USE OF LABORATORY TESTS IN THE EVALUATION OF CARDIAC INJURY & FUNCTION - PowerPoint PPT Presentation

Loading...

PPT – USE OF LABORATORY TESTS IN THE EVALUATION OF CARDIAC INJURY & FUNCTION PowerPoint presentation | free to view - id: 3d908d-MjhlM



Loading


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation
Title:

USE OF LABORATORY TESTS IN THE EVALUATION OF CARDIAC INJURY & FUNCTION

Description:

USE OF LABORATORY TESTS IN THE EVALUATION OF CARDIAC INJURY & FUNCTION Daniel Albertson, Ph.D. Enzyme Tissue Distribution Tissue skeletal muscle brain heart smooth ... – PowerPoint PPT presentation

Number of Views:61
Avg rating:3.0/5.0
Slides: 43
Provided by: cmspathEd
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: USE OF LABORATORY TESTS IN THE EVALUATION OF CARDIAC INJURY & FUNCTION


1
USE OF LABORATORY TESTS IN THE EVALUATION OF
CARDIAC INJURY FUNCTION
  • Daniel Albertson, Ph.D.

2
DIFFERENTIATION OF CARDIOVASCULAR DISEASES
  • ON BASIS OF THE HEARTS
  • COMPONENTS
  • Myocardium- cardiomyopathies not associated with
    HTN, congenital, valvular, or coronary disease.
  • Valves- stenosis regurgitation of tricuspid,
    pulmonary,mitral or aortic valve.
  • Electrical Conduction System- arrhythmias.
  • Blood Supply- ischemia

3
HOW IS THE DIAGNOSIS OF HEART DISEASE MADE?
  • HISTORY
  • PHYSICAL EXAMINATION (SIGNS SYMPTOMS
    PRESENTING COMPLIANT)
  • NONINVASIVE TESTS
  • EKG, HOLTER MONITORING, X-RAY, MRI, PET, ECHO
    (Transthoracic or Transesophageal)
  • INVASIVE TESTS
  • BLOOD, SERUM, OR PLASMA, TESTS, THALLIUM
    PERFUSION, TECHNETIUM VENTRICULOGRAM,
    CATHETERIZATION, ELECTROPHYSIOLOGY
  • NOTE not all tests required for every diagnosis!

4
Why are cardiac markers essential?
  • Chest pain if present is often nonspecific. One
    of most frequent reasons for visit to ER.
  • Chest pain of acute coronary syndrome must be
    distinguished from aortic dissection and
    pulmonary embolism which are also
    life-threatening.
  • About 25 of patients with infarction do not
    experience characteristic chest pain.
  • Non-diagnostic ECG is found in about 50 of
    patients with chest pain and MI.

5
WHEN ARE LABORATORY TESTS NEEDED FOR CARDIAC
EVALUATION?
  • IN ASSESSING ACUTE CORONARY SYNDROMES
  • Stable angina, Unstable angina, NSTEMI, STEMI
  • IN ASSESSING AMBULATORY PATIENTS PRESENTING WITH
    fatigue /or edema, and/or SOB, and/or decreased
    exercise tolerance, etc.

6
European Society of Cardiology American College
of Cardiology Definition of AMI (2000)
  • Ischemic symptoms (on exertion, at rest, or
    intermittent)
  • ECG changes indicative of ischemia (i.e. ST
    segment elevation or depression)
  • Increased levels of cTn or CK-MB
  • Coronary artery intervention (e.g. coronary
    angioplasty)

7
CARDIAC BIOMARKERS
  • CARDIAC ENZYMES total CK, AST, LDH
    isozymes(LDH-1).
  • NOT used currently. Of historical interest only.
  • BIOMARKERS used presently to evaluate cardiac
    injury or function CK-MB(isoenzyme), Troponin I
    Troponin T, B-type natriuretic peptide, A-type
    natriuretic peptide,
  • biomarker- a biochemical that can be
    objectively measured or evaluated to give insight
    into a normal bodily function or the occurrence
    of a pathological process

8
Activity of Myocardial Enzymes in serum following
MI
9
USE OF CARDIAC BIOMARKERS IN CLINICAL PRACTICE
  • Ordering a biomarker should always be guided by
    patients history, signs symptoms, physical
    exam to avoid misuse.
  • Ordering without a high index-of-suspicion (i.e.
    pretest probability).

10
Markers of Tissue Injury
  • Intracellular contents are liberated into the
    extracellular matrix when tissue is injured or
    cells die.
  • Enzymes in serum are useful markers of tissue
    injury.
  • Skeletal Muscle enzymes
  • CK, LDH, AST
  • Liver enzymes
  • AST, ALT, LDH, Alk. Phos., g GT
  • Myocardial enzymes
  • CK, LDH, AST

11
A CONSIDERATION OF SERUM ENZYMES USED AS MARKERS
A E c n t z i y
v m i e t y
cytosol enzymes
anoxia
time
0
2 hr
12
ANOTHER CONSIDERATION OF CELLULAR RELEASE OF
ENZYMES
A E c n t z i y
v m i e t y
anoxia
time
0
30 min
13
Release into the circulation of intracellular
contents from infarcted, necrotic tissue depends
upon diffusion
Enzyme MW (KD) CK 80 AST 90 LDH 140
14
TIME COURSE IN PLASMA DETERMINED BY
  • Diffusion from membranes compromised by anoxia or
    released from necrotic cells.
  • Governed by molecular weight
  • Elimination from plasma (via the liver or kidney).

