Cardiac

Front 1

The heart is enclosed in a sac called the ...

Back 1

pericardium

Front 2

The right side of the heart pumps blood to the ____, whereas the left side pumps blood to the _______.

Back 2

The right side of the heart pumps blood to the lungs, whereas the left side pumps blood to the body.

Front 3

The top, smaller chambers are called _______

Back 3

atria

Front 4

The lower, larger chambers are called _______

Back 4

ventricles

Front 5

What is arteriosclerosis pathogenesis?

Back 5

• the start of heart disease starts with damage to the endothelial lining of the blood vessels
  
• vascular cell injury causes inflammation due to toxins (smoking) and infections
  
• results from lipid deposition on arterial walls of primarily esterified LDL
  

Front 6

What is the body's response to arteriosclerosis pathogenesis in order to repair the endothelium lining?

Back 6

• macrophage infiltration and cell proliferation (particularly smooth muscle cells) to repair damage
• lipids and macrophages with LDL modified by oxidative processes (foam cells) accumulate in endothelium to form fatty streak (first indication of arteriosclerosis pathogenesis)
  
• macrophages with LDL move to the basement membrane where they release cytokines to form fibrous connective tissue that results in streaks enlarging to form plagues
  

Front 7

What is arteriosclerosis?

Back 7

When the plagues of arteriosclerosis pathogenesis deposits in various parts of the body

Front 8

What is peripheral vascular disease?

Back 8

a type of arteriosclerosis that results in plague formation in arms and legs

Front 9

What is coronary heart disease (CHD) or coronary artery disease (CAD)?

Back 9

a type for arteriosclerosis that results in plague formation in the heart

Front 10

What is cerebrovascular disease?

Back 10

a type of arteriosclerosis that results in plague formation in the vessels of the brain

Front 11

Which lipoprotein is most associated with atherogenesis?

Back 11

LDL cholesterol (the "bad" cholesterol) so treatments typically involve lowering the LDL

Front 12

What condition poses the highest risk for an acute myocardiac infarction (AMI)?

Back 12

coronary heart disease (or other forms of atherosclerotic disease, diabetes or multiple risk factors etc.)

Front 13

What are the major independent risk factors for acute myocardiac infarction (AMI)?

Back 13

• smoking
• hypertension
• low HDL
• high HDL
• familial history of CHD
• age
  

Front 14

What are other life-habit risk factors for AMI?

Back 14

• obesity
• physical inactivity
• atherogenic diet: high cholesterol intake, saturated fats and trans fat
  

Front 15

How can the risk for AMI be reduced?

Back 15

• stop smoking
• healthy diet: low cholesterol intake, low ratio of saturated to polyunsaturated fats, high omega-3 fatty acids (fish and fish oil), olive oil
• moderate red wine consumption
• weight reduction
• increased physical activity
• lower LDL with plant sterols, increase fiber
  

Front 16

What drugs are used to treat patients who are at risk for AMI?

Back 16

• statins
• bile acid sequestrants
• nicotinic acid
• fibric acids
  

Front 17

What is the effect, adverse effect and monitoring levels of statins (HMG-CoA reductase inhibitors)?

Back 17

• effect: decreased LDL and TG, increased HDL
• adverse effects: myopathy and increased liver enzymes
• monitor: CK and liver function tests
  

Front 18

What is the effect, adverse effect and monitoring levels of bile acid sequestrants?

Back 18

• effect: decrease LDL, increase HDL
  
• adverse effects: constipation, nausea, hypothrombinemia
  
• monitor: PT time
  

Front 19

What is the effect, adverse effect and monitoring levels of nicotinic acid (Niacin)?

Back 19

• effect: decrease LDL and TG, increase HDL
• adverse effects: flushing, hyperglycemia, hyperuricemia, hepatotoxicity
• monitor: glucose, liver function tests and uric acid

Front 20

What is the effect, adverse effect and monitoring levels of fibric acids (gemfibrozil and fenofibrate)?

