Atherosclerosis & Other Vascular Pathology Flashcards
What are the basic constituents of the walls of blood vessels
Endothelial cells
Smooth muscle cells
Extracellular matrix (ECM) including elastic fibres, collagenic fibres, and glycosaminoglycans.
Arterial wall thickness gradually diminishes as the vessels become …….. (smaller, larger). The ratio of wall thickness to lumen diameter becomes ……….. (smaller, greater) with reducing size
Smaller, greater
The intima consists of …….
The intima consists of a single layer of endothelial cells with minimal underlying subendothelial connective tissue.
What is arteriosclerosis
It means hardening of arteries; group of disorder that have in common thickening & low elasticity of arterial wall
What are the three components of arteriosclerosis
Atherosclerosis is characterized by intima thickening & lipid deposition affecting elastic arteries(aorta, carotid & iliac) and muscular large & medium sizes arteries (coronary & renal arteries)
What is Monckeberg’s medial calcification sclerosis
Monckeberg’s medial calcific sclerosis:-
●characterized by ring like calcification of the media layer of muscular arteries occurring in both sexes above 50yrs. No associated inflammation.
●Vessels involved are : femoral, radius, ulnar, genital tract.
●Does not narrow the lumen
●can occur with atherosclerosis
What is arteriolosclerosis
Arteriolosclerosis is characterized by marked proliferative or hyaline thickening of the walls of small arteries and arterioles
What disease is the major cause of heart attack, CVA, and gangrene of the extremities and is responsible for about 50% of all deaths in the United State, Europe, and Japan
Atherosclerosis
What are the major RFs for atherosclerosis
Diet & hyper lipidemint hyper cholesterolemia, high TG)
Hypertension
Cigarette smoking
Diabetes Mellitus
What is the role of endothelial injury in arteriosclerosis
Increased endothelial permeability
Increased enhanced leukocyte adhesion,
Increased alterations in expression of endothelial cell gene products
What are the causes of endothelial dysfunction
cigarette smoke,
homocysteine,
viruses and other infectious agents.
hemodynamic disturbances that accompany normal circulatory function
adverse effects of hypercholesterolemia.
What is the role of inflammation in arteriosclerosis
recruitment and subsequent differentiation of macrophages is initially protective as they remove potentially harmful lipid particles,
●progressive accumulation ultimately results in lesion progression.
●Macrophages produce IL-1 and TNF, which increase adhesion of leukocytes
Several chemokines generated by macrophages, including monocytes Chemotactic protein-1 (MCP-1), may recruit more leukocytes into the plaque.
●Macrophages produce toxic oxygen species that also cause oxidation of the LDL in the lesions,
●They elaborate growth factors that may contribute to SMC proliferation.
What is the change of lipids in arteriosclerosis
Chronic hyperlipidemia, particularly hypercholesterolemia, may directly impair endothelial cell function through
Increased production of oxygen free radicals that deactivate NO, the major endothelial-relaxing factor.
With chronic hyperlipidemia, lipoproteins accumulate within the intima at sites of increased endothelial permeability.
Chemical change of lipid induced by free radicals generated in macrophages or endothelial cells in the arterial wall yields oxidized (modified) LDL
Oxidized LDL is invested by
macrophages through the scavenger receptor, distinct from the LDL receptor , thus forming foam cells
What is the role of oxidized LDL in arteriosclerosis
Increases monocytes accumulation in lesions;
Stimulates release of growth factors and cytokines; and
It is cytotoxic to endothelial cells and smooth muscle cells
What are the roles of smooth muscle cells to arteriosclerosis
Smooth muscle cells migrate from the media to the intima, where they proliferate and deposit Extra cellular matrix components, converting a fatty streak into a mature fibrofatty atheroma, and contribute to the progressive growth of atherosclerotic lesions
Several growth factors have been implicated in the proliferation of SMCs, including PDGF (released by platelets adherent to a focus of endothelial injury, and by macrophages, Endothelia Cells, and Smooth Muscle Cells), FGF, and TGF-αlpha
SMCs may also take up modified lipids, contributing to foam cell formation
Vascular SMCs synthesize extracellular matrix molecules (notably collagen) that stabilize atherosclerotic plaques.
