PBL #3

Question 1

What are the physics and physiology of the S1 (lub) heart sound?

Answer 1

• Occurs during Isovolumetric ventricular contraction
  
  • closure of mitral and tricuspid valves
  • ventricular pressure exceeds atrial pressure

Question 2

What are the physics and physiology of the S2 (dub) heart sound?

Answer 2

• due to closure of the aortic and pulmonic valves
  
  • L. ventricular pressure drops below pressure in the aorta
  • R. ventricular pressure drops below pressure in the pulmonary trunk
• at the beginning of isovolumetric ventricular relaxation

Question 3

What are the physics and physiology of the S3 heart sound?

Answer 3

• Occurs early in ventricular filling
• May represent tensing of the chordae tendineae and the atrioventricular ring
  
  • which is the connective tissue supporting the AV valve leaflets
• Children → normal
• Adults →associated with ventricular dilation as occurs in systolic ventricular failure.

Question 4

What are the physics and physiology of the S4 heart sound?

Answer 4

• Caused by vibration of the ventricular wall during atrial contraction.
• This sound is usually associated with a stiffened ventricle (low ventricular compliance), and therefore is heard in patients with ventricular hypertrophy, myocardial ischemia, or in older adults.

Question 5

What is edema?

Answer 5

swelling caused by excess fluid trapped in the body’s tissues

Question 6

What are the cardiovascular parameters that regulate tissue fluid balance?

Answer 6

Typically, high hydrostatic pressure at the arteriole end of the capillary causes filtration OUT of the vessel and then on the venule side there is a net reabsorption as the hydrostatic pressure falls.

Question 7

How would alterations in the normal cardiovascular tissue fluid balance parameters lead to edema formation?

Answer 7

• CHF → increased central venous pressure due to mitral stenosis
  
  • resulting in increased pressure in the left atrium which pushes fluid back into lungs
  • making it harder for the right ventricle to pump blood to the lungs→ RV hypertrophy
  • this increased pressure in the lungs (pulmonary hypertension) causes increased hydrostatic pressure in the capillaries, which causes net filtration throughout the capillary⇒ PULMONARY EDEMA!
• The release of ADH and aldosterone both promote retention of fluid which contributes to the edema associated with CHF.

Question 8

What is shortness of breath?

Answer 8

feeling or feelings associated with impaired breathing

Question 9

What are possible pathophysiologic mechanisms that would lead a patient to feel “short of breath”?

Answer 9

• dyspnea results when a “mismatch” occurs between afferent and efferent signals:
  
  • when the need for ventilation (afferent signaling) is not being met by physical breathing (efferent signaling)
  • Chemoreceptors in the carotid bodies and medulla supply information regarding the blood gas levels of O2, CO2 and H+
• specifically: poor ventilation leading to hypercapnia + left heart failure leading to interstitial edema (impairing gas exchange) contribute to the feeling of dyspnea

Question 10

What does the measurement of oxygen saturation tell you?

Answer 10

• Oxygen saturation is an estimation of the oxygen saturation level.
• It measures the percentage of hemoglobin binding sites in the bloodstream occupied
  
  • _{Be careful: measures percent of hemoglobin binding sites occupied by any substance, for example Carbon Monoxide has higher affinity and will bind to hemoglobin and show good sat levels but in reality the person has low perfusion of oxygen}

Question 11

What is the physics and physiology of heart murmurs due to mitral stenosis?

Answer 11

• Narrowing of the mitral valve orifice (usually due to chronic rheumatic valve disease)
• Clinical features:
  
  • Opening Snap followed by diastolic rumble
• Volume overload leads to dilation of left atrium, resulting in:
  
  • Pulmonary congestion w/ edema and alveolar hemorrhage
  • Pulmonary hypertension and rt-sided heart failure

Question 12

What is the physics and physiology of heart murmurs due to mitral insuffiency?

