Gastrointestinal Hormones PDF

Gastrointestinal Hormones Jason Ryan, MD, MPH Gastrin Hormone for acid secretion in stomach Produced by G-cells Found in mucosa of antrum of stomach Secreted into portal vein blood Physiologic action on parietal cells Little Gastrin Big...

Gastrointestinal Hormones Jason Ryan, MD, MPH Gastrin Hormone for acid secretion in stomach Produced by G-cells Found in mucosa of antrum of stomach Secreted into portal vein blood Physiologic action on parietal cells Little Gastrin Big Gastrin  Parietal Cells Gastrin in mucosa of body Nephron/Wikipedia G cells in glands Antrum of mucosa layer Indolences /Wikipedia Gastrin Effects Stimulates H+ secretion by parietal cells Stimulates growth of gastric mucosa Important in gastrin tumors Hypertrophy and hyperplasia Increases gastric motility Gastrin Mechanism of Effect Enterochromaffin-like cells mediate gastrin effects Gastrin → ECL Histamine → Parietal cell Parietal cell receptors: Histamine (most important) Gastrin Ach (vagus nerve) Parietal cell + G cell + ECL Histamine Cell Gastrin Stimuli Released in response to: Stomach distention Alkalinization Amino acids (especially phenylalanine and tryptophan) Vagal stimulation (mediated by GRP – atropine does not block) Inhibited by low pH, somatostatin Phenylalanine Tryptophan Gastrinoma Zollinger-Ellison Syndrome Gastrin secreting tumors Occur in duodenum or pancreas G cells found in pancreas in fetus Excessive acid secretion Hypertrophy/hyperplasia of mucosa Gastrinoma Zollinger-Ellison Syndrome Abdominal pain Improves with food (raises pH) Chronic diarrhea Excessive gastric acid cannot be neutralized in intestines Low pH inactivates pancreatic enzymes Also inhibits sodium/water absorption in small intestines Result: Poor digestion, steatorrhea, secretory diarrhea Ulcers Most in distal duodenum (often past bulb) or jejunum Refractory to PPI therapy Heartburn Gastrinoma Diagnosis Fasting serum gastrin level >10 times upper limit of normal in gastrinomas Secretin test Differentiate gastrinomas from other causes ↑ gastrin Normal G cells inhibited by secretin (leads to ↓ gastric pH) Gastrinomas stimulated by secretin Gastrin level will rise after secretin administration Gastrinoma Treatment High dose proton pump inhibitors Omeprazole, lansoprazole, pantoprazole Octreotide (somatostatin) Inhibits gastrin release for some patients Surgical excision Pernicious Anemia Autoimmune gastritis Loss of parietal cells → loss of intrinsic factor Cannot absorb vitamin B12 High gastrin levels typical finding Also G-cell hyperplasia Databese Center for Life Science (DBCLS) Cholecystokinin Hormone for gall bladder contraction Pancreatic enzyme secretion Released by I cells Small intestine (mostly duodenum and jejunum) Cholecystokinin Contraction of gall bladder Pancreatic enzyme secretion CCK receptors in vagus nerve CCK stimulates vagus nerve → ACh stimulates pancreas Relaxation of sphincter of Oddi Inhibits gastric emptying Cholecystokinin Stimuli: Fatty acids and monoglycerides (not triglycerides) Amino acids and small proteins Fatty Acid H Mono-glyceride H HIDA Scan Hepatic iminodiacetic acid scan Method of cholecystography Test to evaluate RUQ pain Usually when ultrasound non-diagnostic Procedure 99mTc-hepatic iminodiacetic acid administered Should concentrate in gall bladder, pass to intestines Radioactivity can be followed Failure to fill gall bladder suggests obstruction Sometimes cholecystokinin administered Gall bladder radioactivity measured before/after Gall bladder ejection fraction determined Secretin Hormone to raise pH in small intestine Released by S cells of duodenum Released in response to H+ in duodenum Fatty acids in duodenum Luke Guthmann/Wikipedia Secretin Increases HCO3- secretion