The physiology of gastrointestinal system 3.

Transcription

1 The physiology of gastrointestinal system 3. Stomach, pancreas, bile LO.: 64,65,66 Prof. Gyula Sáry While studying functions of the gastrointestinal system, Pavlov described the conditional response, a form of learning. Pavlov also discovered the phases of gastrointestinal secretions. He was awarded with the Nobel Prize in physiology or medicine for research on the nature of digestion in Ivan Petrovich Pavlov

2 3 sham feeding Bykov, 1960 small stomach Evans,

3 Classical (Pavlovian) conditioning detective mirror bell collecting saliva food 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

4 Corpus Antrum Corpus (oxyntic region) Gastric juice secreting cells Antrum(regulation) Endocrine and paracrine cells Vitamin B12 4

5 Composition of gastric juice(1-1.5 L/day) Proteolytic enzymes pepsinogens Gastriclipase 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, dietaryproteins) Ion transporters of parietal cells 5

6 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. Regulation of gastric HCl secretion 6

7 H + secretionmmol/10 min Feeding Hours 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. 7

8 Gastric acid measurements BAO=basal acid output MAO=mean acid output PAO=peak acid output 25 (Male) vs16 (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 Ca 13 CO 3 Phases of gastric juice secretion Cephalic phase(40%) Gastric phase(50%) Intestinal phase(10 %) Stimulation and inhibition as well 8

9 ACh M rec parietalcell GRP (bombesinerg neurons) G cell gastrin PACAP ECL cell Pituitary adenylate cyclaseactivating polypeptide D cells- Somatostatine 9

10 Secretion of Gastrin underph 4 is progressively inhibited. (-feed back) 19 10

11 21 Mechanisms contributing to mucosal defense Tight junctions between the cells Mucus surface epithelial cells Bicarbonate and other buffers neutralize acids 22 11

12 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 The Zollinger-Ellison syndrome uncontrolled gastrin secretion (tumor)..hcl large volumen of pancreatic juice fluid loss into the gut ph in the duodenum pancreatic enzymes fail to work maldigestion, malabsorbtion osmotic activity diarrhoea lipids (too) are not digested(fat soluble vitamins!!!) bacterial breakdown of carbohydrates in the colon.gases due to low ph, B 12 and intrinsic factor do not bind anemia multiple ulcers hypertrophy of the gastric mucosa cancer? 24 12

13 Urea breath test for the detection of Helicobacter pylori, serology, histology Other disorders affecting gastric juice secretion Zollinger-Ellison-syndrome gastrinoma HCl overproduction, ulcer, hypertrophy 13

14 Chief cells- secretion Pepsinogens proteolytic proenzymes Exocytosis H+ and autocatalitic process Gastric lipase: FFA + glycerin Regulation Vagalnerve(PSY) ACh M 3 gastrin(indirectly through acid secretion) Secretin; CCK 14

15 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 90% VITAL!! Lack of pancreatic function - Maldigestion and diabetes 15

16 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 α-amylase Procolipase Ribo- and dezoxyribonucleases Trypsine inhibitor Sequential-secretory mechanism 16

17 Vagal nerve- VIP, NO vasodilation in connection with secretion HCO 3- and Cl - transportsin pancreaticductcells ACh, Secretin 17

18 18

19 Control of pancreatic juice secretion Vagalnerve-ACh M 3 ; VIP -vasodilation CCK CCK1 Indirect vagovagal reflex Secretin Promotes the effectiveness of CCK on acinar cells PromotesHCO 3- productionin ductalcells (+AChand CCK) 19

20 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 Activation of pancreatic proenzymes in the duodenum 20

21 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 %) bileproduction Cholangiocytes epithelial cells of thebileduct HCO 3- & water secretion(40%) VIP, secretin Significance: Promote lipid digestion and absorption (emulsification, micell formation) Excretionof endogenoussubstances, e.g. bilirubin; cholesterine Excretion of exogenous substances (drugs, copper, iron) Physiology of liver Permeability barrier Canalicular membrane with actin filaments 21

22 Hepatocellular transports Organicanion and cathion transporters Secondary active transporters ABC transporters 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. H 2 O K + HEPATOCYTE Na + B.A. B.A. B.A. HCO

23 Enterohepatic circulation of bile salts Deconjugated bile acids reabsorption from the ileum 95% (primary and secondary) Binded with albumin in blood Na + /bileacidsecondaryactivetrp. intothe hepatocytes Conjugation ABC transporters used for secretion De novosynthesis 2-5% Regulation: negative feedback 23

24 Neural and humoral regulation of bile secretion Bile salts via enterohepatic circulation stimulate secretion of bile salts 24