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Phase 2a Revision Session Sophia and Sally 08/03/16 The Peer Teaching Society is not liable for false or misleading information…

1.The differences between a clot and a thrombus 2.The constituents of an atheromatous plaque and its pathogenesis 3.The complications of atheroma 4.The difference between and consequences of arterial and venous thromboembolism 5.An understanding of the mechanism and causes of pulmonary embolism 6.The nature and causes of infarction 7.To appreciate the sequence: coronary artery atheroma → thrombosis → myocardial infarction → ventricular aneurysm →ventricular thrombosis → systemic arterial embolism → cerebral infarction The Peer Teaching Society is not liable for false or misleading information… What we will cover:

Clot: – Coagulated blood – Extravascular Thrombus: – A solid mass of blood constituents formed within the intact vascular system of life. Its mode of formation, its structure and its appearance are all different to a clot! – Intravascular The Peer Teaching Society is not liable for false or misleading information… Clot vs Thrombus ThrombusClot ConstituentsPlatelets WBC RBC Fibrin RBC Fibrin

The Peer Teaching Society is not liable for false or misleading information… Virchow’s triad- Thrombus formation

Arterial vs Venous ARTERIAL THROMBOSISVENOUS THROMBOSIS Most commonly superimposed on an atheroma Most commonly due to stasis HIGH pressureLOW pressure Made up mainly of platelets – WHITE THROMBUS Made up of mainly coagulation factors (RBC) – RED THROMBUS Can lead to MI/StrokeCan lead to DVT/PE Treatment – ANTI-PLATELETS e.g. Aspirin, Clopidogerel Treatment – ANTI-COAGULANTS e.g. Warfarin, Heparin, NOACs (Rivaroxaban) The Peer Teaching Society is not liable for false or misleading information…

Coagulation Cascade Pathways: INTRINSIC (contact activation) pathway: Activated by contact with collagen from damaged blood vessels Disrupted by heparin EXTRINSIC (tissue factor) pathway: Activated by contact with tissue factor from surface of extravascular cells Interrupted by Warfarin Both end in COMMON pathway: Prothrombin > Thrombin > Fibrinogen > Fibrin

Atheroma – Disease of lining and wall of large and medium blood vessels The Peer Teaching Society is not liable for false or misleading information… The constituents of an atheromatous plaque and its pathogenesis

Atheromatous Plaque

The formation of lesions starts in young children. The earliest significant lesion is called a fatty streak. It is a yellow linear elevation of the intimal lining and is composed of lipid laden macrophages and T cells No clinical significance in patients with few risk factors The Peer Teaching Society is not liable for false or misleading information… Step 1 – Lipid deposition in intima

Over time, the plaque enlarges and protrudes into the lumen This causes turbulence in the blood flow This eventually causes loss of intimal cells Injured cells express adhesion molecules The Peer Teaching Society is not liable for false or misleading information… Step2 – Injury to the endothelium

Injured cells express adhesion molecules for monocytes (ICAM-1, E-selectin) Creates high permeability for LDLs Inflammatory cells and lipids therefore enter the intimal layer and form plaques Macrophages and T-lymphocytes accumulate in the plaque tissue The Peer Teaching Society is not liable for false or misleading information… Step 3 – Inflammatory reaction

Lipid-laden macrophages (foam cells) die through apoptosis and spill their lipid contents into the core of the plaque forming the lipid core Activated T cells secrete TNF-alpha and IFN- gamma, enhancing response IL-6 contributes to inflammation and activation of adhesion molecules The Peer Teaching Society is not liable for false or misleading information… Step 3 – Inflammatory reaction cont.

Fibroblast growth factor and platelet-derived growth factor are secreted by endothelium These attract smooth muscle cells from media and stimulate cellular migration and proliferation Smooth muscle cells proliferate in plaque, migrate into sub-endothelial space, producing a new intima and extracellular matrix components (collagen) Leads to formation of fibrous plaque cap The Peer Teaching Society is not liable for false or misleading information… Step 4 – Tissue repair

The Fibrous Plaque Contains collagen, elastin, smooth muscle cells, macrophages and T cells Impedes blood flow and is prone to rupture Rupture – increased enzyme activity digests plaque, it becomes weak and bits break off. This forms a thrombus which can occlude blood vessels The Peer Teaching Society is not liable for false or misleading information…

Modifiable Hypertension Hyperlipidaemia Diabetes Smoking Obesity/ sedentary lifestyle The Peer Teaching Society is not liable for false or misleading information… Risk factors for atherosclerosis Non-modifiable Age Family history Gender- male Low socio- economic status Low birth weight

The Peer Teaching Society is not liable for false or misleading information… Complications of atheroma Progressive lumen narrowing due to high-grade plaque stenosis can reduce blood flow and lead to ischaemia - can be reversible or irreversible Acute atherothombotic occlusion - plaque rupture leads to coagulation cascade and thrombotic occlusion of vessel lumen in a short time period Embolisation of distal arterial bed – small plaque fragments may occlude small vessels leading to infarctions

The Peer Teaching Society is not liable for false or misleading information… Complications of atheroma cont. Carotid atheroma – TIA, cerebral infarcts Myocardial atheroma – MI, cardiac failure Aortic aneurysm – rupture causes sudden death Peripheral vascular disease – disease with intermittent claudication Gangrene

