Cardiac Injury For The Pathologist

Front 1

What is the most important laboratory risk factor for coronary heart disease?

Back 1

Lipids.

Front 2

What is atheroscleorsis?

Back 2

A chronic process that results in damage to the endothelium and plaque buildup.

Front 3

At what percentage of stenosis in a coronary artery does chest pain develop?

Back 3

>80%.

Front 4

What is acute coronary syndrome (ACS)?

Back 4

Rapid reduction in blood flow caused by a thrombus on top of a plaque in a coronary artery.

Front 5

What causes a myocardial infarction?

Back 5

Blood supply in a coronary artery is completely blocked off by a thrombus.

Front 6

What is unstable angina?

Back 6

This is irreversible damage to myocytes despite incomplete blockage of a coronary artery by a thrombus.

Front 7

What is the most severe type of myocardial infarction?

Back 7

ST-segment elevation (STEMI) MIs, which are caused by transmural damage.

Front 8

What is heart failure?

Back 8

Compromise in the ability of the heart to pump blood. It is a problem with cardiovascular function.

Front 9

How long does it take for ischemia to cause cell death in an area of the heart?

Back 9

20-30 minutes.

Front 10

What determines the percentage of cells that die during a myocardial infarction?

Back 10

Duration of the ischemia.

Front 11

What is the process of plaque formation?

Back 11

First, the development of fatty streaks in the coronary arteries of young adults that is triggered by uptake of LDL by macrophages. These macrophages then invade the coronary endothelium. Inflammatory cells and mediators surround the lipid core (cholesterol esters) as does endothelialized connective tissue. These plaques can also contain calcium deposits and blood vessels. Erosion of the fibrous cap can lead to formation of a thrombi with possible resultant MI.

Front 12

What are the symptoms of congestive heart failure?

Back 12

Fatigue, edema, shortness of breath.

Front 13

What are some risk factors for coronary heart disease?

Back 13

Age, male gender, obesity, diabetes, hypertension, cigarette smoking, sedentary lifestyle, family history of CHD.

Front 14

What defines systolic congestive heart failure?

Back 14

A left ventricular ejection fraction <40%.

Front 15

What is diastolic congestive heart failure?

Back 15

Dysfunction in the filling of the left ventricle during diastole.

Front 16

What is the underlying principle of markers of myocardial disease?

Back 16

Dead cells release enzymes into circulation, and these enzymes can be measured to correlate with myocardial damage.

Front 17

What is lactate dehydrogenase?

Back 17

It is a zinc-containing enzyme that is part of the glycolytic pathway and found in every cell of the human body. It is a tetramer composed of two subunits (H and M).

Front 18

What is creatinine kinase?

Back 18

It is an enzyme found in muscle, brain, and other tissues that transfers high energy phosphate between creatinine and ADP. It is a dimer composed of two subunits (M and B).

Front 19

Which isoenzyme of lactate dehydrogenase is relatively common in cardiac muscle?

Back 19

LD1 (HHHH).

Front 20

Which isoenzyme of lactate dehydrogenase is relatively common in skeletal muscle?

Back 20

LD5 (MMMM).

Front 21

What is the characteristic lactate dehydrogenase pattern seen in patients with a myocardial infarction?

Back 21

"Flipped LDH": the normal finding LD2 > LD1 is reversed.

Front 22

What are the isoenzymes of creatinine kinase (CK)?

Back 22

CK1 (CK-BB), CK2 (CK-MB), and CK3 (CK-MM).

Front 23

What is the distribution of CK-MB in the heart?

Back 23

15-20% of CK in the heart is CK-MB, and the percentage is greater in the right heart than the left.

Front 24

Where is CK-BB (CK1) predominantly found?

Back 24

Brain and smooth muscle.

Front 25

What assay is used to test CK-MB mass?

Back 25

Immunometric assay in which CK-MB is measured as an antigen. Thus, this assay does not depend on the enzymatic activity of CK-MB.

Front 26

How is total CK measured?

Back 26

Enzymatic activity.

Front 27

What is the relative index (RI)?

Back 27

It is the ratio of CK-MB mass to total CK activity.

Front 28

What is the significance of the relative index?

Back 28

A higher relative index is more suggestive of MI.

Front 29

What is an increased relative index?

Back 29

>2%.

Front 30

What is an increased CK-MB?

Back 30

>5 ng/ml.

Front 31

What is troponin (Tn)?

Back 31

It is a regulatory complex of 3 proteins in the thin filament of striated muscle. The 3 proteins are TnT, TnI, and TnC.

Front 32

What is TnT?

Back 32

It is the tropomysin-binding subunit of troponin.

Front 33

What is TnI?

Back 33

The inhibitory subunit of troponin.

