Page 168 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Acute Pancreatitis
Most pancreatic enzymes are activated by mally occurs in the Golgi apparatus, seems
enteropeptidase only when they reach the to be disturbed (→ A5). Thus, the proen-
intestinal lumen. The activation of trypsino- zymes together with the lysosomal proteases
gen to trypsin is a key feature in this, because will be incorporated into the same vesicles,
trypsin activates other enzymes. If it is so that trypsin will be activated there. Trace
activated in the acinar cells, the pancreatic amounts are enough for this, because trypsin
trypsin inhibitor–protein is responsible for can activate itself autocatalytically.
trypsin not being effective there. However, if Trypsin activates other enzymes (phos-
this protective mechanism does not keep up pholipase A 2 , elastase, etc.), clotting factors
with the trypsin activation, or trypsin be- (prothrombin to thrombin), tissue hormones
Liver comes active in the lumen of the pancreatic (bradykinin and kallidin are activated via
kallikrein), and cytotoxic proteins (comple-
duct, self-digestion of the pancreas occurs,
Stomach, Intestines, hol consumption and gallstones in 80% of the computed tomogram) there is at first
ment system). In the pancreas (→ A6; P in
i.e., acute pancreatitis.
Even though there is a history of high alco-
generalized cell swelling (pancreatic edema;
→ A7, P + E). Activated elastase, in particular,
cases, the pathogenetic mechanism is not
causes vessel arrosion with bleeding (hemor-
quite clear. The following possibilities are
rhagic pancreatitis) and ischemic zones in
being discussed as playing a part, either in
enlarged by the formation of thrombi
case:
brought about by thrombin activation, the
! Increased pressure in the pancreatic duct
6 combination or separately depending on the the organ. These ischemic areas are further
(flow resistance and/or flow too high) can result being necrosis. The endocrine islet
play a part in the development of acute pan- cells are also destroyed, causing insulin defi-
creatitis (→ A1). Occlusion of the duct after ciency and thus hyperglycemia. Fat necrosis
the merging of the bile duct (e.g., by a gall- develops around the pancreas with accom-
stone;→ A2) also leads to reflux of bile into panying soap formation, a process that uses
the pancreas, where it damages the duct epi- up Ca 2+ (Ca 2+ sequestration) and also causes
thelium and accelerates fat digestion. hypocalcemia (see below). Mg 2+ ions in the
! While it is unclear, in relation to the above plasma binding to the liberated fatty acids
points, how trypsin is activated, if duodeno- cause hypomagnesemia (→ p.126). All this
pancreatic reflux occurs (e.g., when the duo- damage can spread to neighboring retroperi-
denum is obstructed distally), the enzymes toneal organs, i.e., spleen, mesentery, omen-
activated in the duodenum pass back into tum, duodenum, etc.
the pancreas (→ A3). As the activated enzymes appear in plas-
! Alcohol, acetylsalicylic acid, histamine, ma, where their presence is of diagnostic sig-
etc. increase the permeability of the pancre- nificance, hypoalbuminemia develops with
atic duct epithelium, so that larger molecules resulting hypocalcemia, as well as systemic
can pass through it. Enzymes secreted by the vasodilation and plasma exudation (trig-
acinar cells thus diffuse into periductal inter- gered by bradykinin and kallidin), ultimately
stitial tissue and damage it (→ A4). In addi- ending in circulatory shock. Phospholipase
tion, alcohol in the duct system seems to pre- A 2 and free fatty acids (due to increased li-
cipitate proteins, causing a rise in upstream polysis) in plasma destroy the surfactant on
pressure (→ A4). the alveolar epithelium, causing arterial hyp-
! Research on animal models with acute oxia. Finally, the kidneys will also be dam-
pancreatitis indicates that under some cir- aged (danger of anuria).
cumstances pancreatic enzymes may also be
activated intracellularly. The process of sort-
+
ing out lysosomal enzymes and H -ATPase,
158 on the one hand, and the pancreatic proen-
zymes to be secreted, on the other, as nor-
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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