Answer 12

• Valve does not close fully during systole
  
  • due to flail leaflets, MI, IE, RHD, trauma
• Clinical findings:
  
  • high-pitched holosystolic murmur followed by slight S3
• Complications:
  
  • left atrial/ventricular enlargement
  • Left sided heart failure → rt heart failure
  • fatigue, SOB, pulmonary congestion, a-fib, edema

Question 13

What is the physics and physiology of heart murmurs due to aortic insuffiency?

Answer 13

• Backflow of blood from the aorta to the left ventricle during diastole. Arises due to aortic root dilation
• Clinical features:
  
  • Blowing Diastolic murmur
  • Increased Pulse Pressure
  • Decreased Ejection Fraction

Question 14

What is the physics and physiology of heart murmurs due to aortic stenosis?

Answer 14

• Narrowing of aortic valve orifice.
  
  • Due to fibrosis and calcification from “wear and tear”
  • may also arise from chronic rheumatic valve disease.
• Clinical features:
  
  • Asymptomatic stage during which a systolic ejection click followed by a crescendo-decrescendo murmur.
• Complications:
  
  • Left ventricular hypertrophy
  • angina and syncope w/ exercise

Question 15

What is cardiac catheterization?

Answer 15

• A long, thin, flexible tube called a catheter is put into a blood vessel in your arm, groin (upper thigh), or neck and threaded to your heart.
  
  • measure pressure and blood flow
  • catheter is used to clear a narrowed or blocked artery, or widen a narrowed heart valve opening
• Procedure visualized with contrast dye visible on x-ray

Question 16

What is the MOA of Nitroglycerin?

Answer 16

• Vasodilator of VEINS!
• NO relaxes smooth muscle via an increase in cGMP→ causes a decrease in intracellular Ca²⁺.
  
  • When inhaled, NO can also work as a bronchodilator
• Can also increase the PaO2 by dilating pulmonary vessels in better ventilated areas of the lung, which then redistributes blood AWAY from regions of poor gas exchange TOWARDS regions with better gas exchange.

Question 17

What is the MOA of Furosemide?

Answer 17

• Block NaCl (NKCC) reabsorption in thick ascending limb of the loop of Henle
• acts by inhibiting NKCC2 pump, the luminal Na-K-2Cl symporter in the thick ascending limb of the loop of Henle.
  
  • This increases the excretion of sodium and chloride
  • Water follows salt → gets peed out!

Question 18

What is the MOA of Enalapril?

Answer 18

• Suppresses the renin-angiotensin-aldosterone system
  
  • Competitive inhibitor of ACE (angiotensin-converting enzyme)
    
    • blocks conversion Angiotensin I to Angiotensin II → thus no aldosterone

Question 19

What is the MOA of Metoprolol?

Answer 19

• Inhibits response to adrenergic stimuli by competitively blocking β1-adrenergic receptors within the myocardium
  
  • Blocks β2-adrenergic receptors within bronchial and vascular smooth muscle only in high doses
• Decreases resting HR, reflex orthostatic tachycardia, myocardial contractility, and cardiac output
  
  • _{BP = HR (beta1) x SV (beta1) x TPR (alpha1, beta2)}

Question 20

What is the MOA of Eplerenone?

Answer 20

• Antimineralocorticoid, or an antagonist of the mineralocorticoid receptor
  
  • blocks the action of aldosterone
• Produces sustained increases in plasma renin and serum aldosterone concentrations, reflecting the inhibition of the negative feedback of aldosterone on renin secretion.

Question 21

What is the rationale for using Enalapril in acute and/or chronic management of CHF?

Answer 21

Used in management of symptomatic heart failure, usually in conjunction with cardiac glycosides, diuretics, and β-adrenergic blocking agents.

Question 22

What is the rationale for using Metoprolol in acute and/or chronic management of CHF?

Answer 22

Management of mild to moderately severe (NYHA class II or III) heart failure of ischemic, hypertensive, or cardiomyopathic origin (in conjunction with ACE inhibitors, diuretics, and cardiac glycosides)

Question 23

What is the rationale for using Eplerenone in acute and/or chronic management of CHF?

