Vasculities- Bricks Flashcards
Vasculitis is _
Vasculitis is inflammation of the blood vessel walls stimulated by activation of the immune system
* It often manifests in predisposed individuals after an environmental trigger
Vasculities can arise as primary conditions or they can be secondary to conditions such as:
Vasculities can arise as primary conditions or they can be secondary to conditions such as hepatitis C, rheumatoid arthritis, lupus
What are some of the consequences of untreated vasculitis?
If left untreated, vasculitis can lead to
* Tissue ischemia
* Organ necrosis
* Aneurysms
Some general findings of vasculitides include _
Some general findings of vasculitides include fever, malaise, elevated ESR and CRP
Large vessel vasculitis includes _ and _
Large vessel vasculitis includes Giant Cell arteris and Takayasu arteritis
Giant cell arteritis most commonly affects _
Giant cell arteritis most commonly affects carotid artery branches
Takayasu arteritis involves _ and _
Takayasu arteritis involves aortic arch and proximal great vessels
* Including subclavian, carotid, mesenteric, renal arteries
* Sometimes called pulseless disease
A patient with new-onset unilateral severe headache in the context of systemic illness may have _
A patient with new-onset unilateral severe headache in the context of systemic illness may have Giant Cell arteritis
* Left untreated, this can progress to blindness
Medium vessel vasculitis includes _ and _
Medium vessel vasculitis includes polyarteritis nodosa (PAN) and Kawasaki disease
_ is a medium vessel systemic vasculitis that generally involves skin, renal, and visceral vesssels but spares the lungs
PAN is a medium vessel systemic vasculitis that generally involves skin, renal, and visceral vesssels but spares the lungs
The leading cause of chest pain in children comes from _
The leading cause of chest pain in children comes from Kawasaki disease
* Most often seen in young children
Small vessel vasculitis causes _ , _ , and _ disease but may involve other organs too; patients sometimes have _ or _ skin findings
Small vessel vasculitis causes renal , lung , and skin disease but may involve other organs too; patients sometimes have petechiae or palpable purpura skin findings
5 types of small vessel vasculitis
- Granulomatosis with polyangiitis (GPA)
- Eosinophilic granulomatosis with polyangiitis (EGPA)
- IgA vasculitis
- Microscopic polyangiitis (MPA)
- Anti-glomerular basement membrane disease (anti GBM)
The mechanism behind vasculitides involve _
The mechanism behind vasculitides involve immune complex deposition and the presence of:
* Antineutrophil cytoplasmic antibodies (ANCAs)
* Anti-endothelial cell antibodies
* Autoreactive T cells
ANCAs are _
ANCAs are a group of antibodies directed against components of neutrophils, monocyte lysosomes, endothelial cells
* The exact role of ANCAs in the pathogenesis of vasculitis is unknown but they are thought to mediate damage through the activation of neutrophils –> which then release proteolytic enzymes and reactive oxygen species
C-ANCAs are _ and they target _
C-ANCAs are cytoplasmic ANCAs and they target proteinase 3, a component of neutrophil azurophilic granules
P-ANCAs are _ and they target _
P-ANCAs are perinuclear ANCAs and they target myeloperoxidase
* Recall that myeloperoxidase is found in lysosomal granules and forms ROS
Name the histologic features of vasculitis
Histologic features of vasculitis include:
* Infiltration of WBC fibrinoid necrosis
* Granuloma formation
Fibrinoid necrosis is a type of tissue death seen when _
Fibrinoid necrosis is a type of tissue death seen when antigens and antibodies are deposited in vessel walls –> mediates vessel wall destruction
Fibrinoid necrosis is seen in _ and _ vasculitis
Fibrinoid necrosis is seen in PAN and SLE vasculitis
Granulomas are characteristic of four types of vasculitides:
Granulomas are characteristic of four types of vasculitides:
1. GCA
2. Takayasu arteritis
3. GPA
4. EGPA
Giant cell arteritis (GCA) classically affects _ population
Giant cell arteritis (GCA) classically affects older females (50+)
GCA commonly affects _ arteries; it may also involve the vertebral and opthalamic arteries and cause blindness
GCA commonly affects temporal arteries; it may also involve the vertebral and opthalamic arteries and cause blindness
* The branches of the ophthalamic artery that arise from the internal carotid artery are at risk
GCA has a strong associated with an inflammatory condition called _ that causes diffuse pain and stiffness of the shoulders, neck, and hips
GCA has a strong associated with an inflammatory condition called polymyalgia rheumatica (PMR) that causes diffuse pain and stiffness of the shoulders, neck, and hips
Giant cell arteritis can be characterized by _ on histology; however it is not required for diagnosis
