Objectives:

Identify the main groups of enzymes in

plasma.
Enumerate examples of enzymes reflecting
organ pathophysiology.
Discuss enzymes useful in diagnosis of
myocardial infarction.
Discuss enzymes useful in diagnosis of
hepatobiliary disorders.
Discuss enzymes useful in diagnosis of
pancreatitis.
Plasma enzymes are divided into
A. Enzymes that have definite physiological
functions in the circulation
Lipoprotein lipase
Lecithin cholesterol acyl transferase LCAT
Butyrylcholine esterase
Proenzymes of blood coagulation and
fibrinolysis
B. Enzymes that reflect organ pathophysiology
Normally present in extremely low
concentrations in plasma as compared with
their high concentrations in various tissues.
In case of tissue damage, they are released
in greater amounts causing higher plasma
levels which have diagnostic and
sometimes prognostic significance.
:Among this group are
1) Enzymes present in exocrine secretions,
which diffuse passively into circulation
e.g. amylase and lipase in pancreatic
disorders.

2) Intracellular enzymes. These include most

of the enzymes used to detect underlying
pathological disorders of the various
organs of the body e.g. myocardial
infarction and hepatitis.
Increased release of intracellular
enzymes in the circulation may be due
:to
 Cell necrosis due to ischaemia or toxic agents
Myocardial infarction, viral hepatitis.

 Increased turnover rate e.g. in malignancy

Ca prostate →↑Acid phosphatase
↑osteoblastic activity →↑alkaline phosphatase

↑Production by the cell (enzyme induction)

↑alkaline phosphatase in cholestasis.
PLASMA ENZYMES USEFUL IN DIAGNOSIS
OF MYOCARDIAL INFARCTION
Creatine kinase (CK).
Creatine kinase-MB (CK-MB) isoenzyme
Lactate dehydrogenase (LDH).
Aspartate aminotransferase (AST).
Other Cardiac Markers:
Troponin T
Troponin I
Myoglobin
 Creatine kinase CK
Mainly useful in detecting damage to myocardial and
skeletal muscle tissue.

It is composed of two polypeptide chains designated

M (muscle) and B (brain)

Three isoenzymes are present human tissues.

CK-BB (Brain form) N: Absent in blood
CK-MB (Cardiac form) N < 6% of total CK activity
CK-MM (Skeletal Ms. form) N > 95% of total activity
Reference range of total CK activity:
Males: Up to 180 U/L at 37°C
Females: 25-40% lower than in males
(proportional to the muscle mass).
↑ total CK activity
Myocardial damage
Skeletal muscle damage.
Muscular exercise
Repeated intramuscular injections
Drugs e.g. digoxin and lidocaine
↑ CK- MB isoenzyme
myocardial damage
Time sequence of serum total CK after
myocardial infarction
• begins to rise 4-6 hours
• peaks 24 hours
• returns to normal in 3-4 days

Time sequence of CK-MB

• Rises and returns to normal sooner than total
CK
• Rises in 3-4 hours
• Returns to normal in 2 days
• Serial estimations of total CK and MB
isoenzyme four or six hourly for 24-36 hours
after onset of chest pain are most valuable.

• Absent elevation of MB form during this

period is against myocardial infarction and
its increase is very suggestive.

• The MB fraction is rapidly cleared from the

circulation. Usually absent 36 hours after an
attack.
Aspartate aminotransferase
•Starts to rise 4 to 6 hs after attack
• Peaks after 24-36 hs (2 – 10x ULN)
•Falls to normal in 4 to 5 days.
N.B.
• In acute liver cell damage, level may reach
100 x ULN, returns normal after 3 – 5 weeks
• In chronic liver disease, smaller elevations
occur
Lactate Dehydrogenase
• Present in almost all tissues
• ↑in disorders affecting many organs and systems
• Most often measured in myocardial infarction.
Structure
4 polypeptide chains either H (heart) or M (muscle)
Five isoenzymes with different subunit combinations:
LD1 LD2 LD3 LD4 LD5
(H4) (H3M) (H2M2) (HM3) (M4)

Cardiac Ms Liver, Skeletal Ms

Time sequence of LDH after myocardial infarction
• ↑ after 12-24 hours
• peak after 3-5
• days
↓ to normal after 7-
12 days range < 250 U/L
Reference
Normally, all 5 isoenzymes can be detected in serum
with LD2 predominating followed LD1 and LD3,
whereas LD5 and LD4 are least detectable.
• Troponin T
• appears 3-5 hours after onset of chest pain
• stays elevated for 6 days
• Troponin I
• Rises 3-8 hours
• Peak 12-18 hours
• Stays elevated 6-10 days.
• Myoglobin
• Rises fast (2 hours)
• Peaks at 6 - 8
• hours
Returns to normal
Time sequence of changes in cardiac markers
after myocardial infarction
Enzyme tests in skeletal muscle disease
Abnormalities in serum enzymes are found primarily
in myopathy (disease of the muscle fiber) not a
disorder of motor innervations
• Total CK
• CK-MM: marked increase
• CK-MB: less marked increase
• Aldolase
• LD-5
Enzymes useful in hepatobiliary
disorders
• Hepatocellular damage:
Alanine aminotransferase (ALT)
Aspartate aminotransferase (AST)
• Cholestasis:
Alkaline phosphatase,
Gamma glutamyl transferase
(GGT) 5-nucleotidase
Leucine aminopeptidase.
 :Alkaline phosphatase
• Main sources: liver, bone, placenta and intestines
• Physiological ↑:
– Infancy and childhood: from growing bones
– Pregnancy due to placental isoenzyme.
– After meals, intestinal isoenzyme causes a
transient ↑
• Pathological ↑:
– Bone diseases with increased osteoblastic
activity: Paget’s disease, hyperparathyroidism,
active rickets, osteomalacia and osteoblastic
metastasis
– Cholestasis
– Hepatic malignancy: cholestasis, osteoblastic
secondary deposits, tissue damage
Pancreatic
Enzymes

AMYLASE LIPASE
N: 25-125 U/L N: 10-150 U/L

↑acute pancreatitis ↑acute pancreatitis

↑ starts at 4-12 h ↑ starts at 12-18 h

maximum 12-24 h

Returns N 48-72 h Returns N 5-7 days

of Lab Report for interpretation
 Clinical Problem

A sixty year old male arrived at the

emergency dept. one hour after he had a
severe chest pain. The pain was so severe
that he fell and collapsed. His physician gave
him an injection of morphia to ease the pain.
The patient had history of anginal pains and
an old myocardial infarction. ECG changes
on admission were not conclusive. The
following lab investigations were performed
as soon as he was admitted.
 General Hospital Laboratory Report
Clinical Chemistry Unit
Name:-----------------------------------------------------------------------------------------------
-
Sex: -----Male-----------------------------------
PID:---------------------------------------------
Ward: -------------------------------------------Doctor:----------------------------------------
Sample collection date/time: 4/1/2006 at 9:00 a.m
Sample type: Serum C/ Diagnosis:? MI
Chemisrtry Result Reference Range
Total CK 264 < 180 U/L
AST 45 10 – 40 U/L
ALT 39 10 – 35U/L
Na 143 135 – 145 mmol/L
K 3.9 3.6 – 5 mmol/L

Has the patient had a myocardial infarction?

What other biochemical tests would confirm the diagnosis?
What are the causes of an elevated serum total CK?