"Man often becomes what he believes himself to be.

Mahatma Gandhi 1869-1948, Indian Political Leader

Pathology of Myocardial Infarction:

Dr. Venkatesh M. Shashidhar
Associate Professor & Head of Pathology

Coronary Arteries
Left Coronary A. L.Anterior Descending Left Circumflex Right Coronary A.
L.Cx

LAD

Coronary Thrombosis With Infarction

Ischaemic Heart Disease

Etiology Obstruction to blood flow.

Most common - Atherosclerosis increased demand / Obstruction Ischemia / Infarction.

Angina Cardiac chest pain.

Stable / Unstable / Variant

Risk factors (atherosclerosis)

Non Modifiable: Male Sex, Age, Genetic factors. Modifiable: Hypertension, Diabetes, Smoking, Life style, Diet (High LDL, Low HDL).

No Q wave - Q wave

Why spared?

Coronary Atherosclerosis with Thrombosis -(MI)

Coronary Atherosclerosis

IHD Clinical Features:

Angina Pectoris: (no infarction)

Stable angina, common, Exercise or excitement. stable atherosclerotic narrowing of CA. Unstable/crescendo/Preinfarction angina Increasing pain/attacks, less effort/exercise, advanced atheroma prone to complications. Prinzmetal variant angina occurs at rest. spasm of coronary arteries (may not be a atheroma).

Acute Myocardial Infarction:

Sudden Cardiac Death (SCD): Chronic IHD (Heart failure):

Pathogenesis:

Obstruction to blood flow.

Arteriosclerosis, Atheroma, Thrombosis, Embolism, Rupture/hemorrhage.

Diminished coronary perfusion. Ischemic cell injury Chemical mediaters Chest Pain (Angina) Infarction Necrosis (MI)
Inflammation Granulation tissue Healing by Fibrous scarring.

Complications:
Acute: Cardiac death, conduction defects, Rupture Late: CCF, Aneurysm, Infection.

IHD Pathogenesis:
Coronary block:

<70% - Asympto.
>70-75% - Angina 90% - Fixed stenosis Chronic IHD Plaque change:
Unstable angina
Rupture, fissure, ulcer.

> 90% - MI / SCD

Location of IHD / MI

LAD: 40% to 50%

anterior left ventricle, anterior septum, and apex circumferentially.

RCA: 30% to 40%

Posterior LV, posterior septum & RV free wall in some.

LCX (Left circumflex): 15% to 20%

Lateral LV except the apex. (Read clinical & ECG features for each)

Morphology - Gross & Microscopic

Time (approx)

GROSS
None Gradually developing pale centre dark mottling at periphery. Oedematous. Clearly visible Yellow rubbery centre with haemorrhagic border Infarcted area pale, thin yellow, red gray border. (loss of tissue mass) Small Silvery scar becoming tough and white

MICROSCOPY
None (loss of glycogen/LDH) Beginning coagulation necrosis contraction bands. Eosinophilia, pyknotic nuclei, Oedema, acute inflammatory cells. Obvious necrosis of muscle and plenty of Neutrophils hemorrhage few macrophages & early granulation tissue. Granulation tissue, macrophages prominent capillaries, fibroblasts. Replacement of granulation tissue by dense fibrosis

Up to 4 hour 4 - 24 hours

3-7 days

1-3 weeks

3-6 weeks (permanent)

Myocardial Infarction 3-7 day

Hemorrhagic periphery

Pale centre

Recent MI 3-7 day.

RV LV

Hemorrhagic periphery

Myocardial Infarction ? Recent ? old

MI - Triphenyl Tetrazolium Cl. Stain for LDH. old MI recent MI & Hemorrhage

MI: ?Clinical features, ? Time, ? Artery

?ECG

Acute- MI

Acute- MI

Acute Post. Infarct: 1-3 Days. Reddish Brown color Hemorrhagic No significant loss of muscle mass. Mural thrombus. Complications: H.failure, Rupture, Tamponade,

?Clinical features, ?Time, ?Artery ?ECG

Old MI

Chronic / old: Weeks to months. Whitish grey scar. Significant loss of muscle mass thin wall. No hemorrhage, thrombus, not dark.. Complications: CCF, aneurysm.