Giant cell arteritis can be characterized by multinucleated giant cells on histology; however it is not required for diagnosis
The definitive diagnosis for giant cell arteritis is _
The definitive diagnosis for giant cell arteritis is temporal artery biopsy
* In patients with high suspicion, start treatment right away without biopsy to avoid vision loss
Halo seen on doppler ultrasound
Treatment for giant cell arteritis is _
Treatment for giant cell arteritis is high-dose corticosteroids like prednisone
The classic population affected by Takayasu arteritis is _
The classic population affected by Takayasu arteritis is younger females of Asian descent
* Age of onset 10-40
Takayasu arteritis presents with _ symptoms
Takayasu arteritis presents with generalized symptoms as well as arthralgias, myalgias, claudication, limb pain
The histology of Takayasu is similar to GCA, showing arterial wall inflammation of _ cells
The histology of Takayasu is similar to GCA, showing arterial wall inflammation of CD4, CD8, histocytes, macrophages, plasma cells
_ is a complication of Takayasu that occurs because of proximal narrowing of the subclavian artery –> retrograde blood flow into the vertebral artery causes syncope, dizziness, and neuro deficits
Subclavian steal syndrome is a complication of Takayasu that occurs because of proximal narrowing of the subclavian artery –> retrograde blood flow into the vertebral artery causes syncope, dizziness, and neuro deficits
* Essentially we take blood flow from the brain to perfuse the arm –> causes lightheadedness
Another complication of Takayasu is vasculitis of the _ arteries which can consequently activate RAAS
Another complication of Takayasu is vasculitis of the renal arteries which can consequently activate RAAS
* Renovascular hypertension
Patient presents with a bruit of the subclavian or abdominal aorta and has a difference in systolic blood pressure between the arms; this might be _
Patient presents with a bruit of the subclavian or abdominal aorta and has a difference in systolic blood pressure between the arms; this might be Takayasu arteritis
Treatment for Takayasu arteritis is _
Treatment for Takayasu arteritis is corticosteroids
Explain the process of immune complex deposition of vasculitis
Immune complexes deposit in the walls of vessels –> activates complement –> recruits neutrophils –> neutrophils release lysosomal enzymes which damage the vessel wall
* This occurs in PAN and IgA
The body develops antibodies against components of neutrophils, monocyte lysosomes, and endothelial cells called _
The body develops antibodies against components of neutrophils, monocyte lysosomes, and endothelial cells called anti-neutrophil cytoplasmic antibodies (ANCAs)
How are ANCAs involved in immune-mediated vasculities?
ANCAs activate neutrophils –> release proteolytic enzymes and ROS –> this ends up injuring the vasculature
C-ANCA targets _ in the PMN azurophilic granules
C-ANCA targets proteinase 3 in the PMN azurophilic granules
P-ANCA targets _ in the lysosomal granules
P-ANCA targets myeloperoxidase in the lysosomal granules
We can also have some anti-endothelial cell antibodies involved in _ types of vasculitis
Anti-endothelial cell antibodies:
* GPA
* Kawasaki disease
* Takayasu arteritis
Autoreactive T cells can also trigger vascular injury via _
Autoreactive T cells can also trigger vascular injury via cytokine production –> macrophage activation –. B cell activation –> antibody formation against SM and endothelial cells
The deposition of Ag:Ab complex in the vessel wall leads to a special kind of necrosis called _
The deposition of Ag:Ab complex in the vessel wall leads to a special kind of necrosis called fibrinoid necrosis
Two defining features of vasculitis include _ and _
Two defining features of vasculitis include inflammatory WBCs and fibrinoid necrosis
Granulomas are nodules of _ and _ cells; they are characteristic of:
Granulomas are nodules of macrophages and giant cells; they are characteristic of:
* GCA
* Takayasu arteritis
* GPA
* EGPA
Patient presents with a focal granulmona formation and has impaired vision
Patient presents with a focal granulmona formation and has impaired vision –> giant cell arteritis
Two stages of takayasu
Recall that it is caused by granulomatous inflammation of med-large arteries
1. Inflammatory phase fever, fatigue, weight loss
2. Stenosis effects decreased pulses, claudication
The best definitive way to diagnose giant cell arteritis is _
The best definitive way to diagnose giant cell arteritis is biopsy
We can detect Takayasu arteritis via _ imaging
We can detect Takayasu arteritis via MR angio or CT angio
Kawasaki disease is idiopathic? or may be caused by _
Kawasaki disease is idiopathic? or may be caused by incidental infection with nonspecific immune system activation –> systemic necrotizing vasculitis in small-medium vessels
How does Kawasaki disease present?
