Vascular Pathology Flashcards
What factors are related to risk of rupture of berry aneurysms?
Size
Episodes of HTN
What is the main site for a berry aneurysm?
AComm: 40%
What is the main site for a berry aneurysm?
AComm: 40%
What are Charcot-Bouchard aneurysms?
Aneurysms occurring in straight segments of small intracerebral arteries in basal ganglia, caused by chronic HTN
What is vasculitis?
Acute or chronic inflammation that results in structural damage to the vessel wall
What is vasculitis?
Acute or chronic inflammation that results in structural damage to the vessel wall
List 4 types of immune-mediated vasculitis
Henoch-Schonlein purpura
Cryoglobulinaemic vasculitis
Serum sickness
Connective tissue diseases
Direct Ab attack
Goodpastures’ syndrome
Kawasaki disease
ANCA associated
??
Unknown
Giant cell (temporal) arteritis ??
Unknown
Giant cell (temporal) arteritis ??
Unknown
Giant cell (temporal) arteritis ??
How can you tell if there are small vessel changes?
Retina Kidney Neuropathy Purpuric rash that won't blanch, usually lower limbs more than upper limbs GI bleeding and infarcts Pancreatitis
How can you tell if there are small vessel changes?
Retina Kidney Neuropathy Purpuric rash that won't blanch, usually lower limbs more than upper limbs GI bleeding and infarcts Pancreatitis
Wegener’s
Respiratory tract and kidneys
Churg-Strauss
Granulomas
Eosinophils
Histological changes in small vessel vasculitis
May be thrombus Wall often dead with fibrinoid necrosis Inflammation around vessel Blood leaking out of vessel May do other tests to assess whether there are e.g. Igs depositing in cell wall Leukocytoclasis
Histological changes in small vessel vasculitis
May be thrombus Wall often dead with fibrinoid necrosis Inflammation around vessel Blood leaking out of vessel May do other tests to assess whether there are e.g. Igs depositing in cell wall Leukocytoclasis
Pathological process in small vessel vasculitis
Infiltrate of neutrophils causing vessel injury
Fibrin deposition (in lumen or vessel wall)
Leakage of RBCs
Lymphocytes and macrophages attract later to help in vessel repair
Fibrois of vessel wall
May progress direct to giant cell inflammation in giant cell vasculitis
List 7 small vessel vasculitides
Microscopic polyangitis
Wegener’s granulomatosis
Churg-Strauss syndrome
Henoch-Schonlein purpura (IgA deposition)
Cryoglobulinaemic vasculitis (test for cryoglobulins)
Serum sickness
Rheumatoid and lupus vasculitis (Rh factor, anti-dsDNA)
List 3 manifestations of small vessel vasculitis
Nephritis: usually a necrotising and crescentic GN
Pulmonary haemorrhage: haemorrhagic alveolar capillaritis, heals as interstitial fibrosis
Pulmonary-renal syndrome: in microscopic polyangitis and Goodpastures’ syndrome
Goodpasture’s disease
Anti-BM Abs
List 3 manifestations of small vessel vasculitis
Nephritis: usually a necrotising and crescentic GN
Pulmonary haemorrhage: haemorrhagic alveolar capillaritis, heals as interstitial fibrosis
Pulmonary-renal syndrome: in microscopic polyangitis and Goodpastures’ syndrome
Goodpastures’
Anti-BM Abs
List 3 manifestations of small vessel vasculitis
Nephritis: usually a necrotising and crescentic GN
Pulmonary haemorrhage: haemorrhagic alveolar capillaritis, heals as interstitial fibrosis
Pulmonary-renal syndrome: in microscopic polyangitis and Goodpastures’ syndrome
Skin: purpura
Abdominal pain: bowel necrosis, ulceration and haemorrhage, ??
List 3 manifestations of small vessel vasculitis
Nephritis: usually a necrotising and crescentic GN
Pulmonary haemorrhage: haemorrhagic alveolar capillaritis, heals as interstitial fibrosis
Pulmonary-renal syndrome: in microscopic polyangitis and Goodpastures’ syndrome
Skin: purpura (non-blanching, more common in lower limbs, rapid onset)
Abdominal pain: bowel necrosis, ulceration and haemorrhage, ??
List 3 manifestations of small vessel vasculitis
Nephritis: usually a necrotising and crescentic GN
Pulmonary haemorrhage: haemorrhagic alveolar capillaritis, heals as interstitial fibrosis
Pulmonary-renal syndrome: in microscopic polyangitis and Goodpastures’ syndrome
Skin: purpura (non-blanching, more common in lower limbs)
Abdominal pain: bowel necrosis, ulceration and haemorrhage, ??
