SACCM 41: Mechanisms of Heart Failure Flashcards
What are the neurohormonal pathways implicated in the development of heart failure?
- RAAS
- sympathetic nervous system
- natriuretic peptides
- endothelin-1 system
- vasopressin system
List the pathways of RAAS
renal perfusion decreased –> macula densa in the ascending thick limb of the loop of Henle senses decreased tubular flow (specifically Cl-) –> sends signal to the juxtaglomerular apparatus of the same nephron –> renin-secreting cells release renin
renin –> converts angiotensinogen to angiotensin I
ACE (produced by endothelial cells, predominantly in the lungs) –> converts angiotensin I to angiotensin II
Angiotensin II –> increases production and release of aldosterone
Explain how the RAAS system contributes to the development of heart failure
Angiotensin II and Aldosterone lead to:
* sodium and water retention
* myocardial apoptosis
* cardiac and vascular remodeling and fibrosis
* increased thirst
* vasoconstriciton
–> fluid retention (CHF) and maladaptive myocardial and vascular remodeling –> further cardiac injury and depressed cardiac function
What are the adverse effects of chronic sympathetic nervous system activation in patients heart disease?
- downregulation of adrenergic receptors
- persistent tachycardia
- increased myocardial oxygen demand
- myocyte necrosis
What are the two natriuretic peptides, what are their effects and how are they implicated to play into the development of heart failure?
atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)
produced in response to stretch or stress of myocardial tissue –> lead to natriuresis, diuresis, and vasodilation
help counteract RAAS activation, but becomes ultimately insufficient because of:
* receptor downregulation
* inadequate production and processing
* increased clearance/degradation
What is the stimulus for Ebndothelin 1 production, what are its effects?
stimuli for production:
* sheer stress
* angiotensin II
* various cytokines
effects:
* vasoconstriction –> increased cardiac afterload
* alters normal Ca++ cycling within myocytes –> toxic to myocardiocytes
What causes dilutional hyponatremia in patients with heart failure?
decreased CO –> decreased intravascular pressure –> stimulates baroreceptors in the carotid arteries and aortic arch –> release of vasopressin/ADH –> water retention in the distal collecting ducts –> water retained in excess of Na –> dilutes Na
BUT total body sodium is actually high from excessive RAAS activation
poor prognostic indicator
Describe the different complications associated with eccentric versus concentric hypertrophy of the cardiac myocytes
concentration - increased pressure –> sarcomeres replicate in parallel –> thickness increase
* increased myocardial oxygen demand
* endocardial ischemia
* fibrosis
* collagen disruption
* injury to small coronary vessels
eccentric - increased volume –> sarcomeres replicate in series –> elongation of myocytes
* increased myocardial wall stress
* myocyte injury or necrosis
* myocyte slippage
Explain the Ca++ movement during cardiac muscle contraction
CONTRACTION
Ca++ enters the myocardial cell –> triggers the release of additional Ca++ from the sarcoplasmic reticulum (SR) –> Ca++ flows through the ryanodine channel –> binds to troponin C located on the actin and myosin complex –> sarcomere contraction
RELAXATION
Ca++ released from troponin C –> Ca++ sequestered back into the SR via the sarcoplasmic/endoplasmic reticulum Ca++-ATPase
What are the heart’s main substances for energy production and how does heart failure affect the preferred substance?
- free fatty acids or glucose
- in heart failures the heart prefers glucose –. requires less oxygen to metabolize than fatty acids
What is the function of Phospholamban?
cardiac myocyte intracellular Ca++ regulator –> inhibits reuptake by SERCA2a
Above what venous pulmonary venous pressure is pulmonary edema likely to occur?
> 25 mm Hg
At what systemic venous pressures is right-sided congestion likely to occur?
> 20 mm Hg
