Tutorial in cardiovascular histopathology for 5th year medical students at Cambridge University.

1. Histopath Tutorial 1:
Cardiovascular Pathology
Christiane Riedinger 27/2/14

2. Today
● overview of CV path
● some pathology of most important topics
○ MI
○ endocarditis
● an example case

3. Overview of Cardiovascular Path
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Ischaemic Heart Disease - insufficient blood supply
○ Atherosclerosis
○ Angina pectoris
○ MI, sudden cardiac death
Hypertensive Heart Disease - pumping against elevated pressure
Valvular Disease
Inflammation / Infection of the layers of the heart
Congenital Heart Disease - embryological defects
Cardiomyopathies - acquired and genetic problems of heart muscle
Tumours
Vasculitides
Aneurysms and Dissections
(vascular vs. more heart related)

4. List of Pathological Causes
A
– autoimmune
V
– vascular
I
– infective, inflammatory
T
– traumatic
A
– acquired
M
– metabolic
I
– iatrogenic
N
– neurological, neoplastic, nutritional
C
– congenital
D
– degenerative, drugs
E
– environmental, endocrine
P
– psychosomatic

5. Overview of CV Path
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what’s most important!
Ischaemic Heart Disease - insufficient blood supply
○ Atherosclerosis
○ Angina pectoris
○ MI, sudden cardiac death
Hypertensive Heart Disease - pumping against elevated pressure
Valvular Disease
Inflammation / Infection of the layers of the heart
Congenital Heart Disease - embryological defects
Cardiomyopathies - acquired and genetic problems
Tumours
Vasculitides
Aneurysms and Dissections
=> pretty much all the “vitamins”

6. Today
● overview of CV path
● some pathology of most important topics
○ MI
○ endocarditis
● an example case

7. Pathology of MI’s
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Definition: A myocardial infaction is ischaemia of an area of cardiac
muscle, leading to necrosis of muscle tissue that can be fatal.
Aetiology: coronary artery thrombosis: disruption of existing plaque,
embolism (mainly from mural thrombus or valve vegetations), vasospasm,
increased demand on marginally perfused heart
○ risk almost 50% >65y! female sex hormones protective
Pathogenesis:
○ disruption of plaque => new clotting => thrombus↑ => occlusion of
lumen => ischaemia, irreversible after 20-40min => necrosis
○ molecular pathogenesis: loss of contractility and electrical instability
○ Buzz words: “non-contractile state”, “stunned myocardium”, “transient
cardiac failure”

8. Pathology of MI’s ctnd.
Patterns of MIs
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Patterns of blood supply:
○ L CA => fatal => widow maker
○ 40-50% L ant ↓ => ant. LV wall, IV septum, apex
○ 30-40% prox. R CA => RV
○ (post. becomes post. ↓ in 90% => LV)
Relating to the heart wall:
○ Subendocardial infarction (last to receive blood at high intramural
pressure, most susceptible zone)
○ Transmural = full thickness infarction => ST ELEVATION!
○ Microscopic infarction
http://www.sciencedirect.com/science/journal/13573039/38/7

9. Pathology of MI’s ctnd.
Timing of MI morphology =>
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Clinical Features:
○ severe chest pain
○ not relieved
○ …
Complications:
○ ¾ of pt. >1!
○ contractile dysfunction
○ structual dysfunction
○ electrical dysfunction
○ clotting
○ chronic: IHD, cardiomyopathy

10. Pathology of MI’s ctnd.
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Investigations:
○ CK-MB (myocardial isoform of creatine kinase)
○ LDH
○ Troponin
○ ECG: Q-waves, ST elevation, T-wave inversions, arrhythmias
○ U&E for raised K+
○ LFTs for raised AST
○ ABG
Timing
○ BNP
● Myoglobin ↑ 2h
○ Lactate
● CK-MB ↑ 4-8h GOLD STANDARD!
○ potential cardiac scintigram
● Troponin I ↑ 12h (peak)
● LDH ↑ 72h (peak)

11. Pathology of MI’s ctnd.
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Management:
○ ABCDE + help
○ 12 lead ECG - cardiac monitor - IV access (2x antecubital, think
forward as arrest possible!)
○ Oxygen!
MONAC
○ Drugs:
Morphine+metoclopramide
O2
■ morphine
Nitrates
■ oxygen
Aspirin (if not yet given)
■ nitrates - GTN spray
Clopidogrel 300mg
■ aspirin/clopidogrel
■ fondaparinoux (FXa inhibitor)
○ PCI percutaneous coronary intervention if ST elevation or new onset
bundle branch block within 12h (if no centre nearby then clot lysis)

