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59 Cards in this Set
- Front
- Back
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What is vasculitis?
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A primary inflammatory disease process of vasculature
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What are the determinants of the clinical manifestations of vasculitis?
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-Target organ involved
-Size of vessel involved -Pathobiology of the inflammatory process of involved vasculature |
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What are the classifications of vasculitis for large-sized vessels?
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-Giant cell arteritis
-Takayasu's arteritis |
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What are the classifications of vasculitis for medium-sized vessels?
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-Polyarteritis nodosa
-Kawasaki's disease |
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What are the classifications of vasculitis for small-sized vessels?
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-Anti-neutrophil cytoplasmic Ab Associated
-Wegener's Granulomatosis -Microscopic Polyangitis -Churg-Strauss Syndrome -Immune complex mediated: -Cryoglobulinemia -Henock-Schonlein purpura -Hypocomplementemic Urticarial Vasculitis -Vasculitis associated with SLE, Rheumatoid arthritis, or other autoimmune diseases -Serum sickness or drug-induced vasculitis |
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What are the sequelae of vasculitis?
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-Stenosis and/or occlusion of involved vasculature resulting in organ ischemia or infarction
-Necrosis of vessel wall rupturing in aneursymal dilation/rupture or intravascular thrombosis causing organ ischemia or infarction |
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What are the diagnostic approaches for assessing vasculitis?
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-Biopsy of involved organs
-Radiographic evaluation of involved vessels -Conventional Angiography -CT Angiography -MR Angiography -Serology (e.g. autoantibodies) |
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What is the epidemiology of Giant Cell Arteritis?
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Age: >50 years-old
Racial/Ethnic Background (annual incidence) -20/100,000 N. European -2/100,000 African americans/Hispanics -<1/100,000 Asians |
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What is the vasculature involved in Giant Cell Arteritis?
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Thoracic aorta and major branches:
-Carotid artery extra-cranial branches -Temporal artery -Occipital artery -Opthalmic artery -Posterior ciliary artery -Subclavian/axillary artery |
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From the inside-> out, what are the layers of a muscular artery?
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Lumen
Tunica interna Tunica media Tunica externa |
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What are the clinical manifestations of giant cell arteritis?
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-Constitutional
-Fatigue -Weight loss -Fever -Headache -66% of patients -Most commonly temporal, but frontal or occipital pain also common -Jaw pain (claudication) -50% of patients -Visual loss -Acute onset partial or complete visual field loss in 15-20% of patients -Arm claudication -15% of patients |
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What is the beginning of pathogenesis of giant cell arteritis (from start to T cell activation)?
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There is a resident population of dendritic cells at the junction of the adventia and the media.
A stimulus transforms these into mature, activated dendritic cells which proliferate and secrete chemokines and interleukins and upregulate surface molecules. The chemokines attract T cells from the vaso vasorum into the adventia and the DC cells help activate them. |
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What is the other name for giant cell arteritis?
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Temporal arteritis
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What feeds the adventia of large arteries?
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Vaso vasorum
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What is responsible for fusion in giant cells?
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IFNgamma from Th1 cells
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What is the pathogenesis of giant cell arteritis (from T cell activation on)?
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The T cell activation, in turn, results in the activation of macrophages, which secrete IL-1, IL-6. Activated Th1 cells secrete IFN-gamma. IFN-gamma stimulates macrophages and is responsible for the fusion process that generates giant cells. There is a general migration from the adventia into the media with the production of various cytokines, such as platelet derived growth factor which leads to new blood vessel formation. There are other inflammatory species such as metalloproteinases and ROS and you have this gradual transformation from a process that began in the adventia that gradually migrates towards the vascular lumen.
Initially the intima is proliferative more to a mild degree, then over a period of days you can increase this proliferation and you will have either stenosis or total occlusion of the vessel. It is not a process that begins in the lumen and then evolves towards the outer most portion of the wall. TI is something that involves the adventia first and then migrates medially. |
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What is an eventuality of giant cell arteritis?
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Stenosis or occlusion of the lumen
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What is the leading cause of death in giant cell arteritis?
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Rupture of aortic aneurysms
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What are the laboratory abnormalities with giant cell arteritis?
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-Elevated Acute Phase Reactants
-Erythrocyte sedimentation rate (ESR) -C-reactive protein -Elevated IL-6 levels |
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How do you diagnose giant cell arteritis?
