Transcript The Heart - LSH Student Resources

The Heart
Cardiac Structure and
Specializations
Myocardium
 Valves
 Conduction system
 Blood supply

Effects of Aging on the Heart

Table 12-1
Heart disease: Overview of
Pathophysiology
Failure of the pump
 Obstruction to flow
 Regurgitant flow
 Shunted flow
 Disorders of cardiac conduction
 Rupture of the heart or a major vessel

Heart Failure
Heart is unable to pump blood as a rate sufficient to meet the metabolic
demands of the tissues or can do so only at elevated filling pressures
 Systolic dysfunction – progressive deterioration of myocardial contractile
function
 Diastolic dysfunction – inability of the chamber to expand and fill during
diastole
 Several physiologic mechanisms maintain arterial pressure and perfusion of
vital organs
 Frank-Starling mechanism
 Myocardial adaptations, including hypertrophy with/without chamber
dilation – ventricular remodeling
 Activation of neurohumoral systems
 Release of norepinephrine – increases HR, contractility, vascular
resistance
 Activation of the renin-angiotensin-aldosterone system
 Release of atrial natriuretic peptide

Heart Failure
Cardiac Hypertrophy: Pathophysiology and
Progression to Failure
 Left-sided Heart Failure
 Right-sided heart failure

Cardiac Hypertrophy
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Increased mechanical work due to pressure or volume overload or trophic
signals causes myocytes to increase in size
Increased protein synthesis, increased in DNA ploidy, increased number of
mitochondria, increased size of nuclei
Pressure-overload hypertrophy – concentric increase in wall thickness,
sarcomere in parallel
Volume-overload hypertrophy – ventricular dilation – sarcomeres in series
Oxygen supply to hypertrophied heart is tenuous, deposition of fibrous
tissue, shift to fetal gene expression pattern, heightened metabolic demand
Vulnerable to decompensation
Physiologic vs pathologic hypertrophy
CHF – variable degrees of decreased cardiac output and tissue perfusion, as
well as pooling of blood in the venous system
Left-sided Heart Failure
Causes
 Ischemic heart disease
 Aortic and mitral valvular disease
 Myocardial diseases
 Pulmonary edema – heart failure cells,
Kerley B lines
 Clinically – cough, dyspnea, orthopnea, PND,
atrial fibrillation, increased vascular and
extracellular volume, pre-renal azotemia,
hypoxic encephalopathy

Rigth-sided Heart Failure

Causes
 Most
common is left-sided failure
 Cor pulmonale (pulmonary hypertension)
Congestion – liver and portal system,
pleural, pericardial, peritoneal spaces,
peripheral edema
 Clinically – hepatosplenomegaly,peripheral
edema, pleural effusions, ascites, hypoxia
of CNS

Congenital Heart Disease
CHD = Abnormalities of the heart or great
vessels present from birth
 Most – faulty embryogenesis during the
3rd-8th week when the CVS form and begin
functioning
 Worst ones don’t survive to term
 Those who do usually have only discrete
regions of the heart affected e.g. septal
defect or valvular defect

CHD

Dx
Some when change from fetal to postnatal
circulation
 50% diagnosed by one year of life
 Mild forms - adulthood
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CHD
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Incidence
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1% of all live births
CV defects among most common malformations and are the most
common cause of heart disease in children
Higher in premies and stillborns
Table 12-2
VSD most common
Tetralogy of Fallot most common cyanotic
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Many survive into adulthood – repairs
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Common problems
Arrhythmias
Additional surgery
Ventricular dysfunction
Use of prosthetics
Risk of childbearing
CHD
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ECM – swellings – endocardial cushions
Future valve development
Day 50 – 4 chambered heart
Signaling pathways regulating TFs
Wnt
VEgf
bone morphogenetic factor
TGF-beta
FGF
Notch
Heart – mechanical organ – exposed to flowing blood from earliest
stages – hemodynamic forces play a role
Specific micro RNAs – critical role- patterns and levels of TF
expression
CHD
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Cardiac Development – figure 12-3
First heart field
TFs: TBX5, Hand1
Mainly LV
Second heart field
TF: Hand2, FGF=10
Outflow tract, RV, most of atria
Cardiac neural crest
Septation of outflow tract, aortic arches
CHD
AD mutations – partial loss of function in
one or more required factors, TFs usually
 “The main known cause of CHD consist of
sporadic genetic abnormalities.”