12. Today
● overview of CV path
● some pathology of most important topics
○ MI
○ endocarditis
● an example case

13. Pathology of Endocarditis
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Definition: Inflammation of the endocardium, i.e. the innermost endothelial
layer of the heart that lines its chambers, potentially including heart valves,
aorta, septum, chordae tendinae or any artificial structures present in the
heart. Distinguish:
○ infective endocarditis <= discussed here
■ acute
(virulent, on normal valve)
■ subacute
(low virulence, on abnormal valve)
○ non-infective endocarditis
■ non-bacterial thrombotic endocarditis NBTE - sterile lesions
■ Libman-Sacks endocarditis - sterile lesions in patients with SLE or
antiphospholipid syndrome

14. Pathology of Endocarditis ctnd.
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Aetiology:
○ 60% Strep. viridans on pre-existing damage on valve
○ 10-20% Staph. aureus on normal and damaged valves
○ HACEK
○ other: fungal, Rikettsiae, Chlamydia
○ 10% culture -ve
○ predisposing factors: valve abnormalities or T2DM, EtOH, CA, IVDU
Pathogenesis:
○ microbes entering the bloodstream settling on valves (L,R => IVDU?)
○ valves vulnerable due to lack of blood supply
3V’s
○ => vegetations
○ potential shedding of emboli
○ possible mycotic aneurysms!

15. Pathology of Endocarditis ctnd.
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Vegetations: what they consist of and where the are
○ fibrin, necrotic debris, thrombi, organisms
○ subacute: less destructive, regenerative granulation tissue
predisposing to fibrosis and calcification
RHD: many small (Rheum: Aschoff bodies, small granulomatous nodules,
lymhocytes and macrophages, “Anitschkow cells”), IE: large destructive,
NBTE: medium thrombotic, LSE mixed, either side

16. Pathology of Endocarditis ctnd.
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Clinical Features
○ fever! chills!
○ flu-like if subacute, more stormy onset acute
○ splinter haemmorhages
○ Roth spots = retinal haemorrhages
○ Janeway lesions = palmar erythema
○ Osler nodules = fingertip nodules
Complications
○ sepsis, embolisation / multi-organ failure
○ glomerulonephritis
○ valve insufficiency => heart failure!
○ abscesses => fistulae and septal defects
○ mycotic aneurysms

17. Pathology of Endocarditis ctnd.
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Investigations
○ 3x blood cultures
○ FBC
○ CRP/ESR
○ U&E
○ LFTs
○ Echocardiogram
○ ECG
○ CXR
○ Urinalysis

18. Pathology of Endocarditis ctnd.
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Management
○ eradicate infection and manage complications of valve damage
○ valve damage
■ like congestive heart failure
■ oxygen, manage BP
■ potential surgery: valve replacement
○ infection
■ long-term antibiotics
■ empirical: flucloxacillin (b-lactamase resistant pen, gram +ve
bacilli/cocci) and gentamycin (aminoglycoside, gram -ve)
■ strep: ben-pen and gentamycin
■ staph: flucloxacillin or vancomycin and rifampicin (if allergic)
■ HACEK: amoxicillin and gentamycin

19. Today
● overview of CV path
● some pathology of most important topics
○ MI
○ endocarditis
● an example case

20. A cardiovascular case
A 60 year old male was admitted with a 2h history of
persistent severe chest and interscapular pain, as well as
nausea and sweating.
On examination, he was cold and clammy. His BP was
195/115 and his HR was 90bpm and regular. Chest
sounds were clear and the heart sounds unremarkable.

21. His ECG was unremarkable.

22. •What is the differential diagnosis?
•What further investigations would you request?

23. • What is the differential diagnosis?
• Dissecting aneurysm
• Acute myocardial infarction
• Acute oesophageal spasm
• Pulmonary embolism
• What further investigations would you request?
Chest x-ray, US, CT, cardiac enzymes/troponin, MRI angiography, VQ
scans

24. Several hours later the pain had extended to the abdomen.
His left hand was cold and white and the left radial and
brachial pulses were absent. He had been anuric in the
last 2 hours.

25. •
Which pathological
observations?
process
explains
these

26. Extension of the dissection to occlude left
subclavian and renal arteries.

27. Shortly afterwards the patient died.
At necropsy, the specimen shown in the
photograph was removed.

28. • What does the photograph show and what is
your diagnosis?

29. Formation of a blood filled space in the media of the aorta
=> dissection aneurysm.
• What is the pathogenesis of this pathological
process?

30. What is the pathogenesis of this pathological process?
•
weakening of vessel wall
•
acquired: ischaemia of the media by atherosclerosis and/or
hypotension (ischaemia of vasa vasorum, atherosclerotic
plaques have increased metalloproteases that degrade media)
•
genetic: structural abnormalities of connective tissue as in
Marfan or Ehlers Danlos Syndrome (fibrillin vs. collagen
defect) => cystic medial necrosis