Digestion In The Intestine Notes

Lecture 9

Digestion in the intestine

• Secretions in the intestine

  • Duodenum

    • 1 litre per day, pH 7.6

    • Composition: mucus, water enterokinase, water etc.

  • Liver

    • 0.5 litres per day, pH 7.4

    • Composition: bile acids, cholesterol, phospholipids etc.

  • Pancreas

    • 1~2 litres per day, pH 7.8-8.4 (very alkaline, secretes lots of HCO3-)

    • Composition: salts and enzymes (enteropeptidase)

• Secretions of the pancreas

  • Endocrine- insulin and glucagon

  • Exocrine- salts and water, enzymes

  • Functions of pancreatic juices

    • Salts and water (HCO3-, NaCl, Water)= make right environment for enzymes

    • Enzymes (proteases, lipases, a-amylases)= digest major classes of foodstuffs

  • Structure of the pancreas

    • Like a bunch of grapes

    • Main collecting duct= large stalk; Interlobular duct= small stalk; Acinar= grape

    • Acinar cells fall of zymogen granules for secretory purposes

  • Movement of newly synthesised proteins through secretory pathway (in Acinar cell)

    • Rough ER-->Golgi-->Condensing vacuoles-->Zymogen granules

    • 5-15g of protein each & every day

  • Secretion of enzymes

    • Key stimulators: CCK & Secretin (lesser role but does give rise to cAMP)

    • Cause the release of vesicles by exocytosis

    • CCK acts on receptor on basolateral membrane giving rise to IP3 and DAG in cell that leads to exocytosis of materials into lumen (enteric NS acting on M3 receptors has same effect)

    • Secretin receptors activated to give rise to cAMP, Somatostatin inhibits this

    • Things released into lumen:

      • Proteases (Trypsin, chymotrypsin, carboxypeptidases)= as Zymogens

      • Lipases & a-amylases= as enzymes

  • Composition of pancreatic juice made by both Acinar & duct lining epithelial cells

    • Acinar cells

      • “Leaky” epithelium

      • Active/inactive enzymes & Cl1 secreted transcellularly

      • Na+ and H20 secreted paracellularly

    • Duct-lining epithelial cells

      • “Leaky” epithelia (unlike in salivary glands)

      • HCO3- secreted and Cl- absorbed transcellularly

      • Na+ and H20 secreted paracellularly

  • Flow dependence of ion composition of pancreatic juices

    • Na+ level (high) and K+ level (low) remain constant as flow increases

    • HCO3- increases and Cl- decreases as flow increases

  • Isotonic NaCL secretion by pancreatic Acinar cells

    1. Na/K pump creates inwardly directed Na+ gradient (basolateral)

    2. Na+/K+/2Cl- co-transporter (NKCC) accumulates Cl- intracellularly, driven by Na+ gradient

    3. Ca2+ activated K+ channels (i) recycle K+ ions (basolateral) & (ii) maintain driving force for Cl- exit (apical)

    4. Ca2+ activated Cl- channels (apical) provide pathway for Cl- to exit

    5. Movement of Cl- into lumen draws Na+ & H2O paracellularly= NaCl secretion

    6. Cholinergic neurotransmitter acetylcholine (M3 receptors) and CCK potently stimulate NaCl secretion by Acinar cells

  • Secretion of salts and water by duct-lining epithelial cells

    1. Na-K pump creates inwardly directed Na+ gradient (basolateral)

    2. HCO3- accumulate intracellularly, 2 mechanisms: (i) direct entry across basolateral by Na+/HCO3- co-transporter & (ii) intracellular generation from CO2 & H2O via carbonic anhydrase

    3. Na+/H+ exchanger removes H+ (from HCO3- generation)

    4. Cl-/HCO3- exchanger secretes HCO3- into lumen of duct in exchange for Cl-

    5. cAMP-stimulated Cl- channels (CFTR) secrete Cl- required by Cl-/HCO3- exchanger

    6. Basolateral K+ channels maintain driving force for Cl- exit across apical

    7. HCO3- secretion into duct lumen draws Na+ and H2O paracellularly to complete NaHCO3- secretion

    8. Secretin= most powerful stimulus for HCO3- secretion. Activates cAMP cascade leading to phosphorylation of CFTR

  • Activation of pancreatic enzymes

    • Zymogens (trypsinogen, chymotrypsinogen, precarboxypeptidases)=INACTIVE

    • Activated by brush border enzyme=...

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