Plasma Enzymes And iso Enzymes In Diagnosis Flashcards
Clinical Enzymology is defined as the _______ in body fluids and the use of this information to _______ or to _________
assay of enzymes
make a diagnosis
monitor a clinical condition.
An isoenzyme refers to ___________ but from __________
multiple forms of an enzyme
the same genetic origin.
Isoenzymes have the same ________ but different ______ such as electrophoretic mobility, solubility or resistance to inactivation
catalytic function
physical properties
A macroenzyme is a _________ form of the native enzyme which is often ________
high molecular weight
complexed with immunoglobulins
Macroenzymes are more commonly seen in individuals with ________ and they often times present a source of ________
autoimmune disease
diagnostic confusion.
Causes of increased Plasma enzyme levels
Specific Causes
High plasma enzyme activities are seen in situations of
•Increased ________ eg in cancer
•Increase in _______ eg in viral hepatitis
•Increase in _______ (eg in microsomal enzyme induction)
•Decreased _______ eg amylase in renal impairment.
proliferation of cells
cell damage
enzyme synthesis
clearance from the plasma
Non specific causes of raised plasma enzyme activity
Mild increases in ______ are seen in many illnesses
Increase in ____ is seen in moderate exercise and IM injection
Increase in ____ seen in phenytoin use
Increase in ______ seen in renal impairment or macroamylsaemia
AST
CK
GGT
amylase
Physiological factors that affect plasma enzyme assays
Age eg ____
Sex –_____ and ____ activity are higher in men than women
ALP
GGT and CK
Physiological factors that affect plasma enzyme assays
Race and ethinicity - plasma ____ is higher in the negroid race than in caucasians
Physiological conditions – high _____ in pregnancy.
CK
ALP
Creatine Kinase
CK is an enzyme with a molecular weight of approximately 82,000 that is generally associated with _____ in the ______
ATP regeneration
muscle
Creatine Kinase
Tissue Source
CK is widely distributed in tissue, with highest activities found in _______,________, and ______.
skeletal muscle, heart muscle, and brain tissue
Creatine Kinase
Diagnostic Significance
Because of the high concentrations of CK in ____ tissue, CK levels are frequently elevated in disorders of _____ and ____ muscle.
The CK level is considered a sensitive indicator of ___________ and ________.
muscle
cardiac and skeletal
acute myocardial infarction (AMI) and muscular dystrophy
________________ (AMI)
acute myocardial infarction
Creatine Kinase
Because enzyme elevation is found in numerous disorders, the separation of total CK into its various isoenzyme fractions is considered a more specific indicator of various disorders than total levels.
T/F
T
Creatine kinase
CK occurs as a _____ consisting of two subunits that can be separated readily into three distinct molecular forms.
The three isoenzymes have been designated as _______,_________, and_________
dimer
CK-BB (brain type), CK-MB (hybrid type), and CK- MM
(muscle type).
Based on electrophoretic mobility, the iso enzymes of creatine kinase are also designated thus:
CK-1 (_____) – migrates fastest to the anode
CK-2 (_____)
CK-3 (______)
CKBB
CKMB
CKMM
Creatine Kinase
Reference Range
Total CK:
Male, ______ U/L (37°C)
Female,______ U/L (37°C)
CK-MB: __% total CK
15–160
15–130
6
Creatine kinase
The higher values in males are attributed to _________
increased muscle mass.
Aspartate aminotransferase
Aspartate aminotransferase (AST) is involved in the transfer of an ____ between ______ and _____
amino group
aspartate and -keto acids.
Aspartate aminotransferase
The older terminology, ____________________ may also be used.
________ functions as a coenzyme. The reaction proceeds thus:
serum glutamic- oxaloacetic transaminase (SGOT, or GOT),
Pyridoxal phosphate
Aspartate aminotransferase
Aspartate + α – ketoglutarate → ________ + _________
oxaloacetate + glutamate
Aspartate aminotransferase
The transamination reaction is important in intermediary metabolism because of its function in the synthesis and degradation of amino acids. The ketoacids formed by the reaction are ultimately ___ by the ______ cycle to provide a source of energy.
oxidized
tricarboxylic acid
Aspartate aminotransferase
Tissue Source
The highest concentrations are found in ______,________, and _______ , with smaller amounts found in the ____,____, and _____
cardiac tissue, liver, and skeletal muscle
kidney, pancreas, and erythrocytes.
