Pancreatic and Biliary Physiology

Pancreatic and Biliary Physiology

Pancreatic Duct Cell Secretion

Pancreatic duct cells secrete an isosmotic, HCO₃⁻-rich fluid (up to ~140 mEq/L HCO₃⁻ at high flow rates). Mechanism: CO₂ enters duct cell → carbonic anhydrase → H⁺ + HCO₃⁻. H⁺ is pumped out basolaterally (Na⁺/H⁺ exchanger, H⁺/K⁺ ATPase). HCO₃⁻ exits apically via Cl⁻/HCO₃⁻ exchanger; CFTR recycles Cl⁻ to keep the exchanger running. This fluid neutralises acid chyme entering the duodenum (optimal pH for pancreatic enzymes ~7–8) and lubricates enzyme flow down pancreatic ducts. Secretin (from S cells) is the main stimulus.

Pancreatic Acinar Cell Secretion (Enzymes)

Acinar cells synthesise and store digestive proenzymes (zymogens): trypsinogen, chymotrypsinogen, proelastase, procarboxypeptidase A and B, prophospholipase A₂. Pancreatic amylase and lipase are secreted in active form; others as zymogens. Enterokinase (enteropeptidase) on the duodenal brush border activates trypsinogen → trypsin → trypsin then activates ALL other zymogens (cascade). Pancreatic secretory trypsin inhibitor (PSTI) is stored with trypsinogen (1:5 ratio) to prevent premature activation.

Pancreatitis: if PSTI is overwhelmed (alcohol, gallstones, mutation) → premature intra-pancreatic trypsin activation → autodigestion → acute pancreatitis (epigastric pain, raised amylase/lipase, Grey Turner's/Cullen's signs in haemorrhagic pancreatitis).

Cystic Fibrosis

CFTR is the Cl⁻ channel on duct cell apical membranes. CFTR mutations → defective Cl⁻ secretion → viscous, dehydrated secretions that obstruct pancreatic ducts → enzymes accumulate → fibrosis → exocrine pancreatic insufficiency → fat malabsorption. Also affects lungs, biliary system, and vas deferens.

Bile and Gall Bladder

Hepatocytes synthesise bile (bile salts, phospholipids, cholesterol, bilirubin, electrolytes). Bile is stored and concentrated in the gall bladder. CCK (from I cells, stimulated by fat + AA) causes: gall bladder smooth muscle contraction + sphincter of Oddi relaxation → bile enters duodenum. Gallstones: cholesterol supersaturation of bile → crystal nucleation → stones. Biliary colic: fatty meal → CCK → gall bladder contracts around stone in cystic duct → episodic severe RUQ pain. Management: laparoscopic cholecystectomy or lithotripsy. Enterohepatic circulation: ~95% of secreted bile salts reabsorbed in terminal ileum → portal vein → liver → re-secreted (cycle ~6–10×/day).