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109 Cards in this Set
- Front
- Back
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Why was gout thought to be a rich person's disease?
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occurs more in those who have a purine rich diet with rich foods and alcohol
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What is gout?
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Gout is a problem with having too much uric acid causing an arthritis
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Do all people with hyperuricemia get gout?
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no, only 25 %. duration and magnitude of hyperuricemia are the major risk factors.
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What are normal uric acid vulaues?
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men-5.1 mg/dl
women-4 mg/dl |
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How is hyperuricemia defined?
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2 standard deviations above normal
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Hyperuricemia-Pathogenesis?
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Production of uric acid
Loss of uric acid Lack of uricase |
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How do we produce uric acid?
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endogenous purine synthesis (we make it) and dietary intake (red meat, alcohol, etc.)
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How do we lose uric acid?
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kidney gets rid of most of the uric acid while some of it is secreted into the gut where bacteria oxidize urate (accounts for only 1/3 of excretion). So, someone with kidney failure would have a higher uric acid level.
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How often is hyperuricemia due to over production versus underexcretion?
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10% overproduction
90% underexcretion |
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What are the routes of overproduction?
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Nucleic acid turnover, breakdown of cells
Derangements in purine synthesis |
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What are the derangments that occur?
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upregulation of PRPP synthetase
downregulation of HGPRT |
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What enzyme can you inhibit to treat gout?
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xanthine oxidase
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What are some of the diseases associated with increased breakdown of cells?
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Myeloproliferative/lymphoproliferative disorders, hemolytic anemia, Paget’s disease (breakdown of bone, constant bone turnover), Psoriasis
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What are the causes of underexcretion leading to gout?
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Hereditary factors Medications
lead intoxication increased organic acids hyperinsulinemia |
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What medications can lead to gout?
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cyclosporine
diuretics low-dose aspirin |
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When do you develop monosodium urate crystals?
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when the uric acid level crosses the soluability threshold of 6.7 mg/dL
lower temperatures also which could explain tophi in ears and toes. |
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What are tophi?
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foreign body granulomas surrounding an MSU crystal core
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What is the pathogenesis of inflammation is gout?
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crystals are taken up by phagocytes and synovial cells which subsequently release cytokines that attract neutriphils and trigger neutrophils-endothelial adhesion
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how does gout present?
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-painful, red, swollen joint or bursa
-first MTP is most commonly affected (podagra) -tophi in chronic forms in distal joints, bursa, or pinnae |
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Gout: Epidemiology
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-40-50 years old
-males to females with gout is 5:1; even for women post menopausal -tophi in chronic forms in distal joints, bursa, or pinnae |
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What do you do with a patient with cyclosporine induced gout?
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try to lower uric acid to less than 6
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how do you diagnose gout?
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synovial fluid sample and analyze it for cell count, culture, and crystals
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What would you find in a synovial fluid sample with someone with gout?
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-increased WBC
-septic arthritis may coexist of trigger gout -negative bifringence-yellow, parallel crystals -white cells with crystals inside |
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What would an xray show in gout?
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punched out erosions with sclerotic borders and overhanging edges.
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What color does perpindicular crystals show?
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blue
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Vasculitis: Definition
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Vasculitis is a term that refers to a heterogenous group of disorders characterized by blood vessel inflammation
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What things can the pathogenesis of vasculitis involve?
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cellular immunity
complement pro-inflam. cytokines ANCA antigens |
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What symptoms are common to all vasculatides?
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fever, malaise, arthralgias, fatigue
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Name two examples that are Large vessel vasculitis?
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giant cell arteritis
takayasu arteritis |
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Name two examples that are medium vessel vasculitis?
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Polyarteritis nodosa
Kawasaki’s disease |
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Name the examples of small vessel vasculitis?
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Wegener's granulamatosis
Churg-Strauss Henoch-Schonlein purpura Hypersensitivity vasculitis |
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Specific symptoms of vascular diseases are associated with what?
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size of the vessels involved
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Giant Cell Arteritis patients are commonly?
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“elderly white female.”
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What are the symptoms of giant cell arteritis related to external carotid?
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Headache
Scalp tenderness/infarction Ischemic optic neuropathy “amaurosis fugax” – descending of a dark curtain, can lead to blindness Jaw claudication TIA |
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What are the symptoms of giant cell arteritis related to subclavian/brachial?
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Arm claudication
Pulselessness |
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What are the symptoms of giant cell arteritis related to aorta?
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Aortic Aneurysm
aortic insufficiency |
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What would the labs show in giant cell arteritis?
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Mild anemia (maybe)
Elevated markers of inflammation, like ESR or CRP (almost always) |
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How would you diagnose giant cell?
