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Explain the causes, mechanisms and consequences of the failure of the defences
of the stomach against injury by acid and pepsin acutely.
Regulation of acid secretions.
Regulation of acid secretion is a combination of neural, endocrine
and paracrine control.
Potentiation occurs where the effect of a combination of
stimulants is greater than the sum of the individual responses.
Stimulation of
Description:
parietal cells
secretion by:
Acetylcholine
Ach is released from the vagus nerve acting
(Ach).
through muscarinic M3 receptors.
Gastrin.
Gastrin is released in blood from G cells in the
antrum, in response to acetylcholine.
Gastrin acts through the gastrincholecystokinin receptors on parietal cell.
Histamine.
It is released from enterochromaffin-like (ECL)
cells in the stomach body and acts through
histamine H2 receptors. Both gastrin and Ach
can stimulate histamine release.
o NSAIDs/aspirin
o Bile, alcohol, drugs (chemical injury)
o Stress (shock, burns, severe trauma)
o Head injuries
o Septicaemia,
staphylococcal food poisoning (due to
Causes
o Autoimmune
o H. pylori
o Chemical
Mechanism
o Autoimmune - immune-mediated destruction of acid-secreting tubules
in corpus
o Chemical - reflux of duodenal alkali juices and bile; prolonged NSAID
use
Consequences
o Autoimmune
Achlorhydria (loss of acid production)
Pernicious anaemia (loss of intrinsic-factor production or
intrinsic-factor antibody binding to B12, leading to
malabsorption of vitamin B12)
Hypergastrinaemia (due to loss of feedback of H+ on D cells,
leading to lack of somatostatin production, causing lack of
inhibition of G cells)
Linear/nodular ECL hyperplasia (due to hypergastrinaemia
overstimulating ECLs), occasional carcinoidosis
Production of autoantibodies against parietal cell membrane
H+/K+ ATPase, intrinsic factor and gastrin receptor
o H. pylori
infiltration of chronic inflammatory cells
expression of non-curative antibodies
Loss of parietal cells due to atrophic pan-gastritis leads to loss
of acid production, predisposing to GIT infections (no acid to
kill other bacteria)
Loss of intrinsic factor production leads to B12 pernicious
anaemia
o (General)
Explain the process of inflammation and healing in acute and chronic peptic
ulcers.
Damaged barrier allows H+ to leak back across the epithelium into the lamina
propria
Superficial accumulation of
inflammatory cells
Breach into
submucosa.