Bilirubin - Questions and Casuistry

Make sure to read all the correct answers thoroughly!

Click on the blue button "expand" to see the answers with further explications

For more information see Jaundice (icterus).

Questions

1. Which type of bilirubin has a toxic effect on the basal ganglia?

A — conjugated (direct) bilirubin

B — unconjugated (indirect) bilirubin bound to albumin by van der Waals force
C — bilirubin that is covalently bound to albumin
D — free-of-bound bilirubin (does not bind to albumin)

2. Ligandin is a small protein enabling:

A — conjugation of bilirubin and glucuronic acid, first creating bilirubin glucuronide and then diglucuronide
B — transfer of bilirubin on the intracellular site into the smooth ER of a hepatocyte
C — transfer of conjugated bilirubin through the "bile pole" to the primary bile capillaries
D — a covalent bond between bilirubin molecule and albumin

Answers

Otázka 1.

A — incorrect — conjugated bilirubin can be dissolved in an aqueous solution; therefore it can be excreted in bile; only unconjugated bilirubin can cross the hematoencephalic barrier
B — incorrect — unconjugated bilirubin that is albumin-bound does not cross the hematoencephalic barrier (the molecule is too big to come through) - cannot endanger the basal ganglia
C — incorrect — bilirubin that is covalently bound to albumin cannot infiltrate through the hematoencephalic barrier

D — CORRECT — "a free-of-bound" bilirubin, can easily enter through the barrier and dissolve in lipid substances (phospholipids) of the basal ganglia, causing the alteration of the physiological function that may lead to a complete destruction

Otázka 2.

A — incorrect — the glucuronidation reaction behind the conjugation of bilirubin and glucuronic acid is catalyzed by the enzyme UDP-glucuronosyltransferase

B — CORRECT — the bilirubin-albumin complex "trapped" on the membrane of hepatocyte dissociates; "free" bilirubin crosses the membrane; in the cytoplasm, it binds to the transfer protein, which is ligandin, and in this form, the transport is operated to the smooth ER, where glucuronidation occurs

C — incorrect — although conjugated bilirubin needs a transferring ligand at the apical part of the hepatocyte, it is provided by MRP2 (synonym for ABCC2)
D — incorrect — a covalent bond between bilirubin and albumin does not require the presence of any small protein

Casuistry

1. Jaundice in an adult patient

A 42-year old man with severe icterus, abdominal pain localized in the upper right abdominal area, pale, fever, and shivers.

Lab. test results:

ALP = 8,4 μkat/l
cholesterol = 7,9 mmol/l (5-nukleotidáza – zvýšená hodnota)
AST = 0,64 μkat/l
total bilirubin = 421 μmol/l
prothrombin time: prolonged, physiological after intravenous application of vitamin K

Questions:

According to the clinical evidence given, what is probably the origin of jaundice (icterus) in the patient?
Why is the prothrombin time prolonged?

Answers

Extrahepatic obstruction (possible causes - gallstones and bile duct stones (cholelithiasis), tumor in the head of the pancreas, postoperative stricture, wedged parasite)
Avitaminosis due to vitamin K deficiency (crucial for coagulation) - there might be a lack of this fat-soluble vitamin due to fat malabsorption, or a complete restriction of lipids in a diet

2. Patient with jaundice and nausea

A patient has been admitted for an unintentional significant weight loss in a short period of time, severe nausea, vomiting, and later on developed jaundice and hepatomegaly

Lab. test results:

total bilirubin = 342 μmol/l
conjugated bilirubin = 171 μmol/l
ALP = 2,2 μkat/l
AST = 12,4 μkat/l
ALT = 11,2 μkat/l
albumin = 22 g/l
γ-globulin = 23,8 g/l (34 % of total proteins)

Questions:

According to the clinical evidence, what is probably the cause of his condition; are there any other examinations you would suggest for a better differential diagnosis?

Answer

apparently, it could be hepatocellular damage either for viral hepatitis, alcoholic hepatitis, or toxic substances (e.g. trichloroethylene, toluene ...). The diagnosis can be clarified by examination of specific antigens and antibodies against viral hepatitis; also liver biopsy might be indicated due to the ambiguity of symptoms

References

Source

MASOPUST, Jaroslav – PRŮŠA, Richard. Patobiochemie metabolických drah. 1. edition. Prague : Charles University, 1999. 125–126 pp. pp. 182. ISBN 80-238-4589-6.