Cardiac Pathology 1: Aging, CHF, Congenital/Ischemic Heart Dz (Hillard) Flashcards
1
Q
In pt’s with what underlying disease may the onset of an MI be completely asymptomatic?
How is the disease discovered?
A
- Diabetic neuropathy
- Discovered ONLY by EKG and lab findings
2
Q
What are the most sensitive and specific markers of myocardial damage?
A
cTnT and cTnI
3
Q
Why is CK-MB a sensitive but not specific marker for myocardial damage?
A
Can also be elevated after skeletal m. injury
4
Q
How many hours post-MI do levels of CK-MB, cTnT and cTnI begin to rise in the serum?
A
3-12 hours
5
Q
After how many hours are levels of cTnI and CK-MB at their maximum levels following myocardial damage?
A
24 hours
6
Q
How long after myocardial damage does it take for CK-MB, cTnI and cTnT levels to normalize?
A
- CK-MB = 48-72 hours
- cTnI = 5-10 days
- cTnT = 5-14 days
7
Q
Half of all MI deaths occur within 1 hour of onset, and are usually secondary to what complication?
A
Arrhythmia
8
Q
What is the contractile dysfunction following an MI proportional to?
Severe “pump failure” can lead to what potentially lethal complication?
A
- Size of the infarct
- Cardiogenic shock = 70% mortality rate
9
Q
Myocardial rupture following an MI occurs when there is what type of necrosis?
A
Transmural
10
Q
What is the most common site of myocardial rupture seen following an MI and complications that ensue?
A
- Rupture of the ventricular free wall (anterolateral wall at mid-ventricular levels)
- Hemopericardium and cardiac tamponade
11
Q
Myocardial rupture occurring as a complication post-MI most often occurs when and is due to what?
A
- 2-4 days after MI
- When coagulative necrosis + neutrophilic infiltrate + lysis of myocardiac CT —> weaken infarcted myocardium
12
Q
What is a late complication of large transmural myocardial infarcts that experience early expansion?
A
Ventricular aneurysm = True aneurysm
13
Q
What are 3 possible complications of ventricular aneurysms occurring post-MI?
A
- Mural thrombus
- Arrhythmias
- Heart failure = most common complication
14
Q
Large transmural myocardium infarcts have a higher probability of which 3 potentially lethal complications?
A
- Cardiogenic shock
- Arrhythmias
- Late CHF
15
Q
Ventricular remodeling post-MI involves what 2 compnsatory changes occurring in the non-infarcted segments?
A
Hypertrophy and Dilation
16
Q
Hearts from patients with chronic IHD (ischemic cardiomyopathy) have what gross morphological changes?
A
Cardiomegaly w/ LV hypertrophy and dilation
17
Q
Which congenital heart disease presents as early cyanosis - “blue babies?”
A
Right-to-left shunts
18
Q
What are the 5 T’s associated with right-to-left shunts?
A
- Truncus arteriosus (1 vessel)
- Transposition (2 switched vessels)
- Tricuspid atresia (Tri = 3)
- Tetraology of fallot (Tetra = 4)
- TAPVR (5 letters) = total anomalous pulmonary venous connection
19
Q
What occurs in Eisenmenger Syndrome?
Consequences include?
A
- Uncorrected left-to-right shunt (VSD, ASD, PDA) –> ↑ pulmonary blood flow –> remodeling of vasculature –> pulmonary arterial HTN
- RVH occurs to compensate –> shunt becomes right to left (reversal)
- Causes: late cyanosis, clubbing, and polycythemia
20
Q
How does pressure-overload hypertrophy differ from that of volume-overload in terms of myocyte and ventricular changes?
A
- P.O. = myocytes thicken w/ concentric increase in wall thickness
- V.O. = myocytes elongate and ventricles dilate; wall thickness may be increased, normal, or decreased
21
Q
A hypertrophied heart is vulnerable to?
A
Ischemia-related decompensation
22
Q
Aerobic exercise tends to be associated with volume-overload hypertrophy that may be accompanied by what other compensatory mechanism not seen in pathological hypertophy?
