Neural-Humoral-Paracrine Control of the GI TractSecretory ProductsProductSource Action RegulationNotes

Intrinsic Factor

Parietal cellsNecessary for B12 absorption in terminal ileumAutoimmune destruction of parietal cells( chronic gastritis and pernicious anemia

Gastric Acid

Parietal CellsProvide acidic environment by histamine, ACh, gastrin

by somatostatin,GIP, PG, secretinGastrinoma: gastrin-secreting tumor that causes continuous high levels of acid secretion and ulcers.

Pepsin

Chief CellsDigestion of proteins by vagal stimulation, local acidInactive pepsinogen( pepsin by H+

HCO3-

Mucosal cells in stomach and duodenumNeutralize acid in stomach; prevents autodigestion by secretinHCO3- is trapped in mucus that covers the gastric epithelium

Hormone/ Paracrine/ NeurotransmitterSite of ProductionStimulus for ProductionTarget Organ and Action

Acetylcholine Parasympathe- tic nerves

Enteric nerves Neural reflexes Salivary glands: stimulate secretion

Esophagus: stimulates motility

Stomach: stimulates motility and secretions of acid, pepsinogen

Small intestine: stimulate motility and secretion

Gallbladder: stimulates contraction

Pancreas: stimulates enzyme secretion

Bombesin(Gastrin-releasing peptide, GRP) Vagal & enteric neurons in stomach mucosa Neural reflexes

Dietary protein, amino acids Stomach: stimulates release of gastrin

Pancreas: stimulates secretion

Cholecystokinin (CCK) I cells in duodenal, jejunal submucosa Fatty chyme

Partially digested proteins, amino acids Stomach: decreases motility and delays emptying; inhibits acid secretion

Small intestine: stimulates motility

Gallbladder: stimulates contraction to expel stored bile; relaxes sphincter of Oddi (Cholelythiasis = CCK) Pancreas: stimulates enzyme secretion; potentiate action of secretinMediates satiety

Gastric Inhibitory Polypeptide (GIP) K cells in duodenal, jejunal mucosa Fatty chyme

Glucose containing chyme Stomach: inhibits acid (H+) secretion

Small intestine: inhibit motility

Pancreas: stimulates insulin release

Gastrin G-cells in gastric antrum of stomach (enteroendocrine cells) in submucosa Protein, amino acids, Ca++, alcohol in gastric chyme

Elevated gastric pH

Gastric distension

Neural reflexes

Stomach: stimulates motility (to enhance gastric emptying) and secretions of acid, pepsinogen

Small intestine: stimulate motility

Ileocecal valve: relaxation

LES: contraction

Large intestine: stimulate mass movement

Gallbladder: mild contraction

Pancreas: mild stimulation of enzyme,HCO3 secretion

Trophic hormone in Zollinger-Ellison syndrome

Ghrelin Stomach

Small intestine Hunger Stimulates eating via NPY in lateral hypothalamus hunger center

Release of growth hormone

Histamine Stomach mucosa (entero- chromaffin cells

Mast cells) Gastrin

Food in stomach

Acetylcholine (reflexes)

Irritation Stomach: stimulate acid secretion

Small intestine: stimulate secretions

Motilin Endocrine cells in duodenal, jejunal mucosa Unknown Regulates interdigestive migrating myoelectric complex

in fasting state Strong LES, gastric, small intestinal contraction during interdigestive phase

Neuropeptide Y (NPY) CNS, PNS

Pancreatic islet cells Oral nutrient ingestion

Decreased leptin in CNS

Activation of SNS Inhibits glucose-stimulated insulin secretion

Stimulates lateral hypothalamus hunger center

Nitric Oxide Enteric neurons Neural reflexes Relaxes intestinal smooth muscle, including LE sphinctersAchalsia: loss of NO secretion may lead to LE tone

Norepinephrine, Epinephrine Sympathetic nerves

Adrenal medulla Neural reflexes Relaxes GI smooth muscle, except constricts sphincters

Inhibits secretions

Decreases blood flow

Opioids/ Enkephalins Enteric neurons Neural reflexes Circular smooth muscle contraction

Intestine: decreases secretion

Inhibits release of VIP, acetylcholine, substance P

Secretin S cells in duodenal, jejunal mucosa Acidic chyme

Partially digested proteins, fats, hypertonic or hypotonic fluids

Irritants in chyme (bile salts) Stomach: inhibit motility (delay emptying) and secretions

Small intestine: inhibit motility

Liver: bile output, especially ductal secretion of HCO3 to neutralize gastric acid in duodenum Gallbladder: potentiate CCKs action to contract

Pancreas: stimulate secretion of HCO3; potentiate CCKs action on enzyme secretion

Somatostatin Enterochromaf-fin D cells in gastric and duodenal mucosa; cells of pancreatic islets Food in stomach

Acidic pH in stomach

Neural reflexes Inhibits release of neuroendocrine factors

Stomach: inhibits secretion

Intestine: fluid absorption; inhibit secretion

Pancreas: inhibits secretion

Liver: decrease bile flowUsed to treat VIPomas and carcinoid tumors

Substance P Enteric neurons Neural reflexes

by Distension, vagal stimulation Food in gut Relaxes intestinal smooth muscle, including sphincters

Intestine: stimulates secretion

Vasoactive Intestinal Peptide (VIP) Duodenal mucosa

Enteric neurons

CNS & PNS Chyme containing partially digested foods Relaxes GI smooth muscle, including sphincters

Intestine: stimulates secretion; smooth muscle relaxation

Pancreas: secretion; ?regulate release of insulin & glucagonVIPoma: non-alpha, non-Beta islet cell pancreatic tumor that secretes VIP( copious diarrhea

Blood supply Arterial anastomoses which form anastomoses Internal thoracic (subclavian) Inferior epigastric (external iliac)

Venous portal system anastomoses with systemic Esophageal(> Left gastric

Clinical sign: Esophageal varices

Paraumbilical (>superficial and inferior epigastric Clinical sign: Caput Medusae

Superior rectal(>middle and inferior rectal

Clinical sign: hemorrhoids (external are painful,due to somatic innervation)