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Heart - Pathology
Ischemic Heart Disease
 Hypoxemia (diminished transport of oxygen by
the blood) less deleterious than ischemia
 Also called coronary artery disease (CAD) or
coronary heart disease
 IHD =Syndromes
late manifestations of coronary
atherosclerosis
 Cause => 90% of cases, coronary
atherosclerotic arterial obstruction
1
Dr. Krishna Tadepalli, MD, www.mletips.com
Heart - Pathology
Ischemic Heart Disease
 Classification = mainly 4 types
Myocardial infarction (MI)
Sudden cardiac death
Angina pectoris
Chronic IHD with heart failure
 Acute Coronary syndromes
important predisposing factor -Plaque
disruption or Acute plaque change
Acute myocardial infarction
Unstable angina
Sudden cardiac death

2
Dr. Krishna Tadepalli, MD, www.mletips.com
Heart - Pathology
Ischemic Heart Disease
 75% stenosis = symptomatic ischemia induced by
exercise
 90% stenosis = symptomatic even at rest
 Pathogenesis
 ↓ coronary perfusion relative to myocardial demand
 Role of Acute Plaque Change
(Erosion/ulceration, Hemorrhage into the atheroma,
Rupture/fissuring, Thrombosis)

 Role of Inflammation

T cell, Macrophages (MMPs), CRP

 Role of Coronary Thrombus

The most dreaded complication

 Role of Vasoconstriction (VC)

Platelet & Endothelial factors, VC substances

3

Dr. Krishna Tadepalli, MD, www.mletips.com
Heart - Pathology

4
Dr. Krishna Tadepalli, MD, www.mletips.com
Heart - Pathology
Plaque
Disruption

Syndrome

Stenoses

Plaque-Associated Thrombus

Stable angina

>75%

No

No

Unstable angina

Variable

Frequent

Non-occlusive

Transmural MI

Variable

Frequent

Occlusive

Subendocardial
MI

Variable

Variable

Widely variable

Sudden death

severe

Frequent

Often small

5
Dr. Krishna Tadepalli, MD, www.mletips.com
Heart - Pathology
Ischemic Heart Disease
 Angina Pectoris
 Chest discomfort = prolonged, recurrent, different qualities
 Cause = transient myocardial ischemia( seconds to minutes)
 Patterns
Stable = 75% vessel block, transient ( <15 minutes),
aggravated by exertion, relived by rest & Nitroglycerin
(VD)
Prinzmetal = coronary spasm, episodic, Typical EKG
change – ST elevation, Relived by VD but not rest
Unstable = 90% vessel block or Acute plaque change
( superimposed thrombus), prolonged ( >15 min.), not
relived by rest, VD, Pre-infarction Angina
6
Dr. Krishna Tadepalli, MD, www.mletips.com
MI - Types
Transmural
 Full thickness
 Superimposed thrombus in
atherosclerosis
 Focal damage

Sub-endocardial
 Inner 1/3 to half of
ventricular wall
 Decreased circulating blood
volume( shock,
Hypotension, Lysed
thrombus)
 Circumferential

7
Dr. Krishna Tadepalli, MD, www.mletips.com
Heart - Pathology
Ischemic Heart Disease
 MI= Also called Heart attack
 Incidence = disease of old
 elderly (45% in 65 yrs. old)
 young ( 10% in 40yrs. Old),

 Sex = Male > Female
 Ethnic = same in African & American
 Risk factors
 Major modifiable- DM, HTN, Smoking,
Hypercholesterolemia
 HRT for Postmenopausal females – will not protect
the heart
8
Dr. Krishna Tadepalli, MD, www.mletips.com
Heart - Pathology

Ischemic Heart Disease

 MI
 Pathogenesis
 Coronary vessel occlusion
Atherosclerosis with thrombus = MC cause ( 90% cases)
Others = vasospasm (10%)

 Most important mechanism = dynamic changes in
the plaque (rather than plaque size),
 Plaque disruption PLTS aggregation thrombus
and VC (happens in minutes)
 Irreversible changes = after 30 minutes of ischemia
ATP < 10% of normal

 Mechanism of cell death = necrosis ( Coagulative)
9
Dr. Krishna Tadepalli, MD, www.mletips.com
Heart - Pathology
Ischemic Heart Disease
TTC

