9-3 Pathology of the Heart Flashcards
1
Q
What does the SA node consist of?
A
Small, modified mm cells which generate the electrical signal that controls the heart
2
Q
What are intercalated discs?
A
specialized end-to-end junctions of adjoining cells
3
Q
What are the histological layers of a heart valve?
A
ventricularis
spongiosa
fibrosa
4
Q
What are some changes in the chambers associated with the aging heart?
A
Increased left atrial cavity size
Decreased left ventricular cavity size
Sigmoid-shaped ventricular septum
5
Q
What are some changes in the valves associated with the aging heart?
A
Aortic valve calcific deposits
Mitral valve annular calcific deposits
Fibrous thickening of leaflets
Buckling of mitral leaflets toward the left atrium
Lambl excrescences
6
Q
What are some changes in the epicardial coronary aa associated with the aging heart?
A
Tortuosity - heart tends to shrink A-P diameter, so aa no longer straight
Diminished compliance
Calcific deposits
Atherosclerotic plaque
7
Q
What are some changes associated with the myocardium in the aging heart?
A
Decreased mass
Increased subepicardial fat
Brown atrophy
Lipofuscin deposition (aging pigment)
Basophilic degeneration (glycogen breakdown)
Amyloid deposits
8
Q
What change is associated with the aorta in the aging heart?
A
Dilated ascending aorta with rightward shift
- often due to sigmoid shaped venticular septum that can obstruct outflow tract
to aortic valve
Elongated (tortuous) thoracic aorta
Sinotubular junction calcific deposits
Elastic fragmentation and collagen accumulation
Atherosclerotic plaque
9
Q
Mortality related to heart disease is on the decline, and cancer is on the rise. Why?
A
heart disease is better controlled, and less fatal
people are living long enough to get cancer
10
Q
How has the picture of mortality from cardiac death changed from 1999-2010?
A
number of deaths declined 18%
death rate declined 33% (total deaths to total population)
↑ Congenital heart disease deaths
↑ Hypertensive heart disease deaths
↓ Ischemic heart disease deaths (prevention)
↓ Valvular heart disease deaths (↓ rheumatic heart disease)
↓ Nonischemic (primary) myocardial disease deaths
11
Q
How is someone able to lose a significant amount of cardiac function before becoming sick?
A
- Cardiac output is ~10-20% of maximum at rest in normal adults
- “Cardiac Reserve” 5-fold margin for increased output
- Have lost 70-80% of cardiac function by the time patient is symptomatic!
Heart disease is predominantly a long-term chronic disease with superimposed acute episodes
12
Q
What are the 6 different basic causes of cardiac dysfxn?
A
1.Pump failure - diminished myocardial contractility
Primary cardiomyopathy; ischemic cardiac disease
2.Obstruction to blood flow through the heart
Stenotic valvular disease; hypertensive disease
3.Regurgitant flow
Valvular disease with incompetence
4.Shunted flow
Congenital heart diseases
5.Disorders of cardiac conduction
Atrial fibrillation; ventricular tachycardia
6.Disruption of continuity of the circulatory system
Gunshot wound; ventricular rupture; ruptured aneurysm
13
Q
What are 3 methods of cardiac compensation?
A
- Activation of neurohumoral systems
•Norepinephrine from adrenergic nerves
•Renin-angiotensin-aldosterone system
•Natriuretic peptides - Myocardial adaptations - ventricular remodeling
- Frank-Starling mechanism - enhance contractility and stroke volume
14
Q
How is A-type natriuretic peptide produced?
A
A-type natriuretic peptide produced by specialized atrial myocytes with specific atrial granules and released with atrial distension
15
Q
How is B-type natriuretic peptide produced?
A
B-type natriuretic peptide (BNP) produced by ventricles (2ry to increased pressure) and is used for determination of CHF/stressed out heart
16
Q
How is C-type natriuretic peptide produced?
A
C-type produced by endothelial cells (secondary to shear stress)
17
Q
What do natriuretic peptides do? What hormones do they oppose?
A
Cause vasodilation, natriuresis and diuresis
Antithesis of renin-angiotensin-aldosterone system
18
Q
What leads to increases in cardiac work and wall stress?
A
HTN - pressure overload
Valvular disease - pressure and/or volume overload
MI - regional dysfxn with volume overload
19
Q
Increased cardiac work and wall stress will lead to what downstream cellular response?
A
cell stretch, leading to hypertrophy and/or dilation
leads to remodeling
20
Q
What does remodeling of the heart include?
A
Increased heart size and mass
increased protein synthesis
inducton of immediate-early genes
induction of fetal gene program
abnormal proteins
fibrosis
inadequate vasculature
21
Q
Remodeling has happened, what is the proper term for “you’re screwed, you’re heart doesn’t work no good no more”?
A
Cardiac dysfxn, happens due to remodeling
22
Q
What is cardiac dysfxn characterized by?
A
- inability to pump blood at a rate necessary for metabolizing tissues
Includes:
heart failure (systolic/distolic)
arrhythmias
neurohumoral stimulation
23
Q
How is CHF and cardiac dysfxn related?
