Pathophysiology of Coronary Artery Disease Flashcards Preview

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Flashcards in Pathophysiology of Coronary Artery Disease Deck (28):
1

Right Coronary Artery

  • Origin
  • In 90% of people
  • In 10% of people
  • Right coronary artery

  • Origin
    • Right coronary ostium --> right in the AV groove
  • In 90% of people
    • --> right dominant artery --> posterior descending artery --> posterior interventricular septum
    • Dominant right coronary artery --> AV nodal artery
  • In 10% of people
    • --> left dominant artery --> circumflex artery --> posterior descending artery
    • Dominant circumflex artery --> AV nodal artery
  • Right coronary artery
    • --> branches --> anterior right ventricular wall
    • --> acute marginal branch --> free margin of the RV
    • --> posterolateral branches distal to the posterior descending artery

2

Left Coronary Artery

  • Origin: left coronary ostium
  • --> left main coronary artery
    • --> left anterior descending (LAD) coronary artery
      • --> anterior interventricular groove overlying the septum
      • --> diagonal vessels that traverse the anterolateral wall
      • --> septal perforator vessels that penetrate the interventricualr septum
    • --> circumflex artery
      • --> AV groove to the left
      • --> obtuse marginal vessels
    • --> ramus artery at the bifurcation of the LAD & circumflex artery

3

Coronary Artery Disease

  • Coronary atherosclerosis
  • Atherosclerotic lesions in a coronary artery
    • Two types
    • Differences
  • Angiography
  • Techniques that can image the vessel wall & provide additional info regarding total disease burden

  • Coronary atherosclerosis
    • Frequently diffuse down vessel wall w/ segmental areas of more severe obstruction
    • Frequently eccentric in vessel wall
  • Atherosclerotic lesions in a coronary artery
    • Two types
      • Circumferential (sometimes)
      • Eccentric (often)
    • Differences
      • Vulnerability to vasospasm at the site of the lesion
      • Respond differently to interventional procedures
  • Angiography
    • Silhouette technique to visualize the lumen
    • Gives info about the degree of obstruction of the vessel lumen
    • Limited ability to quantify the extent of the disease b/c the atherosclerotic burden is intramural
  • Techniques that can image the vessel wall & provide additional info regarding total disease burden
    • Intracoronary ultrasound
      Cardiac CT imaging
    • Cardiac MRI

4

Cardiovascular Disease and Mortality

  • CV disease: largest cause of mortality in th eUS
  • Equal frequency in men & women
  • Occurs 10 years later in women during post-menopause

5

Of asymptomatic men 30-60yo, 5% per year will develop symptomatic CAD manifested by...

  • Myocardial infarction
  • Stable angina pectoris
  • Sudden death
  • Unstable angina pectoris

6

Oxygen Requirements of the Heart

  • Heart: obligate aerobic organ
    • To do more work, it has to consume more oxygen
  • It has a limited capacity to generate energy through anaerobic metabolism
  • Oxygen requirements of the heart are 5x greater than the rest of the body
    • LV: particularly oxygen demanding, 20x greater than the rest of the body

7

Oxygen Consumption

  • Total amount of oxygen delivered to an organ is a product of...
  • Normal arterial blood
  • Oxygen consumption of an organ is a product of...
  • Arteriovenous oxygen difference (AVO2 difference)

  • Total amount of oxygen delivered to an organ is a product of...
    • Oxygen carrying capacity of the blood
      • Determined by the hemoglobin concentration in the RBCs
    • Total blood flow
  • Normal arterial blood
    • Fully saturated w/ oxygen
  • Oxygen consumption of an organ is a product of...
    • Blood flow to the organ
    • Extraction of oxygen from the blood that perfuses it
  • Arteriovenous oxygen difference (AVO2 difference)
    • Extraction of oxygen from the blood as it passes through an organ
    • Systemic AVO2 difference (total body oxygen extraction) = (oxygen content of the systemic arterial blood) - (oxygen content of blood returning to the pulmonary artery)

8

Oxygen Extraction

  • Blood returning to the pulmonary artery to be re-oxygenated
    • Rest
    • Exercise
  • Blood in the coronary sinus (venous drainage of coronary circulation)
    • Rest
    • Exercise

