Lab Diagnostics of Liver Disease

Question 1

What are the enzymes which indicate hepatocellular damage? Where do these enzymes come from?

Answer 1

ALT, AST, SDH, GLDH
Leaked directly from hepatocytes and indicate damage/necrosis of liver cells

Question 2

What is the hepatocellular enzyme most commonly used for dogs and cats?

Answer 2

ALT

Question 3

How many hours after injury does ALT increase and how long after injury does it peak? Over how long does it decrease?

Answer 3

ALT will increase within 12 hours of injury and peaks at 1-2 days post injury and gradually decreases over next 2-3 weeks

Question 4

What does ALT indicate?

Answer 4

ALT = liver damage
T = TRAUMA
Almost completely specific to the liver

Question 5

Is ALT appropriate to use for large animals?
What values should you use for large animals?

Answer 5

No - ALT activity in large animals is very low
Use SDH or GLDH instead

Question 6

Is AST a liver specific enzyme? Where else can this liver enzyme be derived from? What other enzyme is similar?

Answer 6

No - but AST and ALT can be derived from muscle damage and erythrocyte damage (hemolysis)

Question 7

What do high AST levels indicate?

Answer 7

The need for further investigation/testing

Question 8

What does creatinine kinase (CK) indicate?

Answer 8

Muscle-specific enzyme and most sensitive indicator of muscle injury

Question 9

How long after muscle injury does CK increase? When does it peak and how quickly does it decrease?

Answer 9

Will increase within 1-2 hours of injury, peaks at 6-12 hours post, and decreases quickly over next 24-48 hours

Question 10

What does persistently elevated CK indicate?

Answer 10

Ongoing damage

Question 11

Does ALT/AST change slower or faster than CK?

Answer 11

ALT/AST increase and decrease more slowly than CK

Question 12

If CK is elevated what other issue should you think about besides just muscle damage?

Answer 12

Think about concurrent liver damage

Question 13

What is cholestasis?

Answer 13

Obstruction of bile flow with regurgitation of biliary substances into the blood

Question 14

What are the 2 enzymes which indicate cholestasis?

Answer 14

ALP - Alkaline phosphatase
GGT - gammaglutamyltransferase

Question 15

Where does ALP derive from? When does it increase?

Answer 15

Bile duct epithelium
Increases with cholestasis

Question 16

Why is ALP increased in young animals?

Answer 16

ALP found in bone so increased in young growing animals

Question 17

Where does ALT derive from?

Answer 17

Hepatocytes (primarily)

Question 18

In what species is the steroid induced isoform of ALP found? Why is this significant in sick animals?

Answer 18

Steroid induced isoform in dogs only - sick dogs with steroids on board (whether its stress, meds, etc) will have an increase in ALP
Not found in cats - any increase is significant!

Question 19

What is special about the half-life of ALP in cats?

Answer 19

VERY short half-life
VERY difficult to make a significant increase in ALP in cats as it is excreted/degraded quickly

Question 20

Which 2 conditions in cats could cause an increase in ALP?

Answer 20

Hyperthyroidism
Hepatic lipidosis

Question 21

Where is GGT derived from?

Answer 21

Bile duct epithelium

Question 22

What does GGT indicate in large animals?

Answer 22

More sensitive indicator of cholestasis than ALP

Question 23

Why is GGT increased in nursing animals?

Answer 23

Contained in colostrum so will be increased in nursing animals

Question 24

What level will be increased in the situation of renal tubular damage? Why?

Answer 24

GGT present in renal tubular cells so could be found in urine (not blood) if renal tubular damage is present

Question 25

What does the "T" in ALT mean and the "P" in ALP? What do these values indicate? Which of these values are expressed more easily?

Answer 25

ALT - Trauma (comes out of cells very easily) ALP - Production (needs induction)

Question 26

What are the 7 BW measures of hepatic function?

Answer 26

Question 27

What is bilirubin the breakdown product of? Where is it conjugated and excreted?

Answer 27

Breakdown product of hemoglobin Conjugated in the liver and excreted with bile into the gut

Question 28

What is bilirubin converted into before its excreted in the feces?

Answer 28

Urobilinogen

Question 29

What substance gives serum/plasma yellow color?

Answer 29

Bilirubin

Question 30

What value will increase in horses fasted for 24+ hours?

Answer 30

Bilirubin

Question 31

T/F - low levels of bilirubin can be found in normal dog urine

Answer 31

True

Question 32

T/F - low levels of bilirubin can be found in normal cat urine

Answer 32

False - not normal and is always a significant finding in the cat

Question 33

In cats is an elevation in bilirubin first noticeable in the urine or the blood?