However, activated inflammatory and immune cells in the plaque can lead to the death of intimal SMCs by apoptosis
What is the important abnormality of arteriosclerosis
The important abnormality is focal intima thickening & lipid accumulation which later forms atheromatous plaques
Affect arterial wall partially around the circumference (i.e. eccentric lesion)
What are fatty streaks
Fatty streaks
●are the precursor lesion and appear in aorta in childhood, in coronary in adolescence
●Begins as multiple yellow, flat, spots < lmm
●These coalesce - elongated streaks
Composed of lipid-filled foam cells, T- lymphocytes & Endothelial Cell lipid present in small amount, Collagen, proteoglycan & elastic fibers in variable amount
●Not all fatty streaks progress to plaques
Describe atheromatous plaques
Appear as white to whitish yellow material that impinge on the lumen of the artery
●Sizes vary from 0.3 to 1.5cm in diameter which could coalesce larger masses
●The lesions are eccentric(affect part of wall)
●Cut section-
●superficial portion – fibrous yellow cap
●Deep portion yellow or whitish yellow & soft
●In larger plaque, the center contains cellular debris
It has 3 components in varying proportion:
●(1) cells – Smooth Muscle cell, macrophages, other leukocytes
●(2) connective tissue –Extracellular material including collagen,elastic fibres, proteoglycans
[Fibrous cap is composed of (1) and (2)]
(3) Intracellular & extracellular lipid deposits- disorganized mass of lipid material, cholesterol clefts, cellular debris, plasma proteins, fibrin, thrombus in varying stages of organization. (Necrotic core )
●Progressive fibrosis of the plaque may convert the atheroma to a fibrosis scar
What are the distributions of the lesions in arteriosclerosis
Aorta-abdominal> thoracic>ostia of its major branches
Coronary arteries(first 6cm)
Popliteal A
Descending thoracic aorta
Internal carotid A
Vessels of the circle of Willis
Vessels of the upper extremeties, mesenteric and renal arteries are relatively spared except at their ostia
What are some complications of arteriosclerosis
(1) calcification
(2) focal ulceration or rupture of plaque discharge of debris into blood cholesterol emboli
(3) thrombus formation
(4) haemorrhage into the plague
(5) aneurysmal dilatation
What is the clinico-pathological correlation of arteriosclerosis
●manifestation varies depending on the vessel affected, extent and configuration of the atheroma.
●Cause disease by:
●Slow insidious narrowing of vascular lumen involving small arteries ischaemia of tissues perfused such as IHD, CVA,gangrene of the leg.
●Sudden occlusion by superimposed thrombus or haemorrhage infarction
●Thrombo- embolism-large vessels
●Aneurysmal rupture-large vessels
●Although any organ may be affected, most often the vessels supplying the heart, brain, kidneys, lower extremeties and small intestine are affected
What are some complications of an atheroma aorta
Ulceration
●Thrombosis
●Haemorrhage
●Calcification
●Embolism
●Aneurysmal dilatation
Describe Mockeberg’s medial sclerosis
Affects muscular arteries e.g radial ulnar, femoral.
●Xterised by degeneration fragmentation of medial muscle fibres followed by ring-like calcium deposition within the media
●Rarely occurs below 50years
What are the types of arteriosclerosis
●Hyaline arteriolosclerosis
●Hyperplastic
●Fibrinoid arteriolosclerosis or necrotising arteriolitis
Describe hyaline arteriosclerosis
Seen in the kidney in benign hypertension
●DM
●Elderly Patients
●Deposition of homogenous pink, hyaline material in the wall of arterioles
●There is loss of underlying structural details
●Narrowing of lumen
What is the pathogenesis of arteriosclerosis
Haemodynamic stress of hypertension
●Metabolic stress of DM
●Both accentuate endothelial injury, leads to leakage & hyaline deposition
Describe hyperplasticity arteriosclerosis
Associated severe hypertension
●Xterised by cellular proliferation of the intima,hypertrophy & hyperplasia of the media.
●Onion- skin appearance
Describe necrotising arteriolitis
Frequently associated with hyperplastic arteriolosclerosis
●Xterised by deposition of intensely eosinophilic amorphous material which is fibrinoid in nature in the wall of a vessels
●Malignant Hypertension
What is an aneurysm
Localised abnormal dilatations of a blood vessel or the heart.
●These dilatations are either cogenital or acquired
What are some aetiology for aneurysms
•Atherosclerosis
●Hypertension
●Syphilis
●Cystic medionecrosis
•Poly Ateritis Nodosa.
