Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Cardiology > Pathophysiology of Congestive Heart Failure > Flashcards

Pathophysiology of Congestive Heart Failure Flashcards

1
Q

Heart Failure

  • Definition
  • Systolic factors that contribute to HF
  • Diastolic factors that contribute to HF
  • Extracardiac factors that contribute to HF
A
  • Definition
    • Clinical syndrome
    • Heart can’t pump blood at a rate commensurate w/ the metabolic requirements of the body (or does so only w/ elevated ventricular filling pressures)
  • Systolic factors that contribute to HF
    • Cardiomyopathies (e.g., ischemic, dilated, infeciton, peripartum, drug/toxin, inflammatory, late hypertropihc, cardiomyopathy, endocrinopathy)
    • Valvular (e.g., aortic stenosis)
  • Diastolic factors that contribute to HF
    • Cardiomyopathies (e.g., infiltrative, hypertensive, early ischemia, hypertrophic)
    • Valvular disease (e.g. mitral stenosis)
    • Pericardial disease (e.g., constriction)
    • Endocardial disease (e.g., endomyocardial fibrosis)
    • Myocardial disease (e.g., amyloidosis)
    • HTN w/o cardiomyopathy
    • Age
    • Gender (esp women)
  • Extracardiac factors that contribute to HF
    • Renal failure
    • Excess hydration (e.g., IV fluids, blood transfusion)
    • High output failure (e.g., anemia, hyperthyroidism)
    • Liver disease
    • Malnutrition (e.g., hypoalbuminemia)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Pathophysiology of HF

  • Low cardiac output
    • Reflects…
    • Symptoms
    • Signs
  • Excess volume
    • Reflects…
    • Symptoms
    • Signs
A
  • Low cardiac output
    • Reflects…
      • Inability to delivery sufficient blood flow (& oxygen) to other organs
    • Symptoms
      • Decreased appetite
      • Weakness & fatigue
      • Poor sleep
      • Forgetfulness
    • Signs
      • Decreased mentation & confusion
      • Cool extremities
      • Cyanosis / pallor
      • Renal dysfunction
  • Excess volume
    • Reflects fluid retention within…
      • Intravascular spaces (distended jugular veins, elevated JVP, S3)
      • Interstitial spaces (wet crackles or rales, dependent edema)
      • Both intravascular & interstitial spaces (hepatic congestion)
    • Symptoms
      • Shortness of breath (orthopena when laying flat)
      • Nocturnal dyspnea
      • Dependent edema
      • Abdominal bloating
      • RUQ tenderness
    • Signs
      • Distended jugular veins
      • Elevated JVP
      • Wet crackles or rales
      • S3
      • Liver congestion
      • Ascites
      • Pedal or sacral edema
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

HF Classifying & Staging Symptoms

  • NYHA functional class
  • ACC/AHA HF stages
  • Comparison
    • ACC/AHA HF stage A
      • NYHA class
    • ACC/AHA HF stage B
      • NYHA class I
    • ACC/AHA HF stage C
      • NYHA class II
      • NYHA class III
    • ACC/AHA HF stage D
      • NYHA class IV
A
  • NYHA functional class
    • Based on the ability or inability to perform routine daily activities
    • Dependent on the level of physical incapacitation due to HF related symptoms at the time of evaluation
    • Dynamic
      • Respond well to medical therapy –> decrease NYHA class
      • Symptoms worsen –> increase NYHA class
  • ACC/AHA HF stages
    • Progressive illness
    • Begins w/ the presence of existing risk factors
    • Stages aren’t reversible even if symptoms improve w/ medical therapy
  • Comparison
    • ACC/AHA HF stage A: predisposing condition (e.g., HTN, CAD) for HF, no structural or funcitonal abnormalities
      • NYHA class: no comparable class
    • ACC/AHA HF stage B: structural (e.g., valve disease) & functional abnormalities associated w/ HF, no signs/symptoms
      • NYHA class I: no limitation of ordinary physical activity from fatigue, dyspnea, palpitations, etc.
    • ACC/AHA HF stage C: structural/functional abnormalities + prior/current signs/symptoms of HF
      • NYHA class II: slight limitation of ordinary physical activity but still able to perform them, comfortable at rest
      • NYHA class III: marked limitation & symptoms at less-than-ordinray physical activities (e.g., dressing, bathing)
    • ACC/AHA HF stage D: advanced structural/functional disease + marked HF symptoms at rest depsite max medical therapy, require specialized interventions
      • NYHA class IV: unable to carry out any physical activity, symptoms of cardiac insufficiencty at rest, discomfort increased w/ minimal activity (e.g., talking, eating)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