Back 20

• effect: inc HDL, dec TG
• adverse effects: dyspepsia, hepatic, myopathy, gallstones
• monitor: liver function tests, CK, K, CBC

Front 21

The concentration of what 3 substances are all good indicators of cardiac risk in the future?

Back 21

• lipoprotein (a)
• homocysteine
• high sensitivity C-reactive protein
  

Front 22

What is lipoprotein (a)?

Back 22

• a variant of LDL with an extra apoprotein, apo (a) attached by disulfide bond to apo-B 100
• size and serum concentrations are genetically determined
  

Front 23

What is hemocysteine?

Back 23

• it's an amino acid that's part of the synthetic pathway of methionine to cystein
• increased plama homocysteine increased risk of CHD (CAD) because it is thought that it damages the connective tissue of arteries which increases the formation of fatty deposits in the vessels and promote blood clotting
  

Front 24

Deficiency of what can lead to hyperhomocysteinemia?

Back 24

B vitamins

Front 25

Ingestion of what can reduce homocysteine concentrations?

Back 25

folate, vitamins B6 and B12 help break down homocysteine concentrations

Front 26

What is homocysteine useful for?

Back 26

detect individuals at risk for unexplained premature CAD

Front 27

What is C-reactive protein (hsCRP)?

Back 27

• an acute phase reactant produced primarily by the liver that increases rapidly with inflammation in response to injury and infection
• not present in appreciable amounts in healthy individuals so detection of small increases of CRP indicates cardiac disease
  

Front 28

Elevated baseline hsCRP are correlated with what?

Back 28

higher risk of future cardiovascular morbidity and mortality even in inviduals without hyperlipidemia

Front 29

How should a specimen for hsCRP be collected and analyzed?

Back 29

• must avoid trauma or infection prior to specimen collection (about 2 weeks)
  
• 2 specimens collected 1 month apart to assess risk
  

Front 30

Whati s fibrinogen?

Back 30

• glycoprotein involved in platelet aggregation and coagulation
• an acute phase protein produced in response to inflammation
  

Front 31

What is D-dimer?

Back 31

• end product of thrombus formation and dissolution that occurs at site of plaques
• increases precedes myocardial cell damage, remains elevated for days
• not specific for cardiac damage
  

Front 32

What is myeloperoxidase?

Back 32

• produced by WBCs in response to arterial inflammation and fatty deposits
• indicates increased risk for cardiac death within 6 months of presenting to ER with chest pain
  

Front 33

What happens first to the heart muscle when a heart attack occurs?

Back 33

• microscopically, no change for 12 hours after the artery is blocked and oxygen can't reach the heart.
  
• between 18-24 hours after blockage occurred, the cells in that region have died and becomes eosinophilic, fewer cross striations and nuclei undergo fragmentation
• neutrophils attract to the necrotic myocardium can be seen 18-24 hours, present in all AMI by 38 hours and peak on day 3
  

Front 34

What happens on day 4 to the heart muscle when a heart attack occurs?

Back 34

• macrophages, fibroblasts, and capillaries appear
• macrophages phagocytize the necrotic myocytes
• fibroblasts produce collagen/scar tissue
• most likely time that the patient passes from the effects of the initial heart attack even if they survived the necrotic cells
  

Front 35

What happens between day 4 and 10 to the heart muscle when a heart attack occurs?

Back 35

Cardiac rupture most likely to occur as myocardium softens and fibrosis is poorly developed and unable to withstand the pressure of the ventricles as it works to pump the blood which results in the blood entering the pericardial sac causing cardiac tamponade.

Front 36

What is cardiac tamponade?

Back 36

When the blood from the heart leaks and fills the space between the heart and the pericardial sac, there is less room for the heart to function. The pressure outside the heart prevents adequate filling of the chambers. Eventually, the heart will stop beating.

Front 37

What specimens are preferred to assess a patient's condition when they have a heart attack?