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Temporal Artery Biopsy-you would see granulomatous inflammation and maybe multinucleated giant cells. Also see disruption of the internal elastic lamina
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Giant Cell Arteritis: Pathophysiology
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Cell mediated inflammation in cell wall, causing disruption of the internal elastic lamina.
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Describe the Cyclical fluctuation of GCA Incidence
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occurs every 60 years
may be infectious just theoretical |
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Polymyalgia Rheumatica
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syndrome in elderly patients of constitutional symptoms and stiffness of shoulders and hips
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How would you treat a patint with PMR?
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low dose of steroid and see very dramatic recovery
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How is PMR treated differently form GSA?
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GSA is high steroid dose
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How often are PR and GSA comorbid?
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50% of GCA have PMR
15% of PMR have GCA |
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What is the typical patient with takayasu's arteritis?
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“Young Asian Female”
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Takayasu’s Arteritis: Symptoms
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Ischemic Symptoms determined by artery affected.
Carotid/vertebral-TIA Subclavian-pulseless/claudication Aorta-aneurysms or insuff. Coronary-MI in young females |
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Takayasu’s Arteritis: Pathology
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Early, granulomatous inflammation in adventitia and outer layers of affected arteries. This progresses to include the entire cell wall.
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How do takayasu's and GSA differ?
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takayasu is not limited to extracranial and can therefore cause TIA
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How would you diagnose Takayasu's?
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angiogram-narrowing and dilation with vessel cut off past dilation.
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What is palpable purpura?
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characteristic slightly raised, red or purple rash we can see in medium and small vessel vasculitis. Caused by inflammation in the capillary venules allowing RBCs to leak
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What would the histology report say for PP?
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leukocyte occlastic vasculitis-means that there’s fibrinoid necrosis inside the vessel wall, neutrophils present, and extravasation of blood cells
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What defines a small vs medium vessel?
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Medium vessels: 50-150 micrometers with a muscular wall
Small vessels: Less than 50 micrometers without a muscular wall |
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Polyarteritis Nodosa
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Inflammation of medium and small arteries
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What specific organs are targeted in PN?
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skin
peripheral nerves GI Kidney Musculoskeltal Testicular pain |
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What organ is spared in PN?
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lungs
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What is the pathology of PAN?
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Patchy involvement
Minimal immune This association is must less deposits ANCA usually negative Used to be associated w HEP B |
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What is the diagnosis of PAN?
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Angiogram
Biopsy of involved organ |
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What distinguishes PAN from other vasculatides?
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No glomerular nephritis, but do get involvement of small arterioles supplying the kidney, causing renin-mediated hypertension. Can also (much rarer) get infarction of kidney or renal insufficiency
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Kawasaki’s Disease
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A medium vessel vasculitis
Seen in childhood Fever, Rash (often with desquamination of palms and soles), eye inflammation |
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Why do you treat KD aggressively with IVIG?
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coronary ateries can be involved and cause aneurysms in 25% of untreated patients
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What are the two main groups of small vessel vasculitides?
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ANCA-associated
Cutaneous vasculitides |
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What disease is associated with c-ANCA (cytoplasmic)?
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Wegener’s granulomatosis
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What disease is associated with p-ANCA (perinuclear)?
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Churg-Strauss syndrome
Microscopic Polyangitis |
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What are the antigens associated with ANCA?
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c-ANCA 90% proteinase-3
p-ANCA 80% myeloperoxidase |
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Wegener’s Granulomatosis
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Granulomatous necrotizing vasculitis affecting the airways and kidney
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What are the clinical manifestions of WG?
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Saddle nose deformity
Chronic Sinusitis Subglottic Stenosis Cough, hemoptysis Glomerulonephritis Ocular Cutaneous |
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Which ANCA is WG associated with?
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c-ANCA-PR3
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How do you diagnose WG?
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biopsy
sinus-non specific lung-granulomatous inflammation, inflammation in capillaries kidney-pauciimmune glomerulonephritis |
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Churg Strauss Syndrome occurs in the setting of what conditions?
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Asthma(frequent flares) or Allergies
Eosinophils in tissue or blood Pulmonary Infiltrates |
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What lab tests for CSS?
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pANCA
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What is the main difference between small and medium vessel vasculitis?
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Difference in vessel size allows it to involve the lung and glomerulonephritis
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Microscopic Polyangitis
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Pauciimmune necrotizing glomerulonephritis Capillaritis
Most serious complication is alveolar hemorrhage pANCA Dx by biopsy |
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Henoch-Schonlein purpura
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Tetrad of purpura, arthritis, abdominal pain, and glomerulonephritis
Most frequent in kids, and usually a self-limited process When seen in adults, there is more kidney disease and chronic kidney disease Mediated by IgA, you could visualize IgA via immunofluorescence |
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Mixed Cryoglobulinemia
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90% of cases are due to Hepatitis C
Involves small vessels to skin Immune-complex mediated-IgM and IgG and rheumatoid factor that can fix complement |
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What are the non ANCA diseases?
