Gastrointestinal Hormones

Introduction to Gastrointestinal Hormones

 Bioactive peptides secreted in response to food intake, regulating motility,

enzyme secretion, and nutrient absorption.
Classification of Gastrointestinal Hormones
1. Gastric hormones (e.g., gastrin).
2. Intestinal hormones (e.g., CCK, secretin).
3. Pancreatic hormones (e.g., somatostatin).
Three Basic Types of Gastrointestinal Hormones
Endocrine Mechanisms
 Hormones directly enter the bloodstream (e.g., gastrin).
Paracrine Mechanisms
 Hormones act locally on nearby tissues (e.g., somatostatin).
Neurocrine Mechanisms
 Hormones secreted by neurons (e.g., ghrelin).
 Gastrin

Produced by G cells in the stomach, gastrin stimulates HCl secretion,

enhances gastric motility,supports growth and maintenance of gastric
mucosa,promotes the secretion of pepsinogen, which is converted into
pepsin for protein digestion and indirectly supports the secretion of intrinsic
factor a protein vital for vitamin B12 absorption.
Stimuli for Release
 Gastrin release is stimulated by proteins, peptides, and amino acids (e.g.,
phenylalanine, tryptophan), stomach distension during food intake, vagal
nerve stimulation via acetylcholine, increased gastric pH, and gastrin-
releasing peptide (GRP) from the enteric nervous system.
Mechanism of Action
Gastrin binds to CCK-B receptors on ECL and parietal cells, stimulating histamine
release from ECL cells. Histamine activates H2 receptors on parietal cells, enhancing
HCl secretion. Gastrin can also directly stimulate parietal cells for HCl production.
Feedback Mechanisms
 Negative feedback: Gastrin is inhibited by low pH (<3) and somatostatin from D cells.
 Positive feedback: Gastric proteins and peptides sustain gastrin release until digestion
ends.
Measurement
 Fasting Plasma Gastrin Levels: These are measured using blood tests, with normal
values ranging between 50–100 pg/mL.
 Provocative Tests:
 Secretin Stimulation Test: Differentiates gastrinomas from other causes of elevated
gastrin.
 Calcium Infusion Test: Stimulates gastrin secretion in cases of gastrinomas.
Clinical Significance
Hypergastrinemia:
 Zollinger-Ellison Syndrome (ZES): Gastrin-secreting tumor causing excessive acid,
leading to peptic ulcers, diarrhea, and GERD.
 Achlorhydria: Absence of gastric acid due to conditions like atrophic gastritis or
chronic PPI use, reducing gastrin levels.
 Chronic Atrophic Gastritis: Loss of parietal cells lowers acid, causing compensatory
gastrin increase.
 Chronic PPI Use: Prolonged acid suppression elevates gastrin.
Clinical Features:
 Peptic ulcers, diarrhea, malabsorption, heartburn, and abdominal pain.
Diagnosis:
 Elevated fasting serum gastrin (>1000 pg/mL suggests ZES).
 Gastric pH measurement to differentiate acid overproduction from achlorhydria.
Hypogastrinemia
 Hyperacidity: Increased acid suppresses gastrin via feedback inhibition.
 Pernicious Anemia: Autoimmune destruction of G cells lowers gastrin.
 Surgical Resection: Gastrectomy or antrum removal eliminates G cells.
 Somatostatin Excess: Increased somatostatin inhibits gastrin secretion.
Clinical Features:
 Symptoms of low gastric acid (e.g., poor digestion, bacterial overgrowth).
 Signs of underlying conditions (e.g., fatigue in pernicious anemia).
Diagnosis:
 Reduced fasting serum gastrin levels.
 Secretin

Produced by S cells in the duodenum, secretin regulates pH by stimulating bicarbonate

