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2.2 Clinical Chemistry > Cardiac > Flashcards

Cardiac Flashcards

(77 cards)

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1
Q

What is CHD

A

Coronary Heart Disease

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2
Q

What is IHD

A

Ischemic Heart Disease

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3
Q

What exactly is CHD
(4)

A

The atherosclerosis of the arteries that supply the heart

The arteries which start out smooth and elastic get plaque on their inner walls which can make them more rigid and narrowed

This restricts blood flow to your heart, which can then become starved of oxygen

The plaque can rupture, leading to a heart attack or sudden cardiac death

When this occurs, immediate emergency treatment is necessary to stop the injury from widening, killing additional heart cells, and increasing the risk of complications or death

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4
Q

What are the 5 steps to a heart attack

A

Plaque rupture
Coronary thrombus
Reduced blood flow
Myocardial ischaemia
Myocardial infarction

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5
Q

What are the steps of progression in CHD?

A

Angina -> unstable angina -> AMI -> sudden cardiac death

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6
Q

What is ACS

A

Acute coronary syndrome

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7
Q

What does acute coronary syndrome encompass?

A

Unstable angina [UA]
Non-ST-segment elevation myocardial infarction (NSTEMI)
ST-segment elevation myocardial infarction (STEMI)

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8
Q

What is NSTEMI

A

Non-ST-segment elevation myocardial infarction

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9
Q

What is STEMI

A

ST-segment elevation myocardial infarction

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10
Q

What is stable angina?

A

Transient episodic chest pain due to myocardial ischaemia, reproducible, frequency constant over time, usually relieved with rest/Nitroglycerin

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11
Q

What is left ventricular hypertrophy [LVH]?

A

Enlargement and thickening (hypertrophy) of the walls of your heart’s main pumping chamber (left ventricle)

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12
Q

What might cause left ventricular hypertrophy?

A

High blood pressure or a heart condition that causes the left ventricle to work harder

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13
Q

What is the cardiac muscle cell called?

A

Myocyte

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14
Q

Comment on myocardial proteins as biomarkers

A

Size and subcellular distribution of myocardial proteins determines time course of biomarker appearance in the general circulation

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15
Q

Classify laboratory tests used in cardiac disease
(4)

A

Markers of cardiac tissue damage

Markers of myocardial function

Cardiovascular risk factor markers

Genetic analysis for candidate genes or risk factors

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16
Q

Describe how cardiac markers are used

A

Ischemia -> hypoxia -> decreased ATP -> cell damage

Reperfusion within 15 to 20 minutes

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17
Q

What is the clinical definition of myocardial infarction?

A

Myocardial infarction denotes presence of acute myocardial injury detected by abnormal cardiac biomarkers in the setting of evidence of acute myocardial ischemia

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18
Q

What is the laboratory definition (4th Universal Definition) of myocardial infarction?

A

The detection of a rise and/or fall of cardiac biomarker values, with at least one of the values being elevated

i.e. > 99th percentile upper reference limit

In addition at least one abnormal change in ECG or imaging changes

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19
Q

What is the preferred biomarker used in detection of Myocardial Infarction?

A

cTn

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20
Q

Write about cTN
(3)

A

Cardiac specific form of Troponin (T or I)

The preferred cardiac biomarker of necrosis

It is highly sensitive and specific

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21
Q

What is myocardial injury

A

Patients with elevated blood troponin levels but without clinical evidence of ischemia

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22
Q

What is ischemia

A

Diminished blood supply to any tissue or organ of the body, causing a shortage of oxygen

