Pathology of Myocardial Infarction

Medical school pathology lecture. Pathology of myocardial infarction.

1. "Man often becomes what he "Man often becomes what he
believes himself to be.believes himself to be.

Mahatma Gandhi
1869-1948, Indian Political Leader

2. Pathology of Myocardial Infarction:Pathology of Myocardial Infarction:
Dr. Venkatesh M. ShashidharDr. Venkatesh M. Shashidhar
Associate Professor & Head of Pathology

3. Coronary Coronary
ArteriesArteries
•Left Coronary A.
•L.Anterior Descending
•Left Circumflex
•Right Coronary A.
L.CxL.Cx
LADLAD

4. Coronary Coronary
Thrombosis With Thrombosis With
InfarctionInfarction

5. Ischaemic Heart DiseaseIschaemic 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).

6. No Q wave - Q waveNo Q wave - Q wave
Why spared?Why spared?

7. Coronary Atherosclerosis with Thrombosis -(MI)Coronary Atherosclerosis with Thrombosis -(MI)

8. Coronary AtherosclerosisCoronary Atherosclerosis

9. IHD Clinical Features: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):

10. Pathogenesis: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.

11. IHD Pathogenesis:IHD Pathogenesis:
Coronary block:
<70% - Asympto.
>70-75% - Angina
90% - Fixed stenosis
Chronic IHD
Plaque change:
–Unstable angina
–Rupture, fissure, ulcer.
> 90% - MI / SCD

12. Location of IHD / MILocation 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)

13. Morphology - Morphology - GrossGross & & MicroscopicMicroscopic
Time (approx) GROSS GROSS MICROSCOPYMICROSCOPY
Up to 4 hourNone None (loss of glycogen/LDH)
4 - 24 hoursGradually developing pale
centre dark mottling at
periphery. Oedematous.
Beginning coagulation necrosis
contraction bands.
Eosinophilia, pyknotic nuclei,
Oedema, acute inflammatory
cells.
3-7 days Clearly visible Yellow
rubbery centre with
haemorrhagic border
Obvious necrosis of muscle and
plenty of Neutrophils
hemorrhage few macrophages
& early granulation tissue.
1-3 weeks Infarcted area pale, thin
yellow, red gray border.
(loss of tissue mass)
Granulation tissue,
macrophages prominent
capillaries, fibroblasts.
3-6 weeks
(permanent)
Small Silvery scar
becoming tough and white
Replacement of granulation
tissue by dense fibrosis

14. Myocardial Infarction – 3-7 dayMyocardial Infarction – 3-7 day
Pale centre
Hemorrhagic periphery

15. Recent MI – 3-7 day. Recent MI – 3-7 day.
Pale centre
Hemorrhagic periphery
MI – Papillary M
LV
RV
Papillary Muscle

16. Myocardial Infarction Myocardial Infarction ? Recent ? old? Recent ? old
1-3wk
- Thin wall, white,
thin hemorrhagic periphery

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

18. MI: MI: ?Clinical features,?Clinical features, ? Time, ? Artery ?ECG? Time, ? Artery ?ECG
Acute Post. Infarct:
1-3 Days.
Reddish Brown
color
Hemorrhagic
No significant loss
of muscle mass.
Mural thrombus.
Complications:
H.failure, Rupture,
Tamponade,
Acute- MI
Mural Thrombus
Acute- MI

19. ?Clinical features,?Clinical features, ?Time, ?Artery ?ECG…?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.

20. Myocardial Infarction Myocardial Infarction ? time? time
Old & Recent

21. Normal Myocardium:Normal Myocardium:
Capillary-RBC
My. Neucleus
IC disc

22. MI 18hr MI 18hr loss of nucleus, contraction bands.loss of nucleus, contraction bands.
C.Bands

23. MI 18-24 hr MI 18-24 hr loss of nucleus, contaction bands, loss of nucleus, contaction bands,
coagulative necrosis.coagulative necrosis.

