Page 304 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Histamine, Bradykinin, and Serotonin
Histamine (→ A1) is formed by the tissue mast peptidases and some toxins. Kallikrein pro-
cells and basophils. Its release is stimulated by motes its own activation via stimulation of fac-
antigen–antibody (IgE) complexes (type 1 aller- tor XIIa (→ p. 60). It is broken down very quick-
gy; → p. 48, 52), activated complement (C3a, ly (in < 1 min) in blood by the action of kini-
C5a), burns, inflammation, and some drugs. A nases.
rare cause of increased histamine release can The effects of bradykinin resemble those of
be a mast cell tumor. Histamine release is in- histamine, namely vasodilation, increased vas-
hibited via cAMP by epinephrine, prostaglan- cular permeability, fall in blood pressure,
din E 2 , and histamine itself. tachycardia, increased cardiac contractility,
Histamine causes the endothelial release of raised catecholamine release, and stimulation
NO, a dilator of arteries and veins, via H 1 recep- of bronchial, intestinal, and uterine contrac-
tors and a rise in endothelial cellular Ca 2+ con- tion. In contrast to histamine, however, brady-
centration. Via H 2 receptors it also causes the kinin causes pain at nerve endings. In the gut
dilation of NO-independent small vessels. and glands it promotes secretion, while it acts
This peripheral vascular dilation can lead to a as a diuretic in the kidneys. Bradykinin also
massive fall in blood pressure, despite the his- plays a role in inflammations (especially pan-
Hormones tractility (H 2 receptors), heart rate (H 2 recep- edema), and pain.
tamine-mediated stimulation of cardiac con-
creatitis), edemas (especially angioneurotic
tors), catecholamine release (H 1 receptors),
central nervous system (→ p. 350), serotonin
tors). Histamine increases protein permeabil-
9 and contraction of the larger vessels (H 1 recep- Serotonin. In addition to being formed in the
ity in the capillaries. Plasma proteins are thus (→ B) is formed in the enterochromaffin cells
filtered under the influence of histamine, the of the gut, in thrombocytes, proximal tubular
oncotic pressure gradient across the capillary cells, and the bronchi. Its release is increased
wall falls, and edemas are formed. The edema especially in tumors of the enterochromaffin
fluid is lost at the expense of the plasma vol- cells (carcinoid).
ume, the resulting hypovolemia contributing Serotonin leads to contraction of the
to the fall in blood pressure. Edemas of the smooth muscles in the bronchi, small intes-
glottis can cause asphyxia by occluding the air- tine, uterus, and blood vessels either directly,
way. Histamine, in addition, promotes con- or via the release of other mediators (prosta-
traction of smooth muscle in the intestines, glandins, catecholamines). The effects of these
uterus, and bronchi. This results, among other actions are, among others, diarrhea, broncho-
consequences, in increased airway resistance spasm, and a rise in blood pressure. Neverthe-
(bronchospasm) and abdominal cramps. By less, serotonin can also have a vasodilating ef-
stimulating peripheral nerve endings hista- fect. Its action on blood vessels can cause
mine causes itching. Via H 2 receptors hista- headache (migraine). Serotonin promotes the
mine stimulates the secretion of HCl in the aggregation of thrombocytes; it causes pain,
stomach. H 2 receptor antagonists are effective can increase the permeability of peripheral
in the treatment of gastric ulcers (→ p.144ff.). capillaries, and can produce edemas. The sud-
Histamine is largely responsible for the symp- den flushes that occur with tumors of the en-
toms of type 1 allergy, such as a fall in blood terochromaffin cells are probably due to other
pressure, skin edema (urticaria), rhinitis, and mediators (especially kinins, histamine). The
conjunctivitis. cause of endocardial fibrosis associated with
tumors of the enterochromaffin cells remains
Bradykinin. The enzyme kallikrein is required undetermined. As serotonin is broken down in
for bradykinin synthesis (→ A2). It is formed the liver, the systemic symptoms of serotonin-
from kallikreinogen in inflammations, burns, producing intestinal tumors (such as broncho-
tissue damage (especially pancreatitis; → spasm) commonly occur only after they have
294 p.158), and on activation of blood coagulation metastasized to the liver.
(factor XIIa) as well as under the influence of
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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