secretion and inhibiting gastric acid.It also enhances the release of digestive enzymes
indirectly by promoting pancreatic activity, increases bile secretion aiding in fat
digestion and absorption, slows gastric emptying to allow time for proper
neutralization and digestion.
Stimuli For Release
• Acidic chyme (pH < 4.5) entering the duodenum.
• Fatty acids and hyperosmolar solutions in the small intestine.
Mechanism of Action
• Secretin binds to receptors, activating the cAMP pathway.
• Stimulates pancreatic bicarbonate secretion to neutralize acidic chyme.
• Suppresses gastrin release and reduces HCl secretion.
Feedback Mechanisms:
Negative Feedback: Secretin decreases as duodenal pH rises and acid is neutralized.
• Positive Feedback: Acidic or fatty chyme maintains secretion until neutralization.
Measurement:
• Plasma Secretin Levels: Normal fasting levels <100 pg/mL.
• Provocative Tests: Secretin stimulation test diagnoses pancreatic diseases (e.g.,
ZES) by assessing gastrin and bicarbonate response
Clinical Significance
Hyposecretion of Secretin Causes
•Damage to Duodenal Mucosa
•Genetic Deficiency
•Chronic Inflammation
Effects on the GIT:
•Impaired gastric acid neutralization due to reduced bicarbonate secretion.
•Inactivation of digestive enzymes, impairing digestion and nutrient absorption.
•Increased risk of peptic ulcers from insufficient acid neutralization.
Hypersecretion of Secretin Causes:
•Tumors (Secretinoma): Rare tumors overproduce secretin.
•Chronic High Acid Levels: Conditions like Zollinger-Ellison syndrome stimulate excess
secretin.
•Prolonged Stimulation: Chronic alcohol use or gallbladder disease can overstimulate
the duodenum.
Effects on the GIT:
•Excess bicarbonate secretion can lead to alkalosis.
•Suppressed gastric acid secretion (hypochlorhydria) reduces digestion efficiency.
•Pancreatic overstimulation causes excessive enzyme secretion.
Clinical Features:
•Alkalosis symptoms (nausea, vomiting, muscle weakness).
•Reduced appetite, indigestion, and diarrhea due to hyperactive pancreatic secretion.
 CCK
Produced by I cells in the duodenum, CCK stimulates bile and pancreatic enzyme secretion
and slows gastric emptying.
Stimuli for Release
 Fatty acids, monoglycerides, amino acids, and small peptides in the duodenum.
 Mechanical stretching of the duodenum during digestion.
 Secretin and vagal nerve stimulation.
Mechanism of Action
 CCK binds to CCK-A receptors on the gallbladder and pancreas, activating the PLC
pathway and increasing intracellular calcium.
 Gallbladder Contraction: Releases bile for fat emulsification.
 Pancreatic Enzyme Secretion: Stimulates secretion of lipase, amylase, and proteases.
 Relaxation of the Sphincter of Oddi: Allows bile and enzymes to flow into the
duodenum.
Feedback Mechanisms
Positive Feedback: Nutrients (especially fats and proteins) in the duodenum sustain
CCK release until digestion is complete.
Negative Feedback: As digestion progresses and bile/pancreatic enzymes decrease,
CCK levels decline. Increased bile acids inhibit further CCK secretion .

Measurement
Plasma CCK Levels: Normal fasting levels <10 pmol/L.
Tests: Stimulation with fatty meals or amino acids to evaluate CCK secretion.
Immunoassays: ELISA and RIA are used for CCK measurement.

Clinical Significance
CCK Deficiency
 Damage to Intestinal Mucosa
 Chronic Low Fat Intake
 Pancreatic Disorders
 Congenital Deficiency: Rare genetic defects affecting CCK production or receptor
function.
Effects on the GIT:
 Impaired digestion of fats and proteins due to reduced pancreatic enzyme
secretion.
 Delayed gallbladder emptying, causing fat malabsorption and steatorrhea.
 Sluggish gastric emptying, disrupting motility coordination.
Clinical Features:
 Bloating, abdominal pain, diarrhea (due to undigested fats).
 Fatty stools (steatorrhea), malnutrition, and weight loss in severe cases.
 Altered appetite regulation, leading to overeating or undereating.
CCK Excess
 Small Intestinal Overstimulation: High-fat or protein-rich diets overstimulate I cells.
 CCK-secreting Tumors: Rare neuroendocrine tumors overproduce CCK.
 Gallbladder Diseases: Conditions like gallstones lead to prolonged CCK stimulation.
 Pancreatic Disorders: Overactive feedback loops can cause excessive CCK secretion.
Effects on the GIT:
 Excessive gallbladder contraction, potentially causing biliary colic or worsening
gallstones.
 Overproduction of pancreatic enzymes, leading to digestive discomfort.
 Delayed gastric emptying, causing bloating and nausea.
Clinical Features
 Upper abdominal pain, nausea (linked to gallbladder activity).
 Diarrhea or steatorrhea from enzyme and bile overactivity.
 Satiety issues, leading to reduced appetite and unintentional weight loss.
 GIP

Produced by K cells in the duodenum, GIP enhances insulin release and reduces gastric
motility also Inhibit Gastric Acid Secretion and Lipid Metabolism Regulation.

