Page 154 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Ulcer
The H + ions in gastric juice are secreted by c In addition, the epithelium itself (apical
+
+
the parietal cells that contain H /K -ATPase cell membrane, tight junctions) has barrier
in their luminal membrane, while the chief properties that largely prevent the penetra-
+
cells enrich the glandular secretion with pep- tion of H ions or can very effectively remove
+
sinogen (→ A). The high concentration of H + those H ions that have already penetrated
+
+
(pH 1.0–2.0) denatures the food proteins (Na /H exchange carrier only basolaterally).
and activates pepsinogens into pepsins which These properties are regulated, among oth-
are endopeptidases and split certain peptide ers, by the epidermal growth factor (EGF) con-
bindings in food proteins. tained in saliva and bound to receptors of the
The regulation of gastric secretion (→ A1) apical epithelial membrane. Glutathione-de-
Liver is achieved through neural, endocrine, para- pendent, antioxidative mechanisms are also
crine, and autocrine mechanisms. Stimula-
part of this cytoprotection.
Stomach, Intestines, ganglionic transmitter of vagal parasympa- the last “line of defense” that, among other
tion is provided by acetylcholine, the post-
d Finally, good mucosal blood flow serves as
+
actions, quickly removes H ions and pro-
thetic fibers (muscarinic M 1 receptors and
–
via neurons stimulating gastrin release by
vides a supply of HCO 3 and substrates of en-
ergy metabolism.
gastrin-releasing peptide [GRP]), gastrin (en-
Epithelial repair and wound healing. The
docrine) originating from the G cells of the
fects that occur despite the protective factors
tor), secreted by the ECL cells and mast cells
of the gastric wall. Inhibitors are secretin (en-
listed above (→ B, bottom left):
6 antrum, and histamine (paracrine, H 2 recep- following mechanisms repair epithelial de-
docrine) from the small intestine, somato- The epithelial cells adjoining the defect
statin (SIH; paracrine) as well as prostaglan- are flattened and close the gap through side-
dins (especially E 2 and I 2 ), transforming ward migration (→ p. 4) along the basal
growth factor α (TGF-α) and adenosine (all membrane. This restitution takes about 30
paracrines and autocrines). The inhibition of minutes.
gastric secretion by a high concentration of Closing the gap by cell growth takes long-
+
H ions in the gastric lumen is also an impor- er (proliferation; → p. 4). EGF, TGF-α, insulin-
tant regulatory mechanism (negative feed- like growth factor (IGF-1), gastrin-releasing
back; → A1, left). peptide (GRP), and gastrin stimulate this
Protection of the gastric and duodenal process. When the epithelium is damaged,
mucosa. Because the acid–pepsin mixture of especially those cell types proliferate rapidly
gastric secretion denatures and digests pro- that secrete an EGF-like growth factor.
tein, the protein-containing wall of the stom- If ultimately the basement membrane is
ach and duodenum has to be protected from also destroyed, acute wound healing pro-
the harmful action of gastric juice. The fol- cesses are initiated: attraction of leukocytes
lowing mechanisms are involved in this and macrophages; phagocytosis of necrotic
(→ A2): cell residua; revascularization (angiogen-
a A gel-like mucus film, 0.1–0.5 mm thick, esis); regeneration of extracellular matrix as
protects the surface of the gastric epithe- well as, after repair of the basement mem-
lium. The mucus is secreted by epithelial brane, epithelial closure by restitution and
cells (and depolymerized by the pepsins so cell division.
that it can then be dissolved). The danger of epithelial arrosion and sub-
–
b The epithelium secretes HCO 3 ions that sequent ulcer formation exists whenever the
are enriched not only in the liquid layer di- protective and reparative mechanisms are
rectly over the epithelium, but also diffuse weakened and/or the chemical attack by the
into the mucus film, where they buffer H + acid–pepsin mixture is too strong and per-
ions that have penetrated from the gastric lu- sists for too long (→ A3 and B, top). Gastric
144 men. Prostaglandins are important stimu- and duodenal ulcers may thus have quite dif-
–
lants of this HCO 3 secretion. ferent causes.
"
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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