AST is widely distributed in human tissue.
T/F
T
Aspartate aminotransferase
Diagnostic Significance
The clinical use of AST is limited mainly to the evaluation of ______ disorders and ___________ involvement.
hepatocellular
skeletal muscle
In AMI, AST levels begin to ___________, then it _______, and generally _______________
rise within 6 to 8 hours
peaks at 24 hours
return to normal within 5 days.
AST levels are useful in the diagnosis of AMI.
T/F
F
because of the wide tissue distribution,
AST levels are highest in ________ disorders.
acute hepatocellular
In viral hepatitis, AST levels may reach _____ times ULN. In cirrhosis, , levels may reach ___ times ULN
100
4
Aspartate aminotransferase
Source of Error
_______ should be avoided because it can dramatically increase serum AST concentration.
Reference Range
AST, 5 to 30 U/L (37°C)
Hemolysis
Alanine aminotransferase
Alanine + α ketoglutarate → _____ + ______
_________ is the co factor for the reaction
Pyruvate + Glutamate
Pyridoxal phosphate
Alanine aminotransferase is AKA _____
Glutamate pyruvate aminotransferase
Alanine aminotransferase
Tissue Source
ALT is distributed in many tissues, with comparatively high concentrations in the ______.
liver
__________ is considered the more liver- specific enzyme of the transferases.
Alanine aminotransferase
Alanine aminotransferase
Diagnostic Significance
Clinical applications of ALT assays are confined mainly to evaluation of ____ disorders. Higher elevations are found in ______ disorders.
hepatic
hepatocellular
ALT levels have historically been compared with levels of AST to help determine the source of an elevated AST level and to detect ______ involvement concurrent with ______ injury.
liver
myocardial
ALT levels are increased by hemolysis.
F
ALT is relatively unaffected by hemolysis.
Alkaline Phosphatase
ALP belongs to a group of enzymes that catalyze the hydrolysis of various _______ at (acidic or alkaline?) pH.
phosphomonoesters
alkaline
Alkaline phosphatase
ALP is a specific enzyme
T/F
F
It’s a nonspecific enzyme capable of reacting with many different substrates.
Alkaline phosphatase
The optimal pH for the reaction is ____ to ____
ALP requires ____ as an activator.
9.0 to 10.0
Mg2+
Alkaline Phosphatase
Tissue Source
ALP activity is present on cell surfaces in most human tissue.
The highest concentrations are found in the intestine, liver, bone, spleen, placenta, and kidney.
T/F
T😂
Alkaline phosphatase
In the liver, the enzyme is located on _________________________
Its activity in bone is confined to the ________, those cells involved in the production of ______
both sinusoidal and bile canalicular membranes.
osteoblasts; bone matrix..
Alkaline Phosphatase
Diagnostic Significance
Elevations of ALP are of most diagnostic significance in the evaluation of _______ and _______ disorders.
hepatobiliary and bone
Alkaline Phosphatase
Diagnostic Significance
In hepatobiliary disorders, elevations are more predominant in _____ conditions such as in ___________, than in ______ disorders such as _______ and ______
obstructive
hepatocellular
hepatitis and cirrhosis.
Alkaline Phosphatase
In bone disorders, elevations are observed when there is involvement of _______.
Elevated ALP levels may be observed in various bone disorders such as ____ disease (____—-) osteo______, rickets, hyper_________, and osteogenic _____.
In addition, increased levels are observed in healing ________ and during periods of physiologic _________.
osteoblasts
Paget’s; osteitis deformans
malacia; parathyroidism
sarcoma
bone fractures ; bone growth.
In normal pregnancy, increased _____ have been observed as well.
ALP
ALP exists as a number of isoenzymes - the _____,———,_______,———.
———— is used to separate the iso enzyme fractions.
The ____ fraction migrates the fastest, followed by ______,_____,_______,_______ fractions.
liver, bone, intestine, and placenta
Electrophoresis
liver
bone, placental, and intestinal
Alkaline Phosphatase
Difference in ______ is the basis of a second approach used to identify the isoenzyme source of an elevated ALP.
