Clin path exam 3

3 categories of liver disease

hepatocellular injury, cholestasis, and decreased hepatic functional mass

Can you have more than 1 category of liver disease at the same time

yes

Is liver disease usually a primary or secondary problem

secondary

Primary liver enzyme types

leakage enzymes and inducible enzymes

Are liver leakage enzymes from the cytoplasm/mitochondria or membrane bound

cytoplasm/mitochondria

Are inducible enzymes from the cytoplasm/mitochondria or membrane bound

membrane bound

Increases in liver leakage enzymes tell you there is

hepatocellular injury

Increases in inducible enzymes tells you there is

cholestasis

Why is it important to evaluate liver enzyme trends overtime

animals with acute injury and animals with low level chronic injury can have the same values at the same time

ALT, AST, SDH, GLDH, LDH are all indicators of

hepatocellular injury

ALT, AST, SDH, GLDH, and LDH are what kind of liver enzymes

leakage enzymes

Alanine aminotransferase

ALT

Increased ALT in a small animal

hepatocellular injury

Increased ALT in a large animal

muscle injury

Besides hepatocellular injury, what else can increase ALT in small animals

endocrinopathies

Preferred hepatocellular injury marker in dogs and cats

ALT

Is ALT a good hepatocellular injury marker for large animals

no

Aspartate transaminase

AST

Increased AST

hepatocellular injury and muscle injury

How should you interpret AST

in conjunction with CK and ALT to differentiate liver vs muscle injury

½ life of AST in cattle

1 day

½ life of AST in horses

7-8 days

What is a better marker for hepatocellular injury in small animals ALT or AST

ALT

Does AST or ALT half a longer half life in a dog

ALT

Because AST has a shorter half life it is a better marker for

active liver injury

Sorbitol dehydrogenase

SDH

Increased SDH in large animals and small animals

hepatocellular injury

SDH is both sensitive and specific for hepatocellular injury in SA and LA so why is it not always available on panels

unstable enzyme that is impractical for mailed samples

Hepatocellular injury enzyme of choice in large animals

SDH

Glutamate dehydrogenase

GLDH

GLDH is a sensitive and specific marker for hepatocellular injury in both SA and LA so why don’t we see it often

it is not commonly used in the US

Lactate dehydrogenase

LDH

LDH is very

nonspecific

Increased LDH could mean

hepatocellular injury, muscle injury, or even mild hemolysis

What sample handling error can easily skew LDH levels

hemolysis

What leakage enzymes are typically seen on a SA panel

ALT and AST

Drugs that can cause hepatocellular injury

carprofen, glucocorticoids, and phenobarbital

Drug that causes variable increase in hepatic leakage enzymes that can be severe

carprofen

Drugs that cause a consistent mild increase in hepatic leakage enzymes

glucocorticoids and phenobarbital

What is an example of a hepatotoxin in LAs that cause low level injury over a long period of time

pyrrolizidine alkaloids

2-3x URL is mild, moderate, or severe hepatocellular injury

mild

4-10x URL is mild, moderate, or severe hepatocellular injury

moderate

>10x URL is mild, moderate, or severe hepatocellular injury

severe

Hepatic leakage enzymes below LRL

clinically insignificant

If hepatic leakage enzymes stay elevated for months this indicates

active damage is still occurring

Cholestasis

obstruction of bile flow

2 types of obstructive cholestasis

intra-hepatic and extra-hepatic

Intra-hepatic obstructive cholestasis

swelling in the liver occludes the bile canaliculi and ductules

Extra-hepatic obstructive cholestasis

obstruction of the gall bladder or pancreatitis that blocks off the bile duct

Functional cholestasis

during sepsis the liver stops processing bile as well

Membrane-bound inducible enzymes

ALP and GGT

An increase in inducible enzymes indicates obstructive or functional cholestasis

obstructive

Indicators of cholestasis

ALP, GGT, hyperbilirubinemia, and hypercholesterolemia

Will cholesterol be high or low during cholestasis

high

Cholelithiasis can cause extra-hepatic or intra-hepatic obstructive cholestasis

extra-hepatic

Alkaline phosphatase

ALP

What ALP isoform is specific to dogs

c-ALP

c-ALP

corticosteroid isoform of ALP found only in dogs

3 ALP isoforms

L-ALP, B-ALP, C-ALP

ALP can increase in response to

cholestasis, bone remodeling or growth, and corticosteroids in dogs

A young animal may have an increased ALP due to

bone growth

What drugs can increase ALP

glucocorticoids in dogs and anticonvulsants

Gamma glutamyl transferase

GGT

GGT is found in the liver, renal tubular epithelium, and mammary epithelium. Why won’t the renal tubular GGT and mammary GGT contribute to serum levels of GGT

it is excreted in the urine and milk

Increased GGT

cholestasis, biliary hyperplasia, colostrum ingestion, glucocorticoids and anticonvulsants

Colostrum ingestion in what animal won’t increase GGT

foals

What inducible liver enzyme will increase with colostrum ingestion

GGT

In dogs what inducible enzyme is more sensitive for cholestasis

ALP

In cats what inducible enzyme is more sensitive for cholestasis

GGT

In LAs what inducible enzyme is more sensitive for cholestasis

GGT

Hepatic lipidosis in cats will have a disproportionate increase in

ALP

Mixed hepatopathy

both hepatocellular injury and cholestasis together

If you have a mixed hepatopathy, how can you determine the primary cause

which enzymes are more severely increased

Muscle injury is a disruption in myofiber cell membranes that allows for

leakage of cytoplasmic/mitochondrial enzymes

3 processes of muscle injury

degeneration, necrosis, and inflammation

Will muscle atrophy cause increased muscle injury enzymes

no

Muscle injury enzymes

CK, AST, ALT in LAs, and LDH

What might be seen on urinalysis with muscle injury

myoglobinuria

Should you use skeletal muscle markers to assess cardiac muscle injury

no

Creatine kinase

CK

The skeletal muscle isoenzyme of CK has the most

serum activity

Enzyme of choice for skeletal muscle injury

CK

Does CK have a long or short half life

short

An increase in CK indicates a

recent or ongoing muscle injury

Horse CK

very high levels with muscle injury take a few days to go back into reference range

What enzyme has a longer half life in horses, AST or CK

AST

Pre-hepatic hyperbilirubinemia

increased production of bilirubin

Hepatic hyperbilirubinemia

decreased hepatic uptake or secretion of bilirubin

Post-hepatic hyperbilirubinemia

cholestasis

Where is bilirubin conjugated

hepatocyte

Uncojugated bilirubin is transported in the blood with

albumin

What form of bilirubin is excreted in feces

conjugated bilirubin

Phagocytosis of a RBC by a macrophage causes breakdown of hemoglobin into

heme and globin

Phagocytosis of a RBC by a macrophage causes breakdown of heme into

iron and biliverdin

Pre-hepatic hyperbilirubinemia is seen with an increase in what kind of hemolysis

extravascular

RBC phagocytosis produces what kind of bilirubin

unconjugated

Prehepatic hyperbilirubinemia will have high direct or indirect bilirubin

indirect

Indirect bilirubin

unconjugated

Direct bilirubin

conjugated

Formation of Bu exceeds the liver’s capacity for uptake and excretion causing indirect bilirubin to be higher than direct bilirubin in what kind of hyperbilirubinemia

pre-hepatic