Arteriosclerosis
- Arteriosclerosis includes conditions which result in narrowing of
the arteries
Aetiology
- Atheroma or atherosclerosis
- Due to lipid deposits within the intima of the arterial wall
- Monckeberg’s arteriosclerosis (medial calcific sclerosis)
- Due to calcification of the media of medium sized arteries
- Arteriolosclerosis
- Characterised by hyaline thickening of small sized arteries
- Commonly seen in kidneys
- Secondary to hypertension or diabetes mellitus
Atheroma
- Atheroma is the single most important cause of morbidity and
mortality in Western countries
- The most important effects of atheroma are ischaemic heart disease,
peripheral vascular disease and cerebrovascular disease
- The cause of atheroma is not known, but many risk factors, and
factors which accelerate disease development have been identified
Pathology
- Lipid depositions in the intima
- These deposits are known as atheromas or plaques
- Develop from fatty streaks
- All arteries down to 1 mm diameter can be affected
- Atheroma formation occurs at sites of haemodynamic stress e.g.
bifurcations
Fatty streaks
- These are fatty deposits seen as early as infancy
- Fatty streaks comprise a slightly elevated zone on the arterial wall
caused by accumulation of a small number of lipid laden histiocytes,
with some free lipid
Fibrous plagues
- Fibrous plaques are the second stage of atheroma formation
- Lipid accumulates, free and in foamy histiocytes
- Smooth muscle cells migrate from the media and proliferate
- Fibrosis develops around the lipid, and forms a cap over the lesion
- Structure of plaques
- Central core consisting of cholesterol crystals, foam cells,
debris and thrombus
- Foam cells are lipid filled macrophages
- Superficial cap made up of mainly smooth muscle cells and
connective tissue
- Advanced disease is associated with calcification
- Usually involves large to medium sized arteries
Complicated plaques
- Ulcers and fissures of the fibrous cap reveal plaque contents,
resulting in thrombosis
- The plaque may undergo calcification, visible on x-ray
- Inflammation associated with the plaque destroys the media which
undergoes fibrosis, and is weakened
Major risk factors for atherosclerosis
- Hyperlipidaemia
- Hypertension
- Smoking
- Diabetes
- Age
- Sex
- Family history
- Alcohol
- Low socioeconomic status
Aetiology
- High plasma LDL cholesterol may promote accumulation of cholesterol
in the intima and ultimately plaques
- Endothelial injury may be an initiating factor for atheroma
- It has been proposed that lipid rich plaque contents are derived
from thrombus over such endothelial injuries
- Growth factors such as PDGF from platelets involved in thrombosis
may promote proliferation of cells in plaques
- Especially cells of smooth muscle origin derived from the arterial
media
- Inflammation is certainly a feature of atheromatous plaques
- May be involved in progression, but whether it is an important
initiator is debatable
- Macrophages produce various intercellular communication molecules
which promote various aspects of inflammation
- Lymphocytes accumulate and fibroblasts proliferate and produce
collagen
Vascular consequences
- Arterial narrowing causing ischaemia
- Arterial occlusion resulting in infarction
- Arterial wall weakening resulting in aneurysm formation
- Arterial embolism
Thrombosis
- Solid mass of blood constituents formed in vascular system
- Can occur in both the arterial and venous systems
- Thrombosis is different from clot formation
- Clotting means coagulation which can occur within or outside the
vascular system in life or post mortem
- Thrombus consists of fibrin, platelets and entrapped red blood cells
- Contact with damaged endothelium or atheromatous plaque contents
triggers the coagulation cascade
- Converts fibrinogen monomer to the jelly like fibrin polymer
- On contact with fibrin or collagen platelets release granules which
promote aggregation of adjacent platelets
- Forms a mass which covers an endothelial defect
- Factors which promote thrombosis are
- Vessel wall changes
- Changes in blood constituents
- Changes in blood flow
- These are know as Virchow's Triad