single gene mutations

small chromosome deletions

additions or deletions of whole
chromosomes
 Table 12-3

CHD
Heterozygotes = 50% reduction in activity
= deranged cardiac development
 Factors work together- large protein
complexes – different single gene
mutations produce similar defects
 Signaling pathways or structural roles
NOTCH1 – bicuspid AV
NOTCH2, JAGGED1 – TOF
Fibrillin – Marfan’s
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CHD
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DiGeorge Syndrome
Small deletion of 22q11.2 in 50%
4th branchial arch and 3rd and 4th pharyngeal
pouches
Thymus, parathyroids, heart
TBX1
Chromosomal aneuploidies
Turner Syndrome
Trisomies 13,18, 21
21- most common genetic cause of CHD
endocardial cushion defects
CHD
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First-degree relatives of affected patients are at
increased of CHD – subtle forms of genetic variation
Environmental factors?
+/- genetic factors
congenital rubella infection
gestational diabetes
exposure to teratogens
nutritional factors?
transient environmental stresses during 1st
trimester?
CHD
Clinical features
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Left-to-right shunts
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Right-to-left shunts
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Obstructive lesions
 Shunt= abnormal communication between
chambers or vessels
 Obstruction = narrowing (if completeatresia)

CHD
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R to L
Hypoxemia
Cyanosis
Emboli bypass lungs – brain infarction,
abscess ( paradoxical embolism)
Clubbing (hypertrophic
osteoarthropathy)
Polycythemia
CHD
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L to R
Normally low-pressure, low-resistance pulmonary circulation now sees high
flow volumes and pressures
RVH
Atherosclerosis of pulmonary vessels
medial hypertrophy
vasoconstriction
irreversible obstructive intimal lesions
Pulm pressures reach systemic levels
R to L shunt
Eisenmenger Syndrome
Altered hemodynamics of CHD
Dilation, hypetrophy or both
Decreased volume and muscle mass – hypoplasia – before birth, atrophy –
postnatally
CHD
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L to R
ASD
VSD
PDA
AV septal defects
CHD

ASD
abnormal, fixed opening in the atrial septum
usually asymptomatic until adulthood
3 types
Secundum (90%) – center of the septum
Primum (5%) –adjacent to the AV valves
Clinical

Sinus venosus ( 5%) – SVC, associated with APVR
L to R
Pulmonary blood flow -2-4 times normal
murmur from increased pulmonic valve blood flow
Surgical or catheter correction – low mortality, normal long-term
survival
PVO –oval fossa, 80% closed permanently, 20% potential opening that can become
clinically important r-to-l
CHD
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VSD
Most common congenital anomaly
20-30% isolated finding
Most are associated with other cardiac anomalies
Classified by size and location
90% membranous
Rest are infundibular ( below the PV) or muscular
Muscular can be multiple ( “Swiss-cheese”)
Clinical
Large – problems from birth, RVH, pulmonary
hypertension, correct before irreversible
changes
Smaller – well-tolerated
CHD
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PDA
DA stays open, allowing L to R shunt from
aorta to pulmonary artery
90% isolated anomaly
“machinery-like” murmur
close as soon as possible to prevent
irreversible PH
Some congenital lesions are ductus
dependent and there by need to keep
the DA opene.g. aortic atresia, use prostaglandin E
CHD
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AV septal defect
Complete atrioventricular canal defect
Partial – primum ASD with mitral
insufficiency
Complete – large combined AV septal
defect and a common AV valve – all 4
chambers communicate, all have
hypertrophy
1/3 have Down syndrome
Surgically correctible
CHD
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R to L
Tetralogy of Fallot
Transposition of the Great Arteries
Truncus arteriosus
Tricupsid Atresia
Total Anomalous Venous Connection
CHD