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-Temporal artery biopsy
-Elevation of acute phase reactants |
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Describe the histopathology of giant cell arteritis of the temporal artery
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There is a dense infiltrate of mononuclear cells. The lumen is somewhat compromised. There are scattered amongst the infiltrate some giant cells.
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What is the treatment for giant cell arteritis?
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-Glucocorticoids
-Prednisone 1mg/kg q d with tapering regimen over 4-6 months Some people are eventually able to discontinue the medication all together while others exhibit a relapsing and remitting course where you get to a specific dose reduction and then you have a reactivation of the disease process. It is not capable of being predicted at the beginning who will respond in what way. |
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Describe polyarteritis nodosa
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Necrotizing arteritis of medium-sized muscular arteries
Pathology: fibrinoid necrosis |
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Contrast giant cell arteritis and polyarteritis nodosa
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This necrotizing arteritis does not occur with giant cell arteritis. This is a more destructive process in terms of affecting the vessel wall.
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What is the vasculature involved in polyarteritis nodosa?
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-Superior mesenteric artery
-Celiac and hepatic arteries -Renal artery -Muscular arteries of the extremities |
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What is the epidemiology of polyarteritis nodosa
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-Age: 20-70 years old
-No racial or ethnic predilection -Incidence -2-4/100,000 annual incidence -70-80/1,000,000 in regions which are endemic for Hep B No genetic association |
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Describe the hepatitis B association of polyarteritis nodosa
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-Usually occurs during the first 6 months after infection
-Usually positive for surface and e antigen |
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Describe the histopathology of polyarteritis nodosa
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It is a focal, destructive process. There is an area of inflammation and destruction in the vessel wall, dilation and aneurysm formation and there is thrombus formation in that part of the infected vessel, which may propagate and occlude the entire wall.
There can be extravasation of red cells from the lumen into the perivascular space |
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What are the clinical manifestations of polyarteritis nodosa?
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-Constitutional symptoms
-Fatigue -Weight loss -Fever -Gastointestinal -Abdominal pain -Kidney -Hypertension -Peripheral nervous system -Mononeuritis multiplex (wrist drop, foot drop) -Skin -Nodules or ulcers -Digital gangrene |
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What do you see on an angiogram with polyarteritis nodosa?
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-Abruptly truncated vessels
-Small aneurysms |
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What causes wrist drop in polyarteritis nodosa?
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Ischemia of the radial nerve
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What would you see on a sural nerve biopsy with polyarteritis nodosa?
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Marked inflammation of the vaso nevorum and destruction of the vessel wall. There will be occlusion of the lumen.
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Why do you use an angiogram instead of a biopsy in polyarteritis nodosa?
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The arteries are not accessible to biopsy.
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What is the 5yr survival untreated rate for polyarteritis nodosa?
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13%
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What is the treatment for polyarteritis nodosa?
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Disease onset
-Prednisone 1mg/kg q d -Oral cyclophosphamide 2 mg/kg q d Duration of treatment -At least one year +HBV PAN -Interferon-alpha During the year of treatment you try and taper the prednisone, but you keep the cyclophosphamide |
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What is wegener's granulomatosis?
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This is for the smaller vasculature and vasculytic processes that involve the capillaries or the post capillary venules or small arterioles.
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What is a granuloma
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A nodular aggregate of macrophages or cells derived from the monocyte-lineage, which is typically surrounded by a "rim" of lymphocytes, and commonly associated with the presence of multinucleated giant-cells
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What is the serology associated with Wegener's granulomatosis?
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There is a distinct serologic antibody refered to as ANCA - anti neutrophil cytoplasmic antibody.
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What is the epidemiology of Wegener's granulomatosis
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Age: 25-60 years old
No racial or ethnic predilection Prevalence: 5-7/100,000 |
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What is the vasculature involved in Wegener's granulomatosis?
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-Upper respiratory tract arterioles/capillaries
-Lung -Arterioles and cpaillaries -Kidney -Glomerulonephritis ("pauci immune") |
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What are the clinical manifestations of Wegener's granulomatosis?
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-Upper Respiratory Tract
-Chronic sinusitis -Chronic otitis -Lower Respiratory Tract -Pulmonary nodules -Alveolar hemorrhage (hemoptysis) -Kidney -Glomerulonephritis -Peripheral nervous system -Mononeuritis multiplex -Skin -Purpura |
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What is ANCA?
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Anti-neutrophil cytoplasmic Ab
Cytoplasmic Reactivity (C-ANCA) -Antigenic target= Proteinase 3 -Serine proteinase of lysosomal granules of monocytes and azurophilic granules of neutrophils |
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What is p-ANCA for?
