Pathophysiology of Heart Failure Flashcards
how are the following parameters affected by systolic vs diastolic heart failure?
a. ejection fraction
b. cardiac output
c. morphology of cardiomyocytes
systolic heart failure: reduced ejection fraction, reduced CO, eccentric hypertrophy (sarcomeres added in series)
diastolic heart failure: preserved ejection fraction but lower CO, concentric hypertrophy (sarcomeres added in parallel)
mitral valve regurgitation and congenital heart defects can develop into what kind of heart failure?
systolic heart failure - ventricle is stressed by increased volume (eccentric hypertrophy) —> decreased contractibility
in what kind of heart failure might you observe a lateral shift of PMI, S3 heart sound, and mitral regurgitation?
lateral shift of PMI: point of maximal impulse
S3 heart sound: due to ventricle filling more than it should
mitral regurgitation: back-flow of blood from ventricles into atria
these are all possible findings of systolic heart failure: volume overload —> eccentric hypertrophy —> decreased contractibility —> reduced ejection fraction / cardiac output
how is the LV pressure-volume loop affected by systolic heart failure?
systolic heart failure = volume overload, eccentric hypertrophy, decreased contractibility
pressure volume loop shows lower ESPVR (end-systolic pressure-volume relationship): slope of graph, representing maximal pressure developed by the LV at any given volume, measure of contractibility
right shift due to higher ventricular volume, upward shift due to higher ventricular pressure
systolic heart failure is due to ______overload, while diastolic heart failure is due to ______ overload
systolic HF = volume overload
diastolic HF = pressure overload
what kind of heart failure can be caused by HTN and aortic valve stenosis?
diastolic heart failure: pressure overload —> concentric hypertrophy (sarcomeres add in parallel) —> reduced compliance —> reduced SV/CO (but preserved ejection fraction)
in what kind of heart failure might you observe sustained PMI, S4 heart sound, and RV heave?
sustained PMI: point of maximal impulse
S4 heart sound: due to stiff ventricle
RV heave: right ventricle heave, due to RV hypertrophy, feels like heavy beating against chest wall
these can all be observed in diastolic heart failure (pressure overload)
how is PMI (point of maximal impulse) affected by systolic vs diastolic heart failure? what pathogenic heart sounds would you heart with each?
systolic HF = volume overload, eccentric (sarcomere in series) hypertrophy —> lateral shift in PMI, S3 heart sound (too much filling)
diastolic HF = pressure overload, concentric (sarcomere in parallel) hypertrophy —> PMI unchanged, S4 heart sound (stiff ventricle)
how would diastolic heart failure affect the LV pressure-volume loop?
diastolic HF = pressure overload, reduced compliance, reduced SV/CO (but maintained ejection fraction)
increased end-diastolic pressure volume relationship (slope on the bottom of the loop)
left shift due to decreased ventricular filling (volume), upward shift due to higher ventricular pressure
how would systolic vs diastolic heart failure affect the left-ventricle pressure-volume loop?
systolic HF = volume overload —> right/upward shift (more filling, higher pressure)
diastolic HF = pressure overload —> left/upward shift (less filling, higher pressure)
what 3 compensatory mechanisms occur to maintain homeostasis in the case of reduced cardiac output?
- sympathetic nervous system activation
- RAAS activation (renin-angiotensin-aldosterone system)
- increased vasopressin/ADH (anti-diuretic hormone) synthesis
where in the brain do high pressure baroreceptors in the carotid sinus and aortic arch signal to? how do they get there?
carotid sinus —> glossopharyngeal nerve (CN IX) —> solitary tract nucleus (medulla)
aortic arch —> vagus nerve (CN X) —> solitary tract nucleus
solitary tract nucleus then signals to cardioinhibitory center in vasomotor area (A1, C1) of medulla , which sends out efferent PNS fibers to the heart
describe how the SNS is activated to increase cardiac output
baroreceptors in carotid sinus and aortic arch usually provide inhibitory input to the CNS (to solitary tract nucleus)
but when arterial filling drops, baroreceptors stop firing, and SNS tone increases (disinhibition)
explain why excessive SNS stimulation in a state of decreased CO is counter-productive
SNS activates beta1 receptors (heart) and peripheral alpha1 receptors
beta1 —> increased inotropy/chronotropy (—> increased oxygen demand, ventricular remodeling), increased RAAS activity (—> increased blood volume)
alpha1 —> vasoconstriction (—> increased afterload —> increased oxygen demand)
overall, SNS causes an increase in oxygen demand and afterload in a heart that is already struggling to maintain CO
where in the kidney are changes in blood sodium detected? which cells respond to decreases in plasma sodium?
