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Mechanism Of Gastric Secretion

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Mulyaningsih
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3415150046
Types of Gastric Glands and Cells
• Gastric cells • Gastric glands
1. Mucous neck cells (secrete 1. The oxyntic glands (80% of
mucus) gastric glands)-body and fundus
2. Surface epithelial cells 2. Pyloric glands (20% of gastric
(secrete mucus) glands)- antrum region
3. Chief cells (secrete
pepsinogen)
4. G cells (secrete gastrin - in
antrum)
5. Parietal (oxyntic) cells (secrete
HCl and intrinsic factor)
6. Enterochromaffin-like-cells
(ECL) secrete histamine.
Mucosal Protection Of Gastric Epithelium

• Mucus layer on gastric surface forms a mucosal barrier against damage to gastric
epithelium
• a gel about 1 mm thick
• secreted by neck cells, surface epithelium
• release is stimulated by acetylcholine from nerve endings
• also rich in bicarbonate
• HCO3- content creates a "micro-environment" around surface cells to prevent
acid damage
• HCO3- secretion is inhibited by adrenergic input (prominent in stress!)
• Prostaglandins are protective agent (increase mucus production and blood flow)
• inhibition of enzymes involved in prostaglandin production (cyclo-oxygenases
=COX) by NSAIDs (non-steroidal anti-inflammatory drugs) such as aspirin,
ibuprofen, etc. results in gastric damage
Gastric Mucous layer
• The surface epithelial cells of the
stomach secrete thick insoluble,
unstirred mucus that lines the
surface of the stomach.

• This mucus contains glycoproteins that


form an almost gelatinous coating which
contains relatively high concentrations of
bicarbonate ion.
• This coating protects the stomach
epithelium from gastric acid and pepsin.
• Glycosylation of mucin makes it relatively
resistant to proteolysis by pepsin.
HCl Secretion
Three chemicals stimulate production of HCl from
parietal cells:

1. Acetylecholine: released from cholinergic nerve


fibres (parasympathetic)
- acts on muscarinic receptors (M3 )

2. Gastrin: released from G cells of pyloric glands acts


on G receptors

3. Histamine: released from enterochromaffin-like-cells


(ECL) and mast cells. It acts on H2 receptors
(activates adenyl cyclase enzyme). inhibited by H2
receptor antagonists (eg. cimetidine)
EFFECT of parietal stimulation by
-ECL are stimulated by gastrin and acetylcholine the three stimulants are:
**more H+/K+-ATPase
** each one of the three stimulants insertion in membrane
potentiates the effects of the others **more Cl- channels insertion
Mechanism H+ and Cl- Secretion
• The stomach’s parietal cells actively secrete H+ and Cl- by the actions of two separate pumps
• Hydrogen ion is secreted into the lumen by a primary H+ - K+ ATPase active-transport pump at
the parietal cell’s luminal border.
• The K+ transported into the cell by the pump promptly exits through a luminal K+ channel, thus
being recycled between the cell and lumen
• The secreted H+ is derived from the breakdown of H2O into H+ and OH- Catalyzed by carbonic
anhydrase, the OH- combines with CO2
to form HCO3-
• Chloride is secreted by secondary active transport. Driven by the HCO3- concentration gradient, a
Cl- antiporter
in the basolateral membrane transports HCO3- down its concentration
gradient into the plasma and simultaneously transports Cl- into the parietal
cell against its concentration gradient.
• Chloride secretion is completed as the Cl- that entered from the plasma diffuses out of the cell
down its electrochemical gradient through a luminal Cl- channel into the lumen
Regulation of Pepsinogen Secretion

1. Stimulation of chief cells by acetylcholine released from


a. Vagus nerve endings
b. Gastric enteric nervous plexus
2. Presence of acid in the stomach: through eliciting enteric reflexes.
Absence or less acid secretion will cause less pepsinogen
formation
Phases of Gastric Secretion
1. Cephalic Phase: Occurs before food enters stomach~30% of total
secretion, direct vagal stimulation + gastrin
release

2. Gastric Phase : Occurs while food is in stomach >60% of total


secretion, Involvement of: vagal and enteric nerves
paracrine (local) hormones (histamine) endocrine
hormones (gastrin), Gastrin secretion is inhibited
at lumen pH <2

3. Intestinal phase: Occurs after food enters small intestine,Largely


hormonal: - stimulatory effects (gastrin)
- inhibitory effects (secretin, GIP,
cholycystokinin)

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