A
Increase in capillary density
23
Q
Clinical and morphological effects of left-sided CHF are a consequence of what?
A
- Congestion of pulmonary circulation
- Decreased perfusion of down-stream tissues –> organ dysfunction
24
Q
Most common morphology of the LV in left-sided heart disease?
A
Hypertrophied and massively dilated
25
Kerley B and C lines noted on CXR are associated with CHF of which side?
Left-sided CHF
26
Which type of immune cells are seen in the lungs of pt with left-sided CHF and are a telltale sign of previous episodes of pulmonary edema?
**Heart failure cells** = *Hemosiderin-laden macrophages*
27
Cough, dyspnea on exertion, orthopnea, and paroxysmal nocturnal dyspneas are all signs of what type of CHF?
**Left-sided CHF**
28
A reduced ejection fraction in left-sided CHF leads to diminished renal perfusion and resultant activation of what?
Exacerbates what?
- Activates **RAAS** ---\> Na+ and H2O retention
- Exacerbates ongoing **pulmonary edema**
29
In left-sided CHF due to diastolic failure, the LV is stiff and cannot relax during diastole, so any increase in filling pressure is immediately transferred where and leads to?
Back into **pulmonary circulation** = rapid onset **pulmonary edema** (**flash pulmonary edema**)
30
Diastolic failure of left-sided CHF is seen more commonly in which sex and what is the most common underlying etiology?
- **Women** \>65 yo
- **HTN** is most common etiology
31
The common feature of the disorders that cause **primary right-sided CHF** (aka **cor pulmonale**) is what?
**Pulmonary HTN**
\*1' pulmonary HTN, recurrent pulmonary thromboembolism, and conditions causing pulmonary **vasocontriction** (i.e., obstructive sleep apnea, and altitude sickness)
32
Where are the major effects seen in right-sided CHF vs. left-sided?
- Mainly in the **systemic** and **portal venous systems**
- Pulmonary congestion is **minimal** (unlike in **left-sided**)
33
Hepatosplenomegaly, nutmeg liver, centrilobular necrosis and cardiac cirrhosis are all seen in what type of CHF?
**Right-sided** CHF
34
Systemic venous congestion in right-sided CHF can lead to fluid accumulations in which spaces?
- Pleural, pericardial, or peritoneal spaces
- **Effusions**
35
Edema in which areas of the body are a **hallmark** of right-sided CHF?
- **Peripheral** and dependent portions of body, especially **ankle (pedal)** and **pretibial edema**
- Generalized massive edema (**anasarca**) may occur
36
Renal congestion w/ greater fluid retention and more pronounced azotemia is more pronounced in CHF of which side?
**Right-sided** CHF
37
What is the single most common genetic cause of congenital heart disease?
**Trisomy 21 - Down syndrome**
38
*GATA4 + TBX5 + NKX2-5* are TF's implicated in what types of congenital heart defects?
**Atrial** and **ventricular septal** defects
39
Pt's with down syndrome have one or more heart defects, most often affecting structures derived from which heart field?
**2nd** heart field (i.e., **AV septae**) = **endocardial cushions**
40
Mutations in which gene are associated with **bicuspid aortic valve?**
*NOTCH1*
41
Mutations in which 2 genes are implicated in **Tetralogy of Fallot**?
***JAG1** and* ***NOTCH2***
42
Deletion of chromosome 22q11.2 is associated with what syndrome?
DiGeorge syndrome
43
Which gene located on chromosome 22q11.2 is the most likely culprit of cardiac abnormalities seen in deletion of this chromosome?
Gene is reponsible for regulating what?
***TBX1*** --\> regulates **NCC** migration
44
The deficits associated with DiGeorge syndrome can be remembered using CATCH-22, what are they?
- **C**ardiac abnormality
- **A**bnormal facies
- **T**hymic aplasia
- **C**left palate
- **H**ypocalcemia
- All on **chromosome 22**
45
Which chromosomal aneuploidies are most often associated with congential heart defects?