Tetralogy of Fallot
4 cardinal features
VSD
Obstruction of the right ventricular outflow tract (subpulmonary stenosis)
An aorta that overrides the VSD
RVH
Embryoloigcally – anterosuperior displacement of the infundibular septum
“Boot-shaped” heart – marked apical RVH
Sometimes PVS, PV atresia
Sometines AV insufficiency, ASD
25% right aortic arch
Clinical – Classic TOF – r-to-l shunt
Pink TOF – l to r shunt because of mild subpulmonary stenosis
As child grows obstruction becomes worse
Stenosis protects pulmonary arteries from overload and RV failure rare
because RV decompressed by the VSD
CHD
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TGA
Ventriculoarterial discord
Aorta from RV
PA from LV
Separation of the systemic and pulmonary
circulations – incompatible with life
unless a shunt exists VSD or PFO or
PDA or artificial shunt –balloon atrial
septostomy
Surgical repair
CHD
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TA
Failure of separation into the aorta and
PA
Single vessel giving rise to the
systemic, pulmonary and coronary
circulation
Associated VSD
CHD
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TAPC
Pulmonary veins fail to join the left
atrium
PFO or ASD
Aplastic Left atrium
LV normal size
CHD
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Obstructive Congenital Anomalies
Coartation of the aorta
PS and atresia
AS and atresia
CHD
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Coarctation of the Aorta
Males 2x females
Associated with Turner syndrome
2 classic types
“Infantile” –
hypoplasia of the arch proximal to a PDA, symptomatic in
early childhood, cyanosis over lower half of body,
surgical correction needed early
“Adult” –
discrete ridgelike infolding of the aorta, just opposite a
closed DA (ligamentum arteriosus) distal to the arch
vessels, hypertension in upper extremities, signs of arterial
insufficiency in lower, notching of the ribs due to collateral
circulation
Clinical –
murmur with thrill
LVH
CHD
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PS and atresia
Obstruction of the PV
Isolated or part of a more complex anomaly
RVH
Poststenotic dilation of PA
Complete obstruction- need shunt to survive
Mild – asymptomatic
Symptomatic – surgical correction
CHD
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AS and atresia
Vavular-hypoplastic, dysplastic, decreased number
Subvalular-dense fibrous tissue below the cusps
Supravavular- aortic dysplasia, thickened and constricted,
deletion on chromosome 7, elastin gene, WilliamsBeuren syndrome,
hypercalcemia, cognitive abnormalities, facial
anomalies
Hypoplastic left heart syndrome – severe stenosis of atresia –
underdevelopment of LV and aorta – endocardial
fibroelastosis
Clinical – systolic murmur, thrill, LVH, antibiotic prophylaxis for
SBE, avoid strenuous activity, sudden death
Ischemic Heart Disease
Leading cause of death worldwide for both
men and woman.
 Ischemia = oxygen and nutrients
insufficiency
 90% cause is atherosclerotic lesions in the
coronary arteries, thus “coronary artery
disease”
 Other causes – emboli, blockage of small
myocardiql blood vessels, shock

Ischemic Heart Disease
Angina Pectoris
 Myocardial Infarction
 Chronic IHD – ischemic cardiomyopathy
 Sudden cardiac death
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Ischemic Heart Disease
Peak in mortality in 1963, fallen by 50% since
then due to prevention, diagnostic and
therapeutic advances
 The dominant cause of the IHD syndromes is
insufficient coronary perfusion relative to
myocardial demand, due to chronic, progressive
atherosclerotic narrowing of the epicardial
coronary arteries, and variable degrees of
superimposed acute plaque change, thrombosis,
and vasospasm
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Ischemic Heart Disease
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Fixed lesion obstructing > 75% of the lumen leads
to Symptomatic ischemia precipitated by exercise
Obstruction of 90% leads to symptoms even at rest
May lead to formation of collateral vessels over time
Clinically significant stenotic lesions tend to
predominate in the first several centimeters of the
LAD and LCX and along the entire length of the RCA
Angina Pectoris
Paroxysmal and usually recurrent attacks
of substernal or precordial chest
discomfort cause by transient myocardial
ischemia that fall short of inducing
myocyte necrosis
 Three overlapping patterns
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 Stable
or typical angina
 Prinzmetal variant angina
 Unstable or crescendo angina
Myocardial Infarction
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Death of cardiac muscle due to prolonged severe ischemia
Sequence of events in typical MI
 Sudden change in an atheromatous plaque
 Platelets adhere, become activated, release their granule
contents, and aggregate to form microthrombi when exposed to
subendothelial collagen and necrotic plaque contents
 Vasospasm is stimulated by mediators released by platelets
 Tissue factor activates the coagulation pathway, adding to the
bulk of the thrombus
 Frequently within minutes, the thrombus evolves to completely
occlude the lumen
Myocardial Infarction
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Myocardial response
 Cessation of aerobic metabolism within seconds leading to
inadequate high-energy phosphates and accumulation of lactic
acid
 Severe ischemia induces loss of contractility within 60 seconds
 Ultrastructural changes – potentially reversible, develop within a
few minutes
 Myofibrillar relaxation
 Glycogen depletion
 Cell and mitochondrial swelling
Myocardial Infarction
Table 12-4 Approximate time of onset of
key events in ischemic cardiac myocytes
 Key feature in the early phases of myocyte
necrosis – disruption of the integrity of the
sarcolemmal membrane allowing
intracellular macromolecules to leak out of
cells into the cardiac interstitium and
ultimately into the microvasculature and
lymphatics in the region of the infarct
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Myocardial Infarction
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In most cases of acute MI, permanent damage
to the heart occurs when the perfusion of the
myocardium is severely reduced for an extended
interval (usually at least 2-4 hours). This delay in
the onset of permanent myocardial injury
provides the rationale for rapid diagnosis in
acute MI – to permit early coronary intervention,
the purpose of which is to establish reperfusion
and salvage as much “at risk” myocardium as
possible.
Myocardial Infarction