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Henoch-Schonlein purpura
Mixed Cryoglobulinemia Hypersensitivity vascultis Cutaneous Vasculitis |
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What drugs can cause hypersensitivity reactions?
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antibiotics such as penicillin, sulfa- drugs, NSAIDs, methotrexate, anti-depressants, anti-hypertensives
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Hypersensitivity vascultis
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Immune-complex (Antigen-antibody) mediated
Immune complex deposition leads to complement activation C3a and C5a bring in neutrophils |
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DEFINITIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS
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Immunologic aberrations give rise to excessive autoantibody production, some of which causes cytotoxic damage, while others participate in immune complex formation resulting in immune inflammation
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EPIDEMIOLOGY SLE
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ages of 15-40
female 5:1 1 in 2000 Increased in African american |
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Genetics of SLE
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high concordance in identical twins and increased frequency of disease among 1st degree relatives
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Disturbance of what system predisposes someone to lupus?
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complement-C1q if highly associated and C4 put you at increased risk
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What makes us think lupus has a hormonal component?
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it mainly affects women at child bear age
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What is the central abnormality in pts with SLE?
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autoantibody production
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what are some other abnormal mechanisms of SLE?
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-uncontrolled b cell prolferation
-uncontrolled T cells activating b cells -aberrant clearing of immune complexes -increased apoptosis and impaired clearance |
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What causes the morbidity and mortality in SLE?
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organ failure
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SLE patients should have 4 of 11. what are they?
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• Malar Rash
• Discoid Rash • Photosensitivity • Oral ulcers • Arthritis • Serositis • Renal disorder • Neurologic disorder • Hematologic disorder • Immunologic disorder • Antinuclear Antibody |
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What are the skin manifestations of SLE?
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Malar rash
discoid rash photosensitivity butterfly rash interarticular dermatitis subacute cutaneous lupus panniculitis urticarial lesions vasculitis non-scarring alopecia |
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Malar Rash
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fixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds.
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Discoid Rash
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Characterized by erythematous raised patches with adherent keratotic scaling and follicular (hair follicles) plugging. Atrophic scarring may occur in older lesions
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Photosensitivity
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Characterized by a skin rash as a result of unusual reaction to sunlight. Patients will become sick from sun exposure and it may cause a flare in the lupus. Some believe that the sun kills skin cells, causing exposure to nuclear debris, leading to a flare in the lupus.
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Classic “butterfly” rash is
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an erythematous, elevated pruritic and/or painful rash in a malar distribution that is precipitated by sun exposure and spares the nasolobial folds
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How can you tell if a rash is autoimmune?
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immunofluoresence at the dermal epidermal junction
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What are the acute skin manifestions?
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malar rash
generalized erythema bullous lesions |
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What is subacute lupus?
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presents with annular papulosquamous rash that resembles psoriasis
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How would chronic lupus manifest on the skin?
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discoid lupus or lupus profundus, which is more of a panniculitis (deeper beneath the skin, an inflammation of the fat).
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Mucus membrane lesions of lupus
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-mouth ulcers of the hard palate behind the front teeth
vaginal ulcers nasal septal erosions serositis (pleuritis and pericarditis) |
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Musculoskeletal features of SLE
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arthralgia
arthritis Jaccoud’s arthropathy Myopathy |
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What is the differnce between jaccouds and arthritis in RA?
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hand position is completely reducible
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What are the renal manifestations of SLE?
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persistent proteinuria
cellular casts hematuria(RBC) pyuria(WBC) elevated serum creatinine. |
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what are cellular casts?
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white cells and red cells that have been filtered into the renal tubules and congeal together to take the form of the renal tubules
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What are the neurological manifestations of lupus?
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Seizures
psychosis |
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What are the pulmonary manifestations of SLE?
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pneumonitis
pulmonary hemorrhage pulmonary hypertension |
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What are the cardiovascular manifestations of SLE?
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Pericarditis
myocarditis endocarditis non-bacterial verrucous disease coronary artery disease raynauds nailfold capillary changes |
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What are the hematologic abnormalities of SLE?
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hemolytic anemia
leukopenia lymphopenia thrombocytopenia |
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What are the immunological abnormalities of SLE?
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ANA (95%)
anti-RO anti-DNA anti-Smith false + for syphillis |
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anti-dsDNA
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very specific for lupus, especially renal disease in lupus
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anti-histone
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drug induced and will usually go away after time
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anti-ROLA
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put patient at risk for having neonatal lupus in their child bc the abs cross the placenta and cause rash and heart block in the fetus
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anti-ROLA
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put patient at risk for having neonatal lupus in their child bc the abs cross the placenta and cause rash and heart block in the fetus
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