Back 37

4 serum preferred (heparinized plasma acceptable) specimens collected upon admission, a specimen 2-4 hours later, 6 hrs, 8 hrs, then 12 hrs later.

Front 38

What is creatine kinase?

Back 38

• catalyzes the reversible phosphorylation of creatine by ATP
• 8x more phosphocreatine than ATP
• provides energy needed for muscle contraction
• localized in the cytosol
• associated with myofibrillar structures
• composed of 2 proteins (dimer)
  

Front 39

What are the 2 types of protein subunits of creatine kinase?

Back 39

muscle (M)

brain (B)

Front 40

What are the 3 typical isoenzymes of creatine kinase?

Back 40

CK-BB (CK-1)

CK-MB (CK-2)

CK-MM (CK-3)

Front 41

What are the 2 atypical CK isoenzymes of creatine kinase?

Back 41

macro-type 1: CK-1 bound to IgG and CK-3 bound to IgA

macro-type 2: CK-Mt from mitochondria

Front 42

CK activity is greatest in what?

Back 42

striated muscle, brain and heart

Front 43

The skeletal muscle has the highest concentration of which CK isoenzyme?

Back 43

CK-3

Front 44

The brain has the highest concentration of which CK isoenzyme?

Back 44

CK-1

Front 45

The left ventricle has the highest concentration of which CK isoenzyme?

Back 45

CK-3 and CK-2

Front 46

The heart in general as the highest concentration of which CK isoenzyme?

Back 46

CK-2

Front 47

What is Duchenne's?

Back 47

a skeletal muscle disease where there is increased muscular dystrophy and it affects young boys with females being carriers

Front 48

What clinical symptoms are seen in Duchenne's?

Back 48

enzyme activity is highest in infancy and childhood (7-10 yrs of age) and shows a 3-6 fold increase of CK activity

Front 49

What diseases of skeletal muscle are CK levels increase in?

Back 49

Duchenne's

viral myositis (inflammation of the heart)

Front 50

What conditions would NOT increase CK concentration in the plasma?

Back 50

• myasthenia gravis
• multiple sclerosis
• poliomyelitis
• parkinsonism
  

Front 51

An increase in serum CK-1 indicates what?

Back 51

head injury

Front 52

An increase in serum CK-2 indicates what?

Back 52

• head in injuries
  
• subarachnoid hemorrhage (suggests cardiac damage)
  

Front 53

What conditions would cause an increase in CK-3 (but not CK-1)?

Back 53

• acute cerebrovascular disease
• neurosurgical intervention
• cerebral ischemia
  

Front 54

CK may increase in the CSF in what conditions?

Back 54

• epilepsy
• brain tumors
• cerebral infarcts
• meningitis
• autism
  

Front 55

CK increases six-fold in females during what?

Back 55

childbirth

Front 56

Gastrointestinal infarction would have an increase in which CK isoenzyme?

Back 56

CK-1

Front 57

What conditions would increase CK-1?

Back 57

variety of cancers

Front 58

What is the specimen requirements for CK?

Back 58

serum preferred because plasma containing heparin, EDTA, citrate, or fluoride may produce unpredictable reaction rates but it is still unstable in the serum and lost rapidly during storage

Front 59

CK is inactivated by what?

Back 59

bright sunlight

Front 60

Which CK isoenzyme is most unstable and least unstable?

Back 60

most unstable: CK-3

least unstable: CK-1

Front 61

T/F: Hemolyzed specimens are ok for CK testing

Back 61

T (slight hemolysis is ok because RBCs contain no CK)

Front 62

Why is severely hemolyzed samples not acceptable for CK testing?

Back 62

RBCs contain ATP and G6P which are often substrates for reactions so it may affect the lag phase and side reactions in the assay

Front 63

CK concentration in the serum varies with what?

Back 63

• exercise
• surgery
  
• intramuscular injections
  

Front 64

How is total CK determined?

