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Clinical Lab: Liver enzymes, Panreatic enzymes


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Functions of the liver
-major site for synthesis of proteins, endogenous lipids, and lipoproteins
-major site for metabolism of lipid soluble drugs and other toxic compounds
-involved in storage of energy as glycogen
-vitamins A, D, B12
-endorcrine organ that synthesizes angiotensinogen and triiodothyronine
-site for clearance for many hormones (inuslin, parathyroid hormone, estrogen, cortisol)
Purpose of Liver function tests?
-give indication of hepatic structure, intregity, and function
-measure substances released by damaged tissues
-measures substances metabolized/produced by the liver
-used for screening, identifying, and monitoring pts with liver disease
Liver enzymes include:
-alkaline phosphatase (ALP)
-Aspartate aminotransferase (AST); formerly SGOT
-Alanine Aminotransferase (ALT); formerly SGPT
-Lactate dehydrogenase (LDH)
-Gamma glutamyltransferases (GGT)
How are patterns in enzyme changes determined?
liver injury determines the pattern
Cytoplasic enzymes
Example of cytoplasmic related injury
cell death resulting in leakage of cytoplasmic enzymes LDH, AST, ALT
Mitochondrial enzymes
Examples of mitochondrial injury
alcohol rapidly releases mitochondrial AST
Example of canalicular injury
obstructive process and accumulation of bile acids releases canalicular enzymes ALP and GGT
-alkaline phosphatase
-liver enzyme
Where is ALP found?
-liver, bone, biliary tract, epithelium, intestinal mucose, placenta
-each source has its own isoenzymes
What is ALP used for?
-index of liver and bone disease
-enzyme rises in proportion to new bone cell production
-blood levels rise when excretion from the liver is impaired
ALP is normally elevated in...
children due to bone growth
Liver and biliary tract excrete ALP into the ...

So if bile ducts are blocked, ALP ends up in the serum
Increased ALP suggests:
-liver tumor or absess
-metastatic disease
-alcoholic cirrhosis
-drug induced liver dz
-biliary tract obstruction
-bone tumors
-pagets dz
-fracture healing
-aspartate aminotransferase
-liver enzyme
AST elevated in...
-following MI
-liver disease or injury
-liver tumor or absess
-drug or ETOH damage
AST is a good indicator of...
acute liver cell damage

bc levels rise and fall quickly
-Alanine Aminotransferase
-liver enzyme
ALT is found in..
-small amts in kidney, heart, and skeletal muscle
Elevation in ALT suggests...
-liver disease

-can help sort out binge drinker from alcoholic
-elevated to same degree in hepatitis, mono, drug induced acute liver injury
-ALT less than AST in acute alcoholic liver disease or active cirrhosis
-ALT elevated longer than AST d/t longer half life
-ALT often used to confirm AST elevations are d/t liver injury
-Gamma Glutamyltransferase
-liver enzyme
Where is GGT found?
-mainly in liver
-small amounts in biliary tract, heart, intestine, brain, pancreas and spleen
GGT is elevated in...
-active liver disease (acute damage or biliary obstruction)
-chronic ETOH use and binge drinking
GGT is NOT elevated in...
-bone disease, growth or pregnancy (unlike ALP)
-not significantly elevated with normal ETOH use
Differences between ALP, ALT, AST and GGT
-ALP increases in bone disease, bone growth, and pregnancy whereas others do not
-GGT may help confirm that rise is d/t liver damage
-AST is more sensitive thand ALT for acute alcoholic liver disease or active cirrhosis
-GGT has same or better sensitivy as ALP for obstruction
-GGT has better sensitivity for tumor than ALP
-GGT elevated with same frequency as AST for actue liver injury
ALT often used to confirm AST elevations are d/t liver injury
-ALT and AST elevated to same degree in hepatitis, mono, drug induced acute liver injury
Bilirubin basics
-results from metabolism of heme (found in hemoglobin, myoglobin, and cytochromes
-byproduct of hemolysis (RBC destruction)
-small amount in serum is normal
-is cleared in liver
Unconjugated bilirubin (Indirect)
-found in serum
-proetin bound
-NOT water soluble
-cannot get into urine
Conjugated bilirubin (Direct)
-water soluble
-normally excreted in the bile after being processed in the liver
Normal ranges of bilirubin:
Total < 1.5 mg/dl

Direct < 0.4 mg/dl

Indirect cannot be measured, must be calculated

Take note that there is usually far more unconjugated (indirect) than conjugated (direct)
Extra-hepatic biliary tract obstruction
-common bile duct obstruction (gall stones, carcinoma at the head of pancreas)
-conjugated bilirubin rises initially
-as levels of conjugated bilirubin rise, it becomes protein bound and ratio of conjugated to unconjugated approached 1:1 (usually there is far more unconjugated bilirubin)
Intra-hepatic biliary tract obstruction
-from liver cell injury (hepatitis, cirrhosis, drugs, mononucleosis)
-conjugated and unconjugated both rise
-conjugated rises d/t blockage of small bile passages between cells
-unconjugated rises d/t inability of the liver to conjugate/metabolize
Pts >60 with a bilirubin increase:
Cancer 45%
Gallstones 25%
ETOH 10%
Meds 10%
pts 30-60 with total bilirubin (indirect and direct) increase:
viral infection 30%
ETOH 30%
Gallstones 30%
Cancer 10%
Pts <30 with bilirubin increase:
viral >80%
Normal level of total bilirubin rules out....
any significant impairment of the excretory function of the liver or excesive hemolysis of RBCs
Bilirubin: Critical Values
Newborn >15 mg/dl (treatment is initiated or mental retardation may result)

Adult >12 mg/dl (indicated sever liver problems)
mental retardation secondary to increased bilirubin

To prevent/treate, put under UV light which breaks down bilirubin
Hepatic Function Panel
Total Bilirubin
DIrect Bilirubin
Total protein
Pancreatic enzymes
-secreted from pancreatic cells into pancreatic duct
-aids in catabolism of carbs in the intestines
Amylase test used to ..
-detect and monitor pancreatitis
-often ordered when pt presents with acute abdominal pain
Abnormal values rise and normalize...
-rise within 12 hours of onset of disease
-clear within 48-72 hours of initial insult (cleared by kidneys)
Do abnormal levels of amylase correlate with severity of disease?
No, levels rise and fall easily - they do not indicate how severe the disease is
Amylase increases in...
-pancreatic disease
-biliary disease
-renal failure
-intestinal obstruction or infarction
-obstructed salivery duct
-secreted by pancreas into duodenum to break down triglyerides
-excreted by kidney
Lipase test is used for..
acute pancreatitis
Lipase increases in...
-pancreatic disease
-biliary disease
-renal failure
-intestinal obstruction or infarction
Lipase elevation and normalization
-peaks at 24-48 hours
-normalizes in 7-10 days
Lipase vs Amylase
-lipase levels parallel the rise in amylase but rise later (peak 24-48 hours vs 12 hrs)
-lipse levels normalize later than amylase (7-10 days vs 48-72 hrs)
-lipase is less sensitive but more specific then amylase as indicator for pancreatitis
-amylase will rise with blocked salivary duct as well
Serum immunoreactive trypsin
-produced only by pancreas
SIT increases with...
pancreatitis (95% of the time)
Advantages of SIT
VERy specific and VERY sensitive (~95%)
Disadvantages of SIT
not widely available
time delay in results

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