Stimuli for GIP Release

 Ingestion of fats, carbohydrates, and proteins, with fats and glucose being the
most potent stimuli.
 Oral glucose enhances GIP secretion more than intravenous glucose.
 Duodenal distension during food intake also stimulates GIP release.
Mechanism of Action
 GIP binds to receptors on pancreatic beta cells, activating the cAMP pathway.
 Insulin Secretion: Enhances insulin release in response to glucose (incretin effect).
 Inhibition of Gastric Acid Secretion: Reduces parietal cell activity.
Feedback Mechanisms:
 Positive Feedback: Elevated dietary nutrients (especially glucose and fats)
sustain GIP release.
 Negative Feedback: High insulin levels and normalized blood glucose
suppress GIP secretion.
Measurement:
 Plasma GIP Levels: Fasting levels typically <50 pg/mL.
 Stimulated Tests: Postprandial GIP levels are measured after glucose or fat
ingestion to assess the response.
Clinical Significance
GIP Deficiency Causes:
 Intestinal Damage: Disorders like celiac disease, Crohn’s disease, or small intestine
surgery can impair GIP secretion.
 Congenital Deficiency: Rare genetic mutations affect GIP secretion or receptor function.
 Endocrine Disorders: Hormonal dysregulation (e.g., somatostatin excess) may inhibit
GIP.
 Chronic Diseases: Conditions like diabetes mellitus may alter GIP secretion and
sensitivity.

Effects on the GIT and Metabolism:

 Impaired Insulin Secretion: Reduced GIP leads to poor glucose control, especially
post-meal.
 Reduced Gastric Inhibition: Unchecked gastric acid production may cause acid
reflux or peptic ulcers.
 Clinical Features
 Postprandial hyperglycemia (high blood sugar after meals).
 Fatigue and symptoms of uncontrolled blood sugar.
 Gastric hyperacidity symptoms (heartburn, epigastric pain).
GIP Excess Causes
 Obesity and Metabolic Syndrome: Excess fat tissue leads to hypersecretion
of GIP.
 Hyperinsulinemia: High GIP levels overstimulate insulin secretion,
especially in insulin resistance.
 Endocrine Tumors: Rare GIP-secreting tumors cause hormone
overproduction.
 Dietary Factors: High fat and sugar intake overstimulates GIP secretion.
Effects on the GIT and Metabolism
 Hyperinsulinemia: Excess insulin can lead to hypoglycemia (low blood
sugar).
 Reduced Gastric Motility: Overly inhibited gastric emptying causes bloating
and nausea.
 Adipogenesis: GIP promotes fat deposition, contributing to obesity.
Clinical Features
 Hypoglycemia symptoms (dizziness, sweating, palpitations).
 Weight gain and difficulty losing weight.
 Postprandial bloating, nausea, or discomfort.
 Motilin

Produced by M cells, motilin regulates fasting motility through MMC (migrating

motor complex).Enhances gastric emptying by stimulating antral and duodenal
contractions.Ensures smooth propulsion of chyme through the digestive
tract.Contributes to hunger signaling through interactions with neural pathways.
Stimuli for Motilin Release
 Secreted cyclically during fasting every 90-120 minutes to initiate the
migrating motor complex (MMC).
 Alkaline conditions in the duodenum stimulate motilin release.
 Vagal stimulation enhances motilin secretion.
 Motilin secretion decreases after food intake due to the presence of
nutrients.
Mechanism of Action
 Motilin binds to motilin receptors on smooth muscle cells, triggering muscle
contraction through increased intracellular calcium.
Feedback Mechanisms:
 Positive Feedback: Motilin release is stimulated cyclically during fasting to maintain
MMC activity.
 Negative Feedback:After food intake, nutrient presence inhibits motilin
secretion, adjusting digestive motility.
Measurement
 Plasma Motilin Levels: Measured using ELISA or RIA, with normal fasting levels
between 10-40 pg/mL.
 Dynamic Tests: Fasting levels and postprandial suppression are evaluated to assess
motility disorders.
Clinical Significance
Motilin Deficiency Causes
 Damage to Intestinal Mucosa
 Chronic Illnesses: Conditions like diabetes mellitus affecting motilin-mediated
motility.
 Medications: Chronic use of motility-inhibiting drugs (e.g., anticholinergics,
opioids).
 Neuromuscular Disorders: Diseases like scleroderma or Parkinson’s affecting gut
motility.
Effects on the GIT
 Delayed Gastric Emptying: Leads to gastroparesis.
 Impaired Intestinal Cleansing: Increases bacterial overgrowth risk.
 Bloating and Indigestion: Inefficient peristalsis causing discomfort.
Clinical Features
 Gastroparesis symptoms (nausea, vomiting, early satiety).
 Chronic bloating, abdominal discomfort.
 Risk of small intestinal bacterial overgrowth (SIBO) with diarrhea or malabsorption.
Motilin Excess Causes
 Hormonal Dysregulation: Rare endocrine disorders overstimulate motilin secretion.
 Fasting States or Overstimulation
 Post-Surgical Changes: Certain surgeries (e.g., gastric bypass) alter motilin
secretion.
 Tumors: Rare motilin-secreting tumors (e.g., neuroendocrine tumors).