by pancreatic duct cells Neutralizes gastric acids Allows pancreatic enzymes to function Inhibits gastric H+ secretion Many mechanisms described Suppresses gastrin release Increases bile production Promotes pancreatic flow Water secreted with bicarb Flushes pancreatic enzymes into intestines Secretin Key clinical use: gastrinomas Secretin stimulation test Increases gastrin production only in gastrinoma cells Somatostatin Inhibits most GI hormones Released by D cells throughout GI tract Also found in nerves throughout entire body Originally discovered in hypothalamus Shown to inhibit growth hormone release Can act as: Hormone (via blood to affect distant targets) Paracrine (affects nearby cells) Somatostatin Stimuli Inhibitory Effects Gastric H+ Pepsinogen secretion ↑ Low pH Gall bladder contraction ↓ Vagus Nerve Pancreatic fluid secretion Intestinal fluid secretion Insulin/Glucagon release Food in stomach → ↓ Somatostatin → hormone release Acid in stomach → Somatostatin release → hormone shutdown Regulates digestion/acid secretion Octreotide Analog of somatostatin Used in GI bleeding and other niche roles Bleeding varices: Reduces splanchnic blood flow Samir/Wikipedia Octreotide Carcinoid Syndrome Somatostatin receptors found on majority of carcinoid tumors Flushing and diarrhea significantly improve Acromegaly Inhibit growth hormone secretion Gastrinoma/Glucagonoma Inhibit release of hormones GIP Glucose-dependent insulinotropic peptide Stimulates insulin release from pancreas Also blunts H+ secretion Released by K cells of duodenum/jejunum Stimuli: Glucose, fatty acids, amino acids Only hormone release in response to fats, protein, and carbs Special note: Oral glucose metabolized faster than IV glucose IV glucose does not stimulate GIP release VIP Vasoactive Intestinal Peptide Neurocrine Synthesized in neurons Released in response to action potential onto target cells Causes relaxation of smooth muscle Important for LES Raises pH (similar to secretin) Stimulates pancreatic HCO3- secretion Bicarb draws water → increased fluid secretion Inhibits gastric H+ secretion VIPoma Rare VIP secreting tumors in pancreas (islet cells) Watery diarrhea (secretory diarrhea) VIP promotes bicarb secretion → water secretion Tea-colored, odorless diarrhea Resembles cholera (“pancreatic cholera syndrome”) Hypokalemia(from high volume diarrhea) Achlorhydria Absence of gastric acid WDHA syndrome Watery diarrhea, hypokalemia, achlorhydria VIPoma Typical case Adult (30-50 years old) Long-standing watery diarrhea (no blood, pus) No response to diet changes (elimination of lactose) Endoscopic sampling: High pH in stomach Elevated VIP on serum testing VIPoma Initial treatment: Fluid/electrolyte replacement Octreotide (somatostatin) Often metastatic at presentation Surgical resection sometimes possible Often progresses Median survival ~ 8 year Motilin Released by cells in stomach, intestines, colon Promotes motility in the fasting state Highest levels found between meals Key clinical point: Erythromycin binds motilin receptors Used to treat gastroparesis  Major Hormone Locations Antrum Duodenum Jejunum Ileum Gastrin CCK Secretin GIP Motilin VIP Somatostatin  Think about eating Cephalic Sight/smell food Phase Vagus Nerve Stomach H+ Gastric Distention Secretion ↑ Gastric pH Amino Acids Gastrin (G cells)  Think about eating Gastric Sight/smell food Phase Consume Vagus Food Nerve Stomach H+ Gastric Distention Secretion ↑ Gastric pH Amino Acids Gastrin (G cells)  Think about eating Intestinal Sight/smell food Phase Consume Vagus Food Nerve Small Intestine Stomach H+ Fatty Acids Gastric Distention Secretion Amino Acids ↑ Gastric pH H+ Amino Acids - GIP CCK Secretin Bicarb Gall bladder Pancreatic enzymes Sphincter of Oddi