Atherosclerosis, thrombosis, embolism, ischaemia and infarction.

Question 1

What is ischaemia

Answer 1

Loss of blood supply to a tissue because of a blocked blood vessel

Results in tissue coagulative necrosis

Mostly due to blockage of artery

Sometimes due to blockage of vein

Question 2

What is infarction

Answer 2

Death of tissue (necrosis) secondary to ischaemia following abrupt interference with the blood supply.

Question 3

What is arterial infarction (white)?

Answer 3

Follows sudden obstruction to the arterial supply to a tissue or organ.

Shpaed according to the territory of vessel supply

Pale with red hyperaemic border late stages scarring.

Question 4

What is venous infarction (red)?

Answer 4

Follows sudden and persistent obstruction to venous drainage of an organ or tissue.

Congestion, increased pressure leading to rupture of small vessels, red / black (haemorrhagic).

Question 5

What are the consequences of infarct?

Answer 5

Insufficient oxygen

Insufficient nutrients

Excess waste products

Question 6

How does ischaemia affect the cells?

Answer 6

Cells like homeostasis

If there are slight changes the cells can adapt

If the changes are too great:

Cell injury

Cell (necrosis)

Question 7

Is ischaemia acute or chronic?

Answer 7

Both

Question 8

More details on infarct. Where, causes, acute or chronic?

Answer 8

Area of ischaemic necrosis within a tissue or organ

From acute arterial or venous occlusion

Most caused by arterial thrombosis or embolism

Acute

Heal by organization and fibrosis

Different cells types have differing vulnerabilities to ischaemia

Question 9

Where do pale infarcts occur?

Answer 9

In tissues supplied by end arteries.

Question 10

What is a haemorrhagic infarct?

Answer 10

Venous occlusion

Tissues with a dual or rich collateral blood supply

Reperfusion

Question 11

What is thrombosis?

Answer 11

Normal haemostasis

Thrombus formation: Clotted mass of blood forming within the CVS during life: pathologic

Complex process involving the interaction of blood vessel walls, platelets and various plasma proteins.

Balance between factors that promote thrombogenesis and those that promote thrombolysis

Question 12

What is the endothelial walls role in thrombus formation?

Answer 12

Barrier

Antithrombic: Molecules on surface
Molecules released into blood: Prostacyclin annd NO inhibit platelet aggregation

Can be prothrombotic

Secrete vasodilators and vasocontrictors

Normally resistant to leukocyte adhesion.

Question 13

Platelets role in thrombus formation?

Answer 13

Flow in center of stream

Do not normally adhere to endothelium

Activated by collagen exposed following vessel injury

Release chemicals leading to activation and aggregation of more platelets

Question 14

What do you need to know about clotting cascade?

Answer 14

Normal blood flows through steadily through endothelial lumen. At some stages there is an increase in clotting agents that cause blood to clot.

Question 15

What is a thrombus?

Answer 15

Clotted mass of blood forming within the cardiovascular system during life.

Question 16

What is virchows triad. Explain the components.

Answer 16

Alterations in blood flow - plays an important role in both venous and arterial thrombosis

Hypercoagulability - plays greater role in venous thrombosis than arterial thrombosis

Damage to endothelium - plays a greater role in arterial thrombosis

Question 17

More details of virchows triad - Alterations in blood flow

Answer 17

Turbulence:

In aneurysms

Over atherosclerotic plaques

Around abnormal cardiac valves

Slowing:

restricted mobiligy e.g. elder, post surgical, unconscious

Cardiac failure

Question 18

More details of virchows triad - Hypercoagulability of blood.

Answer 18

Post operative

Genetic

Certain malignancies

High oestrogens: peri-partum, some oral contraceptives

Injury to endothelium or endocardium:

Direct trauma

Inflammation

Atherosclerosis

Question 19

What is an arterial thrombi?

Answer 19

Most caused by atherosclerosis (endothelial injury)

or aneurysms (turbulence)

Question 20

What is a cardiac thrombi?

Answer 20

Occurs in left ventricle:

Following infarction

in LV aneurysms

Left atrium in atrial fibrillation

Question 21

What is venous thrombi?

Answer 21

Slowing of blood flow and hypercoagulability are especially important

Deep leg and pelvic veins important sites

Question 22

What can happen to the thrombus?

Answer 22

Embolisation

Fibrinolysis (breakdown)

Organisation

Persistence e.g. thrombi in aortic aneurysms

Question 23

What are some complications of thrombosis?

Answer 23

Obstruction to blood flow (usually arterial)

Embolism (Both arterial and venous)

Question 24

Define Embolus

Answer 24

Intravascular solid, liquid or gaseous mass carried in the blood stream to some site remote from its origin or point of entrance into the blood stream

e.g. thrombo-emboli

athero-emboli

septic emboli

gaseous nitrogen bubbles in ‘the bends’

Question 25

What is Deep vein thrombosis (DVT)?

