GI Secretion

GI Secretion

Overview

The GI tract secretes approximately 8 litres of fluid per day (saliva, gastric juice, bile, pancreatic juice, intestinal secretions). Almost all of this is reabsorbed; only ~150 mL is excreted in faeces. The ion driving secretion is Cl⁻ (secreted into the lumen; Na⁺ and water follow). Na⁺ drives absorption (Na⁺/K⁺-ATPase at the basolateral membrane powers secondary active transport of nutrients and Na⁺).

Gastric Acid Secretion

Parietal cells secrete HCl via the H⁺/K⁺-ATPase (proton pump) on their apical membrane. Mechanism: CO₂ + H₂O (catalysed by carbonic anhydrase) → H₂CO₃ → H⁺ + HCO₃⁻. H⁺ is pumped into the lumen by H⁺/K⁺-ATPase (K⁺ leaks back into lumen to keep pump running). HCO₃⁻ exits basolaterally via Cl⁻/HCO₃⁻ exchanger (Cl⁻ enters cell, HCO₃⁻ exits to blood — the "alkaline tide" after meals). Cl⁻ exits apically into the lumen through CFTR-related channels.

Regulation of gastric acid — three phases:

• Cephalic phase (thought/smell/taste of food → vagus → ACh → directly stimulates parietal cells + G cells + ECL cells)
• Gastric phase (food in stomach → amino acids + distension → G cells release gastrin → ECL release histamine → parietal cells via H₂ receptors)
• Intestinal phase (amino acids in duodenum → minor stimulation; fat + acid → inhibition via enterogastrones: secretin, CCK, GIP, somatostatin)

Somatostatin from D cells inhibits G cells (reduces gastrin) and parietal cells directly. Proton pump inhibitors (PPIs, e.g., omeprazole) block H⁺/K⁺-ATPase. H₂ receptor antagonists ("-tidines", e.g., ranitidine) block histamine's action on parietal cells.

Pancreatic Secretion

Pancreatic duct cells secrete HCO₃⁻-rich fluid (neutralises acid chyme in duodenum). Mechanism: CO₂ → HCO₃⁻ inside cells → Cl⁻/HCO₃⁻ exchanger secretes HCO₃⁻ into lumen; CFTR (Cl⁻ channel) recycles Cl⁻. HCO₃⁻ concentration increases with secretory flow rate (up to ~140 mEq/L). Secretin (from S cells, stimulated by acid chyme) stimulates HCO₃⁻ secretion. Acinar cells secrete digestive enzymes as inactive zymogens (trypsinogen, chymotrypsinogen, proelastase, procarboxypeptidase); CCK (from I cells, stimulated by fat + AA) is the main stimulus.

Intrinsic Factor

Parietal cells secrete intrinsic factor (IF) along with HCl. IF binds dietary vitamin B₁₂ in the stomach → IF-B₁₂ complex is absorbed in the terminal ileum via specific receptors. Parietal cell loss or autoimmune gastritis → pernicious anaemia (B₁₂ deficiency → megaloblastic anaemia + subacute combined degeneration of the spinal cord).