Gastric Secretion

Surface epithelial cells in stomach

line pits - secrete visible, alkaline mucus protects mucosa from mechanical /chemical damage

Mucous neck cells

secrete soluble (clear) mucus; serve as parent cells for replacement of other cell types

HCL

secreted by Parietal cells to initiate protein digestion in stomach

IF

secreted by Parietal cells, required for vit b12 abosrption in ileum.

Gastric Muscosal Cells

Secrete gastric juices

Pepsinogen

Secreted by chief cells to initiate protein digestion in stomach

3 substances stimulate H+ secretion

1. ACh (neurocrine) 2. Histamine (paracrine) 3. Gastrin (hormone)

Gastric Parietal Cell secretion

1. CO2 + H2O = H2CO3 - catalyzed by carbonic anhydrase (CA) H2CO3 dissociates to H+ + HCO3 2. H+ secreted into lumen via H+-K+ ATPase - Cl- follows H+ through channels 3. Basolaterally - HCO3 - absorbed via Cl- exchanger 4. Overall net secretion HCl and net absorption HCO3

Pvloric glands contain

1. G cells: Secrete gastrin not into pyloric ducts but into circulation 2. Mucous neck cells: Secrete mucus, HCO3 and pepsinogen (HCO3 and mucus - protective neutralizing effect on gastric mucosa)

Inhibition of HCl Secretion

1. Inhibited when HCl no longer needed to convert pepsinogen - pepsin when chyme moves to small intestine - decreased pH of gastric contents 2. Food acts as buffer - when moves to small intestine lose buffering capacity - further H+ secretion reduces pH - inhibits gastrin - decreases H+ secretion 3. Major inhibitory factor: Somatostatin Direct: binds to receptors on parietal cells - reduces cAMP levelsantagonizes histamine effects on H+ secretion Indirect: inhibits histamine and gastrin release to reduce stimulatory effects of these peptides Prostaglandins: Antagonize histamine's stimulatory action on H+secretion- inhibit adenylyl cyclase

Intestinal Phase HCL Secretion

10% of total HCl secretion Chyme in duodenum and products of protein digestion stimulates acid secretion

Cephalic Phase HCL Secretion

30% of total HCl secretion -in response to a meal Stimuli for secretion: smelling and tasting, chewing, swallowing and conditioned reflexes in anticipation of food 2 mechanisms promote HCl secretion: 1. Direct stimulation of parietal cell by vagus nerve - Ach release 2. Indirect stimulation of parietal cells by gastrin- vagal release of GRP

Gastric Phase HCL Secretion

60% of total HCl secretion in response to meal Stimuli for secretion: (i) Distension of stomach (ii) Protein breakdown products - amino acids and small peptides 4 secretory mechanisms: 1. Distension causes direct vagal stimulation of parietal cells 2. Distention causes indirect stimulation of parietal cells by gastrin 3. Distension of antrum involves local reflexes that stimulate gastrin release 4. Direct effect of amino acids and peptides on G cells to stimulate gastrin FYI - Alcohol and caffeine stimulate HCl secretion

What are agonists of parietal cell HCl secretion?

Acetylcholine (neurocrine) Gastrin (endocrine) Histamine (paracrine) Gastrin-releasing peptide (GRP), which acts to increase gastrin secretion

Acetylcholine

Acetylcholine is released by cholinergic nerve terminals of the vagus nerve, act on M3 muscarinic receptors to increase intracellular IP3 and Ca2+ via the Gq pathway. The vagus nerve can thus increase gastric acid secretion through direct action on parietal cells (acetylcholine), or indirectly through gastrin and histamine.

By what method of transport do amino acids cross the basolateral membrane of enterocytes into the bloodstream?

Amino acids then traverse the basolateral membrane into the bloodstream by facilitated diffusion.

What enzyme catalyzes the reaction producing gastric acid? In which cells does this reaction take place?

Carbonic anhydrase in parietal cell cytosol catalyzes the reaction CO2 + H2O → H+ + HCO3-.

3 phases of HCL secretion stimulation

Cephalic Phase Gastric Phase Intestinal Phase

Tagamet is a drug used to prevent H+ secretion. Which one of the following does Tagamet actively block?

H2 receptor

Upon entering the duodenum, which two components of chyme cause inhibition of gastric secretions?

Chyme entering the duodenum contains lipids from fat digestion as well as hydrochloric acid (HCl). These lipid degradation products along with the pH-lowering effect of HCl within chyme causes inhibition of gastric secretion.

