Plasma enzymes Flashcards
what is an Enzyme?
enzymes are proteins that act act as biological catalysr, altering reaction rates and providing a means of regulating metabolic rxn?
how are plasma enzymes measured?
by their biological activity or their masses
which enzymes fulfil their physiological function in the plasma?
renin and coagulation factors
enzymes are naturally present in the plasmadue to turn over.What happens when damage to cell occurs?
there is increased amounts of enzymes willbe released and their concentrations in the blood will rise.
Not all increases of enzymes levels are due to cell damage. what are other factors?
- increase cell turnover
- cellular proliferation ( e.g. neoplasmia)
- increased enzyme synthesis ( enzyme induction)
- decreased clearance
- obstruction to secretion
Reduced plasma enzyme activity maybe caused by ?
- genetic abnormality
- reduced activity
- reduced cell production
most enzymes are removed by which cells?
reticuloendothelial cells and amylase is removed by glomeruli cells becasue the component is small enough to be filtered
plasma amylase activity rises in which diease forms?
acute renal failure, change in clearance is not as important as changes in plasma enzymes
what is an isoenzyme?
different molecular forms of proteins with the same catalyic activity. an isoenzyme may be unique to a tissue or several may be present in proportion charactistic of a tissue.
how are isoenzymes measured?
individually measured or detected by exploiting differences in their biological or physio-chemical properties.
enzyme assays usually depend on the measurement of?
measurement of catalytic activity of the enzyme, rather than the concentration of the enzyme protein itself.
why does assays for enzymes require optimised and standardised testing ot be reliable?
because each enzyme molecule can catalyse the reaction of many reactions of many molecules of substate , measurement of activity provides great sensitivity.
Disadvantages of enzyme assay
- lack of specificity to a particular tissue or cell types especiallly in diagnosis of tissue damage.
- many enzymes are common to more than one tissue, and hence if may be hard to determine where the tissue is damage.
- after a singly damage to the tissue there is a rise in the level as the ezyme is release and as the enzyme is cleared it is released. it is important to check the time the test was taken and not the result.
Many enzymes are common to more than one tissue, hence when there is an increase in enzyme it is likely that the tissue origin is not known. this problem may be obviated in two ways
- different tissues may contain two or more enzymes in different portions. e.g ASt and ALT are both release in the heart and liver cells. but ALT is more common in liver cells .
- some enzymes exist in different form such as isoenzymes. individual isoforms are often characteristic of a particular tissue, although they may have similiar catalytic activities they often differ in some other measureable property such as heat stability.
3.
There are two types of Aminotranferase. what are they?
- alanine aminotransferase
- aspartate aminotransferase
AST Is lower or higher in most cells except the liver
LOWER
Where is AST found in liver cells?
Mitochondria and cytosol
ALT is found where in liver cells?
Cytosol only
AST is released in which tissue other than the liver?
- caradiac muscle
- skelItalianpancreas
- RBC
high levels of AST and ALT are indicative of ?
severe liver damage, acute hepatitis, crush injuries and tissue hypoxia
what does ULN mean?
Upper limit of normal
In inflammatory or infective conditions, such as viral hepatitis which enzyme is higher
ALT
In inflitative disorder which liver enzyme is higher
AST because there is damage to both mitochondrial and cytoplasmi membranes .
in hepatocellular disease plasma levels of transaminases are
10- 100 times higher ULN
in uncomplicated Cholestasis (obstruction) what is the rate of of transminase
less than 10 times ULN
levels of AST to up 2x ULN without cell damage
Alcoholism
ALP means?
Alkaline Phosphatase
What is alkaline phosphatase?
a group of glycoprotein enzymes that act as a phosphotransferases by hydrolysing various types of monophosphate bond at alkaline pH.
where is ALP found?
liver, bone (osteoblast), placenta and intestinal epithelium.
Pathological increases in ALP activity are seen in?
Cholestatic liver disease and in bone diseases in which there is an increase in osteoblastic activity e.g. Paget disease and osteomalacia.
what is the level of ALP in obstructive cholestasis?
Greater than 3 times the ULN. approximately 350 ULN
hepatocelular disease the level of ALP is?
a slight increase but less than three times ULN (150 - 300)
in the liver ALP is found on two sites. which are?
- the sinusoidal surfaces of hepatocytes
- the microvilli of the bile canaliculi
The isoenzyme of ALP is found in which conditions?
- pregnancy
- growing children
Is ALP activity higher or lower in normal healthy eldery people?
Higher , thi smay reflect the high incidence of mild sub-clinical Paget’s disease in the elderly.
Is ALP increased in osteoporosis?
No, unless it there is a fracture .
ALP levels are increased in which type of tumours.
Bony and hepatic origin and seen in primary and secondary tumours.
Regan Isoenzyme
- found in patients with bronchial carcinoma
- similiar heat stablity to placental ALP
The origin of isoenzyme ALP is done by measuring ?
tissue specific isoenzyme of ALP
an alternative tp meeasuring ALP is?
- gamma- glutamyl transferase
What does GGT Stands for?
Gamma- Glutamyl transferase
Where is GGT found?
in widely distrubuted thoughout the body and is present in the kidneys, liver and pancreas
elevated plasma levels of GGT indicates ?
Hepatic disease
Where in the liver is GGT found?
bile canaliculi, the epithelial cells lining the bile ducts and to a certain extend the periportal hepatocytes.
Measurement of its plasma activity provides a sensitive indicator of?