  • Blood returning to the pulmonary artery to be re-oxygenated
    • Rest: 70% saturated w/ oxygen
    • Exercise: increase total oxygen consumption by extracting more oxygen from blood it's already receiving
  • Blood in the coronary sinus (venous drainage of coronary circulation)
    • Rest: 30% satured w/ oxygen
    • Exercise: little capacity to increase its oxygen consumption by increasing oxygen extraction
  • Only way the heart can increase its oxygen consumption
    • Increase oxygen delivery (perfusion)
      • B/c areriovenous oxygen difference in the heart is nearly max at rest
      • Heart can't control hemoglobin concentration to increase oxygen delivery
    • Explains why coronary blood flow is so essnetial to myocardial performance
    • Explains why CAD limiting this flow has such severe implications

9

Coronary Blood Flow

  • Autoregulation
  • Primary determinants of myocardial oxygen demand (& coronary blood flow)
  • Congestive heart failure & digoxin

  • Autoregulation
    • Demand of heart for oxygen is kept in balance w/ supply of oxygen to the heart
  • Primary determinants of myocardial oxygen demand (& coronary blood flow)
    • HR
      • Greatest determinant
      • Increase HR --> increase myocardial oxygen demand
    • Systolic BP
      • Determines wall tension & myocardial oxygen demand
      • More expensive to the heart in terms of myocardial oxygen demand
      • Hypertension or aortic stenosis --> increase pressure in ventricle --> greater oxygen requirement than increased volume
    • LV volume/radius (LaPlace relationship)
      • Determines wall tension & myocardial oxygen demand
      • Less expensive to the heart in terms of myocardial oxygen demand
      • Aortic or mitral regurgitation --> increase volume in ventricle --> less oxygen requirement than increased pressure
    • Contractility
      • Increase contractility --> increase myocardial oxygen demand
  • Congestive heart failure & digoxin
    • Increase HR, BP, & volume --> increase myocardial oxygen demand
    • Digoxin: increase contractility --> resolve congestive heart failure --> decrease HR, BP, & volume --> decrease myocardial oxygen consumption

10

Perfusion Pressure

  • Coronary perfusion pressure
  • LV systolic pressure vs. aortic systolic pressure

  • Coronary perfusion pressure
    • Difference b/n aortic pressure & pressure in coronary sinus (venous drainage of coronary circulation)
  • LV systolic pressure vs. aortic systolic pressure
    • Since LV systolic pressure = aortic systolic pressure, there's no pressure gradient to drive coronary blood flow through the LV myocardium in systole
    • In the LV, coronary blood flow is limited to diastole
    • Aortic diastolic pressure primarily drives pressure for coronary perfusion

11

Systolic Coronary Blood Flow

  • Blood flow in the LV during systole
    • When flow is limited to systole, transmyocardial flow in teh LV drops
    • Flow is preserved to the epicardial vessels for capacitance
      • Flow doesn't proceed through the myocardial wall
    • Systolic LV pressure = central aortic pressure
      • --> no pressure gradient to drive coronary flow through the LV
    • ► coronary blood flow in the LV is primarily a diastolic phenomenon
    • ► perfusion to the endocardium is exclusively diastolic
  • Blood flow in the RV during systole
    • RV systolic pressure is lower than systemic arterial pressure
      • --> pressure gradient during systole to drive coronary perfusion to the RV

12

Resistance to Coronary Perfusion

  • R1 vessels: epicardial coronary arteries & larger intramyocardial vessels
  • R3: vessels contained within myocardium
  • R2: smaller arteries & precapillary arterioles
  • R2 + R3
  • High R3 component in systole in the LV
  • Lower R3 component in epicardial regions

  • R1 vessels: epicardial coronary arteries & larger intramyocardial vessels
    • Vessels seen on a coronary angiogram
    • Contribute little to resistance to coronary perfusion
    • Primarily serve a capacitance function
  • R3: vessels contained within myocardium
    • Coronary arteries penetrate from epicardium --> myocardium --> endocardium
    • Any force exerted against the myocardium is unevenly distributed across the myocardial wall
      • Greatest in the subendocardium
      • Least in the subepicardium
  • R2: smaller arteries & precapillary arterioles
    • Contribute more to coronary perfusion
    • Vasodilate in the subendocardial region --> decrease R2 resistance --> overcome R3 resistance & protect subendocardial perfusion
  • R2 + R3
    • Kept constant to preserve subendocardial perfusion
  • High R3 component in systole in the LV
    • Systolic wall tension
    • Limits perfusion of the LV to diastole
  • Lower R3 component in epicardial regions
    • Why some systolic perfusion to that region can still occur
    • Blood can't flow into distal vasculature in systole, but its capacitance can flow
    • Fills epicardial vessles w/ blood that then perfuses distally during diastole