HF vs. Cardiomyopathy

A
  • Cardiomyopathies
    • Depend on the nature of organ involvement & relative involvement of extra-cardiac disease
    • Cause myocardial dysfunction & arrhythmias
    • May or may not cause systolic myocardial dysfunction
      • Ex. WPW syndrome manifests primarily w/ arrhythmias w/ no effect on systolic or diastolic function
  • Cardioyopathies in literature
    • Common to describe myocardial dysfunction resulting from other CV abnormalities (e.g., ischemic, valvulra, hypertensive, congenital) as specific cardiomyopathies
      • Even though they’re not really included in the classificaiton of primary or secondary cardiomyopathies
    • These diseases of myocardial dysfunction result from other primray CV diseases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Systolic vs. LV Diastolic Dysfunction

A
  • Systolic dysfunction
    • Defect in the ability of heart myofibrils to shorten against increased load
    • Found in both symptomatic & asymptomatic patients
    • Can occur after an MI due to cardiac structural changes (i.e., LV remodeling)
    • Can occur as the end-stage of chronic heart disease (e.g., hypertensive or valvular heart disease)
  • LV diastolic dysfunction
    • Impaired LV filling at normal LA pressure
    • More common in elderly & women
    • Reponsible for up to 40-50% of HF in adults
    • Many patients have both LV systolic & diastolic dysfunction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

HF Epidemiology

  • Cardinal manifestations of HF
  • Age
  • Gender
  • LV dysfunction causes both…
  • Patients w/ preserved EF
  • Factors that impact HF mortality
  • HF survival
  • Medicaire
  • Goals of therapy
    • Short term
    • Long term
A
  • Cardinal manifestations of HF
    • Dyspnea
    • Fatigue
    • Fluid retention
  • Age
    • Increase age –> increase HF incidence (esp after 45yo)
    • Increase age –> increase other diseases (e.g., HTN, DM, obesity) –> survive early stage cardiac disease (ex. acute MI) –> old enough for HF
  • Gender
    • Women have better survival than men
    • HF in women is more commonly associated w/ diastolic HF which has a better survival risk than systolic HF
  • LV dysfunction causes both…
    • Systolic dysfunction: imparied ability to pump blood (worse prognosis)
    • Diastolic dysfunction: impaired ability to fill w/ blood (better prognosis)
  • Patients w/ preserved EF
    • Often have other co-morbidities that increase risk of death
    • Directly related to HF (e.g., valvular disease, CHD, HTN)
    • Indirectly related (e.g., renal disease, DM, obesity)
  • Factors that impact HF mortality
    • Etiology of cardiac & myocardial disease
    • Severity of symptoms (not always related to cardiac disease severity)
    • Severity of LV dysfunction
    • Pharmacologica & non-pharmacologic therapies
      • ICD: reduce risk of arrhythmic deat, allow HF paitens to survive later disease stages & pump failure
      • Ventricular assist devices: increase survival w/o transplant, avoid pump failure related death, but may still develop arrhythmias or infection- or end-organ-failure-related death
  • HF survival
    • Improved but still dismal
    • Poor prognosis
    • Sudden death –> most deaths in patients w/ HF, esp in lower NYHA classes
    • Better prognosis: dilated, non ischemic, asymptomatic
  • Medicaire
    • More $ is spent for diagnosing & treating HF than any other diagnosis
  • Goals of therapy
    • Short term: relieve symptoms & improve quality of life
    • Long term: prolong life by slowing & reversing the progressive course of the disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Normal Pressure-Volume Relationship

  • Point A
  • Line AB
  • Point B
  • Line BC
  • Point C
  • Line CD
  • Point D
  • Line DA
  • Shaded area
A
  • Point A: end diastole
  • Line AB: isovolumic contraction during LV systole
    • Myofibrils begin to contract but no ejection occurs
    • Allows LV to generate enough pressure to overcome peripheral arterial resistance & deliver blood forward (cardiac output)
  • Point B: aortic valve opening
  • Line BC: ejection of blood into aorta
    • Difference in LV volume = stroke volume
  • Point C: aortic valve closure, end systole
  • Line CD: isovolumic relaxation during LV diastole
    • Myofibris relax/stretch to allow LV pressure to fall below LA pressure so blood can passively move across the mitral valve
    • Factors that impair this phase (e.g., ishcemia, myocardial infiltration, inflammation) –> diastolic HF
  • Point D: mitral valve opening
  • Line DA: LV diastolic filling
  • Shaded area: external LV stroke work
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Pressure-Volume Relationship Dysfunction

  • Systolic dysfunction
    • PV loop changes
    • How HF develops
  • Diastolic dysfunction
    • PV loop change
    • How HF develops
  • Coexisting systolic & diastolic dysfunction
A
  • Systolic dysfunction
    • PV loop changes
      • PV loop shifts to the right
      • Less steep nd-systolic PV relationship (contractility) –> increased LVEDP
    • How HF develops
      • LV requires increased LVEDP & LVEDV to maintain SV & CO
  • Diastolic dysfunction
    • PV loop changes
      • Bottom curve shifts upward
      • Decreased LVEDV –> increased LVEDP to maintain volume
    • How HF develops
      • LVEDP is increased during LV filling for any given blood volume
      • LV compliance worsens –> increased LVEDP –> decreased SV (pre-load dependence)
  • Coexisting systolic & diastolic dysfunction
    • Systolic dysfunction –> hypertrophy & fibrosis –> decrease compliance –> impair LV filling –> disrupt diastolic function
    • Underlying hemodynamic presses differ
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Frank-Starling Curve