A
CHF is a type of cardiac dysfxn
- chronic and symptomatic
24
Q
What are the main causes of increased workload to myocardial myocytes?
A
- Increased physiologic need by a normal heart (aerobic exercise)
- Cardiac failure increases workload per myocyte due to overall decreased intrinsic myocardial contractility (ischemia, etc.)
25
Why do myocytes undergo hypertrophy instead of hyperplasia in response to stress?
**Myocyte hypertrophy**
- Response available for increased cardiac workload per myocardial fiber
- Myocytes are terminally differentiated, cannot undergo significant amounts of regeneration
26
What is the difference between cardiac hypertrophy and cardiomegaly?
Cardiac hypertrophy – increase in ventricular thickness or weight
Cardiomegaly - increase in heart size or weight
27
A heart weight of 350-600 g indicates what?
•350-600 gm: Pulmonary HTN, IHD
Normal: Male 300-350 gm; Female 250-300 gm
28
A heart weight of 400-800g indicates what?
•400-800 gm: Systemic HTN, aortic stenosis, mitral regurgitation, dilated cardiomyopathy
Normal: Male 300-350 gm; Female 250-300 gm
29
A heart weight of 600-1000 gm indicates what?
•600-1000 gm: Aortic regurgitation, hypertrophic cardiomyopathy
Normal: Male 300-350 gm; Female 250-300 gm
30
"pressure overload" hypertrophy is also known as concentric hypertrophy.
What is this?
Increase in the thickness of wall subjected to the increased work load
Left ventricle - systemic HTN or Aortic stenosis
Right Ventricle - Pulmonary HTN
31
Volume overload hypertrophy is also known as?
Characterize the cardiac muscle mass!
Volume overload hypertrophy
Overall cardiac muscle mass is increased
32
Cardiac failure in CHF is due to either or both...
* Insufficient pump rate to meet metabolic demands
* Pump can marginally meet demands with elevated filling pressure
33
CHF can be caused by forward failure. What is this?
Diminished cardiac output.
**Systolic dysfunction-** progressive deterioration of myocardial contractility
**Diastolic dysfunction-** Inability of the heart chambers to relax (distend) sufficiently to allow filling during diastole
34
CHF can also be caused by backward failure. What is this?
Damming of blood in the venous system
* Left-side failure leads to accumulation of fluid within the lungs and pleural cavities
* Right-side failure leads to accumulation of fluid in all other body sites and all body cavities
35
Left sided heart failure can be acute or chronic. What are the 4 most common causes?
Ischemic heart disease
Hypertensive heart disease
Aortic and mitral valvular disease
Primary nonischemic myocardial disease (cardiomyopathy)
36
A BNP \> 500 pg/mL is most consistent with?
CHF
37
BNP \< 100 pg/mL is...
unlikely to be CHF
38
What are the extracardiac effects of left sided heart failure on the following...
1. Lungs
2. Kidney
3. Brain
1. Lungs
* Dyspnea
* Orthopnea
* Paroxysmal nocturnal dyspnea
* Pulmonary congestion and edema
* Long-term get siderophages (heart failure cells)
2. Kidney
* Renal hypoperfusion
3. Brain
* hypoxic encephalopathy
39
What is right sided heart failure most commonly a consequence of?
Left sided heart failure
## Footnote
↑ pressure in the pulmonary circulation →↑workload right ventricle →right-sided heart failure
40
Pure, or isolated right sided heart failure is uncommon, but will present with cardiac hypertrophy and dilatation confined to the right atrium and ventricle.
What causes this?
Cor Pulmonale - heart disease secondary to lung disease
41
What are the right sided heart failure cardiac effects on...
1. Subcutaneous tissues
2. Liver
3. Spleen
4. Pleura
5. Peritoneum
6. Pericardium
1. Subcutaneous tissues
* pitting edema of lower extremities or generalized anasarca
2. Liver
* Congestive hepatomegaly
* Chronic passive congestion in hepatic sinusoids
* cardiac cirrhossis - increased fibrous tissue in the centrilobular zone
3. Spleen
* congestive splenomegaly
4. Pleura, Peritoneum, Pericardium effusions - transudates
42
In order, what are the congenital heart defects associated with Trisomy 21?
1. AVSD
2. VSD
3. ASD
4. PDA
5. TOF (tetrology of fallot)
6. TGA (transposition of great arteries)
43
What are the top three congenital cardiac malformations?
Bicuspid aortic valve
VSD
ASD
44
What gene defect is responsible for ASD or conduction defects?
NKX2.5
45
What gene defect is responsible for DiGeorge syndrome?
TBX1 (Deletion 22q11.2)
46
What gene defect is responsible for Marfan syndrome?
FBN1
47
What are the defects associated with Digeorge syndrome?
"CATCH-22"
**C**ardiac
**A**bnormal facies
**T**hymic aplasia
**C**left palate
**H**ypocalcemia (d/t parathyroid hypoplasia)
48
What are the left to right shunts?
