Circulatory pathology

Question 1

What are the layers of an blood vessel wall? from lumen out

Answer 1

Intima
Internal elastic lamina
Media
Adventitia

Question 2

What are the functions of endothelial cells?

Answer 2

Permeability barrier
Release anti-coagulant, anti-thrombotic and fibrinolytic regulators
Regulate prothrombotic molecules
Regulate ECM
Regulate blood flow and vascular reactivity
Inflammation and immunity
Regulate cell growth
Regulate oxidation of LDL

Question 3

What are endothelial cells like in the basal state?

Answer 3

Non-adhesive, non-thrombogenic surface

Question 4

What are endothelial cells like in the activated state?

Answer 4

Increased expression of procoagulants, adhesion molecules, and proinflammatory factors
Altered expression of chemokines, cytokines and growth factors

Question 5

What stimuli cause endothelial cells to take on an activated state?

Answer 5

Turbulent flow, hypertension, cytokines, complement, bacterial products, lipid products, hypoxia/acidosis, viruses, cigarette smoke

Question 6

What is the role of vascular smooth muscle?

Answer 6

Mediate vasoconstriction/vasodilation
Role in normal vascular repair and pathologic processes e.g. atherosclerosis
When stimulated, can proliferate, upregulate ECM collagen, elastin and proteoglycan production, and secrete growth factors and cytokines

Question 7

How can blood pressure be calculated?

Answer 7

Cardiac output x peripheral resistance

Question 8

What factors infleunce cardiac output?

Answer 8

Blood volume:
- Sodium
- Mineralcorticoids
- Atrial natriuretic peptide
Cardiac factors:
- Heart rate
- Contractility

Question 9

What factors influence peripheral resistance?

Answer 9

Humoral factors: constrictors/dilators
Local factors: autoregulation, pH, hypoxia
Neural factors: contrictors/dilators

Question 10

What is hypertension?

Answer 10

Persistent elevation of BP in systemic arterial circulation
Accelerates atherosclerosis and causes degenerative changes in walls of large and medium sized arteries > lead to aortic dissection and cerebrovascular haemorrhage

Question 11

What is the aetiology of hypertension?

Answer 11

95% idiopathic/’essential’ due to reduced renal Na+ secretion, increased vascular resistance, genetic factors, environmental factors
Rest is secondary hypertension due to primary renal/endocrine/CVS/neurologic disease

Question 12

What examples of renal, endocrine, CVS and neurologic disease can cause hypertension?

Answer 12

Renal: chronic renal disease, polycystic disease, acute glomerulonephritis
Endocrine: hypo/hyperthyroidism, pre-eclampsia
CVS: increased intravascular volume, increased cardiac output
Neurologic: psychogenic, increased intracranial pressure, acute stress

Question 13

What pathological changes may be seen with hypertension?

Answer 13

Hyperplastic atherosclerosis:
- onion skinning
- concentric proliferation of smooth muscle cells
- causes luminal obliteration
Hyaline atherosclerosis:
- Arteriolar wall thickened by deposited amorphous, proteinaceous material

Question 14

What is the vascular wall response to injury?

Answer 14

Neointimal response
Injury > endothelial cell loss/dysfunction > smooth muscle cell migration and mitosis into intima, ECM synthesis in the intima > thickened intima
Forms a neointima covered by an intact EC layer

Question 15

What are the three factors that promote thrombosis?

Answer 15

Virchow’s triad:
- Endothelial injury
- Abnormal blood flow
- Hypercoagulability
This are interacting factors:
EI > ABF > H
EI >H
ABF > EI > H

Question 16

How can endothelial injury lead to thrombosis?

Answer 16

Promotes platelets adhesion and aggregation
> production of pro-coagulant factors
In heart and arterial circulation due to:
- over ulcerated plaques in atherosclerosis
- endocardial injury in MI - mural thrombus (attached to a wall)
- traumatic or inflam vascular injury - vasculitis

Question 17

How can abnormal blood flow lead to thrombosis?

Answer 17

Prevents blood diluting activated clotting factors. Causes:
Stasis > venous thrombosis
- allows platelets to encounter endothelium and slows washout of activated clotting factors
Turbulence > arterial, near valves/cardiac thrombosis
- physical trauma to endothelial cells/dysfunction
- counter-currents and local pockets of stasis

Question 18

What causes a hypercoagulable state?

Answer 18

Primary (born with):
- Leiden factor V mutation, congenital deficiency of antithrombin III, protein C&S
Secondary (increased concentration of fibrinogen and prothrombin):
- Immobilisation, MI, neoplasia, tissue damage, cancer, prosthetic cardiac valves
- Various syndromes

Question 19

How do arterial and venous thrombi differ?

Answer 19

Arterial:
Secondary to atheroma
Consists of platelets
Common in brain, middle cerebral artery, coronary arteries
Cause - Endothelial injury
Venous thrombosis:
Slow BF, low pressure
Consists of red cells, platelets and fibrin
Common in Deep calf veins, deep hepatic portal vein
Cause - Stasis

Question 20

What are pathological features of arterial thrombus?

Answer 20

Lines of Zahn: laminations of fibrin and platelets

Question 21

What can happen to thrombi?

Answer 21

Lysis: due to thrombolytic activity of blood
Propagation: increase size as acts as focus for further thrombosis
Organisation: invasion of connective tissue elements, causes thrombus to become firm and grey/white
Canalisation: new lumens lined by endothelial cells form in an organised thrombus
Embolisation: thrombus becomes dislodged, travels through circulation, lodges in blood vessel some distance from site of thrombus formation

Question 22

What is embolism?