  • Normal ventricles
  • LV systolic dysfunction
    • Effect of decreased contractility
    • Curve changes
    • Mild vs. severe dysfunction
  • Factors that may contribute to a plateau in the presence of pressure-volume curve
A
  • Normal ventricles
    • Steep & positive relationship b/n LV filling pressures (LVEDP) & SV or CO
  • LV systolic dysfunction
    • Decrease contractility –> decrease CO & SV
      • –> increase sympathetic activity –> increase contractility & HR –> restore cardiac output
      • –> renal salt & water retention –> expand blood volume –> increase end-diastolic pressure –> enhance ventricular performance –> restore SV
    • Curve changes
      • Curve shifts to the right: higher filling pressures are needed to achieve the same CO
      • Curve flattens: increasing LV filling pressures has less of an effect on increasing CO
    • Mild vs. severe dysfunction
      • Mild: initial reduction in cardiac function can be overcome by raising the LVEDP & via fluid retention
      • Severe: stroke volume isn’t recoverable, & continued incresaed in LVEDP & fluid retention –> pulmonary edema
  • Factors that may contribute to a plateau in the presence of pressure-volume curve
    • Heart reaches its max capacity to increase contractility in response to increasing stretch
      • Sarcomeres lengthen to more-than-optimal degree of overlap of thick & thin myofilaments
      • –> decrease Ca2+ affinity for / binding to troponin C
      • –> decrease Ca2+ available within myocardial cells
      • –> prevents LV from increasing contractile force in response to increased load
    • Reduce in cardiac complicance
      • Reduced compliance –> small increase in volume produces a large elevation in LVEDP –> not substantial stretching of the cardiac muscle –> little change in cardiac output
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Determinants of Cardiac Performance

A
  • Preload
  • Afterload
  • Contractility
  • Relaxation
  • Heart rate
  • Preload, afterload, contractility & relaxation influence SV
  • HR * SV = CO
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Preload

  • Definition
  • Determined by…
  • Effect on SV & LVEDV
  • Factors that influence preload (venous return to the heart)
    • Total body volume
    • Body position
    • Venous tone
    • Atrial contraction
    • Skeletal muscle contraction
    • Intrapericardial pressure
    • Intrathoracic pressure
  • Measures of preload
  • Effect on myocardial fibers
A
  • Definition
    • Hemodynamic load on the myocardial wall (or fiber stretch) at the end of diastole just before contraction begins
    • Creates wall tension
  • Determined by…
    • Venous return to the ventricle
    • Any regurgitant blood across the aortic valve (LV preload) or pulmonic valve (RV preload)
  • Effect on SV & LVEDV
    • Decrease preload
    • –> decrease SV (normal individuals)
    • –> increase SV (patients w/ HF
    • –> decrease LVEDV
  • Factors that influence preload (venous return to the heart)
    • Venous return
      • Decrease venous return –> decrease preload
      • Increase venous return –> increase preload
    • Total body volume
      • Dehydration / blood loss –> decrease preload
      • Hydration / transfusion –> increase preload
    • Body position
      • Supine to upright –> decrease preload
      • Upright to sitting/supine –> increase preload
    • Venous tone
      • Venodilation –> decrease preload
      • Venoconstriction –> increase preload
    • Atrial contraction
      • Atrial fibrillation –> loss of atrial contraciton –> decrease preload
      • Sinus rhythm –> restore atrial contraction –> increase preload
    • Skeletal muscle contraction
      • Muscle inactivity –> decrease venous return –> decrease preload
      • Muscle activity –> increase venous return –> increase preload
    • Intrapericardial pressure
      • Cardiac tamponade –> decrease preload
      • Pericardiocentesis –> increase preload
    • Intrathoracic pressure
      • Expiration / pneumothorax –> decrease preload
      • Inspiration –> increase preload
  • Measures of preload
    • Key measure: LVEDV
    • Other measures
      • LVEDP
      • Pulmonary capillary wedge pressure –> LA pressure
      • Central venous pressure –> RA pressure
      • LVED diameter
      • End-diastolic wall tension
      • Sarcomere length
  • Effect on myocardial fibers
    • Decrease preload –> insufficient ventricle filling during diastole –> submaximal stretch –> myocardial ocntraction doesn’t occur w/ optimal force
    • Increase preload –> ventricle overfilling –> overstretch mycoardial fibers –> exceed contractile capacity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Afterload