13

Coronary Vascular Resistance vs. Pressure

  • R1 vessels: epicardial & larger intramyocardial vessels
  • R2 vessels: prearteriolar & arteriolar vessels

  • R1 vessels: epicardial & larger intramyocardial vessels
    • Contribute little to resistance to coronary blood flow
    • Serve primarily a capacitance function
    • Decrease in pressure as blood flows through them is minor
  • R2 vessels: prearteriolar & arteriolar vessels
    • Where greatest decrease in pressure occurs as blood flows through the arterial bed to the venous circulation

14

Autoregulation of Coronary Blood Flow

  • Autoregulatory range of perfusion
  • As perfusion pressure drops below a critical level...
  • If perfusoin pressure increases to very high levels...

  • Autoregulatory range of perfusion
    • Rest: coronary blood flow is maintained at a constant level through this wide range of coronary perfusion pressures (circled)
  • As perfusion pressure drops below a critical level...
    • Coronary perfusion can't be futher protected
    • Coronary blood flow decreases proportionally to decreasing perfusion pressure (solid arrow)
    • Occurs when the R2 resistance vessels have maximally vasodilated
  • If perfusoin pressure increases to very high levels...
    • It overwhelms the resistance vessels' ability to regulate it
    • Coronary blood flow increases proportionally to increasing perfusion pressure (open arrow)

15

Determinants of Myocardial Oxygen Demand at Rest & During Exercise

  • At exercise
    • Myocardial oxygen demand & coronary blood flow
    • HR
    • Systolic BP
    • LV volume
    • Contractility
  • Double product

  • At max exercise
    • Myocardial oxygen demand & coronary blood flow increase
    • HR increases --> coronary blood flow increases (most important determinant)
    • Systolic BP increases --> myocardial demand increases
    • LV volume may or may not increase depending on the type of exercise & the position
    • Contractility increases by direct rate related effects (Treppe effect) & by an increase in circulating catecholamines
  • Double product
    • Product of HR & systolic BP
    • Correlates closely w/ coronary blood flow

16

Autoregulation of Coronary Blood Flow

  • Myocardial oxygen demand vs. myocardial oxygen supply
  • Myocardial oxygen extraction in the coronary circulation at rest

  • Myocardial oxygen demand vs. myocardial oxygen supply
    • Increase mycoardial oxygen demand --> increase myocardial oxygen supply in a linear fashion
    • Controlled by the autoregulation of coronary blood flow
  • Myocardial oxygen extraction in the coronary circulation at rest
    • Myocardial oxygen extration is nearly maximal
    • Heart can't increase its oxygen consumption by increasing oxygen extraction from the blood it's already receiving
    • Increase oxygen demand --> increase coronary blood flow --> increase myocardial oxygen supply

17

Myocardial Oxygen Supply During Exercise

  • Systolic vs. diastolic BP during exercise
  • Increasing coronary blood flow
  • As HR increases during exercise...
  • Net effect

  • Systolic vs. diastolic BP during exercise
    • Systolic BP primarily increases
    • Diastolic BP shouldn't increase
  • Increasing coronary blood flow
    • R2 vessels vasodilate --> R2 vessels decrease their resistance --> increase coronary blood flow
  • As HR increases during exercise...
    • Diastole shortens --> coronary perfusion time shortens
  • Net effect
    • Decreased R2 resistance + shortened diastolic time interval --> increase coronary blood flow during max exercise

18

Autoregulation of Coronary Blood Flow

  • R2 vasodilation vs. coronary blood flow
  • Coronary flow reserve
  • Max coronary blood flow & coronary vasodilator reserve

  • R2 vasodilation vs. coronary blood flow
    • Increase vasodilation of R2 vessels --> increase coronary perfusion pressure --> increase max coronary blood flow
  • Coronary flow reserve
    • Difference b/n resting & max coronary blood flow
    • Directly dependent on coronary perfusion pressure
  • Max coronary blood flow & coronary vasodilator reserve
    • 2 different indices that are both directly related to coronary perfusion pressure

