Angel Mahan keywords 7/2010
HBF = approximately 100mL X 100g X min
Portal vein supplies 75% of HBF, 50-55% of hepatic oxygen requirement
Hepatic Artery supplies 25% of HBF, 45-50% of hepatic O2 requirement
-abnormalities in standard liver enzyme tests (AST, ALT, and alkaline phosphatase) occur in 0.1% to 4 % of general population, but clinically significant hepatic dysfxn in asymptomatic pts is <1%.
(normal 8.4-12sec)
- Extrinsic coagulation pathway, measures the activity of fibrinogen ( t1/2 = 4 days), prothrombin (factor II), factors V, VII, IX and X
- Factor VII short half-life (4-6hr, the most rapidly cleared coagulation factor), most important qualitative measure of the liver’s function and ability to synthesize proteins in both ACUTE and chronic liver failure.
-more sensitive index of hepatic fxn than albumin
-PT prolonged > 3-4 secs (correlating to INR approximately > 1.5) is associated with a poor 6 month survival
INR the most sensitive indicator of the severity of hepatocellular dysfunction
-other causes of prolonged PT: vitamin K deficiency (malnutrition, CF), drugs
(coumadin), decreased plasminogen levels, and fibrinolysis and DIC
-failure of PT to correct after parenteral vitamin K (takes up to 24hr) implies severe liver disease
(nml 3.5-5.5 g/dL)
-indirect measure of synthetic capacity of liver, synthesized solely in liver
-half life 2-3 wks (approx. 21 days) so can be nml in acute liver disease
-causes of decreased serum albumin (significant if < 2.5 g/dL): liver disease, severe malnutrition, increased losses i.e.: nephrotic syndrome, burns, ascites, and protein losing enteropathies
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Unconjugated (indirect) bilirubin: (nml 0.2-0.8 mg/dL) may be secondary to hemolysis or congenital (Gilbert’s syndrome) or acquired defects in bilirubin conjugation.
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Conjugated (direct) bilirubin: (nml 0-0.3 mg/dL) elevated (>50% of t. bilirubin) associated with increased urinary urobilinogen and may reflect hepatic cellular dysfxn, intrahepatic cholestasis, or extrahepatic biliary obstruction (gallstones)
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Jaundice occurs with total bilirubin levels > 3mg/dL (nml t. bili= , 1.1)
-released in response to acute hepatic injury (active disease), magnitude of rise does not necessarily correlate with severity of disease (i.e. can be decreased in end stage liver dz)

-not good indication of synthetic hepatic fxn (which is better measured by serum bilirubin, albumin, and PT)
- AST and ALT sensitive but not specific for liver dz
-AST less specific of cellular hepatic injury compared to ALT
-circulating t1/2 18-36 hr
-high AST/ALT suggestive of Etoh liver dz.
Aspartate aminotransferase (AST or SGOT) (nml 12-31 U/L)
nonspecific for liver, is located in liver, heart, skeletal muscle, brain, pancreas, adipose bld and kidneys so can be elevated after MI or skeletal muscle injury
Alanine amino transferase (ALT) (nml 10-32 U/L)
primarily located in liver so more specific than AST for liver dz.
Glutathione S transferase
relatively sensitive and specific test for detecting drug induced hepatocellular damage, t1/2 90 min. so rapidly released into circulation following hepatocelluar injury
(nml 90-240 U/dL)
t ½ approx. 7 days
released from bile ducts in response to acute liver dz., elevated in obstructive jaundice
Increased AP and sourced of serum AP: liver, bone (metastatic bone dz i.e...
Paget’s dz, hyperparathyroidism, rickets and osteomalacia, or nml bone when growing rapidly around puberty), placenta (usually around 3 rd
trimester of pregnancy), intestine (can be released after fatty meal), kidney, leukocytes, neoplasms (pancreatic CA)
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5’ nucleotidase (5’-NT):
sensitive (similar to AP) and specific for detecting hepatobiliary disorders
Gamma-glutamyl-transpeptidase (GGTP ): less specific than 5/-NT but more specific in comparison to AP alone as marker for hepatobiliary dz., bone has very little GGTP so good for differentiating hepatic vs. osseous source of AP.
increased serum gaba globulin level is a marker for chronic severe hepatic dz.
Quantitative Tests to assess hepatocellular fxn:
measure clearance of substances that liver acidly extracts: bromsulphalein, indocyanine green, rose Bengal (gives info about the mass of working hepatocytes)
measurement of drug metabolizing capacity: galactose elimination capacity, aminopyrine breath test, antipyrine clearance, monoethylglycinexylidide (MEGXlidocaine metabolite measured in bld taken 15 min after an IV lidocaine 1mg/kg), and caffeine clearance