Week 7 Lecture 1

Week 7 Lecture 1

1. Cells in mucosa

   • Goblet cells produce mucous constantly. Contains muco-polysaccharides which lubricate the contents and protect gut surface from digestion
   • Entero-endocrine cells secrete hormones and paracrime mediators which act on nearby cells
   • Dendritic cells sample for bacteria become activated or conditioned and migrate to mesenteric lymph nodes

2. Anatomy of GI tract

   • Gut forms a continuous tube from mouth to anus
   • Mouth, pharynx, oesophagus, stomach, small intestine, large intestine and anus

3. Gastric Function

   • Motility
     • Upper stomach act as a reservois
     • Lower stomach acts as a pump and grinding mechanism
   • Secretion
     • Acid and intrinsic factor from parietal cells in upper stomach
     • Pepsinogen from Chief cells - upper stomach
     • Mucous from goblet cells throughout the gut
     • HCO3 rich solution from all enterocytes
   • Four hormones and mediators control acid production
   • Four hormones and mediators control acid production
     • Gastrin from G cells - excites acid production
     • Histamine from ECL cells - excited acid production
     • Acetylcholine from enteric nerve cells - excited acid production
     • Somatostatin from D cells - inhibits both acid and gastrin release

4. Gastric Acid

   • Hydrochloric acid
   • pH is from 2-4
   • Acid has several functions
     • Kills many bacteria, fungi, protozoa
     • Activates pepsinogen to form pepsin
     • Helps break up food particles, in conjunction with grinding movements of lower stomach motility
   • Parietal cells in upper stomach produce acid via K+/H+/ATPase ezyme which uses energy from ATP to produce H+ ions
   • Gastrin excites ECL cells to release histamine
   • D cells throughout stomach are excited by low pH in lumen and inhibit ECL cells and G cells

5. Pancreatic function: produces insulin, glucagon

   • exocrine secretory organ stimulated by CCK from duodenum and parasympathetic nerves
   • Proteases
   • Lipase: breaks down fat to monoglycerides+ Fatty acids
   • Amylase: breaks down starches to trisacchardies
   • Secretes large quantities of HCO3 - rich solution that neutralises gastric acid stimulated by secretin

6. Protein digestion

   • Starts with pepsin activated by acid pH of stomach - breaks down proteins into peptides
   • Duodenum - acid of pH is neutralised and pepsin is largely inactived
   • Peptides in duodenum trigger CCK release, activates pancreatic enzyme secretion
   • Digestion of proteins accelerates with trypsin, chymotrypsin, elastase and carboxpeptidase and slightly alkaline of pH of duodenum
   • Enzymes produce amino acids and dipeptides
   • Products are absorbed into enterocytes via Na+ dependent co-transporters
   • Facilitated diffusion transports amino acids into mucosal capillaries and into bloodstream

7. Carbohydrate digestion

   • Starts with salivary amylase which starts the breakdown of starch into monosacchardies, disaccharides and trisacchardies
   • Salivary amylase is inhibited in acid environment in stomach
   • Pancreatic amylase then works efficienctly in slightly alkaline environment of duodenum and jejunum to break down remaining starch
   • Disacchardies and those from diet, are broken down by disaccharidase enzymes located in border of small intestine
   • Uptake is via sodium-dependent co-transporters into enterocyte followed by faciliated diffusion into blood stream

8. Absorption of sugars

   • Enterocytes have low [Na+] due to Na+/K+ ATPase which pumps Na+ out of epithelial cells, in exchange for K+ into cells
   • Sugars are absorbed from lumen, against concentration gradient
   • Pass via faciliated diffusion transporters into sub-epithelial space and thereby into blood vessels

9. Digestion of fats

   • Water-insoluble
   • Bile breaks up fat globules into emulsion with larger surface area for lipase to work on
   • Lecithin it forms 'tiny micells' which transport fat digestion products to surface epithelium
   • Micells, monoglycerides, fatty acids and cholestrol are taken up by enterocytes and converted back into triglycerides
   • Triglycerides are mixed with lipopoteins in enterocytes to form chylomicrons - ejected from the cells and diffuse into lacteals and then lymph vessels - chyle

10. Bile

    • Enters duodenum via common bile duct but between meals, it is diverted into gall bladder where it is concentrated
    • Bile is released from gall bladder by hormone CCK
    • Primary bile acids are produced from cholestrol as cholic acid
    • In intestines, these are converted to secondary bile acids; deoxycholic acid and lithocholic acid by bacteria
    • primary and secondary bile acids are taken up into hepatocytes and conjugated to form bile salts
    • Conjugation makes bile acids more water soluble in small intestine - making them better able to disperse fat

11. Portal Circulation

    • Oxygenated blood passes though arteries, arterioles and capillaries becomes de-oxygenated and returns via vencules and veins to vena cava and heart
    • Gut, partially deoxygenated blood, loaded with nutrients passes into hepatic portal vein
    • Hepatic portal vein blood then enters the liver is mixed with fully oxygenated hepatic arterty blood and flows through liver sinusoids
    • Liver, nutrients are modified and absorbed, bacteria removed and bile salts reabsorbed
    • Filtered blood then enters the hepatic vein and drain into vena cava

12. Hepatic function

    • Liver cells are remarkably homogenous - take part in metabolic functions of this organ
    • Hepatocytes - make plasma proteins, transport protiens, modify and store fats and carbohydrates, remove and modify toxins, synthesse glucose, remove bacteria etc

13. Small intestine

    • End of small intestine, most digestion is complete and great majority of water has been reabsorbed along with salts and vitamins
    • Proximal colon, contents are slowly mixed and moved, water and ions are reabsorbed
    • Dehydration, increased circulating ngiotension and aldosterone promote reabsorption of Na+ ad water and reduce secretion of Cl- ions

14. Epithelial secretion in gut

    • Chloride is taken up into enterocytes from extracellular fluid via Na/K+/Cl- cotransporter/channel
    • Secreted by cyistic fibtrosis transmembrane-conductance regulator
    • H2O is passively drawn into lumen by osmosis
    • Cystic fibrosis is asociatted with mutations of CFTR