  • Definition
  • Determined by…
  • Drugs that improve cardiac output
  • Effect on SV & LVEDV
  • Measures of afterload
A
  • Definition
    • Force that resists myocardial contraction & blood volume ejection out of the ventricle during systole
    • Force that mycoardial fibers must overcome in order to shorten
    • Tension in the myocardium during active contraction
  • Determined by…
    • Resistance against which the myocardium is contracting
    • Degree of myocardial shortening
      • Increase afterload –> decrease myocardial shortening –> decrease SV
      • Systolic HF: ventricle is very sensitive to afterload, so increase afterload –> greater decrease in SV
  • Drugs that improve cardiac output
    • Arterial vasodilators (ACE-Is, angiotensin receptor blockers) increase SV
  • Effect on SV & LVEDV
    • Decrease afterload
    • –> increase SV
    • –> decrease ESV –> decrease LVEDV
      • LV doesn’t need to generate the same pressure to eject blood forward, so LV can decrease EDV
  • Measures of afterload
    • Total systemic peripheral resistance (arterial BP)
      • ​More convenient & readily obtainable estimate of afterload in absence of aortic stenosis or atherosclerosis
    • LV pressure (aortic valve stenosis)
      • More comprehensive measure of LV afterload w/ aortic stenosis or atherosclerosis
    • RV pressure (pulmonic valve stenosis, pulmonary hypertension))
    • Aortic pressure
    • Arterial impedance
    • Myocardial peak wall stress (affected by LV geometry)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Contractility

  • Inotropy
  • Contractility
  • Effect on SV & LVEDV
  • Measures of contractility
A
  • Inotropy / contractility
    • Increase myocardial contractility –> increase SV
    • Describes the forces created by Ca2+ dependent binding b/n myosin & actin
  • Contractility vs. afterload & preload
    • Increase afterload –> increase contractility to maintain SV
      • Also increase LV pressure during isovolumic contraction to maintain systolic ejection
    • Increase preload –> don’t necessarily need to adjust contractility to maintain SV
  • Effect on SV & LVEDV
    • Increase contractility
    • –> increase SV & CO –> decrease ESV
    • –> decrease LVEDV but not to the same degree as afterload reduction (essentially no effect)
      • LV still needs to generate higher pressures to eject blood volume into the aorta than if there were also afterload reduction
      • Need to maintain a greater LV volume in systolic HF
  • Measures of contractility
    • Fractional shortening
    • Ejection fraction
    • Cardiac output
    • Stroke volume
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Relaxation & Heart Rate

  • Compliance
  • Compliance vs. pressure
  • Heart rate
A
  • Compliance = ∆V / ∆P
    • ∆V = ∆ volume = LVEDV - LVESV
    • ∆P = ∆ pressure = LVEDP - LVESP
  • Compliance vs. pressure
    • Increase compliance –> decrease pressure for any increase in volume
    • Decrease compliance –> increase pressure for any increase in volume
  • Heart rate
    • CO = SV * HR
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Wall tension

  • Increased & decreased by…
  • Transient vs. chronic changes
  • Laplace relationships
  • What happens in a chronically volume overloaded state
A
  • Increased & decreased by…
    • Increased by…
      • Signs of failing LV
      • Intracardiac diameter/radius of the LV from remodeling
      • Intracardiac pressure from volume overload
    • Decreased by…
      • Increased wall thickness
  • Transient vs. chronic changes
    • Transient changes –> little damage or injury
    • Chronic changes –> persistent or permanent changes to the myocardium over time (ex. HTN)
  • Laplace relationships
    • How risk factors for HF –> copmensatory changes ot the myocardium & LV over time
    • Ex. HTN –> increased afterload –> increased pressure –> chornic exposure to increased wall tension –> LV wall thickening –> hypertrophy
  • What happens in a chronically volume overloaded state
    • Increase volume –> increase preload –> increase LVEDP –> decrease SW –> dilated LV
    • –> LV can accommodate increased volumes at reduced pressure & still maintain optimal interaction b/n myosin & actin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Hemodynamic Pathophysiology Summary

  • Pressure-volume loops describe…
  • Frank-Starling curves describe…
  • Preload affects…
  • Afterload affects…
  • Stroke volume
  • Contractility
  • Laplace relationship
  • LV compliance
A
  • Pressure-volume loops describe…
    • Pressure-volume relationship throughout the cardiac cycle
    • Systolic & diastolic dysfunction separately (may co-exist)
  • Frank-Starling curves describe…
    • Impact of LVEDV on SV
  • Preload affects…
    • End-diastolic measurements (volume & pressure)
  • Afterload affects…
    • End-systolic measurements & LV systolic pressure during isovolumic contraction
  • Stroke volume
    • Increased by increasing preload & decreasing afterload
    • Doesn’t necessarily mean increased CO unless HR is maintained or increased
  • Contractility
    • Not affected by preload
      • If contractility is kept constant, increasing preload increases SV
      • HF: may not be able to maintain contractility –> decrease SV
    • Increased by increasing afterload to maintain SV
      • Inability to increase contractility decreases SV & CO
  • Laplace relationship
    • Relates wall diameter & intracardiac pressure to wall tension
    • Hypertrophy –> increase wall thickness –> decrease wall tension/stress
  • LV compliance
    • Increase LV compliance –> LV can fill w/ greater volume in diastole while maintaining constant LVEDP
17
Q