Answer 23

Aldosterone antagonist recommended in selected patients with New York Heart Association (NYHA) class II-IV heart failure and left ventricular ejection fraction ≤ 35%, to reduce morbidity and mortality.

Question 24

What is the MOA of Digoxin?

Answer 24

• Inhibits the activity of sodium-potassium-activated adenosine triphosphatase (Na+-K+-ATPase), an enzyme required for active transport of sodium out of myocardial cells
  
  • This leads to a higher increase of sodium inside the cell
  • Sodium/Calcium exchanger (antiporter) are present on membranes of myocardial cells.
  • Thus more calcium can be transported into myocardial cells.
  • Calcium is needed for contraction (Binds to Calmodulin, blah, blah)
• The main pharmacologic property is its ability to increase the force and velocity of myocardial systolic contraction (positive inotropic action) by a direct action on the myocardium.

Question 25

What is the MOA of Hydralazine?

Answer 25

• Arterial vasodilator
  
  • release of NO from drug & endothelial cells → arteriole dilation (not venous) (not well understood)
  • Increased CO & SV, direct relaxation of vascular smooth muscle
  • Decrease diastolic more than systolic
  • ***only give with HTN

Question 26

What is the MOA of Isosorbide Dinitrate?

Answer 26

• Stimulates cGMP production → vascular smooth muscle relaxation.
• Peripheral VENOUS resistance is decreased via a selective action on VENOUS capacitance vessels→ venous pooling of blood AND decreased venous return to the heart.
• Effects on arteriolar resistance is not as great as the action on the venous side
  
  • but venous and arterial effects together result in decreased preload (venous filling) and to a lesser extent, afterload.

Question 27

What are the possible microbial etiology of infectious endocarditis?

Answer 27

• Staph Aureus
• Strep viridans
• Strep Pyogenes
• Staph Epidermidis
• Enterococcus

Question 28

Describe infectious endocarditis due to Staph Aureus.

(Gm +/-, virulence factors, ensuing inflammatory process, and the mechanisms by which valvular function is compromised)

Answer 28

• Most common cause of ACUTE endocarditis
  
  • majority of infective endocarditis in IV drug users
  • Results in large vegetations that destroy previously normal valves
• Gram + → Cocci → Catalase + → Coagulase +
• Virulence factors:
  
  • biofilm formation, capsule, adhesins, hemolysins, Protein A

Question 29

Describe infectious endocarditis due to Streptococcal species (viridans).

(Gm +/-, virulence factors, ensuing inflammatory process, and the mechanisms by which valvular function is compromised)

Answer 29

• Low-virulence organism that infects previously damaged valves (i.e. Rheumatic Fever).
  
  • Results in small vegetations that don’t destroy the valve (SUBACUTE endocarditis).
  • Very abundant in the mouth.
• Gram + → cocci → Catalase Negative → alpha hemolytic
• Virulence factors:
  
  • production of dextran for glycocalyx formation and surface adhesion proteins that assist colonization

Question 30

Describe infectious endocarditis due to Enterococcus species.

(Gm +/-, virulence factors, ensuing inflammatory process, and the mechanisms by which valvular function is compromised)

Answer 30

• 3rd major cause of infectious endocarditis
  
  • most frequently following GU procedures in older men and OB procedures in younger women
• Virulence factors:
  
  • Pili
  • Surface proteins
  • Extracellular enzymes: proteases and hyaluronidases
• Gram + → Cocci

Question 31

Describe infectious endocarditis due to Strep pyogenes.

(Gm +/-, virulence factors, ensuing inflammatory process, and the mechanisms by which valvular function is compromised)

Answer 31

• Can cause rheumatic heart disease in genetically predisposed individuals
  
  • affects the mitral valve
  • type II hypersensitivity reaction between M protein of strep and meromyosin
• Virulence factors:
  
  • streptokinase→ converts plasminogen to plasmin
  • M protein → resists phagocytosis
  • Hyaluronidase → breaks down connective tissue
  • Streptolysin O → Destroys RBC’s
  • Streptolysin S → Destroys WBC’s
• Gram + → cocci → catalase negative → Beta hemolytic → bacitracin sensitive

Question 32

Describe infectious endocarditis due to Staph epidermis.