ASD
VSD
PDA
AVSD
49
What is Eisenmenger syndrome?
The muscular pulmonary arteries develop medial hypertrophy and vasoconstriction to normalize distal pressure.
Eventually develop pulmonary HTN, leading to shift from left to right shunt to *right to left shunt,* and **late cyanotic congenital heart disease, occurring months to years after birth.**
50
90% or VSD involves what?
The membranous septum
51
What type of defect is shown here?
VSD, membranous type
Note proximity to the valve
52
What are the three major types of ASD?
Where are these each located?
1. Secundum (90%) - involves fossa ovalis
2. Primum (5%) - adjacent to AV valve
3. Sinus venosus (5%) - near superior vena cava
53
The ductus arteriosis typically closes at 1-2 days secondary to what three changes?
* ↑O2
* ↓ Pulmonary vasculature resistance
* ↓ Prostaglandin E2
54
What would you use to tx a PDA?
NSAID (Indomethacin or ibuprofen) to close
or prostaglandin E to keep open until surgery
**_but, don't do this before looking for other defects, you might kill the baby._**
55
What is this?
In what population is this particularly common?
Atrioventricular Septal Defect (AVSD)
more than 30% of down syndrome patients have this.
56
What are the types of AVSD?
Partial - ASD and cleft anterior mitral leaflet with mitral insufficiency
Complete - large combined AV septal defect and large common AV valve, all 4 chambers communicate and develop volume hypertrophy.
57
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
58
What are some presentations we might see with right to left shunts?
1. Clubbing tips of fingers and toes (hypertrophic osteoarthropathy)
2. polycythemia d/t hypoxia
59
What is a paradoxical embolism?
•emboli from periphery bypass lungs through cardiac defect and enter systemic circulation
60
What... is the tetralogy of fallot?
1. Ventricular Septal Defect (VSD)
2. Subpulmonic (+/- pulmonic valve) stenosis with obstruction of right ventricular outflow tract
3. Aorta overrides the VSD
4. Right ventricular hypertrophy
61
Direction of shunting in tetralogy of fallot is dependent upon?
Severity of subpulmonic stenosis
When severe, a right to left shunt results
62
How does Pink tetralogy of fallot differ?
mild subpulmonic stenosis
with well perfused lungs (behaves like VSD)
63
What is this radiographic finding referred to as? What does this patient have?
"Boot shaped" heart
Tetralogy of fallot
64
Is this a normal heart?
Nope, this is an example of transposition of the great arteries. Note the aorta arising from the right ventricle.
65
TGA creates two seperate circulatory circuits.
What can allow a patient with transposition of the great arteries to survive?
A patent ductus arteriosis, VSD or patent foramen ovale are the only ways a patient with this can survive. For a while.
66
What is the defect that leads to TGA?
Truncal and aortapulmonary septae
67
What are the obstruvtive congenital cardiac anomolies?
1. Aortic stenosis and atresia
2. Pulmonary stenosis and atresia
3. Coarctation of the aorta
68
What are the types of congenital aortic stenoses?
1. Valvular aortic stenosis
2. subaortic stenosis
3. supravalvular aortic stenosis
69
What is abnormal in valvular aortic stenosis?
What can happen if this is severe?
Abnormal valve cusps
if severe, get hypoplastic left heart syndrome
70
What is stenosed in subaortic stenosis?
Ring or collar above the cusps
71
Supravalvular aortic stenosis arises due to the ring or collar above the cusps. What is the mutation that commonly leads to this?
What is the syndrome associated with this?
Elastin gene mutation with aortic dysplasia (thickening)
William-Beuren Syndrome -
•deletion of about 28 genes from chromosome 7 with ELN gene (elastin) haploinsufficiency, hypercalcemia, glucose intolerance, facial and cognitive defects
72
What are the two forms of coarctation of the aorta?
**Infantile** - hypoplasia of aorta prior to patent ductus arteriosus. See cyanosis of the inferior body and weak femoral pulses.
**Adult -** Ridge like fold opposite ligamentum arteriosus. See HTN in the upper extremities with low pressure and pulses in lower extremities.
73
What type of coarctation of the aorta is shown here?
Infantile form
Stenosis is just proximal to the patent ductus arteriosis. So, upper extremities are oxygenated, and lower extremeties are getting deoxygenated blood.
74
What would you see in this patient as far as blood pressures?
Adult form coarctation of the aorta, causing HTN in the upper extremities and low pressure and pulses in the lower extremeties.
75
What are some other important associated anomalies that are common with coarctation of the aorta?
More than half also have a bicuspid aortic valve
Sometimes see coexisting circle of willis aneurysms
76
This is an example of postductal, adult type coarctatoin of the aorta. What would you see on x-ray?
Subcostal notching, d/t increased flow through the intercostal arteries.
77
What are the four clinical syndromes associated with IHD?
1. Sudden Cardiac death
2. angina pectoris
3. chronic IHD with heart failure
4. MI
78
What is the most common cause of ischemic heart disease?
90% of cases are d/t atherosclerotic coronary arterial obstruction
79
As mentioned before, atherosclerosis is the major cause of IGD. What are some other causes?
