Liver Enzymes - Etzion Flashcards
List of Liver Tests
Liver Associated Enzymes:
AST, ALT-more specific (alanine and aspartate aminotransferase for pyruvate and OAA, levels of 30-40U/L-updated: males <=30, females 19)
Alkaline Phosphatase (20-85 umol/L, principal marker of cholestatic injury)
GGT (confirms ALT)
True Liver Function Tests:
Bilirubin
Albumin
Protime/INR (Most important abnormality to signify development of fulminant hepatic failure in course of acute liver disease, correlate with synthetic production or absorption of vitamin K).
Production, Secretion and Excretion of Bilirubin
Breakdown product of heme
70-80% of normal production is from breakdown of hemoglobin in senescent RBCs
Remainder: prematurely destroyed erythroid cells & turnover of hemoproteins (mainly from liver)
Bilirubin released into plasma is water insoluble and thus conjugated to albumin
After bilirubin uptake to the liver it is conjugated mainly to glucoronic acid. This step enables secretion of conjugated bilirubin into the bile system.
In the small intestine, conjugated bilirubin is broken down into urobilogen, excreted in the feces (most) and urine (via kidney).
Urinary bilirubin is broken down and thus never unconjugated (always conjugated).
Total bilirubin= conjugated + unconjugated fractions
Direct bilirubin = conjugated fraction
Indirect bilirubin = unconjugated fraction
Why does increased bilirubin occur?
Increased bilirubin can occur from:
Mainly Unconjugated:
Overproduction of bilirubin (hemolysis)
Uncomplicated hemolysis (rarely levels >5 mg/dL)
Impaired uptake (shunt, drugs), conjugation (Wilson’s disease, neonatal, hyperthyroid), or excretion
Unconjugated and conjugated mixed:
Blockage of bile duct
Regurgitation from damaged hepatocytes of bile ducts
Hepatocellular damage (acute or chronic)
Intrahepatic cholestasis (stroids, allergic)
Canalicular excretion defect
Most common causes of elevated LAEs
Incidental
Acute hepatitis( very high ALT, usually symptomatic)
Chronic hepatitis( modest ALT ↑)
Cholestasis( predominant ALP ↑)
Cirrhosis( portal HTN)
Jaundice
Causes of intrahepatic cirrhosis
Flowchart for liver enzyme evaluation
Send for immediate evaluation:
If >5x upper limit of normal
or
Signs/symptoms or poor liver function
or
Risk factors for liver disease
If <3x ULN:
Repeat every 3-6 months
If 3-5x ULN:
Repeat enzymes in 1-3 months
If ALT and AST <2 ULN:
If asymptomatic: observe
If symptomatic and ruled out previous tests: do liver biopsy
Medications predisposing to elevated liver enzymes
Almost any medication can cause an elevation of liver enzymes
Nonsteroidal anti-inflammatory drugs (controversial), antibiotics, statins, antiepileptic drugs, and antituberculous drugs
herbal preparations and illicit drug use may also be the cause.
Temporal relationship is not always apparent!!! (Make sure to ask about complete drug history and prior visits to doctors)
How to identify alcohol damage in liver enzymes
Dx difficult: many pts conceal alcohol consumption.
Dx is supported by an AST to ALT ratio of 2:1 or greater (but can also be advanced cirrhosis and other diseases)
A twofold elevation of the gamma glutamyltransferase (GGT)
an elevated GGT by itself is insufficiently specific to establish the diagnosis
Hereditary Hemochromatosis Properties and Tests
Highly prevalent gene in caucasians (Autosomal recessive. USA/western Europe-more prevalent than CF. 10% carriers, 1/250 homozygous.)
Increased absorption of iron, not regulated by stores
Diabetes is present in 50% of HH symptomatic patients d/t pancreatic accumulation
Fasting serum iron &TIBC → S-iron/TIBC
Not symptomatic in women until later in life.
hyperpigmentation
fatigue
hepatomegaly (elevated serum aminotransferase)
arthropathy
hypogonadism (impotence in males)
hypothyroidism
cardiomyopathy
Iron sat. > 45%
Serum ferritin > 300ng/mL( M), 200ng/mL(W)
Liver biopsy
Genetic testing
High risk for HCC
Hepatic steatosis: Non-alcoholic Fatty Liver Disease
Properties and tests
Look for metabolic syndrome
Usually mild elevations of TA
AST/ALT<1
US –initial imaging screening test.
Differentiation between simple steatosis and NASH requires a liver biopsy (but no practical difference)
Liver biopsy usually not performed
Non Hepatic Causes of elevated LAE
Muscle disorders (CPK, LDH, aldolase)
Thyroid disorders (TSH, FT3,FT4)
Celiac disease ( TTG, anti endomesial antibodies-confirm with endoscopy/biopsy)
Adrenal insufficiency
Anorexia nervosa
Rare Liver Disorders that cause elevated LAEs
Autoimmune hepatitis:
Young to middle aged women
Elevated TA
Elevated gammaglobulins
Presence of other AI disorders (thyroid,celiac UC)
Serologic markers: ANA, ASMA, anti LKMA
Liver biopsy
Wilson disease
Presentation usually at childhood but should be considered up to 40
Symptoms vary from none to full blown hepatitis
Screening- serum cerruloplasmin, Opthalmologist- Keiser-fleicher ring (iris)
24hr urine collection of quantitative copper excretion
Liver biopsy
Alpha -1 anti trypsin deficiency
Early emphysema worse complication than liver disease
How to determine hepatocellular vs cholestatic (intra/extrahepatic) cause of LFT elevation
Degree of TA elevation
If values 25xULN or higher -hepatocellular
