Download Enzymes in the Diagnosis of Pathology

Enzymes in the
Diagnosis of Pathology
Is the field of the measurement of enzyme
activity in a biological speciment (blood,
urine, tissue), can aids or helps or useful in
the diagnosis of diseases, such measurement
may also helped for the follow up ,
assessment of treatment ,prognosis of the
disease.
Normally each enzyme is present in the circulation
within certain range which is called (normal or
reference range ) which represent the net or the
balance of the rate of the release of enzyme by its
turnover and the rate of its disappearance a phenomena
called some time (wear and tear effect ); wear and tears
: normal physiological turnover of the cell.
Protein
K-sys.
k-deg .
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Enzyme in the blood are either normal or
abnormal , where there is disease process the
enzyme activity will increase distribution of
enzyme in different tissue .Ex : Tissue damage
( as in myocardial infraction ) and infection
( as in hepatitis ) cause release of tissue enzyme
into the bloodstream, also in liver disease
leading to biliary obstruction causes an
increase in some enzymes by blocking their
elimination into the bile.
Levels of normal serum enzyme:
Two enzymes whose primary function is in the blood serum
are ceruloplasmin ( transferrin) and cholinesterase .
Ceruoplasmin is a plasma protein with ferroxidase activity .
Normal values are 280-570 units .
This enzyme is used to establish the presence of Wilson’s
disease ( cirrhotic liver ) in which the levels are decreased
from normal .
Cholinesterase found in blood serum is usually called type ll
cholinesterase or pseudocholinesterase , to distinguish it
from type l ,or true cholinesterase of the nervous system
.Normal levels of cholinesterase are 1900-3800 muper ml
of serum, it used for diagnostic test for liver disease where
the level is decreased from normal.
Levels of abnormal enzymes:
( nonplasma , specific enzymes)
These enzymes may be divided into two groups:
1- Secretory enzymes and function outside the body as in
digestion ex: ∞Amylase is produced by the pancrease
.Its appearance in the blood serum is indicative of
pancreatic disorder . The normal serum level is
increased in acute pancreatitis during the first 72 hours
after the onset of symptoms.
2- Intracellular enzymes include :
Alkaline phosphatase : levels of serum enzyme
are elevated in osteological disease ( e.g
osteogenic sarcoma , rickets) or biliary
disorders ( obstructive jaundice cirrhosis).
Acid phosphatase : levels are elevated in
carcinoma of the prostate.
Creatine phosphokinase (CPK ): This
enzyme found primarily in skeletal and
cardiac muscle is elevated in blood after
myocardial infarction (MI).
CPK is a dimer consisting of one subunit
found in the brain (B) and another in
muscle (M) . It is found as three
isozymes,in normal serum ,95‰f the CPK
activity exists as the CPK3 species .
Following myocardial infarction the serum
CPK2 (MB) species increases specifically.
Serum Transaminases: These are serum
glutamic oxaloacetic transaminase (SGOT)
and serum glutamic pyruvic trasaminase
(SGPT).
The added enzyme , malate dehydrogenase
(MDH), catalyzes the reduction of
oxaloacetate to malate and the oxidation of
NADH .normal values are 5 to 20 mU/ml.
Lactate dehydrogenase :
LDH catalyze the interconvertion of lactate and
pyrovate in the presence of NADH or NADH2 .it is
distributed generally in body cells and fluids.normal
value varies with method . any degree of hemolysis
must be avoided because the conc. Of LDH within
red blood cell is 100 times that in normal serum .
Heparin and oxalate may inhibit enzyme activety.
Elevated in all conditions acompanied by tissue
necrosis . normal values are 125-270 mU/ml.
∞-Hydroxybutyrate dehydrogenase ( ∞-HBDH)
Normal values are 96-210mU/ml . actually this
enzyme appears to be the same as LDH-1, its richest
source in heart muscle, kidney , and erythrocytes . in
myocardial infarction ∞-HBDH is usually elevated
for a longer time than is total LDH . elavation will
continue for 2to 3 weeks after infection .