Front 34

What is TnC?

Back 34

The calcium-binding subunit of troponin.

Front 35

Does TnC have a cardiospecific form?

Back 35

No. TnC is identical in cardiac muscle and type 2 muscle fibers.

Front 36

Does TnI have a cardiospecific form?

Back 36

Yes. In fact, presence of the cardiospecific form (cTnI) has not been reported in tissue other than the heart.

Front 37

Does TnT have a cardiospecific form?

Back 37

Yes. However, the cardiospecific form (cTnC) has been reported in fetal skeletal muscle and diseased skeletal muscle. Despite this finding, though, cTnT from myocardium and that from skeletal muscle can be distinguished due to distinctive posttranslational modification that can be detected through the use of specific antibodies.

Front 38

How long after a myocardial infarction is cTnI and cTnT released and why?

Back 38

These troponins are released slowly over a period of 1-2 weeks because they are predominantly bound to muscle fibers. The free fraction allows early leakage, with cTn peaking at 24 hours following a MI. There can be a small secondary increase in the midst of the decline that should not be mistaken for a reinfarction.

Front 39

What is the normal level of cTn in serum?

Back 39

<0.1 ng/ml.

Front 40

What can cause an increase in cTn?

Back 40

Ischemic heart disease, pericarditis, myocarditis, renal failure, pulmonary embolism, sepsis.

Front 41

What is myoglobin?

Back 41

It is a heme-containing protein in cardiac and skeletal muscle that binds oxygen.

Front 42

Why is myoglobin useful for the detection of MI?

Back 42

It leaks from damaged cells more rapidly than other proteins due to its small size.

Front 43

What are the kinetics of myoglobin?

Back 43

It appears 2-3 hours after MI, peaks at 6 hours, and returns to normal at 24 hours.

Front 44

What factors cause increased myoglobin?

Back 44

Increased age, male gender.

Front 45

What is carbonic anhydrase III (CA III) and how is it useful?

Back 45

It is an enzyme present only in skeletal muscle, so it serves as a negative cardiac marker. An increase in the ratio of myoglobin to CA III is a more specific indicator of MI than myoglobin alone.

Front 46

What is glycogen phosphorylase (GP) and how is it useful?

Back 46

It is an enzyme that catalyzes the first step of glycogenolysis. There are 3 isoenzymes: GPLL (liver), GPMM (muscle), and GPBB (brain and myocardium). GPBB, which is found in myocardium, is released earlier than the other markers and is thought to be released with reversible ischemia.

Front 47

What is the significance of creatinine kinase isoforms?

Back 47

It takes several hours to convert CK-MB2 to CK-MB1 and CK-MM3 to CK-MM1 or CKMM2. Increased ratio of MB2/MB1 or MM3/MM1 suggests MI, and is usually seen before serum MB becomes elevated. Occurs within the first 3-4 hours.

Front 48

What is heart fatty acid binding protein (HFABP)?

Back 48

It is a low-molecular-weight early marker of myocardial injury but is not cardiac specific and is not as useful as myoglobin.

Front 49

What is the significance of ischemia modified albumin (IMA)?

Back 49

It is a variant of albumin that has reduced affinity for metal ions (cobalt) that forms from the interaction of free radicals from ischemia with albumin. Occurs within minutes of ischemia and lasts for 6 hours (due to rapid hepatic clearance). Measured by spectrophotometry.

Front 50

What are the pitfalls of cTn assays?

Back 50

cTn is a highly heterogenous analyte because it is degraded as it is released into circulation. The assay is also susceptible to interference by heterophilic antibodies, fibrin, and other substances and resultant false positives.

Front 51

What is the point-of-care testing for MI?

Back 51

The laboratory should provide reliable results within 1 hour of the patient presenting to the ER. An early marker, such as myoglobin or CK isoforms should be used as well as cTn measured upon presentation, a second specimen at 6-12 hours, and a third specimen at 24 hours.

Front 52

What is the "washout phenomenon"?

Back 52

In the 60-120 minutes following reperfusion, there is a bolus of myocte proteins released (cardiac markers will be increased).

Front 53

With what do the levels of cardiac markers correlate?

Back 53

Infarct size, functional impairment, prognosis.

Front 54

Which cardiac marker is more useful for the diagnosis of reinfarction?

Back 54

CK-MB due to its rapid decline.

Front 55

Which cardiac marker is more useful for the diagnosis of MI following surgical procedures?

Back 55

cTn is more useful because the other cardiac markers are released from damage to skeletal muscle and other noncardiac tissues. cTn is typically >40 ng/mL in these patients.

Front 56

What is a directly associated risk factor for coronary heart disease?

Back 56

LDL.

Front 57

What is a negative risk factor for coronary heart disease?

