GI 3: Pathophysiology of GI Hormones

What cells secrete gastrin, and where are they located?

Secreted by G cells in the gastric antrum.

What are the primary actions of gastrin?

Stimulates gastric acid secretion by acting on CCK2 receptors on parietal cells and ECL cells and promotes gastric mucosal growth.

What stimulates gastrin secretion?

Proteins, peptides, amino acids, gastric distension, high pH, and vagal stimulation via gastrin-releasing peptide.

What inhibits gastrin secretion?

High gastric acidity, VIP, somatostatin, and secretin.

What is Zollinger-Ellison Syndrome (ZES)?

Rare condition characterized by gastrin-producing tumors in the duodenum and/or pancreas that lead to oversecretion of gastrin, which lead to gastric and duodenal ulcers

How does ZES cause steatorrhea?

High levels of gastric acid --> inactivates pancreatic digestive enzymes (lipase)

Loss of parietal cells may lead to...

pernicious anemia

What is achlorhydria?

absence of hydrochloric acid in the gastric secretions (loss of parietal cells) --> Hypergastrinemia

What vitamin are you not able to reabsorb with the absence of intrinsic factor?

Vitamin B12

What are the gastrin levels for Peptic ulcer disease, Duodenal ulcer, Gastrinoma, and Pernicious anemia?

-Slightly elevated for PCD or Duodenal ulcer

-Moderately elevated for Pernicious anemia

-Highly elevated for Gastrinoma (ZES)

What are the primary stimuli for CCK release?

Is released in response to fatty acids, lipids, and proteins in chyme.

What are the key actions of CCK?

-Stimulates gallbladder contraction, sphincter of Oddi relaxation for bile release

-Stimulates pancreatic enzyme secretion

-Inhibits gastric emptying and reduces meal size by inducing satiety.

What role does CCK play in gallbladder disease?

Reduced expression of CCK1 receptors is associated with gallstone formation.

What stimulates the release of secretin?

Released in response to acidic chyme (low pH) in the small intestine.

What are the main actions of secretin?

Stimulates pancreatic bicarbonate and water secretion from the pancreas, inhibits gastric acid secretion, and weakly promotes satiety.

Patients with bulimia nervosa, celiac disease, and conditions that delay gastric emptying (meal size regulation disorders) are reported to have low levels of...

CCK

Weight loss is associated with a reduction in circulating...

levels of CCK

Reduced expression of which receptor is reported with gallbladder disease?

CCK1

What clinical application does secretin have?

Secretin is used in the diagnosis of gastrinomas via the secretin stimulation test, where it paradoxically increases gastrin levels.

What is achalasia?

Motor disorder of the esophagus characterized by impaired relaxation of the lower esophageal sphincter (LES) and loss of peristalsis in the distal 2/3 of the esophagus

[Lack of VIP]

What are the key actions of VIP?

-Relaxes smooth muscles/sphincter relaxation

-Stimulates fluid and electrolyte secretion

-Enhances vasodilation

-Inhibits gastric acid secretion

What is a VIPoma, and what symptoms does it cause?

A VIPoma is a tumor that secretes excessive VIP, causing watery diarrhea, hypokalemia, and achlorhydria (WDHA syndrome).

What cells secrete somatostatin?

secreted by D cells in the GI tract

What stimulates the release of somatostatin?

low pH (high acidity) in the stomach

What are the inhibitory functions of somatostatin?

-Inhibits the secretion of gastrin, gastric acid, and pancreatic enzymes, reduces gastric motility, decreases gallbladder contraction, and reduces nutrient absorption.

Somatostatin = Inhibition

What are clinical applications of somatostatin?

Is used to treat hormone-secreting tumors (e.g., gastrinomas, VIPomas) and secretory diarrhea.

What cells secrete ghrelin?

Secreted by ε cells (epsilon cells)

When is ghrelin released?

During fasting

What are the primary actions of ghrelin?

-Stimulates appetite (hunger hormone) by acting on the hypothalamus and vagal afferents, enhances gastric emptying and acid secretion, and promotes energy storage and growth hormone release.

How does ghrelin level change in response to food intake?

Ghrelin levels rise during fasting and decrease after eating.

Levels of which GI hormone (other than ghrelin) raise with fasting and fall with ingestion of food?

Motilin

What is the only peripheral peptide that increases appetite?

Ghrelin