1. **Localized platelet aggregation**
2. **Thrombosis overlying a disrupted plaque**
3. **Vasospasm**
4. Emboli
5. Hypotension
6. Coronary artery vasculitis
80
What level of fixed obstruction is required to cause IGD symptoms during exercise?
75% or greater obstruction
81
What level of obstruction is required to produce IHD symptoms at rest?
90% obstruction or greater
82
Acute atherosclerotic plaque change can play a role in IHD, what are the types of changes that can be problematic?
Rupture/Fissuring
Erosion/Ulceration
Hemorrhage into an atheroma (plaque)
83
What is prinzmental angina?
Sustained vasospasm that causes angina
84
What is cardiac Raynaud?
cold or emotion induced cardiac vasospasm
85
What is Takotsubo cardiomyopathy?
dilated cardiomyopathy secondary to emotional or physical stress with normal coronary angiogram (sometimes due to vasospasm)
86
What is the most common mechanism of sudden cardiac death (SCD)?
Most common cause?
Most often a lethal arrhythmia from
1. electrical instability
2. ventricular fibrillation
3. asystole
Most common cause is IHD
87
What pathologies should you suspect non-ischemic SCD in young people? (More of an FYI card)
Possibilities (% are from study on deaths in young athletes)
* 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%)
* Dilated cardiomyopathy (\<1%)
* Aortic valve stenosis
* Mitral valve prolapse
* Pulmonary hypertension
* Cardiac hypertrophy of any cause (e.g., hypertension)
* Systemic metabolic and hemodynamic alterations (vasculitis)
* Catecholamines and drugs of abuse (cocaine and methamphetamine)
88
What is another name for ischemic cardiomyopathy?
Chronic Ischemic Heart Disease
89
What does ischemic cardiomyopathy usually present with?
with insidious onset of **congestive heart failure**
90
In addition to CHF, what also frequently presents with ischemic cardiomyopathy?
* Cardiomegaly with left ventricular hypertrophy & dilatation
* Evidence of previous healed MIs or ischemia (areas of myocardial fibrosis)
* Develop arrhythmias, congestive heart failure and MIs
91
Chronic ischemia that does not cause necrosis can lead to what?
hypokinetic myocardium with myocyte **hibernation** that can become **functional after reperfusion**
92
What is angina pectoris?
**Paroxysma**l and usually **recurrent** attacks of **substernal or precordial chest discomfort**
93
What causes angina pectoris?
transient myocardial ischemia that falls short of inducing the cellular necrosis that defines infarction
94
What is stable/typica angina?
What provokes it?
How common is it?
What relieves it?
Stable (Typical) 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
95
What is unstable/crescendo/pre-infarction angina?
Caused by transient myocardial ischemia that falls short of inducing the cellular necrosis that defines infarction
Usually have acute plaque change
96
How are the attacks characterized in terms of frequency with unstable angina? How are they provoked?
* Progressive increase in frequency and severity of attacks
* Provoked by progressively less effort and may occur at rest
Still have angina symptoms of:
Paroxysmal and usually recurrent attacks of substernal or precordial chest discomfort
97
How are crescendo angina attacks relieved?
Sometimes they are not relieved by rest or nitroglycerin
98
What the heck is Prinzmetal angina?
Prinzmetal Angina: episodic angina due to coronary artery spasm
99
How is Prinzmetal angina relieved?
Nitroglycerin or Ca++ channel blockers
100
What is the definition of an MI?
The death of cardiac muscle from ischemia
101
What are some facts about the epidemiology of MI that you might want to remember?
Think age, gender, risk factors, genetics...
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%
102
What is a transmural infarction? What is it frequently associated with?
Ischemic necrosis involves **\>50%** of the ventricular wall thickness
- Commonly associated with acute plaque change with thrombosis
103
What is a subendocardial infarction?
Subendocardial infarction:
Area of ischemic necrosis limited to inner 1/2
104
What can cause a subendocardial infarct?
May occur as a result of acute plaque change and thrombosis
May result from reduction in systemic blood pressure (shock)
105
Why does a small band of subendocardial tissue remain viable?
Perfusion still present - myocardium right underneath endocardium is perfused via diffusion from the ventricle
106
What does triphenyltetrazolium chloride staining reveal on gross specimens?
lactate dehydrogenase leakage following cell death
- necrotic areas won't take up stain
- helpful in dx'ing MI in gross specimens
107
What is the typical sequence of events for the pathogenesis of an MI?
Typical Sequence of Events (90% Patients)
_•Sudden change in plaque →_
_•Immediate formation of platelet plug →_
- Vasospasm (vasoactive substances from platelets)
- Propagation of platelet plug and formation of stable clot (clotting system)
_•→Coronary artery occlusion within minutes_
108
What type of stimulation can induce an MI?
Adrenergc stimulation:
- peak incidence 6am-noon, cortisol levels increase just prior to wake
- intense emotional stress
109
How does an MI happen in patients with no associated atherosclerosis?
