T2: Atheroma, thrombosis and Embolism

Question 1

Define atheroma.

Answer 1

Intimal lesion that protrudes into a vessel wall. It consists of a raised lesion with a soft core of lipid (mainly cholesterol and cholesterol esters) and is covered by a fibrous cap.

Question 2

List the risk factors for atheroma development.

Answer 2

Non-modifiable risk factors:

• Non-Modifiable
• Increasing age
• Male gender
• Family history
• Genetic abnormalities

Modifiable risk factors:

• Hyperlipidemia (LDL: HDL)
• Hypertension
• Cigarette smoking
• Diabetes
• C-reactive proteins

Question 3

Describe the morphological changes that occur in a vessel wall in the various stages of development of atheroma.

Answer 3

Atherosclerosis starts with damage or injury to the inner layer of an artery. The damage may be caused by:
• High blood pressure
• High cholesterol
• An irritant, such as nicotine
Certain diseases, such as diabetes.

Atherosclerosis develops as a chronic inflammatory response of the arterial wall to endothelial injury. Lesion progression occurs through interactions of modified lipoproteins, monocyte-derived macrophages, T-lymphocytes, and the normal cellular constituent of the arterial wall.
The contemporary view of atherosclerosis is expressed by the response-to-injury hypothesis.

Damage to the overlying endothelium allows an influx of cells and lipids. The cells try to engulf the lipids. Often macrophages and smooth muscle recruited from the media. These cells become foam cells. Foam cells are smooth muscle cells/macrophages that have engulfed lipids. The fibrous cap overlies the central necrotic core.

Question 4

Describe the term thrombus.

Answer 4

A thrombus is a solid mass of blood constituents formed within the vascular system in vivo.

There are two types:

• Arterial thrombosis are most commonly superimposed on atheroma.
• Venous thrombosis are most commonly due to stasis.

Question 5

Describe the differences between a thrombus and a clot.

Answer 5

A thrombus occurs during life and requires active recruitment and activation of platelets and the clotting cascade. A clot occurs when blood is just left to stand.

Clot:

• Platelets not involved
• Occurs outside vessel (test tube or hematoma) or inside (postmortem)
• Red
• Gelatinous
• Not attached to the vessel wall

Thrombus:

• Platelets involved (lines of Zahn)
• Occurs only inside vessel
• Red (venous), pale (arterial)
• Firm
• Attached to the vessel wall

Question 6

Describe the mechanisms that normally prevent thrombus formation.

Answer 6

Both calcium and vitamin K are needed to synthesize Protein C, an anticoagulant that prevents excessive coagulation after the coagulation cascade occurs.

Question 7

Define the term embolus.

Answer 7

A mass of material in the vascular system able to become lodged in the vessel and block its lumen.

Question 8

Describe the causes of systemic emboli.

Answer 8

Systemic emboli
- Generally originate from the heart (LHS) or atheromatous plaque

• Sequelae of myocardial infarction - in an MI there is damage to the myocardium and the endocardium which can damage to endocardium which predisposes to thrombosis (Virchow’s triad). The myocardium in that part of the heart is not functional. This can cause turbulence and so we can get thrombus forming on an area of myocardial infarction.
• Atrial fibrillation - miscoordination contraction of the aorta. This can lead to turbulence and pockets of stasis both of which can predispose to thrombus formation.
• Infective endocarditis – heart valve vegetations. Due to turbulence and damage endothelium, thrombotic vegetations can form and subsequently embolise.
• Can cause – CVA (can get an infarct in part of the brain), TIA (lasts less than 24 hours, there is a blockage that is subsequently resolved), gangrene, bowel necrosis

Question 9

Describe Virchow’s triad.

Answer 9

If you alter any factor there is a shift in the haemostatic balance. When a thrombus forms in a pathological manner it may be due to:

• Endothelial injury (the blood and components of the clotting cascade are exposed to the factors in the underlying tissue which promote the binding of platelets and coagulation)
• Abnormal blood flow (turbulence or stasis and so prothrombotic factors build up and antithrombotic factors are not brought in)
• Hypercoagulability (e.g. defects in some components of the clotting cascade).

Question 10

What is a paradoxical embolism?

Answer 10

Thrombus that arises in the venous system is able to travel through into the heart. But crosses through a septal defect into the LHS of the heart and access the arterial circulation and can cause some kind of sequalae. This is relatively rare.

Question 11

What are the sequelae of thrombosis?

Answer 11

• Occlusion of vessel - causing downstream occlusion or infraction
• Dissolution - fibrin is broken down and the thrombus disappears
• Incorporation into vessel wall - leading to narrowing of the vessel lumen
• Recanalization (new blood vessels grow into a thrombus) there may be still be blood flow
• Embolization - can cause blockage or occlusion of a vessel downstream

Question 12

What is Cor Pulmonale?

Answer 12

Cor pulmonaleis defined as an alteration in the structure and function of the right ventricle (RV) of the heart caused by a primary disorder of the respiratory system. Pulmonary hypertension is often the common link between lung dysfunction and the heart incor pulmonale.