Atheroma, Thrombosis and Embolism

atheroma

focal intimal lesion consisting of lipid-rich necrotic core covered by fibrous cap within medium and large arteries

non-modifiable risk factor

• increasing age

• male gender

• family history/ genetics

modifiable risk factors for atheroma

• hyperlipidaemia

• hypertension

• cigarette smoking

• diabetes mellitus

• obesity

• sedentary lifestyle

• C-reactive proteins

causes of atheroma

• starts with damage or injury to endothelium of artery

• damage may be caused by:

  • high blood pressure

  • high cholesterol

  • irritant e.g. nicotine

  • diseases e.g. diabetes

parts of an atheroma

• fibrous cap

  • smooth muscle cells

  • macrophages

  • foam cells

  • lymphocytes

  • collagen

  • elastin

• necrotic centre

  • cell debris

  • cholesterol crystals

  • foam cells

  • calcium

stages of atherosclerosis formation

1. endothelial dysfunction/injury

2. fatty streak

3. fibrofatty plaque

4. complicated plaque

endothelial dysfunction/injury

• risk factors cause

  • incr. endothelial permeability

  • leukocyte adhesion

  • lipoprotein entry into vessel wall

• results in LDL accumulation within intima

morphology of the fatty streak

• earliest visible lesion

• intimal accumulation of lipid-laden macrophages

key cells in the fatty streak

• monocytes→ macrophages

• foam cells

morphology of fibrofatty plaque

• smooth muscle migration from media

• collagen deposition

• formation of fibrous cap

• lipid-rich necrotic core

components of fibrofatty plaque

• fibrous cap

• lipid core

• inflammatory cells

complications associated with complicated plaque

• plaque rupture

• plaque erosion

• haemorrhage into plaque

• calcification

• superimposed thrombosis

clinical consequences of complicated plaque

• myocardial infarction

• stroke

• peripheral artery disease

pathophysiology of atherosclerosis

• develops as chronic inflammatory response of arterial wall to endothelial injury

• lesion progression occurs through interactions of modified lipoproteins, monocyte-derived macrophages, T lymph. and normal cells

• contemporary view of atherosclerosis expressed by response-to-injure hypothesis

vessels commonly affected by atherosclerosis

• bifurcations→ sites of turbulent flow

• abdo. aorta

• coronary arteries

• popliteal arteries

• carotid vessels

• circle of willis

fatty streak

• earliest lesion in atherosclerosis

• composed of lipid filled foamy macrophages

• starts are multiple flat yellow spots that coalesce into streaks

• lesions not significantly raised and don’t cause flow disturbance

morphological evolution of atherosclerosis

• not all fatty streak are destined to progress to atheromatous plaque

• coronary fatty streaks start to form in adolescence at the same anatomical sites that later tend to develop plaques

atherosclerotic plaque

• consists of intimal thickening and lipid accumulation

• appears white-yellow

• superimposed thrombus on plaque appears red

• impinges on vessel lumen

sequelae of atherosclerosis

• haemorrhage into plaque

• atherosclerotic plaques cause turbulence, damages endothelium→ rupture, ulceration, erosion

  • induces thrombosis

• lumen occlusion→ ischaemia/infarction

• atheroembolism

• aneurysm formation

thrombosis

• solid mass of blood constituents formed within vascular system in vivo

• arterial thrombosis most commonly superimposed on atheroma

• venous thrombosis most commonly due to stasis

virchow’s triad

components leading to thrombosis:

• endothelial injury

• abnormal blood flow

• hypercoagulability

arterial thrombosis

• typically from rupture of atheromatous plaque

• found in arteries/ left heart chambers

• composed mainly of platelets

diseases associated with arterial thrombosis and treatment

• diseases

  • acute coronary syndrome

  • ischaemic stroke

  • claudication

• treatment→ antiplatelet agents (clopidogrel)

venous thrombosis (VTE)

• typically from combination of factors from Virchow’s triad

• found in venous sinusoids of muscle and valves of veins

• mainly composed of fibrin

diseases associated with VTE and treatment

• diseases

  • deep vein thrombosis (DVT)

  • pulmonary embolism

• treatment

  • anticoagulants→ heparin, warfarin

risk factors for endothelial damage

• endothelial dysfunction

  • smoking

  • hypertension

• endothelial damage

  • surgery

  • catheter/PICC lines

  • trauma

risk factors for hypercoagulability

• hereditary

  • factor V Leiden

  • prothrombin G2021OA

  • protein C and S deficiency

• acquired

  • cancer

  • chemotherapy

  • OCR/HRT

  • pregnancy

  • obesity

  • HIT→ heparin-induced thrombocytopenia

risk factors for stasis

• immobility

• polycythemia

sequelae of thrombosis

• dissolution (fibrin broken down)

• incorporation into vessel wall

• re-canalisation

• occlusion of vessel

• embolisation

embolism

• mass of material in vascular system able to become lodged in vessel and block its lumen

• most emboli derived from thrombi

pulmonary embolus

• derived from DVT

• travels through venous system and right side of heart

• lodges in pulm. artery or in smaller arterial branches

types of emboli

• thrombus derived

• atheromatous plaque material

• vegetation on heart valves (infective carditis)

• fragments of tumour

• amniotic fluid

• gas

• fat

systemic emboli

• generally originate from left side of heart or atheromatous plaque

• sequelae of

  • MI

  • AF

  • infective endocarditis

• can cause

  • CVA or TIA

  • gangrene, bowel necrosis