List 3 manifestations of small vessel vasculitis
Nephritis: usually a necrotising and crescentic GN
Pulmonary haemorrhage: haemorrhagic alveolar capillaritis, heals as interstitial fibrosis
Pulmonary-renal syndrome: in microscopic polyangitis and Goodpastures’ syndrome
Skin: purpura (non-blanching, more common in lower limbs)
Abdominal pain: bowel necrosis, ulceration and haemorrhage, ??
Peripheral neuropathy, myalgia, arthralgia: involvement of small arteries and arterioles, may have elevated muscle enzymes
Goodpastures’
Anti-BM Abs
Pauci-immune vaculitis
??
Microscopic polyangitis
Necrotising systemic vasculitis affecting arterioles, capillaries and venules (and sometimes small and medium sized arteries)
Characterised by ??
Incidence of MP
1 in 1000
MP demographics
Slight M>F predominance
Mean age 50 years
Microscopic polyangitis
Necrotising systemic vasculitis affecting arterioles, capillaries and venules (and sometimes small and medium sized arteries)
Characterised by ??
Segmental vascular necrosis
Infiltrate of neutrophils and monocytes
May have leukocytoclasis - split neutrophils?, fibrin and haemorrhage
Thrombosis in small arteries causing infarction
Healing with fibrosis
Pseudoaneurysms may occur in medium sized arties)
MP demographics
Slight M>F predominance
Mean age 50 years
P-ANCA
MP
C-ANCA
??
C-ANCA
??
ANCA-positive
Probably pauci-immune?
ANCA-positive
Probably pauci-immune?
Wegener’s granulomatosis
Granulomatous inflammation, necrosis and vasculitis predominantly affecting respiratory tract
Variable renal involvement
Predominantly C-ANCA positive (75%)
Churg-Strauss syndrome
Granulomatous inflammation Peripheral blood eosinophilia Can have asthmatic symptoms 60% P-ANCA, 10% C-ANCA, 30% negative Systemic disease - may get kidney damage, may diagnose from biopsy
List 7 small vessel vasculitides
Microscopic polyangiitis
Wegener’s granulomatosis
Churg-Strauss syndrome
Henoch-Schonlein purpura (IgA deposition)
Cryoglobulinaemic vasculitis (test for cryoglobulins)
Serum sickness
Rheumatoid and lupus vasculitis (Rh factor, anti-dsDNA)
List 3 manifestations of small vessel vasculitis
Nephritis: usually a necrotising and crescentic GN
Pulmonary haemorrhage: haemorrhagic alveolar capillaritis, heals as interstitial fibrosis
Pulmonary-renal syndrome: in microscopic polyangiitis and Goodpastures’ syndrome
Skin: purpura (non-blanching, more common in lower limbs)
Abdominal pain: bowel necrosis, ulceration and haemorrhage, ??
Peripheral neuropathy, myalgia, arthralgia: involvement of small arteries and arterioles, may have elevated muscle enzymes
Microscopic polyangiitis
Necrotising systemic vasculitis affecting arterioles, capillaries and venules (and sometimes small and medium sized arteries)
Characterised by ??
Segmental vascular necrosis
Infiltrate of neutrophils and monocytes
May have leukocytoclasis - split neutrophils?, fibrin and haemorrhage
Thrombosis in small arteries causing infarction
Healing with fibrosis
Pseudoaneurysms may occur in medium sized arties)
Churg-Strauss syndrome
Granulomatous inflammation Peripheral blood eosinophilia Can have asthmatic symptoms 60% P-ANCA, 10% C-ANCA, 30% negative Systemic disease - may get kidney damage, may diagnose from biopsy
Henoch-Schonlein purpura
??
Medium-sized vasculitides
Polyarteritis nodosa
Polyarteritis nodosa
Ag often unknown (sometimes Hep B/C)
??
Microscopic polyangiitis vs PAN
??
Temporal artery - external carotid system - why blindness?
Potentially internal carotid system leading to retinal artery could also be affected
Temporal artery - external carotid system - why blindness?
Indicates that potentially internal carotid system leading to retinal artery could also be affected
Temporal artery - external carotid system - why blindness?
Indicates that potentially internal carotid system leading to retinal artery could also be affected
Temporal arteritis
Medical emergency - steroids?
Temporal arteritis
Medical emergency - steroids?
List ? causes of haemopericardium
?
List ? causes of haemopericardium
?
How does haemopericardium lead to death of a patient?
When the pericardial pressure exceeds the intra-chamber pressures, the chamber will collapse
CO and systemic BP drops
What are the potential complications of aortic dissection?
Cardiac tamponade Aortic incompetence MI Aneurysm rupture Regional ischaemia Left arm ischaemia/vertebral steal
What abnormalities of the vessel wall are seen in Marfan’s syndrome?
