Cardiovascular Pathology-2

Question 1

What are the 4 clinical syndromes associated with ischemic heart disease?

Answer 1

– Angina pectoris (AP)
– Myocardial infarction (MI)
– Chronic IHD with CHF
– Sudden cardiac death (SCD)

Question 2

What is the common feature of Angina pectoris and the 3 subtypes?

Answer 2

– Stable (Typical) angina pectoris

– Prinzmetal (Variant) angina

– Unstable (Crescendo) angina pectoris

Question 3

What is the common features of STABLE
(TYPICAL) ANGINA

Answer 3

stable when extra stress or excertion

Question 4

What is the common features associated with PRINZMETAL (VARIANT) ANGINA

Answer 4

occurs at rest, vasospasms

Question 5

What are the common features associated with UNSTABLE (CRESCENDO) ANGINA?

Answer 5

Question 6

Common feature of Myocardial infarction?

Answer 6

• Indicates the development of an area of myocardial necrosis caused by local ischemia

• occurs at any age
• more males affected than females affected until menopause where the protection affect of estrogen tapers off

Question 7

What are the Major contributing factors of Myocardial infarction?

Answer 7

• Hypercholesterolemia
• Smoking
• Hypertension
• Diabetes mellitus

Question 8

What is the pathogenesis of Myocardial infarction?

Answer 8

Pathogenesis: 90% of cases due to acute thrombosis that leads to coronary artery occlusion. • Disruption of a pre-existing plaque which in
– 2/3rd have < 50% stenosis – 85% have < 70% stenosis

Remaining 10% of cases due to
• Vasospasm – isolated, intense and relatively prolonged with or without coronary atherosclerosis • Emboli – from the left sided mural thrombus • Unexplained – Disease of small intramural coronary vessels or Hematological abnormalities

Question 9

Transmural Infarctions features?

Answer 9

– Involve the full thickness of ventricular wall in the distribution of a single coronary artery (Regional) also called STEM

• Due to total occulsion of the feeding coronary artery and the collaterals cant compensate for that
  – Usually associated with acute plaque changes and superimposed, completely occlusive thrombosis.
  – Can also occur with Cocaine abuse

Question 10

Subendocardial infarctions features?

Answer 10

Subendocardial infarctions
– Limited to the inner one third or at most one half of the ventricular wall also called NSTEMI

– Associated with diffuse stenosing coronary atherosclerosis or with prolonged hypotension (Global/Circumferential infarctions)

– May occur due to transient/partial arterial obstruction (Regional) – Less serious than transmural infarction

Question 11

What are the essential sequence of events in MI ?

Answer 11

Coagulative necrosis

Inflammation then resorption of necrotic myocardium

Formation of granulation tissue

Organization of granulation tissue to form a collagen rich scar tissue

Question 12

Time sequence of MI

Answer 12

• 1-day-old infarct showing coagulative necrosis and wavy fibers
• Dense polymorphonuclear leukocytic infiltrate in an acute myocardial infarction of a 3 days old
• Removal of necrotic myocytes by phagocytosis (approximately 7 to 10 days)
• Granulation tissue characterized by loose collagen and abundant capillaries
• Healed myocardial infarct, necrotic tissue is replaced by a dense collagenous scar. The residual cardiac muscle hypertrophy

Question 13

Reperfusion therapy in MI

Answer 13

Is the goal of therapy to salvage maximal amount of ischemic cells

• Achieved by:
– Thrombolysis using enzymes e.g. Streptokinase
or tissue plasminogen activator

– Angioplasty or CABG

• Although it is useful, reperfusion of ischemic tissue can cause rebound myocardial damage which can lead to Reperfusion injury

Question 14

Mechanisms of Reperfusion Injury ?

Answer 14

• Mitochondrial dysfunction → promote apoptosis

• High extracellular Ca+2 and impaired Ca+2 cycling → myocyte hypercontracture → cytoskeletal damage
• Free radicals are produced within minutes of reperfusion → myocardial damage

• Leukocytes aggregation & platelet activation → microvasculature injury and occlusion → “no reflow” phenomenon

Question 15

Contraction band necrosis occurs?

Answer 15

– Intense hyper-eosinophilic transverse bands (hypercontracted sarcomeres)

– Induced by high amount of extracellular calcium in restored blood flow which easily crosses the leaky plasma membrane of ischemic myocytes – Actin - myosin interaction in the absence of ATP- the sarcomeres are stuck in this agonal tetanic state

Question 16

Clinical Features of MI

Answer 16

• Chest pain: – Retrosternal pain, Crushing in nature, May radiate to the neck, jaw, epigastrium, shoulder, or left arm
– The pain is persistent >30 mins (unlike angina)
– Not significantly relieved by vasodilators
(nitroglycerine) or rest

• Dyspnea
• Rapid weak pulse
• Diaphoresis, Nausea & vomiting

Question 17

What is a silent MI

Answer 17

• Silent MI (neuropathy)
– Occurs in as many as 25% of cases
– Asymptomatic MI that is discovered only by EKG changes and laboratory tests

– Common in elderly patients

– Underlying Diabetes mellitus/ Hypertension

Question 18

Complication of Ischemic MI

Answer 18

• Extension of the infarction • Reinfarction • Angina

Question 19

Arrhythmic MI complications?