macula dense: senses changes in NaCl
JG (juxta-glomerular) cells: synthesize renin, which converts angiotensin (liver) to angiotensin I
*note that beta1 adrenergic stimulation causes increase in renin secretion from JG cells
what are the basic steps of the RAAS pathway?
- angiotensin (liver) is converted to angiotensin I via renin (JG cells, kidney)
- angiotensin I is converted to angiotensin II via ACE (lung) OR ACE-independent pathway
- angiotensin II induces vasoconstriction, aldosterone secretion (adrenal), AVP (vasopressin/ADH) secretion
overall, causes increase in BP through increased blood volume (fluid retention) and vasoconstriction
how does SNS activation affect the LV pressure-volume loop of a heart with systolic HF?
systolic HF LVPV loop - right shift (increased filling), decreased width (decreased SV/ increased ESV)
after SNS activation - left shift (positive inotropy), increased width (increased preload via RAAS/AVP)
*note that compensation mechanisms will ultimately cause harm via increased afterload (not sustainable)
what are the counter-hormones produced in heart failure to reduce the harmful effects of compensatory mechanisms?
HF induces compensatory mechanisms (SNS, RAAS, ADH/AVP) that will ultimately cause harm via increased afterload and cardiac oxygen demand
in response to volume stress/LV dilation, ANP (atrial natriuretic) and BNP (B-type natriuretic - ventricles) hormones are secreted —> natriuresis (salt excretion, water follows), vasodilation, inhibition of SNS
*however, as HF worsens, ANP/BNP become less effective (not sustainable)
which symptoms of congestive heart failure are related to pulmonary congestion, and which symptoms are related to decreased CO?
pulmonary congestion (LV problem) —> dyspnea w/ exertion, orthopnea, paroxysmal nocturnal dyspnea, and Cheyne-Stokes (“chain smoker”) respirations
decreased CO —> fatigue
*remember that LV causes pulmonary problems, RV causes systemic problems (think about where the backup of blood goes from each of these places)
describe why dyspnea with exertion occurs in congestive heart failure
impaired LV function —> increased pulmonary capillary pressure/ hydrostatic pressure —> pulmonary edema (blood gets backed up, fluid collects in alveoli and around bronchioles) —> impaired gas exchange —> hypoxemia/ dyspnea
what are the signs of dyspnea as seen with the early stages of congestive heart failure?
dyspnea w/ exertion - exercise intolerance, nocturnal cough (non-productive), pink/frothy sputum (acute)
caused by pulmonary edema - note that acute pulmonary edema is a medical emergency (can progress quickly)
what is a key histological finding in the lungs of a patient with congestive heart failure?
“heart failure cells”: hemosiderin-laden macropahges
increased hydrostatic pressure —> increased fluid in alveoli and around bronchioles —> capillary damage —> RBC leak
[recall that hemosiderin indicates breakdown of hemoglobin, and this will get taken up by macrophages]
explain why congestive heart failure causes orthopnea and paroxysmal nocturnal dyspnea, and contrast these 2 symptoms
orthopnea: dyspnea while supine, associated with nocturnal cough (while falling asleep), patients sleep with many pillows to elevate - due to redistribution of fluid from splanchnic circulation/lower extremities to central circulation —> increased pulmonary capillary pressure
paroxysmal nocturnal dyspnea: SOB that wakes patient from sleep, associated with wheezing/cough, persists after patient is upright - due to intestinal edema causing airway resistance/compression
explain why congestive heart failure causes Cheyne-Stokes respiration
Cheyne-Stokes respiration (“chain smoker respirations): cyclic changes in depth of respiration
common in advanced CHF, associated with low cardiac output
due to increased sensitivity of respiratory centers to arterial pCO2
why does nocturia occur with congestive heart failure, and is it usually seen early or late in disease progression?
nocturia: frequent night waking to urinate, occurs with early heart failure
when upright, kidneys see less blood flow, tend to retain Na+/water
when lying flat, circulation improves and more blood reaches kidneys —> diuresis
what are symptoms of congestive heart failure related to RV failure?
recall that symptoms relate to where the blood is backing up to
so RV will back up to SVC/IVC —> anorexia/nausea, abdominal discomfort/ascites (fluid in abdomen), unexpected wait gain, leg swelling (shoes feel tight)
what are the 2 main causes of RV failure?