●Trauma
●Congenital
●Infection: mycotic aneurysm (Staph, Salmonella spp)
●Drugs e.g cocaine
What is a true aneurysm
Involves an attenuated but intact arterial wall or thinned ventricular wall of the heart
●Examples are Artherosclerosis, syphilitic, congenital vascular aneurysms,ventricular aneurysms following myocardial infarctions
What is a false aneurysm
Defect in the vascular wall leading to extravascular haematoma that freely communicates with the intravascular space – pulsating aneurysms
●Examples include post MI ventricular rupture contained by pericardial adhesion, a leak at the sutured junction of a vascular graft with the natural artery
What are the descriptive classifications of aneurysms
- Saccular aneurysms
Spherical outpouchings involving only a portion of vessel wall, 5-20cm in diameter. Often contain thrombus - Fusiform aneurysms
Circumferential spindle shaped dilatations of a long vascular segment. Vary in diameter up to 20cm and in length.
What are the other forms of aneurysm
- Berry aneurysm
●Small spherical dilatation 1-1.5cm - Dissecting. hypertension , Marfan’s syndrome or cystic medial necrosis and Ehlers Danlos syndrome.
What are De-Bakey’s classification of aneurysms
Type I- Ascending, arch and descending aorta
●Type II- Ascending aorta alone
●Type III- Descending aorta alone
What are Charcoat Bouchard aneurysms
●Minute (microaneurysms) in the brain
●Small penetrating blood vessels
●Common in Lenticulostriate branches of middle cerebral artery
●Associated with systemic hypertension
●May rupture and cause intracerebral haemorrhage.
What is the pathogenesis of aneurysms
Occur as a result of compromise to the structure and function of the connective tissue within vascular wall
●The defects may be inherited or sporadic
What are some conditions which cause a poor quality of vascular wall
Marfan Syndrome
Loeys-Dietz syndrome
Ehlers-Danlos syndrome
What is Marfan syndrome
Defective synthesis of scafolding protein fibrillin leading to abberant TGF-B activity and weakening of elastic tissue
What is Loeys-Dietz syndrome
Mutation in TGF-B receptor leading to defective synthesis of elastin and collagen I & III
What is Ehlers-Danlos syndrome
Weak blood vessels as a result of defective synthesis of collagen type III
What are some other factors which cause a weakness in vascular wall
●Alter of the balance of synthesis and degradation of collagen by inflammation and associated proteases
Increase in Matrix metalloprotease expression and decrease in tissue inhibitors of metalloprotease. Cytokines like IL-4 and IL-10 stimulate release of MMP from collagen
●Weakening of vascular wall by loss of smooth muscle cells or synthesis of non collageneous or non elastic extracellular matrix
Ischaemia of the media leads to destruction of smooth muscle cells and increase production of ground substance like glycosaminoglycans – Cystic media degeneration
What are varicose veins
●Abn. Dilated & tortuos veins which occur as a result of prolonged increased intraluminal press./or incompetent venous valves
●Superfical veins of the upper and lower leg are commonly involved due to postural effect
What are some causes of varicose veins
Portal Hypertension
●Pregnancy
●Intra-abdominal tumour
●Common >50yrs
●F>m
What are some sites for varicosity in portal hypertension
Oesophageal varices
●Caput medusae
●Haemorrhoids
What are some complications of varicose veins
Oedema of affected part
●Pain
●Thrombosis
●Bleeding
●Phlebothrombosis
●Thrombophlebitis
●Chronic Skin Ulcers
What are some diseases of the lymphatics
Lymphoedema
1. Congenital
—- Simple congenital
—- Milroy dx (Heredofamilial cogenital)
2. Acquired
●obstructive
—-Tumours
—-Infection filariasis
—–Post radiation.
●Lymphangitis
What are some tumors of blood vessels
Benign
●haemangioma
Intermediate
●haemangioendothelioma
Malignant
●angiosarcoma
●Kaposi sarcoma : classic, African type(endemic), epidemic (AIDS associated). Transplant associated (Immunosuppressive)
●Haemangiopericytoma.
What are some etiology of vasculitis
Bacteria
●Physical trauma
●Radiation injury
●Immunological injury: scleroderma, rheumatoid arthritis, SLE
What are some classifications of vasculitis
Giant cell (temporal ) arteritis
(Large to small size arteries)
●Takayasu arteritis
(Large to medium size arteries)
●Polyarteritis Nodosa
(Medium to small size)
●Kawasaki dx
(Large , medium and small size)
Small vessel vasculitis could be caused by which conditions
Churg-Strauss Syndrome
●Behcet disease
●Granulomatosis with Polyangitis formerly called Wegeners granulomatosus
●Thromboangiitis obliterans (Buergers disease)
What are some disorders associated with vasculitis
Rheumatoid arthritis
●Systemic lupus erythematosus
●Malignancy
●Mixed cryoglobulinaemia
●Antiphospholipid antibody syndrome
●Henoch-Schonlein purpura