* Vasospasm (e.g., cocaine)
* Emboli (e.g. mural thrombus, valve vegetations, paroxysmal emboli)
* Vasculitis
* Hemoglobinopathy
* Etc.
110
An MI has happened. What is the first thing that happens, and how quickly does it happen?
Onset of ATP depletion (↓ glycolysis)
happens in seconds
111
An MI has occurred and ATP depletion has started. What is next? When does it happen
Loss of contractility
\< 2 min after MI
112
An MI has occurred, with ATP depletion and loss of contractility. What happens next? Timeframe?
ATP reduced:
50% of normal - 10 min
down to 10% of normal - 40 min.
113
Along with grossly reduced ATP levels and loss of contractility, what also happens after an MI?
**_Irreversible cell injury/necrosis_**
**_- starts 20-40 min._**
114
An MI has occurred, and there is loss of contractility, depletion of ATP, and irreversible cell injury. What 2 things can happen to the heart tissue now, and when?
Microvascular injury - \>1 hour
Complete unsalvageable necrosis 6-12 hours
115
Summarize the changes that take place following an MI on the cellular level. (I know, repetition, but I think there might be TQ stuff here.)
Onset of ATP depletion (↓ glycolysis) - Seconds
Loss of contractility - \< 2 min
ATP reduced:
to 50% of normal - 10 min
to 10% of normal - 40 min
Irreversible cell injury (necrosis) - 20-40 min
Microvascular injury - \>1 hr
Complete unsalvageable necrosis - 6 -12 hours
116
What are some early biochemical findings after MI?
Increasing/accumulating lactate
decreased/depleted ATP
117
When is MI potentially reversible?
~30 min after onset of ischemia
118
When is reperfusion most effective after an MI?
Earlier the better - more myocytes saved
119
A coronary aa has become occluded, and myocardial necrosis has set in. Where does necrosis set in first? Where are myocytes 'at risk'?
Necrosis begins in a small zone of the myocardium beneath the endocardial surface in the center of the ischemic zone.
The area that depends on the occluded vessel for perfusion is the “at risk” myocardium
Note that a very narrow zone of myocardium immediately beneath the endocardium is spared from necrosis because it can be oxygenated by diffusion from the ventricle.
120
What layer of the heart mm do most MIs start? Why? What kinds of infarcts result from full versus partial blockages?
most MIs start on subendocardial region and travel towards outside
- Heart tends to get better perfusion on the outside
partial blockage will not result in transmural infarct, often results in subendocardial infarct
- complete blockage = transmural MI
121
How is the location of MIs determined? What arteries are at the most risk for occlusion?
1.Specific coronary artery obstructed
LAD 40-50%; RCA 30-40%; LCX 15-20%
122
How is the size of tissue deemed at risk from MI determined? What factors should you keep in mind?
Consider aa blocked and:
- Duration of occlusion (spontaneous or therapeutic lysis of initial thrombus)
- Metabolic requirements of affected myocardium
- Presence, site and severity of associated vasospasm
- Extent of collateral blood supply
123
What regions would you expect to be at risk (left or right ventricle, ant or posterior) from the following transmural infarcts?
LAD
left circumflex
right coronary aa
- or post descending branch
LAD = anterior left ventricle
left circumflex = lateral left ventricle
right coronary = post left ventricle
post descending branch RCA = post left ventricle
124
What regions would you expect to at risk for ischemic necrosis from the following non-transmural infarcts?
transient/partial obstruction
global hypotension
small intramural vessel occlusions
transient/partial obstruction =
- regional subendocardial infarct
- anterior left ventricle wall
global hypotension=
- circumferential subendocardial infarct
- entire wall of left ventricle
small intramural vessel occlusions=
- microinfarcts
- small areas of necrosis scattered throughout
125
A patient with no previous symptoms of cardiac ischemia gets a septic infection, then has an MI. Why did this happen?
Patient probably had a significant occlusion - 75% or so - on a coronary aa
- hypotension secondary to sepsis, trauma, etc, can result in too little blood flow, ischemia and MI to tissue downstream of stenosis
126
How do myocytes get collateral circulation?
- chronic ischemia of the heart leads to better collateralization of vessels due to VEG-F expression
- no ischemia, no collateralization
- oft better on posterior heart, LAD area not good
127
What is the time frame for a reversible ischemic injury in MI? Associated histological findings?
time: 0-30 min.
no gross or light microscopy changes
EM changes:
Relaxation of myofibrils; glycogen loss; mitochondrial swelling
128
When does irreversible injury from MI start to occur?
After 30 min mark
129
In the half hour - 4 hour timeframe, what would you expect to find as far as:
gross features
light microscopy findings
gross features
none
light microscopy findings
- Usually none; variable waviness of fibers at border
130
In the 12-24 hour timeframe after an MI, what would you expect to find as far as morphological changes in:
gross features
light microscope findings
gross features
- dark mottling
light microscope findings
- Ongoing coagulation necrosis; pyknosis of nuclei; myocyte hypereosinophilia; marginal contraction band necrosis; **early neutrophilic infiltrate**
131
In the 1-3 days timeframe after an MI, what would you expect to find as far as morphological changes in:
gross features
light microscope findings
gross features:
mottling with yellow-tan infarct center
Light microscope:
Coagulation necrosis, with loss of nuclei and striations; **brisk interstitial infiltrate of neutrophils**
132
What is the goal of MI infarct modification by reperfusion?
