Git hoGIT HORMONESrmones G
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Transcript of Git hoGIT HORMONESrmones G
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GIT HORMONES
DR.NILESH KATE. M.D.
ASSOCIATE PROFESSOR,DEPARTMENT OF
PHYSIOLOGY,
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OBJECTIVES INTRODUCTION. HISTORY. CLASSIFICATION. COMMON DESCRIPTION.
CELLS PRODUCING – SOURCE. CLASSIFICATION. LOCATION. STIMULUS. MECHANISM OF ACTION. ACTIONS. APPLIED.
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INTRODUCTION Earlier ---Believed Regulatory mechanisms were
controlled by the nervous system
Later numerous chemicals in the name of hormones were found
Hormones -- Play an integral role in most of the regulatory mechanisms in our body
Main objective of learning this topic in detail
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INTRODUCTION. (Cont….)
Largest endocrine organ Enteric endocrine system. Total about 30 GIT hormones. These are biologically active
polypeptide & act in a paracrine fashion.
Main function is: 1. To regulate the git secretion 2. To regulate the movement of GI
tract.
PARACRINE HORMONES.
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SITE OF ACTION.Endocrine Autocrine Paracrine
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HISTORY. BAYLISS & STARLING (1902) discovered the first
GIT hormone secretin. GREGORY AND TRACY (1964) --chemical
definition of Gastrin. YALOW AND BENSON (1966) invented RIA to
estimate quantity . JORPES AND MUTT (1996) chemical nature of
secretin and cholecystokinin and a group of other hormones.
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Endocrinal cells.Endocrinal cells. Origin - Neuroectodermal Act - On surfaces Mechanism - 1. Neurocrine 2. Paracrine 3. Classic endocrine
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Endocrine cells - GIT“Enteroendocrine cells” More than 15 types present Spread all over --stomach, small
intestine, colon
Many cells secrete only one hormone
eg. G cells, S cells, K cells, M cells
Cells that manufacture Serotonin in addition to polypeptides – Entero- chromaffin cells.
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APUD cells or Neuroendocrine cells(Amine Precursor Uptake and
Decarboxylase).
Cells that manufacture amines in addition to polypeptides
Found in lungs and other organs in addition to GIT
Can form carcinoid tumors
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GI HORMONES
GASTRIN FAMILY SECRETIN FAMILY OTHERS
1. Secretin2. Glucagon3. Glicentin4. VIP5. GIP
1. Gastrin2. Cholecystokinin (CCK)
1. Peptide YY2. Ghrelin3. Motilin4. Somatostatin5. Neurotensin6. Substance P7. GRP8. Bombesin9. Glucagon10.Guanylin
CLASSIFICATION
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GASTRIN.Source: G cells (stomach pyloric antral
region)Flask shaped, granules +Also -- hypothalamus,
Pituitary –ant, intermediate
Medulla, Fetal pancreas,
Nerves --Vagus, sciatic nerves
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G cells-secrete gastrin
STRUCTURE:
APUD CELLS polypeptide3 types
G14 G17 G34
G17– Principal formHalf life 2-3 minMetabolised – kidney, SI.
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G.I. HORMONES
Structure of Structure of SecretinSecretin (27 AA) (27 AA) (comparison with other GI hormones)(comparison with other GI hormones)
Gastrin (17 AA)Gastrin (17 AA)
Cholecystokinin (CCK (33 AA))Cholecystokinin (CCK (33 AA))
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LOCATION.
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STIMULATION FOR RELEASE
STIMULATION HORMONES RELEASED
VAGAL STIMULATION, HCL & PRODUCT OF DIGESTION
GASTRIN
DIETARY PROTEIN GASTRIN & CCK
DIETARY CARBOHYDRATE GIP & GLUCAGON LIKE SUBSTANCES
DIETARY FAT CCK & GIP
HYDROGEN IONS SECRETIN
• “TASTE” – the luminal environment & Respond
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STIMULATION OF GASTRIN Stimulation increases
Luminal * peptides & amino acids- phenylalanine & tryptophan
* Distention of pyloric antrum.Heidenhain pouch – denervated antral
pouchPavlov pouch – small pouch with intact
nerve & blood supply. Neural
* vagal through GRP Blood borne
* Calcium * Epinephrine
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DECREASESDECREASES
Luminal
* Acid – by negative
feedback effect
* Somatostatin
Blood borne
Secretin
VIP, GIP
Glucagon
Calcitonin
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Mode of actionGastrin Receptor (parietal cells)
Intracellular calcium(IP3) H+-K+ ATPase Ca++ activates
protein kinase
Acid secretion
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Function of gastrin. Stimulate Gastric Acid and pepsin
secretion Trophic action – growth of gastric
mucosa and intestinal mucosa Stimulate Gastric Motility Contraction of muscle at gastro
esophageal junction cardiac sphincter prevents reflux oesophagitis Peristaltic
contraction
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Functions of Gastrin. Stimulate Exocrine pancreas secretion Stimulate Insulin secretion Stimulate mass movement of large
intestine Colonic contraction that initiates Gastro-colic
reflex – defecation after meal Stimulate Histamine secretion from ECL cells
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Food in the stomach (gastric distension)
Products of protein digestion (peptides and amino acids)
Vagal stimulation(Non – cholinergic)
G cells of stomach
Secretion of gastrin
Parietal cells of stomach
HCI secretion
High acidic gastric content(auto regulation of gastrin secretion
Acidic duodenal chyme(secrete hormones)
Intestinal hormones(GIP, VIP, somatostatin, secretin
& glucagon)
REGULATION
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CHOLECYSTOKININ-pz.