10
Dr. Krishna Tadepalli, MD, www.mletips.com
Heart - Pathology
Ischemic Heart Disease
 MI -Morphology
 light microscopy

 First 12 hrs. after MI – no change
 Up to 3 days = Coagulative necrosis, neutrophils
 1-2 weeks = Granulation tissue
 ≥ 3 weeks = fine scar
 ≥ 2 months = dense scar

 EM – membrane disruption and Mitochondrial densities
 Special stain = TTC ( Triphenyl Tetrazolium chloride),
 Detects and stains Mahogany brown with Lactate dehydrogenase
 Unstained area = infarction
 Mahogany brown = viable
 White, glistening= scar

 Most common and nonspecific change in ischemia = subendocardial myocyte vacuolization

11

Dr. Krishna Tadepalli, MD, www.mletips.com
MI- Microscopic features
One-day-old infarct

Up to 3 days duration

wavy fibers

coagulative necrosis

1 -2 weeks

Granulation tissue

Neutrophilic infiltrate

>3 weeks

Scar

12

Dr. Krishna Tadepalli, MD, www.mletips.com
Heart - Pathology
Ischemic Heart Disease
 MI –Reperfusion
 Mechanisms
 Intrinsic
 Extrinsic =
Thrombolytic drugs = < 1hr. After onset of MI
PTCA/CABG = > 1hr. After onset of MI

 Target = clot lysis and restoration of blood flow
 Post- reperfusion changes =
 Contraction bands = hyper contracting myocytes,
 Stunned myocardium = transient, protective dysfunction
 Reperfusion damage = mostly apoptosis by free radicals
( unlike MI)

13
Dr. Krishna Tadepalli, MD, www.mletips.com
Heart - Pathology
Ischemic Heart Disease

14
Dr. Krishna Tadepalli, MD, www.mletips.com
Heart - Pathology
Ischemic Heart Disease
 MI = Clinical
 Silent MI = DM, Elderly, Cardiac transplantation
recipients,
 Typical features = Rapid, weak pulse and sweating
profusely (diaphoretic), Dyspnea, chest pain
 Lab=
 Diagnostic
Best markers = Troponins ( T & I), both sensitive and
cardio – specific
Next best – CK-MB

 Predictive
CRP- >3mg/l – highest risk

15
Dr. Krishna Tadepalli, MD, www.mletips.com
Heart - Pathology
Ischemic Heart Disease
MI –Complications



In 75% of Patients with MI
Poor prognosis in = elderly, females, DM, old case of MI, Anterior
wall infarct – worst, posterior –worse, Inferior wall – best
 1. Arrhythmia = Ventr. Fibrillation – MC arrhythmia lead to
sudden death in MI patients, before they reach hospital
 2. pump failure – LVF, cariogenic shock, if >LV wall infarcts,
lead to death ( 70% of hospitalized MI patients)
 3.Ventricular rupture = Free or lateral LV wall – MC site,
later cause false aneurysm,
 4.True aneurysm = rupture is very rare
 5.Pericarditis = Dressler’s syndrome ( Late MI complication)
 6.Recurrence

16

Dr. Krishna Tadepalli, MD, www.mletips.com
Heart - Pathology
Ischemic Heart Disease
 Sudden cardiac death = unexpected death in one hour
due to cardiac causes with or without clinical symptoms
 Cause – Atherosclerosis ( 90%), others (10%)
 Romano- Ward syndrome – Long Q-T syndrome
( K+, Na+ channel defects)
 Mechanism- Most likely due to arrhythmias ( VF)
 Patients – young athletes, with Pul. HTN, IHD
 Morphology
 Prominent finding – increased heart mass
 Vacuolations in Sub – endocardial myocardium
17
Dr. Krishna Tadepalli, MD, www.mletips.com
Heart - Pathology
Ischemic Heart Disease
 Chronic IHD = also called ischemic cardiomyopathy
 Patients = post heart transplant receipts, previous MI or
CABG pts
 Cause =compromised ventricular function
 Morphology =vacuoles, Myocyte Hypertrophy
 Diagnosis= by exclusion

18
Dr. Krishna Tadepalli, MD, www.mletips.com
Heart - Pathology
What is it?

19
Dr. Krishna Tadepalli, MD, www.mletips.com
Heart - Pathology
What are these?

20
Dr. Krishna Tadepalli, MD, www.mletips.com

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3. heart patghology; ischemic heart diseases

