Histopath Tutorial 1: Cardiovascular Pathology

Christiane Riedinger 27/2/14

Today● overview of CV path● some pathology of most important topics

○ MI○ endocarditis

● an example case

Overview of Cardiovascular Path● 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)

List of Pathological CausesA – autoimmuneV – vascularI – infective, inflammatoryT – traumaticA – acquiredM – metabolicI – iatrogenicN – neurological, neoplastic, nutritionalC – congenitalD – degenerative, drugsE – environmental, endocrineP – psychosomatic

Overview of CV Path 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”

Today● overview of CV path● some pathology of most important topics

○ MI○ endocarditis

● an example case

Pathology of MI’s● 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”

Pathology of MI’s ctnd.

Patterns of MIs● 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

Pathology of MI’s ctnd.

Timing of MI morphology =>● Clinical Features:

○ severe chest pain○ not relieved○ …

● Complications:○ ¾ of pt. >1!○ contractile dysfunction○ structual dysfunction○ electrical dysfunction○ clotting○ chronic: IHD, cardiomyopathy

Pathology of MI’s ctnd.

● 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○ BNP○ Lactate○ potential cardiac scintigram

Timing● Myoglobin ↑ 2h● CK-MB ↑ 4-8h GOLD STANDARD!● Troponin I ↑ 12h (peak)● LDH ↑ 72h (peak)

Pathology of MI’s ctnd.

● Management:○ ABCDE + help○ 12 lead ECG - cardiac monitor - IV access (2x antecubital, think

forward as arrest possible!)○ Oxygen!○ Drugs:

■ morphine■ oxygen■ nitrates - GTN spray■ 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)

MONACMorphine+metoclopramideO2NitratesAspirin (if not yet given)Clopidogrel 300mg

Today● overview of CV path● some pathology of most important topics

○ MI○ endocarditis

● an example case

Pathology of Endocarditis● 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

Pathology of Endocarditis ctnd.

● 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!

Pathology of Endocarditis ctnd.

● 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

Pathology of Endocarditis ctnd.

● 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

Pathology of Endocarditis ctnd.

● Investigations○ 3x blood cultures○ FBC○ CRP/ESR○ U&E○ LFTs○ Echocardiogram○ ECG○ CXR○ Urinalysis

Pathology of Endocarditis ctnd.

● 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

Today● overview of CV path● some pathology of most important topics

○ MI○ endocarditis

● an example 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.

A cardiovascular case

His ECG was unremarkable.

•What is the differential diagnosis?

•What further investigations would you request?

• 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

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.

• Which pathological process explains these observations?

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

Shortly afterwards the patient died. At necropsy, the specimen shown in the

photograph was removed.

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

Formation of a blood filled space in the media of the aorta

=> dissection aneurysm.

• 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

What is the pathogenesis of this pathological process?