Answer 19

Factors that can cause arrhythmias following MI:

• Myocardial irritability and conduction disturbances
• Electrolyte imbalance
• Hypoxia Arrhythmias are the most common cause of SCD

Question 20

Complication of an Embolic MI?

Answer 20

• Wall motion abnormalities endocardial damage → Mural thrombus
• Mural thrombi are common in the left ventricle→ Systemic emboli
• Stroke (most common), limb ischemia, renal infarction or mesenteric ischemia can occur

Question 21

Mechanical complication of an MI?

Answer 21

1. Contractile dysfunction: • Depend on size, site, thickness of the infarction • Can cause variable range of ventricular failure • If severe → Cardiogenic Shock(10-15% of cases) • Progressive heart failure (chronic
   IHD)
2. Papillary muscle dysfunction: • Rupture • Ischemia • Fibrosis
   → Mitral Valve Incompetence or → Tricuspid Valve Incompetence
3. Myocardial Rupture
   • Occurs between 3-10 days when necrosis, neutrophilic infiltration
   and myocardial tissue lysis → weakened myocardium

It includes: • Ventricular free wall rupture → tamponade • Ventricular septum rupture → VS

4. Ventricular aneurysm
   • Late complication of large transmural infarcts • Scar tissue wall of an aneurysmbulges during systole • Mural thrombus, arrhythmias
   and heart failure may occur • Unlikely to rupture due to tough
   fibrotic wall

Question 22

Inflammaotry complications of MI

Answer 22

Pericarditis
2 types can occur following MI:

1. Acute fibrinous/ fibrinohemorrhagic: - Due to direct irritation of the pericardium in transmural infarcts. - Usually in day 2 or 3 post MI
2. Autoimmune – Dresslers’ syndrome - Occurs 10-14 days post MI - Autoantibodies that target damaged pericardial antigens

Question 23

What is seen in the EKG of an MI

Answer 23

EKG: Transmural infarct: • ST segment elevation • Q wave: delayed appear after 6 hours of onset

Subendocardial infarct • No specific changes • No ST segment elevation • May show T wave depression

Question 24

What are the cardiac injury markers seen in MI?

Answer 24

A. Myoglobin
– First biomarker to rise (1-4 hrs)
– Highly sensitive but not specific for the heart
– Rarely used in practice

B. Troponins (I and T)
– Most sensitive and specific marker
– Normally not detectable in circulation
– Rises in 3-12 hrs, peaks at 48 hrs and persists for 5-14 days

C. Creatine Kinase isoenzymes (CK-MB)
– A dimer composed of M & B subunits: MM, MB, BB
– CK-MB: most specific for the heart among the CKs
– Rises in 3-12 hrs, Peaks at 24 hrs and disappears by 72 hrs – Useful for detection of reinfarction
D. Lactate dehydrogenase (LDH)
– Rises in 24 hrs, peaks at 3-6 days and returns to baseline within 8-12 days

Question 25

Why is an Echocardiogram used in MI?

Answer 25

• Useful in detecting complications of MI
• Evaluate ventricular function and wall- motion abnormalities
• Can identify pericardial effusion, valve regurgitation and cardiac tamponade

Question 26

What are the intervetions that can be used in an MI

Answer 26

• • Primary prevention • Thrombolysis • Defibrillation • Angioplasty • Coronary bypass graft (CABG)

Question 27

Chronic Ischemic Heart Disease pathogenesis?

Answer 27

• Insidious onset of CHF in patients who have past episodes of MI or anginal attacks

• Cardiac decompensation owing to exhaustion of the compensatory hypertrophy of non- infarcted viable myocardium or severe coronary
obstructive disease leading to diffuse myocardial
dysfunction

• Arrhythmia, intercurrent MI are common and fatal

Question 28

What is the gross and histologically findings of Chronic Ischemic Heart Disease

Answer 28

Morphology

• Gross
– Enlarged and heavy heart due to hypertrophy and
dilation

– Discrete gray white scars of healed previous infarcts

– Patchy fibrous thickening of mural endocardium

• Histologically
– Myocardial hypertrophy
– Diffuse subendocardial vacuolization

• Myocytolysis
  – Scars of previously healed infarcts

Question 29

What is Sudden Cardiac Death and what are the most common causes in adults and younger patients?

Answer 29

• Unexpected death from cardiac causes without symptoms or within 1-24 hours of onset of symptoms
• In adults: CAD is the most common cause

• In younger victims: the causes could be
− Congenital coronary
− Conduction system defects (AD long QT syndrome)
− Sarcoidosis
artery abnormalities − Aortic valve stenosis − Pulmonary hypertension − Mitral valve prolapse − Cardiomyopathy − Myocarditis

Question 30

Sudden cardiac death morphology?

Answer 30

• Ultimate mechanism of SCD is a lethal arrhythmia - left ventricular fibrillation

• Morphology
– 80-90% of cases – critical stenosis of one or more coronary arteries
associated with acute plaque disruption

– 10-20% - non atherosclerotic in origin