GREEK –
chole, "BILE"; cysto, "SAC"; kinin, "MOVE"; so MOVE THE BILE-SAC
Source: I cells – Granular mucosal cells of duodenum & jejunum.
Also – cerebral cortex, somatic nerves, distal ileum, colon.
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STRUCTURE:
CCK 58 39 33 12 8 4
Stimuli: Acid, protein, fat Digested products in duodenum
Initially considered 2 hormones later found to be one
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Functions of CCK-pz Contraction of gall bladder –
increased bile release Stimulate pancreatic secretion
rich in enzyme Augments the action of secretin Inhibit gastric acid secretion Inhibit gastric motility Delay gastric emptying
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Regulation of secretions.
•CCK-PZ –• Increased by
Acid in duodenumProducts of carbohydrates, fats, & proteins digestion. Mainly peptides & amino acidsPositive feedback–
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SECRETIN.Bayliss & Starling (1902)
discovered the first gastro intestinal hormone SECRETIN
SOURCE : S cells – upper SI (Argentaffin cells)
Structure : 27 AA
Stimuli : Acid in duodenum
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Function of secretin.
Stimulate secretion of pancreatic juice rich in HCO3
-
Stimulate bile secretion. Augment action of CCK to produce pancreatic
secretion rich in enzymes Reduces the gastric acid secretion and
motility Contraction of pyloric sphincter
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HCL & MOTILITY
NaHCO3
HCL +NaHCO3Nacl , CO
2 , H2 O
REGULATION OF SECRETION
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GASTRIC INHIBITORY PEPTIDE( GIP)
Source: K cells – jejunum & duodenum
Initially called Enterogastrone. Discovered as a factor in extracts of
intestine that inhibited gastric motility and secretion of acid.
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GASTRIC INHIBITORY PEPTIDE( GIP)
Another activity of GIP is its ability to Enhance the release of insulin in response to infusions of glucose. -- Glucose-dependent insulinotropic peptide.
Regulation – Increases by fat in duodenum
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Source – Mucosal cells in jejunum
Stimuli – fatty meal
Structure -- polypeptide 28 amino acids
Other sites— Nerves in GIT, Blood, Brain ( cerebral cortex) Autonomic nerves.
VASOACTIVE INTESTINAL POLYPEPTIDE (VIP)
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Stimulate Intestinal secretion of electrolytes & water.
Vasodilatation – decreases BP Induce smooth muscle relaxation (lower
esophageal sphincter, stomach, gallbladder) Stimulate secretion of water into pancreatic
juice and bile. Inhibition of gastric acid secretion and
absorption from the intestinal lumen. Decreases the GI motility.
ACTIONS.
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ENTEROGLUCAGON AND ENTEROGLUCAGON AND GLUCAGON-LIKE PEPTIDES. GLUCAGON-LIKE PEPTIDES.
Source : Terminal SI and LI - L cells.
Given the name "Enteroglucagon",
"Proglucagon-derived Peptides". In both pancreas and gut, 3 types of products are
generated: • Glucagon-like Peptide-1 (GLP-1)• Glucagon-like Peptide-2 (GLP-2)• Glucagon-like Peptide-3 (GLP-3)
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GLP-1GLP-1 Inhibit gastric
emptying, Inhibit gastric
secretion and Inhibit pancreatic
secretion, Decreases food
intake.
Glucagon-like peptide-2
It stimulates proliferation of intestinal epithelial cells.
