Crr Week 5: Heart Failure Pathology (Murray)

Front 1

List 5 causes of left ventricular injury.

Back 1

1. Hypertension
2. Diabetes
3. Coronary artery disease
4. Cardiomyopathy
5. Valvular disease

Front 2

Left ventricular injury can cause a series of events that increase pathologic cardiac remodeling. List some of these events.

Back 2

1. Neurohormal stimulation
2. Endothelial dysfunction
3. Myocardial toxicity
4. Vasoconstriction
5. Na+/water retention

Front 3

Decreased ejection fraction will result in what symptoms?

Back 3

1. Dyspnea
2. Fatigue
3. Edema

Front 4

List 2 signs of systemic congestion.

Back 4

1. Jugular venous distension (JVD)
2. Peripheral edema

Front 5

How can an echocardiogram be used to gauge systolic heart failure?

Back 5

The LV chamber size is measured to get a value for ejection fraction.

Front 6

How is an echocardiogram used to gauge diastolic heart failure?

Back 6

Measurements across the mitral valve are taken.

Front 7

Which 3 adaptive mechanisms have evolved to maintain function during heart failure?

Back 7

1. Frank starling mechanism
2. Neurohormonal activation
3. Myocardial remodeling

Front 8

Sympathetic activation during heart failure leads to what events?

Back 8

1. Increased myocardial contractility
2. Tachycardia
3. Sodium retention
4. Renin release
5. Vasoconstriction

Front 9

What mechanism regulates sympathetic outflow during heart failure?

Back 9

Baroreceptor reflex
(negative input stimulates increase in sympathetic outflow, decrease in parasympathetic outflow)

Front 10

Which 3 mechanisms regulate vasoconstriction during heart failure?

Back 10

1. Sympathetic NS
2. Renin-angiotensin system
3. Endothelin system

Front 11

What is the result of the Sympathetic NS on blood flow redistribution?

Back 11

Blood flow is redistributed under stress to perfuse vital organs (brain and heart)

*Less for skin, skeletal muscle, gut, and kidney

*leads to anaerobic metabolism, lactic acidosis, oxygen debt, and fatigue

Front 12

How is NO produced in endothelial cells?

Back 12

NO synthase produces NO from precursor L-arginine

Front 13

What kind of cardiac remodeling occurs as a result of pressure overload?

Back 13

(Systolic wall stress)

*Concentric hypertrophy

Front 14

What kind of cardiac remodeling occurs as a result of volume overload?

Back 14

(Diastolic wall stress)

*Eccentric hypertrophy

Front 15

During early hypertrophy, what happens to the myocytes and cellular organization?

Back 15

Myocytes increase in SIZE
Cellular organization is preserved

Front 16

As hypertrophy advances, what happens to the myocytes and cellular organization?

Back 16

Myocytes increase in size AND number
Cellular organization is disrupted with irregular addition of contractile elements and large volume myofibrils

Front 17

What happens to cardiac fibers in the late stage of hypertrophy?

Back 17

1. Loss of contractile elements, with disruption of z-bands
2. Disruption of normal parallel arrangement of sarcomeres
3. Fibrous deposition
4. Dilated, tortuous T tubules

Front 18

What happens to the expression of L-type Ca2+ channels and Na+/Ca2+ exchangers during heart failure?

Back 18

L-type Ca2+-channels DECREASE
Na+-Ca2+-exchange INCREASE

(Result: less intracellular Ca2+, decreased contractility)

Front 19

What happens to the expression of B1-adrenergic receptors during heart failure?

Back 19

Decreased

Front 20

What happens to the expression of B2 and alpha-1 adrenergic receptors during heart failure?

Back 20

Increased

Front 21

What happens to the expression of ryanodine receptors and phospholamban due to heart failure?

Back 21

Decreased

Front 22

What sort of cellular changes happen as a result of myocardial remodeling?

Back 22

1. Myocyte hypertrophy
2. Myocyte apoptosis/necrosis
3. Reexpression of fetal genes
4. Altered expression of contractile proteins
5. Changes in ECM

Front 23

How is the cellular matrix changed during cardiac remodeling?

Back 23

Metalloproteinases alter deposition of types I and III fibrillar collagen

*increased fibrosis, stiffness, wall thickness

Front 24

How is the LV chamber geometry changed during cardiac remodeling?

Back 24

1. LV dilation
2. Increased LV sphericity
3. LV wall thinning
4. Mitral valve incompetence

Front 25

Which 3 classes of drugs counteract the renin-angiotensin system?

Back 25

1. ACE inhibitors
2. AT receptor blockers
3. Aldosterone blockers

Front 26

Which group of drugs counteract the increased sympathetic outflow during heart failure?

Back 26

Beta blockers
(metoprolol, carvedilol)

Front 27

What is the effect of ACE inhibitors and beta blockers on myocardial hypertrophy?

Back 27

Decreased

Front 28

What is the effect of ACE inhibitors and beta blockers on E-C coupling?

Back 28

Increased

Front 29

What is the effect of ACE inhibitors and beta blockers on fetal gene expression?

Back 29

Decreased

Front 30

What is the effect of ACE inhibitors and beta blockers on beta-adrenergic desensitization?

Back 30

Decreased

Front 31

What is the effect of ACE inhibitors and beta blockers on myocyte contractility?

Back 31

Beta blocker increases contractility
(ACE inhibitors have no change)

Front 32

Which two groups of drugs can be combined to maximally reduce mortality rate from heart failure?

Back 32

ACE inhibitors and Beta-blockers