Effects on the GIT

 Accelerated Gastric Emptying: Leads to dumping syndrome with rapid stomach
content movement into the small intestine.
 Excessive MMC Activity: Causes abdominal cramps and diarrhea.
 Impaired Nutrient Absorption: Rapid transit reduces nutrient absorption.
Clinical Features
 Symptoms of dumping syndrome (nausea, abdominal cramps, diarrhea after
meals).
 Weight loss and malabsorption-related deficiencies.
 Increased intestinal motility causing urgency and frequent bowel movements.
 Somatostatin

Produced in multiple sites of the body including Hypothalamus, Pancreas,GI,CNS.Is an

inhibitory hormone regulating gastric acid, motility, and hormone release.It Inhibit
secretion of growth hormone (GH) from the anterior pituitary,Suppress the release of
insulin and glucagon from the pancreas,Reduce gastric acid secretion and
gastrointestinal motility and Inhibit the secretion of gastrointestinal hormones, such as
gastrin, secretin, and cholecystokinin.
Stimuli for Release
•High blood glucose and amino acids.
•Acidic pH in the stomach.
•Presence of nutrients (fats, carbohydrates) in the GI lumen.
•Hormonal stimulation (e.g., gastrin, secretin).
Mechanism of Action
•Binding: Somatostatin binds to somatostatin receptors (SSTRs), inhibiting adenylate
cyclase and decreasing cAMP levels in target cells.
Effects:
•Inhibits Hormone Secretion: Suppresses release of gastrin, secretin, and CCK.
•Reduces Gastric Acid Secretion: Inhibits parietal cells and reduces histamine release from
enterochromaffin-like cells.
•Feedback Mechanism
Negative Feedback:
•Elevated levels of growth hormone, gastrin, and insulin suppress somatostatin release.
•Reduced acidity or fewer nutrients in the gut downregulate somatostatin secretion.
Measurement
•RIA (Radioimmunoassay): Sensitive for low concentrations.
•ELISA (Enzyme-linked Immunosorbent Assay): Common for specificity and convenience.
Clinical Significance
Somatostatin Deficiency
•Pancreatic Dysfunction: Damage to delta cells from chronic pancreatitis or pancreatic
resection.
•Gastrointestinal Disorders: Conditions like Crohn's disease reduce somatostatin
secretion.
•Congenital Defects: Rare genetic conditions affecting somatostatin production or
receptor function.
Effects
•Increased Hormone Secretion: Overproduction of insulin, glucagon, and gastrin due
to the loss of inhibitory effects.
•Gastrointestinal Hyperactivity: Enhanced gastric acid secretion and motility, increasing
the risk of peptic ulcers and diarrhea.
•Blood Sugar Instability: Imbalance in insulin and glucagon secretion, leading to
hypoglycemia or hyperglycemia.
Clinical Features
Gastric hyperacidity (heartburn, peptic ulcers).
Diarrhea from increased gastrointestinal motility.
Blood sugar instability (hypoglycemia or hyperglycemia).
Somatostatin Excess:
•Somatostatinomas: Rare neuroendocrine tumors in the pancreas or duodenum
•causing excessive somatostatin secretion.
•Endocrine Disorders: Hormonal dysregulation may lead to elevated somatostatin
levels.
•Chronic Diseases: Conditions like diabetes or hypothalamic dysfunction can alter
somatostatin regulation.
Effects
•Inhibition of Hormones: Suppresses insulin, glucagon, gastrin, and growth
hormone secretion.
•Reduced Gastric and Intestinal Activity: Delayed gastric emptying, reduced
motility, and decreased digestive enzyme secretion.
•Hyperglycemia: Suppressed insulin secretion leads to elevated blood sugar
levels.

Clinical Features
• Symptoms of diabetes mellitus (hyperglycemia, polyuria, polydipsia).
• Weight loss from malabsorption due to reduced digestive enzyme and bile
secretion.
• Steatorrhea (fatty stools) from impaired fat digestion.
• Gallstones resulting from reduced bile flow.
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