Cardiovascular - Pathology (1)

Question 1

Congenital heart diseases:
Right-to-left shunts

• Characteristic findings
• Diseases

Answer 1

• Characteristic findings
  
  • Early cyanosis
  • “Blue babies.”
  • Often diagnosed prenatally or become evident immediately after birth.
  • Usually require urgent surgical correction and/or maintenance of a PDA.
• Diseases (The 5 Ts)
  
  1. Truncus arteriosus (1 vessel)
  2. Transposition (2 switched vessels)
  3. Tricuspid atresia (3 = Tri)
  4. Tetralogy of Fallot (4 = Tetra)
  5. TAPVR (5 letters in the name)

Question 2

Persistent truncus arteriosus

• Type of disease
• Characteristics

Answer 2

• Type of disease
  
  • Right-to-left shunt congenital heart disease
• Characteristics
  
  • Failure of truncus arteriosus to divide into pulmonary trunk and aorta
  • Most patients have accompanying VSD.

Question 3

D-transposition of great vessels

• Type of disease
• Characteristics

Answer 3

• Type of disease
  
  • Right-to-left shunt congenital heart disease
• Characteristics
  
  • Aorta leaves RV (anterior) and pulmonary trunk leaves LV (posterior) –>Ž separation of systemic and pulmonary circulations.
  • Not compatible with life unless a shunt is present to allow mixing of blood (e.g., VSD, PDA, or patent foramen ovale).
  • Due to failure of the aorticopulmonary septum to spiral.
  • Without surgical intervention, most infants die within the first few months of life.

Question 4

Tricuspid atresia

• Type of disease
• Characteristics

Answer 4

• Type of disease
  
  • Right-to-left shunt congenital heart disease
• Characteristics
  
  • Absence of tricuspid valve and hypoplastic RV
  • Requires both ASD and VSD for viability.

Question 5

Tetralogy of Fallot

• Type of disease
• Characteristics

Answer 5

• Type of disease
  
  • Right-to-left shunt congenital heart disease
• Characteristics
  
  • Caused by anterosuperior displacement of the infundibular septum.
  • Most common cause of early childhood cyanosis.
  • Tetralogy: PROVe
    
    1. Pulmonary infundibular stenosis (most important determinant for prognosis)
    2. RVH—boot-shaped heart on CXR
    3. Overriding aorta
    4. VSD
  • Pulmonary stenosis forces right-to-left flow across VSD –>Ž early cyanotic “tet spells,” RVH.
  • Squatting: increased SVR, decreased right-to-left shunt, improves cyanosis.
  • Treatment: early surgical correction.

Question 6

Total anomalous pulmonary venous return (TAPVR)

• Type of disease
• Characteristics

Answer 6

• Type of disease
  
  • Right-to-left shunt congenital heart disease
• Characteristics
  
  • Pulmonary veins drain into right heart circulation (SVC, coronary sinus, etc.)
  • Associated with ASD and sometimes PDA to allow for right-to-left shunting to maintain CO.

Question 7

Congenital heart diseases:
Left-to-right shunts

• Characteristic findings
• Diseases

Answer 7

• Characteristic findings
  
  • Late cyanosis
  • “Blue kids.”
• Diseases
  
  • Frequency: VSD > ASD > PDA
    
    • Ventricular septal defect (VSD)
    • Atrial septal defect (ASD)
    • Patent ductus arteriosus (PDA)
  • Eisenmenter syndrome

Question 8

Ventricular septal defect

• Type of disease
• Characteristics

Answer 8

• Type of disease
  
  • Left-to-right shunt congenital heart disease
• Characteristics
  
  • Most common congenital cardiac defect.
  • Asymptomatic at birth, may manifest weeks later or remain asymptomatic throughout life.
  • Most self resolve
  • Larger lesions may lead to LV overload and heart failure.

Question 9

Atrial septal defect

• Type of disease
• Characteristics

Answer 9

• Type of disease
  
  • Left-to-right shunt congenital heart disease
• Characteristics
  
  • Defect in interatrial septum
    
    • Loud S1
    • Wide, fixed split S2.
  • Usually occurs in septum secundum
    
    • Septum primum defects usually occur with other anomalies.
  • Symptoms range from none to heart failure.
  • Distinct from patent foramen ovale in that septa are missing tissue rather than unfused.

Question 10

Patent ductus arteriosus

• Type of disease
• Characteristic findings

Answer 10

• Type of disease
  
  • Left-to-right shunt congenital heart disease
• Characteristic findings
  
  • In fetal period, shunt is right to left (normal).
  • In neonatal period, decreased lung resistance –>Ž shunt becomes left to right –> progressive RVH and/or LVH and heart failure.
  • Associated with a continuous, “machine-like” murmur.
  • Patency is maintained by PGE synthesis and low O2 tension.
    