24. MI 1day MI 1day loss of nucleus, contraction bands, few loss of nucleus, contraction bands, few
neutrophils.neutrophils.
C.Bands
Neutro

25. MI 2-3 day – MI 2-3 day – Marginal inflammation.Marginal inflammation.
DeadDead LiveLive

26. MI 1-2 dayMI 1-2 day Hemorrhage & contraction bands in reperfusion injury.Hemorrhage & contraction bands in reperfusion injury.

27. MI 1-2 dayMI 1-2 day Hemorrhage & contraction bands in reperfusion injury.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).

28. MI 1-3 day – MI 1-3 day – Plenty of Neutrophils.Plenty of Neutrophils.

29. MI 1-3 wk – MI 1-3 wk – Granulation tissue, capillaries.Granulation tissue, capillaries.

30. MI 3-6wk - MI 3-6wk - Scar, inflam, outer viable myocardiumScar, inflam, outer viable myocardium
Live My.
Scar.

31. MI >6-Years - MI >6-Years - Collagen Scar no inflammation.Collagen Scar no inflammation.

32. Morphology - Morphology - GrossGross & & MicroscopicMicroscopic
Time (approx) GROSS GROSS MICROSCOPYMICROSCOPY
Up to 4 hourNone None (loss of glycogen)
4 - 24 hoursGradually developing pale
centre dark mottling at
periphery. Oedematous.
Beginning coagulation necrosis
contraction bands.
Eosinophilia, pyknotic nuclei,
Oedema, acute inflammatory
cells.
3-7 days Clearly visible Yellow
rubbery centre with
haemorrhagic border
Obvious necrosis of muscle and
plenty of Neutrophils
hemorrhage few macrophages
& early granulation tissue.
1-3 weeks Infarcted area pale, thin
yellow, red gray border.
(loss of tissue mass)
Granulation tissue,
macrophages prominent
capillaries, fibroblasts.
3-6 weeks
(permanent)
Small Silvery scar
becoming tough and white
Replacement of granulation
tissue by dense fibrosis

33. Complications: Complications: 75% cases.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.

34. Complications of MI: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

35. MI - RuptureMI - Rupture

36. MI – 3 days MI – 3 days ? diagnosis? diagnosis

37. MI – MI – Papillary muscle RupturePapillary muscle Rupture

38. MI - AneurysmMI - Aneurysm
Non contractile
Reduced stroke vol.
Mural thrombi

39. Old MI – Ventricular AneurysmOld MI – Ventricular Aneurysm
Aneurysm

40. Old MI – Ventricular AneurysmOld MI – Ventricular Aneurysm
After an infarct, stretching of
collagenous scar causing
aneurysmal bulging of the
ventricular wall (V).

41. MI – MI – Rupture & TamponadeRupture & Tamponade

42. 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. 100 F. 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.

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

44. What is the diagnosis?What is the diagnosis?
1 2 3 4 5
2
14
0
3
2
1.Acute MI
2.Old healed MI
3.Atherosclerotic IHD
4.Acute on chronic MI
5.Bacterial carditis (SBE)

45. 56y, fatigue, Heart - 56y, fatigue, Heart - ? Diagnosis? Diagnosis
A. B. C. D. E.
4 4
9
2
3
A.Acute on Chronic MI
B.Atherosclerosis & MI.
C.Acute MI only.
D.Old MI + aneurysm
E.Old MI + rupture.

46. MI treated, Myocardial Biopsy: Diagnosis?MI treated, Myocardial Biopsy: Diagnosis?
1 2 3 4 5
5
4
1
10
0
1.Acute MI – 1day.
2.Old MI - 6 wk + Hemorrhage.
3.Acute on Chronic MI
4.Acute MI + Reperfusion.
5.MI 1-3 weeks.

47. 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 2 3 4 5
5
4
1
10
0
1.Hypertrophic cardiomyopathy.
2.Myocardial infarction.
3.Prinzmetal angina.
4.Commotio cordis.
5.Long-QT Syndrome.

48. What is the diagnosis?What is the diagnosis?
1 2 3 4 5
2
14
11
3
1.Healed MI with aneurysm.
2.Acute MI with mural
thrombus
3.Acute Mi with aneurysm.
4.Acute on chronic MI
5.Acute MI with bacterial
Infection.

49. 52y chest pain, post mortem Heart 52y chest pain, post mortem Heart
(paper arrow) (paper arrow) what is the most likely Cause of death?what is the most likely Cause of death?
1 2 3 4 5
7
1 1
5
7
A.Cardiac tamponade
B.Acute MI
C.Ventricular aneurysm
D.Mitral incompetence
E.Thromboembolism

50. Myocardial Biopsy: MI duration?Myocardial Biopsy: MI duration?
1 2 3 4 5
0
4
0
6
11
1.< 4 hours
2.4-24 hours
3.1-3 days
4.1-3 weeks.
5.> 3 weeks.

51. Myocardial Biopsy: MI duration?Myocardial Biopsy: MI duration?
1 2 3 4 5
1
7
0
2
12
1.< 4 hours
2.4-24 hours
3.1-3 days
4.1-3 weeks.
5.> 3 weeks.

52. Myocardial Biopsy MI duration?Myocardial Biopsy MI duration?
(Blue collagen stain):(Blue collagen stain):
1 2 3 4 5
0 0
15
3
0
1.< 4 hours
2.4-24 hours
3.1-3 days
4.1-3 weeks.
5.> 3 weeks.

53. 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 5
5
4
1
10
0
1.Unstable angina (Prinzmetal).
2.MI - STEMI
3.Pulmonary Embolism.
4.MI - Non-STEMI
5.GERD (Hyperacidity-esophagitis).

54. 72y M, CCF: Complication shown by arrow?72y M, CCF: Complication shown by arrow?
1 2 3 4 5
14
5
00
1
1.Endocardial fibrosis
2.Old healed MI
3.Ventricular Aneurysm
4.Mitral incompetence
5.Mural thrombosis

55. 62y chronic IHD: ? complication62y chronic IHD: ? complication
1 2 3 4 5
0
15
2
0
2
1.Old Healed MI
2.LV Aneurysm
3.Mural thrombosis
4.Acute on Chronic MI
5.Cardiac tamponade.

56. Myocardial Biopsy: MI duration?Myocardial Biopsy: MI duration?
1 2 3 4 5
8
2
9
2
0
1.< 4 hours
2.4-24 hours
3.1-3 days
4.1-3 weeks.
5.> 3 weeks.

57. 62y chronic CHD: ? complication62y chronic CHD: ? complication
1 2 3 4 5
1
5
8
1
5
1.Old Healed MI
2.Old MI +Aneurysm+Thrombus
3.Old MI + Mural thrombus
4.Acute on Chronic MI
5.Acute on Old MI + Thrombus.

58. Myocardial Biopsy: MI duration?Myocardial Biopsy: MI duration?
1 2 3 4 5
10
6
2
0
2
1.< 4 hours
2.4-24 hours
3.1-3 days
4.1-3 weeks.
5.> 3 weeks.

59. CPC1.1. – Learning Issues: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.

60. Our progress towards success Our progress towards success
begins with a simple begins with a simple
fundamental question...?fundamental question...?
Where am I going...?Where am I going...?

61. Laboratory DiagnosisLaboratory Diagnosis

62. Self Study CasesSelf Study Cases
& Questions: & Questions:
Nice video of Pathogenesis of Acute MI online:
http://pri-med.com/PMO/Home.aspx
(Select “Pathogenesis of Acute MI” from list)

63. CaseCase
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.

64. CaseCase
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 <5μg/L)
Troponin I = <0.1 (R.Range <0.1μg/L)

65. Questions: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
information?

66. Case 2: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
otherwise well.

67. Case 2: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
0.6μg/L(Reference Interval = <0.1μg/L)

68. Questions: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?

69. Case 3: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 37.5°C,
BP=105/55, PR= 95/minute and regular.
There is a soft early

70. Case 3: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
= <0.1μg/L)
CRP = 28 (Reference Interval = 0-3mg/L)

71. Questions: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?