Myocardial Hypertrophy and Heart Failure

Question 1

What is the normal ejection fraction?

Answer 1

60%

Question 2

What compensatory mechanisms occur when minor functional impairment of the heart occurs chronically?

Answer 2

Increase in diastolic ventricular filling pressure and end-diastolic volume

Question 3

What is the Frank-Starling mechanism (Law)?

Answer 3

Cardiac stroke volume is a function of diastolic fiber length (w/i certain limits, the heart will pump whatever volume is brought to it by the venous circulation)

Question 4

What is the most prominent feature of heart failure?

Answer 4

Abnormally high atrial filling pressure relative to stroke volume.

Question 5

What are four important signaling molecules associated with heart failure?

Answer 5

Angiotensin II, Endothelin-1, Insulin-Like Growth Factor-I, ECM

Question 6

What causes the release of Angiotensin II? What effect does it have?

Answer 6

Released locally in response to load or stress stimuli? Paracrine and Autocrine mechanisms that promote protein synthesis and hypertrophy through MAP Kinase and CaM Kinase Pathways

Question 7

What cardiovascular effects does Endothelin-1 have?

Answer 7

Potent vasoconstrictor, acts thru MAP Kinase to promote hypertrophy

Question 8

What cardiovascular effects does Insulin-Like Growth Factor-I have?

Answer 8

Growth-promoting peptide that acts thru PI3K pathway to cause cardiac hypertrophy

Question 9

What role does ECM play in heart failure?

Answer 9

Interstitial fibrosis is an obligatory feature of the hypertrophic response in CHF

Question 10

What role does the Mitogen-Activated Protein Kinase Pathway play in heart failure?

Answer 10

MAPK leads to the activation of the extracellular receptor kinase 1/2 which promotes growth/survival of myocytes while activation of the c-Jun N-terminal kinase (JNK) and p38 MAPK cascades is involved in pathologic remodeling/apoptosis of cardiac myocytes

Question 11

What role does the Phosphatidylinositol-3-Kinase Pathway (PI3K) play in heart failure?

Answer 11

The p110gamma PI3K promotes internalization of Beta-adrenergic receptors and inhibits SERCA activity

Question 12

What role does Beta-Adrenergic Signaling and Desensitization play in heart failure?

Answer 12

Increased levels of catecholamines cause the heart to withdraw it Beta-adrenergic receptors so that it will do less work.

Question 13

What are the major proteins/pathways perturbated in CHF? Describe the pathogenesis of each

Answer 13

1. Ryanodine Receptor - Numbers decrease and therefore decreases the amount of Ca released on contraction (contraction decreases)
2. SERCA - Decreased Ca reuptake impairs heart relaxation
3. Phospholamban increases - it couples with SERCA (inhibiting SERCA) leading to higher levels of cytoplasmic Ca
4. CaMK Pathways increase in HF leading to perturbations in levels of SERCA, phospholamban and voltage-gated L-type Ca channels

Question 14

What protooncogenes are expressed in acute pressuere overload? What mediates this expression?

Answer 14

Protooncogenes c-jun and c-fos and heat shcok protein 70 mediated by AngII

Question 15

Where is ANP expressed in the fetus? After birth?

Answer 15

Ventricle and Atrium; Atrium

Question 16

When is BNP expressed?

Answer 16

In the hypertrophied heart

Question 17

What are ANP and BNP used for?

Answer 17

Used as biomarkers to determine the severity of heart failure

Question 18

Describe the changes that occur in Beta-myosin in pathologic heart hypertrophy

Answer 18

Slow contraction, low ATPase Beta-myosion (fetal form) is reexpressed in the atrium of hypertrophied hearts

Question 19

Describe the changes in metabolism that occur in a failing heart. How is this adaptive?

Answer 19

The hypertrophied heart reexpresses genes that encode for glucose oxidation instead of fatty acid oxidation. Glycolytic pathways use less oxygen (advantageous)

Question 20

What is the general trend of cardiac myocyte proliferation in heart failure?

Answer 20

Apoptosis increases

Question 21

What accounts for more than 80% of deaths from heart disease?

Answer 21

Ischemic heart disease

Question 22

What condition is seen in virtually all types of heart failure?

Answer 22

Left ventricular hypertrophy

Question 23

How does the heart compensate in left heart failure? Describe the process leading to pulmonary edema

Answer 23

1. Left atrial and pulmonary venous pressure increase
2. Pulmonary congestion occurs
3. Small ruptures in the vasculature cause RBCs to leak into lung
4. Macrophages uptake hemosiderin

Question 24

What are heart failure cells?

Answer 24

Hemosiderin-laden macrophages

Question 25

Describe the complications resulting from right heart failure

Answer 25

1. Right atrial and systemic venous pressure increase
2. jugular venous distention, edema of lower extremities, congestion of liver/spleen

Question 26

What are the findings in the liver in right heart failure?

Answer 26

Nutmeg liver - hepatic congestion causing distended central veins

Question 27

What are common causes of right heart failure?

Answer 27

Pulmonary HTN/disease

Question 28

What is the pathologic process occuring in this section of heart? What is actually occurring?

Answer 28

Myocytolysis; Chronically injured cells exhibit loss of myofibrils and sarcomeres and increase cytosol and glycogen

Question 29

In what population is diastolic heart failure seen? What is the process that occurs in DHF?

Answer 29

Elderly; Ventricles become stiffer with age and require greater diastolic filling pressures

Question 30

What are Syx of LHF? Why?

Answer 30

Dyspnea on exertion, Orthopnea, Paroxysmal Nocturnal Dyspnea due to pulmonary congestion

Question 31

What are examples of backward failure? Forward failure?

Answer 31

Venous congestion; inadequate perfusion of vital organs