Vascular pathology - Fung Flashcards
Describe developmental or Berry aneurysms.
- Occur in cerebral vessels - ie. Circle of Willis
- Majority occur sporadically
- Some are genetic and are associated with:
AD polycystic kidney disease, Ehler-Danlos syndrome, NF1, Marfan syndrome - Referred as congenital but not present at birth; develop over time
What are some risk factors associated with Berry aneurysms?
- smoking
2. hypertension
What are atriovenous fistulas?
Small, direct connections between arteries and veins that bypasses capillaries.
Atriovenous fistulas occur due to…?
Developmental defects
Rupture of arterial aneurysm into an adjacent vein
Penetrating injuries that pierce arteries and veins
Inflammatory necrosis of adjacent vessels
Iatrogenic
Describe fibromuscular dysplasia.
- Focal irregular thickening of the walls of medium and large muscular arteries
- Results in luminal stenosis
- Can occur at any age but is most frequent in young women
What are aneurysms?
Localized, abnormal dilation of blood vessels or the heart.They can be congenital or acquires and may be saccular or fusiform in shape.
How are true aneurysms different from false?
- Involves an intact attenuated arterial wall or thinned ventricular wall
- Examples:
Atherosclerotic
Syphilitic
Congenital
Ventricular following transmural infarction
Describe false aneurysms.
- Also called pseudo-aneurysm
- Defect in the vascular wall leading to an extravascular hematoma that freely communicates with the intravascular space
- Example:
Ventricular rupture with pericardial adhesion
Describe Saccular true aneurysms.
- Spherical outpouchings involving only a portion of the vessel
- 5-20 cm in diameter
Describe Fusiform true aneurysms.
- Diffuse, circumferential dilation of a long vascular segment
- Up to 20 cm in diameter
- Involve extensive portions of the aortic arch, abdominal aorta, iliac arteries
What causes aneurysms?
Any process that causes weakening of the vessel wall. Examples are:
1. Sporadic
2. Connective tissue diseases such as:
Marfan syndrome: defect of fibrillin
Ehlers-Danlos syndrome: defect in the synthesis or structure of fibrillar collagen
Vitamin C deficiency: altered collagen cross-linking
Loeys-Dietz syndrome: defect in elastin, collagen I and III
3. congenital defects
4. infections due embolization, direct extension or circulation of organisms
What are some processes that can weaken a vessel wall and lead to aneurysm formation?
- Inflammation that alters the balance of synthesis and destruction of collagen such as
Increased matrix metalloproteases (MMP) that degrade the extracellular matrix (released by macrophages) - Loss of smooth muscle cells or proliferation of non- collagenous/non-elastic extracellular matrix
- Thickening of the intima decreases diffusion of oxygen and nutrients to the medial causing cystic medial degeneration
What are the most important predisposing factors for aneurysm formation?
- Atherosclerosis - aneurysms often form in the abdominal aorta
- hypertension - aneurysms often form in the ascending aorta
What are the clinical consequences of an AAA?
- Rupture with potential fatal hemorrhage
- Obstruction of branch vessel
- Embolism from atheroma or mural thrombus
- Impingement on adjacent structures
Describe thoracic aortic aneurysms.
- Most commonly associated with hypertension
- Signs and symptoms include
encroachment on:
Mediastinal structures
Lungs and airways
Esophagus - Cough due to pressure on recurrent laryngeal nerve
- Bone pain
- TAA leads to aortic valve dilation with insufficiency
What is the most common area for an aneurysm in older men?
Abdominal aorta.
What is dissection?
- After an intimal tear blood splays apart the laminar planes of the media to form a blood filled channel within the vessel wall
- May or may not be associated with vessel dilation
- Not usually seen with atherosclerosis because of medial fibrosis
Dissection occurs in….?
- Men 40-60 years with hypertension
- Younger patients with systemic and localized abnormalities of the aorta
- May be Iatrogenic
Describe the pathogenesis of dissection.
- Hypertension is the major risk factor causing:
Medial hypertrophy of the vasa vasorum with degenerative changes of the media suggest injury due to diminished flow - this is also called cystic medial degeneration. - Inherited or acquired tissue disorders can also lead to dissection due to abnormal vessel wall. Examples are Marfans, vitamin C deficiency and Ehler-danlos syndrome.
What is the most frequent histologically detectable lesion in cases of dissection?
Cystic medial degeneration.
What are two types of dissections?
- Type A
2. Type B
Describe Type A dissections.
- These are proximal lesions
- Called DeBakey type I and II
- Involving the ascending aorta and descending aorta - Debakey Type I
- Involving just the ascending aorta - Debakey type II
Describe Type B dissections.