Compensatory Mechanisms

A
  • HF
    • –> insults (ischemic injury, HTN, infiltration, valvular heart disease, etc.)
    • –> increase preload &/or afterload
  • LV remodeling changes size & shape of heart in response to…
    • Excessive neurohormonal activation
    • Altered loading conditions
    • Myocardial injury
18
Q

Ventricular Remodeling

  • Benign adaptive response
    • Ex. trained athlete
    • Ex. increased metabolic efficiency
  • Adverse changes to copmensate for decreased myocardial performance
    • Ex. initial MI
    • Ex. LV hypertrophy
    • Ex. LV dilation
A
  • Benign adaptive response
    • Ex. trained athlete
      • Enlarged, muscular heart –> decreased EF & HR + maintained SV
      • Due to physiologic hypertrophy of muscles & increased compliance of blood vessels
    • Ex. increased metabolic efficiency
      • –> decrease oxygen demand in peripheral muscle
      • –> enhance oxygen delivery int he myocardium to improve cardiac performance
  • Adverse changes to copmensate for decreased myocardial performance
    • Ex. initial MI
      • Gradual scarring & thinning in the area of infarction –> global remodeling of the LV (ex. dilation)
    • Ex. LV hypertrophy
      • Negatively affects compliance –> systolic dysfunction –> dilation
    • Ex. LV dilation
      • Hallmark change in CHF
      • Initial dilation –> accommodate increaed volume w/o increasing LVEDP –> maintain SV
        • Doesn’t imply sarcomere lengthening
        • May include myocyte hypertrophy & increased myocyte spacing w/ increased interstitial fibrosis & collagen deposition
      • Long term dilation –> increased wall stress –> histologic changes
        • As cellular function –> dysfunctional, disrupted actin/myosin interaction –> decreased power of filament shortening
        • –> clinical decompensation & progression of HF (stage C or D)
19
Q

Compensatory Changes

  • Goal of compensatory changes
  • Compensatory mechanisms to adapt & maintain LV function
  • Ex. of how adverse compensatory mechanisms: neurohormonal activation
  • Types of initial insults
  • Causes of cardiac injury/dysfunction
A
  • Goal of compensatory changes
    • Restore LV function following an initial myocardial insult that adversely affects ventricular function
    • Recover LV performance & delay the onset/progression of HF
    • Long term exposure to these mechanisms may –> adverse remodeling –> secondary myocardial damage –> further LV decline
  • Compensatory mechanisms to adapt & maintain LV function
    • Salt & water retention –> increase circulating volume & maintain SV
    • SNS activation –> preserve CO
    • Release of circulating vasodilatory molecules (ex. NO, prostaglandins, & natriuretic peptides) –> increase preload & decrease afterload
  • Ex. of how adverse compensatory mechanisms: neurohormonal activation
    • Underlying cardiac disease –> declining LV contractility –> decreased CO
    • Goal: maintain BP & tissue perfusion by increasing peripheral vascular resistance & LV afterload
    • Long term response –> hasten myocardial deterioration –> worsen ventricular performance
  • Types of initial insults
    • Acute (ex. MI)
    • Insidious (ex. HTN, valvular heart disease)
  • Causes of cardiac injury/dysfunction
    • Hereditary (ex. hypertrophic cardiomyopathy)
    • Acquired (ex. peripartum cardiomyopathy)
20
Q

Cellular Basis of Myocardial Dysfunction in HF

  • Contractile proteins of the heart
  • Normal resting energy supply
  • Myocardial contraction
  • Metabolic & energetic derangements in HF
A
  • Contractile proteins of the heart
    • Lie within myocaridal muscle cells (cardiomyocytes or myocytes)
    • Each myocyte has myofibrils & mitochondria to resist fatigue & maintain aerobic metabolism
  • Normal resting energy supply
    • 2/3: free fatty acids & triglycerides
    • 1/3: carbohydrates
    • Trace amount: amino acids & ketons
  • Myocardial contraction
    • Na+ ions initiate APs propogated along the sarcolemma
    • Ca2+ influx –> myocardial contraction –> release of additional Ca2+ from the SR
    • Ca2+ binds to troponin C –> shift in troponin I & T –> tropomyosin release from the actin –> exposed myosin binding sites
    • Binding of myosin to actin: energy dependent
  • Metabolic & energetic derangements in HF
    • Adversely affect AP propogation, Ca2+ homeostasis, & ATP balance
21
Q

