Interpreting Enzymes And Other Biomarkers

Front 1

enzymes

Back 1

-catalyze chemical rxns within cells
-usually located intracellularly until released with cell death or necrosis
-cleared via kidney once in circulation
-clinical uses for measurement: specific organ damage, follow pts with disease, isoenzyme concentrations helpful for dx

Front 2

Liver anatomy

Back 2

-2 main lobes: thousands of lobules--> hepatocytes (metabolically activE) and kupfer cells
-blood supply: hepatic artery (brings in O2 rich blood), portal vein (brings in nutrient rich blood)
-biliary tree

Front 3

liver cell functions

Back 3

1. production of fat dissolving bile
2. regulation of aa/protein synthesis
3. production of cholesterol and lipoproteins
4. conversion of excess glucose into glycogen
5. storage depot for fat solubule vitamens ADEK
6. iron and other mineral storage
7. conversion of poisonous ammonia to urea
8. clearance of drugs and other waste products from blood

Front 4

Markers of hepatocellular injury

Back 4

-aspartate aminotransferase (AST)
-alanine aminotransferase (ALT)

Front 5

markers of cholestasis (bile doesnt flow normally)

Back 5

-alkaline phosphatase (ALP)
-gamma- glutamyltransferase (GGT)
-bilirubin

Front 6

indicators of liver function/dysfunction

Back 6

-total bilirubin
-albumin
-prothrombin time
-blood ammonia

Front 7

Aspartate Aminotransferase (AST)

Back 7

-tissue sources: myocardial muscle, liver, skeletal muscle, kidney, brain, pancreas, spleen
-function: mediates aspartic and alpha-ketoglutamic acids in the production of proteins

Front 8

AST cont

Back 8

-specimen collection: serum, no pt prep, avoid hemolysis
-elevations most commonly assoc with HEPATOCELLULAR injury
-low levels seen in: severe liver disease, vit B6 deficiency

Front 9

Alanine Aminotransferase (ALT)

Back 9

-tissue sources: Primarily liver, also heart, muscle and kidney
-function: mediates alanine and alpha-ketoglutamic acids in the production of proteins
-more specific for liver damage

Front 10

ALT cont

Back 10

-specimen collection: serum, no pt prep, avoid hemolysis and ASA use
-elevations: HEPATOCELLULAR injury, obese pts, males, AA's and hispanic pop
-chart!

Front 11

1. AST/ALT >1
2. AST/ALT < 1

Back 11

1. think alooholic hepatitis or cirrhosis
2. think acute hepatitis

Front 12

Alkaline phosphatase (ALP)

Back 12

-tissue sources: liver, bone, placenta, intestine, spleen, kidney
-function: removal of phosphate group from proteins and other molecules

Front 13

ALP cont

Back 13

-specimen collection: serum, fasting sample preferred, note pt age and gender on tube
-elevations: CHOLESTASIS
-chart!

Front 14

Gamma-glutamyltransferase (GGT)

Back 14

-tissue sources: liver, kidney, pancreas, brain, heart, salivary glands, prostate
-function: tri-peptide glutathione metabolism

Front 15

GGT cont

Back 15

-specimen collection: serum, avoid concomitant use of phenytoin or barbiturates (causes elevated GGT)
-elevations: BILIARY OBSTRUCTION AND ALCOHOL USE (inc GGT synthesis and release)
-GGT NOT affected by preg or bone disease/growth

Front 16

clinical correlations for GGT

Back 16

-useful for moderate alcohol intake and monitor alcohol rehabilitation
-useful as an adjunct to ALP to diagnose and monitor obstructive liver disease
-inc ALP & inc GGT consider: hepatobiliary disease
-inc ALP & N GGT --> bone disease or growth
-inc GGT & inc AST/ALT ratio --> alcoholic liver disease

Front 17

bilirubin

Back 17

-specimen collection: serum, nonhemolyzed fasting specimen is best, protect from light

Front 18

Jaundice

Back 18

-yellow discoloration
-usually caused by inc bilirubin in circulation
-typically not noted until serum bilirubin >2.5 mg/dL

Front 19

Prehepatic jaundice

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-problem is prior to bilirubin reaching the liver
-excessive production of unconjugated bilirubin
-etiologies: hemolysis, ineffective erythropoiesis
-consequences: could lead to inc amts of conjugated bilirubin entering the gut
lab findings: inc serum indirect and total bilirubin, inc urobilinogen in stool and urine, direct bilirubin is nml

Front 20

intrahepatic jaundice

Back 20

-problems within liver
-varying degrees of hyperbilirubinemia
-sample etiologies and consequences:
1. unconjugated hyperbilirubinemia: gilerts syndrome
2. Conjugated hyperbilirubinemia: intrahepatic inflamm disrupting transport of conjugated bilirubin from hepaticytes, inherited metabolic defects disrupting transport of conjugated bilirubin from hepatocytes, drug induced liver disease

Front 21

posthepatic jaundice

Back 21

-obstruction of bile flow occurs after bilirubin conjugation
-conjugated bilirubin "backs up" into circulation with decreased conjugated bilirubin sent to gut and kidneys
-Etiologies: bile duct stones, gallbladder cancer, pancreative cancer, cholangitis, biliary strictures, pancreatitis

Front 22

posthepatic jaundice- lab findings

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-inc serum direct bilirubin
-inc serum total bilirubin
-dec fecal urobilinogen
-dec urine urobilinogen
-inc urine bilirubin

Front 23

bilirubin:
other causes of elevated and low levels

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Elevated:
1. dark yellow colored specimens (foods and meds)
2. prolonged fasting/ anorexia
Low:
1. exposure to light
2. recent high fat meal
3. specimen vigorously shaken

Front 24

other indicators of liver function

Back 24

1. albumin (low albumin could be liver damage)
2. prothrombin time
3. blood ammonia