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p is for perinuclear. p-ANCA is associated with an immune response against myloperoxidase (MPO). Myloperoxidase is a serine protease that is present in the samegranules that the protease-3 is in.
It can be used for microscopic polyangitis and chrug-strauss syndrome. |
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What is the survival rates for Wegener's granulomatosis?
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Untreated: 10% at 2 years (primarily due to kidney failure)
Treated: 80% at 8 years |
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What is the morbidity of Wegener's Granulomatosis?
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These are the consequences of the inflammatory vasculitic processes in Wegener's granulomatosis. This disease does not affect the oxygenation of the blood. There is no significant pulmonary deficit in terms of oxygenation of the blood.
-Permanent renal insufficiency - 42% -End-stage renal disease -11% -Hearing loss- 35% -Nasal deformities - 28% -Tracheal stenosis- 13% |
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Why is the palpable purpura of Wegener's granulomatosis mostly on the lower extremities?
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Gravity causing interluminal pressure in the small vasculature to be greater.
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Describe the histopathology of purpuric dermal vasculitis
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There is a lot of infiltration by mononuclear cells and neutrophils. There are remnants of vasculature that is all but destroyed, which results in extravasation of RBCs into the tissues. This leads to a purpuric distribution of lesions.
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What do you see on a chest x-ray in a patient with Wegener's granulomatosis?
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Pulmonary nodules and hemorrhage
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What occurs if you biopsy alveolar vessels in a patient with Wegener's granulomatosis?
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You would find destruction of the vasculature of the small vessels in the alveoli. This leads to the alveoli filling with RBCs, which can lead to coughing up blood.
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Describe the renal histopathology of a patient with Wegener's granulomatosis
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There is necrotizing glomerulonephritis. It is called necrotizing because you can see the glomerular tufts exhibiting fibrinoic necrosis. You see a marked reduction in patent lumen of the vasculature of the glomeruli. This is referred to as Pauci immunebecause if you were to stain this looking for antibodies or complement you would find no evidence of that. It is not currently known what is driving this process.
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What is the treatment for Wegener's granulomatosis?
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-Prednisone 0.5-1mg/kg q d (tapered) plus cyclosporine 2mg/kg q d for approximately one years
-85-90% response rate -75% complete remission -30-50% at least one relapse |
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What is the epidemiology of Henoch Schonlein Purpura?
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Age: 5-7 years old (range: 5-15)
Children: 20/100,000 50% preceded by URT infection Adults:<1/100,000 Gender: male/female: 1.5/1 |
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What is the vasculature involved in Henoch Schonlein Purpura?
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-GI Tract
-Submucosal arterioles/venules -Kidney -Glomerulonephritis -Skin -Dermal arterioles/venules |
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What are the clinical manifestations of Henoch Schonlein Purpura?
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-Abdominal pain
-Intussusception -Hematuria/proteinuria -Renal insufficiency infrequent -Purpura -Arthralgia/arthritis |
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What is intusseusception
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Telescoping of the bowel such that it telescopes on itself and can cause obstruction
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What is the difference between purpura in Wegener's granulomatosis and in Henoch Schonlein Purpura?
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In Henoch Scholein Purpura the purpura are common on the posterior, proximal lower extremities and the buttocks area. It can also be more common in the upper extremities as well.
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Describe the renal histopathology in Henoch Schonlein Purpura
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Most t of the deposition of protein here is in the mesangium. Most of the glomerular capillaries remain patent, therefore you don’t get the renal insufficiency that you see in Wegener's. This is a much more benign process that does not cause destruction of the glomeruli.
With immunofluorescence you see IgA antibodies distributed throughout the glomerulus. |
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Describe the pathogenesis of Henoch Schonlein Purpura
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Tissue (Vascular) deposition of IgA-containing immune complexes
The implication is that somehow there is a stimulation of the immune system due to this upper respiratory viral infection creating IgA antibodies that are somehow reacting some still yet to be defined antigenic components, perhaps of the virus or of your own tissue that is being mimicked by the virus. |
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What is the treatment for Henoch Schonlein Purpura?
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The disease tends to resolve rather spontaneously. If arthritis or arthralgias are a problem, then non-steroidal anti-inflammatory agents would be appropriate.
-Prognosis: very favorable -No indication for immunosuppression -Supportive therapy: -Hydration -Bed rest -Analgesia -Non-steroidal anti-inflammatory agents |