Precise location, size, and specific morphologic features of an acute
MI depend on:
 Location, severity, and rate of development of coronary
obstruction
 Size of the vascular bed perfused by the obstructed vessels
 Duration of the occlusion
 Metabolic/oxygen needs of the myocardium at risk
 Extent of collateral vessels
 Presence, site, severity of coronary arterial spasm
 Other factors – HR, rhythm, blood oxygenation
Myocardial Infarction

Typically
 LAD
– apex, anterior wall of LV, anterior 2/3
of ventricular septum
 The coronary artery that perfuses the
posterior third of the septum is called
dominant ( either the LCX or RCA)
 Right dominant circulation (4/5 of population)
 LCX
– lateral wall of the LV
 RCA – entire RV free wall, posterobasal wall of the
LV, posterior third of the septum
Myocardial Infarction

Transmural vs subendocardial infarction
 Most
MIs are transmural – full thickness in the
distribution of a single artery, ST elevation
 Subendocardial – area of necrosis limited to
inner 1/3 to1/2 of ventricular wall, non-ST
elevation, normally the least perfused area of
the myocardium, most vulnerable to ischemia
Myocardial Infarction

Infarct modification by reperfusion
 Reperfusion
– most effective way to “rescue”
ischemic myocardium
 May trigger deleterious complications
 Arrhythmias
 Myocardial
hemorrhage with contraction bands
 Irreversible cell damage superimposed on the
original ischemic injury (reperfusion injury)
 Microvascular injury
 Prolonged ischemic dysfunction (myocardial
stunning)
Myocardial Infarction

Appearance of reperfused myocardium
 Hemorrahagic
 Irreversibly
injured myocytes – contraction
bands
 Reperfusion not only salvages reversible
injured cells but alters the morphology of
lethally injured cells
Myocardial Infarction

Consequences and Complications
 Contractile dysfunction
 Arrhythmias
 Myocardial rupture
 Pericarditis
 Right ventricular infarction
 Infarct extension
 Infarct expansion
 Mural thrombus
 Ventricular aneurysm
 Papillary muscle dysfunction
 Progressive late heart failure
Morphologic Changes in Acute
Myocardial Infarction
Early – Risk of Arrhythmia
Time
Gross
LM
½-4 hours
None
None, variable waviness of
fibers at border
4-12 hours
Occasional dark
mottling
Early coagulation necrosis,
edema, hemorrhage
12-24 hours
Dark mottling
Ongoing coagulation
necrosis, pyknosis of nuclei,
myocyte
eosinophilia,contraction
band necrosis, early
neutrophilic inflitration
1-3 days
Mottling with
yellow-tan
infarct center
Coagulation necrosis with
loss of nuclei and striations;
Brisk interstitial neutrophil
infiltration
Middle – Risk of Myocardial Rupture
Time
Gross
LM
3-7 days
7-10 days
10-14 days
Hyperemic
border; central
yellow-tan
softening
Maximally
yellow-tan and
soft, with
depressed
margins
Red-gray
depressed
infarct borders
Beginning disintegration
ofdead myofibers,
dyingneutrophils, early
phagocytosis by
macrophages
Well-developed
phagocytosis of dead cells;
early formation, of
granulation tissue at
margins
Well- established
granulation tissue
Late – Risk of Ventricular Aneurysm
Time
Gross
LM
2-8 weeks
Gray-white scar,
progressive
from border
toward core of
infarct
Scarring
complete
Increased
collagen with
decreased
cellularity
>2 months
Dense
collagenous
scar
Serum Enzyme changes in Acute MI
Time
CK-MB
Troponin I
LDH
(most sensitive and
specific)
6 hours
Weakly
positive
Weakly
positive
12-16
hours
24 hours__
2 days____
3 days____
4-7 days
Strongly
positive
Peaks____
Persists___
Negative__
Strongly
positive
Peaks____
Persists___
Persists___ Peaks____
Persists
Persists
Sudden Cardiac Death
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Usually the consequence of a lethal arrhythmia
Acute myocardial ischemia is the most common trigger for fatal
arrhythmias
Nonatherosclerotic causes
 Congenital structural of coronary arterial abnormalities
 AS
 MVP
 Myocarditis
 Dilated or hypertrophic cardiomyopathy
 Pulmonary hypertension
 Hereditary or acquired arrhythmias
 Cardiac hypertrophy of any cuase
 Other miscellaneous
Hypertensive Heart Disease

