CV Pathology

Question 1

Describe the pathogenesis of atherosclerosis

Answer 1

Exess LDL accumulates in tunica intima due to increased permeability of the artery to LDL (can be due to endothelial dysfunction or injury e.g. in hypertension)
LDL is oxidised via ROS released from damage endothelial tissue, or is glycosylated in diabetes
Oxidised/glycosylated LDL stimulates production of inflammatory cytokines (e.g. IL-1, IL-8) by resident tissue cells (e.g. macrophages)
Inflammatory cytokines induce expression of leukocyte adhesion molecules on endothelial receptors for leukocyte extravasation (e.g. selectins, ICAMs) and act as chemoattractants (e.g. IL-8 for macrophages)
Monocytes mature to macrophages, macrophages and lymphocytes enter the intima
Macrophages phagocytose the oxidised LDL, becoming foam cells, and release cytokines which recruit smooth muscle cells and promote formation of ECM (e.g. TGF-B)
With time, foam cells and other debris break down by apoptosis and matrix metalloproteinases, forming a lipid rich necrotic core with cholesterol crystals
Initial smooth muscle proliferation preserves the lumen diamete, but eventually the intima thickens to obstruct the lumen and the plaque becomes susceptible to rupture
Endothelial dysfunction also contributes to narrowed lumen as it cannot release vasoactive substances (e.g. NO) to vasodilate, and does not produce prostacyclin (creates a prothrombotic environment)

Question 2

What are the main abnormalities/risks of an atherosclerotic plaque?

Answer 2

Thickened intima may narrow lumen
Dysfunctional endothelium leads to decreased NO and prostacyclin (loss of vasodilatory tone, production of a prothrombotic environment)
Plaque becomes unstable and susceptible to rupture

Question 3

Types of tissues that have pale infarcts

Answer 3

Spleen
Kidney
Heart
Brain

Question 4

Types of tissues that have haemorrhagic infarcts

Answer 4

Bowel
Brain
Lung

Question 5

Reasons for haemorrhagic infarct

Answer 5

Dual circulation or natural collateral circulation (e.g. lung)
Reperfusion (e.g. brain)
Venous occlusion (e.g. bowel volvulus)

Question 6

Describe the time course of histological changes following MI

Answer 6

6-12 hours: no change
1 day: karyolysis, evidence of coagulative necrosis
2 days: acute inflammation (PMNs, pyknosis, karryorrhexis)
1-2 weeks: granulation tissue
Months to years: fibrosis, scarring and remodelling

Question 7

Describe the different macroscopic presentations of infarcts over time

Answer 7

Wihin hours: normal
12-24 hours: mottled
1-2 days: more obvious, yellow and creamy appearance
Old infarct: white scar, thinned wall

Question 8

Describe the arterial territories of the heart

Answer 8

LAD: anterior LV and RV, anterior 2/3 of IV septum
Circumflex: lateral LV
PDA (usually from RCA, can be from circumflex): inferior LV, part of RV, posterior 1/3 of IV septum
RCA: AV node

Question 9

What is the myocardial perfusion pressure?

Answer 9

~equal to aortic diastolic pressure (drives blood flow into coronary arteries)

Question 10

Which area of the myocardium is most susceptible to ischaemia? Why?

Answer 10

Subendocardium

Subjected to greatest pressure, potentially impairing blood flow

Question 11

How is blood supply increased to the myocardium at times of high O2 demand?

Answer 11

Vasodilation

Question 12

What factors influence myocardial O2 demand?

Answer 12

Wall stress
HR
Contractility

Question 13

What disease states can be caused by a stable plaque?

Answer 13

Stable angina
CHF
Arrhythmias

Question 14

What causes chest pain in MI?

Answer 14

ATP depletion leads to anaerobic metabolism and local accumulation of metabolic products (e.g. H+, adenosine) which cause pain

Question 15

How long does it take for myocardial ischaemia to cause irreversible injury?

Answer 15

20-40 minutes

Question 16

What are the 2 types of MI?

Answer 16

Regional transmural: develops from subendocardium outwards over a period of 6-8 hours
Regional subendocardial: following early intervention, spontaneous lysis of an occlusive thrombus or severe atherosclerotic narrowing (not occlusion)
Circumferential subendocardial: severe triple vessel coronary narrowing resulting in a systemic reduction in tissue perfusion (e.g. IN SHOCK)

Question 17

What ECG changes are seen in MI?

Answer 17

ST elevation in severe (often transmural) MI

Non-ST elevation MIs are generally smaller subendocardial

Question 18

How is MI diagnosed?

Answer 18

Troponins and CK-MB (myocardium-specific CK)

Elevated within 6 hours

Question 19

What are the main complications of MI?

Answer 19

Fatal arrhythmias (BIGGEST RISK, e.g. VF or VT)
Pericarditis (fibrinous or Dressler’s syndrome)
Thrombo-emboli (e.g. to brain)
Rupture of free wall of LV, causing cardiac tamponade
Rupture of papillary muscle (causing MR)

Question 20

Occlusion of which artery is more likely to cause arrhythmia?

Answer 20

RCA (supplies AV node)

Question 21

What changes occur to the bronchial epithelium in smokers?

Answer 21

Squamous metaplasia (change from pseudostratified columnar to stratified squamous)

Question 22

How does MR or MS predispose to AF?

Answer 22

LA not effective at transferring blood to ventricle
Increases LAP to increase LV filling by hypertrophy or dilation
Hypertrophy/dilation can cause problems with conduction