Síndrome riñón pulmón

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Síndrome riñón pulmón

  1. 1. Pulmonary-Renal Syndrome
  2. 2. Pulmonary-Renal Syndrome  Potentially life-threatening disorder,  Diffuse alveolar hemorrhage  pulmonary capillaritis  Rapidly progressive glomerulonephritis  AGN/RPGN +/- lung hemorrhage is and emergency requires early diagnosis and treatment.
  3. 3. Diffuse Alveolar Hemorrhage  Presentation of patients with DAH can range from cough with or without hemoptysis to severe respiratory distress.  Onset is usually abrupt.  Suspect DAH:  Hemoptysis (Absent in 1/3 of patients)  Radiographic Abnormalities (Alveolar opacities, Interstitial opacities, Fibrosis)  Unexplained drop in Hematocrit Capillaritis: neutrophile infiltrates and hemorrhage
  4. 4. Rapidly Progressive Glomerulonephritis  Acute onset (days to weeks)  Acute renal failure and oliguria (400mL/day)  Renal Blood flow and GFR fall  Obstruction of the glomerular capillary lumen  By infiltrating inflammatory cells  Proliferating resident glomerular cells.  Intrarenal vasoconstricion and mesangial cell contraction  Local imbalances of vasoconstrictors (leukotrienes, endothelins, thromboxanes, platelet-activating factor) and vasodilators (NO, prostacyclin) in the microcirculation of the kidney.
  5. 5. Pulmonary-Renal Syndromes ANCA-associated vasculitides account 60% Goodpasture's Syndrome 20%. Other causes 20% ANCA GP-GN Other
  6. 6. Work-up for GN  ANCA  Anti-GBM  Complement levels (C3,C4)  Depending on history/clinical suspicion:  ANA  ASLO  BCx  Cryocrit  Hepatitis serologies  Renal Biopsy  Immunofluorescence  Electron microscopy  (Light microscopy)  Consider GN mimics: thrombotic microantiopathy, cholesterol emboli, AIN, myeloma For Pulmonary-Renal Syndrome you will also want to bx other tissues.
  7. 7. Goodpasture´s Syndrome  Autoimmune  Autoantibodies directed against type IV collagen  RPGN and crecentic glomerulonephritis.  50-80% have lung hemorrhage.  Bimodal distribution:  Typically young males (5-40years) Male:Female ratio = 6:1  Presentation in second peak, 6th decade, generally do not have lung hemorrhage and have almost equal sex distribution.
  8. 8. Goodpasture’s Syndrome  Common presentation:  Hematuria  Nephritic urinary sediment (dysmorphic RBC &/or RBC casts)  Subnephrotic proteinuria (<3.5 g/24 hours)  Rapidly progressive renal failure over weeks  With or without pulmonary hemorrhage  Pulmonary hemorrhage, when it does occur, usually predates nephritis by weeks or months.  Lung involvement can vary from fluffy pulmonary infiltrates on CXR with mild dyspnea on exertion to potentially fatal pulmonary hemorrhage  Usually not hypertensive.
  9. 9. GP Diagnosis  Diagnostic serologic marker is anti-GBM antibodies with a specificity for NCI domain of the alpha3 chain of type IV collagen.  These antibodies are detected in >90% of patients with anti-GBM nephritis.  RENAL BIOPSY is the GOLD STANDARD for diagnosis of anti-GBM nephritis.  Light microscopy: diffuse proliferative GN with focal necrotizing lesions and crescents in >50% of glomeruli.  Immunofluorescence: linear ribbon-like deposits of IgG  Electron Microscopy: inflammatory change without immune deposits
  10. 10. Normal Glomerulus RPGN/Crescentic GN Immunofluoresence Microscopy: “Linear ribbon like” deposition of IgG along GBM
  11. 11. GP Treatment  Emergency plasmapheresis is done daily or on alternate days until anti-GBM antibodies are not detected in circulation  Prednisone (1mg/kg per day) is started simultaneously along with cyclophosphamide (2 to 3 mg/kg per day) or azathioprine (1 to 2 mg/kg per day) to suppress new synthesis of anti-GBM antibodies.