19

Myocardial Oxygen Supply: Coronary Artery Disease

  • Atherosclerotic coronary artery disease
  • Compensation for increased resistance to flow in the R1 vessel
  • Remaining ischemia
  • Overall compensations

  • Atherosclerotic coronary artery disease
    • Primarily a disease of the R1 (epicardial & large intramyocardial coronary) vessels
    • CAD --> resistance to flow through the stenotic lesion --> increased R1 resistance
    • Creates a perfusion pressure gradient to flow through the luminal narrowing
  • Compensation for increased resistance to flow in the R1 vessel
    • Dilate distal R2 vessels --> decreased R2 resistance --> maintain total resistance to perfusion --> preserve flow
  • Remaining ischemia
    • Some ischemia may remain in the most vulnerable subendocardial region
    • Early manifestation: diastolic dysfunction (shift of pressure/volume curve up & to the left)
    • Result: localized diastolic dysfunciton in R1 (epicardial) vessels --> increase LVEDP --> increase R3 (subendocardial) resistance
  • Overall compensations
    • Increased R1 resistance --> decrease R1 resistance
    • Increased R3 (subendocardial) resistance --> stenosis in R2 vessels --> R2 (subendocardial) vasodilation --> preserve flow

20

Coronary Blood Flow in CAD

  • CAD coronary blood flow: rest
  • CAD coronary blood flow: exercise
  • In the presence of coronary stenosis...
  • As the ventricle becomes ischemic...

  • CAD coronary blood flow: rest
    • Preserved via autoregulation despite obstructions
    • Primarily preserved via vasodilated R2 vessels
  • CAD coronary blood flow: exercise
    • R2 dilate --> decrease resistance to flow --> increase coronary blood flow
  • In the presence of coronary stenosis...
    • R2 vessels have already vasodilated maximally to preserve perfusion at rest
    • There's nothing more coronary circulation can do to increase perfusion
    • Increase demand + flow can't increase --> supply/demand mismatch --> ischemia
  • As the ventricle becomes ischemic...
    • Systolic & diastolic functions deteriorate
    • LVEDP & LVEDV incrase --> increaes R3 resistance --> increase ischemia

21

Autoregulation of Coronary Blood Flow

  • Myocardial oxygen demand vs. myocardial oxygen supply
  • In the presence of coronary artery obstruction...
  • Ischemic area
  • Ischemic threshold
  • Ischemic threshold for mild coronary disease vs. severe obstructive disease

  • Myocardial oxygen demand vs. myocardial oxygen supply
    • Increase myocardial oxygen demand --> increase myocardial oxygen supply linearly
  • In the presence of coronary artery obstruction...
    • Myocardial oxygen supply increases linearly to increase myocardial oxygen demand
    • When R2 vessels vasodilate maximally, coronary circulation autoregulatory reserve is expended
    • Further increases in myocardial oxygen demand don't further increase mycoardial oxygen supply
  • Ischemic area
    • Difference b/n normal & coronary artery obstruction curves
    • Supply < demand
  • Ischemic threshold
    • Point at which the two curves digress
    • Point of max R2 vessel vasodilation
    • Measure of severity of obstructive disease
  • Ischemic threshold for mild coronary disease vs. severe obstructive disease
    • Mild: ischemic threshold occurs at high levels of myocardial oxygen demand
    • Severe: ischemic threshold occurs at a lower level of demand

22

Autoregulation of Coronary Blood Flow vs. Stenosis

  • Max coronary blood flow in coronary artery stenosis decreases relative to coronary perfusion pressure
  • Curve S1: mild stenosis
  • Curve S2: severe stenosis

23

Coronary Blood Flow Relative to % Stenosis, Rest, & Peak Exercise

  • Coronary blood flow at rest
  • Coronary blood flow during max exercise
    • Stenosis < 50%
    • Stenosis > 50%
      • Critical zone
  • Stenosis length vs. flow

  • Coronary blood flow at rest
    • Remains normal w/ obstructions up to 80-90% in severity
    • Reflection of the vasodilatory reserve of R2 vessels
  • Coronary blood flow during max exercise
    • Stenosis < 50%: peak coronary blood flow is maintained at normal levels
    • Stenosis < 50%: sharp decline in peak coronary blood flow w/ increasing obstructions
      • Critical zone: small increase in obstruction --> large decrease in blood flow
  •  Stenosis length vs. flow
    • Increase length of vessel --> decrease peak flow

