L17: Clinical Approach To Elevated LIV Enzymes (Gallagher) Flashcards
Hepatic enzymes
-Alkaline phosphataseALKP
-Gamma-glutamyl transferase (GGT)
-Alanine aminotransaminase (ALT)
-Aspartate aminotransaminase (AST)
(LDH in large animal)
do NOT tell anything about liver function!!
Where are liver enzymes located in the hepatocytes?
ALP: on apical hepatocyte membranes, and bile canaliculi membranes
AST: majority in mitochondria, some in cytosol (requires more cell damage to be released)
GGT: same places as ALP, except more in canaliculi
ALKP properties
- an inducible enzyme released in response to cholestatic dz, drugs (anti-convulsants, steroids)
- has multiple isoenzymes esp. In liver and bone
- will be increased in young growing puppies, and older dogs with nodular hyperplasia
- dogs have a steroid-inducible isoenzyme that is not present in the cat
- cat ALP has shorter half-life than in dogs, so if ALP is elevated in cats, it is always important!
GGT properties
- membrane-associated
- inducible enzyme from cholestatic dz, drugs
- Dogs have higher SPECIFICITY: If GGT is increased in dogs, there is a lower likelihood of it being a false + than in cats
- Cats have higher SENSITIVITY: if increased, less likely it is a false neg.
- If ALP is normal but GGT is elevated in a cat, still suspicious of liver dz
ALT properties
- Cytosolic
- Liver specific enzyme
- necrosis/inflammation (due to drug toxicity, trauma, etc.) –> greatest increases
- small amount can come from the muscle
AST properties
- in cystosol/mitochondria
- requires more damage before released
- less specific to liver (also comes from muscle, RBCs)
- can be falsely elevated in iatrogenic hemolysis or IMHA
- If AST > ALT, muscle damage or hepatobiliary disease likely –> irreversible damage
If AST > ALT**
Muscle damage is likely
-look for CK for marker of muscle damage: if CK is normal but AST > ALT, suggests irreversible damage to the hepatocytes
Breed-related liver problems: Dobies, Bedlingtons, Labs, Yorkies, Chis, Schnauzer, Scotties
Dobies: chronic hepatitis Bedlingtons: Cu storage hepatopathy Labs: Cu-associated hepatitis Yorkies, Chis, schnauzers: PSS Scotties: benign hyperalkaline phosphatemia
Common drugs or toxins causing liver damage
- steroids, NSAIDs, anti-convulsants
- sago palms, mushrooms, aflatoxins
Abnormalities on PE with liver damage
-Icterus
-Hepatomegaly
-Ascites
-Skin lesions
(Hepatocutaneous syndrome: ulcerative, hyperkeratotic skin lesions, commonly on pad)
Where do cats usually become icteric first?
Soft palate
MILD increase in ALP, ALT, AST is what X above upper reference range?
2-5X
MODERATE increases in ALP, ALT, AST is what X above upper reference range?
5-10X
MARKED increases in ALP, ALT, AST is what X above upper reference range?
> 10X
Indirect markers of liver function
Chem: BUN, Albumin, Cholesterol, Glucose, Bilirubin
CBC: microcytosis
UA: ammonium urate crystals
Why can liver damage –> microcytosis?
Liver responsible for making transferrin which shuttles Fe. If transferrin low, have problems making normal RBCs
-can also see with PSS
Which breeds predisposed to urate crystals?
Dalmatians and bulldogs (so not necessarily assoc. with liver dysfx)
If ALP is highest liver enzyme, main differentials should include:
Things that cause cholestatic dz or drugs that induce isoenzymes
If ALT is highest liver enzyme, should suspect what kind of dz?
Dz that causes hepatocellular damage (ie. NSAIDs)
Increased ALP with normal or near normal GGT indicative of:***
Hepatic lipidosis
Anything that causes cholestatic dz will also cause a degree of hepatocellular damage and vice versa
Rarely isolated increases in enzymes
Liver function tests
Bile acids/urine bile acids
Ammonia (fasting and tolerance testing)
Circulation of bile acids
Synthesized in liver –> GB –> duodenum during a meal –> ileum
90% reabsorbed back into portal circulation, 10% in feces
95% of bile acids in portal circulation goes back to liver, 5% goes to systemic circulation
Bile acids test
Fast, then measure bile acids in systemic circulation before and after giving a small fatty meal
- can be influenced by biliary obstruction, GI dz in ileum –> false negatives
- false positives due to whether animal truly fasted or not, if GB contracted or not
- degree of increase not assoc. with specific liver dz, unless >100, which is assoc. with PSS
- hemolysis and lipemia can also affect results
- don’t do in PSS or icteric patients
Urine bile acids test
- indication: animals with PSS that can’t do normal bile acids test w/o becoming very hypoglycemic
- doesn’t require fasting
- measures bile acids in urine
Ammonia tolerance test
Measures ammonia level before and after injecting ammonium chloride in the colon.
- if high, liver not functioning properly
- rarely used
Fasting ammonia level
- useful in icteric patients that can’t do bile acids test
- can evaluate liver fx and look for evidence of encephalopathy
Why don’t do bile acids test in icteric patient?
Is redundant because bile acids follow same pathway so if bilirubin is increased, bile acids are also increased most likely
Why can fasting ammonia lvl be normal in patient with encephalopathic signs?
If fasted long enough, blood will eventually get to liver and ammonia will get down to normal; we aren’t actively challenging the liver
Coagulation tests
- PT/PTT
- Protein C
*important tests to do if planning to biopsy the liver
If PT/PTT is prolonged, what should you give before performing liver biopsy in dogs?
fresh frozen plasma
If cats have prolonged PT/PTT and hepatic lipidosis, what should be supplemented before liver biopsy?
Vitamin K
Usefulness of measuring Protein C
To differentiate between PSS and portal vein hypoplasia
- if low, more likely PSS
- if normal, more likely portal vein hypoplasia (aka microvascular dysplasia)
Imaging for detecting liver dz: pros and cons of abd. Rads, US, CT
Abd rads: can evaluate liver size and look for problems outside liver, but not very helpful otherwise
Abd US: can see nodules but won’t know what they are w/o aspirates or biopsy. If used with contrast, may be able to differentiate b/w malignant and benign nodule
Abd CT: can diagnose PSS and location of shunt
Types of tissue sampling for liver
- FNA, cytology of specific masses, diffuse neoplasia, or poor inflammatory conditions
- Biopsy
Pros and cons of liver cytology
- only about 40% correlation between cytology and histo results
- poor for inflammatory conditions, cholestasis, fibrosis
- good ID of masses, diffuse neoplasia, vacuolar hepatopathy +/- hepatic lipidosis
Liver anatomy
- hepatocytes are functional unit and metabolically active
- stellate cells part of immune system in liver
- bile duct flows opposite blood flow
- portal and hepatic a. At periphery, central vein in center
- central v. Carries blood out liver and back to vena cava
3 types of liver biopsy and pro/con of each
1) US guided: relatively noninvasive, can’t get large samples
2) Laparoscopy: can get larger samples and look at other organs and the liver, more invasive
3) Laparotomy: good for when you suspect mass will need to be removed, most invasive