    • “Endomethacin” (indomethacin) ends patency of PDA
    • PGE** kEEps it open (may be necessary to sustain life in conditions such as transposition of the great vessels).**
  • Uncorrected PDA can eventually result in late cyanosis in the lower extremities (differential cyanosis).
  • PDA is normal in utero and normally closes only after birth.

Question 11

Eisenmenger syndrome

• Type of disease
• Characteristics

Answer 11

• Type of disease
  
  • Left-to-right shunt congenital heart disease
• Characteristics
  
  • Uncorrected left-to-right shunt (VSD, ASD, PDA)
    
    • –>Ž increased pulmonary blood flow
    • –>Ž pathologic remodeling of vasculature
    • –> pulmonary arteriolar hypertension.
  • RVH occurs to compensate –>Ž shunt becomes right to left.
  • Causes late cyanosis, clubbing, and polycythemia.
  • Age of onset varies.

Question 12

Coarctation of the aorta

• Associated with…
• Infantile type
• Adult type

Answer 12

• Associated with bicuspid aortic valve, other heart defects.
• Infantile type
  
  • Aorta narrowing is proximal to insertion of ductus arteriosus (preductal).
    
    • Infantile: in close to the heart.
  • Associated with Turner syndrome.
  • Can present with closure of the ductus arteriosus (reverse with PGE2).
• ​Adult type
  
  • Aorta narrowing is distal to ligamentum arteriosum (postductal).
    
    • Adult: distal to ductus.
  • Associated with notching of the ribs (collateral circulation), hypertension in upper extremities, and weak, delayed pulses in lower extremities (radiofemoral delay).

Question 13

Defects associated with these congenital cardiac disorders

• 22q11 syndromes
• Down syndrome
• Congenital rubella
• Turner syndrome
• Marfan syndrome
• Infant of diabetic mother

Answer 13

• 22q11 syndromes
  
  • Truncus arteriosus
  • Tetralogy of Fallot
• Down syndrome
  
  • ASD
  • VSD
  • AV septal defect (endocardial cushion defect)
• Congenital rubella
  
  • Septal defects
  • PDA
  • Pulmonary artery stenosis
• Turner syndrome
  
  • Bicuspid aortic valve
  • Coarctation of aorta (preductal)
• Marfan syndrome
  
  • MVP
  • Thoracic aortic aneurysm and dissection
  • Aortic regurgitation
• Infant of diabetic mother
  
  • Transposition of great vessel

Question 14

Hypertension

• Definition
• Risk factors
• Features
• Predisposes to…

Answer 14

• Definition
  
  • A systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg
• Risk factors
  
  • Increased age
  • Obesity
  • Diabetes
  • Smoking
  • Genetics
  • Black > white > Asian.
• Features
  
  • 90% of hypertension is 1° (essential) and related to increased CO or increased TPR
  • Remaining 10% mostly 2° to renal disease, including fibromuscular dysplasia in young patients [A].
  • Hypertensive emergency—severe hypertension (≥ 180/120 mmHg) with evidence of acute, ongoing target organ damage (e.g., papilledema, mental status changes).
• Predisposes to…
  
  • Atherosclerosis
  • LVH
  • Stroke
  • CHF
  • Renal failure [B]
  • Retinopathy
  • Aortic dissection.

Question 15

Hyperlipidemia signs

Answer 15

• Xanthomas
  
  • Plaques or nodules composed of lipid-laden histiocytes in the skin [A], especially the eyelids (xanthelasma [B]).
• Tendinous xanthoma
  
  • Lipid deposit in tendon [C], especially Achilles.
• Corneal arcus
  
  • Lipid deposit in cornea, appears early in life with hypercholesterolemia.
  • Common in elderly (arcus senilis [D]).

Question 16

Arteriosclerosis

• Mönckeberg (medial calcific sclerosis)
• Arteriolosclerosis

Answer 16

• Mönckeberg (medial calcific sclerosis)
  
  • Uncommon.
  • Calcification in the media of the arteries, especially radial or ulnar.
  • Usually benign
  • “Pipestem” arteries on x-ray [A].
  • Does not obstruct blood flow
  • Intima not involved.
• Arteriolosclerosis
  
  • Common.
  • Two types:
    
    • Hyaline (thickening of small arteries in essential hypertension or diabetes mellitus [B])
    • Hyperplastic (“onion skinning” as seen in severe hypertension [C]).