•salvage ischemic myocardium from potential infarction by restoration of tissue perfusion as quickly as possible (reperfusion)
133
What intervention techniques are available for MI modification by reperfusion?
* Intervention techniques include:
* **Lysis of thrombus** by fibrinolytic therapy (streptokinase, urokinase, or tissue plasminogen activator (TPA)
* **Balloon angioplasty**
* Coronary artery **bypass** graft
134
If flow is restored to ischemic heart tissue following MI, what happens?
If flow is restored, then some necrosis is prevented, myocardium is salvaged, and at least some function will return.
The earlier reperfusion occurs, the greater the degree of salvage.
However, the process of reperfusion itself may induce some damage (reperfusion injury), and return of function of salvaged myocardium may be delayed for hours to days (post-ischemic ventricular dysfunction).
135
At what time point does reperfusion not change the MI infarct size?
Reperfusion beyond 6 hours does not appreciably reduce myocardial infarct size
136
What is myocardiocyte stunning?
a type of reversible injury - cells viable but not functional
137
What are some pathological changes associated with reperfusion of an MI?
* Reperfusion-induced **arrhythmias**
* Myocardial **hemorrhage with contraction bands**
* **Reperfusion injury** – additional permanent myocardial damage
* **No-reflow** - Microvascular injury with endothelial swelling
* **Reversible “myocardial stunning”** (prolonged ischemic dysfunction with CHF)
138
What are the classic acute onset symptoms, signs and findings with an MI?
**•Severe substernal chest pain with radiation of pain down left arm, neck, jaw, epigastrium**
•Weak, rapid pulse
•Sweating profusely (diaphoretic)
•Nausea
•Dyspnea secondary to pulmonary congestion and edema
•**STEMI** –ST segment Elevation Myocardial Infarct (transmural)
•**NSTEMI** – Non-ST segment Elevation Myocardial Infarct (subendocardial)
139
What percent of MI patients are asymptomatic? How do you find MI on these people?
10-25% asymptomatic
- seen with DM, transplant patients
•MI discovered by EKG (Q waves, ST-segment changes, T-wave inversion) or other types of testing
140
What cardiomyocyte proteins are released following MI? When?
myoglobin - peaks ~6 hours after MI
CK-MB - peaks 10-24 hrs after MI
MB isofroms - peaks 4-12 hr aft MI
Troponin I/cTnI - peaks 10-24 hours after MI
Troponin T/cTnT - peaks 12-24 hrs aft MI
141
In addition to MI, what can elevate myoglobins? What do you use in addition to this biomarker for suspected MI dx?
can be elevated by trauma
use with EKG to rule out MI:
normal myoglobin + normal EKG = no MI
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According to Dr. Gomez, how should you order cardiac enzyme labs and why?
Order cardiac enzymes x3 every 2 hours
- will climb gradually, get total pic over time to get full clinical picture
- go ahead and use other things to treat MI and start reperfusion immediately, use labwork later to confirm MI
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What biomarkers start to increase first after an MI?
1 hour:
myoglobin
MB-isoforms
3 hours:
CK-MB
troponins
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What biomarkers return to baseline when after an MI?
myoglobin - 18-24 hours
MB-isoforms - 38 hours
CK-MB - 48-72 hours
cTnI - 5-10 days
cTnT - 5-14 days
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What enzyme markers will change after an MI, in addition to myoglobin and troponins?
liver enzymes - AST - peaks in ~1.5 days, done by 5 days
lactate dehydrogenase - LDH - peaks in ~2 days, done by 6 days
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What is the clinical outcome from MIs?
**½ of deaths occur in patients within one hour** of onset symptoms
vast majority of these patients never reach Emergency Department
5% In-hospital death rate (once was 30%)
- 2/3 die from cardiogenic shock (which has a 70% mortality rate)
**¾ of MI patients have one or more complications** of an acute MI
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What are some physiological complications of MIs?
Contractile dysfunction: Severe pump failure occurs in 10-15% of patients
Arrhythmias: Conduction disturbances along with myocardial “irritability”
Papillary muscle dysfunction: mitral regurgitation
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What are some pathological/morphological complications of acute MI?
Myocardial rupture (1-5% of MIs)
- Free wall (usually anterior) → cardiac tamponade
- Interventricular septum → VSD/ASD
- Papillary muscle → acute valvular regurgitation
Pericarditis (fibrinous or hemorrhagic)
Right ventricular infarction (isolated in 1-3% of cases)
Infarct extension (enlargement) and expansion (thinning and dilation)
Mural thrombus
Ventricular aneurysm (usually anteroseptal)
Progressive late heart failure (IHD)
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What is the criteria for Dx for systemic HTN heart disease? What side of the heart does this affect?