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SOMATOSTATIN (GHIH). Source -- S Cells or δ cells
GIT MUCOSA.
Structure– SS14, SS28 (more active)
Somatostatin is also secreted by the Hypothalamus & pancreas.
Stimuli – Acid in stomach stimuli which increases insulin secretion
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ACTIONS Secretions of Gastrin, secretin, Motilin,
Pancreatic – Exocrine & Endocrine secretions
Gastric acid secretions & motility ( Dyspepsia & slow gastric emptying)
Gall bladder contractions ( Precipitate gall stone)
Absorption of glucose amino acid, & triglyceride.
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MOTILIN
• Source -- Endocrinocytes (Mo Cells) in the mucosa of the proximal Small Intestine.
• Based on 22 AA sequence,
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MOTILIN participates in controlling the pattern of smooth muscle contractions in the upper GI tract that increases the MIGRATING MYOELECTRIC COMPLEX ("Housekeeping contractions“).
It sweep the stomach and SI clear of undigested material and stimulates the production of PEPSIN.
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GHRELIN-28 AA ’Ghre’’ – Growth ---- Europian name. Source -- Endocrine cells in the stomach,
especially when one is hungry; Action-- acts on the hypothalamus to stimulate
feeding;
This action counteracts the inhibition of feeding by leptin and Pyy 3-36.
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GHRELIN-28 AA
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GUANYLIN 15 amino acid residues Source: Cells of the intestinal mucosa Stimulant: Stimulation of Guanylin Function: It increase Cl- movement to intestine
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Other hormonesHormonesHormones sourcesource EffectsEffects
Neurotensin Neurotensin Neurons & ileal Neurons & ileal epitheliumepithelium
Inhibit GI motility - ileal Inhibit GI motility - ileal blood flowblood flow
GRPGRP Vagal nerveVagal nerve Gastrin releaseGastrin release
GuanylinGuanylin Paneth cellsPaneth cells Secretion of chloride ionsSecretion of chloride ions
ChymodeninChymodenin Duodenal mucosaDuodenal mucosa Selective secretion of Selective secretion of chymotrypsinogen from chymotrypsinogen from pancreatic acinar cellspancreatic acinar cells
Substance PSubstance P Entire GIT Entire GIT Increases the motility of SIIncreases the motility of SIIncreases local vasodilationIncreases local vasodilationPerception of pain sensationPerception of pain sensation
BombesinBombesin Entire GITEntire GIT Increases gastric secretionIncreases gastric secretionIncreases motility of gall Increases motility of gall bladderbladderIncreases motility of SIIncreases motility of SI
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SUMMARY OF ACTIONS
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SUMMARY
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APPLIED PHYSIOLOGY.
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ZOLLINGER-ELLISON SYNDROME (GASTRINOMA)
ULCER
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Zollinger-Ellison Syndrome (Gastrinoma)
Caused by a tumor (or tumors) called
Gastrinoma gastrin stomach acid.
SIGNS & SYMPTOMS:Pain in the stomach and esophagus,NauseaVomiting of blood, Difficulty in swallowing Sore throat, coughing, and wheezing Sour or bitter taste in the mouth Blood in the stool
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VERNER MORRISON SYNDROME ( VIPOMAS)
VIP Cause profound and chronic WDHA-syndrome (or) pancreatic cholera syndrome Watery Diarrhoea and resultant
Dehydration, Hypokalemia, Achlorhydria, Acidosis,
vasodilation (flushing and hypotension),
Hypercalcemia Hyperglycemia.
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VERNER MORRISON SYNDROME
TREATMENTSymptomatic
control Somatostatin
analogues Resection
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CARCINOID TUMORS( APUDOMAS) Carcinoid tumors originate from the diffuse
neuroendocrine system, specifically the enterochromaffin (EC) cells (submucosa of the intestine)
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Gastrointestinal Peptides and Amines Secreted by Carcinoid Tumors
ACTH Gastrin Pancreatic polypeptide Insulin Vasoactive intestinal polypeptide (VIP) Serotonin 5-hydroxyindoleacetic acid
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SUMMARY INTRODUCTION HISTORY COMMON DESCRIPTION
CELLS PRODUCING CLASSIFICATION LOCATION STIMULUS MODE OF ACTION
DETAIL ABOUT EACH HORMONES GASTIN CHOLECYSTOKININ SECRETIN MOTILIN VASOACTIVE INTESTINAL
POLYPEPTIDE GASTIC INHIBITORY
POLYPEPTIDE GLUCOGAN LIKE PEPTIDE OTHER HORMONES
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Thank You
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