Myocardial Infarction ? time

Old

&

Recent

Normal Myocardium:
My. Neucleus Capillary-RBC

IC disc

MI 18hr loss of nucleus, contraction bands.

C.Bands

MI 18-24 hr loss of nucleus, contaction bands,

coagulative necrosis.

MI 1day loss of nucleus, contraction bands, few

neutrophils.

Neutro

C.Bands

MI 2-3 day Marginal inflammation.

Dead

Live

MI 1-2 day

Hemorrhage & contraction bands in reperfusion injury.

MI 1-2 day

Hemorrhage & contraction bands in reperfusion injury.

MI with reperfusion. A Gross and B microscopy: Following streptokinase therapy. (triphenyl tetrazolium chloride-stained transverse section; posterior wall at top.) B, Myocardial necrosis with hemorrhage and contraction bands, visible as hypereosinophilic bands spanning myofibers (arrow).

MI 1-3 day Plenty of Neutrophils.

MI 1-3 wk Granulation tissue, capillaries.

MI 3-6wk - Scar, inflam, outer viable myocardium

Live My. Scar.

MI >6-Years - Collagen Scar no inflammation.

Morphology - Gross & Microscopic

Time (approx)

GROSS
None Gradually developing pale centre dark mottling at periphery. Oedematous. Clearly visible Yellow rubbery centre with haemorrhagic border Infarcted area pale, thin yellow, red gray border. (loss of tissue mass) Small Silvery scar becoming tough and white

MICROSCOPY
None (loss of glycogen) Beginning coagulation necrosis contraction bands. Eosinophilia, pyknotic nuclei, Oedema, acute inflammatory cells. Obvious necrosis of muscle and plenty of Neutrophils hemorrhage few macrophages & early granulation tissue. Granulation tissue, macrophages prominent capillaries, fibroblasts. Replacement of granulation tissue by dense fibrosis

Up to 4 hour 4 - 24 hours

3-7 days

1-3 weeks

3-6 weeks (permanent)

Complications:

75% cases.

Acute Complications: Dysfunction, Arrhythmias, Extension of infarction, or re-infarction Congestive heart failure (pulm edema) Cardiogenic shock Pericarditis Mural thrombosis, embolization Myocardial wall rupture, tamponade (3-7days) Papillary muscle rupture

Chronic Complications: Ventricular aneurysm CCF cardiac failure. Mural thrombosis Papillary muscle contraction Mitral regurgitation.

Complications of MI:

A Anterior myocardial rupture . B Rupture ventricular septum C Rupture papillary muscle. D Fibrinous pericarditis (dark, rough) E Thinning and mural thrombus. F aneurysm

MI - Rupture

MI 3 days ? diagnosis

MI Papillary muscle Rupture

MI - Aneurysm

Non contractile Reduced stroke vol. Mural thrombi

Old MI Ventricular Aneurysm

Aneurysm

Old MI Ventricular Aneurysm

After an infarct, stretching of collagenous scar causing aneurysmal bulging of the ventricular wall (V).

MI Rupture & Tamponade

CASE STUDY: 40y diabetic woman - chest pain. P/H Hypertension, 30 pack-year smoking history. She is on antihypertensives and Statins Had several years ago uncomplicated, myocardial infarct. She had had angina for many years, averaging one bout of angina a month. Her usual angina lasted 10-15 minutes and was relieved by nitroglycerine. Angioplasty several years ago relieved her symptoms for six months, but eventually exercise-induced angina returned. There were no clinical changes until two weeks prior to her emergency room admission, when she began having daily anginal attacks that lasted 30 minutes or more. In the hour prior to her admission, she had awakened with severe chest pain, nausea, and dyspnea. There had been severe unrelenting pain for 45 minutes, and it had not been relieved by nitroglycerine. Vital signs: HR 105, BP 100/50 (her usual BP was about 155/95), temp. 100F. She was obese and diaphoretic (sweating profusely) with pale skin and labored respirations. Rales were heard over both lung fields. An EKG and serial cardiac markers were ordered. QUESTIONS: ? Differential Diagnosis, ? Further investigations, ? Prognosis, ? Pathology of Coronary Art. & Myocardium ? Type of Infarct, ? Complications (short term & long term) ? Advice.

"Slow down and enjoy life. It's not only the scenery you miss by going too fast, you also miss the sense of where you are going and why."
Eddie Cantor 1892-1964, Comedian

What is the diagnosis?

1.
2. 3. 4.

5.

Acute MI Old healed MI Atherosclerotic IHD Acute on chronic MI Bacterial carditis (SBE)
14

3 2 2 0
1 2 3 4 5

56y, fatigue, Heart - ? Diagnosis

A. B. C. D. E.

Acute on Chronic MI Atherosclerosis & MI. Acute MI only. Old MI + aneurysm Old MI + rupture.
9

4 3 2

A.

B.

C.

D.

E.

MI treated, Myocardial Biopsy: Diagnosis?

MI 1day. 2. Old MI - 6 wk + Hemorrhage. 3. Acute on Chronic MI 4. Acute MI + Reperfusion. 5. MI 1-3 weeks.
1. Acute
10

5 4

1 0
1 2 3 4 5

17y male found in cardiac arrest following blow to chest while playing football. Spontaneous recovery following defibrillation. Paramedic ECG strop at the site showed ventricular fibrillation. On arrival at ER X-ray chest & ECG showed no abnormality, Cardiac markers high normal cardiac troponin-1. What is the most likely diagnosis?
1. Hypertrophic

10

cardiomyopathy. 2. Myocardial infarction. 3. Prinzmetal angina. 4. Commotio cordis. 5. Long-QT Syndrome.

5 4

1 0
1 2 3 4 5

What is the diagnosis?

1.
2. 3.

4.
5.

Healed MI with aneurysm. Acute MI with mural thrombus Acute Mi with aneurysm. Acute on chronic MI Acute MI with bacterial Infection.
14

3 2 1 1

52y chest pain, post mortem Heart (paper arrow) what is the most likely Cause of death?
A. B. C. D. E.
7

Cardiac tamponade Acute MI Ventricular aneurysm Mitral incompetence Thromboembolism

7

Myocardial Biopsy: MI duration?

1. 2. 3. 4. 5.

< 4 hours 4-24 hours 1-3 days 1-3 weeks. > 3 weeks.
11

6 4

0
1 2 3 4

0
5

Myocardial Biopsy: MI duration?

1. 2. 3. 4. 5.

< 4 hours 4-24 hours 1-3 days 1-3 weeks. > 3 weeks.
12

2 1 0
1 2 3 4 5

Myocardial Biopsy MI duration? (Blue collagen stain):

1. 2. 3. 4.

5.

< 4 hours 4-24 hours 1-3 days 1-3 weeks. > 3 weeks.

15

3 0
1

0
2

0
3 4 5

52year woman, worst heartburn ever experienced since 8 hours intermittent. Tired for last few days, truble taking deep breath. No pain radiation, initially relieved by antacids, but now not responding to Ranitidine and rest. Hypertension 8 years, Hyperlipidemia 3 years. P/E BP 146/90, Chest X-ray & Troponin normal, ECG 1-2mm ST depression in anterior leads. What is the most likelyosis?
1. 2. 3. 4.
10

5.

Unstable angina (Prinzmetal). MI - STEMI Pulmonary Embolism. MI - Non-STEMI GERD (Hyperacidity-esophagitis).

5 4

1 0
1 2 3 4 5

72y M, CCF: Complication shown by arrow?

1. 2. 3. 4. 5.

Endocardial fibrosis Old healed MI Ventricular Aneurysm Mitral incompetence Mural thrombosis
14

1 0
1 2 3 4

0
5

62y chronic IHD: ? complication

1.
2. 3.

4.
5.

Old Healed MI LV Aneurysm Mural thrombosis Acute on Chronic MI Cardiac tamponade.

15

2 0
1 2 3

2 0
4 5

Myocardial Biopsy: MI duration?

1. 2. 3. 4. 5.
8

< 4 hours 4-24 hours 1-3 days 1-3 weeks. > 3 weeks.
9

0
1 2 3 4 5

62y chronic CHD: ? complication

1. 2. 3. 4.

5.

Old Healed MI Old MI +Aneurysm+Thrombus Old MI + Mural thrombus Acute on Chronic MI Acute on Old MI + Thrombus.
8

Myocardial Biopsy: MI duration?

1. 2. 3. 4. 5.
10

< 4 hours 4-24 hours 1-3 days 1-3 weeks. > 3 weeks.

2 0
1 2 3 4

CPC1.1. Learning Issues:

Atherosclerosis:

Etiology / Risk factors, Pathogenesis. Morphology/types dot, streak, soft, hard, c Complications :BV / Tissue, Acute/Chronic Lipids LDL, HDL, ratio, interpretation. Epidemiology & Research in AS*

Ishemic Heart Disease:

Angina types & pathophysiology. Clinical features LAD, RC, LC pathological basis. MI etiology, pathogenesis, gross, micro (time), MI Complications acute/chronic.

Our progress towards success begins with a simple fundamental question...?

Where am I going...?

Laboratory Diagnosis

Self Study Cases & Questions:

Nice video of Pathogenesis of Acute MI online: http://pri-med.com/PMO/Home.aspx (Select Pathogenesis of Acute MI from list)

Case
A 42-year-old man presents to your surgery with central chest and left shoulder pain which came on during his weekly game of squash, lasted for about 20 minutes and was relieved by rest. He is otherwise well but smokes 25 cigarettes a day. On examination his BP is 140/85 and pulse rate is 65 and regular. Heart sounds are normal and lung fields are clear on auscultation.

Case
You perform an ECG in your rooms which is normal apart from some LVH. You refer the patient to the pathology lab for CK-MB and troponin I tests and send the patient home to rest and await the results. The blood is taken three hours after the onset of pain. Results: CK-MB = 9 (R.Range <5g/L) Troponin I = <0.1 (R.Range <0.1g/L)

Questions:
Is troponin useful when measured 3 hours after onset of chest pain? What is the diagnostic utility of measuring CK-MB and troponin I levels at the same time? What further testing would confirm or rule out an evolving myocardial infarct? Is the measurement of troponin T likely to provide better diagnostic

Case 2:
A 58-year-old woman visits your surgery at 7pm with a history of three episodes of chest pain during the day. The first occurred at 8am after her morning swim, and lasted about an hour. The second occurred soon after lunch lasting 30 minutes, and the third episode came on during a walk after dinner and is continuing, although not as severe as initially. She has no history of chest pain and is

Case 2:
Physical examination is unremarkable and the ECG shows ST depression of 1-2mm in the anterior leads. You call an ambulance and send her to the emergency department. In the emergency department the ECG is repeated and is unchanged. Blood is sent to the lab for troponin I level which is reported as 0.6g/L(Reference Interval = <0.1g/L)

Questions:
Is this a significant rise in troponin I or a borderline insignificant result? Does the troponin I level confirm MI? How should this patient be investigated?

Case 3:

A 35-year-old man presents to your surgery with a two-day history of malaise, fever and intermittent chest pain. He is a non-smoker with no other significant medical history. The chest pain is described as sharp and pleuritic and is worse on lying flat. He does not complain of dyspnoea, but has felt very tired and lethargic in the past few days and has not been able to exercise as usual. On examination he is febrile at 37.5C, BP=105/55, PR= 95/minute and regular. There is a soft early

Case 3:

systolic murmur at the left sternal edge which you think is a flow murmur. No added sounds are heard and the lung fields are clear. An ECG reveals widespread T-wave inversion with poor R-wave progression over the chest leads. You arrange for the patient to be transported to the nearest emergency department where blood is drawn for troponin and C-reactive protein (CRP) levels. Results Troponin I = 0.9 (Reference Interval

Questions:
How do you interpret these results in the context of the clinical presentation and ECG? What further investigations need to be done? What is the usual indication for CRP measurement? What other information may CRP provide that is particularly relevant to patients with coronary artery disease?