- most common cause is LV failure (backs up into RV) - so patients with symptoms of LV failure will also have symptoms of RV failure
- cor pulmonale: RV failure caused by primary lung problem (such as chronic obstructive lung disease)
backward failure vs forward failure in heart failure
backward failure: blood backup causes symptoms (L - pulmonary edema, R - JVD)
forward failure: reduced CO causes exercise intolerance
what are 2 notable changes in heart sounds indicative of systolic heart failure? what type of murmur might you hear?
soft S1 (AV valves) due to decreased contractile force
S3 due to rapid ventricle filling (more than it should)
mitral/tricuspid regurgitation due to ventricular dilation
[recall that systolic HF is due to fluid overload]
explain why it makes sense that heart failure causes a narrowing of pulse pressure
pulse pressure = systolic blood pressure - diastolic blood pressure
systolic BP is influenced by stroke volume
diastolic BP is included by arteriolar tone
with ventricular dysfunction, SV decreases… therefore PP becomes more narrow
primary vs secondary mitral regurgitation
primary - due to structural problem with valve
secondary - due to ventricular dilation stretching the leaflets (enlarges the valve annulus)
which of these is always pathological, S3 or S4 heart sound?
S3: due to rapid ventricular filling in an enlarged ventricular chamber, normal finding in children and young adults (<40)
S4: atrial contraction causes forceful entry of blood into stiff/non-compliant ventricle, always pathological
what causes the following signs of heart failure?
a. JVD
b. crackles/rales
c. cool extremities
d. ascites
e. pitting edema (symmetric)
a. JVD: via blood backup from right ventricle (can measure central venous pressure via jugular vein distention)
b. crackles/rales: via pleural effusion (fluid in alveoli)
c. cool extremities: via low perfusion
d. ascites: aka abdominal fluid, via backup into hepatic vein
e. pitting edema: via high hydrostatic pressure
how can jugular venous pressure be used to diagnose cardiopulmonary disease?
patients with dyspnea or edema —> check jugular venous pressure
if there is high JVP —> cardiopulmonary disease
if JVP is okay —> patient has liver or kidney disease (such as hyperalbuminemia)
what is a key metric in diagnosing heart failure?
BNP (B-type natriuretic peptide): HIGH BNP (>100pg/ml) correlates with uncompensated heart failure
also look for symptoms/signs, chest x-ray (CXR) for large heart or pulmonary congestions (systolic HF), echocardiogram (ejection fraction)
what is the function/use of a neprilysin inhibitor?
neprilysin breaks down natriuretic peptides
neprilysin inhibitors block this enzyme, therefore are used in heart failure to boost the effects of ANP/BNP (decrease volume overload and blood pressure caused by activation of RAAS)
what is the function of SGLT2 inhibitors?
SGLT2: sodium-glucose secondary active transport in kidney
SGLT2 inhibitors developed for diabetics, but found to be useful in heart failure
low-output vs high-output heart failure
low-output: problem is within heart
high-output: problem is within peripheral vasculature (something is causing peripheral vasodilation —> decreased afterload —> raises CO/SV)
what are 5 main causes of high-output heart failure?
recall high output HF is due to peripheral vasodilation problem, rather than problems in heart
- obesity: higher body mass means more blood vessels to fill
- cirrhosis
- anemia: not enough Hgb = not enough O2 —> increased CO, anaerobic glycolysis —> metabolite production that cause vasodilation
- systemic AV fistulas: artery connected to vein, bypasses pressure system in capillary bed —> increased venous return —> increased SV/HR/CO, eccentric LV hypertrophy, increased O2 demand
- thiamine deficiency (beri beri)
also:
6. hyperthyroidism
7. multiple myeloma
8. paget disease of the bone
