Laboratory Diagnosis of Liver Disease

Question 1

How can the liver be evaluated?

Answer 1

Enzymes
Metabolites
Function tests

Question 2

What enzymes indicate hepatocellular damage?

Answer 2

Alanine aminotransferase (ALT)
Aspartate aminotransferase (AST)
Sorbitol dehydrogenase (SDH)
Glutamate dehydrogenase (GLDH)

These are leaked directly from the hepatocytes and indicate damage or necrosis of these cells

Question 3

Which liver is most commonly used in dogs and cats to indicated hepatocellular damage?

Answer 3

ALT

• Will increase within 12 hours of injury
• Peak at 1-2days
• Decrease over 2-3weeks

GLDH
Considered to be liver specific but assays for smallies rarely available

Question 4

What is the sequence of events of hepatocellular damage?

Answer 4

1. ATP depletion due to hypoxia or mitochondrial toxins
2. Membrane damage due to oxidants or other agents
3. NECROSIS
4. Membrane blebbing

Question 5

Why are SDH and/or GLDH used to indicate damage in large animals?

Answer 5

Hepatic ALT activity is very low

Question 6

What pattern of AST and ALT would you expect in an animal that had undergone muscle damage?

Answer 6

Increased AST
Slight increased ALT
Check creatinine kinase levels as more muscle specific

Question 7

Describe the pattern of CK following muscle injury…

Answer 7

Increased within 1-2hours of injury
Peaks at 6-12 hours
Decreases over the following 24-48hours

Question 8

What does persistent elevation of CK indicate?

Answer 8

Persistent muscle damage

Question 9

What is cholestasis?

Answer 9

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

Question 10

What enzymes indicate cholestasis?

Answer 10

ALP - Alkaline phosphatase

GGT - Gammaglutamyltransferase

Question 11

Where is alkaline phosphatase (ALP) found?

Answer 11

Derived from the bile duct epithelial

Bone (so increased in growing animal)

Question 12

Where has ALP been isolated in dogs?

Answer 12

Kidney
Liver
Bone
Placenta
Intestines
Sterioids

Question 13

What can cause an increased ALP in dogs?

Answer 13

Age
Breed
Drug induced
Cushing's
Primary hepatic biliary disease
Systemic disorders 
Bone related disorders

Question 14

What other compound could be mistaken for ALP? In which species?

Answer 14

Steroid isoform (dogs)
Not found in cats, so any increase in ALP is always significant (e,g hyperthryoid)

Question 15

Why does ALP increase? How is it different from ALT?

Answer 15

Some ALP ready formed on membrane. An induced induces ALP production by the cells (-1week)

ALT is released due to trauma

Question 16

Where is gammaglutamyltransferase (GGT) found?

Answer 16

Bile duct epithelium

Colostrum
Increased in nursing animals

Renal tubular cells
can be found in urine (not blood) if renal tubular damage is present

Question 17

What can be used to measure hepatic function?

Answer 17

Bilirubin
Albumin
Urea
Glucose
Cholesterol
Ammonia
Bile acids

Question 18

How is bilirubin metabolised?

Answer 18

1. Broken down RBC releases BU (not water soluble)
2. Bound to albumin in blood
3. Enters liver (but must be unbound from albumin)
4. Metabolised and conjugated - becomes water soluble
5. Enters canaliculi (rate limiting step)
6. Bile -> gut
7. Bacteria act on conjugated BU and forms urobilirubin or stercobilirubin
8. Taken up by receptors in ileum, enters hepatic portal vein and re-enters liver or blood stream
9. Urobilinogen and albumin bound in blood where it passes through the kidneys and is excreted as unbound bilirubin or urobilinogen

Question 19

What does bilirubinuria indicate?

Answer 19

Low levels are normal in the dog

In the cat, always significant

Question 20

What can cause increases in cholesterol?

Answer 20

Cholestasis due to decreased excretion

Hepatic disease (but may decrease)

Post prandial

Endocrine disorders including diabetes mellitus and hyperadrenocorticism

Increases variation with T4
+ Increased with hypothyroidism
- Decreased with hyperthyroidism

Question 21

What can cause decreases in cholesterol?

Answer 21

Hepatic failure
decreased synthesis

Hyperthyroidism

Question 22

Is a change in blood glucose a reliable indicator for hepatic disease?

Answer 22

No; decreases only with end stage disease

+ Hyperglycaemia may be caused by stress and DM

• Hypoglycaemia also caused by sepsis, neoplasia, starvation

Question 23

What is the basis of the bile acid test?

Answer 23

Measure fasting and postprandial

During the fasting stage, bile acid are stored in the gall bladder, released after feeding.

Measure singularly in the horse as no gall bladder

Question 24

Why do you need to be careful when measuring ammonium concentration?

Answer 24

It has very low stability.

Question 25

What can lead to hyperammonaemia?

Answer 25

Decreased NH4+ clearance from portal blood
e.g. PSS

NH4+ production
e.g. postprandial, urea toxicosis in cattle, strenuous exercise, UTI

Question 26

What should be investigated with:
Increased urea in blood
Decreased urea in blood

Answer 26

Kidneys and liver (decreased)

• See increased ammonia
• May see ammonium biurate crystals in urine

Question 27

Does cholesterol change with liver disease?

Answer 27

May increase or decrease (increase if failure to excrete, decrease if failure to synthesise)