- Thrombi can:
- Occlude a vessel which may result in infarction
- Release fragments which can travel in the bloodstream to occlude
distal vessels
Thrombolysis
- Thrombosis can be cleared by the fibrinolytic system
- Plasminogen activator released from endothelial cells converts
plasminogen to plasmin which dissolves fibrin
Recanalisation
- Thrombus can undergo recanalisation
- Endothelial cells grow out from the vessel wall and create new
channels through the thrombus
Embolism
- An embolus is a mass of material in the blood which can lodge in a
vessel and block its lumen
- Embolism to the lungs (pulmonary arteries ) originates in the deep
veins
- Embolism to organs and limbs originates in the heart or large
arteries
- A embolus can be made up of
- Thrombus
- Atheromatous plaque
- Infected thrombus
- Endocardial or valve vegetations
- Fat
- Gas
- Amniotic fluid
- Tumour
- Foreign material
Ischaemia and infarction
- Ischaemia occurs when organ or tissue has perfusion lowered relative
to metabolic needs
- Infarction occurs when tissue necrosis result from ischaemia
- Both can occur as a result from arterial, venous or capillary
disease
- Arterial ischaemia can occur as a result of
- Atheromatous narrowing
- Thrombosis
- Embolism
- Low flow states
- Vasculitis
- Hypertensive vascular disease
- Spasm
- Outcome of ischaemia depends on
- Adequacy of cardiac function
- Anatomy of arterial supply
- Speed of onset
- Susceptibility of tissue
- Most infarcts are pale
- Where there is a dual blood supply (e.g. lung), the infarct can be
red
- Red infarction occurs when some blood continues to get in to the
infarcted area
- Following infarction
- Polymorphs and macrophages remove dead tissue
- Capillaries grow into area and granulation tissue forms
- Fibroblasts grow into area creating a scar
Capillary ischaemia
- Blocked or damaged capillaries can cause tissue ischaemia
- Occurs in
- Frostbite
- Cryoglobulinaemia
- Disseminated intravascular coagulation
- Diabetic microangiopathy
Aneurysms
- Localised dilatation of the vessel wall any where in the circulatory
system
- Can be classified as true or false aneurysm
- Common sites of true aneurysms are
- Abdominal aorta
- Iliac artery
- Popliteal artery
- Femoral artery
- True aneurysm
- Wall of the aneurysm consists of one or more of the vessel wall
layers
- False aneurysm
- Wall of the aneurysm is made up of connective tissue
Aetiology
- Atherosclerosis
- Vasculitis (e.g. Kawasaki disease)
- Syphilis
- Infective (Mycotic)
- Trauma
- Congenital (e.g. Berry aneurysm)
Abdominal aortic aneurysm
- Dilatation of the aortic wall of more than one and a half times the
aortic diameter
- Diameter of more than three centimetres is usually regarded as an
aneurysm
- More common in men
- Incidence increases with age
- Atherosclerosis plays an important role in the aetiology
- Most arise below the renal arteries (> 90%)
- Elective open surgery has an associated mortality rate of 2-6%
- Emergency surgery has an associated mortality of more than 50%
Raynaud’s disease
- Paroxysmal cyanosis of the digits of hand or feet
- More commonly affects hands
- Caused by local spasm of small blood vessels
- Usually precipitated by cold
- Occurs in more commonly in young females
- Raynaud’s phenomenon can be secondary to conditions such as:
- Scleroderma
- Mixed connective tissue disease
- Atherosclerosis
- Systemic lupus erythematosus
- Buerger’s disease
- If no cause is found it is known as Raynaud’s disease
Buerger’s disease
- Inflammation of the small and medium sized arteries
- May also involve adjacent nerves
- Also known as thromboangitis obliterans
- More commonly affects males
- May begins at young age
- Clinical features include
- Claudication
- Rest pain
- Ulceration
- Gangrene
- Strongly associated with heavy cigarette smoking
- The involvement is segmental
- Occlusive inflammatory thrombi are seen within the lumen
- Microscopically all the layers of the vessel wall are involved
- There is polymorphonuclear infiltration
- Angiogram typically show occlusive thrombi and cork screw
collaterals
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