  • 1. Heart - Pathology Ischemic Heart Disease  Hypoxemia (diminished transport of oxygen by the blood) less deleterious than ischemia  Also called coronary artery disease (CAD) or coronary heart disease  IHD =Syndromes late manifestations of coronary atherosclerosis  Cause => 90% of cases, coronary atherosclerotic arterial obstruction 1 Dr. Krishna Tadepalli, MD, www.mletips.com
  • 2. Heart - Pathology Ischemic Heart Disease  Classification = mainly 4 types Myocardial infarction (MI) Sudden cardiac death Angina pectoris Chronic IHD with heart failure  Acute Coronary syndromes important predisposing factor -Plaque disruption or Acute plaque change Acute myocardial infarction Unstable angina Sudden cardiac death 2 Dr. Krishna Tadepalli, MD, www.mletips.com
  • 3. Heart - Pathology Ischemic Heart Disease  75% stenosis = symptomatic ischemia induced by exercise  90% stenosis = symptomatic even at rest  Pathogenesis  ↓ coronary perfusion relative to myocardial demand  Role of Acute Plaque Change (Erosion/ulceration, Hemorrhage into the atheroma, Rupture/fissuring, Thrombosis)  Role of Inflammation T cell, Macrophages (MMPs), CRP  Role of Coronary Thrombus The most dreaded complication  Role of Vasoconstriction (VC) Platelet & Endothelial factors, VC substances 3 Dr. Krishna Tadepalli, MD, www.mletips.com
  • 4. Heart - Pathology 4 Dr. Krishna Tadepalli, MD, www.mletips.com
  • 5. Heart - Pathology Plaque Disruption Syndrome Stenoses Plaque-Associated Thrombus Stable angina >75% No No Unstable angina Variable Frequent Non-occlusive Transmural MI Variable Frequent Occlusive Subendocardial MI Variable Variable Widely variable Sudden death severe Frequent Often small 5 Dr. Krishna Tadepalli, MD, www.mletips.com
  • 6. Heart - Pathology Ischemic Heart Disease  Angina Pectoris  Chest discomfort = prolonged, recurrent, different qualities  Cause = transient myocardial ischemia( seconds to minutes)  Patterns Stable = 75% vessel block, transient ( <15 minutes), aggravated by exertion, relived by rest & Nitroglycerin (VD) Prinzmetal = coronary spasm, episodic, Typical EKG change – ST elevation, Relived by VD but not rest Unstable = 90% vessel block or Acute plaque change ( superimposed thrombus), prolonged ( >15 min.), not relived by rest, VD, Pre-infarction Angina 6 Dr. Krishna Tadepalli, MD, www.mletips.com
  • 7. MI - Types Transmural  Full thickness  Superimposed thrombus in atherosclerosis  Focal damage Sub-endocardial  Inner 1/3 to half of ventricular wall  Decreased circulating blood volume( shock, Hypotension, Lysed thrombus)  Circumferential 7 Dr. Krishna Tadepalli, MD, www.mletips.com
  • 8. Heart - Pathology Ischemic Heart Disease  MI= Also called Heart attack  Incidence = disease of old  elderly (45% in 65 yrs. old)  young ( 10% in 40yrs. Old),  Sex = Male > Female  Ethnic = same in African & American  Risk factors  Major modifiable- DM, HTN, Smoking, Hypercholesterolemia  HRT for Postmenopausal females – will not protect the heart 8 Dr. Krishna Tadepalli, MD, www.mletips.com
  • 9. Heart - Pathology Ischemic Heart Disease  MI  Pathogenesis  Coronary vessel occlusion Atherosclerosis with thrombus = MC cause ( 90% cases) Others = vasospasm (10%)  Most important mechanism = dynamic changes in the plaque (rather than plaque size),  Plaque disruption PLTS aggregation thrombus and VC (happens in minutes)  Irreversible changes = after 30 minutes of ischemia ATP < 10% of normal  Mechanism of cell death = necrosis ( Coagulative) 9 Dr. Krishna Tadepalli, MD, www.mletips.com
  • 10. Heart - Pathology Ischemic Heart Disease TTC 10 Dr. Krishna Tadepalli, MD, www.mletips.com