Answer 33

Bilirubinuria first noticeable before elevation detected in circulation

Question 34

What are 2 products of protein metabolism detectable on BW?

Answer 34

Ammonia and Urea

Question 35

Where is ammonia derived from? How does it travel to the liver? How is it converted to urea?

Answer 35

Product of PROTEIN metabolism (from diet) Ammonia derived from gut and travels to liver via portal circulation Ammonia is converted to urea via the urea cycle

Question 36

What happens to ammonia in liver failure? What does this mean for the levels of urea?

Answer 36

Ammonia is not able to be converted to urea in liver failure --> buildup of ammonium in blood Urea levels will be decreased, Ammonium will be increased

Question 37

What is the main route of excretion for urea? What system is urea primarily used to evaluate?

Answer 37

Primary route of excretion is via the kidneys, hence urea is primarily used to evaluate the renal system

Question 38

In what organ does some production of glucose occur?

Answer 38

Liver

Question 39

In what stage of liver disease do decreases in glucose occur? What are some other causes of hypoglycemia?

Answer 39

End-stage liver disease Other causes of hypoglycemia - neoplasia, bacterial sepsis

Question 40

What can cause hyperglycemia?

Answer 40

Stress (mild increase) Diabetes mellitus

Question 41

Is glucose a sensitive indicator of hepatic dysfunction?

Answer 41

No

Question 42

Where is cholesterol synthesized? Where is it excreted?

Answer 42

Synthesized in the liver and excreted in bile

Question 43

How does cholesterol change in the following situations: - Hepatic disease - Cholestasis - Hepatic failure

Answer 43

Hepatic disease - may increase or decrease Hepatic failure - decrease (due to decreased synthesis) Cholestasis - increase (due to decreased excretion)

Question 44

What would happen to cholesterol levels if there is biliary obstruction but also liver failure?

Answer 44

Cholesterol level will seem unchanged, though there are 2 issues going on

Question 45

How does cholesterol level change post-prandially?

Answer 45

Increase

Question 46

How does cholesterol level change with endocrine disorders?

Answer 46

Increase in cholesterol with diabetes mellitus and hyperadrenocorticism

Question 47

How does cholesterol change with hyper/hypothyroidism?

Answer 47

Varies inversely with T4 - Hypothyroidism = increased cholesterol - Hyperthyroidism = decreased cholesterol

Question 48

What is the difference between bile and bile acids?

Answer 48

Bile flowing from the liver is concentrated in the gallbladder and, in response to a meal, released into the upper intestine. In the intestines, bile acids act as detergents and help to emulsify fats, aiding in their digestion and absorption.

Question 49

How are bile acids measured?

Answer 49

Fasted and post prandial levels measured

Question 50

Where are bile acids stored during fasting? How are they released?

Answer 50

Bile acids stored in gallbladder Released by gallbladder contraction after feeding

Question 51

What does bile acid concentration test?

Answer 51

Tests hepatic uptake

Question 52

How is bile acid concentration [BA] tested in horses? What about their anatomy is different from dogs/cats?

Answer 52

Horses measure single sample No gallbladder in horses (no storage)

Question 53

Why is bile acid concentration [BA] not an appropriate test in ruminants?

Answer 53

Range is too wide

Question 54

What are the 2 main pathological processes responsible for increase in [BA] in serum or plasma?

Answer 54

Question 55

How does bile acid challenge test work?

Answer 55

A bile acids “challenge” test with both a pre- and two-hour post-prandial blood collection is recommended over a single fasting or random sample (in dogs and cats) because it has substantially higher sensitivity for detecting disease. Feeding stimulates gall bladder contraction and the release of bile acids into the intestine and eventual portal circulation. This increased load can better “challenge” the liver’s ability to clear the increased bile acids presented to it.

Question 56

What can cause false increases in NH4+ in blood samples?

Answer 56

Hemolysis (poor sampling technique) Delayed sample analysis Serum (not plasma)

Question 57

What can cause false decrease in NH4+ in blood samples?

Answer 57

Exposure to air

Question 58

What are the factors which can cause hyperammonemia?

Answer 58

Question 59

T/F - Enzymes and function tests ARE specific enough to determine underlying cause of liver lesion

Answer 59

False

Question 60

What do you need to do in order to confirm underlying cause of liver lesion if suspected based on hematology?

Answer 60

FNA or Biopsy