Back 64

• forward or reverse coupled enzyme, photometric and fluorometric methods
• reaction temperature must be controlled
• all reactants must be in excess to ensure that CK is the limiting factor
  

Front 65

For total CK determination, which reaction has a longer lag phase?

Back 65

forward (so the reverse reaction is preferred because it proceeds faster)

Front 66

T/F: Spectrophotometric methods are more sensitive than bioluminescent methods

Back 66

false

Front 67

Normal amount of _______ with trace amounts of __________ represents normal turnover of muscle, but _______ is NOT normally present!

Back 67

Normal amount of CK-3 with trace amounts of CK-2 represents normal turnover of muscle, but CK-1 is NOT normally present!

Front 68

An increase of what is most often indicative of damage tot eh myocardium?

Back 68

CK-MB

Front 69

Total CK parallels with what, but remains elevated longer?

Back 69

CK-MB

Front 70

The immunoassay CK-MB measures what?

Back 70

• CK-MB mass (g/L), NOT activity
• considered the current "gold standard" for diagnosis of AMI
  

Front 71

CK-MB2 converts to CK-MB1 by what enzyme?

Back 71

lysine carboxypeptidase

Front 72

Normally, concentrations of _______ and _______ are about equal. However, after a heart attack, ______ rises faster than ______ .

Back 72

Normally, concentrations of CK-MB2 and CK-MB1 are about equal. However, after a heart attack, CK-MB2 rises faster than CK-MB1. (RATIO IS > 1)

Front 73

The CK-MB2:CK-MB1 ratio begins to rise at what time, peaks at what time and returns to baseline at what time?

Back 73

• begin to rise in 2-6 hours
• peaks at 6-12 hours
• returns to baseline 24-36 hours
  

Front 74

What substance is released when cells are damaged, increased in a wide range of diseases?

Back 74

lactate dehydrogenase (LD)

Front 75

LD concentrations are highest where?

Back 75

• skeletal muscle
• liver
• heart
• kidney
• RBCs

(all cells contain LD but in different concentrations of the isoenzymes)

Front 76

Describe the structure of LD

Back 76

It has 2 proteins, heart (H) and muscle (M) that result in 5 isoenzymes:

LD1(HHHH): most anionic

LD2 (HHHM)

LD3 (HHMM)

LD4 (HMMM)

LD5 (MMMM): most cationic

Front 77

LD preferred specimens

Back 77

• serum (some anticoagulants interfere with reaction)
• avoid hemolysis (RBCs high in LD)
• analyze ASAP and store at RT for 2-3 days because different isoenzymes are stable at different temperatures and the activity is lost with freezing
  

Front 78

What inhibits LD in the assay?

Back 78

• excess lactate and pyruvate
• borate
• oxalate
• EDTA
  

Front 79

Alkaline pH favors what in the lactate dehydrogenase assay?

Back 79

lactate (pH 9.5)

Front 80

Neutral pH favors what in the lactate dehydrogenase assay?

Back 80

pyruvate (pH 7.4)

Front 81

Total levels of limited value in what conditions?

Back 81

multiple organs are diseased

Front 82

LD begins to rise at what hours, peaks at and returns to baseline?

Back 82

• rise 12-24 hours post-MI
• peaks in 2-4 days post-MI
• returns to baseline by 2 weeks
  

Front 83

Which LD isoenzyme predominates in heart muscle and RBCs?

Back 83

LD1 (LD2 is high in these tissues too)

Front 84

Which LD isoenzyme predominates in the liver and skeletal muscle?

Back 84

LD5

Front 85

Which LD isoenzyme predominates in varying degrees in all tissues?

Back 85

LD2, LD3, and LD$

Front 86

Which LD isoenzyme predominates in platelets?

Back 86

LD3 and LD4

Front 87

LD isoenzymes can aid in identifying what?