  • 11. Heart - Pathology Ischemic Heart Disease  MI -Morphology  light microscopy  First 12 hrs. after MI – no change  Up to 3 days = Coagulative necrosis, neutrophils  1-2 weeks = Granulation tissue  ≥ 3 weeks = fine scar  ≥ 2 months = dense scar  EM – membrane disruption and Mitochondrial densities  Special stain = TTC ( Triphenyl Tetrazolium chloride),  Detects and stains Mahogany brown with Lactate dehydrogenase  Unstained area = infarction  Mahogany brown = viable  White, glistening= scar  Most common and nonspecific change in ischemia = subendocardial myocyte vacuolization 11 Dr. Krishna Tadepalli, MD, www.mletips.com
  • 12. MI- Microscopic features One-day-old infarct Up to 3 days duration wavy fibers coagulative necrosis 1 -2 weeks Granulation tissue Neutrophilic infiltrate >3 weeks Scar 12 Dr. Krishna Tadepalli, MD, www.mletips.com
  • 13. Heart - Pathology Ischemic Heart Disease  MI –Reperfusion  Mechanisms  Intrinsic  Extrinsic = Thrombolytic drugs = < 1hr. After onset of MI PTCA/CABG = > 1hr. After onset of MI  Target = clot lysis and restoration of blood flow  Post- reperfusion changes =  Contraction bands = hyper contracting myocytes,  Stunned myocardium = transient, protective dysfunction  Reperfusion damage = mostly apoptosis by free radicals ( unlike MI) 13 Dr. Krishna Tadepalli, MD, www.mletips.com
  • 14. Heart - Pathology Ischemic Heart Disease 14 Dr. Krishna Tadepalli, MD, www.mletips.com
  • 15. Heart - Pathology Ischemic Heart Disease  MI = Clinical  Silent MI = DM, Elderly, Cardiac transplantation recipients,  Typical features = Rapid, weak pulse and sweating profusely (diaphoretic), Dyspnea, chest pain  Lab=  Diagnostic Best markers = Troponins ( T & I), both sensitive and cardio – specific Next best – CK-MB  Predictive CRP- >3mg/l – highest risk 15 Dr. Krishna Tadepalli, MD, www.mletips.com
  • 16. Heart - Pathology Ischemic Heart Disease MI –Complications   In 75% of Patients with MI Poor prognosis in = elderly, females, DM, old case of MI, Anterior wall infarct – worst, posterior –worse, Inferior wall – best  1. Arrhythmia = Ventr. Fibrillation – MC arrhythmia lead to sudden death in MI patients, before they reach hospital  2. pump failure – LVF, cariogenic shock, if >LV wall infarcts, lead to death ( 70% of hospitalized MI patients)  3.Ventricular rupture = Free or lateral LV wall – MC site, later cause false aneurysm,  4.True aneurysm = rupture is very rare  5.Pericarditis = Dressler’s syndrome ( Late MI complication)  6.Recurrence 16 Dr. Krishna Tadepalli, MD, www.mletips.com
  • 17. Heart - Pathology Ischemic Heart Disease  Sudden cardiac death = unexpected death in one hour due to cardiac causes with or without clinical symptoms  Cause – Atherosclerosis ( 90%), others (10%)  Romano- Ward syndrome – Long Q-T syndrome ( K+, Na+ channel defects)  Mechanism- Most likely due to arrhythmias ( VF)  Patients – young athletes, with Pul. HTN, IHD  Morphology  Prominent finding – increased heart mass  Vacuolations in Sub – endocardial myocardium 17 Dr. Krishna Tadepalli, MD, www.mletips.com
  • 18. Heart - Pathology Ischemic Heart Disease  Chronic IHD = also called ischemic cardiomyopathy  Patients = post heart transplant receipts, previous MI or CABG pts  Cause =compromised ventricular function  Morphology =vacuoles, Myocyte Hypertrophy  Diagnosis= by exclusion 18 Dr. Krishna Tadepalli, MD, www.mletips.com
  • 19. Heart - Pathology What is it? 19 Dr. Krishna Tadepalli, MD, www.mletips.com
  • 20. Heart - Pathology What are these? 20 Dr. Krishna Tadepalli, MD, www.mletips.com