- These are distal lesions
- Called DeBakey type III
- Beginning distal to the subclavian artery and NOT involving the ascending aorta
Which type of dissection only involves the descending aorta?
Type B or DeBakey type III dissections.
What is a common clinical presentation of dissection>
A patient comes in with chest pain that radiates to the back. Can look like a heart attack.
What is vasculitis?
Inflammation of a vessel wall.
The clinical features of vasculitis depend on……?
The vascular bed affected.
Vasculitis affects vessels of what size?
Any size.
What are the most common pathogenic mechanisms of vasculitis?
- immune-mediated inflammation
- direct invasion of vascular walls by infectious agents (this can also initiate a non-infectious vasculitis due to antigen-antibody immune complex deposition)
Large vessel vasculitis affects what type of vessels?
- aorta
2. large branches to extremities, head and neck
Medium vessel vasculitis affects what type of vessels?
The main visceral arteries and their branches. Examples are renal and pulmonary arteries.
Small vessel vasculitis affects what type of vessels?
- arterioles
- venules
- capillaries
- small arteries
Name some types of large vessel vasculitis.
- Giant cell (temporal) arteritis
2. Takayasu arteritis
Name some medium vessel vasculitis.
- polyarteritis nodosa - immune complex mediated
2. kawasaki disease - anti-endothelial cell antibodies
Name some small vessel vasculitis.
- Wegener granulomatosis - patient’s have granulomas but no asthma
- Churg-Strauss syndrome - patient’s have eosinophilia, asthma, and granulomas
- Microscopic polyangiitis - vasculitis without asthma or granulomas
4. Immune complex vasculitis: Anti-GBM disease Cryoglobulinemic vasculitis IgA vasculitis Hypocomplementemic urticarial vasculitis Goodpasture's syndrome
What is variable vessel vasculitis?
Vasculitis that effects no predominant type of vessel. Examples are Behcet’s disease and Cogan’s syndrome.
Giant cell arteritis and Takayasu arteritis both cause vasculitis. How can you tell them apart?
Histologically they will look the same. The clue to tell the difference is the age of the patient. Giant cell arteritis occurs in patients over 50 years old while Takayasu arteries occurs in patients under 50 years of age.
Non-infectious vasculitis can be caused by what….?
- immune complex deposition
- anti-neutrophil cytoplasmic antibodies
- anti-endothelial cell antibodies (as seen in Kawasaki disease)
What are some diseases that have an immune complex associated vasculitis?
- SLE
- polyarteritis nodosa
- drug hypersensitivity
What are anti-neutrophil cytoplasmic antibodies (ANCA)?
These are circulating antibodies that react with neutrophil cytoplasmic antigen. They are a heterogenous group of antibodies that are directed against neutrophil primary granules, monocyte lysosomes and endothelial cells.
What are the two types of ANCA?
- p-ANCA
2. c-ANCA
Describe p-ANCA.
- Also called Anti-myeloperoxidase (MPO-ANCA)
- p in p-ANCA stands for perinuclear - this is where they stain
- MPO is a lysosomal granule constituent
- Seen in therapeutic agents (propylthiouracil)
- Seen in microscopic polyangiitis and Churg-Strauss syndrome
Describe c-ANCA.
- Also called Anti-proteinase-3 (PR3-ANCA)
- The c in c-ANCA stands for cytoplasmic - this is where the antibody stains
- PR3 is a neutrophil azurophilic granule constituent
- Shares homology with microbial peptides
- Seen in Wegener granulomatosis
Describe the mechanism by which ANCA causes vasculitis.
- Drugs or cross-reactive microbe (antigens) induce ANCA formation or
- Neutrophil release MPO/PR3 and cause ANCA formation in a susceptible host
- Host release cytokines (TNF) that causes expression of MPO/PR3 on neutrophils or other cell types
- ANCA react and directly induce endothelial cell injury or activation of other neutrophils
- ANCA-activated neutrophils degranulate and release reactive oxygen species further injuring endothelial cells
Describe Giant cell arteritis.
- Chronic, granulomatous inflammation of large to small-sized arteries
- Affects principally arteries of the head: temporal artery, vertebral artery, ophthalmic artery and aorta
- Medical emergency because injury to the ophthalmic artery can cause blindness)
What is the most common vasculitis among elderly individuals of 50 years or older?
Giant cell arteritis.
What is the pathophysiology of Giant cell arteritis?
- T-cell lymphocytic immune response against an unknown antigen
- TNF and anti-endothelial cell humoral immune responses also contribute
What are some histological findings in Giant cell arteritis?
- Discontinuous involvement of the vessel (multiple biopsies)
- Intimal thickening
- Medial granulomatous inflammation with giant cells
- Elastic lamina fragmentation
Describe Takayasu arteritis.
