Gastrointestinal secretions

Daily volumes and fistula losses

Saliva 1–1.5 L, gastric juice 2 L, pancreatic juice 1.5 L, bile 0.5–1 L, intestinal secretion 1–2 L. With about 2 L of oral intake, roughly 9 L enters the small intestine; the small bowel absorbs most of it, the colon about 1.5 L, and only 100–200 mL leaves in faeces.

• Everything secreted below the pylorus is alkaline, so a high-output ileal fistula losing 2 L a day causes hyperchloraemic (normal anion gap) acidosis.

Saliva

• Parotid: serous; parasympathetic from the glossopharyngeal nerve (inferior salivatory nucleus, lesser petrosal nerve, otic ganglion, auriculotemporal nerve).
• Submandibular: mixed; facial nerve (superior salivatory nucleus, chorda tympani, submandibular ganglion); makes most resting saliva. Sublingual: mainly mucous, same supply. The lacrimal gland is supplied through the greater petrosal nerve and pterygopalatine ganglion.
• Two-stage formation: acinar cells secrete an isotonic, plasma-like fluid; the ducts reabsorb Na⁺ and Cl⁻ and secrete K⁺ and HCO₃⁻, but are almost impermeable to water. Final saliva is therefore hypotonic with a higher K⁺ than plasma.
• Flow dependence: at high flow there is less contact time in the ducts, so Na⁺ and Cl⁻ rise towards plasma values and osmolality rises, though saliva stays hypotonic. A parotid fistula leaks more when the patient eats, and the resting fluid is hypotonic with high K⁺. Saliva is the only hypotonic GI secretion.
• Contents: α-amylase (ptyalin), lingual lipase, lysozyme, lactoferrin (binds iron so bacteria cannot use it), IgA, mucin, kallikrein.
• Control is almost entirely neural. Both divisions increase secretion: parasympathetic (acetylcholine on M3 receptors) gives copious watery saliva and dominates; sympathetic gives scanty thick saliva. Drugs with antimuscarinic action (amitriptyline, atropine, antihistamines) cause a dry mouth. Aldosterone increases ductal Na⁺ reabsorption.

Gastric secretion

• Making acid: carbonic anhydrase forms H⁺ and HCO₃⁻ inside the parietal cell; the H⁺/K⁺-ATPase (proton pump) on the luminal membrane exchanges H⁺ for K⁺; Cl⁻ follows through channels. HCO₃⁻ leaves into the blood in exchange for Cl⁻, producing the alkaline tide after a meal.
• Three stimulants potentiate each other: acetylcholine (vagus) on M3; gastrin on CCK-B receptors, mainly by releasing histamine from ECL cells; histamine on H2 receptors (cAMP).
• Inhibitors: somatostatin; antral pH below about 3 (switches off gastrin); secretin, GIP; prostaglandins (PGE2), which also increase mucus and bicarbonate.
• Drugs: proton pump inhibitors block the final common step and are most effective; H2 blockers; misoprostol (PGE1 analogue).
• Uses of HCl: converts pepsinogen to pepsin (optimum pH 2), kills ingested microbes, frees vitamin B12 from food protein, and reduces dietary Fe³⁺ to absorbable Fe²⁺.

• Intrinsic factor is the only gastric secretion essential for life. Autoimmune gastritis destroys parietal cells of the body and fundus, causing achlorhydria, high gastrin and pernicious anaemia.
• Gastrinoma (Zollinger–Ellison): persistent gastrin drives acid hypersecretion, multiple or distal ulcers and diarrhoea (acid inactivates lipase).

Pancreatic exocrine secretion

• Ductal cells: bicarbonate-rich fluid via CFTR chloride channels and apical Cl⁻/HCO₃⁻ exchange, stimulated mainly by secretin (acid in the duodenum), potentiated by CCK and the vagus. Defective CFTR in cystic fibrosis gives thick secretions and pancreatic insufficiency.
• Acinar cells: enzymes, stimulated by CCK (fat and amino acids in the duodenum) and the vagus (acetylcholine).
• Flow dependence: pancreatic juice is isotonic at every flow rate. As flow rises, HCO₃⁻ rises and Cl⁻ falls reciprocally (their sum stays constant); Na⁺ and K⁺ stay near plasma values.
• Enzymes: α-amylase; lipase with colipase; phospholipase A₂; cholesterol esterase; nucleases; proteases secreted as inactive precursors (trypsinogen, chymotrypsinogen, procarboxypeptidase, proelastase).
• Enterokinase (enteropeptidase) on the duodenal brush border converts trypsinogen to trypsin, which activates the rest. Pancreatic trypsin inhibitor (SPINK1) prevents autodigestion; premature activation causes acute pancreatitis.
• Brush-border enzymes are not pancreatic: aminopeptidase, dipeptidases, lactase, sucrase-isomaltase, maltase and enterokinase belong to the enterocyte.
• Pancreatic insufficiency (chronic pancreatitis from alcohol, cystic fibrosis) mainly causes fat malabsorption: pale, bulky, greasy stools, no chylomicron formation and fat-soluble vitamin deficiency, because lipase has no adequate substitute. Low faecal elastase is the best simple stool test; a very watery sample can give a falsely low value.
• Endocrine link: glucose enters β cells by GLUT2, is metabolised to ATP, and the rise in ATP closes K-ATP channels; the cell depolarises, voltage-gated Ca²⁺ channels open and insulin is released. Sulfonylureas close the same channels.

Bile

• Hepatocytes secrete bile acids, phospholipid, cholesterol and conjugated bilirubin; ductular cells add bicarbonate-rich fluid under secretin.
• The gallbladder concentrates bile 5–20 fold by active Na⁺ absorption with water following. CCK contracts the gallbladder and relaxes the sphincter of Oddi, which is why fatty meals provoke biliary colic.
• Bile acids (cholic, chenodeoxycholic) are conjugated with glycine or taurine to form bile salts, which form micelles carrying fat and fat-soluble vitamins to the brush border.
• About 95% of bile salts are reabsorbed in the terminal ileum by the apical sodium-dependent bile acid transporter and return to the liver (enterohepatic circulation, 6–10 cycles a day). Ileal resection or Crohn disease causes bile salt diarrhoea and fat malabsorption; colestyramine binds bile salts.
• Small bowel bacterial overgrowth (jejunal diverticula, blind loops, loss of the migrating motor complex): bacteria deconjugate bile acids, so micelles fail and fat is malabsorbed; they also consume B12 (low B12) and make folate (high folate).
• Gallstones form when bile is supersaturated with cholesterol relative to bile salts and lecithin.

Remember Secretin brings bicarbonate (water); CCK brings enzymes and empties the gallbladder.

Exam trap Intrinsic factor comes from parietal cells, not chief cells.

How FCPS asks about this

• Cell secreting intrinsic factor: parietal cell of the body and fundus.
• Saliva composition at rest compared with plasma: hypotonic, high K⁺ and HCO₃⁻, low Na⁺ and Cl⁻; less hypotonic at high flow.
• Dry mouth with tricyclics: blockade of muscarinic M3 receptors on acinar cells.
• Pancreatic fluid as flow rises: bicarbonate up, chloride down, always isotonic.
• Hormone for pancreatic enzymes and gallbladder contraction: CCK; for bicarbonate: secretin.
• Enzyme not secreted by the pancreas: aminopeptidase (brush border); enterokinase is also brush border.
• Ileal fistula output: normal anion gap metabolic acidosis.

Exam trap Pancreatic juice stays isotonic at every flow rate; only saliva changes tonicity with flow.