Systemic (Left-sided) hypertensive heart
disease
 LVH
(concentric usually) in absence of other
CV pathology
 History of pathological evidence of
hypertension

Pulmonary (Right-sided) hypertensive
heart disease (Cor pulmonale)
 Table
12-6 -disorders predisposing to cor
pulmonale
Valvular Heart Disease
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Valvular degeneration associated with calcification
 Calcific aortic stenosis
 Calcific stenosis of congenitally bicuspid aortic valve
 Mitral annular calcification
Mitral Valve Prolapse (Myxomatous degeneration of the mitral valve)
Rheumatic Fever and rheumatic heart disease
Infective endocarditis
Noninfected vegetations
Nonbacterial thrombotic endocarditis
 Endocarditis of systemic lupus erythematosus (Libman-Sacks disease)
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Carcinoid heart disease
Complications of artificial valves
Valvular Heart Disease
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Stenosis – pressure overload
Insufficiency (regurgitation) – volume overload
Acquired stenosis of the aortic and mitral valves account
for 2/3 of all cases of valve disease
Most frequent
 AS – calcification of normal or bicuspid valve
 AI – dilation of ascending aorta
 MS – RHD
 MI – MVP
 Table 12-7 Major etiologies of acquired lesions
Mitral Valve Prolapse
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One or more of the leaflets are floppy and prolapse into the left
atrium during systole
Myxomatous degeneration
Most patient are asymptomatic
Midsystolic click
Chest pain, dypsnea, fatigue
Complications
 Infective endocarditis
 MI
 Stroke
 Arrhythmias
Rheumatic Fever and Rheumatic
Heart Disease

Rheumatic fever
 Acute, immunologically mediated, occurs a few weeks after an
episode of group A strep pharyngitis
 Antibodies and T cell-mediated reactions against M proteins
cross-react with heart self- antigens
 Jones criteria
 Major – migratory polyarthritis of large joints, pancarditis,
subcutaneous nodules, erythema marginatum, Sydenham
chorea
 Minor – fever, arthralgia, elevated acute-phase reactants
 2 major or 1 major and 2 minor + evidence of a preceeding
strep infection
Rheumatic Fever and Rheumatic
Heart Disease

RF – Aschoff bodies, caterpillar cells, Mac
Callum plaques

RHD – leaflet thickening, commissural
fusion and shortening, thickening and
fusion of the tendinous cords
Infective Endocarditis
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Colonization or invasion of the heart valves or the mural
endocardium by a microbe
Vegetations – thrombotic debris and organisms,
destruction of the tissue
Acute – infection of a previously normal heart by a
virulent organism, S. Aureus
Subacute – insidious infection of deformed valves with
less virulent organisms, S viridnas, HACEK, S.
epidermidis
Table 12-8 Diagnostic criteria for IE
Cardiomyopathies

Dilated cardiomyopathy
 Arrhythmogenic
cardiomyopathy
right ventricular
Hypertrophic cardiomyopathy
 Restrictive cardiomyopathy
 Myocarditis
 Other causes of myocardial disease

Cardiomyopathies
Table 12-10 Cardiomyopathy and Indirect
Myocardial Dysfunction
 Table 12-11 Conditions associated with
Heart Muscle disease
 Figure 12-32 Causes and consequences of
Dilated and Hypertrophic
Cardiomyopathy
 Table 12-12 Major Causes of Myocarditis

Other Causes of Myocardial
Disease
Cardiotoxic drugs
 Catecholamines
 Amyloidosis
 Iron overload
 Hyperthyroidisn
 Hypothyroidism

Pericardial Disease

Pericardial effusion and hemopericardium
 Cardiac

tamponade
Pericarditis – Table 12-13 - causes
 Acute
pericarditis – friction rub, fever, pain
 Chronic or healed pericarditis – adhesive,
constrictive

Heart disease associated with
rheumatologic disorders
Tumors of the heart

Primary cardiac tumors
 Myxoma
– most common in adults, ball-valve
obstruction. Carney complex
 Lipoma
 Papillary fibroelastoma
 Rhabdomyoma – most commonin children, TS
 Sarcoma

Cardiac effects of noncardiac neoplasms –
Table 12-14
Cardiac Transplantation
Rejection – resembles myocarditis
 Graft arteriopathy – silent Mis
 1-year survival - 70-80%, 5-year - >60%