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Change of izoenzyme in MI
The measurement of the serum levels of numerous enzymes has
been shown to be of diagnostic significance. This is because
the presence of these enzymes in the serum indicates that
tissue or cellular damage has occured resulting in the release
of intracellular components into the blood. Hence, when a
physician indicates that he/she is going to assay for liver
enzymes, the purpose is to ascertain the potential for liver cell
damage.
Commonly assayed enzymes are the amino transferases: alanine
transaminase, ALT (sometimes still referred to as serum
glutamate-pyruvate aminotransferase, SGPT) and aspartate
aminotransferase, AST (also referred to as serum glutamateoxaloacetate aminotransferase, SGOT); lactate dehydrogenase,
LDH; creatine kinase, CK (also called creatine phosphokinase,
CPK); gamma-glutamyl transpeptidase, GGT. Other enzymes
are assayed under a variety of different clinical situations but
they will not be covered here.
The typical "liver enzymes" measured are AST and ALT. ALT is
particulary diagnostic of liver involvement as this enzyme is
found predominantly in hepatocytes. When assaying for both
ALT and AST the ratio of the level of these two enzymes can
also be diagnostic. Normally in liver disease or damage that is
not of viral origin the ratio of ALT/AST is less than 1.
However, with viral hepatitis the ALT/AST ratio will be
greater than 1. Measurement of AST is useful not only for liver
involvement but also for heart disease or damage. The level of
AST elevation in the serum is directly proportional to the
number of cells involved as well as on the time following
injury that the AST assay was performed.
Following injury, levels of AST rise within 8 hours and peak 2436 hours later. Within 3-7 days the level of AST should return
to pre-injury levels, provided a continuous insult is not present
or further injury occurs. Although measurement of AST is not,
in and of itself, diagnostic for myocardial infarction, taken
together with LDH and CK measurements the level of AST is
useful for timing of the infarct.
The measurement of LDH is especially diagnostic for myocardial
infarction because this enzyme exist in 5 closely related, but
slightly different forms (isozymes). The 5 types and their
normal distribution and levels in non-disease/injury are listed
below.
LDH 1 - Found in heart and red-blood cells and is 17% - 27% of
the normal serum total.
LDH 2 - Found in heart and red-blood cells and is 27% - 37% of
the normal serum total.
LDH 3 - Found in a variety of organs and is 18% - 25% of the
normal serum total.
LDH 4 - Found in a variety of organs and is 3% - 8% of the
normal serum total.
LDH 5 - Found in liver and skeletal muscle and is 0% - 5% of the
normal serum total.
Following a myocardial infarct the serum levels of LDH
rise within 24-48 hours reaching a peak by 2-3 days and return
to normal in 5-10 days. Especially diagnostic is a comparison
of the LDH-1/LDH-2 ratio. Normally, this ration is less than 1.
A reversal of this ration is referred to as a "flipped LDH.".
Following an acute myocardial infart the flipped LDH ratio
will appear in 12-24 hours and is definitely present by 48
hours in over 80% of patients. Also important is the fact that
persons suffering chest pain due to angina only will not likely
have altered LDH levels.
CPK is found primarily in heart and skeletal muscle as well as the
brain. Therefore, measurement of serum CPK levels is a good
diagnostic for injury to these tissues. The levels of CPK will
rise within 6 hours of injury and peak by around 18 hours. If
the injury is not persistent the level of CK returns to normal
within 2-3 days. Like LDH, there are tissue-specific
isoenzymes of CPK and there designations are described
below.
CPK3 (CPK-MM) is the predominant isoenzyme in muscle and is
100% of the normal serum total.
CPK2 (CPK-MB) accounts for about 35% of the CPK activity
in cardiac muscle, but less than 5% in skeletal muscle and is
0% of the normal serum total.
CPK1 (CPK-BB) is the characteristic isoenzyme in brain and
is in significant amounts in smooth muscle and is 0% of the
normal serum total.
Since most of the released CPK after a myocardial
infarction is CPK-MB, an increased ratio of CPK-MB
to total CPK may help in diagnosis of an acute
infarction, but an increase of total CPK in itself may
not.
CPK-MB levels rise 3-6 hours after a myocardial infarct
and peak 12-24 hours later if no further damage
occurs and returns to normal 12-48 hours after the
infarct.