Metabolism And Excretion Lecture 4- Laboratory Investigations Of The Liver And Biliary System

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Serum-

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fluid without clotting factors

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Plasma-

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fluid with clotting factors

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ALT

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Alanine aminotranferase
Present in the cytosol of HEPATOCYTES
“liver specific” in dogs, cats and primates
Half life approx 2-4 days

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SDH

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Sorbitol dehydrogenase
Present in cystosol of HEPATOCYTES
“liver specific” in all species
Half life approx .5 day

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GLDH

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Glutamate dehydrogenase
Present in cytosol of HEPATOCYTES
“liver specific” in all species
Half life approx .5 days

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AST

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Aspartate aminotransferase
Present in the cytosol of HEPATOCYTES, associated with MITOCHONDRIA
NOT liver specific in any speices
Also found in cardiac and skeletal muscles, and kidney, brain, pancreas and RBC
Half life approx 2-4 days
Useful when interpreted with concurrent CK (CPK) measurmeant
CK is essentially a “muscle speficic” enzyme, there an increase in CK and AST suggests active )skeletal) muscle injury VS an increase in AST only suggests resolving muscle damage or active hepatic injury

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AP

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Alkaline phosphtase; SAP, Alk Phos
Bound to MICROSOMAL MEMBRANES WITHIN CELLS
Present in many tissues, most importantly: biliary canaliculi, osteoblasts
Several isoenzymes which are tissue specific, however they are rarely measured. Total AP is measured – sum of isoensymes
Most species half life is approx 2-3 days
cat half life approx 8 hours, therefore increase AP values in cats uncommon

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AP is found in intestines, kidney, plasma and leukocytes but:

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Intestinal disease causes modest increase in circulating AP values
Renal tubular damage the renal enzyme is lost in the urine
The other 2 are too short to be of clinical significance

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Circulating AP values increase with

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INCREASED OSTEOBLAST ACTIVITY
Young actively gorwing animals may have values that are up to twice adult reference values

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Cholesostasis

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AP is a useful indicator of cholestasis in dogs, horses and pigs
Increased AP valyes preceded and increase in conjugated Bilirubin in these species
AP is not so useful for this purpose in cats or ruminants

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Corticosteroids

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Endogenous and exogenous croticosteriods induce canine hepatocytes to synthesise an isoenzyme which is not normally produced
This “steroid induced” induced isoenzyme may increase AP values by 2-5 times within 2-3 days of therapy commencing and be 30-40 times in 17 days
ALT valyes ill increase to a lesser degree, because of hepatic lipidosis

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GGT

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Gamma glutamyl tranferase; gamma GT
Principally in the BILE CANALICULLI
A useful marker for cholesostasis in dogs, cats, horses and ruminants
Also found in kidney, but renal tubular damage results in loss into urine

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Cholesterol

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Routinely measured in bichem profiles in cats and dogs
Changes are non specific

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total Bilirubin=

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unconjugated Bilirubin+conjugated Bilirubin

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Unconjugated Bilirubin

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Aka indirect Bilirubin
Calculated as the difference between total Bilirubin and conjugated valyes
Onsoluable in water and therefore bound to albumin in blood

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Conjugated Bilirubin

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Aka direct Bilirubin
Soluble in water and therefore is free in blood

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Low rental rubular threshold for conjugated Bilirubin- diesbt absorb, excretes in urine- therefore bilirubinuria (+1 in concentrated urine) is normal
Circulating conjugated Bilirubin values may increase more slowly

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Dog

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Radily develops a marked increase in unconjugated Bilirubin when fasted- liver does not take bilirubin up when aneroxic
Unconjugated Bilirubin predominates in perhapetic and hepatic icterus

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Horse

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Bile acid toerlance test
Method:

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1-2 hour fast
Collect resting serum sample
Feed dog minimum 3 tablespoons commercial dog food containg approx .5% fat
Collected another serum sample 2 hours later

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Bile acid tolerance test
reference values
resting
2-hour

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Reference values
Resting sBA 0-9 micromoles/liter
2-hour sBA 0-31 micromoles/liter

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Bile acid tolerance test
rationale

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Rationale
Fatty meal stimulates gallbladder to contract
Bile acids absorpbed across gut and returned to liver by portal vein
If animal has decreased functional hepatic mass, then less BA are removed by liver and therefore enter the systemic circulation
Animals with a chronic hepatopathy have an INCREASE POST PRANDIAL BA