**Turner syndrome** (monosomy X) and **trisomies 13, 18, 21**
46
What are 3 enviornmental factors that alone or in combo w/ genetic factors are implicated in congenital heart disease?
- **Congenital rubella**
- **Gestational diabetes**
- **Teratogen exposure**
47
Which type of left-to-right defect causes an increase in RV and pulmonry outflow volumes **only**?
ASD
48
Which 2 left-to-right defects cause an **increase pulmonary blood flow and pressure**?
VSD and PDA
49
Left-to-right shunting causes volume overload on the right side which may lead to what 2 complications?
- **Pulmonary HTN**
**- Reversal (L--\>R becomes R--\>L = Eisenmenger syndrome)**
- **Right heart failure**
50
Paradoxical embolism is associated with what kind of shunt?
**Right** ---\> **Left**
\*Emboli from veins bypass the lungs and directly enter systemic circulation
51
Severe long-standing cyanosis associated with right-to-left shunts can cause what do conditions?
- **Clubbing** of fingers and toes = **hypertrophic ostroarthropathy**
- **Polycythemia**
52
Which type of ASD is not associated w/ other anomalies, may be of any size, and can be multiple or fenestrated?
**Secundum ASD**
53
Which location for an ASD is the most common?
**Septum Secundum** ASD
54
Which type of murmur may be associated with an ASD?
**Pulmonary valve** murmur; Pulm. blood flow = **2-8x normal**
55
At what age do ASD's generally become symptomatic?
Usually **not before** age **30**
56
In pt's with a patent foramen ovale what events can cause the unsealed flap to open and produce brief periods of right-to-left shunting?
Possible complication?
- **Anything that can ↑ right-sided pressures**
- Pulmonary HTN + Bowel movement + Coughing + Sneezing
- Complication = **paradoxical emboli**
57
90% of VSD's occur in which region and are classified as?
**Membranous** interventricular septum = **Membranous VSD**
58
Functional consequences of VSD's are dependent on what?
Size
59
Large VSDs can cause what 2 complications and almost universally lead to what overtime?
- Early **RV hypertrophy**
- **Pulmonary HTN** ---(**over time**)--\> **IRREVERSIBLE** **PVD**; shunt **reversal**, **cyanosis**, and **death**
60
PDA can arise due to delayed closure in infants with?
**- Hypoxia** (due to respiratory distress or heart disease)
**-** Presence of **VSD,** which ↑ pulmonary vascular pressures
61
A harsh "machinery-like" murmur is characteristic of what congenital heart defect?
PDA
62
What are the 4 cardinal features of Tetraology of Fallot?
\*Use the mnemonic PROVe
1) Sub**P**ulmonary stenosis (obstruction of the RV outflow tract)
2) **R**V hypertrophy
3) **O**verriding aorta
4) **V**SD
63
What does the clinical severity of Tetralogy of Fallot depend on?
Degree of **subpulmonary stenosis**, since this determines direction of flow
64
Classic TOF is associated with what degree of stenosis and has what consequences?
**Severe** stenosis --\> **right-to-left** shunt -\> **cyanosis**
65
Mild stenosis in TOF resembles what and has what type of shunt?
Resembles **VSD** w/ **L to R** shunt
66
Majority of infants with TOF are what at birth?
Cyanotic
67
Transpositon of the Great Arteries is **not** compatible with life unless what is present?
**Shunt** for adequate mixing of blood (VSD, PDA, or PFO)
68
What occurs in the RV and LV in pt's with Transposition of the Great Arteries?
- **RV** **hypertophy** due to functioning as **systemic** ventricle
- **LV** becomes **thin-walled** (**atrophic**)
69
Coarctation of the Aorta is common in which sex and seen in which chromosomal disease?
- **2x** more common in **males**
- **Females** w/ **Turner syndrome** are more commonly affected
70
How does the **infantile** form differ from the **adult** form of Coarctation of the Aorta?
