Chapter 8: Clinical Enzymes Flashcards
Elevated levels of enzymes in serum usually indicates
Tissue damage
- these enzymes have no physiological function in the blood
- increased levels indicate cell damage or death
Release of cellular enzymes is caused by, what?
Necrosis as a result of ischemia, trauma, or toxic substances.
- cells swell in damaged tissue
- damage to cell membrane leads to release of cytoplasmic and membrane bound enzymes
- as holes become larger, more and larger proteins are able to escape as the cell dies
TISSUE DAMAGE —> ENZYME RELEASE INTO BODY FLUIDS
Extent of increase in serum enzymes is a marker of what?
Severity of cell damage.
More tissue damaged —> greater number of cells lyse —> greater increase in enzyme levels
More severe tissue damage —> release of enzymes from intercellular organelles —> cell death
What are the exceptions in which elevated enzymes levels do NOT imply tissue damage?
- Cell proliferation
- Increase in enzyme synthesis within tissues
- Increase turnover rates
Describe cell proliferation
Cell proliferation is the process that results in an increase of the number of cells , and is defined by the balance between cell divisions and cell loss through cell death or differentiation. Cell proliferation is increased in tumors.
Even if the same percent of cells turns over, there are more cells lysing at any given time which results in higher serum levels.
Example: serum levels of PSA increase in cases of benign prostatic hypertrophy and prostate cancer
Describe increase in enzyme synthesis within tissues
GGT synthesis is induced in response to certain medications and to alcohol consumption.
With normal cell turnover, each cell will “spill” larger amounts of GGT into the serum.
In addition, GGT is a plasma membrane protein which may be released without cell death.
Describe increased turnover rates.
ALK is expressed at high levels in bone and, if a bone is broken, serum ALK will be elevated.
However, elevated serum ALK will be seen in pediatric patients during periods of rapid growth due to bone remodeling.
In the case of bone remodeling, elevated ALK if not associated with tissue injury.
What do enzyme levels in the serum depend on?
On how fast the enzyme enters and is cleared from the bloodstream.
Key factors are molecular weight (size) of the enzyme
Rate of lymph drainage (affected by muscle activity)
Since muscle need energy which levels will be expressed highly?
CK, LDH and AST but not ALT, GGT or ALK.
Elevated CK, particularly with normal ALT, GGT and ALK —> can conclude muscle tissue damage
Simple cases of ALK and LDH.
If ALK is high and all other values are normal, conclude bone is damaged.
If LDH is high and all other values are normal. Conclude RBCs are lysed.
Complicated case: if LDH is elevated, how do you know if it was released from liver, muscle or RBC?
Enzyme patterns:
If liver is damaged, LDH is released with AST, GGT and ALK.
If muscle is damaged, LDH is released with CK and AST.
If RBCs are damaged, only LDH is released.
Why are isozymes important?
The different subunit composition of isozymes allows the tissue source of these enzymes to be determined.
CK: Sumer of two different subunits —> 3 isozymes
LDH: reframed of two different subunits —> 5 isozymes
Name the three different types of CK isozymes.
CK-MM = muscle CK-BB = non muscle tissue CK-MB = small concentrations in all tissues
How are isozymes determined?
Most tears for serum levels of CK do not identify which isozyme is present. Additional tests suck as electrophoresis are needed to separate and identify subunit composition. This assay is not routinely done and is one reason cardiac troponin is replacing CK as a marker for acute MI.
What is serial determination used for?
Serial determination (enzyme measurements taken at specific time intervals) are used to document the rise and fall of an enzyme over time.
A single release will give a characteristic rise and fall which depend on the properties of the enzyme.
Rare of elimination from the blood depends on molecular weight.
Different isozymes have different half-lives which affects the clearance rate of the enzyme from the serum.
What are the 5 isozymes of LDH?
LDH 1 - hear muscle and red blood cells LDH 2 - white blood cells LDH 3 - Lung LDH 4 - kidney, placenta and pancreas LDH 5 - lived and skeletal muscle
** isozymes help determine location
LDH will be elevated with all tissues in table except bone. How can you use serial determination of levels in serum to determine damaged tissue without testing for isozyme type?
Hemolysis
- a patient will have extra high levels of LDH in the serum.
- as LDH 1 has a long half life in the blood, levels will remain high for a long time.
Liver damage
- LDH 5 turns over more rapidly. Serial determination will show rapid clearance of LDH.
LDH levels will be much higher if hemolysis is occurring than if liver is damaged.
- initial levels of LDH will be high in RBCs as they rely solely on anaerobic glycolysis for energy
Example of MI.
Heart attack
— vessel partially occluded by plaque
— color forms around plaque to completely block artery —>
— ischemia —> tissue damage —> damage of cardiac enzymes
After an MI, expect elevated CK, normal ALT, GGT, and ALK. Conclude muscle is damaged.
Elevated serum LDH and AST are also seen but only LDH is used clinically.
LDH for MI
LDH detectable days after an MI.
LDH rises 24-72 hours after a heart attack, peaks 3-4 days and returns to normal in 14 days. Because LDH is of higher molecular weight than CK, it enters the blood More slowly and is cleared more slowly.
Normally LDH 2 > LDH 1
After MI, LDH 1 > LDH 2
CK in MI
CK is abundant in muscle and levels rise high after an MI.
Isozymes are key in interpretation of CK results. Large amounts of CK-MM will be seen after an MI but presence does not indicate whether source of CK was heart or skeletal muscle
CK-MB is crucial for CKs importance in MI diagnosis (22x more abundant in heart and skeletal muscle)
Troponin in MI
Troponin is a high molecular weight protein that remains in serum for longer period of time than either CK or LDH.
— important for silent MI because it can be detected days later