Myocytes

  • Held together by…
  • Excess collagen
  • Myocardial dysfunction results from…
  • These changes lead to…
A
  • Held together by…
    • Surrounding collagen connective tissue (major component of the ECM) bundled into muscle fibers
    • Damage to these –> remodeling
  • Excess collagen
    • Causes LV diastolic dysfunction
    • Accumulates as part of hte growth response to LV pressure overload
  • Myocardial dysfunction results from…
    • Loss of myocytes by necrosis or apoptosis
    • Replacement of myocytes w/ collagen & fibrosis
    • Dysfunction of viable myocardium
  • These changes lead to…
    • Electrical derangements (ex. atrial or ventricular arrhythmias, conduction defects)
    • Systemic processes affecting other orgnas & tissues (ex. pulmonary contestion, prerenal azotemia)
    • Further myocardial damage
  • Imbalance of neurohomonal release is due to…
    • Increased circulating catecholamine levels
    • Change in cytokine expression patterns & inflammatory pathways
    • Release of vascular mediators like endothelin-1
22
Q

Myocytes

  • Imbalance of neurohomonal release is due to…
  • Myocyte necrosis
  • Loss of myocytes resulting in cardiac remodeling involves…
  • Extracellular changes that contribute to LV dysfunction
A
  • Imbalance of neurohomonal release is due to…
    • Increased circulating catecholamine levels
    • Change in cytokine expression patterns & inflammatory pathways
    • Release of vascular mediators like endothelin-1
  • Myocyte necrosis
    • ​Occurs following myocardial injury (ex. infarction, toxins, inflammation)
    • Triggered by programmed cell death due to…
      • ​Genetic mutations
      • Induced cell signaling by cytokines, circulating catecholamines, or angiotensin
    • Results in cytoskeletal changes & fibrosis that may be histologically tracked or have no evidence
  • Loss of myocytes resulting in cardiac remodeling involves…
    • Early: cardiac myocyte hypertrophy w/ new sarcomeres & elongated/thickened cells
    • Later: myofilament density within myocytes decreases
  • Extracellular changes that contribute to LV dysfunction
    • Deposition of replacement & reparative collagen –> stiffer walls
    • Myocyte hypertrophy + increased extracellular collagen deposition –> ventricular enlargement –> decreased capillary density –> reduced coronray blood flow reserve –> further damage
23
Q

HF that Doesn’t Present w/ Typical Sequence of Events

  • Heart failure w/ preserved EF (diastolic HF)
  • Dysfunction of residual viable myocardium in HF
  • Stress-related cardiomyopathies
A
  • Heart failure w/ preserved EF (diastolic HF)
    • HF patients that experience progressive symptoms in the absence of LV systolic impairment
    • LV structural abnormalities w/o ventricular dilation or systolic dysfunction
    • Progressive hyeprtrophy or increasing chamber wall stiffness –> less compliant LV –> both systolic & diastolic HF
  • Dysfunction of residual viable myocardium in HF
    • LV enlargement + increased wall tension –> progressive ischemia w/o obstructive epicardial disease
    • Metabolic derangements occur in acute & chronic HF
  • Stress-related cardiomyopathies
    • Reduced free fatty acid use –> affected myocardium undergoes a “hibernating” process
    • Reduced myocardial contractility despite excess intramyocyte Ca2+
    • No cellular necrosis or ECM changes –> myocardial impairments are metabolic
24
Q

Neurohormonal Activation in HF

  • Neurohormonal pathway consists of…
  • Neurohormonal pathway cross-talk
  • Vasoactive mediators
  • Adaptive responses
A
  • Neurohormonal pathway consists of…
    • Adrenergic nervous system (mediated by NE & Epi)
    • Renin-angiotensin-aldosterone system (RAAS)
    • Antidiuretic hormone system (vasopressin)
  • Neurohormonal pathway cross-talk
    • Cross-talk occurs b/n different rogans (brian, heart, peripheral circulation, & kidneys)
    • Vascular, central, & peripheral sensory mechanisms respond to changes in BP to regulate sympathetic & parasympathetic tone
  • Vasoactive mediators
    • Maintain normal homeostatic conditions
    • Recruited in HF to maintain SV
  • Adaptive responses
    • Initially helpful
    • Over time contribute to progressive HF & LV remodeling
      • Happens when counter-regultaory hormones fail to restore balace against vasoactive hormones
25
Q

Sympathetic (Adrenergic) Nervous System

  • General
  • Effects to deliver increased blood flow to peripheral muscles
  • Predominant mediators
  • Heart failure syndrome
  • Beta-adrenergic desensitization
  • Goal of increasing sympathetic tone
  • Mechanism
  • Effects of cycle where SNS stimulation necessitates more SNS stimulation
A
  • General
    • Initially adaptive compensatory response to myocardial injury & stress
    • Responds to stress w/ physiologic changes evolved to protect & preserve life
    • Activated by central & peripheral stimuli
  • Effects to deliver increased blood flow to peripheral muscles
    • Increase HR & splanchnic vascular resistance
    • Decrease peripheral vascular resistance
  • Predominant mediators
    • NE & Epi
  • Heart failure syndrome
    • Increased catecholamines
    • Increased myocardial tissue levels
  • Beta-adrenergic desensitization
    • SNS response is reduced despite excess catecholamines
  • Goal of increasing sympathetic tone
    • Preserve perfusion pressure & BP
  • Mechanism
    • Decreased mean arterial pressure –> increae contractility & HR to maintain SV –> arteriolar vasoconstriction –> increase afterload –> myocardial stress
  • Effects of cycle where SNS stimulation necessitates more SNS stimulation
    • Increase catecholamines in blood & tissue
    • Dysregulated adrenergic beta-receptors on myocardial surface
    • Myocardial necrosis & apoptotic signaling
26
Q

