Liver Disease Lab Dx

Question 1

What 3 substances can be used to evaluate the liver?

Answer 1

• Enzymes
• Metabolites
• Function tests

Question 2

Give 4 enzymes which indicate hepatocellular damage. Why are they seen in association with hepatocellular damage?

Answer 2

• ALT
• AST
• SDH
• GLDH
  > leak directly from cells when hypoxia/oxidants/mitochondrial toxins -> ATP depletion -> membrane “blebbing” and production of blebosomes or necrosis of the cell
  > levels increase rapidly with cell damage as substances already produced and contained in cells

Question 3

Which is the most common enzyme looked at in cats and dogs? When will levels rise/fall? Is it liver specific?

Answer 3

ALT - also found in muscle but only at v. low levels

• ^ within 12hours injury
• peak 1-2d
• falls over 2-3w

Question 4

Is the same most common enzyme analysed in large and small animals?

Answer 4

No - ALT activity in large animals is very low

• Use SDH or GLDH
• GLDH = liver specific but rarely available to look at in smallies

Question 5

Which hepatocellular enzyme is found in high levels but is not liver specific? Where else is it found?

Answer 5

AST - also derived from muscle and RBCs in fairly high concentration (~= ALT)

Question 6

Which enzyme is muscle specific? When will levels rise/fall?

Answer 6

CK (more rapid changes)
- ^ within 1-2hrs 
- Peak 6-12hrs
- Decrease over 24-48hrs 
> If persistently high indicates ongoing damage

Question 7

Give 2 enzymes that indicate cholestasis. Where are they derived from?

Answer 7

• ALP
• GGT
  > derived from bile duct epithelium (amongst oher places)

Question 8

Define cholestasis

Answer 8

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

Question 9

Where else is ALP found and hwo may this influence results?

Answer 9

> Bone - will be higher in young growing animals

> Steroid induced isoform in DOGS only (due to stress or dugs)

Question 10

In which species is any increase in ALP particularly significan?

Answer 10

Cats (no steroid induced isoform, short half life)

Question 11

What is the most common cause of ALP in cats?

Answer 11

Hyperthyroidism

Question 12

When would “induction” related increases be seen vs “leakage”?

Answer 12

Induction eg. after steroid injection = 1 week later

Leakage = instantaneously

Question 13

Which enzyme is a more sensitice indicator of cholestasis in large animals?

Answer 13

GGT (ALP has a v. large range)

Question 14

Where is GGT found other than bile duct epithelium?

Answer 14

• Colostrum -> ^ in nursing animals

- renal tubular cells -> urine if tubular damage present

Question 15

How can differences in ALT and ALP be remembered?

Answer 15

• alT = trauma [not related to liver FUNCTION]

- alp = production [induction]

Question 16

Give 7 measures of hepatic FUNCTION

Answer 16

• bilirubin
• albumin
• urea
• glucose
• cholesterol
• ammonia <- specific*

Question 17

What is the average lifespan of a red blood cell?

Answer 17

120d

Question 18

Outline the pathway of RBC breakdown

Answer 18

• RBC breakdown
• Hbg -> bilirubin (not water soluable
• Albumin bound unconjugated bilirubin transported in blood -> liver, dissociates
• Hepatocytes uptake and conjugate -> bile -> gut
• Converted to urobiligen and stercobiligen for excretion

Question 19

How does dogs metabolism of bilirubin differ to other species?

Answer 19

Capable of excreting small amouns of unconjugated bilirubin directly from he kidneys

Question 20

Why is serum/plasma yellow?

Answer 20

Bilirubin”

Question 21

In which species does bilirubin increase dramatically with fasting?

Answer 21

Horses (fasting >24 huors)

Question 22

What effect on bilirubin levels would ^ haemolysis have a) initially? b) longterm?

Answer 22

a) ^ UNconjugated bilirubin

b) ^ conjugated aswell (due to rate limiting step being excretion -> bile)

Question 23

What is the rate limiting step of bilirubin metabolism?

Answer 23

excretion -> bile

Question 24

In which species is low level bilirubinuria found normally?

Answer 24

Dogs (canine renal tubular epithelium can conjugate bilirubin)

Question 25

In which species is bilirubinaemia always significant?

Answer 25

Cats (may be seen before ^ levels deeced in the blood)

Question 26

What are he 2 products of protein metabolism?

Answer 26

Ammonia and Urea (ammonia derived from gut, travels -> liver via poral circulation and converted to urea)

Question 27

Which system does v/^ urea in the blood/urine(?) indicate a problem in? What else may be seen with liver disease?

Answer 27

v = liver
^ = kidney
- ammonium biurate crystals in urine due to high ammonia levels

Question 28

Are glucose levels often affected by hepatic disease?

Answer 28

• Not sensitive - decreases only with end stage liver disease
• hypoglyceamia caused by neoplasia and bacterial sepsis
• hyperglycaemia caused by stress and diabetes mellitits

Question 29

Is cholesterol a useful biomarker of liver function?

Answer 29

NO! Can be
- increased (cholestasis and v excretion)
- decreased (v synthesis)
- the same if both parts diseased!
> ^ with endocrine disorders (DM, Cushings)
> varies inversely with T4 (^hypothyroidism, v hyperthyroidism)

Question 30

WHy are bile acids recycled in enterohepatic recirculation?

Answer 30

High energy for production

Question 31

How is bile acid concentration used to monitor hepatic function in different species?

Answer 31

• measure fasted
• measure post-prandial
  > tests hepatic uptake
• horses: measure single sample as no gall bladder
• not often used in ruminants (range too wide)

Question 32

What 2 major pathologic processes does ^ [BA] indicate?

Answer 32

1. v clearance from portal blood, v functional mass [ie. not being reuptaken by hepatocytes] or PSS
2. v BA excretion via bile ( Obstructive cholestasis)

Question 33

Which parameter can be measured to evaluate hepatic function but rarely is?

Answer 33

Ammonium (NH4+) concentration [indications similar to bile acids]
- test not feasible as stability poor

Question 34

Are liver enzymes and function tests sufficient to determine the undelying cause of liver lesion?

Answer 34

No - FNA or biopsy required

Question 35

Look at lecture for other lab findings to take into account