The Peer Teaching Society is not liable for false or misleading information… Treatment for atherosclerosis PCI – stent Modify risk factors – stop smoking, control BP, lose weight, exercise, eat healthily, statins, low-dose aspirin

The Peer Teaching Society is not liable for false or misleading information… coronary artery atheroma → thrombosis → myocardial infarction → ventricular aneurysm →ventricular thrombosis → systemic arterial embolism → cerebral infarction

Embolus – a mass of material in the vascular system able to become lodged within a vessel and block its lumen Over 90% of major emboli are derived from thrombi Other materials include: atheromatous plaque material, vegetations on heart valves (IE), fragments of tumour, amniotic fluid, gas and fat/ The Peer Teaching Society is not liable for false or misleading information… Thromboembolism

Normal vessels in deep veins of the leg Thrombi form due to stasis and hypercoagulability from fibrin and platelets Thrombi are liable to embolise – can lead to PE RISK FACTORS – Age, BMI >30, varicose veins, travel, immobility, trauma/surgery, cardiac or respiratory failure, recent MI/Stroke, OC/HRT The Peer Teaching Society is not liable for false or misleading information… DVT

SIGNS AND SYMPTOMS: – Swollen, red, painful leg – unilateral – Ankle oedema – Engorged superficial veins – Hormon’s sign – pain in calf on dorsiflexion of foot INVESTIGATIONS: – USS – Venography – injecting contrast The Peer Teaching Society is not liable for false or misleading information… DVT cont.

TREATMENT: – Low-dose heparin – Vitamin K antagonists – Prevent PE PREVENTION: – Frequent walking – Calf exercises – Anti-coagulants - Warfarin, NOACs – Compression stockings The Peer Teaching Society is not liable for false or misleading information… DVT cont.

PE is a blockage of the lungs main artery or one of its branches by an embolism Around 95% of venous thrombosis occurs in leg veins and therefore most emboli from such thrombi will arrive in the pulmonary circulation. The Peer Teaching Society is not liable for false or misleading information… Pulmonary Embolism

The effects of a PE depends on their size: Small emboli – may occur unnoticed. Many small emboli can result in pulmonary hypertension Larger emboli: – Chest/pleuritc pain – Dyspnoea, dizzy, syncope – Shocked/collapse – Leg pain (DVT) Massive – sudden death – usually long thrombi arrived from leg veins. They are often impacted across the bifurcation of one of the main pulmonary arteries – saddle embolus. The Peer Teaching Society is not liable for false or misleading information… Pulmonary Embolism – Presentation

D-dimer Arterial blood gas Doppler (DVT) CTPA, V/Q scan Well’s score ECG, cardiac proteins The Peer Teaching Society is not liable for false or misleading information… Pulmonary Embolism – Investigations

ABCDE LMW Heparin Warfarin (at least 3 months) Thrombolysis if massive The Peer Teaching Society is not liable for false or misleading information… Pulmonary Embolism – Treatment

ISCHAEMIA - Mismatch of oxygen supply and demand due to impaired blood supply or greater demand than blood supply 6 P’s of acute ischaemia: PAIN PALLOR PERISHING COLD PULSELESS PARATHESIA (pins and needles) PARALYSIS INFARCTION - Ischaemic death of tissue within the living body – irreversible The Peer Teaching Society is not liable for false or misleading information… Ischaemia and infarction

1. Define thrombus The Peer Teaching Society is not liable for false or misleading information… QUIZ!!!!

A solid mass of coagulated blood formed within the circulatory system The Peer Teaching Society is not liable for false or misleading information… QUIZ!!!!

2. Give the 3 components of Virchow’s triad The Peer Teaching Society is not liable for false or misleading information… QUIZ!!!!

Hypercoagulability Stasis Endothelial injury The Peer Teaching Society is not liable for false or misleading information… QUIZ!!!!

3. What coagulation pathway does Warfarin interrupt? The Peer Teaching Society is not liable for false or misleading information… QUIZ!!!!

Extrinsic The Peer Teaching Society is not liable for false or misleading information… QUIZ!!!!

4. What is another name for a lipid-laden macrophage? The Peer Teaching Society is not liable for false or misleading information… QUIZ!!!!

Foam cell The Peer Teaching Society is not liable for false or misleading information… QUIZ!!!!

5. Give 4 features of a fibrolipid plaque The Peer Teaching Society is not liable for false or misleading information… QUIZ!!!!

Fibrous cap Lipid core Smooth muscle cells Macrophages Lymphocytes Cholesterol crystals The Peer Teaching Society is not liable for false or misleading information… QUIZ!!!!

6. Give 3 risk factors for DVT The Peer Teaching Society is not liable for false or misleading information… QUIZ!!!!

Age, varicose veins, trauma/surgery, BMI >30, immobility, travel, cardiac or respiratory failure, recent MI/Stroke, OC/HRT/Pregnancy The Peer Teaching Society is not liable for false or misleading information… QUIZ!!!!

7. Name the 6 P’s of acute ischaemia The Peer Teaching Society is not liable for false or misleading information… QUIZ!!!!

PAIN PALLOR PERISHING COLD PULSELESS PARATHESIA (pins and needles) PARALYSIS The Peer Teaching Society is not liable for false or misleading information… QUIZ!!!!