Clinical Laboratory: Cardiac Enzymes

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What are enzymes?: -substances produced by various organs that facilitate chemical reactions
Enzyme measurements are based on ..: activity not quantity
Why do we measure enzymes?: to gain info concerning specific organ function
Comparison in intracellular and plasma enzyme levels?: Intracellular enzyme levels are much higher then plasma levels
Reasons for elevated plasma enzymes levels?: -stress
-injury
-necrosis
background for Cardiac enzymes: -when cardiac cells die, they release enzymes thus measuring enzymes can assess cell death
-serial measurements are made to assess cardiac damage
-serum measurement is the specimen of choice
When are cardiac enzyme measurement taken?: admission
2-4 hours
6-8 hours
12 hours
Types of cardiac enzymes?: -aspartate aminotransferase (AST) - formerly SGOT
-Lactate dehydrogenase (LDH)
-Creatine Kinase (CK)
-Troponin
AST: -aspartate aminotransferase
-fomerly SGOT
-enzyme used by heart cells
-released after cells are damaged
AST and MI: -AST in elevated 90-95% of acute MI pts
-elevation seen in 8-12 hrs
-peak 24-48 hours
-return to normal 3-8 days
Causes of AST elevation:: -MI
-damage to liver, kidney, skeletal muscle, pancreas (good sensitivity, poor specificity)
-certain drugs (demorol, coumadin)
-chornic hypokalemia
LDH: -lactate dehydrogenasee
-released with damage to liver, kidney, skeletal muscle, RBCs, WBCs, lung, and tumor tissue
-good sensitivity, poor specificity
-samples are very sensitive to hemolysis
-NOT A GOOD CARDIAC INDICATOR
-NOT A RELIABLE PREDICTABLE OF MI IF OTHER DAMAGE OR SURGERY HAS OCCURED
LDH supports dx of unjury or dz involving:: -heart
-liver
-RBCs
-Kidney
-Skeletal muscle
-brain
-lungs
LDH isoenzymes:: LDH1 17-27% mainly heart

LDH2 27-37% RE system (RBC)

LDH3 18-25% Lungs

LDH4 Kidneys/placenta

LDH5 Liver/muscle
LDH and MI: -elevated in 92-95% of all acute MI pts
-LDH1 and LDH2 ratios are reversed
-elevated 24-48 hours
-peaks 48-72 hours
-normalized 5-10 days
- Ratio appears in 12-24 hours and is 80% specific
-slighly more sensitive than AST
**Rarely used anymore because too late of detection (too late elevation)
Creatine Kinase: -involved in conversion of creatine phosphate to creatine in muscle contraction
Where is creatine Kinase is located?: -found mainly in the heart, skeletal muscle, and brain tissue
-damage to any these tissue will elevate the total CK
Creatine Kinase indications?: -used to support diagnosis of myocardial injury
-may indicate neurological or skeletal muscle damage
CK Isoenzymes:: MB: heart fraction 0%
MM: Skeletal muscle 100%
BB: brain and lung 0%
CKMB and MI: -elevated in 90-93% of all acute MI pts
-CKMB rises in 3-6 hrs after MI
-CKMB peaks in 12-24 hrs
-CKMB normalizes within 12-48 hrs
CKMB usually rises in..: -unstable angina
-shock
-malignant hyperthermia
-myocarditis
CKMB does not usually rise in..: -angina
-pulmonary embolism
-CHF
What is used to avoid misdiagnosis of MI?: -ratio of MB: total CK

-a CKMB of 3.0 ng ml with a relative index of >2.5 is highly suggestive of an MI
CKMB is useful in...: -quantifying degree of MI and timing the onset and appropriateness of thrombolytic therapy
What causes a rise in AST and LD but not in CK?: acute liver disease
Total CK rises in...: -moderate strenuous exercise
-distance running
-weight lifting
-DTs
-seizures
-surgery
-delivery
-hypothyroidism
-hypokalemia
Total CK and hypothyroidism and hyopkalemia: -elevated in 80% of pts with hypothyroidism or hypokalemia due to muslce damage
Benefits of CK?: -CKMB can help sort out MI versus strained muscle etc
-normalizes in 12-48 hours
-CKMB does not rise with angina, PE, or CHF
-CK does not rise with acute liver damage (unlike AST and LD)
Normal CK value is based on...: patient size and muslce mass
Is single value of CK useful?: single value is of little value; need to look at trend over time
CKMM is elevated in...: -skeletal muslce injury
-hypoxia
-exercise
-seizure
-inflammation
-IM injection
-hypothyroidism
-hypocalcemia
When should CK measurements be taken?: -admission
-4-6 hours
-12 hours
-18 hours
-24 hours
What are Troponins?: -proteins that exist in skeletal and cardiac muscle
-2 types: T and I
What do Troponins do?: -help regulate muscle contraction
How are cardiac specific troponins separated?: -using monoclonal antibodies or ELISA techniques
Troponin values:: TN T <0.2 ng/ml

TN I < 0.3 ng/ml
Troponin elevation, peak, normalization times:: Elevates: 2-6 hours
Peaks: 12-16 hours
TN I normalizes: 7-10 days
TN T normalizes: 10-14 days
TN vs CKMB: -CKMB can be elevated in severe muscle, brain, or lung injury, or renal failure whereas troponins are always normal in non-cardiac injury
-troponins elevate sooner then CKMB (2-6 hours compared to 3-6 hours)
-troponins stay elevated longer (normalize later) than CKMB (7-10 or 10-14 days compared to 24-48 hours)
So if TN I is so good, why bother with CKMB at all?: because TN I remains elevated for 7-10 days whereas CKMB normalizes within 12-48 hours so you can tell if the pt re-infarcts
Disadvantages to Troponin?: Not helpful for reinfarct

cannot tell if elevation is old or new
Indication for Troponin?: -Eval chest pain since they are extraordinary specific for myocardial cell injury
-determine cardiac iscehmia
-differentiate cardiac from non-cardiac chest pain
-eval of pts with unstable angina (divides those with lasting dysfcn from those without)
-may decide if thrombolytic therapy is appropriate
What is Myoglobin?: -oxygen binding protein found in cardiac and skeletal muslce
-NOT AN ENZYME!!
When is myoglobin test indicated?: -early eval of pt with suspected MI (provides early index of damage to myocardium)
-dx disease or injury to skeletal muscle
when does Myoglobin elevate?: rises: 0-3 hours
peaks: 6-8 hours
normalizes: 20-36 hours
Myoglobin vs CK: -myoglobin is more sensitive than CK isoenzymes but less specific (any trauma or injury may elevate myoglobin)
Cardiac enzymes elevation comparison: Myoglobin (0-3 hr)
Troponin (2-6 hr)
CKMB/ CKtotal (3-6 hr)
AST (8-12 hr)
LDH (24-48 hr)
Cardiac enzymes normalization comparison: CKMB (12-48 hr)
myoglobin (20-36 hrs)
AST (3-8 days)
LDH (5-10 days)
Troponin I (7-10 days)
Cardiac enzymes specificity comparison: troponin (cardiac injury ONLY)
CKMB
AST/LDH
Cardiac enzymes sensitivity comparison: myoglobin (most sensitive, BUT not enzyme)
Troponin
CKMB
LDH
AST
Cardiac enzymes peak comparions: ?

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