?
List 5 causes of mitral valve incompetence
Infective endocarditis
Acute rheumatic fever
Ischaemic papillary muscle dysfunction or rupture
LV dilation
Myxomatous degeneration of leaflets or chordae
How is Marfan’s syndrome inherited? What % of cases are sporadic?
AD
Up to 30%
What is the abnormality in Marfan’s syndrome?
Defect in fibrillin-1 gene, a major building block of microfibrils and important in formation and maintenance of elastin in the ECM
Microfibrils also help regulated TGF-B availability, leading to aberrant activation in Marfan’s which is believed to have effects on the integrity of the ECM
List ? manifestations of Marfan’s syndrome
Mitral valve prolapse/myxomatous degeneration
Cystic medionecrosis (cystic medial degeneration) of aorta
Spontaneous pneumothorax
Lens dislocation (ectopia lentis)
List ? manifestations of Marfan’s syndrome
Mitral valve prolapse/myxomatous degeneration
Cystic medionecrosis (cystic medial degeneration) of aorta
OTHER?
What are the main risk factors for aortic dissection?
Marfan's syndrome Ehlers-Danlos syndrome Biscuspid aortic valve Aortic atherosclerosis Aortic dilation Cardiac risk factors (HTN, dyslipidaemia, DM, smoking)
List ? clinical manifestations of Marfan’s syndrome
Mitral valve prolapse/myxomatous degeneration
Cystic medionecrosis (cystic medial degeneration) of aorta
OTHER?
How might mitral valve prolapse present?
Asymptomatic
Mitral incompetence +/- ruptured chordae
Arrhythmias and sudden death
Predisposition to infective endocarditis
Diagnosis of vasculitis
Clinical features
Serology: ANCA, cryoglobulins, Hep B and C, complement, ANAs and rheumatoid factor
Pathology: biopsy if possible
List some potential causes of sudden collapse and death in a young adult
?
List ? causes of mitral (aortic??) valve incompetence
Marfan’s syndrome? dissecting aortic aneurysm?
List ? causes of haemopericardium
?
How does haemopericardium lead to death of a patient?
?
What are the main risk factors for aortic dissection?
?
What are the potential complications of aortic dissection?
?
What abnormalities of the vessel wall are seen in Marfan syndrome?
?
List ? causes of mitral valve incompetence
Marfan syndrome? dissecting aortic aneurysm?
How is Marfan syndrome inherited? What % of cases are sporadic?
AD
Up to 30%
What is the abnormality in Marfan syndrome?
Defect in fibrillin-1 gene, a major building block of microfibrils and important in formation and maintenance of elastin in the ECM
Microfibrils also help regulated TGF-B availability, leading to aberrant activation in Marfan’s which is believed to have effects on the integrity of the ECM
What is the abnormality in Marfan syndrome?
Defect in fibrillin-1 gene, a major building block of microfibrils and important in formation and maintenance of elastin in the ECM
Microfibrils also help regulated TGF-B availability, leading to aberrant activation in Marfan’s which is believed to have effects on the integrity of the ECM
List ? manifestations of Marfan syndrome
Mitral valve prolapse/myxomatous degeneration
Cystic medionecrosis (cystic medial degeneration) of aorta
OTHER?
How might mitral valve prolapse present?
Asymptomatic
Mitral incompetence +/- ruptured chordae
Arrhythmias and sudden death
Predisposition to infective endocarditis
List ? clinical manifestations of Marfan syndrome
Mitral valve prolapse/myxomatous degeneration
Cystic medionecrosis (cystic medial degeneration) of aorta
OTHER?
How might mitral valve prolapse present?
Asymptomatic
Mitral incompetence +/- ruptured chordae
Arrhythmias and sudden death
Predisposition to infective endocarditis
What are some of the possible sequelae of cystic medionecrosis?
Aortic dissection
Annuloaortic ectasia and aortic regurgitation
What are the main risk factors for aortic dissection?
?
List ? causes of mitral (aortic??) valve incompetence
Marfan syndrome? dissecting aortic aneurysm?
Describe the likely pathogenesis of retinal flame haemorrhages
?
Describe the likely pathogenesis of retinal flame haemorrhages
?
What are the potential causes of systemic HTN in a 32 year old?
?
What are the potential causes of systemic HTN in a 32 year old?
?
What are the potential causes of a spontaneous SAH?
?
What are the potential causes of a spontaneous SAH?
?
How should a SAH be managed?
BP control
Analgesia
Find the cause, intervene neurosurgically
What is the pathogenesis of vasospasm post-SAH? What can it cause?
?
