Hepatobiliary

Question 1

What are the cytoplasmic liver enzymes?

Answer 1

ALT (alanine transaminase), AST (aspartate transaminase), LDH (lactate dehydrogenase), SDH (sorbitol dehydrogenase)

Question 2

What are the mitochondrial liver enzymes?

Answer 2

AST (aspartate transaminase), GLDH (glutamate dehydrogenase)

Question 3

What is hepatocellular injury?

Answer 3

A non-specific term for reversible or irreversible injury to hepatocytes due to various causes (hypoxia, toxins, infections, neoplasia, etc.). These enzymes are released when hepatocytes are injured, therefore their levels should be increased.

Question 4

Which enzymes are indicators of hepatocellular injury?

Answer 4

ALT (alanine transaminase), AST (aspartate transaminase), LDH (lactate dehydrogenase), SDH (sorbitol dehydrogenase), GLDH (glutamate dehydrogenase)

All will be increased.

Question 5

What are the membrane enzymes?

Answer 5

ALP (alkaline phosphatase), GGT (ɣ-glutamyltransferase)

Question 6

What is cholestasis?

Answer 6

Decreased or ‘ceased’ bile flow (enzymes are induced as a consequence of cholestasis). Remember, bile is toxic so we do not want a build up of this!

Question 7

Which enzymes are indicators of cholestasis?

Answer 7

ALP (alkaline phosphatase), GGT (ɣ-glutamyltransferase), Cholesterol, Bilirubin

All will be increased.

Question 8

What indicates reduced hepatobiliary function?

Answer 8

≥ 70% of liver needs to be non-functional and unable to carry out its metabolic, synthetic and detoxification tasks. Hepatic markers are either not being produced OR not being removed properly from circulation.

Question 9

What are the indicators of hepatobiliary function?

Answer 9

Albumin, Cholesterol, Glucose, Urea/BUN, Coagulation factors

All will be decreased.

Question 10

With hepatocellular injury, can increased enzyme activities distinguish between reversible or irreversible change?

Answer 10

The degree of increases in enzymes may relate to the severity of the damage, but increased enzyme activities cannot distinguish between reversible or irreversible change.

Question 11

True or False: Serum liver enzyme activities can be indicators of pathology, BUT are NOT specific to any disease.

Answer 11

True.

Question 12

What is the best marker of hepatocellular injury in dogs and cats?

Answer 12

ALT

Exam question.

Question 13

What is the best marker of hepatocellular injury in large animals?

Answer 13

GLDH.

Question 14

Which marker is a poor indicator of hepatocellular injury in cattle and horses?

Answer 14

ALT

Exam question.

Question 15

What is the best marker of hepatocellular injury in exotics?

Answer 15

GLDH.

Question 16

What is the best marker of cholestasis in dogs?

Answer 16

ALP (this enzyme will be increased before icterus presents itself).

Question 17

Which marker is a poor indicator of cholestasis in cats and horses?

Answer 17

ALP (cats and horses are icteric before ALP activity increases). Therefore increased ALP means the cholestasis is chronic.

Question 18

Which enzyme must always be interpreted in conjunction with CK and why?

Answer 18

AST because muscle is a source of AST as well as the liver, so you must determine the origin.

If AST is elevated, check CK. If CK is elevated then it’s likely not liver disease and it’s a muscle problem. If CK is normal, then the AST is truly due to liver damage.

Question 19

What are two other causes for ALP elevations?

Answer 19

1. Increased osteoblastic activity (growth) (dogs)
2. Hyperthyroidism (cats)

Question 20

What is another reason why GGT may be elevated?

Answer 20

With puppies, foals, and calves that are taking in colostrum.

Question 21

True or False: Icterus is always associated with cholestasis.

Answer 21

False!

Question 22

What is the main cause of pre-hepatic hyperbilirubinemia?

Answer 22

Hemolysis (increased RBC breakdown).

Question 23

What is the main cause of hepatic hyperbilirubinemia?

