ACEM Primary
Gastrointestinal Physiology

Gastrointestinal Physiology

Enteric nervous system

  • Myenteric plexus (Auerbach’s) within muscle layer for motor control  
  • Submucous plexus (Meissner’s) between muscle and mucosa for secretions  
  • Autonomic nervous system  

Gastrointestinal hormones: 

HORMONE SYNTHESISED BY ACTION  
Gastrin G cells of antrum Pancreas gastric acid and pepsin secretion  motility  Growth of mucosa  Stimulates insulin secretion  Increased by: luminal peptides/ amino acids/ distension, vagal discharge via GRP, Ca2+ and epinephrine  Decreased by: antral acid, somatostatin, secretin/ VIP/ GIP/ glucagon/ calcitonin.  
Cholecystokinin I cells in SI Pancreas Gallbladder contraction Secretion of pancreatic juice rich in enzymes  ¯ gastric emptying  
Secretin S cells in SI bicarb secretion from pancreas and biliary tract (pancreatic juice watery/ alkaline) 
GIP K cells of SI Stimulates insulin secretion  
VIP Nerves of GIT Stimulates secretion of electrolytes and water   
Peptide YY Jejunum  Inhibits gastric acid secretion and motility  
Ghrelin Stomach Role in central control of food intake  
Motilin Mo/ enterochromaffin cells  Contraction of smooth muscle  
Somatostatin  D cells in pancreatic islets  Inhibits secretion of gastrin/ VIP/ GIP/ secretin and motilin  Inhibits pancreatic secretion, gallbladder contraction and absorption 

Mouth/ Oesophagus  

  • Mastication + saliva from parotid/ submandibular/ sublingual glands ->  containing enzymes, mucin, glycoproteins, IgA 
  •  Swallowing 
    • Reflex response triggered by afferent impulses in trigeminal, glossopharyngeal and vagus nerves 
    • Integrated into nucleus of tractus solitarius/ ambiguous 
    • Efferent via same to pharyngeal muscles  
    • Inhibition of respiration and glottic closure are part of reflex  

Stomach 

  • Fundus cells secrete mucous 
  • Body = parietal cells (HCl and IF) and chief cells (pepsinogen) 
  • Surface epithelium secretes mucus/ HCO3- as barrier against acidic environment  
    • Stimulated by PG  
  • Gastric juice (pH 1.0) contains cations/ anions/ pepsins, lipase, mucous and IF  
  • Parietal cells pump H+ into lumen via H/K ATPase, stimulated by histamine/ gastrin 
  • PUD: breakdown of mucosal barrier secondary to H Pylori, NSAID, ETOH or excess acid secretion in Zollinger Ellison Syndrome (gastrinomas) 

Exocrine pancreas 

  • Pancreatic juice is alkaline (pH ~8.0) 
  • Raise pH of duodenal contents to 6.0-7.0 
  • Contains cations/anions/ digestive enzymes/ proteins  
    • Trypsin, chymotrypsin, elastase, carboxypeptidase  
  • Secretin ->  secretion of enzymes 
  • CCK ->  secretion of­ enzymes  

Liver and Biliary System 

  • Functions of liver: 
    • Formation of bile 
    • Nutrient metabolism (glucose, AA, fats, vitamins) 
    • Inactivation of toxins, steroids, hormones 
    • Synthesis of plasma proteins  
      • Acute phase  
      • Albumin 
      • Clotting factors 
      • Steroid or hormone binding proteins  
    • Immunity via Kupffer cells  
  • Bile: salts + pigments + alkaline electrolyte solution 
    • 500mL secreted daily 
    • Some components reabsorbed via enterohepatic circulation 
    • Bile salts = sodium/ potassium salts of bile acids, from cholesterol 
      • Cholic acid, chenodeoxycholic acid, deoxycholic acid, lithocholic acid 
    • Emulsification of fats prior to digestion  
    • CCK causes contraction  

Small Intestine 

  • Duodenum ->  (ligament of Trietz) jejunum ->  (no sharp anatomic boundary) ileum 
  • High surface area for absorption 
  • Mucosa contain lymphatic nodules (Peyer’s patches) + glands (isotonic fluid) + villi  
  • Plicae circularis  

Colon 

  • Absorption of water, removal 90% fluid that enters 
  • Active transport of Na+ and water follows osmotic gradient 
  • Teniae coli (longitudinal muscle) and haustra (outpouchings)  
  • No villi on mucosa  
  • Gastro-ileal reflex = vagal, when food leaves stomach, caecum relaxes and allows passage of chyme through ICV  
  • Faeces = 30% bacteria in solid part  
  • Defecation = distension of rectum by faeces initiates reflex contraction + SNS/PNS tone to IAS + skeletal (voluntary) to EAS. First urge occurs 18mmHg, at 55mmHg reflex expulsion occurs. Straining leads to abdominal muscle contraction + lowering of pelvic floor + relaxation of puborectalis (anorectal angle reduced 15 deg or less) + relaxation of sphincters. 