24

Percent Stenosis Limitations

  • Reproducibility
  • Diffusibility
  • Techniques that can image both the lumen & vessel wall

  • Reproducibility
    • Percent stenosis is assessed by coronary angiography (visual analysis)
    • Variability in interpretations by coronary angiographers
  • Diffusibility
    • CAD is often diffuse down the length of a vessel
    • Assess percent stenosis
      • Estimate lumen at site of stenosis & compare it to another portion of the lumen of the same vessel that appears normal
      • --> difference estimates percent stenosis
    • If disease is diffuse, area that appears normal may be stenosed
      • --> underestimates the true original lumen size & underestimates the severity of the lesion
  • Techniques that can image both the lumen & vessel wall
    • Intracoronary angiography
    • Cardiac CT & MRI

25

Predicting Flow

  • Visual interpretation of coronary angiogram prediction of flow
  • Percent stenosis prediction of flow
  • Minimal luminal cross sectional area prediction of flow

  • Visual interpretation of coronary angiogram prediction of flow
    • Poor correlation: visual interpretation underestimates disease severity
  • Percent stenosis prediction of flow
    • Poor correlation b/n peak flow velocity by doppler measurement & percent diameter / luminal narrowing
    • Percent stenosis, while a widely used standard for assessing disease severity, is actually a crude measurement w/ limitation
  • Minimal luminal cross sectional area prediction of flow
    • Close correlation b/n peak lumenal area & peak doppler flow
    • Size of remaining lumen matters more than the percent stenosis of the lesion
    • Small vessel w/ 50% stenosis will have a lower peak flow than a large vessel w/ 50% stenosis

26

Endocardium

  • Subendocardium
  • Myocardial oxygen demand in subendocardium vs. middle & epicardial layers
  • R3 component of resistance
  • Oxygen demand in the endocardium

  • Subendocardium
    • Area of myocardium at greatest vulnerability for ischemia
  • Myocardial oxygen demand in subendocardium vs. middle & epicardial layers
    • Subendcardium > middle or epicardial layers
  • R3 component of resistance
    • Greatest in the subendocardial region
    • Unevenly distributed across the myocardial wall
    • Increased subendocardial oxygen demand requires increased subendocardial blood flow to meet that demand
  • Oxygen demand in the endocardium
    • Since pressure is a determinant of myocardial oxygen demand, the increased forces exerted against the endocardial wall increase the oxygen requirements in that area
    • Since oxygen demand is greatest in the endocardial region, the endocardium requires more blood flow at rest than the epicardium to meet that incrased demand

27

Systolic Coronary Blood Flow

  • Systolic vs. diastolic persuion in the epicardium & endocardium
  • Rate of flow in epicardium vs. endocardium
  • Mechanisms by which endocardium receives flow

  • Systolic vs. diastolic persuion in the epicardium & endocardium
    • Coronary perfusion in the LV is primarily diastolic
    • Epicardium: receives more flow/perfusion in systole
    • Endocardium: receives more flow/perfusion in diastole
  • Rate of flow in epicardium vs. endocardium
    • Endocardium receives more flow in less time than epicardium
    • Rate of flow in endocardium > epicardium
  • Mechanisms by which endocardium receives greater rate of flow
    • More vessels per unit area
    • Increased size of the vascular bed
    • R2 vasodilation --> decreased R2 component of resistance at rest

28

Subendocardial Perfusion

  • R2 during exercise
  • Coronary blood flow vs. HR
  • Subendocardial vs. epicardial blood flow at rest
  • Subendocardial blood flow in CAD

  • R2 during exercise
    • R2 vasodilates --> decreases resistance --> provides increased rate of flow to the endocardium
    • Less vasodilating reserve for recruitment int he endocardial region --> makes endocardium more vulnerable to ischemia in the presence of CAD
    • Pts present w/ subendocardial ischemia or infarction
  • Coronary blood flow vs. HR
    • Increase HR --> increase coronary blood flow --> maintain epicardial blood flow at a consistent level
  • Subendocardial vs. epicardial blood flow at rest
    • Subendocardial > epicardial blood flow at rest
    • Increase HR --> decrease subendocardial blood flow
  • Subendocardial blood flow in CAD
    • CAD: subendocardial blood flow is lower than normal at rest & decreases more rapidly than normal as HR increases
    • Peak HR is limited by ischemia