The physiology of gastrointestinal system 3.

Transcription

1 The physiology of gastrointestinal system 3. Stomach, pancreas, bile Dr. Gabriella Kékesi

2 The mechanism and regulation of gastric juice secretion (Lo.) 64. Secretory cells in stomach Composition and role of gastric juice Mechanism of gastric juice secretion Control of gastric juice secretion Phases of gastric juice secretion Mechanisms contributing to mucosal defense Determination of gastic ph

3 Corpus Antrum Corpus (oxyntic region) Gastric juice secreting cells Antrum (regulation) Endocrine and paracrine cells

4 Vitamin B12 absorption

5 Composition of gastric juice (1-1.5 L/day) Proteolytic enzymes pepsinogens Gastric lipase Mucus, intrinsic factor, alkaline fluid HCl (150 mmol/l vs mmol/l; ph: ) Activation of proteolytic proenzymes Protein denaturation Bactericid effect (But Helicobacter pylori) HCO 3- ; buffers (mucus, dietary proteins)

6 Ion transporters of parietal cells

7 Parietal cells in rest vs secreting Intracellular rearrangement - Amplification of the apical surface area is accompanied by an increased density of H/K-ATPase molecules at this site.

8 Regulation of gastric HCl secretion

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10 The composition of gastric fluid depends on volume and flow rate. Potassium level remains relatively constant, but its concentration is greater in gastric secretions than in plasma. The rate of secretion lower in the morning and higher in the afternoon and evening.

11 Gastric acid measurements BAO=basal acid output MAO=mean acid output PAO=peak acid output 25 (Male) vs 16 (Female) mmol/h Conventional aspiration tests via nasogastric tube Measuring the volume and the acidity of the gastric juice aspirated Test meals; pentagastrin augmented, Endoscopic methods Intragastric ph measurements Breath test Mg+2HCl MgCl2+H2 CaCO3+2HCL CaCl2+H2O+CO2

12 Phases of gastric juice secretion Cephalic phase (40%) Gastric phase (50%) Intestinal phase (10 %) Stimulation and inhibition as well

13 ACh M rec parietal cell GRP (bombesinerg neurons) G cell gastrin PACAP ECL cell Pituitary adenylate cyclaseactivating polypeptide

14 D cells - Somatostatine

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17 Mechanisms contributing to mucosal defense Tight junctions between the cells Mucus surface epithelial cells Bicarbonate and other buffers neutralize acids 17

18 Destruction of mucosal barrier Type: - erosion - ulcer - perforation stress vasoconstriction β2-receptor G-cell gastrin - HCl glucocorticoids; NSAID, aspirin alcohol Helicobacter pylori inflammation G-cell gastrin - HCl

19 Urea breath test for the detection of Helicobacter pylori, serology, histology

20 Other disorders affecting gastric juice secretion Zollinger-Ellison-syndrome gastrinoma HCl overproduction, ulcer, hypertrophy

21 Chief cells - secretion Pepsinogens proteolytic proenzymes Exocytosis H+ and autocatalitic process Gastric lipase: FFA + glycerin Regulation Vagal nerve (PSY) ACh M 3 gastrin (indirectly through acid secretion) Secretin; CCK

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23 Exocrine pancreas: secretion and regulation (Lo. 65.) Exocrine pancreas Composition and significance of pancreatic juice Activation of pancreatic (pro)enzymes Neural and humoral control of pancreatic juice secretion Protection against self-digestion maintain integrity of pancreas Pancreatic juice productiom: ml/day

24 90% VITAL!! Lack of pancreatic function - Maldigestion and diabetes

25 Composition of pancreatic juice ml/day digestive (pro)enzymes Proteolytic enzymes Trypsinogenes Chimotrypsinogen Procarboxypeptidase Electrolites Acinar cells: Cl- secretion (small volume) Ductal cells: HCO3- (large volume) Lipases Pancreas lipase Prophospholipase cholesterine-esterase Regulatory molecules Pancreas -amylase Procolipase Ribo- and dezoxyribonucleases Trypsine inhibitor

26 Sequential-secretory mechanism

27 Vagal nerve - VIP, NO vasodilation in connection with secretion

28 HCO 3- and Cl - transports in pancreatic duct cells ACh, Secretin

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32 Control of pancreatic juice secretion Vagal nerve - ACh M 3 ; VIP - vasodilation CCK CCK1 Indirect vagovagal reflex Secretin Promotes the effectiveness of CCK on acinar cells Promotes HCO 3- production in ductal cells (+ACh and CCK)

33 Activation of pancreatic proenzymes in the duodenum

34 Protection against self-digestion Trypsine inhibitors Pressure gradient promotes fluid flow toward the duodenum Secreted as pancreatic proenzymes (zymogens) Cell nucleus Pancreatic enzymes in granules

35 Bile: secretion, storage, mobilization, regulation (Lo. 66.) 600 ml/day Composition: primary & secondary bile salts phospholipids (e.g. lecithin) Cholesterine, bilirubin HCO 3 rich Hepatocytes liver parenchyma cells (60 %) bile production Cholangiocytes epithelial cells of the bile duct HCO 3- & water secretion (40%) VIP, secretin Significance: Promote lipid digestion and absorption (emulsification, micell formation) Excretion of endogenous substances, e.g. bilirubin; cholesterine Excretion of exogenous substances (drugs, copper, iron)

36 Physiology of liver Permeability barrier Canalicular membrane with actin filaments

37 Hepatocellular transports Organic anion and cathion transporters Secondary active transporters ABC transporters

38 MECHANISM OF BILE SECRETION GALLBLADDER Na + Cl - Bile from the gallbladder: dark green components in higher concentration ph slightly acidic Cl - HCO 3 - DUCT CELL HCO 3 - Na + H 2O Bile from the liver: golden yellow ph is close to neutral Na + Cl - B.A. K + H 2 O HEPATOCYTE Na + B.A. B.A. B.A. HCO 3-38

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40 Enterohepatic circulation of bile salts Deconjugated bile acids reabsorption from the ileum 95% (primary and secondary) Binded with albumin in blood Na + /bile acid secondary active trp. into the hepatocytes Conjugation ABC transporters used for secretion De novo synthesis 2-5% Regulation: negative feedback

41 Neural and humoral regulation of bile secretion Bile salts via enterohepatic circulation stimulate secretion of bile salts

42 Control of bile storage and mobilization Choleretic factors: bile acid recirculation secretin Cholekinetic factors: CCK vagal nerve Simultaneous contraction of the gall bladder & relaxation of sphincter of Oddi

43 Emulsification and micelle formation by bile slats

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45 Disorders related to bile secretion Cholestasis bile cannot flow from the liver into the duodenum genetic transporter deficiencies, toxins (falloidin) Cholelithiasis gallstones - bile contains too much cholesterol and not enough bile salts Hyperbilirubinaemia (jaundice sclera, skin)

46 A. Intrinsic defects in RB cells B. Extrinsic causes external to RB cells caused due to disease of parenchymal cells of liver. caused due to obstruction of biliary passage Function test Pre-hepatic jaundice Hepatic jaundice Post-hepatic jaundice Total bilirubin Normal / increased Increased Conjugated bilirubin Normal Increased Unconjugated bilirubin Normal / increased Increased Normal Urobilinogen Normal / increased Decreased Decreased / negative Urine color Normal Dark (urobilinogen + Dark (conjugated conjugated bilirubin) bilirubin) Stool color Normal slightly pale Pale Conjugated bilirubin in urine Not present Present