- Granulomatous arteritis of medium or larger arteries characterized by:
Ocular disturbances
Marked weakening of the pulses in the upper extremities (pulseless disease) - Fibrous thickening of the aorta (aortic arch & great vessels)
- Shares many attributes with GCA (clinical features and histology)
- Patients are less that 50 years old
Describe Polyarteritis nodosa.
- Systemic vasculitis of small or medium-sized muscular arteries such as:
Renal vessels
Visceral vessels (heart, liver, GI tract) - Spares pulmonary circulation
- Does not involve arterioles, capillaries or venues
- Associated with chronic hepatitis B
- HBsAg-HBsAb complexes in vessels (immune complex mediated)
- Cause is unknown in the majority of cases
Describe the pathology of Polyarteritis nodosa.
- Segmental transmural necrotizing inflammation (neutrophils, eosinophils and lymphocytes)
- Affect the vessel circumferentially and prefer vessel branch points
- Inflammatory process can weaken vessel and cause aneurysms
- Acute inflammatory infiltrate is replaced by fibrous thickening of the vessel wall
- Lesions in different stages coexist – recurrent and ongoing insults
Describe Kawasaki disease.
- Acute febrile, self-limited illness of infancy and childhood affecting large to medium sized and small vessels
- Mucocutaneous lymph node syndrome including:
Conjuntival and oral erythema and erosion
Edema of hands and feet
Erythema of palms and soles
Desquamative rash
Cervical lymph node enlargement - less fibrinoid than PAN
Why is Kawasaki disease clinically significant?
It involves coronary arteries and there is a risk of aneurysms that may rupture and thrombus - resulting in MI.
Describe the pathology of Kawasaki disease.
- Vasculitis thought to result from a delayed hypersensitivity reaction of T cells to an uncharacterized antigen (possibly infectious agents)
- Cytokines are produced and B-cells are activated leading to auto-antibody production
- Auto-antibodies are to endothelial and smooth muscle cells
- lesions show marked inflammation of the entire vessel wall
- healed lesions may have obstructive intimal thickening
Describe microscopic polyangiitis.
- Segmental fibrinoid necrotizing vasculitis that affects capillaries, arterioles and venues
2, Resembles PAN but affects smaller vessels
3, Hypersensitivity vasculitis (leukocytoclastic vasculitis) - All lesions are in the same stage at the same time
- MPO-ANCA
What systems are affected by microscopic polyangiitis?
- Skin (palpable cutaneous purpura)
- Mucous membranes
- Lungs (hemoptysis)
- Brain
- Heart
- Gastrointestinal tract (bowel pain, bleeding)
- Kidney (hematuria, proteinuria)
- Muscle (muscle pain, weakness)
What conditions does microscopic polyangiitis occur with?
- Henoch-Schonlein purpura
- Essential mixed cryoglobulinemia
- Vasculitis associated with connective tissue disorders
Describe Churg-Strauss syndrome.
1. Small vessel necrotizing vasculitis associated with: Asthma Allergic rhinitis Lung infiltrates Peripheral hypereosinophilia Extravascular necrotizing granulomas 2. Also called allergic granulomatosis 3. MPO-ANCA's are sometimes present
Churg-Strauss syndrome histologically resembles what?
PAN, or microscopic polyangiitis but it occurs with granulomas and eosinophilia.
What are the clinical manifestations of Churg-Strauss syndrome?
Palpable purpura
GI tract bleeding
Focal and segmental glomerulosclerosis
Describe Wegener granulomatosis.
- Necrotizing vasculitis characterized by:
Acute necrotizing granulomas of the upper respiratory tract and/or lower respiratory tract
Necrotizing granulomatous vasculitis affecting small to medium sized vessels
Focal necrotizing, crescentic glomerulonephritis - Clinically resembles polyarteritis nodosa except has respiratory involvement
Describe the pathology of Wegener granulomatosis.
- T-cell mediated hypersensitivity reaction to an inhaled infectious agent
- Anti-PR3 (c-ANCA) is present in 95%
Describe Thromboangiitis obliterans.
- also called Buerger disease
- Segmental thrombosing acute and chronic inflammation of medium and small sized arteries
- Leads to vascular insufficiency principally in the tibial and radial arteries (sometimes veins and nerves)
- Almost exclusively seen in heavy smokers before 35
- Cigarettes are directly toxic to endothelial cells or an immune response to cigarettes
What are the clinical features of Thromboangiitis obliterans?
- Superficial nodular phlebitis
- Raynaud type cold sensitivity
- Instep claudication
- Severe pain at rest in the extremities
