Lecture 27 - Liver 2

Question 1

What are the two main pathological states that lead to hepatic insufficiency?

Answer 1

1. Disorder that immediately destroys hepatocytes 2. Porto-systemic shunt - leads to hypoxia and decreased nutrients causing death of hepatocytes

Question 2

What causes prehepatic un-conjugated hyperbilirubinaemia and how does this affect amount of bilirubin that is excreted by the liver, the amount of bilirubin that reaches the intestine and amount of urobilinogen?

Answer 2

Increased production of bilirubin. Increased amount of bilirubin excreted by liver, increased bilirubin reaching the intestine, increased urobilinogen in the urine

Question 3

What are the two potential causes of mixed hyperbilirubinaemia?

Answer 3

1. intrahepatic cholestasis 2. extrahepatic bile duct obstruction

Question 4

Briefly explain how fasting causes hyperbilirubinaemia in horses:

Answer 4

the receptor in hepatocytes for fatty acids is the same as that for bilirubin - hence decreased conjugation of bilirubin

Question 5

What is the pathogenesis of obstructive hyperbilirubinaemia?

Answer 5

Conjugated bilirubin in blood –> saturation of bilirubin receptors on hepatocytes –> unconjugated bilirubin uptake is impaired

Question 6

What is the pathogenesis of functional hyperbilirubinaemia?

Answer 6

1. increased TNFa 2. Decreased bile acid transport in hepatocyte membranes 3. Causes decreased conjugated bilirubin secretion

Question 7

Explain how the bilirubin profile would appear in heamolytic disorders:

Answer 7

large increase in bilirubin with a slight increase in conjugated bilirubin

Question 8

How would the bilirubin blood work appear in cases of fasting hyperbilirubinaemia?

Answer 8

large increase in unconjugated bilirubin and slight increase in conjugated

Question 9

How would the bilirubin blood work appear in cases of hepatocellular dysfunction with concurrent cholestasis?

Answer 9

increased conjugated bilirubin and increased unconjuagted bilirubin

Question 10

How does OBSTRUCTIVE CHOLESTASIS bilirubin appear on blood work?

Answer 10

increased conjugated bilirubin and slight increase in unconjugated bilirubin

Question 11

How does FUNCTIONAL CHOLESTASIS appear on blood work?

Answer 11

increased conjugated bilirubin and slight increase in unconjuagted bilirubin

Question 12

What are the four main differentials for increased serum bile acids?

Answer 12

Decreased BA clearance from portal blood: decreased functional hepatic mass or portosystemic shunt Decreased BA excretion in the bile: Obstructive or functional cholestasis

Question 13

Does a fasting sample have any impact upon serum bile acids in a horse?

Answer 13

No

Question 14

What are some limitations of bile acid challenge tests?

Answer 14

Spontaneous contraction of the gall bladder pre-prandially may increase serum bile acids

Question 15

Briefly recap the ammonium cycle:

Answer 15

1. NH4+ is produced mainly in small intestine by bacterial metabolism 2. NH4+ then enters hepatocytes and is used in synthesis of urea 3. Urea diffuses from hepatocytes into blood

Question 16

What are the mechanisms that can result in decreased NH4+ clearance from the portal blood?

Answer 16

Decreased NH4+ clearance from portal blood:

1. Decreased functional mass - diffuse hepatocellular disease
2. Decreased portal blood flow to liver - congenital/acquired portosystemic shunts
3. Cobalamin deficiency - less fixation NH4+ into urea

Increased NH4+ production:

1. Post prandial
2. Intestinal disease in the horse

Question 17

Name the finding that is shown below and what may cause it (BONUS! - what species would this be considered COMPLETELY NORMAL?):

Answer 17

Ammonium biurate crystals - seen as a result of azotaemia - completely normal in dalmations

Question 18

What is hepatic encephalopathy?

Answer 18

Syndrome of cerebral function distrubance cause by hyperammonemia

Question 19

Why is decreased urea seen with hepatic insufficiency?

Answer 19

The urea cycle occurs within the hepatocytes

Question 20

Why is an albumin deficiency not seen with acute hepatic failure?

Answer 20

Albumin has a long half life - 3 weeks

Question 21

Why is hypoglycaemia seen with hepatic insufficiency?

Answer 21

Decreased functional mass means decreased gluconeogenesis and glycogenolysis –> decreased insulin clearance

Question 22

What condition could lead to hypercholesterolemia?

Answer 22

cholestasis

Question 23

What condition could lead to hypocholestrolemia?

Answer 23

End stage liver insufficiency