Affects left side
Criteria for Dx:
1. **Left ventricular hypertrophy** (usually concentric) in the absence of other cardiovascular pathology that may have induced it
2. A history of HTN (BP \> 140/90 mm Hg) or pathologic evidence of systemic hypertension in other organs
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What does left sided HTN heart disease present with, clinically?
CHF or atrial arrythmias
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Someone has died from complications of systemic HTN heart disease (i.e. CHF). What gross changes would you expect to see to the heart?
There is marked concentric thickening of the left ventricular wall causing reduction in lumen size.
- many patients will also have small infarcts too, i.e. subendocardial infarct
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A patient of yours doesn't look good/very healthy, and has a 10 year Hx of COPD. What cardiac changes should you look out for?
Pulmonary/Right sided HTN heart disease
Namely. chronic *C**or pulmonale*
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How does chronic *Cor pulmonale* happen? What gross changes to the heart would you expect?
results from pulmonary disorders that cause chronic severe pulmonary hypertension
- thick and dilated RV & RA
- RV has a thickened free wall and hypertrophied trabeculae
- LV has been distorted by the enlarged right ventricle
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What is acute *Cor pulmonale*? What gross changes would you expect?
occurs from massive pulmonary thromboembolism (saddle embolus, etc.)
- acutely dilated RV and RA
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PHTN = what cardiac change?
PHTN = Pulmonary Hypertension
PHTN = hypertrophy of right side of heart
heart has to work harder to perfuse lung for gas exchange, leading to eccentric hypertrophy of RV
- often see jet lesions (white and fatty plaques) on RV outflow tract
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What types of diseases predispose someone to *Cor pulmonale*?
Diseases of pulmonary parenchyma
Disease of pulmonary vessels
Disorders affecting chest movement
Disorders inducing pulmonary arterial constriction
157
What are the 2 main types of cardiac valve dysfxn?
"pure" = only stenosis or regurg
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Like professors, cardiac valves are often dysfxnal in multiple ways. What is mixed cardiac valve dysfxn?
have stenosis and insufficiency in same valve
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What is cardiac valve stenosis? Is it an acute or chronic problem? Where is the abnormality?
Stenosis: failure of valve to open – leaflet problem
Virtually always a chronic disease
Almost always a cusp abnormality
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What is valve insufficiency? Is it an acute or chronic problem?
**Insufficiency (regurgitation or incompetence)**: failure of a valve to close
Chronic disease or acute insufficiency syndromes may occur
Intrinsic disease of valve cusp or acquired abnormality of the supporting structures
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What is functional regurg?
normal valve leaflets but problem with supporting structures (e.g. dilated annulus from ventricular dilatation)
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What is a major cause of mitral stenosis?
postinflammatory scarring - rheumatic heart disease
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What are some major structural causes of mitral regurg?
abnormalities of leaflets and commissures
abnormalities of tensor apparatus
abnormalities of left ventricular cavity and/or annulus
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What are some major pathologies that cause mitral valve regurg?
_abnormalities of leaflets and commissures_
postinflamm scarring
infective endocarditis
mitral valve prolapse
drugs - fen-phen
_abnormalities of tensor apparatus_
rupture of papillary mm
papillary mm dysfxn/fibrosis
rupture of chordae tendinae
_abnormalities of left ventricular cavity and/or annulus_
LV enlargement - myocarditis, dilated cardiomyopathy
calcification of mitral ring
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What are some major causes of aortic stenosis?
postinflamm scarring - rheumatic heart disease
senile calcific aortic stenosis
calcification of congenitaly deformed valve
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What are some major causes of aortic regurg?
postinflamm scarring
infective endocarditis
Marfan syndrome
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What are some major causes of aortic disease?
degenerative aortic dilation
syphilitic aortitis
ankylosing spondylitis
RA
Marfan syndrome
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Aortic stenosis most commonly is caused by what?
calcification - normal or bicuspid valves
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Aortic insufficiency most frequently results from what?
Dilated ascending aorta
due to HTN and aging
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Mitral stenosis most frequently occurs from what?
rheumatic valvular disease
- due to valve scarring
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Mitral insufficiency most frequently results from what?
Myxomatous degeneration - mitral valve prolapse
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2/3 of all valvular disease is what?
Acquired stenoses of aortic and mitral valves
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Calcific aortic stenosis results from what?
Most common of all valvular abnormalities
Consequence of dystrophic calcification and ossification owing to chronic valve abuse (years of use)
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What are the pathological features of senile calcific aortic stenosis?
Nodular masses of calcium are heaped up within the sinuses of Valsalva
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What are the clinical features of calcific aortic stenosis?
* Clinical symptoms do not occur until 7th (60s) to 9th (80s) decades
* Crescendo-decrescendo systolic murmur (crescendo with severe disease)
* Pressure hypertrophy results from flow obstruction and patient develops significant left ventricular concentric hypertrophy
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Patients with calcific aortic stenosis are at risk for developing left ventricular cardiac mass. This puts them at risk for what sequelae?