Question 17

Atherosclerosis

• Definition
• Risk factors
  
  • Modifiable
  • Non-modifiable
• Progression
• Complications
• Location
• Symptoms

Answer 17

• Definition
  
  • Disease of elastic arteries and large- and medium-sized muscular arteries.
• Risk factors
  
  • Modifiable: smoking, hypertension, hyperlipidemia, diabetes.
  • Non-modifiable: age, sex (increased in men and postmenopausal women), and family history.
• Progression
  
  • Inflammation important in pathogenesis.
  • Endothelial cell dysfunction Ž–> macrophage and LDL accumulation –>Ž foam cell formation –>Ž fatty streaks Ž–> smooth muscle cell migration (involves PDGF and FGF), proliferation, and extracellular matrix deposition –>Ž fibrous plaque –>Ž complex atheromas [A].
• Complications
  
  • Aneurysms, ischemia, infarcts, peripheral vascular disease, thrombus, emboli.
• Location
  
  • Abdominal aorta > coronary artery > popliteal artery > carotid artery [B].
• Symptoms
  
  • Angina, claudication, but can be asymptomatic.

Question 18

Aortic aneurysms

• Definition
• Abdominal aortic aneurysm
• Thoracic aortic aneurysm

Answer 18

• Definition
  
  • Localized pathologic dilation of the aorta.
  • May cause pain, which is a sign of leaking, dissection, or imminent rupture.
• Abdominal aortic aneurysm
  
  • Associated with atherosclerosis.
  • Occurs more frequently in hypertensive male smokers > 50 years old [A].
• Thoracic aortic aneurysm
  
  • Associated with cystic medial degeneration due to hypertension (older patients) or Marfan syndrome (younger patients).
  • Also historically associated with 3° syphilis (obliterative endarteritis of the vasa vasorum) [B].

Question 19

Aortic dissection

Answer 19

• Longitudinal intraluminal tear forming a false lumen [A].
• Associated with hypertension, bicuspid aortic valve, and inherited connective tissue disorders (e.g., Marfan syndrome).
• Can present with tearing chest pain, of sudden onset, radiating to the back +/- markedly unequal BP in arms.
• CXR shows mediastinal widening.
• The false lumen can be limited to the ascending aorta, propagate from the ascending aorta, or propagate from the descending aorta.
• Can result in pericardial tamponade, aortic rupture, and death.

Question 20

Ischemic heart disease manifestations:
Angina

• Definition
• Stable
• Variant angina (Prinzmetal)
• Unstable/crescendo

Answer 20

• Definition
  
  • Chest pain due to ischemic myocardium 2° to coronary artery narrowing or spasm
  • No myocyte necrosis.
• Stable
  
  • Usually 2° to atherosclerosis
  • Exertional chest pain in classic distribution (usually with ST depression on ECG), resolving with rest.
• Variant angina (Prinzmetal)
  
  • Occurs at rest 2° to coronary artery spasm
  • Transient ST elevation on ECG.
  • Known triggers include tobacco, cocaine, and triptans, but trigger is often unknown.
  • Treat with calcium channel blockers, nitrates, and smoking cessation (if applicable).
• Unstable/crescendo
  
  • Thrombosis with incomplete coronary artery occlusion
  • ST depression on ECG (increases in frequency or intensity of chest pain; any chest pain at rest).

Question 21

Ischemic heart disease manifestations:
Coronary steal syndrome

Answer 21

• Distal to coronary stenosis, vessels are maximally dilated at baseline.
• Administration of vasodilators (e.g., dipyridamole, regadenoson) dilates normal vessels and shunts blood toward well-perfused areas –>Ž decreased flow and ischemia in the poststenotic region.
• Principle behind pharmacologic stress tests

Question 22

Ischemic heart disease manifestations:
Myocardial infarction

Answer 22

• Most often acute thrombosis due to coronary artery atherosclerosis with complete occlusion of coronary artery and myocyte necrosis.
• If transmural, ECG will show ST elevations
• If subendocardial, ECG may show ST depressions.
• Cardiac biomarkers are diagnostic.

Question 23

Ischemic heart disease manifestations:
Sudden cardiac death

Answer 23

• Death from cardiac causes within 1 hour of onset of symptoms, most commonly due to a lethal arrhythmia (e.g., ventricular fibrillation).
• Associated with CAD (up to 70% of cases), cardiomyopathy (hypertrophic, dilated), and hereditary ion channelopathies (e.g., long QT syndrome).

Question 24

Ischemic heart disease manifestations:
Chronic ischemic heart disease

Answer 24

• Progressive onset of CHF over many years due to chronic ischemic myocardial damage.

Question 25

Evolution of MI * Commonly occluded coronary arteries * Symptoms * 0-4 hr * Gross * Light microscope * Complications

Answer 25

* Commonly occluded coronary arteries * LAD \> RCA \> circumflex. * Symptoms * Diaphoresis, nausea, vomiting, severe retrosternal pain, pain in left arm and/or jaw, shortness of breath, fatigue. * 0-4 hr * Gross * None * Light microscope * None * Complications * Arrhythmia, HF, cardiogenic shock, death.

