Cardiovascular System Flashcards
How many times does the heart beat a year and how much blood does it pump a day
Which system is the first organ system to become fully functional in the uterus and at approximately how many weeks of gestation
What type of systemic. Disease is a leading contributor to mortality worldwide
What kind of heart disease is the most prevalent?
What is us heart rate and how many times does the heart beat per minute
beating more than 40 million times a year and pumping over 7500 liters of blood a day;
The cardiovascular system is the first organ system to become fully functional in utero (at approximately 8 weeks of gestation); without a beating heart and vascular supply, further development cannot occur, and fetal demise is inevitable. Indeed, cardiovascular disease remains the leading con- tributor to mortality worldwide
ischemic heart disease is the most prevalent form of heart disease,
Heart rate, also known as pulse, is the number of times your heart beats per minute.
60-100bpm
What are the six pathophysiologic pathways or principal mechanisms that result in a broken heart? And explain how they cause the broken heart and give an example each of diseases that work that way
Although a host of diseases can affect the cardiovascular system, the pathophysiologic pathways that result in a “broken” heart distill down to six principal mechanisms:
• Failure of the pump. In the most common situation, the cardiac muscle contracts weakly and the chambers cannot empty properly—so-called systolic dysfunction. In
some cases, the muscle cannot relax sufficiently to permit
ventricular filling, resulting in diastolic dysfunction.
• Obstruction to flow. Lesions that prevent valve opening (e.g., calcific aortic valve stenosis(Stenosis, which means narrowing,) ) or cause increased ventricular chamber pressures (e.g., systemic hyperten- sion or aortic coarctation) can overwork the myocar-
dium, which has to pump against the obstruction.
• Regurgitant flow. Valve lesions that allow backward flow of blood create conditions that add increased volume workload to the affected chambers with each contraction
.
• Shuntedflow.Defects(congenital or acquired)that divert
blood inappropriately from one chamber to another, or from one vessel to another, lead to pressure and volume overloads.
- Disorders of cardiac conduction: Uncoordinated cardiac impulses or blocked conduction pathways can cause arrhythmias that reduce contraction frequency or dimin- ish effective cardiac output.
- Rupture of the heart or major vessel. Loss of circulatory continuity (e.g., gunshot wound through the thoracic aorta) leads to exsanguination, hypotensive shock, and death.
What is heart failure
Most cases of heart failure are due to which three diseases and heart failure can also be caused by which disease and that disease occurs due to what?
Inadequate myocardial contraction function is characteristically a consequence of which two diseases?
Name four other diseases in which there is diastolic dysfunction
Heart failure in which three groups of people are more commonly attributed to diastolic dysfunction
Various studies suggest that 40–60% of cases of CHF may be due to dia- stolic dysfunction
True or false
HEART FAILURE
Heart failure generally is referred to as congestive heart failure (CHF). CHF is the common end point for many forms of cardiac disease and typically is a progressive condition that carries an extremely poor prognosis.
Most cases of heart failure are due to systolic dysfunction—inadequate myocardial contractile function, characteristically a consequence of ischemic heart disease or hypertension. Alternatively, CHF also can result from diastolic dysfunction—inability of the heart to adequately relax and fill, such as in massive left ventricular hypertro- phy, myocardial fibrosis, amyloid deposition, or constric- tive pericarditis.
Indeed, heart failure in elderly persons, diabetic patients, and women may be more commonly attributable to diastolic dysfunction.
. Finally, heart failure also can be caused by valve dysfunction (e.g., due to endocarditis) or can occur in normal hearts suddenly burdened with an abnor- mal load (e.g., with fluid or pressure overload).
True
How does heart failure occur
What is another name for inadequate cardiac output?
Inadequate cardiac output is almost always accompanied by what?
What is the consequence of backward failure
How does heart failure occur in a minority of cases,heart failure may be a consequence of what two things ? And state which disease those two can occur in
CHF onset can be abrupt, as in the setting of a large myocardial infarct or acute valve dysfunction.
True or false
In many cases CHF develops gradually and insidiously ,why?
CHF occurs when the heart cannot generate sufficient output to meet the metabolic demands of the tissues—or can only do so at higher-than-normal filling pressures; In CHF, the failing heart can no longer efficiently pump the blood delivered to it by the venous circulation. The result is an increased end-diastolic ventricular volume, leading to increased end-diastolic pressures and, finally, elevated venous pressures.
Thus, inadequate cardiac output—called forward failure—is almost always accompa- nied by increased congestion of the venous circulation— that is, backward failure. As a consequence, although the root problem in CHF typically is deficient cardiac function,
virtually every other organ is eventually affected by some combination of forward and backward failure.
in a minority of cases, heart failure can be a consequence of greatly increased tissue demands, as in hyperthyroidism, or poor oxygen carrying capacity as in anemia (high-output failure).
In many cases, however, CHF develops gradually and insidiously owing to the cumulative effects of chronic work overload or progressive loss of myocardium.
How does the CVs attempt to compensate for reduced myocardial contractility or increased hemodynamic burden(state and explain the four homeostatic mechanisms)
What is concentric hypertrophy and what is it characterized by?
What is a sarcomere
What is the best measure of hypertrophy in volume overloaded hearts
The cardiovascular system attempts to compensate for reduced myocardial contractility or increased hemody- namic burden through several homeostatic mechanisms:
• The Frank-Starling mechanism:. Increased end-diastolic filling volumes dilate the heart and cause increased cardiac myofiber stretching; these lengthened fibers con- tract more forcibly, thereby increasing cardiac output. If the dilated ventricle is able to maintain cardiac output by this means, the patient is said to be in compensated heart failure. However, ventricular dilation comes at the expense of increased wall tension and amplifies the oxygen requirements of an already-compromised myo- cardium. With time, the failing muscle is no longer able to propel sufficient blood to meet the needs of the body, and the patient develops decompensated heart failure.
• Activation of neurohumoral systems:
Release of the neurotransmitter norepinephrine by
the autonomic nervous system increases heart rate and augments myocardial contractility and vascular resistance.
Activation of the renin-angiotensin-aldosterone system spurs water and salt retention (augmenting circulatory volume) and increases vascular tone.
Release of atrial natriuretic peptide acts to balance the renin-angiotensin-aldosterone system through diure- sis and vascular smooth muscle relaxation.
• Myocardial structural changes:, including augmented muscle mass. Cardiac myocytes cannot proliferate, yet can adapt to increased workloads by assembling increased numbers of sarcomeres, a change that is accompanied by myocyte enlargement (hypertrophy) (Fig. 10–1).
In pressure overload states (e.g., hypertension or valvu- lar stenosis), new sarcomeres tend to be added paral- lel to the long axis of the myocytes, adjacent to existing sarcomeres. The growing muscle fiber diameter thus results in concentric hypertrophy—the ventricular wall thickness increases without an increase in the size of the chamber.
(The heart responds to a pressure overload in strength training by adding new sarcomeres in-parallel to existing sarcomeres. As a consequence, the wall thickness increases. This pathological condition is called concentric hypertrophy. Concentric hypertrophy is characterized by an addition of sarcomeres (the contractile units of cardiac cells) in parallel. The result is an increase in thickness of the myocardium without a corresponding increase in ventricular size.)
In volume overload states (e.g., valvular regurgitation or shunts), the new sarcomeres (A sarcomere is the basic contractile unit of muscle fiber. the smallest functional unit of striated muscle tissue. It is the repeating unit between two Z-lines. Skeletal muscles are composed of tubular muscle cells (called muscle fibers or myofibers )) are added in series with existing sarcomeres, so that the muscle fiber length increases. Consequently, the ventricle tends to dilate, and the resulting wall thickness can be increased, normal, or decreased; thus, heart weight— rather than wall thickness—is the best measure of hypertrophy in volume-overloaded hearts.
What makes the myocardium vulnerable to Ischemic Injury
Hypertrophy is also typically associated with altered patterns of gene what?
In the face of ischemia and chronic increases in workload, other untoward changes also eventually supervene, including myocyte apoptosis, cytoskeletal alterations, and increased extracellular matrix (ECM) deposition.
True or false
Pathological compensatory cardiac hypertrophy is correlated with what?
Cardiac hypertrophy is an independent risk factor for what?
Volume loaded hypertrophy I ducked by regular aerobic exercise is accompanied by increase in what and decrease in what?
Static exercise is associated with what?
What is pressure hypertrophy and volume hypertrophy
Compensatory hypertrophy comes at a cost to the myocyte. The oxygen requirements of hypertrophic myocardium are amplified owing to increased myocardial cell mass. Because the myocardial capillary bed does not expand in step with the increased myocardial oxygen demands, the myocar- dium becomes vulnerable to ischemic injury.
Hypertrophy also typically is associated with altered patterns of gene expression reminiscent of the fetal myocytes, such as changes in the dominant form of myosin heavy chain pro- duced. Altered gene expression may contribute to changes in myocyte function that lead to increases in heart rate and force of contraction, both of which improve cardiac output, but which also lead to higher cardiac oxygen consumption.
True
Pathologic compensatory cardiac hypertrophy is corre- lated with increased mortality; indeed, cardiac hypertro- phy is an independent risk factor for sudden cardiac death. By contrast, the volume-loaded hypertrophy induced by regular aerobic exercise (physiologic hypertrophy) typically is accompanied by an increase in capillary density, with decreased resting heart rate and blood pressure.
These physiologic adaptations reduce overall cardiovascular morbidity and mortality.
In comparison, static exercise (e.g., weight lifting) is associated with pressure hypertro- phy and may not have the same beneficial effects.
Pressure overload mediates hypertrophy through thickening of the left ventricular wall with little or no increase in chamber size, whereas volume overload (valvular regurgitation) results in regular wall thickness but increased chamber size
What’s the difference between concentric and eccentric Hypertrophy
What are the four most common causes of left sided heart failure
The morphologic and clinical effects of left sided heart failure stem from what?
Concentric hypertrophy is associated with increased left ventricular wall thickness whereas eccentric hypertrophy is characterized by dilatation of the left ventricular chamber; however, there occurs a general increase in the overall size of cardiomyocytes under both conditions
Heart failure can affect predominantly the left or the right side of the heart or may involve both sides. The most common causes of left-sided cardiac failure are ischemic heart disease (IHD), systemic hypertension, mitral or aortic valve disease, and primary diseases of the myocardium (e.g., amyloidosis).
The morphologic and clinical effects of left-sided CHF stem from diminished systemic perfusion and the elevated back-pressures within the pulmonary circulation.
With the morphology of the heart in left sided heart failure ,gross cardiac findings depend on what? Usually left ventricle is hypertrophied and can be dilated sometimes massively except in which diseases?
Left ventricular dilation can result in what two things?
Left atrial enlargement is associated with increased what?
The microscopic changes in the heart are what,consisting primarily of what?
Superimposed on this may be what?
What causes the congestion and edema in the lungs and pleural effusion with left heart failure?
What is the morphology of the lungs and what are the four to five things seen microscopically
Subsequent breakdown of RBCs and hemoglobin leads to appearance of what? And what does it reflect?
MORPHOLOGY
Heart. Thegrosscardiacfindingsdependontheunderlying disease process, for example, myocardial infarction or valvu- lar deformities may be present. With the exception of failure due to mitral valve stenosis or restrictive cardiomyopathies (described later), the left ventricle usually is hypertrophied and can be dilated, sometimes massively. Left ventricular dilation can result in mitral insufficiency and left atrial enlarge- ment, which is associated with an increased incidence of atrial fibrillation. The microscopic changes in heart failure are nonspecific, consisting primarily of myocyte hypertrophy with interstitial fibrosis of variable severity. Superimposed on this background may be other lesions that contribute to the development of heart failure (e.g., recent or old myocardial infarction).
Lungs:. Rising pressure in the pulmonary veins is ultimately transmitted back to the capillaries and arteries of the lungs, resulting in congestion and edema as well as pleural effusion due to an increase in hydrostatic pressure in the venules of the visceral pleura. The lungs are heavy and boggy, and micro- scopically show perivascular and interstitial transudates, alveolar septal edema, and accumulation of edema fluid in the alveolar spaces. In addition, variable numbers of red cells extravasate from the leaky capillaries into alveolar spaces, where they are phagocytosed by macrophages .
The subse- quent breakdown of red cells and hemoglobin leads to the appearance of hemosiderin-laden alveolar macrophages— so-called heart failure cells—that reflect previous epi- sodes of pulmonary edema.
State 14 clinical features of left sided heart failure
Which is usually the earliest and most significant symptom?
Why will there be cough in left sided heart failure?
What causes orthopnea in left sided heart failure
The orthopnea is relieved by what?
What causes fine rales in the lung bases ,what causes mitral regurgitation and systolic murmur
What causes atrial fibrillation and how does it manifest
What does atrial fibrillation cause?
Systemically what causes increased intravascular volume and pressure
With further reduction in renal perfusion,what occurs?
In severe heart failure ,diminished cerebral perfusion can manifest as what? With what? That can progress to what?
Clinical Features
Dyspnea (shortness of breath) on exertion is usually the earliest and most significant symptom of left-sided heart failure;
cough also is common as a consequence of fluid transudation into air spaces.As failure progresses, patients experience dyspnea when recumbent (orthopnea); this occurs because the supine position increases venous return from the lower extremities and also elevates the diaphragm. Orthopnea typically is relieved by sitting or standing, so patients usually sleep in a semiseated position. Paroxysmal nocturnal dyspnea is a particularly dramatic form of breath- lessness, awakening patients from sleep with extreme dyspnea bordering on feelings of suffocation.
Other manifestations of left ventricular failure include an enlarged heart (cardiomegaly), tachycardia, a third heart sound (S3), and fine rales at the lung bases, caused by the opening of edematous pulmonary alveoli. With pro- gressive ventricular dilation, the papillary muscles are displaced outwards, causing mitral regurgitation and a systolic murmur.
Subsequent chronic dilation of the left atrium can cause atrial fibrillation, manifested by an “irregu- larly irregular” heartbeat. Such uncoordinated, chaotic atrial contractions reduce the ventricular stroke volume and also can cause stasis. The stagnant blood is prone to form thrombi (particularly in the atrial appendage) that can shed emboli and cause strokes and manifestations of infarction in other organs.
Systemically, diminished cardiac output leads to decreased renal perfusion that in turn triggers the renin- angiotension-aldosterone axis, increasing intravascular volume and pressures
Unfortunately, these compensatory effects exacerbate the pulmonary edema. With further reduction in renal perfusion, prerenal azotemia may supervene, with impaired excretion of nitrogenous wastes and increasing metabolic derangement. In severe CHF, diminished cerebral perfusion can manifest as hypoxic encephalopathy with irritability, diminished cognition, and restlessness that can progress to stupor and coma.
Right heart failure usually is the consequence of left-sided heart failure, why?
Isolated right-sided heart failure also can occur in a few diseases. The most common of these is ?
What does it result in?
What happens in cor pulmonale
Isolated right heart failure can also occur in patients with what?
What is the major morphological and clinical effects of pure right sided failure from left sided failure
What is cor pulmonale?
since any pressure increase in the pulmonary circulation inevitably produces an increased burden on the right side of the heart.
severe pulmonary hypertension, resulting in right-sided heart pathology termed cor pulmonale.
In cor pulmonale, myocardial hypertrophy and dilation generally are con- fined to the right ventricle and atrium, although bulging of the ventricular septum to the left can cause left ventricular dysfunction.
Isolated right-sided failure also can occur in patients with primary pulmonic or tricuspid valve disease, or congenital heart disease, such as with left-to-right shunts causing chronic volume and pressure overloads.
The major morphologic and clinical effects of pure right- sided heart failure differ from those of left-sided heart failure in that engorgement of the systemic and portal venous systems typically is pronounced and pulmonary congestion is minimal.
Right-sided heart failure means that the right side of the heart is not pumping blood to the lungs as well as normal. It is also called cor pulmonale or pulmonary heart disease.
With the morphology of right heart failure what happens to the liver
What is nutmeg liver
What happens to the centrilobular areas in right sided heart failure
When left sided heart failure is present,what happens to the centrilobular areas
With long standing severe right sided heart failure,what happens to the central areas? What does it create?
Right sided heart failure also leads to elevated what in the portal system and what causes congestive splenomegaly
What can be severe enough to interfere w absorption of nutrients and medication
What can happen to the pleural and pericardial spaces in right heart failure ?
When are pleural effusions most pronounced?
When pleural effusions are large ,what can it cause?
State the value that constitutes large pleural effusion
Substantial pericardial effusions can cause what?
State the value
A combination of what and what leads to peritoneal transudates (Ascites)
Effusions into which part of the body are serious with what and what?
What is a hallmark of right heart failure in the subcutaneous tissues?
In chronically bedridden patients,edema may be primarily what,
In which cases will anasarca be seen?
Liver and Portal System. The liver usually is increased in size and weight (congestive hepatomegaly). A cut section displays prominent passive congestion, a pattern referred to as nutmeg liver
congested centrilobular areas are surrounded by peripheral paler, noncongested parenchyma.
When left-sided heart failure is also present, severe central hypoxia produces centrilobular necrosis in addition to the sinusoidal congestion.
With long-standing severe right-sided heart failure, the central areas can become fibrotic, creating so-called cardiac cirrhosis.
Right-sided heart failure also leads to elevated pressure in the portal vein and its tributaries (portal hypertension), with vascular congestion producing a tense, enlarged spleen (congestive splenomegaly).
Chronic passive congestion of the bowel wall with edema can be severe enough to interfere with absorption of nutrients and medications.
Pleural, Pericardial, and Peritoneal Spaces. Systemic venous congestion due to right heart failure can lead to transudates (effusions) in the pleural and pericardial spaces, but usually does not cause pulmonary parenchymal edema.
Pleural effusions are most pronounced when there is increase in pulmonary venous as well as systemic venous pressures, as occurs in combined right and left heart failure.
When large (e.g., 1 L or more), pleural effusions can cause atelectasis, and, very uncommonly, substantial pericardial effusions (greater than 500 mL) can limit cardiac filling and cause cardiac failure (due to tamponade).
A combination of hepatic congestion (with or without diminished albumin synthesis) and portal hypertension leads to peritoneal tran- sudates (ascites)
The effusions into the various body cavities typically are serous, with a low protein content, and lack inflammatory cells.
Subcutaneous Tissues. :Peripheral edema of dependent portions of the body, especially ankle (pedal) and pretibial edema, is a hallmark of right heart failure.
In chronically bedridden patients, the edema may be primarily presacral. In particularly severe cases, generalized massive edema (ana- sarca) may be seen.
The presacral space is the area between the rectum and lowest part of your the spine, which is called the sacrum. The presacral space is inside the pelvis, behind the rectum and in front of the coccyx and sacrum.
State eight clinical features of right sided heart failure
What do most cases of chronic cardiac décompensation present with?
As congestive heart failure progresses,patients may become what due to what resulting from what?
When does CHF occur?
Left sided heart failure is most commonly secondary to which diseaseS,State four
Symptoms of left sided heart failure are mainly a consequence of which two things although systemic hypo perfusion can cause what?
Right sided heart failure is due most often to what, less commonly due to what?
Signs and symptoms of right heart failure are related chiefly to which two things?
Clinical Features
Unlike left-sided heart failure, pure right-sided heart failure typically is associated with very few respiratory symptoms. Instead, the clinical manifestations are related to systemic and portal venous congestion, including hepatic and splenic enlargement, peripheral edema, pleural effu- sion, and ascites. Venous congestion and hypoxia of the kidneys and brain due to right heart failure can produce deficits comparable to those caused by the hypoperfusion caused by left heart failure.
Of note, in most cases of chronic cardiac decompensa- tion, patients present with biventricular CHF, encompassing the clinical syndromes of both right-sided and left-sided heart failure.
As congestive heart failure progresses, patients may become frankly cyanotic and acidotic, as a consequence of decreased tissue perfusion resulting from both diminished forward flow and increasing retrograde congestion.
SUMMARY
Heart Failure
• CHF occurs when the heart is unable to provide adequate perfusion to meet the metabolic requirements of peripheral tissues; inadequate cardiac output usually is accompanied by increased congestion of the venous circulation.
• Left-sided heart failure is most commonly secondary to ischemic heart disease, systemic hypertension, mitral or aortic valve disease, or primary diseases of the myocar- dium; symptoms are mainly a consequence of pulmonary congestion and edema, although systemic hypoperfusion can cause renal and cerebral dysfunction.
• Right-sided heart failure is due most often to left heart failure and, less commonly, to primary pulmonary disor- ders; signs and symptoms are related chiefly to peripheral edema and visceral congestion.
What is congenital heart disease
They account for what percentage of all birth defects and include a broad spectrum of what ranging from what to what?
Congenital heart disease affects 6 to 8 of every 1000 liveborn infants, and the inci- dence is higher in premature infants and in stillborns; roughly 40,000 children are born each year in the United States with clinically significant cardiac malformations, and another 40,000 have subclinical disease. True or false
Defects that permit maturation and live birth usually involve how many chambers or regions of the heart?
Twelve entities account for 85% of cases of congenital heart disease; their frequencies are shown in Table 10–1.
Thanks to surgical advances, the number of patients surviving with congenital heart disease is increasing rapidly, including over 1 million persons in the United States alone.
True or false
Although surgery may correct the hemody- namic abnormalities, the repaired heart may not be
completely normal,
Why?
Degrees of myocardial scarring may lead secondarily to what three diseases
CONGENITAL HEART DISEASE
Congenital heart diseases are abnormalities of the heart or great vessels that are present at birth. They account for 20% to 30% of all birth defects and include a broad spectrum of malformations, ranging from severe anomalies incompat- ible with intrauterine or perinatal survival, to mild lesions that produce only minimal symptoms at birth, or are entirely unrecognized during life.
Defects that permit maturation and live birth usually involve only single chambers or regions of the heart.
since the myocardial hypertrophy and cardiac remodeling brought about by the congenital defect may be irreversible; in addition, virtually all cardiac surgery results in some degree of myocardial scarring. Such changes lead secondarily to arrhythmias, ischemia, and myocardial dysfunction, which occasionally appear many years after surgical correction
What is the pathophysiology of congenital heart disease(what causes it, state the gestational weeks it occurs and around that time what’s structures develop,state the known étiologic factors
The contribution of specific genetic loci has been demonstrated in familial forms of what? And by well define associations with what?
Cardiac morphogenesis involves what?
What are the five key steps in cardiac morphogenesis
Proper orchestration is the key steps depends on networks of what?
What else is essential for cardiac morphogenesis
Since crafting a normal heart involves many steps, even subtle perturbations can adversely influence the outcome true or false
Most of the known egebruc defects are what? Causing loss or gain of what?
Severe mutations involve what?
Give and example
State some other disorders associated with mutations in intracellular signaling cascades that cause constitutive activation
It is likely that even transient environmental stresses at critical junctures early in pregnancy can cause subtle changes in transcription factor activity, intracellular signaling, or morphogenic gradients that may recapitulate the defects produced by heritable mutations.true or false
PATHOGENESIS
In most instances, congenital heart disease arises from faulty embryogenesis during gestational weeks 3 through 8, when major cardiovascular structures develop; the cause is unknown in almost 90% of cases. Of the known etiologic factors, environmental causes, including congenital rubella infection, teratogens, and maternal diabetes, and genetic factors are the best characterized.
The contribution of spe- cific genetic loci has been demonstrated in familial forms of congenital heart disease and by well-defined associations with certain chromosomal abnormalities (e.g., trisomies 13, 15, 18, and 21, and Turner syndrome).
Cardiac morphogenesis involves multiple genes that work together to choreograph a complex series of tightly regulated events.
Key steps include commitment of progeni- tor cells to the myocardial lineage, formation and looping of the heart tube, segmentation and growth of the cardiac chambers, cardiac valve formation, and connection of the great vessels to the heart.
Proper orchestration of these remarkable transformations depends on networks of tran- scription factors and several signaling pathways and mole- cules, including the Wnt, vascular endothelial growth factor (VEGF), bone morphogenetic protein (BMP), transforming growth factor-β (TGF-β), fibroblast growth factor, and Notch pathways.
Also essential for cardiac morphogenesis is the mechanical force imparted by flowing pulsatile blood, which is somehow sensed by the cells of the developing heart and vessels.
. Most of the known genetic defects are autosomal dominant mutations causing loss (or sometimes gain) of function of a particular factor (Table 10–2).
Several mutations involve tran- scription factors. For example, atrial and ventricular septal defects (ASDs and VSDs, respectively) and/or conduction defects may be caused by transcription factor mutations, such as TBX5 mutations in the Holt-Oram syndrome and NKX2.5 or GATA4 mutations in sporadic, nonsyndromic cases.
Other disorders (e.g., Noonan syndrome) are associated with muta- tions in intracellular signaling cascades that cause constitutive activation.
microRNAs, as well as epigenetic changes (e.g., DNA methylation), also are increasingly recognized as impor- tant contributors.
Give six example of gene defects associated with congenital heart disease,the gene involve and the gene product function
The gene defects are grouped into syndromic and non syndromic
Note that different mutations can cause the same phenotype, and that mutations in some genes can cause multiple phenotypes (e.g., NKX2.5). Many of these congenital lesions also can occur sporadically, without specific genetic mutation.
†Only the cardiac manifestations of the syndrome are listed; the other skeletal, facial, neurologic, and visceral changes are not.
True or false
State the full meaning of ASD,CHARGE,PDA,VSD
Disorder Nonsyndromic ASD or conduction defects Gene: NKX2.5 Gene product function:Transcription factor Disorder:ASD or VSD Gene:GATA4 Transcription factor
Disorder: Tetralogy of Fallot
Gene/ZFPM2 or NKX2.5
Gene product function:Transcription factors
Syndromic:
Alagille syndrome—pulmonary artery stenosis or tetralogy of Fallot
Gene: JAG1 or NOTCH2
Gene product function: Signaling proteins or receptors
Disorder:
Char syndrome—PDA
Gene:TFAP2B
Gene product function:Transcription factor
CHARGE syndrome—ASD,VSD, PDA, or hypoplastic right side of the heart
Gene:CHD7
Gene product function: Helicase-binding protein
DiGeorge syndrome—ASD,VSD, or outflow tract obstruction
Gene:TBX1
Transcription factor
Holt-Oram syndrome—ASD,VSD, or conduction defect
Gene:TBX5
Transcription factor
Noonan syndrome—pulmonary valve stenosis,VSD, or hypertrophic cardiomyopathy
Gene:PTPN11, KRAS, SOS1
Gene product function:Signaling proteins
* ASD:atrial septal defect; CHARGE:posterior coloboma,heart defect,choanal atresia,retardation,genital and ear abnormalities PDA:patent ductus arteriosus VSD:Ventricular septal defect
What are the clinical features of congenital heart disease
The various structural anomalies in this kind of disease can be grouped into three major groups based on what two things and name the three groups
What is a shunt
Depending on pressure relationships,shunts permit what?
What clinical manifestations are seen in the three groups and why
What is atresia?
In some disorders (give an example) an obstruction can be associated with a shunt (right to left through a VSD )
True or false
The altered hemodynamics of congenital heart disease usually lead to what?
However some defects result in what?
Explain hypoplasia and atrophy with regards to what the defects result in
Clinical Features
The various structural anomalies in congenital heart disease
can be assigned to three major groups based on their hemodynamic and clinical consequences:
(1) malformations
causing a left-to-right shunt;
(2) malformations causing a
right-to-left shunt (cyanotic congenital heart diseases); and
(3) malformations causing obstruction.
A shunt is an abnormal communication between cham- bers or blood vessels. Depending on pressure relationships, shunts permit the flow of blood from the left to the right side of the heart (or vice versa).
• With right-to-left shunt:a dusky blueness of the skin
(cyanosis) results because the pulmonary circulation is bypassed and poorly oxygenated blood enters the systemic circulation.
• Bycontrast,left-to-right shunts increase pulmonary blood
flow and are not associated (at least initially) with
cyanosis. However, they expose the low-pressure, low-
resistance pulmonary circulation to increased pressures
and volumes; these conditions lead to adaptive changes
that increase lung vascular resistance to protect the pulmonary bed, resulting in right ventricular hypertrophy and—eventually—failure. With time, increased pulmonary resistance also can cause shunt reversal (right to
Left) and late onset cyanosis
Some congenital anomalies obstruct vascular flow by narrowing the chambers, valves, or major blood vessels;
a malformation characterized by complete obstruction is called an atresia.
In some disorders (e.g., tetralogy of Fallot), an obstruction (pulmonary stenosis) can be asso- ciated with a shunt (right-to-left, through a VSD).
The altered hemodynamics of congenital heart disease usually lead to chamber dilation or wall hypertrophy. However, some defects result in a reduced muscle mass or chamber size; this is called hypoplasia if it occurs before birth and atrophy if it develops postnatally.
What are the most common type of congenital cardiac malformation
Left to right shunts include which three diseases?
Which type of left to right shunt disease causes increase only right ventricular and pulmonary outflow volumes?
Which type of left to right shunt disease causes both increased pulmonary blood flows and pressures ?
Manifestations of these shunts range in severity from no symptoms at all to fulminant heart failure.
True or false
Which sign is not an early feature of these left to right shunt defects
Prolonged left to right shunting with volume and pressure overloads eventually causes what what two things?
At that point what three things occur?
What is Eisenmenger syndrome?
Once significant pulmonary hypertension develops ,the structural defects of congenital heart disease are considered what?
This is the rationale for what?
Left-to-Right Shunts
Left-to-right shunts are the most common type of congeni- tal cardiac malformation. They include atrial septal defects (ASDs), ventricular septal defects (VSDs), and patent ductus arteriosus (PDA) (Fig. 10–2).
ASDs typically increase only right ventricular and pulmonary outflow volumes, while VSDs and PDAs cause both increased pulmonary blood flows and pressures.
Cyanosis is not an early feature of these defects. However, prolonged left-to-right shunting with volume and pressure overloads eventually causes pulmonary hypertension and secondarily right-sided pressures that exceed those on the left; at that point, reversal of blood flow occurs, with resultant right-to-left shunting, and the development of cyano- sis.
Such reversal of flow and shunting of unoxygenated blood into the systemic circulation is called Eisenmenger syndrome.
Once significant pulmonary hypertension develops, the structural defects of congenital heart disease are considered irreversible. This is the rationale for early surgical (or even nonsurgical) intervention.
How does patent foramen ovale occur
Foramen ovale allows oxygenated blood from where to flow from where to where thereby sustaining what?
At later stages of intrauterine development,what occurs ?
In 80 percent of cases ,the higher left sided pressures in the heart that occur at birth do what?
In the remaining 20percebt of cases,what results?
Although the flap is of adequate size to cover the foramen,what can occur?
What can also occur if right sides atrial pressures increase during what?
What is an atrial septal defect ?
A majority of ASDs are so called what in which what is insufficient to occlude what?
Atrial Septal Defects and Patent Foramen Ovale
During normal cardiac development patency is maintained between right and left atria by a series of ostia (primum and secundum) that eventually become the foramen ovale; this arrangement allows oxygenated blood from the mater- nal circulation to flow from the right to the left atrium, thereby sustaining fetal development.
At later stages of intrauterine development, tissue flaps (septum primum and septum secundum) grow to occlude the foramen ovale, and in 80% of cases, the higher left-sided pressures in the heart that occur at birth permanently fuse the septa against the foramen ovale.
In the remaining 20% of cases, a patent foramen ovale results; although the flap is of adequate size to cover the foramen, the unsealed septa can potentially allow transient right-to-left blood flow.
Paradoxical embo- lism, defined as venous emboli (e.g., from deep leg veins) that enter the systemic arterial circulation, may also occur if right-sided atrial pressures increase, such as with pulmo- nary hypertension or a Valsalva maneuver during sneezing or bowel movements.
In contrast to a patent foramen ovale, an ASD is an abnormal fixed opening in the atrial septum that allows unrestricted blood flow between the atrial chambers.
A majority (90%) of ASDs are so-called ostium secundum defects in which growth of the septum secundum is insuf- ficient to occlude the second ostium.(a mouthlike opening in a bodily part (such as a fallopian tube or a blood vessel), an opening into a vessel or cavity of the body.)
What is the morphology of ostium secundum ASDs
Hemodynamically significant lesions are accompanied by what four things reflecting the effects of what?
Ostium primum ASDs occur where and can be associated with what abnormalities reflecting the close relationship between what and what?
In more severe cases,additional defects what include what and what?
Where are sinus venosus ASDs located and they’re often accompanied by what?
What are the clinical features of ASDs ,
Although VSDs are the most common congenital malfor- mations at birth (Table 10–1), many close spontaneously
True or false
What are the most common defects to be diagnosed in adults ?
ASDs initially cause what kind of shunts as a consequence of what?
In general, these defects are well tolerated, especially if they are less than 1 cm in diameter; even larger lesions do not usually produce any symptoms in childhood.
True or false
Over time, however what and what can cause pulmo- nary hypertension. What kind of closures are thus performed to reverse the hemodynamic abnor- malities and preempt the development of heart failure, paradoxical embolization, and irreversible pulmonary vas- cular disease.
Mortality is low, and postoperative survival is comparable to that for a normal population. True or false
MORPHOLOGY
Ostium secundum ASDs (90% of ASDs) typically are smooth-walled defects near the foramen ovale, usually without other associated cardiac abnormalities.
Hemody- namically significant lesions are accompanied by right atrial and ventricular dilation, right ventricular hypertrophy, and dilation of the pulmonary artery, reflecting the effects of a chronically increased volume load
. Ostium primum ASDs (accounting for 5% of these defects) occur at the lowest part of the atrial septum and can be associated with mitral and tricuspid valve abnormalities, reflecting the close relationship between development of the septum primum and the endo- cardial cushions.
In more severe cases, additional defects may include a VSD and a common atrioventricular canal.
Sinus venosus ASDs (accounting for another 5% of the cases) are located high in the atrial septum and often are accompanied by anomalous drainage of the pulmonary veins into the right atrium or superior vena cava.
Clinical Features
A majority of ASDs are asymptomatic until adulthood.. Consequently, ASDs—which are less likely to spontane- ously close—are the most common defects to be first diag- nosed in adults.
ASDs initially cause left-to-right shunts, as a consequence of the lower pressures in the pulmonary circulation and the right side of the heart.
chronic volume and pressure overloads
Surgical or intravascular ASD
Defects in the ventricular septum allow what? And constitute the most common what?
How is the ventricular septum normally formed?
Which part of the septum is the last part to develop ?
What is the site of approximately 90percent of VSDs?
Although more common at birth, most VSDs close spontaneously in childhood, so that the overall incidence in adults is lower than that for ASDs. Only 20% to 30% of VSDs occur in isolation; most are associated with other cardiac malformations.
True or false
What are the clinical features of VSDS(talk about the signs and symptoms of the small VSDs and the large VSDs)
What disease occurs earlier and more frequently with VSDs than with ASDs?
What is therefore indicated for large lesions?
Small or medium sized defects that produce jet lesions in the right ventricle which can cause endothelial damage also increase the risk for what?
Ventricular Septal Defects
Defects in the ventricular septum allow left-to-right shunt- ing and constitute the most common congenital cardiac anomaly at birth
The ventricular septum normally is formed by the fusion of a muscular ridge that grows upward from the apex of the heart to a thinner membranous partition that grows downward from the endocardial cushions.
The basal (membranous) region is the last part of the septum to develop and is the site of approximately 90% of VSDs.
Clinical Features:
Small VSDs may be asymptomatic, and roughly half of those in the muscular portion of the septum close sponta- neously during infancy or childhood.
Larger defects, however, result in chronic severe left-to-right shunting, often complicated by pulmonary hypertension and conges- tive heart failure.
Progressive pulmonary hypertension, with resultant reversal of the shunt and cyanosis, occurs earlier and more frequently with VSDs than with ASDs.
Early surgical correction is therefore indicated for such lesions.
Small or medium-sized defects that produce jet lesions in the right ventricle—which can cause endothelial damage—also increase the risk for development of infec- tive endocarditis.
In the morphology of VSDs ,the size and location of VSDS are what? Ranging from what to what?
In defects associated with a significant left to right shunt,what happens to the right ventricle and the pulmonary artery? And why?
MORPHOLOGY
The size and location of VSDs are variable (Fig. 10–3), ranging from minute defects in the membranous septum to large defects involving virtually the entire interventricular wall.
In defects associated with a significant left-to-right shunt, the right ventricle is hypertrophied and often dilated. The diam- eter of the pulmonary artery is increased, owing to the greater volume ejected by the right ventricle.
Vascular changes typical of pulmonary hypertension are common
Ductus arteriosus arises from where and joins the aorta to where?
What is the function of the ductus arteriosus during intrauterine life?
What happens tho the ductus shortly after birth in healthy term infants?
Complete obliteration of ductus occurs when ,leaving what?
When is ductal closure delayed?
These changes occur in response to which three things?
PDAs account for about 7% of congenital heart lesions (Table 10–1 and Fig. 10–2), and the great majority of these (90%) are isolated defects.
True or false
What are the clinical features of PDAs
Large PDA defects may lead to what syndrome with associated symptom of what and what disease?
While there is general agreement that isolated PDAs should be closed as early in life as is feasible, pres- ervation of ductal patency (by administering prostaglandin E) can be lifesaving when a PDA is the only means to sustain systemic or pulmonary blood flow ( example in infants with aortic or pulmonary atresia)
True or false
Patent Ductus Arteriosus
The ductus arteriosus arises from the left pulmonary artery and joins the aorta just distal to the origin of the left sub- clavian artery.
During intrauterine life, it permits blood flow from the pulmonary artery to the aorta, thereby bypassing the unoxygenated lungs.
Shortly after birth in healthy term infants, the ductus constricts and is function- ally closed after 1 to 2 days; these changes occur in response to increased arterial oxygenation, decreased pulmonary vascular resistance, and declining local levels of
prostaglandin E2.
Complete obliteration occurs within the first few months of extrauterine life, leaving only a strand of residual fibrous tissue known as the ligamentum arterio- sum.
Ductal closure often is delayed (or even absent) in infants with hypoxia (related to respiratory distress or heart disease).
True
Clinical Features
PDAs are high-pressure left-to-right shunts that produce harsh, “machinery-like” murmurs. The high-pressure shunt also predisposes affected patients to development of infective endocarditis.
A small PDA generally causes no symptoms, although larger defects eventually can lead to Eisenmenger syndrome with cyanosis and
congestive heart failure.
True
Cardiac malformations associated with right-to-left shunts are distinguished by? And why does it occur?
What are the two most important conditions associated with cyanotic congenital heart disease (look at the diagram on page 386 of 924 for the right to left shunt and 384 of 924 for the left to right shunt)
What are the three major clinical consequences of severe systemic cyanosis
Tetralogy of Fallot is the most common cause of cyanotic congenital heart disease and accounts for about 5% of all congenital cardiac malformations true or false
What are the four cardinal features of tetralogy of Fallot
All of the features of tetralogy of Fallot result from where? Leading to what?
Early cyanosis
This occurs because poorly oxygenated blood from the right side of the heart flows directly into the arterial circulation.
Two of the most important conditions associated with cyanotic congenital heart disease are tetralogy of Fallot and transposition of the great vessels (Fig. 10–4).
Clinical consequences of severe, systemic cyanosis include clubbing of the tips of the fingers and toes (hypertrophic osteoarthropathy), polycythemia, and paradoxical embolization.
Tetralogy of Fallot
The four cardinal features are (1) VSD; (2) right ventricular outflow tract obstruction (subpulmonic stenosis); (3) overriding of the VSD by the aorta; and (4) right ventricular hypertrophy
All of the features of tetralogy of Fallot result from anterosuperior displacement of the infundibular septum leading to abnormal septation between the pulmo- nary trunk and the aortic root.
State four things seen in the the morphology of the heart in Tetralogy of Fallot
What happens to the VSD un tetralogy Of Fallot
What is the major site if egress
Why is there obstruction of the right ventricular outflow
In such cases what are the only routes for blood to reach the lungs
MORPHOLOGY
The heart is large and “boot-shaped” as a consequence of right ventricular hypertrophy;
the proximal aorta is dilated, while the pulmonary trunk is hypoplastic. (Hypoplastic (left heart syndrome or HLHS is a birth defect that affects normal blood flow through the heart.)
The left-sided cardiac chambers are of normal size, while the right ventricu- lar wall is markedly hypertrophied, sometimes even exceed- ing the thickness of the left ventricle.
The VSD usually is large and lies in the vicinity of the membranous portion of the interventricular septum;
the aortic valve lies immediately over the VSD (overriding aorta) and is the major site of egress or exit for blood flow from both ventricles.
The obstruction of the right ventricular outflow most often is due to narrowing of the infundibulum (subpulmonic stenosis) but also can be caused by pulmonary valve stenosis or complete atresia of the valve and the proximal pulmonary arteries. In such cases, a persistent PDA or dilated bronchial arteries may be the only route for blood to reach the lungs.
What are the clinical features of tetralogy of Fallot(state the three hemodynamic consequences of Tetralogy of Fallot )
Clinical severity largely depends on what?
If pulmonic obstruction is mild,ToF resembles what and why?
More commonly, more severe degrees of pulmonic stenosis cause what?
By chance,what stops pulmonary hypertension from developing
What is the sequelae of cyanotic heart disease
Right to left shunting increases risk for which two diseases?
Complete surgical repair is possible with classic tetralogy of Fallot but is more complicated in the setting of pulmonary atresia.
True or false
What is pulmonary atresia
What causes progressive worsening of functional stenosis in a child as he or she grows and the heart increases in size
Clinical Features
The hemodynamic consequences of tetralogy of Fallot are right-to-left shunting, decreased pulmonary blood flow, and increased aortic volumes.
The clinical severity largely depends on the degree of the pulmonary outflow obstruction; even untreated, some patients can survive into adult life. Thus, if the pulmonic obstruction is mild, the condition resembles an isolated VSD because the high left-sided pres- sures cause only a left-to-right shunt with no cyanosis.
More commonly, more severe degrees of pulmonic stenosis cause early cyanosis.
Moreover, as the child grows and the heart increases in size, the pulmonic orifice does not expand proportionately, leading to progressive worsening of functional stenosis.
By chance,the pulmonic outflow stenosis protects the pulmonary vasculature from pressure and volume overloads, so that pulmonary hypertension does not develop, and right ventricular failure is rare.
Nev- ertheless, patients develop the typical sequelae of cyanotic heart disease, such as polycythemia (due to hypoxia) with attendant hyperviscosity and hypertrophic osteoarthropa- thy;
right-to-left shunting also increases the risk for infec- tive endocarditis and systemic embolization.
Pulmonary atresia is a birth defect (pronounced PULL-mun-airy ah-TREE-sha) of the heart where the valve that controls blood flow from the heart to the lungs doesn’t form at all. In babies with this defect, blood has trouble flowing to the lungs to pick up oxygen for the body
Atresia is a condition in which an orifice or passage in the body is closed or absent.
What is transposition of the great arteries
What are the great arteries?
What’s the function of the pulmonary artery and the aorta
State the atrium to ventricle connections
What is the functional outcome of transposition of great arteries
What happens to the right ventricle in transposition of great arteries and why
What is the function of PDA in patients with transposition
What is the result of the closing of the PDA in infants
Transposition of the Great Arteries
Transposition of the great arteries is a discordant or abnormal connec- tion of the ventricles to their vascular outflow. The embryo- logic defect is an abnormal formation of the truncal and aortopulmonary septa so that the aorta arises from the right ventricle and the pulmonary artery emanates from the left ventricle (Fig. 10–4, B).
(The normal is that the pulmonary artery emanates or connect to from the right ventricle and the aorta emanates from the left ventricle)
The “great arteries” in this anomaly refer to the aorta and the pulmonary artery, the two major arteries carrying blood away from the heart. In cases of transposition of the great arteries, these vessels arise from the wrong ventricle.
Pulmonary artery: the vessel that carries oxygen-depleted blood from the right ventricle to the lungs.
Aorta: the blood vessel through which oxygenated blood from the left ventricle enters the systemic circulation.
The atrium-to-ventricle con- nections, however, are normal (concordant), with the right atrium joining the right ventricle and the left atrium emp- tying into the left ventricle.
The functional outcome is separation of the systemic and pulmonary circulations, a condition incompatible with postnatal life unless a shunt such as a VSD exists for ade- quate mixing of blood and delivery of oxygenated blood to the aorta.
Indeed, VSDs occur in a third of cases and provide stable shunts (Fig. 10–4, B). There is marked right ventricular hypertrophy, since that chamber functions as the systemic ventricle; the left ventricle is atrophic, since it pumps only to the low-resistance pulmonary circulation.
Some patients with transposition of the great arteries have a patent foramen ovale or PDA that allows oxygenated blood to reach the aorta, but these tend to close; as a result, such infants typically require emergent surgical interven- tion within the first few days of life.
What are the clinical features of transposition of great arteries
What is the dominant manifestation or feature ?
What three things does the prognosis depend on?
Without surgery (even with stable shunting), most patients with uncorrected transposi- tion of the great arteries die within the first months of life. However, improved surgical techniques now permit definitive repair and such patients often survive into adulthood. True or false Congenital obstruction to blood flow can occur where? What are the three common examples of congenital obstruction of blood flow
Clinical Features
The dominant manifestation is cyanosis, with the progno- sis depending on the magnitude of shunting, the degree of tissue hypoxia, and the ability of the right ventricle to maintain systemic pressures.
Obstructive Lesions
Congenital obstruction to blood flow can occur at the level of the heart valves or more distally within a great vessel. Obstruction can also occur proximal to the valve, as with subpulmonic stenosis in tetralogy of Fallot.
Relatively common examples of congenital obstruction are pulmonic valve stenosis, aortic valve stenosis or atresia, and coarcta- tion of the aorta.
What is coarctation of the aorta
What’s the difference between aortic stenosis and aortic coarctation
Which gender is more affected?
What are the two classic forms of AC(look at the diagram on page 387 of 924)
Coarctation can occur as a solitary defect, but in more than half of the cases it is accompanied by what?
Which other four diseases can also be present?
What is the morphology of infantile coarctation?
What happens to the pulmonary trunk and why ?
Why is the right ventricle hypertrophied ?
What happens to the aorta in the adult coarctation?
What is the constricted segment made up of?
Proximal to the coarctation,what happens to the aortic arch and it’s branch vessels and the left ventricle
Coarctation of the aorta, postductal type. The coarctation is a segmental narrowing of the aorta (arrow). Such lesions typically mani- fest later in life than preductal coarctations. The dilated ascending aorta and major branch vessels are to the left of the coarctation. The lower extremities are perfused predominantly by way of dilated, tortuous col- lateral channels.
True or false
Aortic Coarctation
Coarctation (narrowing, or constriction) of the aorta is a common form of obstructive congenital heart disease
This spectrum is dichotomized by the idea that aortic coarctation occurs in the aortic arch, at or near the ductus arteriosis, whereas aortic stenosis occurs in the aortic root, at or near the aortic valve
AS is the narrowing of the aortic valve but AC is the narrowing of the aorta
AC is a birth defect but AS is due to age related progressive calcification or calcification of congenital bicuspid aortic valve
Males are affected twice as often as females, although females with Turner syndrome frequently have coarctation.
There are two classic forms (Fig. 10–5): (1) an “infantile” form featuring hypoplasia of the aortic arch proximal to a PDA and (2) an “adult” form consisting of a discrete ridgelike infolding of the aorta, adjacent to the ligamentum arterio- sum.
Coarctation can occur as a solitary defect, but in more than half of the cases it is accompanied by a bicuspid aortic valve.
Aortic valve stenosis, ASD, VSD, or mitral regurgita- tion also can be present.
MORPHOLOGY
“Infantile” (preductal) coarctation is characterized by circumferential narrowing of the aortic segment between the left subclavian artery and the ductus arteriosus; the ductus typically is patent and is the main source of (unoxygenated) blood delivered to the distal aorta.
The pulmonary trunk is dilated to accommodate the increased blood flow; because the right side of the heart now perfuses the body distal to the narrowed segment (“coarct”), the right ventricle typically is hypertrophied.
In the more common “adult” (postductal) coarcta- tion, the aorta is sharply constricted by a tissue ridge adja- cent to the nonpatent ligamentum arteriosum (Fig. 10–6).
The constricted segment is made up of smooth muscle and elastic fibers that are continuous with the aortic media.
Proxi- mal to the coarctation, the aortic arch and its branch vessels are dilated and the left ventricle is hypertrophied
True .
What is aortic valve stenosis
clinical manifestations of aortic coarctation depend almost entirely on what?
Infantile coarctation usually presents early in life as what?
In adult coarctation,what are the five classical features?
Exuberant col- lateral circulation “around” the coarctation often devel- ops through markedly enlarged intercostal and internal mammary arteries; expansion of the flow through these vessels can lead to radiographically visible “notching” of the ribs.
True or false?
In most cases significant coarctations are associated with what ? And occasionally what
What procedures yield great results in coarctation
Try it summarize congenital heart disease
(What do CHD represent? What causes them? CHD lesions range from what to what? What causes contribute to the lesions? What diseases are mostly associated with left to right shunts?
What do lesions (the diseases) in the left to right shunts result in?
Causes of right to left shunts?
These lesions or causes cause what? And are associated with what three things?
Clinical severity of obstructive lesions depends on what?)
Aortic valve stenosis causes a thickening and narrowing of the valve between the heart’s main pumping chamber (left ventricle) and the body’s main artery (aorta). The narrowing creates a smaller opening for blood to pass through, reducing or blocking blood flow from the heart to the rest of the body.
Clinical Features
Clinical manifestations depend almost entirely on the severity of the narrowing and the patency of the ductus arteriosus.
- PreductalcoarctationwithaPDAusuallypresentsearlyin life, classically as cyanosis localized to the lower half of the body; without intervention, most affected infants do not survive the neonatal period.
- Postductal coarctation without a PDA usually is asymp- tomatic, and the disease may remain unrecognized well into adult life. Classically, there is upper extremity hypertension paired with weak pulses and relative hypotension in the lower extremities, associated with symptoms of claudication and coldness.
In most cases, significant coarctations are associated with systolic murmurs and occasionally palpable thrills.
Balloon dilation or surgical resection with end-to-end anastomosis (or replacement of the affected aortic segment by a pros- thetic graft) yields excellent results.
SUMMARY
Congenital Heart Disease
• Congenital heart disease represents defects of cardiac chambers or the great vessels; these either result in shunt- ing of blood between the right and left circulation or cause outflow obstructions. Lesions range from relatively asymptomatic to rapidly fatal. Environmental (toxic or infectious) and genetic causes both contribute.
• Left-to-right shunts are the most common and typically are associated with ASDs, VSDs, or a PDA. These lesions result in chronic right-sided pressure and volume over- loads that eventually cause pulmonary hypertension with reversal of flow and right-to-left shunts with cyanosis (Eisenmenger syndrome).
• Right-to-left shunts most commonly are caused by tetral- ogy of Fallot or transposition of the great arteries.These lesions cause early-onset cyanosis and are associated with
polycythemia, hypertrophic osteoarthropathy, and para-
doxical embolization.
• Obstructive lesions include forms of aortic coarctation;
the clinical severity of these lesions depends on the degree of stenosis and the patency of the ductus arteriosus.)
Why is cardiac function is strictly dependent upon the continuous flow of oxygenated blood through the coronary arteries?
Ischemic heart disease is a broad term encompassing what three things?
IHD us a leading cause of mortality in US
In more than 90 percent of cases,IHD is a consequence of what? Therefore I less otherwise specified ,IHd is synonymous with what disease?
In most cases syndromes if IHD are late manifestations of what?
Less frequently,IHd can result from what four things ?
Manifestations of IHd are a direct consequence of what?
Clinical presentation of IHd may include which four cardiac syndromes(state and explain)
The term acute coronary syndrome is applied to what three catastrophic manifestations of IHD?
ISCHEMIC HEART DISEASE
Since cardiac myocytes generate energy almost exclusively through mitochondrial oxidative phosphorylation, cardiac function is strictly dependent upon the continuous flow of oxygenated blood through the coronary arteries.
Ischemic heart disease (IHD) is a broad term encompassing several closely related syndromes caused by myocardial ischemia— an imbalance between cardiac blood supply (perfusion) and myocardial oxygen and nutritional requirements.
In more than 90% of cases, IHD is a consequence of reduced coronary blood flow secondary to obstructive atherosclerotic vas- cular disease.
Thus, unless otherwise specified, IHD usually is synonymous with coronary artery disease (CAD).
In most cases, the syndromes of IHD are the late manifestations of coronary atherosclerosis that has been gradually building for decades (beginning even in child- hood or adolescence).
Less frequently, IHD can result from increased demand (e.g., with increased heart rate or hypertension); diminished blood volume (e.g., with hypotension or shock); diminished oxygenation (e.g., due to pneumonia or CHF); or diminished oxygen-carrying capacity (e.g., due to anemia or carbon mon- oxide poisoning).
The manifestations of IHD are a direct consequence of the insufficient blood supply to the heart.
The clinical pre- sentation may include one or more of the following cardiac syndromes:
• Angina pectoris(literally,“chest pain”):Ischemia induces pain but is insufficient to cause myocyte death. Angina can be stable (occurring predictably at certain levels of exertion), can be caused by vessel spasm (Prinzmetal angina), or can be unstable (occurring with progressively less exertion or even at rest).
• Acutemyocardialinfarction(MI):Theseverityorduration of ischemia is sufficient to cause cardiomyocyte death.
• ChronicIHDwithCHF:Progressivecardiacdecompensa- tion after acute MI, or secondary to accumulated small ischemic insults, eventually precipitates mechanical pump failure.
• Sudden cardiac death (SCD): This can occur as a conse- quence of tissue damage from MI, but most commonly results from a lethal arrhythmia without myocyte necro- sis (see later under “Arrhythmias”).
The term acute coronary syndrome is applied to any of the three catastrophic manifestations of IHD—unstable angina, acute MI, and SCD.
Epidemiology
Nearly a half-million Americans die annually of IHD. As troubling as this toll is, it represents a spectacular advance over previous eras; since peaking in 1963, the mortality related to IHD in the United States has declined by 50%. The improvement can be largely attributed to interventions that have diminished cardiac risk factors (behaviors or conditions that promote atherosclerosis) (Chapter 9), in particular smoking cessation programs, hypertension and diabetes treatment, and use of cholesterol- lowering agents. To a lesser extent, diagnostic and therapeu- tic advances have also contributed; these include aspirin prophylaxis, better arrhythmia control, coronary care units, thrombolysis for MI, angioplasty and endovascular stent- ing, and coronary artery bypass graft surgery. Maintaining this downward trend in mortality will be particularly chal- lenging given the predicted longevity of “baby boomers,” as well as the epidemic of obesity that is sweeping the United States and other parts of the world.
True or false
What is the pathogenesis of IHD (IHD is primarily a consequence of what? And what causes that?
Atherosclerotic narrowing can affect which of the coronary arteries singly or in any combination?
Clinically significant plaques tend to occur where?
What are the secondary branches involved ?
What obstructions are asymptomatic and which result in stenosis and cause symptoms
A fixed stenosis that occludes how much of the vascular lumen can lead to inadequate what ?
if an atherosclerotic lesion progressively occludes a coronary artery at a sufficiently slow rate over years, what can be done to provide compensatory blood flow for the area at risk ?
Such collateral perfusion can subsequently protect against MI even if what happens?
What happens with acute coronary blockage
True
IHD is primarily a consequence of inadequate coro- nary perfusion relative to myocardial demand.This imbalance occurs as a consequence of the combina- tion of preexisting (“fixed”) atherosclerotic occlu- sion of coronary arteries and new, superimposed thrombosis and/or vasospasm.(sudden constriction of a blood vessel, reducing its diameter and flow rate.)
Thrombosis occurs when blood clots block veins or arteries.
Atherosclerotic narrowing can affect any of the coronary arteries—left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA)—singly or in any combination.
Clinically significant plaques can be located any- where but tend to occur within the first several centimeters of the LAD and LCX, and along the entire length of the RCA.
Sometimes, secondary branches also are involved (i.e., diago- nal branches of the LAD, obtuse marginal branches of the LCX, or posterior descending branch of the RCA).
Fixed obstructions that occlude less than 70% of a coro- nary vessel lumen typically are asymptomatic, even with exer- tion. In comparison, lesions that occlude more than 70% of a vessel lumen—resulting in so-called critical stenosis— generally cause symptoms in the setting of increased demand; with critical stenosis, certain levels of exertion predictably cause chest pain, and the patient is said to have stable angina.
A fixed stenosis that occludes 90% or more of a vascular lumen can lead to inadequate coronary blood flow with symptoms even at rest—one of the forms of unstable angina (see later discussion).
Of importance, if an atherosclerotic lesion progressively occludes a coronary artery at a sufficiently slow rate over years, remodelling of other coronary vessels may provide compensatory blood flow for the area at risk; such collat- eral perfusion can subsequently protect against MI even if the vessel eventually becomes completely occluded.
Unfor- tunately, with acute coronary blockage, there is no time for collateral flow to develop and infarction results.
Continuation of pathogenesis of IHD
State the three elements that contribute to the development and consequences of coronary atherosclerosis and explain how they contribute
What are the four causes of ischemic heart disease and give an example for each
The following elements contribute to the development and consequences of coronary atherosclerosis:
• Inflammation plays an essential role at all stages of
atherosclerosis, (when there is an injury to the vessel wall,lipids try to get closer to the injury . When white blood cells see this they also try to get closer and they worsen the situation by hardening the lipids and forming plaques and this causes atherosclerosis,)from inception to plaque rupture .Atherosclerosis begins with the interaction of endothelial cells and circulating leukocytes, resulting in T cell and macrophage recruitment and activation. These cells drive subsequent smooth muscle cell accumulation and proliferation, with variable amounts of matrix produc- tion, all overlying an atheromatous core of lipid, choles- terol, calcification, and necrotic debris. At later stages, destabilization of atherosclerotic plaque occurs through macrophage metalloproteinase secretion.
• Thrombosis associated with a disrupted plaque often triggers the acute coronary syndromes. Partial vascular occlusion by a newly formed thrombus on a disrupted atherosclerotic plaque can wax and wane with time and lead to unstable angina or sudden death; alter- natively, even partial luminal occlusion by thrombus can compromise blood flow sufficiently to cause a small infarc- tion of the innermost zone of the myocardium (suben- docardial infarct). Organizing thrombi produce potent activators of smooth muscle proliferation, which can con- tribute to the growth of atherosclerotic lesions. Mural thrombus in a coronary artery can also embolize; indeed, small emboli can be found in the distal intramyocardial circulation (along with associated microinfarcts) at autopsy of patients who have had unstable angina. In the most serious extreme, completely obstructive thrombus over a disrupted plaque can cause a massive MI.
• Vasoconstriction directly compromises lumen diame- ter; moreover, by increasing local mechanical shear forces, vessel spasm can potentiate plaque disruption. Vasocon- striction in atherosclerotic plaques can be stimulated by (1) circulating adrenergic agonists, (2) locally released platelet contents, (3) imbalance between endothelial cell– relaxing factors (e.g., nitric oxide) and –contracting factors (e.g., endothelin) due to endothelial dysfunction, and (4) mediators released from perivascular inflammatory cells.
Increased demand (e.g., with increased heart rate or hypertension)
•Diminished blood volume (e.g., with hypotension or shock)
•Diminished oxygenation (e.g., due to pneumonia or CHF)
•Diminished oxygen-carrying capacity (e.g., due to anemia or carbon monoxide poisoning).
Explain acute plaque change as another factor that causes onset of IHD
Acute Plaque Change. Onset of myocardial ischemia depends not only on the extent and severity of fixed athero- sclerotic disease but also on dynamic changes in coronary plaque morphology true or false
In most patients, unstable angina, infarction, and often sudden cardiac death occur because of what?
What is the initiation event of acute plaque change
State the mechanism of injury involved in the initiation event
In addition,what else can cause plaque change?
Factors that trigger acute plaque change are believed to act how?
What are the two ways intrinsic aspects of plaque composition and structure and extrinsic factors such as blood pressure and platelet reactivity contribute to acute plaque change
Where do fissures frequently occur?
Fibrous caps continuously remodel true or false?
What determines their mechanical strength and plaque stability?
What produces collagen and what degrades it?
What kind of lawsuits are more vulnerable to rupture?
What’s the benefit of statins (state how they work) in IHD and CAD ?
How does adrenergic stimulation put physical stress on plaque?
What may underlie the observation that the incidence of acute MI is highest between what times ?
What else may lead to adrenergic stimulation and what does it explain ?
In majority of cases ,what’s the characteristic of the vulnerable culprit lesion?
Angina symptoms typically o cut with what?
Pathologic and clinical studies show that two thirds of ruptured plaques are 50% stenotic or less before plaque rupture, and 85% exhibit initial stenotic occlusion of 70% or less. Thus, the worrisome conclusion is that a large number of asymptomatic adults are at significant risk for a catastrophic coronary event. At present, it is impossible to predict plaque rupture in any given patient. True or false
What are common,repetitive and often clinically silent complications of atheromas?
What is an important mechanism by which atherosclerotic lesions progressively enlarge?
True
. In most patients, unstable angina, infarction, and often sudden cardiac death occur because of abrupt plaque change followed by thrombosis—hence the term acute coronary syn- drome (Fig. 10–7).
The initiating event typically is sudden disruption of par- tially occlusive plaque.
More than one mechanism of injury may be involved: Rupture, fissuring, or ulceration of plaques can expose highly thrombogenic constituents or underlying subendothelial basement membrane, leading to rapid thrombosis.
In addition, hemorrhage into the core of plaques can expand plaque volume, thereby acutely exac- erbating the degree of luminal occlusion.
In unstable angina some part of the plaque breaks off causing it to flop backwards blocking blood flow but when it moves back , n blood flow is better thats why it can even occur at rest or during exertion cuz it depends on the plaque flapping backwards or going back to bormal
Factors that trigger acute plaque change are believed to act by increasing the lesion’s susceptibility to disruption by mechanical stress
Both intrinsic aspects of plaque composi- tion and structure and extrinsic factors, such as blood pressure and platelet reactivity, may contribute as follows:
• Plaques that contain large atheromatous cores, or have
thin overlying fibrous caps are more likely to rupture, and are therefore termed “vulnerable.”
Fissures frequently occur at the junction of the fibrous cap and the adjacent normal plaque-free arterial segment, where the mechanical stresses are highest and the fibrous cap is thin- nest.
Fibrous caps also are continuously remodeling; their overall balance of collagen synthesis versus degradation determines mechanical strength and plaque stability. Col- lagen is produced by smooth muscle cells and degraded by the action of metalloproteases elaborated by macro- phages.
Consequently, atherosclerotic lesions with a paucity of smooth muscle cells or large numbers of inflam- matory cells are more vulnerable to rupture.
Of interest, statins (inhibitors of hydroxymethylglutaryl Co-A reduc- tase, a key enzyme in cholesterol synthesis) may be of additional benefit in CAD and IHD by reducing plaque inflammation and increasing plaque stability,beyond their cholesterol-lowering effects.
• Influences extrinsic to plaque also are important. Adrenergic stimulation can put physical stress on the plaque by causing hypertension or local vasospasm.
Indeed, the surge in adrenergic stimulation associated with awakening and rising may underlie the observation that the incidence of acute MI is highest between 6 AM and 12 noon. Intense emotional stress also leads to adrenergic stimulation, explaining the association of natural catastrophes such as earthquakes and floods with secondary waves of MIs in susceptible individuals.
In a majority of cases, the vulnerable “culprit lesion” in patients who suffer an MI was not critically stenotic or even symptomatic before its rupture.
As noted previously, anginal symptoms typically occur with fixed lesions exhibiting greater than 70% chronic occlusion.
True
Plaque disruption and ensuing nonocclusive thrombosis also are common, repetitive, and often clinically silent com- plications of atheromas.
The healing of such subclinical plaque disruption and overlying thrombosis is an important mecha- nism by which atherosclerotic lesions progressively enlarge (Fig. 10–7).
What is an atheroma
What’s the difference between it and a plaque
Atheroma is the medical term for the buildup of materials that adhere to arteries. Among others, these include: fat. cholesterol. calcium
Atheromatous plaque (atheromas) can develop on the intima of large- and medium-caliber arteries. Plaque is an accumulation of cholesterol and other lipid compositions that forms on the inner walls of vessels. This deposit is covered by a cap of fibrosity.
What is angina pectoris
What causes the pain
What three variants of angina pectoris are recognized?
How is stable angina pain classically described?(SOCRATES)
What causes variant angina?
Where do the spasms occur?
Variant angina typically responds promptly to what drugs?
What is unstable angina characterized by?
What four things is this kind of angina associated with?
Which kind of angina is often the harbinger of MI caused by complete vascular occlusion
Angina Pectoris
Angina pectoris is an intermittent chest pain caused by tran- sient, reversible myocardial ischemia.
The pain probably is a consequence of the ischemia-induced release of adenosine, bradykinin, and other molecules that stimulate the auto- nomic afferents.
Three variants are recognized:
•Typical or stable angina is predictable episodic chest pain associated with particular levels of exertion or some other increased demand (e.g., tachycardia).
The pain is classically described as a crushing or squeezing subster- nal sensation, that can radiate down the left arm or to the left jaw (referred pain). The pain usually is relieved by rest (reducing demand) or by drugs such as nitroglycerin, a vasodilator that increases coronary perfusion.
• Prinzmetal or variant angina occurs at rest and is caused by coronary artery spasm. Although such spasms typi- cally occur on or near existing atherosclerotic plaques, completely normal vessel can be affected. Prinzmetal angina typically responds promptly to vasodilators such as nitroglycerin and calcium channel blockers.
•Unstable angina(also called crescendo angina)is character- ized by increasingly frequent pain, precipitated by progressively less exertion or even occurring at rest.
Unstable angina is associated with plaque disruption and superimposed thrombosis, distal embolization of the thrombus, and/or vasospasm; it is often the harbinger (a person or thing that announces or signals the approach of another ) of MI, caused by complete vascular occlusion.
What is Myocardial infarction
Roughly 1.5 million people per year in the United States suffer an MI; of these, one third die half before they can get to the hospital. Nevertheless, approximately 10% of MIs occur before age 40, and 45% occur before age 65. Blacks and whites are equally affected True or false
What is the major underlying cause of IHD ? At what age can MIs occur ?
Frequency of MIs rises progressively with what factors?
Which gender is at a greater risk? And why?
Myocardial infarction (MI), also commonly referred to as “heart attack,” is necrosis of heart muscle resulting from isch- emia.
The major underlying cause of IHD is atherosclerosis; while MIs can occur at virtually any age, the frequency rises progressively with increasing age and with increasing atherosclerotic risk factors .
. Men are at significantly greater risk than women, although the gap progressively narrows with age. In general, women tend to be remarkably protected against MI during their reproductive years. However, menopause— with declining estrogen production—is associated with exacerbation of coronary artery disease and IHD is the most common cause of death in elderly women.
What’s the pathogenesis of MI
Majority of MIs are caused by?
In most instances, disruption of preexisting atherosclerotic plaque serves as the nidus for what three things?
In 10percent of MIs transmural infarction occurs in the absence of ?
Such infarcts are mostly attributable to what?
Occasionally, especially with infarcts limited to the innermost (subendocar- dial) myocardium what may be absent
In such cases what leads to marginal perfusion if the heart?
In this setting, what can lead to ischemic necrosis of the myocardium most distal to the epicardial vessels.?
Finally, ischemia without detectable atherosclerosis or thromboembolic disease can be caused by what disorders?
What is a transmural infarction ,how does it occur and what’s the difference between this infarction and subendocardial infarction
PATHOGENESIS
The vast majority of MIs are caused by acute coro- nary artery thrombosis (Fig. 10–7).
In most instances, disruption of preexisting atherosclerotic plaque serves as the nidus for thrombus generation, vascular occlusion, and sub- sequent transmural infarction of the downstream myocar- dium. In 10% of MIs, however, transmural infarction occurs in the absence of occlusive atherosclerotic vascular disease;
such infarcts are mostly attributable to coronary artery vaso- spasm or to embolization from mural thrombi (e.g., in the setting of atrial fibrillation) or valve vegetations.
Occasionally, especially with infarcts limited to the innermost (subendocar- dial) myocardium, thrombi or emboli may be absent. In such cases, severe diffuse coronary atherosclerosis leads to mar- ginal perfusion of the heart.
In this setting, a prolonged period of increased demand (e.g., due to tachycardia or hyperten- sion) can lead to ischemic necrosis of the myocardium most distal to the epicardial vessels.
Finally, ischemia without detectable atherosclerosis or thromboembolic disease can be caused by disorders of small intramyocardial arterioles, including vasculitis, amyloid deposition, or stasis, as in sickle cell disease.
transmural myocardial infarction refers to a myocardial infarction that involves the full thickness of the myocardium.
When a sudden, complete occlusion of a coronary artery prevents blood flow from reaching an area of myocardium, the resulting transmural myocardial ischemia 4–6 is manifested by deviation of the ST segment toward the involved region. An acute ST-elevation myocardial infarction occurs due to occlusion of one or more coronary arteries, causing transmural myocardial ischemia which in turn results in myocardial injury or necrosis.
The transmural type usually consisted of yellowish-brown coagulation necrosis in the center of an infarcted focus and coagulative myocytolysis at the marginal zone. The subendocardial type was characterized by coagulative myocytolysis throughout the entire focus.
In a typical MI state the four sequence of events that occur
Where is the evidence for these events derived from?
Angiography performed within 4 hours of the onset of MI demonstrates what ?
What is seen when it’s performed 12-24 hours after onset of symptoms
How do some occlusions clear spontaneously?
What are the therapeutic implications of the sequence of event that occur
Coronary Artery Occlusion. In a typical MI, the fol- lowing sequence of events takes place:
• An atheromatous plaque is suddenly disrupted by intra-
plaque hemorrhage or mechanical forces, exposing sub- endothelial collagen and necrotic plaque contents to the blood.
• Platelets adhere, aggregate, and are activated, releasing thromboxane A2, adenosine diphosphate (ADP), and serotonin—causing further platelet aggregation and vaso- spasm (Chapter 3).
• Activation of coagulation by exposure of tissue factor and other mechanisms adds to the growing thrombus.
• Within minutes, the thrombus can evolve to completely occlude the coronary artery lumen.
The evidence for this scenario derives from autopsy studies of patients dying of acute MI, as well as imaging studies dem- onstrating a high frequency of thrombotic occlusion early after MI.
Angiography performed within 4 hours of the onset of MI demonstrates coronary thrombosis in almost 90% of cases.
When angiography is performed 12 to 24 hours after onset of symptoms, however, evidence of thrombosis is seen in only 60% of patients, even without intervention. Thus, at least some occlusions clear spontaneously through lysis of the thrombus or relaxation of spasm.
This sequence of events in a typical MI also has therapeutic implications: Early thrombolysis and/or angioplasty can be highly successful in limiting the extent of myocardial necrosis.
