information

GI Hormones

HormoneSourceStimulusAction
GastrinG cells (antrum)Peptides, distension↑Acid secretion, trophic effect
CCKI cells (duodenum)Fat, protein↑Pancreatic enzyme secretion, gallbladder contraction
SecretinS cells (duodenum)Acid↑Pancreatic HCO3⁻ secretion, ↓gastric acid
GIPK cells (duodenum)Glucose, fat↑Insulin secretion (incretin effect)
MotilinM cells (duodenum)FastingInitiates MMC
GLP-1L cells (ileum/colon)Nutrients↑Insulin, ↓glucagon (incretin effect)

Site-Specific Absorption

NutrientPrimary Site of Absorption
IronDuodenum
FolateJejunum
Vitamin B12Terminal ileum
Bile saltsTerminal ileum
Fat-soluble vitamins (A, D, E, K)Jejunum (requires bile salts)
Water and electrolytesColon