Answer 22

Detached fragments from
- solid (thrombus), liquid (amniotic fluid) or gas (nitrogen)
- carried by blood to distant site
Most common is thromboembolism

Question 23

What is a pulmonary embolism?

Answer 23

Most pulmonary emboli are small, then undergo organisation
Or pass through right heart to pulmonary circulation
Smaller emboli - pulmonary hypertension ventilated areas no perfused by blood
Massive embolus - sudden death

Question 24

Differenr effect of emboli in different areas of the lungs

Answer 24

Lungs have dual blood supply
PE less likely to lead to infarction - red infarct, but can occur in peripheral areas or with poor bronchial circulation
Embolus

Question 25

What do different infarcts

Answer 25

Arterial infarct - by thrombus, emboli, vasospasm or compression of vessel
Venous infarct - by strangulated bowel in hernia, torsion, bowel volvulus
> These lead to ischaemic necrosis
Majority due to thromboembolic events
- Ischaemic coagulative necrosis in tissue (called liquefactive necrosis in brain)

Question 26

What are different types of infarct and why are they caused?

Answer 26

Red (haemorrhagic) infarcts:
- Venous blockage
- Loose tissues
- Dual circulation
- Congested organs
- Re-established BF in infarcted tissue
White (anaemic) infarcts:
- Arterial occlusions
- Solid organs
- End arterial circulation organs
- Dense tissues
Septic infarcts:
infected cardiac valve vegetations embolise, microbes seed necrotic tissue
Infarct converted into abcess

Question 27

What factors influence infarct development?

Answer 27

• Anatomy of vascular supply: alternative blood supply is most important factor in determining if occlusion causes damage
• Rate of occlusion: slow developing occlusion less likely to cause infarction as they allow time for collateral blood supply development
• Tissue vulnerability to hypoxia: neurons irreversibly damaged after 3-4 min ischaemia. Myocardial cells die after 20-30 mins of ischaemia

Question 28

What is gangrene and its different types?

Answer 28

Whole areas of limb or region of gut have arterial blood supply cut off and large areas of tissue die in bulk
Dry gangrene: tissue dies, mummified and healing occurs over it (sterile)
Wet gangrene: bacterial infections in a gangrene leads to sepsis. Foul smell, discharge

Question 29

What is arteriosclerosis and what are the different types?

Answer 29

‘Hard arteries’ due to thickening of the blood vessel wall
Three pathologic patterns:
Atherosclerosis
Arteriosclerosis
Monckeberg medial calcific sclerosis

Question 30

What is atherosclerosis?

Answer 30

Intimal lesions called atheromas that impinge on vascular lumen and can rupture > sudden occlusion
Made of soft, friable lipid cores covered by fibrous caps
Involves large and medium sized arteries

Question 31

What are the major non-modifiable risk factors for atherosclerosis?

Answer 31

Genetic
Family history
Age
Sex

Question 32

What are the major modifiable risk factors for atherosclerosis?

Answer 32

Hyperlipidaemia
HTN (hypertension)
Smoking
DM (diabetes mellitus)
Inflammation

Question 33

What is the pathogenesis of atherosclerosis? Response to injury hypothesis

Answer 33

EC injury > endothelial dysfunction > increased permeability , leukocyte adhesion and thrombosis
Accumulation of lipoproteins in the vessel wall
Platelet adhesion
Monocyte adhesion to endo > migration into intima > differentiation into macrophages and foam cells
Lipid accumulation within macrophages, respond by releasing inflam cytokines
Activated platelets, macrophages and vascular wall cells release factors which recruit SMC
SCM proliferation and ECM production

Question 34

What is endartectomy?

Answer 34

Procedure removing plaque from arteries

Question 35

What can be identified in this image?

Answer 35

Lumen, fibrous cap, necrotic lipid core

Question 36

What are the histological features of an atheroma?

Answer 36

Narrowed lumen
Reduced internal and external elastic membranes
Thinned media of artery
Calicifcation
Immune cells
Neurovascularisation

Question 37

What are the different atherosclerotic plaque fates?

Answer 37

• Rupture, ulceration or erosion > thrombus formation: thrombi partially or completely occlude lumen, lead to tissue ischaemia. Thrombi can become organised and incorporated into plaque
• Haemorrhage into plaque (intra-plaque haemorrhage): may cause rapid plaque expansion or rupture
• Atheroembolism: microemboli of plaque contents
• Aneurysm formation: artheroma induced pressure or ischaemic atrophy with loss of elastic tissue > structural weakening that can lead to aneurysmal dilation/rupture

Question 38

Vulnerable vs stable atherosclerotic plaque

Answer 38

Vulnerable: thin fibrous cap
Stable: thick fibrous plaque

Question 39

What are the stages of atherosclerosis in pre-clinical phase vs clinical phase?

Answer 39

Pre-clinical phase:
fatty streak, fibrofatty plaque, advanced/vulnerable plaque
Clinical phase:
Aneurysm and rupture, occlusion by thrombus, critical stenosis

Question 40

What are aneurysms and there predisposing conditions?

Answer 40

Congenital or acquired dilations of blood vessels or the heart
Predisposing conditions: atherosclerosis, hypertension

Question 41

What are the types of aneurysm?

Answer 41

True aneurysm:
- Saccular: balloons out on ones side
- Fusiform: whole vessel widens
False aneurysm: blood filling between layers of vessel wall
Dissection: blood fills between all three layers

Question 42

What are the classifications of dissections?

Answer 42

Type A dissections: involve ascending aorta either extensive down the length (type I) or isolated (type 2)
Type B dissections: arise after the branching of the great vessels