Vascular Effects of Adrenergic Stimuli

  • alpha1
    • Location
    • Effect of SNS
  • beta1
    • Location
    • Effect of SNS
  • beta2
    • Location
    • Effect of SNS
  • Dopamine 1 & 2
    • Location
    • Effect of SNS
A
  • alpha1
    • Location
      • Vascular wall
    • Effect of SNS
      • Arterial vasoconstriction –> increased afterload
      • Venous vasoconstriction –> increased return & increased preload
  • beta1
    • Location
      • Myocardium
    • Effect of SNS
      • Increase HR & contractility –> increase CO
      • Increase relaxation & improve LV filling
  • beta2
    • Location
      • Vascular wall
    • Effect of SNS
      • Peripheral skeletal muscle vasodilatoin –> decrease afterload
  • Dopamine 1 & 2
    • Location
      • Vascular wall
    • Effect of SNS
      • Heart: increase HR & contractility
      • Peripheral circulation: vasoconstriction –> increase afterload
      • Splanchnic circulation: low doses increase splanchnic flow
27
Q

Renin-Angiotensin-Aldosterone System (RAAS)

  • Goal
  • Activated by…
  • Pathway
  • Positive feedback loop
A
  • Goal
    • Restore adequate circulating volume & BP during dehydration or volume depletion
  • Activated by…
    • Volume contraction
    • Occurs during true volume depletion or diminished CO
  • Pathway
    • Kidney releases renin
      • Mediates cleavage of angiotensinogen to angiotensin I
    • ACE
      • Converts angiotensin I into angiotensin II
      • Found predominantly in lung tissue
      • Also found in the kidney, adrenal gland, brian, & vascular endothelium
    • Angiotensin II
      • Increases Na+ reabsorption & water retention in proximal renal tubules
      • Stimulates aldosterone secretion from the adrenal cortex
        • Increases Na+ & water retention
      • Stimulates myocardial fibrosis & cellular hypertrophy mediated by endothelin & tumor necrosis factor (TNF)
      • Causes arterial vasoconstriction –> increases afterload
  • Positive feedback loop
    • RAAS increases sympathetic tone –> activates RAAS
      • Short term: RAAS restores homeostasis in response to decreased intravascular tone
      • Long term: RAAS becomes dysregulated in HF & further contributes to volume overload
    • Ex. patient becomes volume overload
      • Diminished SV & CO –> renal perfusion drops –> kidney perceives volume depletion –> RAAS activation
28
Q

Antidiuretic Hormone (Vasopressin) Systems

  • Vasopressin
  • Effects mediated by…
    • V1 receptors
    • V2 receptors
  • Vasopressin in HF
  • Natriuretic peptide hormones relevant to HF
    • C-type natriuretic peptide (CNP)
    • Atrial natriuretic peptide (ANP)
    • B-type natriuretic peptide (BNP)
    • Both ANP & BNP
    • ANP & BNP at the kidneys
    • ANP & BNP within the myocardium & other organs
    • Synthetic natriuretic peptide (nesiritide)
A
  • Vasopressin
    • Peptide hormone
    • Synthesized in the hypothalamus
    • Stored in the pituitary gland
    • Release stimulated by increased plasma osmolality or decreased effective circulating volume
  • Effects mediated by…
    • V1 receptors
      • Vascular responses to vasopressin –> vasoconstriction
    • V2 receptors
      • Increase membrane permeability in renal cortical & medullary collecting tubules in the kidney –> increased water reabsorption
  • Vasopressin in HF
    • high circulating vasopressin levels –> increased afterload & hyponatremic volume overload
  • Natriuretic peptide hormones relevant to HF
    • C-type natriuretic peptide (CNP)
      • Released in response to vascular shear stress
      • Provides a counterbalance by inhibiting the effects of the vasoconstrictor endothelin
      • Vasodilatory response
    • Atrial natriuretic peptide (ANP)
      • Stored in myocardium within granules
      • Secreted by atrial & ventricular myocardium & kidneys
      • Shorter half-life –> levels fluctuate more rapidly
    • B-type natriuretic peptide (BNP)
      • Responds to genetic up-regultaion before being released
      • Secreted by ventricular ventricular myocardium
      • Longer half-life –> levels don’t fluctuate as much
    • Both ANP & BNP
      • Biomarkers in HF
      • Released in response to myocardial stretch
      • Decrease peripheral vascular tone & increase venous capacitance –> decrease afterload & preload –> decrease intracardiac pressures
    • ANP & BNP at the kidneys
      • Sodium excretion (natriuresis) & diuresis
      • Increases glomerular filtration
        • Vasodilate afferent arterioles going into the renal tubule
        • Constrict efferent arterioles exiting the renal tubules
    • ANP & BNP within the myocardium & other organs
      • Antiproliferative & antifibrotic effects
      • Counter the adverse remodeling changes induced by excess catecholamiens & other molecules like endothelin & TNF
    • Synthetic natriuretic peptide (nesiritide)
      • No clinical benefits compared to conventional HF therapy
29
Q

