Download Clinical usage of enzymes

Clinical usage of enzymes
Diagnosis of myocardial infarction (MI)
Diagnosis of bone disease
Diagnosis of muscle disorders
Diagnosis of acute pancreatitis
Diagnosis of metastasizing cancer of the
prostate
Diagnosis of myocardial infarction
(MI)
 Myocardial infarct is a necrotic area in the heart caused by a
deficient blood flow to that area as a result of a clot in the
coronary vessel and/or narrowing of the vessel lumen.
 When the cardiac cells in the necrotic area die, their
intracellular enzymes diffuse out of the cell into tissue fluid
and end up in plasma.
 The enzymes tests that help in the diagnosis of MI are:
 Creatine kinase (CK), aspartate aminotransferase(AST or
GOT), lactate dehydrogenase (LD or LDH), isoenzyme CK-MB,
and the isoenzyme of LD.
Aspartate aminotransferase (AST)
 AST is found in practically every tissue of the
body, including red blood cells.
It is in high concentration in cardiac muscle
and liver, intermediate in skeletal muscle and
kidney, and in much lower concentration in
other tissues.
AST concentration increased shortly after
occurrence of MI.
Increased activity of AST
 The serum activity of AST increased after MI, in liver
disorders, in trauma to or in diseases affecting
skeletal muscles, after renal infarct, and in various
hemolytic conditions.
 The serum AST activity begins to rise about 6 to12
hours after MI and return back to normal by 4-6
days after infarct.
Lactate dehydrogenase (LD or LDH)
 Lactate dehydrogenase reversibly catalyzes the oxidation of
lactate to pyruvate by transferring hydrogen from lactate to
cofactor, NAD.
 LD is distributed widely in tissues and in high concentration
in liver, cardiac muscles, kidney, skeletal muscles,
erythrocytes, and other tissues.
 The LD activity in serum does not rise as much as CK or AST
after MI but it does remain elevated for much longer
period of time 7-10 days.
Increased activity of LD
 In myocardial infarction. It may remain
elevated for 7-10 days.
In liver disease, but other test more sensitive
(AST and ALT).
Muscle trauma.
Renal infarct.
Hemolytic diseases.
 Pernicious anemia.
LD isoenzymes
 The LD enzyme is composed of 4 subunits. There are
different polypeptide chains : M type of skeletal
muscle and H type from cardiac muscle. 5 different
isoenzymes are possible from this combination:
1)
2)
3)
4)
5)
HHHH (LD1from heart muscle, RBC, kidney).
MHHH (LD2 also in heart).
MMHH (LD3 in lung and other tissues).
MMMH (LD4 in many tissues).
MMMM (LD5 primary in skeletal muscle and liver).
The serum LD isoenzyme
composition of normal individual
as % of total and as units
Diagnosis of bone disease
Alkaline phosphatase(ALP)
 Alkaline phosphatase ALP are group of enzymes that
split off a terminal phosphate group from organic
phosphate ester in alkaline solution(pH 10).
 ALP is widely distributed in the body and is present in
high concentration in bone (osteoblasts, the cells of
growing bone), intestinal mucosa, and renal tubule
cells.
Alkaline phosphatase(ALP)
20-105u/L
Increased concentration
Decreased concentration
 In all bone disorders
 Paget's disease
 Osteoplastic tumors with
metastasis
 Hyperparathyroidism (Ca,P)
 Rickets
 In liver disease(biliary tree)
 During trimester of
pregnancy
 In rare congenital defect
 Hypophosphatasemia
 In dwarfs.
 Hypothyroidism
 In pernicious anemia
Diagnosis of muscle disorders
Aldolase
• The 3 serum enzymes used most frequently for this
purpose, in order of their general usefulness, are CK,AST,
Aldolase (ALD).
• ALD convert fructose 1.6 diphosphate into 2 triose
phosphate esters, dihydroxy acetone phosphate and
glyceraldehyde 3 phosphate.
• Raised serum ALD level are detectable in all neurogenic
muscle atrophy and temporarily raised following muscle
trauma, surgery when muscles are cut, and intramuscular
injections.
Diagnosis of acute pancreatitis
• It is difficult to establish the diagnosis of acute
pancreatitis without the assistance of lab. tests.
• The patient usually complains of intense pain in
the upper abdomen that could be caused by
several different disorders
• The 2 most commonly tests used for diagnostic
purposes are serum amylase and serum lipase
Serum amylase
0.8-3u/L
Acute pancreatitis is
caused by:
 Blockage of the
pancreatic ducts.
 Injury to pancreatic
tissue by toxin.
 Inflammation.(mumps)
 Trauma.
 Impaired blood flow to
pancreas.
 in human, the amylases are enzymes
that randomly split the 1,4-glycosidic
bonds on the starch chain.
 Amylases are secreted by the salivary
and pancreatic glands into their
respective juices, which enter the
gastrointestinal tract.
 The amylases that is normally present
in serum is derived from both pancreas
and salivary glands.
 The activity of serum amylase rises
following obstruction to flow from
either the salivary or pancreatic
glands.
Serum lipase
 Lipase is an enzyme that hydrolyzes emulsified
triglycerides.
 The pancreas is the principal organ for the
production of lipase, which is secreted in pancreatic
juice with other digestive enzymes.
 The serum activity lipase is rapidly elevated in acute
pancreatitis, but remains elevated for a longer
period of time than amylase.
Serum lipase
28-200u/L
Serum lipase activity is elevated in acute
pancreatitis and may reach 10-40 folds.
The serum lipase activity usually reaches its
maximum at 72 to 96 hours after an attack of
acute pancreatitis and declines more slowly
than does the amylase activity.
Diagnosis of metastasizing cancer of
the prostate
 Cancer of the prostate is common disease that primarily
affects elderly men.
 It is difficult to diagnose in early stages because of the
lack of signs and symptoms.
 Prostate gland is rich in acid phosphatase (ACP), which is
present in lower concentration in many tissues (spleen,
kidney, liver, bone, blood platelets).
 ACP acts optimally below pH 6.0.
 Normal serum has a low activity ACP but in metastasizing
carcinoma of the prostate, its activity increases greatly
and may rise to 3-15 fold.
Serum acid phosphatase (ACP)
0.2-1.8u/L
Increased concentration
 Metastasizing carcinoma of
prostate.
 Bone disease (Paget's
disease or female breast
cancer that has
metastasized to bone).
 After prostate massage.
Decreased concentration
 No clinical significance to
low concentration of serum
ACP