(Gm +/-, virulence factors, ensuing inflammatory process, and the mechanisms by which valvular function is compromised)

Answer 32

• Associated with prosthetic valves.
• Virulence factors:
  
  • SD-repeat containing protein-G (SdrG)
  • Biofilm formation→ adhesion

Question 33

What are the pathologic changes you would expect to find in the lungs of a patient with biventricular congestive heart failure?

Answer 33

• Pulmonary HTN and edema due to left side heart failure → fluid backup → increased hydrostatic pressure → net filtration
• There is also likely to be hemosiderin laden macrophages (“heart failure” cells) in the lungs due to microhemorrhages from increased capillary pressure.

Question 34

What are the pathologic changes you would expect to find in the liver of a patient with biventricular congestive heart failure?

Answer 34

• Hepatomegaly is a common symptom of right sided heart failure → fluid backup → increased CVP → increased pressure in the portal vein → congestive hepatomegaly.
• CHF Hepatomegaly can rarely lead to “Cardiac cirrhosis.”
• Congestive hepatomegaly is often associated w/ tenderness (our case epigastric tenderness).

Question 35

What are the pathologic features of mitral stenosis?

Answer 35

• Narrowing of mitral valve orifice
• Due to:
  
  • chronic rheumatic valve disease
  • atherosclerotic/calcific depositions

Question 36

What are the pathologic features of mitral insufficiency?

Answer 36

• Reflux of blood from the left ventricle into the left atrium during systole.
• Arises as a complication of mitral valve prolapse.
• Other causes: LV dilation, infective endocarditis, acute rheumatic heart disease, papillary muscle rupture

Question 37

What are the pathologic features of aortic stenosis?

Answer 37

• Narrowing of the aortic valve orifice.
• Due to fibrosis and calcification from wear and tear.
• Can also arise from chronic rheumatic valve disease

Question 38

What are the pathologic features of aortic insufficiency?

Answer 38

• Backflow of blood from the aorta into the left ventricle.
• Arises due to aortic root dilation (aneurysm or aortic dissection)

Question 39

How does locus heterogeneity add to the complexity of distinguishing which gene or genes contribute to congestive heart failure?

Answer 39

• Locus heterogeneity is a single disorder, trait, or pattern of traits caused by mutations in genes at different chromosomal loci
• Basically, many genes control one disease, so it is tough to know which gene is actually responsible for a given disease and therefore tough to predict risks

Question 40

What are the categories of a patient with CHF based on the New York Heart Association system?

Answer 40

• Class I
  
  • No limitation of physical activity
  • Ordinary physical activity does not cause undue fatigue, palpitations, dyspnea
• Class II
  
  • Slight limitations of physical activity
  • Comfortable at rest
  • Ordinary physical activity results in fatigue, palpitations, dyspnea
• Class III
  
  • Marked limitation of physical activity
  • Comfortable at rest
  • Less than ordinary activity causes fatigue, palpitations, or dyspnea
• Class IV
  
  • Unable to carry on any physical activity without discomfort
  • Symptoms of heart failure at rest
  • If any physical activity is undertaken, discomfort increases

Question 41

What is the basic epidemiology of congestive heart failure in the United States?

Answer 41

• Heart failure (HF) is a major public health issue, with a prevalence of over 5.8 million in the USA, and over 23 million worldwide, and rising.
• The lifetime risk of developing HF is 1 in 5.
• Although promising evidence shows that the age-adjusted incidence of HF may have plateaued, HF still carries substantial morbidity and mortality, with 5-year mortality that rival those of many cancers.
• HF represents a considerable burden to the health-care system, responsible for costs of more than $39 billion annually in the USA alone, and high rates of hospitalizations, readmissions, and outpatient visits.