Kawasaki presents with “crash and burn”
* Conjunctivitis
* Rash
* Adenopathy
* Strawberry tongue
* Hand and foot
* Fever for 5 days
The danger of kawasaki disease is that about 70% of cases involve the _ arteries
The danger of kawasaki disease is that about 70% of cases involve the coronary arteries –> can lead to aneurysm
We treat kawasaki disease with _ and _
We treat kawasaki disease with IVIG and aspirin
The medium vessel vasculitis that affects adults (middle aged) is _
The medium vessel vasculitis that affects adults (middle aged) is Polyarteritis Nodosa
* Affects more males than females
Explain the pathogenesis of PAN
PAN is idiopathic –> type 3 immune response –> necrotizing inflammation of the vessel wall –> fibrinoid necrosis –> thrombosis –> infarct
In about 30% of PAN cases, the causative antigen is _
In about 30% of PAN cases, the causative antigen is Hepatitis B
Classically, PAN affects most organ systems but spares the _
Classically, PAN affects most organ systems but spares the lungs
The complications of PAN include _
The complications of PAN include renal failure, MI, stroke
The classic population affected by GPA (granulomatosis with polyangiitis) is _
The classic population affected by GPA (granulomatosis with polyangiitis) is white middle aged men
Importantly, the pathogenesis of GPA involves _
Importantly, the pathogenesis of GPA involves c-ANCA
The triad of symptoms in GPA include:
- Respiratory tract- saddle nose deformity
- Lung- infiltrates or cavities causing dyspnea, hemoptysis
- Kidney disease- nephritic syndrome and possible glomerulonephritis
GPA may present with _ skin findings
GPA may present with petechia, pupuric skin lesions
Eosinophilic granulomatosis with polyangiitis (EGPA) typically present in _ population
Eosinophilic granulomatosis with polyangiitis (EGPA) typically present in adults aged 40-50
Some of the EGPA cases will be positive for _
Some of the EGPA cases will be positive for p-ANCA (30-40%)
Three stages of progression in EGPA
- Allergic rhinitis/ asthma- or may be sinusitis, nasal polyps
- Eosinophilic stage- high eosinophil count; the lungs and the GI tract are involved –> we have weight loss, fever, malaise, GI bleeding, abdominal pain
- Vasculitic stage- severe blood vessel inflammation –> ischemia to the GI system and heart
How does IgA vasculitis normally present?
IgA vasculitis most commonly occurs in children following a URI –> IgA immune complexes, fibrin, and complement deposits in small blood vessels
Clinical presentations of IgA vasculitis
IgA vasculitis presents as:
* Abdominal pain
* Arthritis
* Glomerulonephritis
* Petechiae/ purpura (on the bum)
How do we treat IgA vasculitis?
IgA vasculitis is usually self-limiting; in severe cases of renal disease we can treat with corticosteroids
Microscopic polyangiitis is another small vessel vasculitis that is associated with _
Microscopic polyangiitis is another small vessel vasculitis that is associated with p-ANCA
MPA can affect multiple organs but the classic triad includes _ , _ , and _
MPA can affect multiple organs but the classic triad includes lungs , kidneys , and skin
* Lungs- hemoptysis
* Kidneys- hematuria, proteinuria, hypertension
* Skin- palpable purpura
Mixed cryoglobulinemia syndrome occurs when _
Mixed cryoglobulinemia syndrome occurs when Ig precipitates at cold temperatures and affects the small vessels
The most common associated pathogen with mixed cryoglobulinemia syndrome is _
The most common associated pathogen with mixed cryoglobulinemia syndrome is hepatitis C
* HBV
* HIV
* Bacteria
* Fungi
* SLE
* RA
Mixed cryoglobulinemia syndrome presents with many of the same symptoms as the other small vessel vasculitides; however, the classic triad is _
Mixed cryoglobulinemia syndrome presents with many of the same symptoms as the other small vessel vasculitides; however, the classic triad is
1. Arthralgias
2. Palpable purpura
3. Weakness
Other symptoms: peripheral neuropathy, liver disease, renal disease, raynauds
Goodpasture’s syndrome is another name for _
Goodpasture’s syndrome is another name for anti-glomerular basement membrane disease
* Caused by autoantibodies directed against collagen epitopes in the kidney and lung glomerular/alveolar basement membranes
* Associated with declining renal function and pulmonary hemorrhage
Describe the pathophysiology of thromboangiitis obliterans
Thromboangiitis obliterans involves acute inflammation of the small-medium arteries of distal limbs –> thombosis –> infarcts –> raynauds, gangrene, etc
* Most commonly caused by smoking!
The classic population to be affected by thromboangiitis obliterans is _
The classic population to be affected by thromboangiitis obliterans is 30-50 year old male who smokes
Raynauds can occur as a primary or secondary phenomenon; it is ultimately a _ in the skin
Raynauds can occur as a primary or secondary phenomenon; it is ultimately a arterial/arteriolar vasospasm in the skin
* Fingers, toes
Raynauds is most classically associated with _
Raynauds is most classically associated with SLE, scleroderma
How does raynauds present?
Finger transition from pallor –> blue –> red
* cold, paresthesia, pain
We can treat Raynaud with _ , _ , _
We can treat Raynaud with Ca2+ channel blockers, alpha blockers, vasodilators