Back 87

tissue source of elevated total LD

Front 88

What substance is present in all fluids (plasma, CSF and saliva) except urine (unless there's a kidney lesion)?

Back 88

AST

Front 89

What substance is increased in hepatitis and liver disease associated with necrosis?

Back 89

AST

Front 90

What is the concentration of AST after AMI?

Back 90

• serum increases 6-8 hrs
• peaks in 18-24 hours
• return to normal in 4-5 days
• normal 8-20 U/L

Front 91

Describe a typical AMI enzyme graph timeline

Back 91

Front 92

Myoglobin is found in what muscles?

Back 92

cytosol of striated muscle: skeletal and cardiac

Front 93

What protein is the first to rise after a heart attack?

Back 93

myoglobin (peaks within 6-9 hrs)

Front 94

Myoglobin specimen

Back 94

serial samples: on admission, 2-4 hrs later, 6-9 hrs later, and 12-24 hrs later

Front 95

AMI is suspected if myoglobin concentration is....

Back 95

doubled in 1-2 hours

Front 96

What interferes with myoglobin assays?

Back 96

hemolysis, bilirubin, lipemia

Front 97

What methodologies are used to measure myoglobin?

Back 97

• turbidimetry
• nephelometry
• immunoassay
• ELISA
  

Front 98

What are troponins?

Back 98

• regulatory protein complex of myofibrils
• bound to tropomysin and actin that mediates interation between actin and myosin during muscle contraction
  

Front 99

What are the 3 subunits of troponin?

Back 99

C, I and T

Front 100

Which troponin subunit is the calcium binding component?

Back 100

C

Front 101

Which troponin subunit is the inhibitory component?

Back 101

I

Front 102

Which troponin subunit that is the tropomyosin binding component?

Back 102

T

Front 103

Troponins are released into circulation upon what?

Back 103

injury

Front 104

What methodology is used to measure troponin?

Back 104

ELISA assays

Front 105

Which troponin is highly specific for cardiac muscle injury?

Back 105

cTnI (cardiac troponin I)

Front 106

What is used for diagnosing AMI in patients with conmitant skeletal muscle trauma/disease or monitor graft vs. host disease in heart transplant patients?

Back 106

cTnI

Front 107

What is used for risk assessment with acute myocardial ischemia?

Back 107

cTnT

Front 108

Following myocardial damage, troponin I in plasma is often found complexed with what? What is the importance of this?

Back 108

Troponin I if complexed with troponin C, undergo structural changes that affect the binding of monoclonal antibodies that are used in the assays for detection

Front 109

Describe the timeline of AMI markers

Back 109

Front 110

What are some thrombolytic agents? What is used for?

Back 110

Streptokinase and urokinase are used to dissolved blood clots and restore blood flow to minimize ischemic injury and cell death but must be administered within 4 hours of onset of symptoms (if given in the 1st hr, there's a 50% reduction in mortality)

Front 111

If reperfusion with thrombolytic agents are successful, what changes are seen?

Back 111

• total CK peaks earlier
• CK-MB peaks earlier
• cTnT day 1/day 4 ratio is greater than 1 (failed if less than 1)
  

Front 112

What is congestive heart failure?

Back 112

failure of the heart to pump sufficiently

Front 113

If the left side of the heart fails, what happens?

Back 113

pressure builds upt owards the lungs and causes pulmonary edema (difficulty breathing)

Front 114

If the right side of the heart fails, what happens?

Back 114

pressure builds up towards the body, and causes abdominal, leg and ankle adema

Front 115

What is the marker for congestive heart failure?

Back 115

B-type natriuretic peptide (BNP)

Front 116

The cardiac ventricles secret what cardiac neurohormone?

Back 116

BNP

Front 117

What does BNP do?

Back 117

stimulates urinary excretion of sodium and increase urine flow without affecting GFR, blood pressure, or renal flow

Front 118

Concentrations of BNP increases in what conditions?

Back 118

• congestive heart failure
• renal and/or hepatic failure