•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)
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Calcific stenosis of the aortic valve can happen due to old age, or to what congenital anomaly that is in 2% of the population?
Bicuspid aortic valve
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What problems is a bicuspid aortic valve at greater risk of acquiring?
* 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
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What types of patients does mitral annular calcification occur in?
1) Women over 60 years of age
2) Individuals with myxomatous mitral valves
3) Patients with elevated left ventricular pressure – e.g., hypertension
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How does mitral annular calcification affect valvular function? What is it occasionally associated with?
Generally does not affect valvular function
Occasionally associated with arrythmias
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How is mitral annular calcification frequently dx'ed?
Large calcium deposits are incidentally detected on radiography done for other reasons
- see it on CXR incidentally
- most are clinically silent - rare arrhythmias d/t calcification of conduction system, valvular dysfxn d/t extensive calcification causing stenosis
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What changes does mitral annular calcification have on the valve?
calcific nodules at the base of the anterior mitral leaflet
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What happens to the valves (grossly) during mitral valve prolapse? How does this cause the characteristic heart sounds?
Mitral valve leaflet(s) is (are) floppy and prolapse into the left atrium during systole
- create midsystolic click, regurgitant murmur
hooding with prolapse of the posterior mitral leaflet into the left atrium
thrombotic plaques at sites of leaflet-left atrium contact
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What populations is mitral valve prolapse more common in?
* 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
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Myxomatous degeneration of the mitral valve is often clinically silent. What complications can develop?
* Small subset (3%) may develop complications
* Infective endocarditis
* Mitral insufficiency
* Stroke or other systemic infarct
* Arrhythmias (both atrial and ventricular, rare sudden death)
* Atypical chest pain
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How is myxomatous degneration of the mitral valve dx'ed?
echocardiogram
auscultation
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What are the primary changes associated with myxomatous degeneration of the mitral valve?
* Intercordal ballooning of mitral valve leaflets
* Leaflets enlarge (thick and rubbery)
* Thinned fibrosa; thickened spongiosa with mucoid (myxoid) material
* Concomitant involvement of tricuspid valve in 20-40% of cases
Valve weakens due to mucoid instead of fibrous material à leads to stretching and ballooning, doesn’t work normally
188
What are the secondary changes associated with myxomatous degeneration of the mitral valve?
Secondary changes
* **Dilation of annulus**
* **Jet lesions** with fibrosis of endocardial surfaces
* Fibrosis of valve leaflets
* Thrombi on atrial surfaces of mitral leaflets
* Focal calcification at base of posterior leaflet
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How does strep pharyngitis cause chronic rheumatic valvular disease?
Beta-hemolytic strep infection -\> imm response, with anti-group A strep antigens
- fever and migratory polyarthritis results
- same infection, several weeks later -or- after new strep infection
- deposition of cross-reactive Ab on heart valves, chordae tendinae, myocardium, and cause of fibrinous pericarditis
Chronic rheumatic heart disease = deformity of heart valves
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What clinical signs and symptoms would you expect with chronic rheumatic valvular heart disease?
pericardial rub - fibrinous pericarditis
Usually occurs 10 days to 6 weeks post strep throat
- can get pancarditis – endocardium and valves,
myocardium and epicardium get granulomas called Aschoff bodies that show acute rheumatic fever
– can hear murmurs or pericardial rub
Aschoff body - Collection of large activated histiocytes
Anitschkow cells – “mononuclear”
Aschoff cells - multinucleated forms
caterpillar" cells - unique linear chromatin pattern
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What are the signs and symptoms of acute rheumatic fever?
Acute rheumatic fever: Acute systemic disease
* Migratory polyarthritis of large joints (swollen, painful joints)
* Acute carditis with cardiac enlargement and diminished function
* Subcutaneous nodules
* Erythema marginatum of skin
* Sydenham chorea (involuntary, purposeless movements of extremities)
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What is the Jones criteria for dx of acute rheumatic fever?
Jones Criteria” for diagnosis
Evidence prior group A Strep infection plus
* 2 major system findings (from above list of 5)
* Or 1 major system finding plus 2 minor manifestations
* Fever
* Arthralgia
* Evidence of acute phase reactants
* elevated sedimentation rate
* elevated C-reactive protein
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What kind of a reaction is acute rheumatic fever?
•Hypersensitivity reaction to M protein cross-reacting with tissue glycoproteins
194
How are subsequent attacks of rheumatic fever prevented after initial episode?
* After initial episode have increased risk of subsequent attacks with repeat group A Strep infections
* Patients may receive long-term antibiotic prophylaxis
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What is rheumatic heart disease? What valves does it affect?
Rheumatic Heart Disease (RHF)
* Term used for the chronic valvular disease that occurs years after ARF
* Commonly affects mitral and aortic valves
* Mitral valve only: 65 – 70 %
* Mitral valve plus aortic valve: 25%
* Uncommonly the tricuspid
* rarely the pulmonic valve
* 99% of all mitral stenosis is caused by RHD
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What are MacCallum plaques?
subendocardial fibrosis from regurgitant jets in RHD
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