Answer 23

Lesions that impair bile flow (hepatocellular swelling that compresses canaliculi, periportal lesions that compress bile ducts, infections, etc.).

Question 24

What is the main cause of post-hepatic hyperbilirubinemia?

Answer 24

Bile duct obstruction (biliary system is the rate limiting step).

Question 25

When can we see mild hyperbilirubinemia in horses and cattle?

Answer 25

When they are anorexic or off-feed.

Question 26

What are two main causes of hypercholesterolemia?

Answer 26

1. Diabetes mellitus 2. Hyperadrenocorticism.

Question 27

With loss of hepatic function, we will see decreases in which products?

Answer 27

Albumin, Cholesterol, Glucose, BUN, Coagulation factors ## Footnote All are synthesized by the liver.

Question 28

With loss of hepatic function, we will see increases in which products?

Answer 28

Bilirubin, Bile acids, Ammonia ## Footnote All increase due to liver damage.

Question 29

What are the ten categories of decreased functional hepatic mass?

Answer 29

Degenerative: Hypoxia (anemia or congestion), Anomalous: Portosystemic shunt, Metabolic: Lipidosis, DM, cushing’s, Neoplastic: Carcinoma, LSA, metastatic, Inflammatory: Infectious (leptospirosis, FIP, clostridium) and non-infectious (chronic hepatitis), Inherited: Copper or lysosomal storage disease, Toxic: Steroid hepatopathy, copper toxicosis, pyrrolizidine alkaloid-containing plants, Traumatic: HBC.

Question 30

Bile salt metabolism initially starts with what molecule?

Answer 30

Cholesterol ## Footnote On exam.

Question 31

What is the function of bile acids/salts?

Answer 31

Bile acids act as detergents and help to emulsify fats, aiding in their digestion and absorption. 70-95% of bile acids get recycled in the enterohepatic circulation, therefore there are very few in systemic blood.

Question 32

True or False: A bile acids assay is a very sensitive test for hepatic disease in cattle.

Answer 32

False, it is a less sensitive test for hepatic disease because of variable bile acid concentrations AND frequency of cholestatic diseases in cattle is low.

Question 33

When are three times you would want to run a bile acids test?

Answer 33

1. In cases of portosystemic shunts (PSS) in small animals (check for copper eyes) 2. Cases of hypoalbuminemia of unknown origin or others where liver disease is suspected but difficult to definitively diagnose 3. Monitoring of potentially hepatotoxic drug therapies.

Question 34

True or False: A bile acids assay should be the next step if hyperbilirubinemia and hypercholesterolemia are seen on a chemistry.

Answer 34

False!!! If there is already hyperbilirubinemia and hypercholesterolemia present on chemistry, you already know there's cholestasis.

Question 35

Which three defects in ammonia metabolism can result in hyperammonemia?

Answer 35

1. Hepatic function 2. Portal blood flow 3. Urea enzymes/intermediates can result in hyperammonemia.

Question 36

What is most likely if you see ALT > ALP in dogs and cats?

Answer 36

It is more likely to be hepatocellular damage with some cholestasis components ## Footnote On exam.

Question 37

What is most likely if you see ALT < ALP in dogs and cats?

Answer 37

The primary process is more likely to be cholestatic disease over hepatocellular injury. ## Footnote On exam.

Question 38

Which two markers are better for hepatocellular injury in large animals?

Answer 38

GLDH and SDH are better detectors than AST and ALT. ## Footnote On exam.

Question 39

Which marker is better for determining cholestasis in large animals?

Answer 39

GGT is better than ALP.

Question 40

Which marker is likely to be elevated in a cat with hepatic lipidosis?

Answer 40

ALP (more likely to be increased than GGT because GGT can be normal or mildly increased with hepatic lipidosis). ## Footnote On exam.

Question 41

What marker is the best overall for determining cholestasis in all species?

Answer 41

GGT ## Footnote On exam.

Question 42

True or False: GGT is high in foals but not due to colostrum intake.

Answer 42

True (we don't know why).