- **Infantile** = tubular hypoplasia of aortic arch **proximal** to **PDA**
- **Adult** = discrete ridge-like infolding of aorta **distal** to **ligamentum arteriosum**
71
50% of cases of Coarctation of the Aorta are accompanied by what valvular anomaly?
**Bicuspid aortic valve**
\*May also be assoc. w/ congenital aortic stenosis, ASD, VSD, mitral regurgitation, or berry aneursyms of the circle of Willis
72
When does coarctation of the aorta **WITH** PDA usually manifest and what are the sx's?
- Manifests **AT BIRTH**
- **Cyanois** localized to **lower half of body**
73
How does coarctation of the aorta **WITHOUT** PDA typically manifest?
Characteristic signs and sx's?
- Usually **asymptomatic** at birth
- Adults = **HTN** in the **UE's** w/ **HYPOtension** + **weak pulses** in **LE's**
- **Claudication** and **cold** **LE's** due to low blood flow
- Development of **collateral** circulation thru **enlarged intercostal internal mammary as. --\> Rib notching** (on **radiographs**)
74
Which ausculatory finding may be appreciated with coarctation of the aorta?
Which ventricle undergoes adaptive change?
- **Murmur** w/ **vibratory "thrill"**
- **Concentric** LV **hypertrophy**
75
Hypoplastic left heart syndrome due to obstruction of LV outflow due to **severe congenital aortic stenosis or atresia** leads to what 3 morphological findings?
- **LV HYPOplasia**
- **HYPOplasia** of the **aorta**
- **Porcelain-**like **LV** endocardial **fibroelastosis**
76
Thickened ring or collar of dense endocardial fibrous tissue below the level of the aortic valve cusps is characteristic of which variation of aortic stenosis?
**Subaortic** stenosis
77
What must be maintained in severe congenital aortic stenosis or atresia to prevent death?
Preservation of **PDA patency**
78
Which variation of aortic stenosis/atresia is associated with a prominent systolic murmur and sometimes a thrill?
**Subaortic** stenosis
79
Supravalvular aortic stenosis is sometimes a component of which syndrome resulting from the deletions of which gene and on which chromosome?
- **Williams-Beuren Syndrome** --\> hypercalcemia, facial anomalies, cognitive abnormalities, and aortic stenosis
- **Elastin** gene on chromosome **7**
80
What are the 2 most common congenital conditions responsible for right-to-left shunts?
- **TOF**
- **Transposition of great arteries (TGA)**
81
Majority (90%) of cases of IHD are secondary to?
Obstructive **Atherosclerosis**
82
What are the 3 major coronary epicardial arteries involved by obstructive atherosclerosis in IHD?
- **LAD**
- **Circumflex branch** of **LCA = LCX**
- **RCA**
83
A fixed lesion obstructing **\>\_\_\_%** of vascular cross-section area defines significant CAD and is generally the threshold for symptomatic ischemia?
**\>75 %**
84
Acute plaque change that induces abrupt thrombotic occlusion, resulting in myocardial necrosis defines what?
Myocardial Infarction (**MI**)
85
Paroxysmal and recurrent attacks of chest pain induced by myocardial ischemia **insufficient** to induce myocyte necrosis (MI) is characteristic of?
Angina Pectoris
86
Severe angina or chest discomfort, described as frank pain that is increasing in frequency, duration, and severity precipitated by lower levels of physical activity or even at rest is characteristic of?
**Unstable** (or "**crescendo**") **angina**
87
Unstable (or "crescendo") angina is caused by what?
**Disruption** of atherosclerotic plaque w/ **partial thrombosis** and possibly **embolization** or **vasospasm** (or **both**)
88
50% of pt's w/ unstable ("crescendo") angina have evidence of what?
**Myocardial necrosis**; acute MI may be **imminent**
89
How soon after onset of severe ischemia does myocardial contractility cease?
Within **1 minute**
90
Severe ischemia (blood flow \<10% normal) for how long is associated with irreversible damage of cardiac myocytes?
**20-40 minutes**
91
Due to the myocardial perfusion pattern, ischemia is most pronounced in which layer and irreversible injury occurs in which zone first?