Endothelium-Derived Vasoactive Substances & Cytokines

  • Endothelium
  • Endothelium-derived relaxing factors (EDRF): vasodilators
  • Endothelium-derived constricting factors (EDCF): vasoconstrictors
  • Cytokines
  • Examples of cytokines
A
  • Endothelium
    • Thin lining of cells within arteries & veins
  • Endothelium-derived relaxing factors (EDRF): vasodilators
    • NO
    • Bradykinin
    • Prostacyclin
  • Endothelium-derived constricting factors (EDCF): vasoconstrictors
    • Endothelin I
  • Cytokines
    • Small protein molecules produced by a variety of tissues & cells
    • Negative inotropes
    • Elevated levels associated w/ worse clinical outcomes
  • Examples of cytokines
    • TNF-alpha
    • IL-1-alpha
    • IL-2
    • IL-6
    • Interferon-alpha
30
Q

Ventricular Remodeling in HF: Summary

  • Adverse ventricular remodeling
  • Pathologic myocardial hypertrophy
  • Interstitial fibrosis & abnormal cardiac myocyte changes
  • Compensatory mechanisms
  • Cellular function & decreased contractile response
  • Neurohormonal model of HF
  • Adrenergic nervous system
  • RAAS pathway
  • Vasopressin
  • Natriuretic peptides
A
  • Adverse ventricular remodeling
    • Effect of chronic adaptive changes of compensatory mechanisms becoming maladaptive
  • Pathologic myocardial hypertrophy
    • Structural change that doesn’t provide functional improvement
    • As opposed to benign hypertrophy in an athletic heart
  • Interstitial fibrosis & abnormal cardiac myocyte changes
    • Underlie remodeling processes that can occur over months to years before progressive HF symptoms develop
  • Compensatory mechanisms
    • Contribute to adverse remodeling
    • Often result in maladaptive cycles contributing to disease progression
  • Cellular function & decreased contractile response
    • Results from structurla canges to myofilaments, derangements in AP propagation, Ca2+ homeostasis, & energy metabolism by cardiac myocytes
  • Neurohormonal model of HF
    • Involves deleterious imbalances of the adrenergic nervous system, RAAS pathway, & circulating vasoactive & inflammatory molecules
    • Results in cell necrosis, apoptosis, tissue fibrosis, & adverse ventricular remodeling
  • Adrenergic nervous system
    • Stimulated by decreases in MAP
  • RAAS pathway
    • Initiated by perceived decrease in intravascular volume
  • Vasopressin
    • Released in response to increased plasma osmolality & decreased effective circulating volume
    • Effects are mediated by V1 (vasoconstriction) & V2 (increased water reabsorption) receptors
  • Natriuretic peptides
    • Provide counter regulatory responses to the adrenergic & RAAS systems
    • Response may become overwhelmed in HF syndrome
31
Q

Neurohormonal Basis for Pharmacotherapy

  • Beta blockers
  • ACE inhibitors (ACE-Is)
  • Angiotensin receptor blockers (ARBs)
  • Aldosterone antagonists
  • Inotropes (dobutamine & milrinone) & oral glycosides (digoxin)
  • Vasopressin V2 receptor antagonist (tolvptan) & human recombinant B-type natriuretic peptide (nesiritide)
A
  • Beta blockers
    • Taget beta-adrenergic receptors on the myocardial surface in competitive inhibition
    • Diminish excess catechol stimulation from the SNS
    • Reduce mortality
  • ACE inhibitors (ACE-Is)
    • Block the conversion of angiotensin I to angiotensin II
    • Reduce mortality
  • Angiotensin receptor blockers (ARBs)
    • Inhibit the RAAS pathway by inhibiting the effects of angiotensin II
    • Reduce mortality
  • Aldosterone antagonists
    • Block the effects of aldosterone in the kidneys
    • Prevent sodium reabsorption
    • Weak diuretic effects
    • Reduce mortality
  • Inotropes (dobutamine & milrinone) & oral glycosides (digoxin)
    • Provide added contractility to failing myocardium
    • May eventually relieve HF symptoms
    • Don’t directly address the neurohormonal pathway
    • Don’t reduce mortality
  • Vasopressin V2 receptor antagonist (tolvptan) & human recombinant B-type natriuretic peptide (nesiritide)
    • Improve acute HF symptoms
    • Don’t reduce survival when combined w/ beta blockers, ACE-Is, or ARBs

Cardiology (40 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions