Heart Pathology (GOMEZ) Flashcards
1
Q
do the flashies for before 41
A
do it
2
Q
coarctation of the aorta
A
Infantile form – hypoplasia of aorta prior to patent ductus arteriosus (cyanosis of inferior body and weak femoral pulses)
Adult form – ridge-like fold opposite ligamentum arteriosus (HTN upper extremities with low pressure and pulses in lower extremities). Pansystolic murmur
Higher pressures in the upper arms, neck, head
Pressure drop in the legs (top half will be pink, bottom half blue)
kidneys sense lower pressure - turn on RAAS
treat with surgery
3
Q
pulmonary stenosis and atresia
A
– smaller the orifice the worse the cyanosis
4
Q
Supravalvular aortic stenosis
A
– elastin gene mutation with aortic dysplasia (thickening)
5
Q
williams-beuren syndrome
A
deletion of about 28 genes from chromosome 7 with ELN gene (elastin) haploinsufficiency, hypercalcemia, glucose intolerance, facial and cognitive defects
6
Q
ischemic heart disease
A
imbalance between the supply (perfusion) and demand of the heart for oxygenated blood
90% due to atherosclerotic coronary arterial obstruction
Leading cause of death in US for both males & females
Higher incidence in males than females
in premenopausal females IHD is uncommon
“Diminished coronary artery perfusion relative to myocardial demand” from interaction one or more of the following:
Fixed atherosclerotic narrowing (stenosis) of coronaries
Thrombosis overlying a disrupted plaque
Localized platelet aggregation
Vasospasm
Emboli (valvular vegetations, etc.)
Hypotension (if there is atherosclerosis)
Coronary artery vasculitis
Fixed obstruction >75% required to cause symptoms with exercise
Fixed obstruction > 90% can lead to ischemia at rest
7
Q
4 clinical syndromes of Ischemic heart disease
A
Sudden Cardiac Death
Angina Pectoris
Chronic IHD with heart failure- killing myocytes progressively
Myocardial Infarction (MI)
8
Q
role of atherosclerotic heart disease in ischemic heart disease
A
Acute plaque change:
Rupture/Fissuring
Erosion/Ulceration
Hemorrhage into an atheroma (plaque)
***abrupt plaque change followed by thrombosis tends to occur in plaques with large cores and thin caps
Acute plaque change does not usually occur in severely stenotic portions of arteries
2/3 of acute ruptures with subsequent thrombosis occur in vessels that are narrowed less than 50%
85% have stenosis < 70%
Plaques tend to involve entire RCA and proximal LAD and LCX
worst scenario = thrombosis that blocks the lumen –> leads to unstable angina and can lead to MI
9
Q
stable angina
A
> 75 % stenosis
no plaque disruption
no plaque associated thrombus
10
Q
unstable angina
A
variable stenoses
plaque distruption frequent
nonocclusive often with thromboemboli
11
Q
transmural myocardial infarction
A
Ischemic necrosis involves >50%*** of the ventricular wall thickness
75% across is transmural as well
Commonly associated with acute plaque change with thrombosis
variable stenosis
frequent plaque disruption
12
Q
subendocardial MI
A
Area of ischemic necrosis limited to the inner 1/3 or at most the inner 1/2
May occur as a result of acute plaque change and thrombosis
May result from prolonged and severe reduction in systemic blood pressure ,as encountered in shock
variable stenoses
variable plaque disruption
Widely variable, may be absent, partial/complete, or lysed
(plaque associated thrombus)
why does a small band of subendocardial tissue remain visible ?
13
Q
sudden death>
A
usually severe stenoses
frequent plaque disruption
often small platelet aggregates or thrombi and /or thromboemboli
14
Q
Prinzmetal angina
A
sustained vasospasm causing angina (chest pain- relieved by Nitroglycerin)
no significant atherosclerosis
very similar to cocaine abuse
15
Q
Cardiac Raynaud
A
cold or emotion induced cardiac vasospasm
- If vasospasm is > 20 minutes can lead to myocardial infarction
16
Q
Takotsubo cardiomyopathy
A
dilated cardiomyopathy secondary to emotional or physical stress with normal coronary angiogram (sometimes due to vasospasm)
17
Q
sudden cardiac death
A
Unexpected death from cardiac causes early after onset of symptoms (1 to 24 hours) or sudden death from cardiac cause without antecedent acute symptoms
In US: > 400,000 deaths annually
Mechanism: Most often a lethal arrhythmia from electrical instability (irritability); ventricular fibrillation (80%) or asystole
Most commonly caused by Ischemic Heart Disease (IHD)
Should suspect non-ischemic SCD in younger people
– particularly in people < 40 years with SCD!!!!!
Possibilities:
Hypertrophic cardiomyopathy (18%)
Coronary artery anomalies (9%)
Myocarditis (3%)
Arrhythmogenic right ventricular cardiomyopathy (2%)
Ion channelopathies (2%)
Commotio cordis (3%) due to sudden v-fib caused by blunt impact to the heart
Congenital structural abnormalities (<1%)
18
Q
long QT syndrome
A
manifests as arrhythmias associated with excessive prolongation of the cardiac repolarization; patients often present with stress-induced syncope or sudden cardiac death (SCD), and some forms are associated with swimming.
19
Q
Short QT syndrome
A
patients have arrhythmias associated with abbreviated repolarization intervals; they can present with palpitations, syncope, and SCD.
20
Q
Brugada syndrome
A
manifests as ECG abnormalities (ST segment elevations and right bundle branch block) in the absence of structural heart disease; patients classically present with syncope or SCD during rest or sleep, or after large meals.
21
Q
CPVT syndrome
A
does not have characteristic ECG changes; patients often present in childhood with life-threatening arrhythmias due to adrenergic stimulation (stress-related).
22
Q
what are channelopathies
A
Disorders of K+, Na+, or Ca++ channel structure or accessory proteins involved in channel function
Mostly autosomal dominant
23
Q
chronic ischemic heart disease
A
Insidious onset of congestive heart failure in patients who have had past myocardial infarcts (MIs) or angina
patients usually have history of HTN
Cardiomegaly with left ventricular hypertrophy & dilatation
Evidence of previous healed MIs or ischemia (areas of myocardial fibrosis)
Develop arrhythmias, congestive heart failure and MIs
Chronic ischemia that does not
cause necrosis can lead to
hypokinetic myocardium with
myocyte hibernation
24
Q
angina pectoris
A
Paroxysmal (anytime- usually stress induced) and usually recurrent attacks of substernal or precordial chest discomfort…..
ischemia doesn’t last long enough to kill myocyte (<20 min) so its reversible
Caused by transient myocardial ischemia that falls short of inducing the cellular necrosis that defines infarction
25
stable angina
↓perfusion 2ry to fixed-narrowing
Most common form of angina
Can be provoked by increased cardiac demand (emotion, exercise)
Usually relieved by rest or sublingual nitroglycerin
26
unstable angina (crescendo, pre-infarction)
usually have acute plaque change partially narrowing the lumen- not 100% occlusion
how do you know its unstable? worse symptoms, happens more often, doesn't go away as quickly with nitro
Progressive increase in frequency and severity of attacks
Provoked by progressively less effort and may occur at rest
May be relieved by rest or sublingual nitroglycerin
27
Prinzmetal angina
episodic angina due to coronary artery spasm
Relieved by rest, nitroglycerin or calcium channel blockers
28
myocardial infarction
Definition: The death of cardiac muscle from ischemia
Epidemiology
Frequency of MI rises progressively with increasing age
10% MIs occur in individuals under age 40
40-45% occur in individuals under age 65
Men at far higher risk than women – women are protected during premenopausal period (but not post menopause w/ or w/o estrogen)
Lipid risk factors account for 50-60 % of MIs
Genetic risk factors for thrombosis (e.g., Prothrombin mutations, Hyperhomocystenemia) account for another 10-20%
29
peak incidence of MI?
peak incidence between 6 am and noon
| intense emotional stress
30
typical sequence of events in MI
90%
Initial sudden change in plaque
Immediate formation of initial platelet plug over plaque
Vasospasm from platelet adhesion (vasoactive substances from platelets)
Propagation of platelet plug into stable clot via extrinsic clotting system
Within minutes, clot occludes lumen of the involved vessel
(thrombosis with coronary occlusion)
10% of transmural MI patients have no associated atherosclerosis
Vasospasm- isolated, prolonged, severe (e.g., cocaine)
Emboli- left atrium (atrial fibrillation) or ventricle (mural thrombus) , valve vegetations, paroxysmal emboli
Vasculitis, hemoglobinopathy, etc.
31
onset of ATP depletion
seconds
32
loss of contractility
<2 min
33
ATP reduced to
50%
10%
50 --> 10 min
| 10% - 40 min
34
Irreversible cell injury (necrosis)
20-40 min
35
microvascular injury
>1hr
36
complete unsalvageable necrosis
6 hrs
37
reversible stage of MI
For approximately 30 minutes after the onset of even the most severe ischemia, myocardial injury is potentially reversible.
Thereafter, progressive loss of viability occurs that is complete by 6 to 12 hours. The benefits of reperfusion are greatest when it is achieved early, and are progressively lost when reperfusion is delayed.
38
0-1/2 hour of MI
no gross feature changes
no light micro findings
Relaxation of myofibrils; glycogen loss; mitochondrial swelling
reversible
39
1/2 hr to 4 hr post MI
no gross feature changes
usually no light micro findings
variable waviness of fibers at border
electron microscopic findings:
Sarcolemmal disruption; mitochondrial amorphous densities
irreversible
40
4-12 hour post MI
dark mottling gross features
usually none though
light microscopic
early coagulation necrosis, edema, hemorrhage
cellular changes
41
12 - 24 hrs post MI
dark mottling gross features
Ongoing coagulation necrosis; pyknosis of nuclei;
myocyte hypereosinophilia;
marginal contraction band necrosis;
early neutrophilic infiltrate***
acute MI - any infarct will have the first cells coming in be neutrophils (so doesn't always = infection)
42
1-3 days post MI
mottling with yellow-tan infarct center
Coagulation necrosis, with loss of nuclei and striations;
brisk interstitial infiltrate of neutrophils***
43
3-7 days post MI
gross features:
Hyperemic border; central yellow-tan softening
light micros
Beginning disintegration of dead myofibers, with dying neutrophils; early phagocytosis of dead cells by macrophages*** at infarct border
44
>2mo post MI
gross features:
scar
dense collagenous scar
can no longer tell WHEN the infarct occurred. scar is a scar is a scar
45
7-10 days post MI
Gross- maximally yellow tan and soft wutg
Well-developed phagocytosis of dead cells; early formation of fibrovascular granulation tissue at margins
myocytes are gone
around 1 week or so the wall may rupture
46
apex of heart
LAD- 40-50 %
| most commonly blocked vessel
47
RCA
blockage tends to give more arrhythmia's
distal RCA- most likely hits posterior wall
48
myocardial infarction modification by reperfusion
time limit on reperfusion?
Goal - salvage ischemic myocardium from potential infarction by restoration of tissue perfusion as quickly as possible (reperfusion)
Intervention techniques include:
Lysis of thrombus by fibrinolytic therapy (Streptokinase, Urokinase, or tissue plasminogen activator (TPA)
Balloon angioplasty
Coronary artery bypass graft
when we reperfuse the heart, we cause injury! but you are still better off reperfusing and it takes time for the myocytes to start working again
Reperfusion beyond 6 hours does not appreciably reduce myocardial infarct size
49
pathologic changes associated with reperfusion?
Reperfusion-induced arrhythmias
Myocardial hemorrhage with contraction bands
Irreversible myocardial damage in addition to that caused by the initial episode of ischemia (reperfusion injury)
Microvascular injury with endothelial swelling (no-reflow)
Reversible “Myocardial stunning” (prolonged ischemic dysfunction) with heart failure for days
50
clinical features of MI
Classic acute onset symptoms and signs:
Severe substernal chest pain with radiation of pain down left arm, neck, jaw, epigastrium
Weak, rapid pulse
Sweating profusely (diaphoretic)
Nausea
Dyspnea (difficulty breathing) secondary to pulmonary congestion and edema
angina is reversible whereas MI is not (pain does not subside)
10-25% of MI patients may be asymptomatic during the acute cardiac event *diabetics, heart transplant patients (no neural connections in new heart)
Occurrence of the MI discovered by EKG (Q waves, ST-segment changes, T-wave inversion) or other types of testing (labs)
STEMI –ST segment Elevation Myocardial Infarct (transmural***)
NSTEMI – Non-ST segment Elevation Myocardial Infarct (subendocardial***)
51
troponin I, C, or T and creatine phosphokinase, MB fraction [CK-MB]
myoglobin
released myocyte proteins in MI !
damage to myocardium does NOT equal MI. must have other factors to diagnose
52
myoglobin
initial elevation 1-4 hr after MI
nonspecific early marker
myoglobin --used to exclude MI not to diagnose
peak at 6 hr
18-24 hrs time to return to baseline after MI
53
CK-MB
go up 3-12 hours after infarct
peak elevation 10-24 hr
48-72 hours is time to return to baseline after AMI
54
troponins
takes 3 hours for these to come up so most likely won't wait this long to get them to cath lab so look at other signs/symptoms
troponins stay elevated for 1-2 weeks
55
systemic (left-sided) HTN heart disease
criteria for diagnosis
Criteria for Diagnosis
1. Left ventricular hypertrophy (usually concentric) in the absence of other cardiovascular pathology that may have induce it.
2. A history or pathologic evidence of systemic hypertension
(BP > 140/90 mm Hg)
May present clinically with CHF or atrial arrythmias
56
HTN heart disease
Pulmonary right sided
Cor Pulmonale results from pulmonary disorders that cause chronic severe pulmonary hypertension.
Occurs with:
Pulmonary Parenchyma Disorders
Chronic Obstructive Pulmonary Disease (COPD)
Diffuse Interstitial Lung Disease
Pulmonary Vessel Disorders
Recurrent Pulmonary Embolism
Primary Pulmonary Hypertension
Chest Movement Disorders
Kyphoscoliosis
Right ventricle --> dilated and has thickened free wall and hypertrophied trabeculae
57
Cardiac valve dysfunction
causes what>
Stenosis***: failure of valve to open completely impeding forward flow
Almost always due to a primary valve cusp abnormality and virtually always a chronic disease
Insufficiency*** (regurgitation or incompetence): failure of a valve to close allowing reverse flow
- ->From intrinsic disease of valve cusp or an acquired structural abnormality of the supporting anatomic structures
- ->In addition to chronic disease, acute insufficiency syndromes may occur (e.g., rupture of a papillary muscle)
- ->Functional regurgitation – normal valve leaflets but problem with supporting structures (e.g. dilated annulus from ventricular dilatation)
“Pure” when only stenosis or insufficiency present
“Mixed” when both present in same valve
acquired stenoses of the aortic and mitral valves accounts for 2/3 of all valvular diseases
58
aortic stenosis
Calcification of anatomically normal and congenitally bicuspid aortic valves
59
aortic insufficiency
Dilatation of the ascending aorta due to hypertension and aging
60
mitral stenosis
rheumatic heart disease
61
mitral insufficiency
Myxomatous degeneration (mitral valve prolapse)
62
senile calcific aortic stenosis
Calcific Aortic Stenosis
Most common of all valvular abnormalities***
Consequence of calcification*** owing to progressive and advanced age
Pathologic Features
Nodular masses of calcium are heaped up within the sinuses of Valsalva (arrow).
can close completely but not open - more problem with stenosis
Clinical features
Clinical symptoms do not occur until 7th (60s) to 9th (80s) decades**
Pressure hypertrophy results from flow obstruction and patient develops significant left ventricular concentric hypertrophy***
Left ventricular cardiac mass tends to be ischemic and leads to:
Congestive heart failure (die within 2 yrs)
Syncope (die within 3 years)
Angina pectoris (die within 5 yrs)
63
Calcific stenosis of congenitally bicuspid aortic valve
Congenital bicuspid aortic valve occurs in ~ 2% population
Two cusps frequently not equal size: larger cusp may have a raphe” (seam) – result of incomplete separation during development
Bicuspid valves more susceptible to progressive degenerative calcification; develop significant calcification earlier ***
Develop clinical symptoms and signs of cardiac dysfunction earlier, 5th and 6th decades (7th to 9th decades with tricuspid aortic valves)
May have coexisting abnormalities of aortic wall
64
mitral annular calcification
what population does this occur in ?
fibrous tissue that leaflets attach to ... is the annulus
Occurs in three types of patients
Women over 60 years of age
Individuals with myxomatous mitral valves
Patients with elevated left ventricular pressure
– e.g., hypertension
Generally does not affect valvular function
Occasionally associated with arrythmias -->
if this calcifies conduction system--> end up with arrythmias
Most diagnosed because:
Large calcium deposits are incidentally detected
on radiography done for other reasons
65
Myxomatous Degeneration of the Mitral Valve (Mitral Valve Prolapse
presentation?
occurs in what population?
serious complications ?
One or both mitral valve leaflets are “floppy” and prolapse into the left atrium during systole (midsystolic click +/- regurgitant murmur)
Affects ~2-3% adults in US, most often young women (7F:1M)
Seen in Marfan syndrome (fibrillin-1/elastic fibers)
Vast majority patients clinically asymptomatic, but small subset (3%) may develop one of four serious complications:
1 Infective endocarditis
2 Mitral insufficiency
3 Stroke or other systemic infarct
4 Arrhythmias (both atrial and ventricular, rare sudden death)
Atypical chest pain
Mitral valve prolapse diagnosis by echocardiography
valves are stretchy and look like "parachute" - translucent valves (less collagen)
presentation:
young women
mid-systolic click (valve closing extra hard, plus leaflet hitting wall of atrium) - cause regurg jet lesion
can show up in psychiatrists office (anxiety, etc. ?)
66
valvular problem predisposes patients to....
predisposed to endocarditis
67
strep pharyngitis leads to what?
Acute rheumatic fever
NOT due to an active infection
body is attacking itself
aschoff bodies?
usually occurs 10 days to 6 weeks post strep throat
68
acute rheumatic fever leads to what?
chronic rheumatic valvular heart disease
69
what is an aschoff body
granuloma - activated macrophages
occurs in acute rheumatic fever
70
anitschkow cell
mononuclear form
71
aschoff cell
multinucleated form
72
caterpillar cells
unique linear chromatin pattern
73
What occurs in the chambers of the heart with aging?
sigmoid shaped ventricular septum --> blocks outflow track, increased pressure in the left ventricle must work against--> LVH--> aren't perfusing coronary arteries as well.
this can also lead to a dilated aorta b/c as you get older things decay so the aorta dilates b/c it is not as strong
74
what occurs in the valves with aging?
Aortic valve calcific deposits
Mitral valve annular calcific deposits
75
what happens with the epicardial coronary arteries with aging?
tortuosity- squiggle shaped b/c shrinking of organs as you age (shrinking of the heart so they are not as tightly coiled around the heart)
76
what changes occur in the myocardium with aging of the heart
brown atrophy which is just a buildup of lipofuscin (aging pigment)
decreased mass
increased subepicardial fat
77
what happens to the aorta with aging?
Dilated ascending aorta with rightward shift
Elongated (tortuous) thoracic aorta
Sinotubular junction calcific deposits
Elastic fragmentation and collagen accumulation
Atherosclerotic plaque
78
what is cardiac reserve>
the 5-fold margin for increased output
patients have lost 70-80% of cardiac function by the time the patient is symptomatic
79
what are the 6 basic causes of cardiac dysfunction
```
Pump Failure (Diminished Myocardial Contractility)
Primary Myocardiopathy
Ischemic Cardiac Disease
Obstruction to Blood Flow Through the Heart
Valvular Disease (Stenosis)
Hypertensive Disease
Regurgitant Flow
Valvular Disease (Insufficiency)
Shunted Flow
Congenital Heart Disease (PDA, ASD and VSD)
Disorders of Cardiac Conduction
Atrial Fibrillation
Sudden Death Syndromes
Disruption of Continuity of the Circulatory System
Gunshot wound
Ventricular rupture
```
80
can heart cells undergo hyperplasia ?
no ONLY HYPERTROPHY
hyperplasia not possible in terminally differentiated cardiac myocytes
81
cardiac remodeling?
```
increase in heart size and mass
increase in protein synthesis
induction of immediate early genes
induction of fetal genes
abnormal proteins
fibrosis
inadequate vasculature
```
occurs as a consequence of HTN, valvular disease, myocardial infarction --> increase cardiac work--> increase wall stress--> cell stretch --> hypertrophy/dilation
82
Pressure overload hypertrophy?
Concentric Hypertrophy -increase in the thickness of wall subjected to the increased workload
Left ventricle: systemic hypertension or aortic stenosis
Right ventricle: cor pulmonale
83
what is volume overload hypertrophy?
Eccentric Hypertrophy - chamber dilatation with increased ventricular diameter caused by volume overload stimulus
Ventricular wall thickness is normal or minimally thickened
Overall cardiac muscle mass is increased because dilatation has increased the overall size of the ventricular wall
Can be seen with valve disorders and congenital heart disease
84
left sided heart failure leads to....
most commonly caused by?
fluid within the lungs and pleural cavities
due to failure of the left ventricle
Chronic: Slowly progressive failure (insidious onset) which may over time develop sufficient severity to cause right sided heart failure
Acute: Rapidly progressive fatal course (with acute pulmonary edema) – Medical Emergency with 50% mortality. Foamy fluid coming from mouth
```
Most commonly caused by :
Ischemic heart disease
Hypertensive heart disease
Aortic and mitral valvular disease
Primary nonischemic myocardial disease (Cardiomyopathy)
```
85
right sided heart failure leads to....
accumulation of fluid in all other body sites and cavities
86
Cardiac Failure (CHF)
due to...
what occurs?
Insufficient pump rate to meet demands
Pump can only meet demands with elevated filling pressure
Characterized by either or both:
Diminished cardiac output (termed forward failure):
2 causes
Systolic dysfunction: progressive deterioration of myocardial contractility; e.g., ischemic heart disease, dilated cardiomyopathy
Diastolic dysfunction: Inability heart chambers to relax (distend) sufficiently to fill during diastole; e.g., restrictive cardiomyopathy
Damning of blood in the venous system (backward failure)
Cardiac Failure may occur as
Left-Sided Failure or Right-Sided Failure or Commonly Both
87
what are the pathological findings in left sided heart failure
cardiomegaly - hypertrophy, chamber dilation or both
secondary enlargement of left atrium - afib, mural thrombosis
tachycardia
S3
if they develop mitral regurg they have systolic murmur (they develop regurg b/c if dilation occurs, there is not enough valve to cover the new open space
88
what are the extracardiac effect in left sided heart failure
Lung Pathology:
2o excessive fluid accumulation
***Pulmonary congestion and edema -pulmonary basilar crackles (rales) and possible pleural effusions
Flash pulmonary edema- extremely rapid onset
***Long-term: siderophages (heart failure cells)
Dyspnea (SOB) - difficulty breathing or breathlessness
Orthopnea - dyspnea when laying relieved by sitting up or standing
Paroxysmal Nocturnal Dyspnea – random severe dyspnea attacks at night
Kidney: Decreased cardiac output leads to renal hypoperfusion
Activates renin-angiotensin-aldosterone system
(fluid retention and expansion of vascular volume – a vicious cycle)
Severe: prerenal azotemia
Brain: In advanced left-sided CHF, hypoxic encephalopathy
89
what are siderophages
heart failure cells
90
what is cor pulmonale
heart disease secondary to lung disease
91
Right sided heart failure
casued by?
Most commonly a consequence of left-sided heart failure
↑ pressure in the pulmonary circulation →↑workload right ventricle →right-sided heart failure
“Pure” or isolated (no left-sided dysfunction) right-sided failure
=Uncommon
-Cardiac hypertrophy and dilatation confined to the right atrium and ventricle
-Sequela of severe chronic pulmonary hypertension
Cor Pulmonale = Heart disease secondary to lung disease
92
what are the extracardiac effects of right sided heart failure
Subcutaneous Tissues: Accumulation edema fluid with
“pitting edema” lower extremities or generalized anasarca
Liver and portal system: Congestive Hepatomegaly
- Chronic passive congestion in hepatic sinusoids
- Centrilobular necrosis
- “Cardiac Cirrhosis” increased fibrous tissue in centrilobular zone
Spleen: Congestive Splenomegaly usually mild with only doubling in size
Pleural and Pericardial Cavities: Effusions (transudates)
93
ANP
release by atrial myocytes when there is atrial distention
94
BNP
what levels indicate pathology?
produced by ventricles 2ndary to increased pressure and is used for determination of CHF
BNP 500 pg/mL are most consistent with CHF
95
what do natriuretic peptides cause?
vasodilation
natriuresis
diuresis
96
what is the most common congential cardiac malformation
2 and 3
bicuspid aortic valve - 1
2- ventricular septal defect
3- atrial septal defect
ASD stated to be most common cardiac anomaly first diagnosed in adulthood and more common than VSD in adult population
97
from what type of cells does the aortic arch and great vessels develop from?
neural crest
98
DiGeorge Syndrome
Affected gene- TBX1 - del 22q11.2 (Catch 22)
```
cardiac outflow defects
ASD, VSD
-abnormal facies
-thymic aplasia-->-T-cell deficiency
-cleft palate
-hypocalcemia
```
gene product function of TBX1 is a transcription factor
abnormal development of neural crest derived cells
99
Marfan syndrome
affected gene- fibrillin
abnormal TGF-beta signaling and structural proteins
congenital cardiac disease--> aortic aneurysm and valve abnormalities
100
NKX2.5?
ASD
or conduction defect
normally gene product is a transcription factor
101
left to right shunts>?
ASD, VSD, PDA, AVSD- start as left to right but can shift to right to left (shunt reversal- baby later turns blue)
usually PINK babies initially b/c oxygenated blood is going to lungs
Right ventricular hypertrophy and potential heart failure
Muscular pulmonary arteries develop medial hypertrophy and vasoconstriction to normalize distal pressure
Eventually develop pulmonary hypertension leading to right to left shunt and late cyanotic congenital heart disease (Eisenmenger syndrome)***
Cyanosis (blue baby) occurs months or years after birth- blood from right side of heart is de-oxy (shunt reversal) – this will require heart and lungs transplant
102
what is Eisenmenger syndrome
left to right shunt reverses into right to left shunt
103
ventricular septal defect
shunt is left to right
pressures about same in both ventricles
pressure hypertrophy of right ventricle
volume hypertrophy of left ventricle
Large defects have murmur, pulmonary hypertension and develop--> Eisenmenger syndrome
90% involve membranous septum
10% in muscular septum or infundibulum
104
atrial septal defect
secundum 90%- involves fossa ovalis
primum 5 % - probe patent foramen ovale is not an ASD
sinus venosus 5% = near SVC
may be asymptomatic - 10% develop pulmonary HTN if untreated
may have murmur from increased flow across pulmonary valve
105
patent ductus arteriosus
what usually closes the ductus
how do you close it?
how do you keep it open?
b/w aorta arch and pulmonary artery
ductus usually closes... at 1-2 days secondary to
- increased O2
- Decreased pulmonary vasculature resistance
- decreased prostaglandin E2
machine like continuous murmur
if chronic--> leads to pulmonary HTN and cyanosis
close--> NSAID's (decrease prostaglandins)
open--> prostaglandin E until surgery
106
atrioventricular septal defect
Partial
– ASD and cleft anterior mitral
Leaflet with mitral insufficiency
```
Complete – large combined AV septal
defect and large common AV valve
All four chambers communicating and
4 chamber volume hypertrophy
(>1/3 of these patients have Down syndrome)
```
107
in what percentage of Down syndrome children is Congenital heart disease present
40-60%
AVSD #1
VSD>ASD>PDA>tetralogy of Fallot
108
right to left shunts
Cause cyanotic congenital heart disease
Mixing of unoxygenated blood with blood in systemic circulation
Decreased amount of blood going to lungs to be oxygenated
Develop clubbing of the tips of fingers and toes (hypertrophic osteoarthropathy) and polycythemia due to hypoxia
Paradoxical embolism – emboli from periphery bypass lungs through cardiac defect and enter systemic circulation
BLUE BABIES
109
tetralogy of fallot
1) Ventricular Septal Defect (VSD)
2) Subpulmonic (+/- pulmonic valve) stenosis with obstruction of right ventricular outflow tract- increases pressure inside RV RVH
3) Aorta overrides the VSD heart is laying on its side (boot shaped heart) (look through hole and you look into the aorta)
4) Right ventricular hypertrophy
(embryologically anterosuperior
displacement of infundibular
septum, get “boot shaped” heart)
110
what is a pink tetrology of fallot
subpulmonic stenosis is mild and the tetralogy of fallot behaves like VSD--> lungs are perfused (pink babies)
left to right shunt or no shunting b/c pressures are just about equal
111
transposition of the greater arteries
aorta leaves RV and pulmonary trunk leaves LV - separation of systemic and pulmonary circulations
not compatible with life unless there is a VSD, PDA, patent foramen ovale
due to failure of aorticopulmonary septum to spiral
if there is a shunt, infuse prostaglandin E and perform atrial septostomy followed by surgical correction
112
infantile form - coarctation of aorta
aorta narrowing is proximal to the insertion of ductus arteriosus (preductal)
associated with Turner syndrome
can present with closure of ductus arteriosus
cyanosis of inferior body and weak femoral pulses
top half pink, bottom half blue
113
coarctation of aorta - adult form
aorta narrowing distal to ligamentum arteriosum (postductal)
associated with notching of the ribs (collateral circulation- dilated and tortuous collateral channels)
HTN in upper extremities and weak, delayed pulses in LE
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causes of aortic stenosis and atresia?
Valvular aortic stenosis – have hypoplastic, dysplastic, or abnormal number of cusps (if severe get hypoplastic left heart syndrome)
Subaortic stenosis – ring or collar below cusps
Supravalvular aortic stenosis – elastin gene mutation with aortic dysplasia (thickening)
Williams–Beuren syndrome -deletion of about 28 genes from chromosome 7 with ELN gene (elastin) haploinsufficiency, hypercalcemia, glucose intolerance, facial and cognitive defects.
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acute rheumatic fever
constellation of clinical findings?
Acute systemic disease characterized by
variable constellation of clinical findings affecting 5 major systems
Migratory polyarthritis of large joints (swollen, painful joints)
Acute carditis with cardiac enlargement and diminished function (pericardial rub)
Subcutaneous nodules
Erythema marginatum of skin
Sydenham chorea (involuntary, purposeless movements of extremities)
Sequellae of group A streptococcus infection (thought to be hypersensitivity reaction to M protein cross-reacting with tissue glycoproteins)
Occurs 10 days - 6 weeks after clinical episode of group A Strep infection
Only 1% or less of patients die during primary episode
After an initial attack there is increased vulnerability to subsequent attacks with repeat group A Strep infections
Patients who have had rheumatic carditis should receive long-term antibiotic (PCN) prophylaxis well into adulthood and perhaps for life
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Jones criteria?
diagnosis of acute rheumatic fever
evidence prior group A Strep infection, plus either:
2 major system findings (from below list of 5)
1) Migratory polyarthritis of large joints (swollen, painful joints)
2) Acute carditis with cardiac enlargement and diminished function
3) Subcutaneous nodules
4) Erythema marginatum of skin
5) Sydenham chorea (involuntary, purposeless movements of extremities)
1 major system finding plus 2 minor manifestations such fever, arthralgia, or evidence of acute phase reactants (Elevated sedimentation rate or elevated C-reactive protein)
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rheumatic heart disease
long term sequellae of ARF
Occurs years or even decades after the episode(s) of ARF ***
Rheumatic Heart Disease (RHD) is the term used for the chronic valvular disease that results
RHD=Rheumatic Valvular Disease
commonly affects mitral and aortic valves
uncommonly the tricuspid
rarely the pulmonic valve
99% of all mitral stenosis is caused by RHD
In RHD patients,
Mitral valve only: 65 – 70 %
Mitral valve plus Aortic valve: 25%
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rheumatoid heart disease
Cardiac involvement in 20-40% of cases of rheumatoid arthritis
Fibrinous pericarditis is most common***
Rheumatoid nodules in myocardium, endocardium, valves and aortic root may be present
Rheumatoid valvulitis with fibrous thickening and calcification of aortic valve cusps
DON"T HAVE aschoff bodies
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INfective endocarditis
Serious, destructive infection of heart valves or mural endocardium by organisms (most commonly bacteria, less commonly pathogenic fungi) leading to
Bulky, friable vegetations*** composed of admixture of fibrin-platelet clot and organisms on leaflets
Destruction (erosion, ulceration) of underlying cardiac structures, especially valves
Risk of systemic microemboli, leading to both vascular infarcts and microabscesses (septic infarcts***) caused by disseminated organisms in the microemboli
Usually involves left valves ***(except in IV drug abusers- b/c these bacteria are injceted into veins and hit right side of heart first)
S. viridans (50-60%)>S. aureus (20-30%)>HACEK (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella)
#1 in artificial valves is S. epidermidis
120
acute bacterial endocarditis
Rapidly progressive destruction of infected cardiac valve, worse presentation
Valve prior to infection frequently normal
Infection by a highly virulent bacteria such as S. aureus ***(IV drug abusers)
Even with aggressive antibiotic therapy, 50% patients die in days or weeks of onset of symptoms.
intermittent high fever
valve leaflet is severly destroyed, can spread to myocardium and cause abscess
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subacute bacterial endocarditis
Insidious onset and protracted clinical course (weeks to months)
Involved valve usually deformed or abnormal (historically RHD, now mitral valve prolapse #1)
Infection by low virulence bacteria such as Streptococcus viridans***
Most patients recover with antibiotic therapy
large, friable vegetations at edge of valves, grow down chordae tendinae
122
Major Diagnostic criteria for infective endocarditis ?
Get 3*** blood cultures in 24 hours *** - positive for characteristic organism or unusual organism . time the blood culture to when the patient is having the fever and draw from different sites
new valve murmur (regurg)
echo + for valve-related or implant -related mass or abscess
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Duke Criteria
diagnosing infective endocarditis
requires either pathologic or clinical criteria;
if clinical criteria are used, 2 major, 1 major + 3 minor, or 5 minor criteria are required for diagnosis.
124
what are janeway lesions
small erythematous or hemorrhagic, macular, nontender lesions on the palms and soles *** and are the consequence of septic embolic events
infective endocarditis
side effect of vegetation breaking off
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what are osler nodes
are small, tender subcutaneous nodules that develop in the pulp of the digits or occasionally more proximally in the fingers*** and persist for hours to several days.
infective endocarditis
126
what are roth spots
oval retinal ***hemorrhages with pale centers.
infective endocarditis
127
nonbacterial thrombotic endocarditis
Small (1-5 mm) along the line of closure of the valve leaflets or cusps
Valvular lesions are sterile (contain no microorganisms)
Major risk factor is hypercoagulable state (debilitated patients with malignancy or in patients with sepsis and DIC)- they have vegetations that are thrombi on the surface of the valve
Clinical significance: NBTE may fragment and produce systemic emboli*** (b/c the thrombi are loosely attached to the valve) which produce obstruction in coronary arteries or brain vasculature
Once termed “Marantic Endocarditis” in debilitated
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Libman-Sacks disease
= Endocarditis of Systemic Lupus Erythematosus (SLE)
Small (1-4 mm) sterile verrucous “vegetations” on any surface of...
AV valve leaflets (mitral and tricuspid)
Valvular endocardium
Chordae tendineae
Ventricle or atrium subjacent to AV valves
SLE Patients with Lupus Anticoagulant (Antiphospholipid Antibody Syndrome) are at risk for Libman-Sachs disease
May be due to immune complex deposition with inflammation, very similar scarring to rheumatic fever!
so how do we differentiate--> new murmur, malar/butterfly rash, autoimmune shit
129
Comparison of the 4 major types of vegetative endocarditis ?
acute rheumatic heart disease
infective endocarditis
nonbacterial thrombotic endocarditis
Libman-sacks
The acute rheumatic heart disease (RHD) is marked by small, warty verrucae along the lines of closure of the valve leaflets. sore throat in history
Infective endocarditis (IE) typically shows large, irregular masses on the valve cusps that can extend onto the chordae.
Nonbacterial thrombotic endocarditis (NBTE) typically exhibits small, bland vegetations, usually attached at the line of closure. One or many may be present.
Libman-Sacks endocarditis (LSE) has small or medium-sized vegetations on either or both sides of the valve leaflets, or elsewhere on the endocardial surface. more widespread vegetations
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carcinoid heart disease
caused by what?
presentation/morphology of heart?
Carcinoid Syndrome: (caused metastatic carcinoid tumor producing serotonin (5HT), kallikrein, bradykinin, histamine, prostaglandin +/- tachykinins) results in diarrhea, flushing, skin rash, bronchoconstriction and
Fibrous intimal thickening of the endocardial surfaces of the right side of the heart, particularly right ventricle***, and the tricuspid and pulmonic valves (except with septal abnormalities and pulmonary carcinoids)
depending on where the tumor is will determine where in the heart the disease process occurs
if in gut?- right side of heart ***
in lung?- left heart ***
The endocardial thickening is composed predominately of smooth muscle proliferation and increased acid mucopolysaccharide matrix
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complications of cardiac valve prostheses
thrombosis/thromboembolism
anticoagulant related hemorrhage- usually on Warfarin
if they have mechanical valve --> makes a lot of noise
prosthetic valve endocarditis
```
structural deterioration (intrinsic)
wear
fracture
poppet failure in ball valves
cuspal tear
calcification
```
inadequate healing
if you use a valve with real tissue it can develop disease processes that develop in any valve
132
when do congenital defects occur
between 3 and 8 weeks gestational age
133
TBX5 gene abnormality
Holt-Oram Syndrome
ASD, VSD, conduction defects
134
#1 infection in artificial valves is ...
S. epidermidis
135
Cardiomyopathy
classifications> 3 types?
most common?
Heart disease resulting from a primary abnormality in the myocardium (include inflammatory and immunologic disorders, muscular dystrophies and genetic disorders of myocardium)
“Idiopathic” or “Primary”: Majority (genetic or acquired)
“Secondary”: Part of systemic or multiorgan disorder
Classification: Three clinical, functional and pathologic groups
1) Dilated (~90%)- most common
Large flabby heart
2) Hypertrophic (6–8 %)
Markedly thickened left ventricle
3) Restrictive (uncommon)
Mild increase in cardiac mass without increase in volume of left ventricle. decreased compliance
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endomyocardial biopsy
usually go into the right side of the heart
biopsy the SEPTUM (not the free wall) b/c if you make a hole in the septum it will just be a little VSD, but if you make a hole in the free wall--> bleed into pericardial sac and die from tamponade
used to differentiate Idiopathic dilated from myocarditis secondary to virus
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myocarditis
most common cause?
how do you make the diagnosis?
inflammation of the myocardium
most common cause is 1) viral --> --Coxsackieviruses A and B and other enteroviruses
lyme disease- can cause AV block
Hypersensitivity - eosinophilic myocarditis (allergic reaction NOT parasite)
trichinosis (trichinell spiralis) - eating undercooked meats
(bear, pork
most likely infiltrate are lymphocytes ***
making the diagnosis-->
infiltrating lymphocytes ?(lymphocytic myocarditis- most likely etiology is viral infection) ****
nuclei are lobated?
average of 2 ish is eosinophils- start looking for drugs in the patients history or allergy
see giant cells multinucleated? this is giant cell myocarditis - most likely a nasty case of lymphocytic myocarditis. these patients tend to die. these are macrophage type cells
see trypanosomes in a myofiber?
minimal inflammation. these bugs are not seen by the immune system and are hiding!-- >this is Chagas disease. hints are the patient just moved to the US.
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major cause of myocarditis in south america?
Chagas disease (trypanosoma cruzi)
a parasitic disease that affects 50% of patients in endemic areas of parasite. In Brazil, Chagas Disease is a more common cause of cardiac disease than ischemic heart disease
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dilated cardiomyopathey
causes
presents like what?
what mimics this?
Impairment of contractility (systolic dysfunction)
```
causees
Genetic-problem in the anchoring proteins /cytoskeleton ***
alcohol- toxic to myocytes
peripartum- happens late in pregnancy
myocarditis- destroys myocytes; hemochromatosis;
chronic anemia;
doxorubicin (Adriamycin); sarcoidosis;
idiopathic
```
indirect myocardial dysfunction
(things that look like cardiomyopathies)
Ischemic heart disease; valvular heart disease; hypertensive heart disease; congenital heart disease
LVEF <40%
Clinical presentation:
show up with CHF*** (SOB) cardiomegaly
large and flabby
140
hypertrophic cardiomyopathy
Synonyms:
Idiopathic hypertrophic subaortic stenosis (IHHS)
Hypertrophic obstructive cardiomyopathy
presentation?
causes?
50-80% LVEF
impairment of compliance- diastolic function
normally they are asymptomatic, the ones that do have symptoms only symptoms b/c they stress their heart/exertion
causes of phenotype
- -Genetic--> most dominant mutations involving proteins of the sarcomere ***(mutatins of B-myosin heavy chain gene on chromosome 14)
- -Friedreich ataxia
- -storage diseases;
- -infants of diabetic mothers
things that look like this:
HTN heart disease
aortic stenosis
features:
exertional dyspnea***
myocardial hypertrophy
abnormal diastolic filling
intermittent ventricular outflow obstruction
can cause sudden death in young patient***
A-fib b/c of atrial dilation working against a ventricle with decreased compliance
on microscopic examination:
massive myocardial hypertrophy without ventricular dilatation
haphazard myofiber diarray**
banana shaped ventricle
141
restrictive cardiomyopathy
45-90% LVEF
impairment of compliance - diastolic function
causes:
Amyloidosis
--radiation-induced fibrosis
idiopathic
things that look like this: pericardial constriction
Heart findings:
ventricles normal size
biatrial enlargement
```
Associated disorders:
Amyloidosis
Endomyocardial fibrosis
Loeffler endomyocarditis--> lots of eosinophils (leukemia)
Endocardial fibroelastosis
```
142
defect in.....
contractile proteins?
cytoskeletal attachment points?
causes what cardiomyopathy?
Chromosome 14 ?
defects in the contractile proteins --> seen in hypertrophic cardiomyopathies
cytoskeletal attachment points- dilated cardiomyopathy
chromosome 14- hypertrophic cardiomyopathy
143
arrythmogenic right ventricular cardiomyopathy (RV dysplasia)
normal heart (color)
whitish areas
muscle has been replaced by fat
make diagnosis by:
younger person
problems with heart
dilated right ventricle
right ventricle is all fat
develop arrhythmias and die from these- sudden cardiac death in young people
most have autosomal dominant mutations in plakoglobin and desmoplakin genes
144
naxos syndrome
palmoplantar keratoderma with arrhythmogenic right ventricular cardiomyopathy and woolly hair (recessive plakoglobin *** mutation)
145
carvajal syndrome
palmoplantar keratoderma with left ventricular cardiomyopathy and woolly hair (recessive desmoplakin*** mutation)
146
Amyloidosis
Systemic Senie cardiac amyloidosis
in the heart, the protein that normally deposits is transthyretin
Amyloidosis primarily in heart: Occurs in “aged” patients (>60 yrs.)
Results in RESTRICTIVE cardiomyopathy
May be localized to both ventricular and atrial myocardium or limited to atria (isolated atrial amyloidosis)
Far more common cause of cardiac amyloidosis than primary systemic amyloidosis
Much better prognosis and milder clinical course
Amyloid composed of transthyretin product
More common in African-Americans (transthyretin mutation)***
Isolated atrial amyloidosis – rare; atrial natriuretic peptide deposition
Diagnosis
Congo red stain --> shows apple-green birefringence
147
Adriamycin
causes heart damage
| chemo agent
148
cyclophosphamide
chemo agent that causes heart disease
149
Metastatic malignancy
most common cardiac tumor
150
myxoma
most common primary tumor in the heart
composed of mucoid/myxoid materia
this tumor arises in the atria of the heart, usually in the left
arises from region of fossa ovale
associated with:
carney complex
mazabraud syndrome
mccune albright syndrome
can cause valvular destruction and emboli
usually this is not malignant but it can grow other places
treatment- cut it out
151
rhabdomyoma
number 1 tumor of the heart in kids***
50% are associated with tuberous sclerosis /TSC1 and TSC2 ***
benign tumor of the heart
described as SPIDER CELLS
152
pericardial effusions can lead to what?
```
serous
serosanguinous
sanguinous
purulent
chylous
malignant (neoplastic)
```
Cardiac tamponade can occur with as little as 250 ml acute accumulation of fluid
Serous: CHF, hypoalbuminemia
Serosanguinous (blood tinged yellow/red tinged fluid): Malignancy, trauma, ruptured MI, aortic dissection
Sanguinous (red): Hemopericardium (aortic/cardiac rupture)
Purulent (neutrophils, yellow/green): Infection
Chylous: Lymphatic obstruction
Malignant (neoplastic): associated with malignant cells
153
Serous pericarditis
RF*, SLE**, scleroderma, tumors, uremia, Dressler syndrome (immune reaction post myocardial/pericardial injury)
154
fibrinous /serofibrinous pericarditis
Myocardial infarct, Dressler syndrome, uremia***, radiation RF, SLE, trauma, cardiac surgery
155
purulent supperative pericarditis
infection
156
constrictivce pericarditis
pericardium is rigid, thickened, scarred, and less elastic than normal
laying down collagen
restrictive cardiomyopathy
157
hemorrhagic pericarditis
Neoplasia, bacteria, TB, bleeding diathesis, cardiac surgery
158
casseous pericarditis
TB or fungus
159
Adhesive pericarditis
fibrous or fibroelastic scar
160
what is the number 1 systemic cause of pericarditis
renal failure
serous fluid
shaggy heart
161
what distinguishes cardiac allograft rejection?
typified by lymphocytic infiltrate associated with cardiac myocyte damage.
occurs early
162
what is allograft arteriopathy
with severe diffuse concentric intimal thickening producing critical stenosis.
the new heart ends up with CAD basically and this occurs years later
The internal elastic lamina (arrow) and media are intact (Movat pentachrome stain, elastin black).
Present in 50% within 5 years and almost 100% in 10 years
163
a patinet with long standing alcohol abuse can develop what
dilated cardiomyopathy (or toxic cardiomyopathy)
he can have CHF with cardiomegaly
acetyl aldehyde is responsible along with alcohol
164
erythema marginatum is seen in what disease?
acute rheumatic fever- get pericarditis (pericardial rub) and heart failure from myocarditis
165
what would troponin level be in inflamed myocardium= acute rheumatic fever
elevated
