GI03 - Gastric Function

What are the storage and emptying functions of the stomach?

Accumulate ingested meal and control rate of emptying into small intestine.

What substances are secreted by the stomach?

HCl, intrinsic factor, pepsinogen.

How does the stomach provide defense?

HCl kills most bacteria.

How does the stomach digest food?

HCl dissolves large food particles; pepsin begins protein digestion.

What is the mixing function of the stomach?

Motility mixes food with gastric secretions.

What is chyme?

Mixture of broken-up food particles and gastric secretions that gets released into the duodenum.

Where are oxyntic (gastric) glands mainly located?

Corpus of the stomach

What characterizes the cardia?

Distal to the lower esophageal sphincter (LES), contains few secretory cells.

What is the corpus?

Body of stomach; site of acid secretion.

What characterizes the antrum of the stomach?

Contains only chief and endocrine cells.

What is the first step in gastric filling?

Receiving and temporary storage.

What is the second step in gastric digestion?

Mixing food and water with gastric secretory products (pepsin and acid.)

What is the third step?

Grinding of food to reduce particle size.

Why is grinding important?

Enhances digestion and permits passage into pylorus.

What is step 4?

Regulating exit of chyme from stomach into duodenum.

How is emptying of liquids regulated?

By proximal smooth muscle.

How is emptying of solids regulated?

By antral smooth muscle.

What do parietal cells secrete?

HCl (pH = 0.8) and intrinsic factor.

What is the function of intrinsic factor?

Required for vitamin B₁₂ absorption.

What do mucus cells secrete?

Viscous alkaline secretion; protects the stomach lining from acid and digestive enzymes.

What do chief cells secrete?

Pepsinogen and gastric lipase.

What is pepsinogen converted into?

Pepsin

What does pepsin digest?

Connective tissue (allows breakdown of proteins)

Is gastric lipase the same as pancreatic lipase?

No, they are different

What are the endocrine cells of the stomach?

G cells, ECL cells. and D cells

What do G cells secrete?

Gastrin (promotes HCl secretion).

What do ECL (enterochromaffin-like) cells secrete?

Histamine (promotes HCl secretion).

What do D cells secrete?

Somatostatin (inhibits HCl secretion).

Into which space are gastrin, histamine, and somatostatin released?

Into interstitial fluid (ISF) surrounding the oxyntic gland.

What is the normal acid secretion of parietal cells?

It is low in the resting state

What happens when parietal cells are activated?

Fusion of tubulovesicles with the membrane → H-K pumps are inserted into the membrane → surface area increases

How is acid secreted by parietal cells?

• H-K pump moves H+ out and K+ in

• K+ leaks into lumen through channel

• Cl- leaks into lumen through channel

• HCl is formed in the lumen

What ensures constant production of H+ from parietal cells?

High expression of carbonic anhydrase

What causes direct stimulation of parietal cells?

Acetylcholine, histamine, and gastrin

What causes indirect stimulation of parietal cells?

Acetylcholine also stimulates secretion of histamine and gastrin, which increase parietal cell secretion

By what processes is acid secretion regulated?

Occurs through activation of cAMP via H2 receptor and PLC/PKC via gastrin and ACh receptors

What inhibits acid secretion?

Prostaglandins and somatostatin; both oppose the action of histamine

How does the autonomic nervous system regulate H+ secretion?

ACh release causes stomach distension and stress → increases HCl and pepsinogen secretion

How does gastrin regulate H+ secretion?

Gastrin hormone stimulates HCl secretion from parietal cells

How does histamine regulate H+ secretion?

Enhances the effects of ACh and gastrin; blocked by H2 antagonists

How does somatostatin regulate H+ secretion?

Inhibits parietal cells, G cells, and ECL cells

How does the intestine regulate gastric H+ secretion?

Foor and acid in the small intestine causes decreased gastric secretion (negative feedback)

What is the role of ACh in gastric acid secretion?

ACh from the vagus nerve stimulates parietal, G, and ECL cells and inhbits D cells

Where is gastrin released after stimulation?

Gastrin is released by both antral and duodenal G cells

Where is histamine released from?

Histamine is released from ECL cells in the corpus of the stomach

What is the main enteric inhibitor of acid secretion?

Somatostatin

Where is somatostatin secreted?

From gastric D cells and delta cells in the pancreas

What other intestinal hormones inhibit acid secretion?

• Cholecytokinin (CCK)

• Secretin

• VIP

• GIP

• Neurotensin

• Peptide YY

Where is CCK secreted?

From the duodenum

Where is secretin secreted?

From the small intestine

Where is VIP secreted?

Secreted from ENS neurons

Where is GIP (glucose-dependent insulinotropic polypeptide) secreted?

Secreted from the small intestine

Where is neurotensin secreted?

From the ileum

Where is peptide YY secreted?

From the ileum and colon

What are the three phases of gastric function?

• Cephalic phase

• Gastric phase

• Intestinal phase

What initiates the cephalic phase?

Site, smell, taste, and chewing of food

What mediates the cephalic phase?

Mediated by efferent parasympathetic pathways (vagus nerve) innervating the GI nerve plexus; affects the secretory and contractile activity of salivary glands and stomach

What initiates the gastric phase?

