Page 178 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Jaundice (Icterus) Cholestasis
Bilirubin, largely originating from hemoglo- Cholestasis (→ A,B), i.e., blockage of bile flow,
bin breakdown (ca. 230 mg/d), is taken up is due to either intrahepatic disorders, for ex-
by the liver cells and coupled by glucuronyl ample, cystic fibrosis (→ p.162), granuloma-
transferase to form bilirubin-monoglucuro- tosis, drug side effects (e.g., allopurinol, sul-
nide and bilirubin-diglucuronide. This wa- fonamides), high estrogen concentration
ter-soluble conjugated (direct reacting) bili- (pregnancy, contraceptive pill), graft versus
rubin is secreted into the bile canaliculi and host–reaction after transplantation, or, sec-
85% is excreted in the stool. The remaining ondarily, extrahepatic bile duct occlusion
15% is deglucuronated and absorbed in the (see above).
intestine for enterohepatic recirculation. In cholestasis the bile canaliculi are en-
Liver bin is maximally 17 µmol/L (1 mg/dL). If it larged, the fluidity of the canalicular cell
The normal plasma concentration of biliru-
membrane is decreased (cholesterol embed-
Stomach, Intestines, come yellow; if the concentration rises fur- deformed (or totally absent) and the function
ding, bile salt effect), their brush border is
rises to more than 30 µmol/L, the sclera be-
of the cytoskeleton, including canalicular
ther, the skin turns yellow as well (jaundice
motility, is disrupted. In addition, one of the
[icterus]). Several forms can be distin-
two ATP-driven bile salt carriers, which are
guished:
meant for the canalicular membrane, is
! Prehepatic jaundice is the result of in-
brane in cholestasis. In turn, retained bile
hemolysis (hemolytic anemia, toxins), inade-
salts increase the permeability of the tight
quate erythropoiesis (e.g., megaloblastic an-
6 creased bilirubin production, for example, in falsely incorporated in the basolateral mem-
emia), massive transfusion (transfused ery- junctions and reduce mitochondrial ATP syn-
throcytes are short-lived), or absorption of thesis. However, it is difficult to define which
large hematomas. In all these conditions un- of these abnormalities is the cause and
conjugated (indirect reacting) bilirubin in which the consequence of cholestasis. Some
plasma is increased. drugs (e.g., cyclosporin A) have a cholestatic
! Intrahepatic jaundice is caused by a action by inhibiting the bile salt carrier, and
+
+
specific defect of bilirubin uptake in the liver estradiol, because it inhibits Na -K -ATPase
cells (Gilbert syndrome Meulengracht), con- and reduces membrane fluidity.
jugation (neonatal jaundice, Crigler–Najjar Most of the consequences of cholestasis
syndrome), or secretion of bilirubin in the (→ B) are a result of retention of bile compo-
bile canaliculi (Dubin–Johnson syndrome, nents: bilirubin leads to jaundice (in neo-
Rotor syndrome). nates there is a danger of kernicterus), cho-
In the first two defects it is mainly the un- lesterol to cholesterol deposition in skin folds
conjugatedplasma bilirubin that isincreased; and tendons, as well as in the cell mem-
in the secretion type it is the conjugated bili- branes of liver, kidneys, and erythrocytes
rubin that is increased. All three steps may be (echinocytes, akanthocytes). The distressing
affected in liver diseases and disorders, for ex- pruritus (itching) is thought to be caused by
ample, in viral hepatitis, alcohol abuse, drug retained endorphins and/or bile salts. The ab-
side effects (e.g., isoniazid, phenytoin, halo- sence of bile in the intestine results in fatty
thane), liver congestion (e.g., right heart fail- stools and malabsorption (→ p.152ff.). Final-
ure), sepsis (endotoxins), or poisoning (e.g., ly, infection of accumulated bile leads to
the Amanita phalloides mushroom). cholangitis, which has its own cholestatic ef-
! In posthepatic jaundice the extrahepatic fect.
bile ducts are blocked, in particular by gall-
stones (→ p.164ff.), tumors (e.g., carcinoma
of the head of the pancreas), or in cholangitis
or pancreatitis (→ p.158). In these conditions
168 it is particularly conjugated bilirubin that is
increased.
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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