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• disorders of blood flow :

  cause of hypoxia and impaired oxygenation of local tissue

  disorders of central and peripheral arterial circulation

  disorders of venous circulation
• disorders can arise from changes of:

  vessel wall (ageing, artheroscelorsis,vasculitis)

  acute vessel obstruction and abnormal vessel dilation (varicose vein)
• Atherosclerosis: a disease of the arteries characterized by the deposition of fatty material on their inner walls.
• lipoproteins: transport lipids in bloodstream, made of cholesterol and proteins
• cholesterol: production of cell membranes and bile acid.
• triglycerides: used in energy metabolism
• abnormal lipoprotein metabolism -predisposing factor to athersclerosis
• HDL high-density lipoprotein:

  • "GOOD" cholesterol

  • cholesterol from arterial walls to liver.
• LDL low-density lipoprotein

  • deposition of cholesterol in arterial walls

  for use

  • accumulates in sub-endothelial space
• VLDL 5 very-low-density lipoprotein

  • triglycerides to cells for energy
• Chylomicrons

  • largest, least-dense lipoprotein

  • transport dietary triglycerides and

  cholesterol from the intestinal epithelial

  cells to liver, skeletal muscle and adipose

  tissue
• total cholesterol

  
• atherosclerosis:risk factors

  non-mod:

  Familial hypercholesterolaemia

  age and gender ( men > 45 years . Women > 55 years)

  Type 1 diabetes mellitus
• atheroscelrosis:risk factors

  mod

  HDL cholesterol <40 mg/dL

  C-reactive Protein levels (CRP)

  High homocysteine levels
• pathogenesis of atheroscelorsis:

  Formation of fibrofatty lesions in the intimal lining

  Pathologic process that causes disease of the coronary,

  cerebral, and peripheral arteries and aorta
• Types of lesions associated with atherosclerosis

  • Fatty streaks

  • Fibrous atheromatous plaque

  • Complicated lesion

  Can begin in childhood with the development of fatty streaks

  Lesions of atherosclerosis advance with aging
• Endothelium dysfunction;

  active biologic interface between blood and tissues

  • risk factor effect

  • dysfunction due to loss of NO and microtears

  • leukocytes recruited and inflammatory process starts
• Endothelium inflammation

  entry of circulating fat and cholesterol

  • oxidisation of LDLs

  • attracts circulating monocytes (become macrophages) to restore vessel wall integrity

  • inflammatory mediators released

  • smooth muscle cells grow and enter

  • macrophages and migrating smooth muscle cells consume ox-LDLs (foam cells)
• atherosclerotic plaque

  Continues to grow and cause narrowing

  of the vessel and production of ischemia

  “Stable” plaque

  • Small lipid pool with thick fibrous cap

  and preserved lumen

  “Vulnerable” plaque

  • Large lipid pool, thin fibrous cap,

  many inflammatory cells

  • Can commonly rupture and cause a

  thrombus which can further lead to

  narrowing
• progression of plaque:

  Two distinct processes

  chronic one - slow narrowing

  acute one - rapid luminal obstruction

  
  

  • plaque cap splits

  • necrotic material traps platelets

  • thrombus formation

  • reduces size of or blocks artery lumen

  • limited NO to vasodilation
• atherosclerosis : Pathogenesis

  —> oxidised LDL is cytotoxic at high levels

  • death of macrophages and smooth muscle cells

  • deposition of cell contents and cholesterol crystals

  • necrotic core forms in arterial wall
• atherosclerosis :

  fibrous cap :

  • fibrin infiltration (stiffening wall)

  • calcium deposition (hardening of vessel wall)

  • fibrous plaque with connective tissue and lipids
• specific arterial involvement in atherosclerosis:

  
• clinical manifestation of atherosclerosis:

  coronary heart disease:

  myocardial infarction, angina pectoris, congestive heart

  failure, and sudden cardiac death

  Cerebrovascular disease:

  • stroke and transient ischemic attack

  Peripheral artery disease:

  intermittent claudication and critical limb ischemia

  Aortic atherosclerosis

  • thoracic or abdominal aortic aneurysm
• differential protein expression in the aorta :

  
• elderly effects on vessels:

  
• disorders of blood flow:

  arterial obstruction : aetiology

  • Thrombosis

  • Atherosclerotic plaque

  • Iatrogenic

  • Traumatic

  • Arterial embolism
• arterial obstruction : clinical manifestations

  • Reduced perfusion in peripheral

  tissues - ischaemia and tissue

  necrosis

  • Depends upon aetiology and if has

  underlying peripheral artery disease
• arterial obstruction : pathogenesis

  • Associated with atherosclerosis and

  diabetes

  • Vasospasm, venous insufficiency,

  embolism and vasculitis
• venous disorders: aetiology

  • Wide range of venous abnormalities

  • Asymptomatic or symptomatic (dilation – ulcers)
• venous disorders : pathogenesis

  • Inadequate muscle pump function

  • Incompetent valves (reflux)

  • Venous thrombosis or non-thrombotic venous

  obstruction

  • Anatomic, physiologic and histologic changes

  leading to vein dilation, skin changes and/or skin

  ulceration
• aneurysms:

  change in characteristic and integrity of arterial wall

  aetiology:

  chronic inflammation , inherited and environmental factors , atherscelorsis

  • Saccular aneurysm

  • Brain: Circle of Willis (cerebral)

  • Fusiform and saccular aneurysms

  • Thoracic and abdominal aorta
• types of aneurysms:

  
• varicose veins:

  Superficial veins

  • Remodelling of vessel wall

  • Possible genetic link

  • More common in women>men

  Clinical manifestations:

  • Oedema, skin changes, venous

  ulceration

  • Chronic venous insufficiency

  • Superficial and/or deep venous

  reflux and/or obstruction
• phlebothrombosis:

  DVT

  if untreated = PE

  
• thrombophlebitis :

  • Thrombus in vein PLUS

  inflammation

  • Superficial or deep veins

  • Secondary to other conditions

  Clinical manifestations

  • Asymptomatic

  • Related to inflammation

  • Pain, swelling, deep muscle

  tenderness

  • Fever, malaise, elevated WBC
• risk factors for thrombophlebitis and varicose veins:

  -venous stasis

  bed rest , immobility

  spinal cord injury

  acurte myocardial infarction

  congestive heart failure

  -vessel trauma

  indwelling venous catheters

  surgery

  trauma /infection

  advancing age , family history,prolonged standing, increased BMI , smoking, high oestrogen states
• disorders of central and peripheral arterial circulation result from:

  -vessel wall (ageing,atherosclerosis,vasculitis)

  -acute vessel obstruction

  -abnormal vessel dilation(aneurysms)
• vasculitis:

  peripheral arterial disease

  pathogenesis :

  Acute or chronic inflammation

  of blood vessels

  • Vessels vary in size, type, and

  location

  • Vessel changes

  • Presence of leukocytes

  • Can be serious/fatal

  • Prompt recognition and therapy
• vasculitis:

  clinical manifestations :

  fever

  night sweats

  arthralgia