Front 25

Pancreatic anatomy

Back 25

-acinar cells (exocrine- into ducts)
enzymatic functions: amylase, lipase, chymotrypsin, phospholipase
-islets of langerhans (endocrine): beta cells-insulin; alpha cells- glucagon

Front 26

Amylase

Back 26

-tissue sources: Pancreas*, salivary glands*, intestine, fallopian tubes, cervical mucosa, skeletal muscle, adipose tissue
-functions: secreted into the duodenum to cleave starches into smaller carbs
-metabolism: cleared from circulation within 2-7 days

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amylase cont

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-specimen collection: serum, urine, can measure in pleural and peritoneal fluid
-test interference: saliva contamination
- > 5x UNL --> acute pancreatitis, pancreatic pseudocyst, morphine administration
- 3-5 x UNL --> pancreatic ca, mumps, salivary gland inflamm, perforated peptic ulcer, ionizing radiation exposure

Front 28

Lipase

Back 28

-tissues: pancreas (more sensitive and specific than amylase!)
-function: secreted into the duodenum to cleave dietary triglycerides into free fatty acids and glyerol
-metabolism: cleared from circulation within 8-14 days
-specimen collection: serum, no pt prep

Front 29

causes of elevated serum lipase

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1. acute pancreatitis
2. morphine use
3. pancreatic cancer

Front 30

Cardiac enzymes and biomarkers

Back 30

-markers are released into circulation when myocardial cell membranes are damaged
-crucial for dx of acute coronary syndrome (ACS)
-EKG may appear nml
-obtain serum samples at admission and then every 8 hrs x 3
-marker patterns helpful for dx

Front 31

Total creatine kinase (CK)

Back 31

-tissue sources: skeletal m (99% MM & <1% MB), cardiac m (80% MM & 20% MB), brain (BB)
-function: catalyzes the production of ATP form creatine phosphatase and ADP
-multiple sources limits diagnostic value
-released with any muscle inflamm, ischemia, necrosis or injury
-specimen collection: serum

Front 32

conditions assoc with increased total CK

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1. MI (>97% sensitive and specific within 48 hrs of symptoms)
2. crush injury
3. electrocution
4. convulsions
5. surgical incisions
6. trauma
7. IM injections
8. muscular dystrophy
9. polymyositis
10. CNA disorders
11. hypothyroidism

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other causes of elevated total CK and low levels

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Elevated:
African Americans
Routine exercise
Marathon runners
Large muscle mass
Weight lifting
Childbirth
Specimen hemolysis
Low: low muscle mass, bedrest

Front 34

CK-MB

Back 34

-predominantly found in cardiac muscle
-used for detection of myocardial infarction
-negative predictive value 95% within 1st hour
-characteristic enzyme changes in MI: rise 4-8 hrs, peak 12-24 hrs, return to baseline 3-4 days

Front 35

clinical disorders assoc with increased CK-MB

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1. MI
2. myocardial ischemia
3. myocarditis
4 muscular dystrophy
5. subarachnoid hemmor

Front 36

CK-MB relative index

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relative index = CK-MB/total CK x 100
-increased CK and CK-MB with ratio >6% indicates cardiac damage

Front 37

Myoglobin

Back 37

-function: O2 binding protein in muscle
-muscle injury leads to release of myoglobin
-earliest and sensitive marker for MI
-characteristic enzyme changes in MI: rise 2-4 hrs, peak 8-10 hrs, return to baseline 24 hrs
-avoid delays in testing
-high myoglobin concentrations interfere with blood test on urine dipstick

Front 38

clinica disorders associated with inc myoglobin

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Myocardial infarction (NPV=99.9% in 1st hour)
Cocaine use
Trauma
IM injection
Polymyositis
Muscular dystrophy
Rhabdomyolosis
Renal failure

Front 39

Troponin (cTnl)

Back 39

-protein components of skeletal and cardiac muscles
-released after myocardial injury
-specific marker for myocardial injury
-characterisitic changes in MI: rise 4-6 hrs, peak 12 hrs, return to baseline 3-10 days
-process test quickly

Front 40

clinical disorders assoc with high Tn I

Back 40

Myocardial infarction
90% sensitivity for MI within 8 hours of symptoms
95% specificity for MI within 8 hours of symptoms
Myocardial injury during surgery/procedure
Myocarditis
Pericarditis
Coronary artery spasm 2o cocaine
Severe heart failure
Pulmonary embolism with cardiac damage
Chronic renal failure

Front 41

analytical interferences for troponin testing

Back 41

1. fibrin clots
2. heterophile ABs
3. rheumatoid factor
4. hemolysis
5. lipemia
-

Front 42

Lactate dehydrogenase (LDH)

Back 42

-tissue sources of isoenzymes
LD1 (heart, brain, RBC)
LD2 (heart, brain, RBC) (normally [LD2]>[LD1])
LD3 (brain, kidney, lung)
LD4 (liver, skeletal muscle, kidney)
LD5 (liver, skeletal muscle, ileum)
-function: catalyzes lactacte + NAD <--> pyruvate

Front 43

LDH cont

Back 43

-released after myocardial damage
-was useful test for detection of "recent: MI (LDH flip) but falling out of use with the advent of troponins
-characteristic changes in MI: rise 8-12 hrs, peak 24-48 hrs, return to baseline 10 days
-avoid hemolysis, take serum off clot asap

Front 44

conditions assoc with LDH1:2 "flip"

Back 44

1. MI
2. Hemolytic anemia
3. prosthetic valve RBC damage

Front 45

other cardiac biomarkers

Back 45

1. Homocystein- aa that can promote atheroscelrosis and clot formation
2. BNP and NT-proBNP
3. High sensitivity C-reactive protein