What is an alternative name for AST (aspartate aminotransferase) used in the laboratory setting?
ALT (alanine aminotransferase)?
SGOT (serum glutamic oxaloacetic transaminase)
SGPT (serum glutamic pyruvic transaminase)
What cellular compartments typically contain AST?
Why might this observation be important to the diagnosis of alcoholic liver disease?
AST: cytoplasm and mitochondria
ALT: cytoplasm only
Alcohol is particularly toxic to mitochondria, resulting in increased release of AST relative to ALT.
Which is more specific for liver disease: AST or ALT?
Where is Alkaline Phosphatase (ALK PHOS) found in the liver? What type of liver injury is it associated with?
Where else is it found?
If we are not sure that the source of elevated ALK PHOS is the liver, what else can we check?
ALK PHOS is found on the surface of liver cells adjacent to the bile canaliculi. Therefore, it is more closely associated with cholestatic/obstructive liver disease.
Also found in: bone, intestine, placenta
If unsure of hepatic source, check:
- GGT (most commonly used)
Increased direct (conjugated) bilirubin might indicate what?
Increased indirect (unconjugated) bilirubin might indicate what disease processes?
- Liver injury
- Bile duct problems
- Rare metabolic problems
What lab values are useful indicators of liver synthetic function?
Serum albumin may be used if the patient is on chronic warfarin therapy (would have diagnostically-useless elevated INR)
Give the normal ranges for:
- ALK PHOS
- Total bilirubin
- Direct bilirubin
- Serum albumin
- 10-45 U/L
- 8-40 U/L
- 40-129 U/L
- 0.2-1.0 mg/dL
- 0-0.2 mg/dL
- 3.5-5 g/dL
- 0-50 U/L
Give the type of liver disease typically caused by each of the following (hepatocellular or cholestatic/obstructive)
- Autoimmune hepatitis
- Wilson's disease
- Fatty liver
- Primary biliary sclerosis (PBC)
- Primary sclerosing cholangitis (PSC)
- Viral hepatitis
- Alpha-1-antitrypsin deficiency
- CO and HC
What is elevated in infiltrative liver disease?
Give some examples
ALK PHOS and (occasionally) bilirubin
Examples: tumors, amyloid, sarcoid
What is GGT useful for determining?
The source of ALK PHOS elevation (Is this the liver? If GGT elevated, then yes)
Name some diseases associated with ALT > 500?
What about the transaminase levels expected in alcoholic liver disease?
ALT > 500
- Hepatitis A, B
- Autoimmune hepatitis
- Ischemia (shock liver)
- Stone passage (rare)
Alcoholic liver disease rarely presents with transaminase levels > 300. The expected AST:ALT ratio is >2:1.
In the case of chronic liver disease, why do ALT and AST ultimately fall, but INR continues to increase?
As the liver scars and degrades, it 'burns out' - ALT and AST fall because there just isn't enough injured/dying tissue left to maintain these at elevated levels. However, INR continues to rise because the synthetic capacity of the liver continues to degrade.
High total bilirubin in the abscence of elevated AST, ALT, ALK PHOS, or INR is indicative of what?
A hemolytic process
What other diagnoses/states are important to consider in the setting of isolated ALK PHOS elevation (ALT, AST, and INR normal)?
What might be helpful in determining if these are relevant?
Consider: bone disease, biliary disease, or pregnancy
GGT, 5'-nucleotidase, or fractionation of ALK PHOS are all useful in determining liver origin (but GGT is way cheaper)
What is the differential diagnosis for a man with elevated ALT & AST (~500) with normal INR?
Hepatitis and ischemia are most likely. The normal INR suggests an acute process and autoimmune hepatitis is more likely in a female patient.
What is the differential diagnosis for an isolated elevated alkaline phosphatase?
Primary biliary cirrhosis (not discussed: stones, parasites or other ductal obstructions).
A patient presents with an ALT 35, AST 87, elevated bilirubin and INR. What treatment is indicated?
This patient has alcoholic fatty liver; treat with steroids & pentoxifylline.
A patient presents mildly elevated aminotransfersases and joint pain. What workup should this patient receive?
The suspicion is of hereditary hemochromatosis; check the patient's transferrin and for HFE mutations. If the patient is >40yo or has sufficiently elevated labs, biopsy for cirrhosis.
Treatment is phlebotomy.
A caucasian woman presents with a history of hypothyroidism and markedly increased aminotransferases.
What lab is appropriate to check?
Suspicion is of autoimmune hepatitis; check ANA/ASMA.
A patient with a history of 90g/day alcoholism presents with severe jaundice, elevated AST/bilirubin/INR.
Is a vitamin K infusion indicated?
Probably not. The elevated INR indiates that this is a chronic process potentially with hepatocyte "blowout"; the synthetic capacity may have been lost.