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23
Q

In your own words what is myocardial infarction

A

Elevated blood troponin levels

AND clinical evidence of ischemia

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24
Q

What specific type of cTn is used in investigation of MI

A

High-sensitivity cardiac troponin

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25
What are the traditional biochemical markers in myocardial ischemia/necrosis? (6)
AST activity LDH activity LDH isoenzymes CK-Total CK-MB activity CK-Isoenzymes
26
What are the recent biochemical markers in myocardial ischaemia/necrosis?
CK-MB (mass) c. Troponins (I or T) Myoglobin
27
What are the future biochemical markers in myocardial ischemia?
Ischaemia Modified Albumin Glycogen Phosphorylase BB Fatty Acid Binding Protein Highly Sensitive CRP
28
What are the eight characteristics of the ideal cardiac biomarker?
Absolute cardiac specificity Specific for irreversible injury Early release High tissue sensitivity Stable release Predictable clearance Complete release (infarct sizing) Measurable by conventional methods
29
What were the two main necrosis biomarkers of the past?
Lactate dehydrogenase (LDH) Aspartate aminotransferase (AST)
30
What is lactate dehydrogenase? (2)
Ubiquitous enzyme found in myocytes, skeletal muscle, liver, kidney, platelets and red blood cells 5 major isoenzymes LD1-LD5
31
What was LD1 and LD2 used to detect?
Myocardial infarction LD1 used more than LD2
32
What was LD4 and LD5 used to detect?
Hepatic or skeletal muscle injury
33
What was LD2, LD3 and LD4 used to detect?
Platelets/lymphatic
34
What was aspartate aminotransferase, and what was is used for
Found in skeletal muscle, liver, rbcs and myocardium Mitochondrial AST and Cytoplasmic AST MAST higher in severe tissue injury Isoenzymes not fractionated for clinical use Takes 6-8 hours to be detected, peak at 18-24hours, return to normal after 4 to 5 days
35
What are the necrosis biomarkers used today (3)
Myoglobin Creatinine Kinase [CK] -> CK-MB Isoenzyme (cardiac) Cardiac Troponin T [cTnT] and I [cTNI]
36
What is myoglobin and why is it used as a cardiac biomarker, are there any limitations? (6)
The major protein responsible for O2 supply of striated muscle Found in cytoplasm of cardiac and skeletal muscle cells Cleared by kidneys - RF up It is released into blood rapidly (as early as 1 hour) after damage to muscle cell Early detectable, more sensitive but non-cardiospecific High negative predictive value -> rule out myocardial necrosis with a negative predictive value approx 9%
37
Write about creatinine kinase and it's isoenzymes (4)
CK exists in skeletal muscle, heart, brain mostly but also in small intestine, tongue, diaphragm, uterus and prostate CK is formed by two subunits, B and M and thus has 3 isoforms: CK-MB, CK-BB and CK-MM CK-MB predominates in cardiac muscle -u p to 45% of total CK in cardiac muscle and less than 1% of total CK in skeletal muscle Not recommended for routine MI
38
Write about how CK-MB measurements used to be taken
Was measured by immuno-inhibition method which can give falsely elevated results due to the presence of atypical CK and CKBB and at times this lead to the misdiagnosis of acute coronary syndrome
39
Write about how CK-MB measurements are taken now (2)
We measure the concentration of CK-MB [CK-MB Mass] protein using the sandwich antibody technique This is more sensitive than the measurement of CK-MB activity
40
Write about skeletal muscle injury and CK (3)
7 fold increase in total CK on a per-gram basis Potential for release of substantial CK-mB upon injury as body mass of skeletal muscle is 100-fold higher than myocardial muscle Because of this we use the CK-MB index
41
What is the CK-MB index
(CK-MB mass/Total CK)*100
42
What does a CK-MB index greater than 2.5% indicate?
Myocardial source of muscle injury
43
What is the main issue with using CK measurements (2)
If both myocardial and skeletal muscle injury occur Skeletal muscle CK-MB may confound the CK-MB index by masking the relatively subtle myocardial Ck-MB and effectively swamping it
44
What are troponins? (3)
Also called the troponin complex A complex of three regulatory proteins (troponin C, troponin I and troponin T) They are integral to muscle contraction in skeletal muscle and cardiac muscle but not in smooth muscle
45
What does TnC do?
Binds to calcium ion
46
What does TnC do?
Binds to calcium ions
47
What does TnI do?
Binds to actin and inhibits actin-myosin interaction
48
What does TnT do?
Binds to tropomyosin, attaching to thin filament
49
What are the cardiac specific isoforms of troponin
cTnI = cardiac Troponin I cTnT = cardiac troponin T
50
What was the main issue with cTnI assays?
Lack of industry standardization as there were many different manufacturers This has been resolved
51
What is the main issue with cTnT assays
Only one manufacturer (Roche) They have the intellectual property rights for use of this test
52
Which troponin should you measure, CTnI or cTnT
It doesn't matter, either will work
53
How long will cTnT last?
10-14 days
54
How long will cTnI last?
4 to 7 days
