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Lecture Schedule

Tissue Biochemistry: Liver

Learning Objectives and Guiding Questions

Reading assignment: Meisenberg, pp 392-396;456-462.

1. Describe the synthesis of primary bile salts in the liver and their conversion to secondary bile salts in the intestine.

A. Why are the bile acids called bile salts?

B. What are the two primary bile salts and how much of the daily cholesterol production is used up in their synthesis? (pg 392)

C. What are the two secondary bile salts that are derived from the primary bile salts? How does this conversion occur?

D. What are the bile salts conjugated with? What is conjugation anyway and what does it accomplish?

2. Outline the symptoms and cause of acute intermittent porphyria (AIP).

A. What is porphyria? What is one of the most likely causes of acute intermittent porphyria?

B. What are the symptoms of AIP? Why isn’t photosensitivity one of the symptoms? (pg 457) Is porphobilinogen a protoporphyrin? A porphyrin?

C. What two compounds accumulate in AIP? (pg 456)

3. Describe the general composition of bile.

4. Describe the process of enterohepatic circulation of bile acids.

A. What is the enterohepatic circulation?

B. How do the intestinal contents get recirculated back to the liver?

C. Are unconjugated bile acids reabsorbed to a greater extent than conjugated? How do the bile acids get unconjugated in the gut?

D. How does the absorption of deoxycholic acid compare with lithocholic acid?

E. Can reabsorbed bile acids be reconjugated?

F. What would happen if you prevented the reabsorption of bile acids? (pg 416) Can you say choleSTYramine?

5. Outline the process of bilirubin formation from heme.

A. Where does bilirubin formation occur?

B. How many steps are required for bilirubin formation? How many for biliverdin formation?

C. What is heme oxygenase and what does it do to heme?

D. What coenzyme does biliverdin reductase require?

6. Explain the hepatic uptake and conjugation of bilirubin.

A. How is bilirubin transported in the blood?

B. What does ligandin in hepatocytes do?

C. How is bilirubin conjugated in the hepatocyte? Why is it conjugated? What precursor molecule is used for the conjugation and what is the conjugation product called?

D. What form is urinary bilirubin in? (Say that last part real fast)

7. Outline the enterohepatic circulation of bilirubin.

A. What is bile pigment? How much of it is conjugated?

B. How is urobilinogen formed? Are you keeping bile salt thinking and bilirubin thinking separate? Good.

C. So, how much urobilinogen is reabsorbed and how much of that is re-excreted?

D. What happens to the little bit of urobilinogen that gets into the bloodstream?

8. Explain cholestasis in terms of what it is, what causes it, and the ways it is manifested.

A. What does the word cholestasis mean?

(Cholecyst, choler, cholera, and cholesterol all share the root word chole from the Greek for bile. Cholecyst is a term for the gall bladder. Choler was believed to be one of the four humors of the body from medieval times. It represented anger and irritability. Cholera was named after choler due to the symptoms of nausea and diarrhea and its relationship to the digestive tract. Cholesterol is a major component of bile and is the main constituent of gallstones. Stasis is Greek for standing and refers to a stoppage of flow.)

B. What are the two causes of cholestasis?

C. What are three causes of biliary obstruction?

D. How does obstructive cholestasis differ from intrahepatic cholestasis?

E. What are some of the biochemical manifestations of cholestasis? What kind of bilirubin is elevated in the blood? What happens to the excretion of urobilinogen? How about the bile acids? What effect does this have on absorption of fat soluble vitamins? Does all of this lead to a fatty stool? Let’s change the subject.

F. So, how about that serum alkaline phosphatase?

9. Describe the process of cholelithiasis. (lithos is Greek for stone; the first lithographs were done with stone before metal plates were used.)

A. What is cholelithiasis? What two steps are required for it to happen?

B. What are the factors that determine whether bile is lithogenic? What role do phospholipids play? Do bile salts play the same role?

C. What would be the source of pigment gallstones?

D. What does nidation mean?

10. Explain the causes and outcomes of hepatic inflammation and necrosis.

A. What type of infection or toxicity can produce hepatic inflammation and/or necrosis?

B. Can elevated bilirubin in the blood appear in the urine? What form would it be in, conjugated or not?

C. Which serum enzymes are elevated?

D. Why would blood clotting be impaired?

(This is a really important clinical correlation that will be repeated many times in the medical curriculum. The liver has so many different functions, such as synthesis of clotting factors, that hepatitis patients are vulnerable to all sorts of complications.)

E. Are bile acids elevated in the serum?

11. Describe jaundice and its basic classification.

A. What is jaundice otherwise known as icterus?

(Icterus was not the guy who flew too close to the sun while trying to escape from Greece, icterus is a Greek word that means jaundice. If Icarus’ dad, Daedalus, had used a wax with more trans fatty acids it would have raised the melting point and saved his wings. Can you name two other ways to raise the melting point of a fat?)

B. What is prehepatic jaundice? What happens to bilirubin conjugation during excessive hemolysis?

C. How are the urinary and fecal urobilinogen levels affected by increased ineffective erythropoiesis? Why is the urinary urobilinogen level increased?

D. Is all of the bilirubin that is produced excreted in the conjugated form?

E. What is posthepatic jaundice? How does this affect conjugation? What are some of the etiologic agents? What is the effect on bilirubin excretion? Would this cause a decrease in urobilinogen? What about urine urobilinogen?

F. What is the Crigler-Najjar syndrome? What is it due to? Does this raise or lower the unconjugated bilirubin levels? What is kernicterus?

12. Explain how you can tell the difference between prehepatic and posthepatic jaundice.

A. Why would urobilinogen in the urine and feces indicate non-obstructive jaundice?

B. What happens to fecal and urine urobilinogen in obstructive jaundice?

C. What factors could cause the conjugated bilirubin levels in the blood to exceed renal capacity for excretion?

D. What is the Lucey-Driscoll syndrome? Is this a permanent condition? Can it lead to kernicterus?

13. Describe the bilirubinuria that accompanies cholestatic jaundice.

A. Which fraction of bilirubin shows up in the urine? What does this indicate about the fraction of bilirubin that has been elevated in the blood?

14. Explain the purpose and the basis for tests of excretion and detoxification.

A. How is bilirubin measured? (page 460) How do you tell the difference between direct reacting and indirect reacting bilirubin?

B. How do you determine urobilinogen?

15. Explain the purpose and the basis for tests for patency of the biliary tract.

A. What does patency mean?

(No, God didn’t register it with the patent office. It comes from the Latin, patere meaning 'to be open')

B. How is serum alkaline phosphatase associated with biliary patency?

C. What do serum bile acid measurements help to detect?

16. Explain the basis for tests for hepatocellular damage.

A. Which serum transaminases are diagnostic for hepatocellular damage? (Usually, more than two drinks of an alcoholic beverage will cause a small elevation in the ALT; don’t let the DPS find out!)

B. Which liver enzyme has isoenzyme forms that can be distinguished from other tissues like heart?

Last revised 10/04/99