Answer 25

Thrombi form within deep veins of lower limbs and embolise to lungs

Question 26

What are risk factors for DVT? (hint virchows)

Answer 26

Stasis: immobilisation Cardiac failure Hypercoagulable states: Post - operative High oestrogens: post partum, oral contraceptive pill Some malignancies Genetic abnormalities in coagulation Obesity Local endothelial injury: Trauma, sugical injury, smoking

Question 27

2 Common veins DVT formed in?

Answer 27

Popliteal vein Femoral vein

Question 28

Give the route of a pulmonary embolism.

Answer 28

Beings in the leg (above the knee) travels to inferior vena cava to right side of heart to pulmonary artery to be lodged in lung.

Question 29

List some possible consequences of a pulmonary embolism.

Answer 29

Asymptomatic and small (60-80%) undergo organization and incorporated into vessel wall. If medium sized may present with haemoptysis, cough and breathlessness Pulmonary haemorrhage (due to dual blood supply) Pulmonary infarct (RARE) Pulmonary hypertension (Multiple emobli over time) Sudden death when 60% of the pulmonary circulation is obstructed. Death by *Cor Pulmonale* right heart failure.

Question 30

Identify what is cause of death, and where.

Answer 30

Question 31

Brief definition of Atherosclerosis, % of deaths in developed world and where highest incidence occurs.

Answer 31

Extremely common Underlying cause of most heart attacks and strokes Chronic accumulation of lipids in intima and medium sized arteries. Causes 50% of deaths in developed world Highest incidence in: North America Europe Australia, NZ Russia

Question 32

What are the risk factors for Atherosclerosis?

Answer 32

Main: Cigarette smoking Hypertension Diabetes mellitus Dyslipidaemia Increasing age Male Other: Genetic Obesity, lack of exercise, stress

Question 33

What is Atherosclerosis?

Answer 33

A disease caused by the formation of plaques on the walls of arteries Plaques consist of: Central lipid core (cholesterol) Fibrous cap Plaques narrow the vessel ----\> ischaemia Plaques + thrombus ----\> infarction plaques + acute plaque event ----\> sudden increase in ischaemia

Question 34

List the seven steps of atherosclerosis in the response to injury hypothesis.

Answer 34

1. Chronic endothelial injury yields an increase in permeability causing WBC adhesion and thrombotic potential 2. Insudation of lipoproteins (LDLs) into the intima of vessel wall. 3. Blood monocytes adhere and migrate into intima transforming into macrophages, engulfing lipid and becoming foam cells 4. Platelets adhere 5. Activated platelets, foam cells and vascular cells release cytokines and growth factors e.g platelet-derived growth factor causing migration of smooth muscle cells from media into intima 6. The smooth muscle cells proliferate, exposing ECM and accumulation of collagen and proteoglycans 7. More lipid accumulates - fibrofatty atheroma

Question 35

What is the morphology of atherosclerosis?

Answer 35

Fatty streaks: Lipid filled foam cells in the intima Flat lesions Children from the age of 10 years Not all will progress

Question 36

Named what the arrows are pointing to.

Answer 36

Question 37

Where does atherosclerosis occur?

Answer 37

Elastic Arteries: Aorta, carotid arteries; iliac arteries Large and medium muscular arteries: Coronary arteries, popliteal arteris, cerebral arteries

Question 38

What happens to people with atherosclerosis?

Answer 38

Decreased blood flow through an artery: Ischaemic heart disease Peripheral vascular disease Cerebrovascular disease Predisposition to thrombosis on plaques: Collagen fibres in plaque are exposed to the circulating blood initiating thrombus formation Complete occlusion of small vessels In large vessels pieces may break off and enter circulation (emoblism) or block an artery elsewhere. Bleeding into a plaque: Sudden ballooning out Rapid narrowing of lumen Weakening of the vessel wall: Aneurysm formation.

Question 39

Normal artery

Answer 39

Acute plaque event: Atherosclerosis and thrombus

Question 40

Examples of complications of atherosclerosis.

Answer 40

Question 41

Examples of complications of atherosclerosis.

Answer 41

Question 42

Examples of complications of atherosclerosis.

Answer 42

Question 43

What is an Aneurysm?

Answer 43

Abnormal focal dilatation in wall of vessel or a cardiac chamber Arise due to weakening of media

Question 44

What causes an Aneurysm?

Answer 44

Atherosclerosis Congenital weakness in the wall: probable predisposing factor of berry aneurysms around the circle of Willis Systemic hypertension ----\> microaneurysms in cerebral arterioles from arteriolar damage (hyaline arteriolosclerosis) Infection in an artery wall (mycotic aneurysm) Other

Question 45

What are some complications of an aneurysm?

Answer 45

Thrombosis Rupture