- **SUBendothelial** layer = most pronounced ischemia
- **SUBendothelial zone** = 1st to undergo irreversible injury
92
How many hours after onset of myocardial ischemia is half the thickness of the myocardium necrotic and how many hours for transmural necrosis?
- **1/2 thickness** = **2-3 hours**
- **Transmural** = **6 hours**
**\*Necrosis** moves from **SUBendocardium** --\> **epicardium**
93
The LAD supplies which 3 areas of the myocardium?
- Apex
- Anterior wall of LV
- Anterior 2/3's of septum
94
The RCA supplies which 3 areas of the myocardium?
- **Entire** RV free wall
- LV **posterior** wall
- **Posterior** 1/3 of septum
95
The LCX generally only supplies which area of the myocardium?
**Lateral** wall of **LV**
96
What is the myocardial damage like in subendocardial (nontransmural) infarction that occur as a result of **global hypotension?**
Damage usually **circumferential**, rather than being limited to distribution of single major coronary artery
97
Subendocardial (nontransmural) infarcts can occur due to plaque disruption followed by a coronary thrombus which undergoes what?
**Lysis** (therapeutically or spontaneously)
98
Multifocal microinfarction involves smaller intramural vessels and most often occurs due to what?
- Vasculitis
- Microembolization
- Vascular spasm --\> epinephrine or cocain
99
Why is there a **narrow** rim of preserved subendocardial myocardium even in a transmural infarction?
Due to **diffusion** of **O2** and **nutrients** from the **ventricular lumen**
100
What is the predominant mechanism of cell death (apoptosis/necrosis) following an MI and become detectable how long after onset?
Ischemic **coagulative necrosis** --\> **6-12 hrs**
101
Immersion of tissue slices into a **solution of what** following death from an acute MI allows for the visualization of necrotic areas?
**Triphenyl-tetrazolium chloride**
102
Which sublethal change may be seen in the margins of infarcts and reflects intracellular accumulation of Na+ and H2O within the sarcoplasmic reticulum?
Myocyte vacuolization or **myocytolysis**
103
When can **pyknosis** of nuclei; myocyte **hypereosinophilia**; marginal **contraction band** necrosis; and early **neutrophilic** infiltrate be visualized microscopically post-MI?
**12-24 hours**
104
How long post-MI will you see **coagulation necrosis** w/ **loss of nuclei** and striation; with **neutrophilic infiltration?**
**1-3 days**
105
What is the gross morphology of heart 1-3 days post-MI?
Mottling w/ **yellow-tan** infarct **center**
106
What is the gross morphology of heart 3-7 days post-MI?
**Hyperemic border**; central yellow-tan softening
107
How long post-MI will you see **beginning disintegration** of **dead myofibers** w/ dying neutrophils and **early phagocytosis** of dead cells by **macrophages**?
**3-7 days**
108
How many days post-MI will there be **well-developed phagocytosis** of dead cells w/ **granulation tissue at margins**?
**7-10 days**
109
How many days post-MI will there be **WELL-established granulation tissue** w/ **NEW blood vessels** and collagen deposition?
**10-14 days**
110
What is seen microscopically and grossly 2-8 weeks post-MI?
**- Micro =** **increased collagen** deposition, w/ decreased cellularity
**- Gross** = **gray-white scar**
111
\>2 months following an MI what will be seen microscopically?
**DENSE** collagenous scar = **Scarring** is **complete**
112
How long post-MI can early coagulation necrosis + **edema; hemorrhage** be visualized?
**4-12 hours**
113
Earliest detectable feature of myocyte necrosis via EM is disruption of what?
**Sarcolemmal disruption**; mitochondrial amorphous densities
114
A heart that is maximally yellow-tan and soft w/ **depressed** red-tan margins is seen how long post-MI?
7-10 days
115
Characteristic morphological finding of irreversibly injured myocytes following reperfusion?
**Contraction bands**
116
Myocardium that is subjected to chronic, sublethal ischemia may enter into a state of lowered metabolism and function called what?
**Hibernation**
117
