Lecture 4: gastrointestinal Function

Contraction and relaxation of smooth muscle wall and sphincters Secretion of enzymes for digestion Secretion of fluid and electrolytes Trophic (growth) effects Some regulate secretion of other GI peptides

Peptides released from endocrine cells of GI tract Secreted into portal circulation and enter systemic circulation Target cells may be in GI tract or may be located elsewhere in body Gastrin, Cholecystokinin, Secretin, and Gastric Inhibitory Peptide

Secreted by endocrine cells of GI tract Act locally within same tissue that secretes them Somatostatin and Histamine

Released by neurons of GI tract following an Action Potential ACh, norepinephrine, Vasoactive Intestinal Peptide (VIP), Gastrin-Releasing Peptide (GRP), Neuropeptide Y, and Substance P

Secreted by G cells in stomach in response to eating Stimuli include proteins, distention of stomach, and vagal stimulation Gastrin-releasing peptide (GRP) is released from vagal nerve endings onto G cells Secretion is inhibited by low pH in stomach Promotes H+ secretion by gastric parietal cells Stimulates growth of gastric mucosa

Cholecystokinin Secreted by I cells of small intestine in response to fatty acids and small peptides 5 Actions: - Contraction of gallbladder Eject bile from gallbladder into small intestine necessary for emulsification lipids • Secretion of pancreatic enzymes Digest lipids, carbohydrates, and proteins • Secretion of bicarbonate (HCO3-) from pancreas • Growth of exocrine pancreas and gallbladder -Inhibition of gastric emptying Ensures adequate time for digestive and absorptive

Secreted by S cells of duodenum in response to H+ and fatty acids Promotes secretion of pancreatic HCO3- Neutralizing H+ allows for pancreatic enzymes to digest fats Inhibits effects of gastrin on parietal cells (H+ secretion and growth)

Secreted by small intestine in response to all 3 types of nutrients Stimulates insulin secretion by pancreas Inhibits gastric H+ secretion

Secreted by endocrine cells in response to decreased luminal pH Inhibits secretion of other GI hormones Inhibits gastric H+ secretion

Secreted in H+-secreting region of stomach Stimulates H+ secretion by gastric parietal cells (along with gastrin and ACh)

ACh (released from cholinergic neurons) Norepinephrine (released from adrenergic neurons)

HCl and pepsinogen initiate protein digestion Intrinsic factor required for absorption of vitamin B12 Mucus protects gastric mucosa from HCl

Body of stomach contains oxyntic glands • Parietal cells → HCl and Intrinsic Factor • Chief cells → Pepsinogen Antrum of stomach contains pyloric glands • G cells → Gastrin into the circulation • Mucous neck cells → Mucus, HCO3-, and Pepsinogen

• Body, HCl and intrinsitic factor • Body, pepsinogen • Antrum, Gastrin • Antrum, Mucous, pepsingon and HCO3-

Released from vagus nerve Binds to receptors on parietal cells Produces H+ secretion by parietal cells Atropine blocks muscarinic receptors on parietal cells

Released from mastlike cells in gastric mucosa Binds to H2 receptors on parietal cells Produces H+ secretion by parietal cells Cimetidine blocks H2 receptors

Gastrin Released into circulation by G cells of stomach antrum Binds to receptors on parietal cells Stimulates H+ secretion

sight, smell, taste or thought of food. These stimuli, processed by the brain, activate enteric neurons via parasympathetic preganglionic neurons traveling in the vagus nerve. Lecture slide

Lecture slide for diagram Food in the stomach, which stimulates acid secretion. Peptides and amino acids in food stimulate G cells to release gastrin (blue). Food also acts as a buffer, raising the pH and thus removing the stimulus for somatostatin secretion (light blue-green).

Lecture slides Chyme enters the duodenum, intestinal phase stimuli activate negative feedback mechanisms to reduce acid secretion and prevent the chyme from becoming too acidic. Enterogastrones are hormones that inhibit stomach processes (in this case, acid secretion). CCK, secretin, GLP-1, and GIP

Maldigestion: impaired breakdown of nutrients (carbohydrates, protein, fat) to absorbable splitproducts (mono-, di-, or oligosaccharides; aminoacids; oligopeptides; fatty acids; monoglycerides) Malabsorption: defective mucosal uptake and transport of adequately digested nutrients including vitamins and trace elements.

Malabsorption causes diarrhea, weight loss, and bulky, extremely foul-smelling stools. The diagnosis is based on typical symptoms along with testing of stool samples for fat and sometimes examination of a tissue specimen removed from the lining of the small intestine.

• H. pylori secretes urease (generates ammonia), protease (breaks down glycoprotein in the gastric mucus) or phospholipases. • Bacterial lipopolysaccharide attracts inflammmatory cells to the mucosa. Neutrophils release myeloperoxide. • A bacterial platelet-activating factor promotes thrombotic occlusion of surface capillaries. • Mucosal damage allows leakage of tissue nutrients in the surface microenvironment , sustaining the bacillus. • Damage of the protective mucosal layer. The epithelial cells are exposed to the damaging effect of acid-peptic digestion. • Inflammation of the gastric mucosa. • Chronically inflamed mucosa more susceptible to acid- peptic injury and prone to peptic ulceration. Ulcers occur at sites of chronic inflammation .

Peptic ulcer caused due to high gastrin level (increased parietal mass) and excess acid production. Peptic ulcers caused due to impaired mucosal defense. The gastric acid and pepsin levels are normal and no H.pylori are present: • Chronic use of aspirin causes suppression of mucosal prostaglandin and direct irritative topical effect. • Repeated use of corticosteroid in high dose. • Cigarette smoking impair healing and favour recurrences. • Alcoholic cirrhosis.