Initiated by distension, acidity, proteins, and peptides in the stomach to regulate stomach functions

What mediates the gastric phase?

Responses are mediated by short and long reflexes, gastrin hormone, and paracrine factors. This is called the vagovagal reflex (vagal afferents → vagal efferents)

What initiates the intestinal phase?

Initiated by distension, acidity, osmorality, and digestive products in the small intestine

What is the purpose of the intestinal phase?

Activates intestinal activity and inhibits stomach activity

What mediates the intestinal phase?

Mediated by short and long reflexes (enterogastric reflex) and by hormones such as secretin, GIP, and CCK

What percentage of gastric acid secretion occurs during the cephalic phase?

~20%

What percentage of gastric acid secretion occurs during the gastric phase?

~70%

What are the main triggers of the cephalic stage?

Sight, smell, taste, or thinking about food

How does the cephalic stage increase gastric secretions?

The vagus nerve (PNS) stimulates:

• Parietal cells

• G cells

• ECL cells

How does the gastric phase increase gastric secretions?

Distension and presence of food causes an enteric reflex that stimulates additional gastrin secretion

What happens in the gastric phase when there is high acid concentration?

The enteric reflex stimulates pepsinogen secretion and stimulates D cells (secrete somatostatin → inhibit acid secretion)

What neural and endocrine reflexes are triggered when chyme is moved into the small intestine?

• Initiates enzyme and HCO3- secretion

• Feed back to slow gastric secretion and emptying (after initial promotion of gastric secretion through intestinal G cells)

• Feed forward to initiate insulin secretion

What is the enterogastric reflex?

Food in the small intestine → ENS → decreased gastric secretion

What is released when acid, fat, or protein is present in the duodenum?

• Secretin: inhibits gastrin and promotes somatostatin secretion

• GIP and CCK: results in decreased gastrin secretion

What is the gastric acid secretion between meals?

There is very little gastric acid secretion between meals. Basal rate = 10% of the max rate.

What cells secrete pepsinogen?

Chief cells

How is pepsinogen activated and destroyed?

Activated into pepsin by low pH; destroyed by high pH

How much does pepsinogen contribute to protein digestion?

Contributes less than 20% of protein digestion

What induces pepsinogen secretion?

Induced by ACh or acid

What cells secrete gastric lipase?

Chief cells

How does gastric lipase compare to pancreatic lipase?

It is different

How does mucus and HCO3- potect the gastric mucosa?

• Mucus and HCO3- create a pH gradient from the gastric lumen (low pH) to the mucosa (neutral pH)

• The mucus serves as a barrier for the diffusion of acid and pepsin

How do epithelial cells protect the gastric mucosa?

Epithelial cells remove excess H+ via membrane transport. They have tight junctions that prevent back diffusion of H+

How does mucosal blood flow protect the gastric mucosa?

Mucosal blood flow removes excess acid that has diffused across the epithelial layer

What is the turnover rate of gastric epithelial cells?

Rapid turnover; replaced every 2-4 days.

What is gastric mucus composed of?

H2O, electrolytes, and glycoproteins (mucin)

What is the role of mucus in the stomach?

Protects gastric epithelial cells from digestion; generates a hydrophobic diffusion barrier

Where is HCO3- secreted?

Gastric epithelial cells secrete HCO3- under the mucus gel layer.

What is the role of HCO3- under the mucus layer?

This maintains a higher pH near epithelial cells.

How does acid escape through gastric glands?

It escapes through the gel/mucus layer through “finger”-like indentations

How do prostaglandins contribute to mucosal defense?

They promote HCO3- and mucus secretion and maintain mucosal blood flow

What happens when acid breaches the diffusion barrier?

Mucosal epithelial cells are injured; leads to activation of mast cells

What happens with mild injury to the mucosa?

Vasodilation allows for continuous HCO3- secretion

What happens with severe injury to the mucosa?

Vasoconstriction results in ischemia

What do prostaglandins do when there is mucosal damage?

• Inhibit acid secretion

• Induce mucus and HCO3- secretion

• Maintain mucosal blood flow

• Downregulate local inflammatory mediators (COX-2)

(primarily via constitutive COX-1)

How do NSAIDs affect prostaglandin synthesis?

NSAIDs inhibit prostaglandin synthesis and can contribute to gastric and duodenal mucosal injury

What do salicylates (aspirin) inhibit?

Primarily COX-1 prostaglandin

What do non-selective COX inhibitors do? (ex: ibuprofen, naproxen)

Inhibit COX-1 and COX-2 prostaglandins

What substances impair the mucosal diffusion barrier?

Bile acids and ethanol (reduce hydrophobicity)

How does the stomach have extra motility?

The stomach has an additional oblique muscle layer; accomodation allows food to enter without increasing pressure greatly

How does stomach motility affect what goes into the duodenum?

During grinding and retropulsion, only material smaller than 2 mm can pass through the pyloric sphincter to the duodenum

What is the pyloric pump?

Contractions in the stomach increase in intensity and propel contents several mL at a time out of the stomach. The waves go in both directions and originate higher up each time.

How do gastric factors regulate stomach emptying?

Stretch increases the activity of the pyloric pump → increase emptying