Hepatobiliary Disease, but it cant distinguish btw cholestatic or hepatocellular disease
In which disease does GGT increase before ALP
Biliary obstruction
Plasma GGT can be raised in the absence of liver disease in which situations?
in taking drugs for TB. anticonvulsant drugs phenytoin and phenobaritone, rifampicin.
the increased plasma GGT is not due to cell damage but
to an increase in enzyme production within cells with the result that an increased during normal cell turnonver.
Plasma GGT can remain elevated for up to how many weeks?
3-4 weeks. following absintence from alcohol, even in the absence of liver damage.
Describe creatine phosphokinase (CPK) or CK
- enzyme found mainly in the skeletal muscle and heart and brain
- it catalyses the transfer of phosphate groups from creatine phosphate to adensoine diphosphate, yielding ATP and creatine.
what are the 3 isoenzymes of Ck.
- MM
- MB
- BB
MM
is found in the cardiac muscle and skeletal muscle
MB
found in the cardiac muscle and trace in skeletal muscle
BB
Brain, only CK form present in the CSF
whic isoenzyme is mainly in the skeletal muscles?
MM
which isoenzyme is found in different porportions thoughout the myocardian, approximately ranging from 10%- 40%
MM
Normal leakage of CK plasma activity is ?
>97MM and < 3 MB. the level of BB is usually low in severe brain danage.
how do you know when the CK is of cardiac origin?
more than 5% of the total CK is due to the isoenzyme MB
in children the levels of CK is higher or lower
2-3 higher in children and then falls in adults.
female or males have a higher CK activity
Males <240 females <170
Why is CK- MB the major marker for cardiac disease?
it located in the heart on an activity per tissue weight basis . (myocardium: skeletal > 20)
the level of which isoenzyme is increased in muscle regenerating and muscle that has prolonged activity, e.g heavy athletic training.
CK- MB
Following an acute myocardium infaction
- level of CK-MB rises within 3-8 hours
- reaches a peak in about 10-24hrs if there is no infarct extension
- with a half life of 12 hours
- MB activity would return to normal after 2-3 days of an uncomplicated MI
what is the suggested way of diagnosing a MI
taking samples at admission. 12 and 24 hours .
CK- MB is found in whAT CONDITIONS?
Crushing Syndrome, major surgery, defibrillation, cardiac procedures, severe exercise, rhabomyolysis, and malignant hypothermia.
CK-MB can be measured by?
- enzyme mass using immunoassay
- enzyme activity in the presence of antibodies.
describe Lactate dehydrogenase
cytoplamsic enzyme found in all tissue and reversibly catalyses the reduction of pyruvate to lactate, using NADH as co enzyme.
LD1
- HHHH
- heart, RBC, kidney
LD2
- HHHM
- heart, RBC, kidney
LD3
HHMM
Lung, Spleen, Platelets
LD4
HMMM
Liver, skeletal muscle
LD5
MMMM
Liver, skeletal muscle
Plasma LD activity indicates?
Normal Leakage from tissue and erthyroctyes
when does the levels of LD in children lower
age 12-15
Total LD level is elevated in non-haemolysed plasma in?
- myocardial infarction
- liver disease
- skeletal muscle
- leukemia
- pernicious anemia
- renal infarction
- congestive cardiac failure
- hypothyriodism
- myeloproliferative disorders
In uncomplicated MI, LD activity?
- starts to rise 8-12 hrs post infaction
- peaks 3-5 days after
- half life of 100 hours
- remain in the plasma for 10 days or more
which LD is seen in a wide variety of malignancies?
LD3
which LD is seen in viral hepatits?
LD5
Very high LD actvity (>15-20 folds) is seen in?
acute leukemia
lymphomas mainly due to LD2, LD3
Describe Amylase?
- breaks down starch and glycogen.
- present in high concentration in pancreatic juice and saliva
- seen in gonads, fallopian tubes, skeletal muscle and adipose tissues
Increased plasma amylase in seen and used to diagnosis whihc conditions?
pancreatitis
Pancreatitis is caused mainly by?
gall stones
alcohol ingestion
the structural damage to the pancreas allows the release of
pancreatic enzymes (lipase and amylase) whihc then attack and damge healthy pancreatic tissue
why are high enzymes level found in the peritoneal area?
the released of the enzymes are absorbed from the peritoneal area by the lymphatic system and enter the bloodstream via the thoracic duct.
Hyperamylasaemia is not a pathogmic for pancreatits, but very elevated activity over the ULn is a?
a diagnosis of pancreatitis
follwing an acute attack, Amylase
- rises 2-12 hrs
- reaches a maximum in 12 hrs
- returns to normal within 3 days
what is the half life of amylase
12 hours.
Marked increase in plasma amylase is found in?
- acute pancreatitis
- severe glomerular impairment
- diabetic ketoacidosis
- perforated peptic ulcer
moderate increase in amylase is seen in?
- acute cholecystitis
- intestinal obstruction
- abdominal trauma
- ruptured ectopic pregnancy
- salivary gland disorder
- severe glomerulay dysfunction
- acute alcohol intoxication
- macroamylasamemia
Acid phosphatase function?
hydrolyses phosphate esters at ph < 7.0
where is acid phosphatase found?
prostate
liver
RBC
platelets
spleen
bone marrow
Half of the serum acid phosphatase in males is found in?
prostate and the remainder are found in bone marrow, platelets, rbc, and liver contributes.
prostate specific phosphatase is markedly raised in the majority of patients with
metastatic prostate cancer.
prostate specific antigen should only be used for?
monitoring treatment purposes only and not diagnosis