Typically, ALP activity is measured before and after heating the serum at ____°C for ____
heat stability
56
10 minutes
The _____ ALP is the most heat stable of the four major fractions, followed by _____,_______,_______ fractions in decreasing order of heat stability.
placental
intestinal, liver, and bone
A third approach to identification of ALP isoenzymes is based on _______
_______ is one of several inhibitors that have been used.
selective chemical inhibition.
Phenylalanine
Phenylalanine inhibits _________ ALP to a much greater extent than ________ ALP.
intestinal and placental
liver and bone
Alkaline Phosphatase
In addition to the four major ALP isoenzyme fractions, certain abnormal fractions are associated with
neoplasms.
The most frequently seen are the _____ and ——- isoenzymes.
They have been referred to as _______ alkaline phosphatases because of their similarities to ____________
The frequency of occurrence ranges from __% to ___% in cancer patients.
Regan and Nagao
carcinoplacental
the placental isoenzyme.
3;15
Lactate Dehydrogenase
This enzyme catalyses the reversible inter conversion of ______ and _____.
The enzyme is widely distributed in the body
It is found in cells of the cardiac and skeletal muscles, liver, kidney, brain and erythrocytes.
pyruvate and lactate
Measurement of plasma total LDH activity is a specific marker of cell injury
F
Measurement of plasma total LDH activity is therefore not a specific marker of cell injury
There are five main iso enzymes of LDH detectable by eletrophoresis
List them
LDH1, LDH2, LDH3, LDH4, and LDH5
Lactate Dehydrogenase
______ is the major isoenzyme in healthy people.
LD2
Lactate dehydrogenase
_____ > _____ is the flipped pattern seen in Myocardial Infarction
LD1>LD2
Amylase
Breaks down ______ and _____ into maltose
starch and glycogen
Amylase
Tissue Source
The _____ of the ______ and ______ are the major tissue sources of serum AMS.
Lesser concentrations are found in skeletal muscle and the small intestine and fallopian tubes.
acinar cells
pancreas and the salivary glands
______ is the smallest enzyme, with a molecular weight of 50,000 to 55,000.
Amylase
Amylase
Because of its small size, it is _______
readily filtered by the renal glomerulus and also appears in the urine.
Amylase
Its assay is useful in the diagnosis of _________
acute pancreatitis
Causes of raised plasma amylase activity
Marked increases may be seen in _______, severe ______ impairment, ______, perforated ______
acute pancreatitis
Glomerular
diabetic ketoacidosis
peptic ulcer
Causes of raised plasma amylase activity
Moderate to slight increases – acute _____, intestinal obstruction, abdominal trauma, mumps , ____ calculi, macroamylasaemia etc
cholecystitis
salivary
Acid phosphatase
Found in the cells of the ____,______,_____,______ and _____
prostate, liver, erythrocytes, platelets and bone
Acid phosphatase
Was used to aid diagnosis and management of ________
Now largely replaced by _____ assay
prostate cancer
PSA
Acid phosphatase
______ ACP is more tartarate labile than other fractions
Prostatic
Macroenzymes are ____________ forms of the serum enzymes (ACP, ALP, ALT, amylase, AST, CK, GGT, LDH, lipase) that can be ___________
high-molecular-mass
bound to an immunoglobulin
Macroenzymes are usually found in patients who have _____________________________
an unexplained persistent increase of enzyme concentrations in serum.
Macroenzymes accumulate in plasma because their ________ prevent them from ___________
high molecular masses
being filtered out of the plasma by the kidneys.
The detection of macroenzymes is clinically significant because the presence of macroenzymes can cause __________________
difficulty in the interpretation of diagnostic enzyme results.
F
F
Hyperlipidemia can mimic ———-
Pseudohyponatremia
In bohr’s effect, the pressure of _____ on Hb displaced ____, the ____ curve shifts to the ________
Co2
O2
Oxygen -hemoglobin
Right
In haldane’s effect, the pressure of _____ on Hb displaced ____, the ____ curve shifts to the ________
Oxygen
Co2
Oxygen -Hb
Left
increase in _______ indicates chronic pancreatitis
Serum lipase
Gold standard for acute myocardial infarction is Troponin ____
T
Hypothyroidism can cause Increase in CK___ levels
MM