What are the 3 elements of the Cushing reflex?
HTN
Bradycardia
Irregular breathing
What are the 3 elements of the Cushing reflex?
HTN
Bradycardia
Irregular breathing
List ? causes of SAH
?
What are the risk factors for formation of berry aneurysms?
?
Where are the most common sites for berry aneurysms?
?
What are the presenting clinical features of SAH?
?
What are the complications of SAH?
?
What proportion of patients with SAH die?
?
Name 3 other types of aneurysms that may occur in vessels supplying the CNS
?
List ? potential causes of renal and splenic infarction
?
List 4 histological findings associated with vasculitis
Fibrinoid necrosis
Thrombosis
Perivascular haemorrhage
Leukocytoclasis
What symptoms are consistent with vasculitis?
Range of clinical manifestations depending on affected organs
Constitutional symptoms of fever, LOW, malaise, arthralgias and myalgias
List the 4 causes of vasculitis
Immune mechanisms (deposition of circulating immune complexes or in situ formation of immune complexes following previous seeding of Ag in the vascular bed)
Infection (direct invasion and immune-mediated)
Radiation
Toxins, drugs
List the 4 causes of vasculitis
Immune mechanisms (deposition of circulating immune complexes or in situ formation of immune complexes following previous seeding of Ag in the vascular bed)
Infection (direct invasion and immune-mediated)
Radiation
Toxins, drugs
List 2 vasculitides predominantly affecting large vessels
Giant cell arteritis
Takayasu arteritis
List 2 vasculitides predominantly affecting medium vessels
Polyarteritis nodosa
Kawasaki disease
List 3 ANCA-associated vasculitides predominantly affecting small vessels
Microscopic polyangiitis
Wegener’s granulomatosis
Churg-Strauss granulomatosis
List 3 ANCA-associated vasculitides predominantly affecting small vessels
Microscopic polyangiitis
Wegener’s granulomatosis
Churg-Strauss granulomatosis
List 4 immune complex vasculitides predominantly affecting small vessels
Anti-GBM disease (Goodpasture’s)
Cryoglobulinaemic vasculitis
IgA vasculitis (Henoch-Schonlein)
Hypocomplementemic urticarial vasculitis
List 4 immune complex vasculitides predominantly affecting small vessels
Anti-GBM disease (Goodpasture’s)
Cryoglobulinaemic vasculitis
IgA vasculitis (Henoch-Schonlein)
Hypocomplementaemic urticarial vasculitis
Distinguish between ANCA-associated and immune complex mediated vasculitides
ANCA-associated: few or no immune deposits, associated with ANCA specific for myeloperoxidase (APO-ANCA) or proteinase 3 (PR3-ANCA)
Immune complex mediated: moderate to marked deposits of Ig and/or complement in vessel walls
Distinguish between ANCA-associated and immune complex mediated vasculitides
ANCA-associated: few or no immune deposits, associated with ANCA specific for myeloperoxidase (APO-ANCA) or proteinase 3 (PR3-ANCA)
Immune complex mediated: moderate to marked deposits of Ig and/or complement in vessel walls
List 3 vasculitides associated with systemic disease
Lupus
Rheumatoid
Sarcoid
List 3 vasculitides associated with systemic disease
Lupus
Rheumatoid
Sarcoid
List 6 causes/associations of small vessel vaculitides
AI Associated with other systemic disease Infections (e.g. hep B, hep C) Malignancy Drugs Idiopathic/unknown
List 6 causes/associations of small vessel vaculitides
AI Associated with other systemic disease Infections (e.g. hep B, hep C) Malignancy Drugs Idiopathic/unknown
List 6 causes/associations of small vessel vaculitides
AI Associated with other systemic disease Infections (e.g. hep B, hep C) Malignancy Drugs Idiopathic/unknown
Describe the likely pathogenesis of retinal flame haemorrhages
?
List 4 potential causes of a spontaneous SAH
Saccular aneurysm rupture
AV malformations
Arterial dissections
Use of anticoagulants
What is the pathogenesis of vasospasm post-SAH? What can it cause?
Believed to result from a delayed and reversible vasculopathy, impaired autoregulatory function and hypovolaemia
Can progress to cerebral infarction
What are the presenting clinical features of SAH?
Headache Photophobia Nausea/vomiting Altered mental state LOC
What are the complications of SAH?
Rebleeding Acute hydrocephalus Vasospasm Pulmonary oedema Hyperglycaemia Seizure Death
What proportion of patients with SAH die?
Up to 50%
Name 3 other types of aneurysms that may occur in vessels supplying the CNS
Fusiform
Dissecting/pseudo-aneurysm
Charcot-Bouchard (micro-) aneurysms