H2 receptor blockers

Cimetidine (Tagamet) Ranitidine (Zantac) inhibit gastric acid secretion

4 Major components of Gastric Mucosal Cells

HCL, IF, Pepsinogen, Mucus

Parietal Cells and HCl Secretion

Function: Secretion of HCl to acidify gastric contents between pH 1-2 converts inactive pepsinogen to active pepsin for protein digestion

Pepsinogen Secretion

Group I: secreted by chief and mucous cells in oxyntic glands when pH of gastric contents is lowered by H+ secretion - conversion to pepsin - begin protein digestion Secretion increased by vagal stimulation (ACh most potent); H+ also triggers local reflexes which stimulate chief cells, pepsinogen secretion Group II: secreted throughout the stomach and by Brunner's glands in duodenum

What is the transporter responsible for the secretion of gastric acid?

H+ is secreted by parietal cells of the stomach in an active process mediated by H+/K+-ATPase. Chloride is secreted through a separate channel to combine with H+ from the H+/K+-ATPase to form HCl.

What glycoprotein secreted by gastric parietal cells is necessary for B-12 absorption?

Intrinsic factor (IF) is secreted by gastric parietal cells and is essential for B12 absorption.

Mucous cells secrete what ion that acts to protect the gastric mucosa?

Mucous cells mainly secrete HCO3- that remains trapped in mucus and acts to protect the gastric mucosa.

Intestinal Phase

Occurs in the presence of chyme in the duodenum, causing initial stimulation and subsequent inhibition of gastric acid secretion.

Inhibits H+- K+ATPase

Omeprazole

Gastric Cells

Oxvntic (acid secreting) Glands - body of stomach - empty secretory products via ducts into lumen of stomach - openings of duct = pits

Which pancreatic enzymes degrade lipids to free fatty acids and monoglycerides?

Pancreatic lipases degrade lipids to free fatty acids and monoglycerides, which combine with cholesterol and bile acids to form micelles.

Which cells secrete pepsinogen?

Pepsin, which is secreted as pepsinogen by chief cells of the stomach, initiates the degradation of proteins to peptides in the stomach.

What is the primary function of gastrin? Through which intracellular signaling pathway does it act? What neuropeptide directly stimulates gastrin release?

Produced by G cells, primarily acts on potentiating histamine release by ECL cells. In addition, it reaches parietal cells through the bloodstream to increase intracellular IP3 and Ca2+ via the Gq pathway. Gastrin is stimulated by vagus nerve release of gastrin releasing peptide (GRP), protein digestion products in the stomach, and gastric distention.

Histamine

Produced by enterochromaffin-like (ECL) cells in the mucosa, is released when stimulated by gastrin. Histamine binds to H2 receptors on parietal cells and increase cAMP via the Gs pathway. The H2 receptors can be targeted via histamine blockers (ranitidine, famotidine, cimetidine).

Gastric Muscosal Barrier

Protective mucus gel on luminal surface of stomach with alkaline secretions entrapped within it. Prevents damage to mucosa by gastric contents. Mucus slows diffusion of acid and pepsins to epithelial cell surface

Which enzyme is the target of proton pump inhibitors?

Proton pump inhibitors (omeprazole, pantoprazole) target the H+/K+-ATPase.

How does somatostatin decrease stomach acid secretion?

Somatostatin inhibits acid secretion by inhibiting adenylyl cyclase and decreasing cAMP levels in parietal cells via the Gi pathway. In addition, somatostatin also acts inhibits acid secretion indirectly by inhibiting release of histamine and gastrin.

H+ is pumped into the gastric lumen in exchange for which ion?

The H+/K+-ATPase pumps 1 K+ ion into the cell in exchange for 1 H+ ion that goes into the gastric lumen.

The cephalic phase of gastric acid secretion is mediated by what nerve?

The cephalic phase occurs before food reaches stomach, and is mediated by vagus nerve stimulation from chewing and swallowing.

The gastric phase of gastric acid secretion involves what two stimuli?

The gastric phase occurs in the presence of food in stomach, stimulated by stomach distention and presence of protein and amino acids. This phase is mediated by cholinergic local and central reflexes, such as the nerves that run through the vagus nerve (vagovagal reflexes).

The intestinal phase of gastric acid secretion involves what stimuli?

The intestinal phase occurs in the presence of chyme in the duodenum, causing initial stimulation and subsequent inhibition of gastric acid secretion.

Pernicious anemia

absence of intrinsic factor. Inability to form mature RBCs oxyntic cell mass is greatly reduced and acid secretion is very low (achlorhydria)