Question 26

Evolution of MI: 4-12 hr * Gross * Light microscope * Complications

Answer 26

* Gross * Occluded artery * Infarct * Dark mottling * Pale with tetrazolium stain * Light microscope * Early coagulative necrosis, release of necrotic cell contents into blood * Edema, hemorrhage, wavy fibers. * Complications * Arrhythmia, HF, cardiogenic shock, death.

Question 27

Evolution of MI: 12–24 hr * Gross * Light microscope * Complications

Answer 27

* Gross * Occluded artery * Infarct * Dark mottling * Pale with tetrazolium stain * Light microscope * Neutrophil migration starts. * Reperfusion injury may cause contraction bands (due to free radical damage). * Complications * Arrhythmia, HF, cardiogenic shock, death.

Question 28

Evolution of MI: 1–3 days * Gross * Light microscope * Complications

Answer 28

* Gross * Hyperemia * Light microscope * Extensive coagulative necrosis. * Tissue surrounding infarct shows acute inflammation with neutrophils. * Complications * Fibrinous pericarditis.

Question 29

Evolution of MI: 3–14 days * Gross * Light microscope * Complications

Answer 29

* Gross * Hyperemic border * Central yellow-brown softening * Maximally yellow and soft by 10 days * Light microscope * Macrophages, then granulation tissue at margins. * Complications * Free wall rupture --\>Ž tamponade * Papillary muscle rupture --\>Ž mitral regurgitation * Interventricular septal rupture due to macrophage-mediated structural degradation. * LV pseudoaneurysm (mural thrombus “plugs” hole in myocardium --\>Ž “time bomb”).

Question 30

Evolution of MI: 2 weeks to several months * Gross * Light microscope * Complications

Answer 30

* Gross * Recanalized artery * Gray-white * Light microscope * Contracted scar complete. * Complications * Dressler syndrome, HF, arrhythmias, true ventricular aneurysm (outward bulge during contraction, “dyskinesia”).

Question 31

Diagnosis of MI * Gold standard * Cardiac troponin I * CK-MB * ECG changes

Answer 31

* In the first 6 hours, ECG is the gold standard. * Cardiac troponin I * Rises after 4 hours * Increased for 7–10 days * More specific than other protein markers. * CK-MB * Predominantly found in myocardium but can also be released from skeletal muscle. * Useful in diagnosing reinfarction following acute MI because levels return to normal after 48 hours. * ECG changes * ST elevation (STEMI, acute transmural infarct) * ST depression (subendocardial infarct) * Pathologic Q waves (evolving or old transmural infarct).

Question 32

Types of infarcts * Transmural infarcts * Subendocardial infarcts

Answer 32

* Transmural infarcts * Increased necrosis * Affects entire wall * ST elevation on ECG, Q waves * Subendocardial infarcts * Due to ischemic necrosis of \< 50% of ventricle wall * Subendocardium especially vulnerable to ischemia * ST depression on ECG

Question 33

ECG diagnosis of MI: Leads with Q waves for these infarct locations * Anterior wall * Anteroseptal * Anterolateral * Lateral wall * Inferior wall

Answer 33

* Anterior wall (LAD) * V1–V4 * Anteroseptal (LAD) * V1–V2 * Anterolateral (LAD or LCX) * V4–V6 * **_L_**ateral wall (**_L_**CX) * I, aV**_L_** * In**_F_**erior wall (RCA) * II, III, aV**_F_**

Question 34

MI complications * Cardiac arrhythmia * Cardiogenic shock * Greatest risk 6–14 days postinfarct * Ventricular pseudoaneurysm formation * Postinfarction fibrinous pericarditis * Dressler syndrome * Other

Answer 34

* Cardiac arrhythmia * Important cause of death before reaching hospital * Common in first few days. * Cardiogenic shock * Large infarct * High risk of mortality. * Greatest risk 6–14 days postinfarct * Ventricular free wall rupture Ž--\> cardiac tamponade * Papillary muscle rupture --\>Ž severe mitral regurgitation * Interventricular septum rupture Ž--\> VSD * Ventricular pseudoaneurysm formation * Decreased CO, risk of arrhythmia, embolus from mural thrombus * Greatest risk approximately 1 week post-MI. * Postinfarction fibrinous pericarditis * Friction rub (1–3 days post-MI). * **Dressler syndrome** * Autoimmune phenomenon resulting in fibrinous pericarditis (several weeks post-MI). * Other * LV failure * Pulmonary edema