Clinical Lab: Liver enzymes, Panreatic enzymes
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- Functions of the liver
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-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?
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-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:
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-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
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LDH
AST
ALT - Example of cytoplasmic related injury
- cell death resulting in leakage of cytoplasmic enzymes LDH, AST, ALT
- Mitochondrial enzymes
- AST
- Examples of mitochondrial injury
- alcohol rapidly releases mitochondrial AST
- Canalicular
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ALP
GGT - Example of canalicular injury
- obstructive process and accumulation of bile acids releases canalicular enzymes ALP and GGT
- ALP
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-alkaline phosphatase
-liver enzyme - Where is ALP found?
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-liver, bone, biliary tract, epithelium, intestinal mucose, placenta
-each source has its own isoenzymes - What is ALP used for?
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-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 ...
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bile
So if bile ducts are blocked, ALP ends up in the serum - Increased ALP suggests:
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-liver tumor or absess
-metastatic disease
-alcoholic cirrhosis
-drug induced liver dz
-biliary tract obstruction
-hyperparathyroidism
-hepatitis
-mononucleosis
-bone tumors
-pagets dz
-fracture healing - AST
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-aspartate aminotransferase
-liver enzyme - AST elevated in...
-
-following MI
-liver disease or injury
-liver tumor or absess
-cirrhosis
-hepatitis
-drug or ETOH damage - AST is a good indicator of...
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acute liver cell damage
bc levels rise and fall quickly - ALT
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-Alanine Aminotransferase
-liver enzyme - ALT is found in..
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-liver
-small amts in kidney, heart, and skeletal muscle - Elevation in ALT suggests...
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-liver disease
-can help sort out binge drinker from alcoholic - ALT vs AST
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-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 - GGT
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-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)
-tumor
-chronic ETOH use and binge drinking - GGT is NOT elevated in...
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-bone disease, growth or pregnancy (unlike ALP)
-not significantly elevated with normal ETOH use - Differences between ALP, ALT, AST and GGT
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-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
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-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)
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-found in serum
-proetin bound
-NOT water soluble
-cannot get into urine - Conjugated bilirubin (Direct)
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-water soluble
-normally excreted in the bile after being processed in the liver - Normal ranges of bilirubin:
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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
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-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
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-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:
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Cancer 45%
Gallstones 25%
ETOH 10%
Meds 10% - pts 30-60 with total bilirubin (indirect and direct) increase:
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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
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Newborn >15 mg/dl (treatment is initiated or mental retardation may result)
Adult >12 mg/dl (indicated sever liver problems) - kernicterus
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mental retardation secondary to increased bilirubin
To prevent/treate, put under UV light which breaks down bilirubin - Hepatic Function Panel
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AST
ALT
ALP
Total Bilirubin
DIrect Bilirubin
Total protein
Albumin - Pancreatic enzymes
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amylase
lipase - Amyalse
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-secreted from pancreatic cells into pancreatic duct
-aids in catabolism of carbs in the intestines - Amylase test used to ..
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-detect and monitor pancreatitis
-often ordered when pt presents with acute abdominal pain - Abnormal values rise and normalize...
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-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...
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-pancreatic disease
-biliary disease
-renal failure
-intestinal obstruction or infarction
-obstructed salivery duct - Lipase
-
-secreted by pancreas into duodenum to break down triglyerides
-excreted by kidney - Lipase test is used for..
- acute pancreatitis
- Lipase increases in...
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-pancreatic disease
-biliary disease
-renal failure
-intestinal obstruction or infarction - Lipase elevation and normalization
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-peaks at 24-48 hours
-normalizes in 7-10 days - Lipase vs Amylase
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-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
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not widely available
time delay in results