15
Circulating Lifetimes of Enzymes
Mitochondrial AST - 1 hrs LDH5 (M4) - 12
CK - 18 Cytosol AST - 1 day ALT -
2 LDH1 (H4) - 5 days
16
Intracellular Contents Measured in Practice to
Diagnose Myocardial Cell Death
Intracellular Enzymes Creatine
kinase CK Lactate Dehydrogenase
LDH Aspartate Amino Transferase AST
New Markers Myoglobin CK-MB isoforms Troponin I
17
Activity of Myocardial Enzymes in serum following
MI
18
CREATINE KINASE ISOFORMS
  • The active CK molecule is composed of dimers of 2
    types of subunits designated B (for brain) and
    and M (for muscle).
  • Three molecularly distinct enzymes (BB, MB, MM)
    exist normally in tissues and plasma which can be
    separated by electrophoresis.
  • Tissues differ in isoenzyme composition.

19
CK Isoenzyme Tissue Distribution
MM 99 - 79 5 10 5 - - 99
MB lt 1 3 20 - - - - - lt 1
BB - 97 1 95 90 95 100 - -
Tissue skeletal muscle brain heart smooth
muscle kidney prostate liver erythrocyte serum
20
LDH ISOZYMES
  • The active molecule is a tetramer with two types
    of subunits (H and M) yielding 5 different
    molecular forms HHHH HHHM, HHMM, HMMM, MMMM
  • These isoforms differ in tissue distribution and
    may be separated by electrophoresis.
  • All isoforms are normally present in plasma.

21
LDH Isoenzyme Tissue Distribution
Predominant Isoenzyme
Tissue skeletal muscle brain heart smooth
muscle kidney prostate liver erythrocyte serum
5 M4 1 H4 1 H4 5 M4 1 H4 2
H3M
22
CREATINE KINASE MB ISOFORM
  • Present primarly in cardiac muscle and active in
    energy generation.
  • Detectable in blood 4 to 6 hours after myocardial
    ischemia.
  • Also comprises up to 5 of skeletal muscle can
    be elevated in noncardiac diseases.
  • Before troponin was gold standard for biochemical
    diagnosis of AMI.
  • Plays an important role in defining infarct size,
    expansion, and reinfarction.

23
CK - MB index
CK-MB may be determined - by measurement of
enzyme activity - immunologically
CK-MB activity
CK-MB 100
total activity
CK-MB (ng/ml) CK-MB index
total activity
24
Electrophoretic Separation of Isoenzymes
25
Corresponding CK LDH Isoenzyme Patterns
26
(No Transcript)
27
(No Transcript)
28
(No Transcript)
29
MYOGLOBIN
  • Heme protein found in cytoplasm of cardiac
    skeletal muscle cell
  • Earliest marker of myocardial cell damage.
  • Detectable in blood within 1-2-hours of myocyte
    damage
  • Not cardiac specific. Frequently elevated in
    presence of renal failure, skeletal muscle
    injury, trauma
  • Not used currently due to non-specificity

30
NEWEST CARDIAC BIOMARKERS
  • TROPONIN I AND TROPONIN T
  • Designated as cTnI and cTnT
  • Normal blood contains very little
  • Skeletal forms do not cross-react
  • ISCHEMIA-MODIFIED ALBUMIN
  • Significance still to be determined

31
(No Transcript)
32
CARDIAC TROPONINS
  • Form the thin filament component of the
    contractile structure in striated muscle. Also
    present in cytoplasm accounting for early
    release.
  • Elevated within 4 to 6 hours of symptom onset
    remain elevated for 4 to 10 days.
  • Current gold standard for myocyte necrosis (most
    sensitive specific).
  • Low threshold in healthy reference population.
  • Cut-off varies with age, sex, and race.
  • Requires high analytical precision.

33
New Markers
34
Enzyme Tissue Distribution
CK 2500 550 475 150 30 110 1 - 0.4
LDH ( U/gwt ) 145 125 105 145 36 0.2
AST 200 250 175 225 1 0.04
Tissue skeletal muscle brain heart smooth
muscle kidney prostate liver erythrocyte serum
35
INFLAMMATORY MARKERS for use in risk
stratification
  • CRP (C-Reactive Protein)
  • Cytokines
  • Martix metaloproteinases
  • Serine cathepsin proteases

36
C-REACTIVE PROTEIN
  • A plasma protein first isolated (1930) from
    patients with pneumococcal pneumonia because it
    bound to the C-polysaccharide of the
    pneumococcus.
  • Found elevated in plasma during many bacterial,
    but usually not viral, infections or inflammatory
    conditions.
  • The original acute phase reactant. Liver
    synthesis is stimulated by interleukin-6.
  • Many epidemologic studies have established that
    higher than baseline levels are associated with
    increased risk for CHD and stroke.

37
(No Transcript)
38
(No Transcript)
39
(No Transcript)
40
(No Transcript)
41
RELEASE OF MYOCYTE PROTEINS IN ANOXIA
42
(No Transcript)
About PowerShow.com