Page 174 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Gallstone Disease (Cholelithiasis)
In about 75% of patients, gallstones consist of (→ B, right), the [Ch]/[BS + Pch] ratio increas-
cholesterol (more women than men are af- es when bile salt secretion is low. This ratio
fected in this way), the rest are so-called pig- rises further under the influence of estrogens,
ment stones that contain unconjugated bili- because they cause an increase in the con-
rubin in the main. What the two types of centration ratio of cholate to chenodeoxy-
stone components have in common is that cholate (activation of 12α-hydroxylase; → B,
they are poorly soluble in water. left), so that more cholesterol is secreted per
Cholesterol (Ch) is normally not precipi- mol bile salts (→ B; compare the two curves).
tated in bile, because it contains sufficient ! A reduced secretion of phosphatidylcho-
conjugated bile salts (BS) and phosphatidyl- line as a cause of cholesterol stones has been
Liver choline (Pch = lecithin) for it to be in a micel- found in Chilean women who live almost ex-
clusively on vegetables.
lar solution (→ A4, green area). If the concen-
Stomach, Intestines, remain, within a small range, in a “supersat- Pigment stones (→ C) consist to a large ex-
tration ratio [Ch]/[BS + Pch] increases, Ch will
tent (ca. 50%) of calcium bilirubinate, which
urated” micellar solution (→ A4, orange
gives them their black or brown color. The
area). This apparent supersaturation is prob-
black stones additionally contain calcium car-
ably based on the liver also secreting choles-
bonate and phosphate, while the brown
terol in a highly concentrated form within
gallbladder (→ A2) in such a way that Pch
cholesterol. A raised amount of unconjugat-
ed bilirubin in the bile, which “dissolves”
makes up the solution-aiding “peel” of this
6 the “nucleus” of a unilamellar vesicle in the stones also contain stearate, palmitate, and
vesicle, 50–100 nm in diameter. If the rela- only in micelles, is the main cause of pigment
tive cholesterol content increases further, stone formation; normally bile contains only
multimicellar vesicles are formed (up to 1–2%. The causes of an increased concentra-
1000 nm). They are less stable and give up tion of unconjugated bilirubin are (→ C):
cholesterol that is then precipitated in the ! Increased liberation of hemoglobin, for
aqueous environment in the form of choles- example, in hemolytic anaemia, in which
terol crystals (→ A2; → A4, red area). These there is so much bilirubin that the glucuroni-
crystals are the precursors of gallstones. dase-mediated process of conjugation in the
Important causes of an increased [Ch]/ liver does not meet demand (→ p.169);
[BS + Pch] ratio are: ! Reduced conjugating capacity in the liver,
! Increased cholesterol secretion (→ A2). for example, in liver cirrhosis (→ p.172);
This will occur because there is either an in- ! Nonenzymatic deconjugation of (especially
creased cholesterol synthesis (raised activity monoglucuronated) bilirubin in bile;
of 3-hydroxy-3-methylglutaryl [HMG]-CoA- ! Enzymatic deconjugation (β-glucosidase)
cholesterol reductase), or an inhibition of by bacteria.
cholesterol esterification, for example, by pro- The latter is almost always the cause of
gesterone during pregnancy (inhibition of brown pigment stones. The bacteria also en-
acetyl-CoA-cholesterol-acetyl transferase zymatically deconjugate the bile salts (de-
[ACAT]). creased micellar formation with cholesterol
! Reduced bile salt secretion (→ A1). This is precipitation) and additionally liberate, by
due to either a decrease in the bile salt pool, as means of its phospholipase A 2 , palmitate
in Crohn’s disease or after gut resection, or a and stearate (from phophatidylcholine)
prolonged sequestration of bile salts in the which precipitate as calcium salts. Black
gallbladder, as in fasting (possibly even if stones, mainly formed by the first three of
only overnight) or parenteral nutrition. The the above mechanisms, contain in addition
latter decreases the enterohepatic circula- to other compounds, calcium carbonate and
tion of bile salts so that their secretion into phosphate, these latter presumed to be
164 the bile is reduced. As cholesterol secretion formed by the gallbladder’s decreased capac-
is not linearly related to bile salt secretion ity to acidify.
"
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
All rights reserved. Usage subject to terms and conditions of license.