55
What are considered the early markers of myocardial necrosis?
CK-MB Ck isoforms Troponin (T or I) Myoglobin (earliest)
56
What are considered the late markers of myocardial necrosis
Troponin I but especially T
57
What does clinical history + ECG changes mean
STEMI
58
What does clinical history - ECG changes + elevated troponin mean
NSTEMI
59
What does clinical history - ECG changes - elevated troponin mean
Unstable angina
60
What does a normal ECD and normal cTn mean for the patient (3)
Low risk of death/AMI Candidate for early discharge Reconsider the diagnosis of ACS (acute cardiac ischemia)
61
What does a normal ECG but high cTn mean for the patient? (4)
Intermediate risk of death/AMI Evaluation for other risk indicators (e.g. history of IHD, CHF or DM) Aggressive anti-thrombotic rx Consider early cardiac cath for those with other risk indicators
62
What does ST-Segment depression with no elevation of troponin mean for the patient (4)
Intermediate risk of death/AMI Evaluation for other risk indicators (e.g. history of IHD, CHF or DM) Aggressive anti-thrombotic rx Consider early cardiac cath for those with other risk indicators
63
What does ST-segment depression with cTn elevation mean for the patient? (3)
High risk of death/AMI Aggressive anti-thrombotic rx Urgent cardiac cath
64
What does other ECG changes that ST segment with elevated cTn mean for the patient? (3)
High risk of death/AMI Aggressive anti-thrombotic rx Urgent cardiac cath
65
What does other ECG change than ST-segment depression with no change in cTn mean for the patient? (2)
Heterogenous group of patients Needs further evaluation
66
When is serial sampling done? (2)
This is done for cardiac markers when the initial results are negative e.g. at admission Sampling done again at 6-9 hours later and after 12 hours is recommended if still negative but suspicion still high
67
What are four biomarkers still in development?
Heart-Type Fatty Acid Binding Protein (FABPs) Carbonic anhydrase (III) (CAIII) Ischemia Modified Albumin Glycogen phosphorylase BB (GPBB)
68
Write about Heart-Type Fatty Acid-Binding Protein(7)
Abundant in cytoplasm of striated muscle Specifically and reversibly bound to long chain fatty acids Found in Myo and Skeletal muscle -> same isoform of FABP, (H-FABP) Content in skeletal muscle is only 10-30% of that found in cardiac muscle Very good tissue/plasma ratio Released soon after onset of MI-early marker Increased less than 3 hours after MI and returns 12 to 24 hours later
69
Write about carbonic anhydrase (III) (CAIII)
Cytosolic protein - exclusively in type 1 (slow-switch) skeletal muscle Myogoblin: CAIII -> from skeletal muscle in 3:1 ration Not present in myocardium Combining CAIII and myoglobin is proposed to improve specificity of myoglobin as an early marker for MI
70
Write about Ischemia Modified ALbumin (5)
Albumin's ability to bind to cobalt is reduced during myocardial ischemia (N-terminal) It rises within minutes of ischemia, stays up for 6-12 hours and normalises within 24 hours Elevated after enduring sports Inhibited by endogenous lactate-limited used in DKA, SEPSIS, CKD Less specific-cancers, liver disease
71
Write about glycogen phosphorylase BB (6)
A glycolytic enzyme which plays an essential role in the regulation of carb metabolism It functions to provide energy supply for muscle contraction Three isoenzymes in humans - GP-LL in liver - GP- MM in muscle - GP- BB in brain
72
Write about GP-BB (6)
Predominant isoenzyme in myocardium With the onset of tissue hypoxia when glycogen is broken down, GP-BB is converted from structurally bound to cytoplasmic form In AMI GP-BB increases 1-4 after onset of chest pain It peaks before CK-MB and cTnT IT returns to normal after 1 to 2 days It is not cardiac specific
73
Write about cardiac natriuretic peptides (3)
Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and pro-peptide forms Family of peptides secreted by cardiac atria + ventricles with potent diuretic, natriuretic and vascular smooth muscle relaxing activity Levels of these neuro-hormonal factors can be measured in blood
74
What are three clinical uses of Natriuretic peptides especially BNP/N-terminal pro-BNP?
Detection of LV dysfunction Screening for heart disease Differential diagnosis of dyspnea
75
What is angiography/arteriography?
A medical imaging technique used to visualise the inside, or lumen, of blood vessels and organs of the body, with particular interest in the arteries, veins and the heart chambers
76
What is coronary artery bypass surgery? (2)
Surgery which improves the blood flow to the heart with a new route or 'bypass' around a section of clogged or diseased artery The surgery involves sewing a section of vein from the leg or artery from the chest or another part of the body to bypass a part of the diseases coronary artery
77
What is the pathophysiology of ACS? (6)
Pro-inflammatory cytokines such as IL-6 Plaque destabilisation - MPO Plaque Rupture - sCD40L Acute Phase Reactants - hs -CRP Ischemia - IMA Necrosis - cTnT and cTnI

2.2 Clinical Chemistry (28 decks)

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