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PY4.1-12 | Gastro-intestinal Physiology — Part 2

Gastric Juice — Composition, Secretion, Functions, Regulation (PY4.4)

The stomach secretes gastric juice at a rate of 2–3 litres/day.

Figure: Gastric Juice — Composition, Secretion, Functions, Regulation (PY4.4)

Composition of gastric juice:
• Hydrochloric acid (HCl) — from parietal cells (also called oxyntic cells), pH 1–2
• Pepsinogen — from chief cells (zymogenic cells) → activated to pepsin by HCl
• Intrinsic factor — from parietal cells → essential for B12 absorption (deficiency → pernicious anaemia)
• Mucus — from neck mucous cells → protects mucosa
• Gastric lipase — minor fat digestion

Mechanism of HCl secretion (parietal cell):
• H⁺ is secreted by the H⁺/K⁺-ATPase proton pump on the luminal membrane.
• Cl⁻ follows via Cl⁻ channels.
• For every H⁺ secreted into the lumen, one HCO₃⁻ is released into the blood — called the alkaline tide.
• Three receptors on the parietal cell stimulate H⁺ secretion: histamine (H₂ receptor), gastrin (CCK-B receptor), acetylcholine (M₃ receptor). This is why triple therapy blocking all three is most effective.

Functions of gastric juice:
1. Protein digestion (pepsin at pH 2)
2. Sterilisation — kills most ingested bacteria
3. Facilitates B12 absorption (intrinsic factor)
4. Converts Fe³⁺ → Fe²⁺ (improves iron absorption)

Regulation — Three Phases:
1. Cephalic phase (30% of secretion): Sight, smell, taste, thought of food → vagal stimulation → gastrin + ACh → acid. "Mental" stimulation.
2. Gastric phase (60% of secretion): Food in stomach → distension (long reflex via vagus, short reflex via ENS) + protein products → gastrin release → acid. Dominated by gastrin.
3. Intestinal phase (10%): Acidic chyme enters duodenum → secretin release → inhibits gastric acid (the "enterogastric reflex").

Gastric function tests:
• Pentagastrin stimulation test — gold standard for measuring maximal acid output (MAO)
• Augmented histamine test (Kay test) — older, less specific
• Serum gastrin level — elevated in Zollinger-Ellison syndrome (gastrinoma)
• Tubeless gastric analysis — Diagnex blue dye test (no nasogastric tube needed)

Pancreatic Juice — Composition, Secretion, Functions, Regulation (PY4.5)

The exocrine pancreas (as distinct from the endocrine islets of Langerhans) produces 1.5–2.5 litres/day of pancreatic juice — the most important digestive juice in the body.

Figure: Pancreatic Juice — Composition, Secretion, Functions, Regulation (PY4.5)

Composition:
• Water and electrolytes — rich in bicarbonate (HCO₃⁻) — up to 120 mmol/L (vs 24 mmol/L in plasma). This neutralises acidic chyme entering the duodenum.
• Proteolytic enzymes (secreted as inactive zymogens): trypsinogen → trypsin, chymotrypsinogen → chymotrypsin, procarboxypeptidase → carboxypeptidase
• Pancreatic amylase — digests starch (already active when secreted)
• Pancreatic lipase — most important fat-digesting enzyme, requires co-lipase and bile salts
• Phospholipase A₂, cholesterol esterase — digest phospholipids and cholesterol esters
• Pancreatic DNase/RNase

Activation cascade: Trypsinogen is activated to trypsin by enterokinase (enteropeptidase) secreted by duodenal mucosa → trypsin then activates all other zymogens. This is the key safety mechanism — enzymes are inert until they reach the duodenum.

Why pancreatic juice is alkaline: Centroacinar and ductal cells secrete HCO₃⁻ in exchange for Cl⁻ (via CFTR channel). Mutations in CFTR gene → cystic fibrosis → thick, inspissated pancreatic secretions → pancreatic insufficiency.

Regulation:
• Secretin → ↑ HCO₃⁻ and water (volume response) — triggered by low duodenal pH
• CCK → ↑ enzyme secretion — triggered by fat and protein in duodenum
• Vagal ACh → ↑ enzyme secretion (amplifies CCK effect)

Pancreatic exocrine function tests:
• Secretin-pancreozymin test — gold standard: measure HCO₃⁻ and enzyme output after IV secretin + CCK
• Faecal elastase-1 — non-invasive, highly specific
• Faecal fat test (Van de Kamer) — detects steatorrhoea (>7g fat/day in faeces)
• Serum amylase/lipase — elevated in acute pancreatitis (lipase more specific, remains elevated longer)

Intestinal Juices (Succus Entericus) — PY4.6

The small intestinal mucosa secretes succus entericus ("juice of the intestine") — about 2–3 litres/day.

Figure: Intestinal Juices (Succus Entericus) — PY4.6

Composition:
• Primarily water and electrolytes (isotonic with plasma)
• Brush border enzymes embedded on microvilli (not truly secreted into lumen):
- Enterokinase (enteropeptidase) — activates trypsinogen
- Disaccharidases: lactase (glucose + galactose), sucrase (glucose + fructose), maltase (glucose + glucose)
- Peptidases: aminopeptidase, dipeptidase — complete protein digestion
• Mucus — protects mucosa from acidic chyme
• IgA — secretory antibody

Large intestine secretions: The colon secretes only mucus (from goblet cells) — no enzymes. The colon's job is water and electrolyte absorption, not digestion. It also houses the colonic microbiome which produces Vitamin K and short-chain fatty acids.

Brunner's glands (submucosal glands in duodenum): Secrete highly alkaline mucus to protect the duodenal mucosa from gastric acid. They are stimulated by vagal nerves and inhibited by sympathetic stimulation. Stress → sympathetic dominance → Brunner's glands suppressed → duodenal ulcers are more common under stress.