Back 57

HDL.

Front 58

What is C-reactive protein?

Back 58

An acute phase reactant that comprises 5 protomers arranged in cyclic symmetry that binds various proteins and phospholipits and opsonizes particles and activates complement by the classical pathway. It is elevated in bacterial infection and MIs.

Front 59

What is high-sensitivity CRP (hsCRP)?

Back 59

This is testing of CRP in patients with elevated baseline CRP, who are at increased risk for coronary heart disease and stroke. Commercial hsCRP assays are available.

Front 60

What is the recommendation of the JCAHA and CDC for testing of high-sensitivity CRP (hsCRP)?

Back 60

hsCRP should be averaged from two specimens drawn 2 weeks apart, and a cause of infection or inflammation should be searched for if levels are >10 mg/L.
Low risk <1 mg/L, intermediate risk 1-3 mg/L, high risk >3 mg/L.
Patient in whom the risk is moderate and the physician wants more information could benefit from an hsCRP assay.

Front 61

What is homocysteine?

Back 61

Sulfur-containing amino acid metabolic intermediate that can either be converted to cysteine through the transsulfuration pathway or be methylated to methionine. Total homocysteine is measured by chromatography.

Front 62

What is homocystinuria?

Back 62

An excess of homocysteine caused by a homozygous defect in cystathionine-β-synthase (CBS) that is manifested by osteoporosis with skeletal abnormalities, dislocation of the optic lens, psychiatric disturbance, mental retardation, and thromboembolic disease.

Front 63

What is the basis of homocysteine toxicity?

Back 63

Homocysteine toxicity is thought to be due to conversion of homocysteine to thiolactone, which modifies LDL so that its uptake by macrophages is enhanced. Endothelial injury, platelet activation, smooth muscle proliferation, and altered NO metabolism have been documented.

Front 64

What is the relationship between homocysteine and coronary heart disease?

Back 64

Homocysteine has been associated with four-fold higher risk of cardiovascular disease with increased levels. Homocysteine should only be measured in patients who develop cardiovascular disease despite being at low risk otherwise.

Front 65

What is brain natriuretic peptide (BNP)?

Back 65

A peptide produced in the cardiac ventricle. Also referred to as B-type natriuretic peptide.

Front 66

How is BNP derived?

Back 66

BNP derives from proBNP, which in the cardiac myocte is cleaved by endoprotease furin to form BNP (active) and N-BNP (inactive).

Front 67

How do the half lives of BNP and N-BNP differ?

Back 67

BNP has a half-life of 22 minutes whereas N-BNP has a half-life of 60-120 minutes.

Front 68

What stimulates the release of BNP?

Back 68

Secretion is stimulated by ventricular wall stretch and volume overload.

Front 69

What does the release of BNP cause?

Back 69

BNP causes the release of cyclic guanosine monophosphate (c-GMP) through two G-protein-coupled receptors, which then downregulates the renin-angiotensin-aldosterone system (causes decreased sympathetic activity, increased renal blood flow, and increased sodium excretion).

Front 70

What levels of BNP are suggestive of CHF?

Back 70

Levels usually <100 pg/mL in normal individuals. Levels >100 p/mL could signify CHF.
BNP is available on large, automated immunoassay platforms but should not be used for CHF screening but rather to rule out CHF in an acute setting.

Front 71

What are the pitfalls of measuring BNP?

Back 71

Limited use due to week-to-week variability of 30-40%, lack of knowledge concerning determinants of BNP level, and elevated BNP also being seen in renal insufficiency. Furthermore, patients with chronic and stable CHF can have normal levels.

Front 72

What is the fastest migrating creatinine kinase isoenzyme?

Back 72

CK-BB (CK1).

Front 73

What is the slowest migrating creatinine kinase isoenzyme?

Back 73

CK-MM (CK3).

Front 74

Which creatinine kinase isoenzyme is the most widely distributed?

Back 74

CK-BB (CK1).

Front 75

What is macro-CK?

Back 75

It is a CK-immunoglobulin complex that migrates electrophoretically between CK-MM and CK-MB.

Front 76

In what type of patients is macro-CK found?

Back 76

Elderly women and AIDS patients.

Front 77

What is mitochondrial CK?

Back 77

It is a type of CK that migrates very closely to MM and is usually slower than MM. Seen in patients with advanced malignancies. Poor prognosis.

Front 78

What is the most sensitive cardiac marker?

Back 78

Myoglobin.

Front 79

How is ischemia modified albumin (IMA) measured?

Back 79

By the Altered Cobalt Binding (ACB) assay, in which a known quantity of cobalt is added to patient plasma and the amount of unbound cobalt is measured. The amount of unbound cobalt is a measure of ischemia modified albumin.