Digestion and Absorption: 

  • Mucosal cells of small intestine are called enterocytes = brush border with microvilli + enzymes  
SUBSTANCE  DIGESTION 
Carbohydrate Polysaccharides = glycogen, starch, Disaccharides = lactose, sucrose, maltose  Monosaccharides = fructose, glucose, galactose (hexose molecule)  Saliva: a amylase (optimal pH 6.7) ->  breaks polysaccharides into disaccharides. Inhibited by gastric juices.  SI: salivary and pancreatic amylase + maltase/ lactase/ sucrase/ a dextrinase/ trehalase ->  break down into monosaccharides. Oligosaccharidases deficiency leads to osmotic diarrhoea. Maximal at mid SI.  Glucose/ galactose absorbed via secondary active transport by glucose/ Na+ cotransport (SGLT1/2) into cell. Transported from cell into interstitium via GLUT 2. Fructose enters via facilitated diffusion by GLUT 5.   Insulin has little effect on intestinal transport of glucose. Maximal rate 120g/ hour.   
Protein  Stomach: pepsins cleave peptide linkages (pepsinogen activated by HCl, optimal pH 1.6-3.2). Inhibited by pancreatic alkaline secretions in duodenum. Duodenal cap pH 2.0-4.0 ->  6.5 rest of duodenum.  SI: Trypsin, chymotrypsin, elastase (endopeptidases) + carboxypeptidases of pancreas (exopeptidases) + brush border peptidases + intracellular peptidases.  Thus occurs at 3 sites = intestinal lumen, brush border and enterocyte.  Mostly require co-transport with Na+.  Maximal at mid SI.   
Fat  Lingual lipase – active in stomach, digest ~30% dietary TG Gastric lipase of little importance.  Duodenum: Pancreatic lipase via colipase, bile-salt acid lipase  Insoluble fats are emulsified by detergent action of bile salts to form micelles ->  FFA absorbed via active transport 
Water, Sodium, Potassium and Chloride  Water moves in response to osmotic gradients – maximal reabs in jejunum  Na+ via active transport Na/K ATPase  K+ secreted as component of mucous and active transport H/K cotransporters in distal colon. Loss of ileal or colonic fluids ->  hypokalaemia.  Cl- via Na/K/Cl cotransporters in basolateral membrane then into lumen via carriers. Cholera ->  increases cAMP concentration thus protein kinase ->  ­ Cl- secretion.  
Vitamins Fat soluble vitamins ADEK Absorbed in upper SI   Water soluble vitamins = Na+ cotransporters Except, B12 and folate are Na+ independent.  **B12 – binds to intrinsic factor from stomach parietal cells, absorbed in terminal ileum, deficiency leads to pernicious anaemia. Required for RBC and CNS sensory pathways.   
Calcium 30-80% absorbed  Requires 1,25-dihydroxycholecalciferol, adjusted to needs  
Iron  3-6% absorbed  Iron in diet is ferric form (Fe3+) however absorbable iron is ferrous (Fe2+) via ferrous reductase at brush border. Stomach: forms complexes with ascorbic acid to permit solubility  Duodenum: absorbed into enterocyte via DMT1 transporter ->  some stored as ferritin, most transported to plasma by ferroportin 1, where it forms ferric form, bound to transferrin. 70% body iron is in Hb.  Intestinal absorption regulated by 3 factors = dietary intake, iron stores and erythropoiesis, signalling mechanisms unknown. 

Endocrine Pancreas

Insulin

  • Anabolic  
  • Secreted by B cells 
  • Polypeptide containing 2x chains AA linked by disulfide bridges  
  • Synthesised from prehormone  
  • Half life = 5 min  
  • Degraded by endosomal proteases intracellularly  
  • Actions
    • Binds to insulin R (a/b subunit ->  tyrosine kinase ->  phosphoinositol 3-kinase ->  translocation GLUT 4 to cell membrane.  
    • Uptake of glucose, AA, K+ into cells 
    • Protein and fatty acid synthesis  
    • Cell growth  
  • Regulation
    • Stimulation
      • Glucose  
      • AA 
      • GIP/ GLP-1/ gastrin/ secretin, CCK 
      • b keto-acids 
      • ACh 
      • Glucagon 
      • cAMP 
      • b R agonist  
      • Theophylline 
      • Sulfonylurea 
    • Inhibition
      • SST 
      • a R agonist 
      • NE/E 
      • b R antagonist  
      • Thiazides 
      • K+ depletion 
      • Phenytoin 
      • Insulin  

Glucagon

  • Catabolic  
  • Secreted by A cells 
  • Half life = 5-10 min 
  • Degraded mainly by liver  
  • Actions
    • Acts via Gs ->  activate adenylyl cyclase and ­ cAMP ->  protein kinase A ->  activation of phosphorylase.  
    • Glycogenolysis, gluconeogenesis, lipolysis and ketogenesis  
    • High doses positive inotropic effect on heart  
    • Stimulates secretion of GH, SST and insulin  
  • Stimulation
    •  AA 
    • CCK, gastrin 
    • Cortisol 
    • Exercise 
    • Infection 
    • Stress 
    • b R agonist  
    • Theophylline 
    • ACh 
  • Inhibition
    • Glucose 
    • SST 
    • Secretin 
    • FFA 
    • Ketones 
    • Insulin 
    • Phenytoin 
    • a R agonist 
    • GABA 

Somatostatin

  • Regulatory hormone 
  • Secreted by D cells
  • Actions
    • Inhibit secretion of insulin, glucagon and pancreatic polypeptides  

Last Updated on September 24, 2021 by Andrew Crofton

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