  12. 12. GP Prognosis  Without treatment, 80% get ESRD within 1 year  Early Treatment  If treatment is started early, before creatinine is over 5mg/dL, then 1 year survival is over 90%. It is 80% if renal failure is more advanced.  If patients require dialysis at time of presentation, they rarely recover renal function.  If crescents exist in >50% of glomeruli, then usually survival <2 yrs  Better response to treatment if ANCA +
  13. 13. ANCA Vasculitis (pauci-immune) Wegener’s Granulomatosis Microscopic Polyangiitis Churg-Strauss
  14. 14. ANCA + Vasculitis (pauci-immune) Disease Granulomas Renal Pulmonary Asthma ANCA type ANCA positive Wegener’s granulo- matosis + 80% 90% - C-ANCA (anti-PR3) 90% Microscopic polyantiitis - 90% 50% - P-ANCA (anti-MPO) 70% Churg- Strauss Syndrome + 45% 70% + P-ANCA (anti-MPO) 50% PR3 = Proteinase 3 MPO = Myeloperoxidase (found in granules of neutrophils/monocytes)
  15. 15. ANCA-associated small vessel vasculitis  More common in Caucasian and elderly (mean age is 57 years)  Usual presentation: nonspecific constitutional symptoms and signs  Lethargy  Mailaise  Anorexia  Weight loss  Fever  Arthralgia  Myalgias
  16. 16. ANCA-associated small vessel vasculitis  Nonspecific lab abnormalities Rapid sedimentation rate Elevated C-reactive protein Leukocytosis Thrombocytosis Normochromic/normocytic anemia Normal complement levels (usually)
  17. 17. C-ANCA  PR3
  18. 18. Wegener’s  Granulomatous vasculitis of the upper and lower respiratory tracts together with glomerulonephritis.  Prevalence is 3/100,000, very rare in blacks. M:F=1:1  Mean age of onset = 40 (but age of onset can vary widely)
  19. 19. Wegener’s  Pathogenesis:  Necrotizing vasculitis of small arteries and veins with granuloma formation (either intra- or extravascular).  Lung involvement typically appears as multiple bilateral, nodular cavitary infiltrates. On biopsy they reveal typical necrotizing granulomatous vasculitis.  Upper airway lesions (especially sinuses and nasopharynx) reveal inflammation, necrosis and granuloma formation.  Renal involvement can be focal and segmental glomerulitis early in the disease but typically progresses to RPGN. RARELY are granulomas seen on renal biopsy.
  20. 20. Wegener’s  Presentation  95% have upper airway involvement  Paranasal sinus pain  Purulent or bloody nasal discharge with or without nasal mucosal ulceration.  Nasal septal perforation can occur leading to saddle nose deformity.  Serous otitis media can occur as a result of blockage of eustachian tube.  16% will have subglottic tracheal stenosis (from active disease or scarring) which can cause airway obstruction.
  21. 21. Wegener’s  Presentation Pulmonary involvement in 85-90%  Cough, hemoptysis, dyspnea, chest discomfort.  Endo-bronchial disease (from active disease or scarring) can leads to obstruction with atelectasis Renal involvement dominates the clinical picture  If left untreated, it accounts directly or indirectly for most mortality of the disease.
  22. 22. Wegener’s  Diagnosis  Demonstration of necrotizing granulomatous vasculitis on tissue biopsy in a patient with compatible clinical features.  Pulmonary tissue biopsy offers the highest diagnostic yield.  Renal biopsy can confirm pauci-immune glomerulonephritis.  Upper airway tissue biopsy usually shows granulomatous inflammation with necrosis but may or may not show vasculitis.
  23. 23. Wegener’s  Treatment  Glucocorticoids (predisone 1mg/kg/day) should be started for symptomatic improvement and then tapered over 6 months.  Cyclophosphamide (2mg/kg/day)  Monitor leukocyte count to adjust dose to maintain count above 3000/microL (neutrophile count of 1500). Gives you clinical remission without severe leukopenia and associated infectious risk.
  24. 24. Wegener’s  Treatment Relapse occurs in about 25% of patients.  Treatment for relapse is the same (goal is to achieve remission again).  Methotrexate or azathioprine can be given after remission is achieved and cyclophosphamide is stopped to maintain remission in patients that do relapse.
  25. 25. P-ANCA  MPO
  26. 26. Churg-Strauss AKA allergic angiitis and granulomatosis.  Asthma  Peripheral and tissue eosinophilia  Extravascular granuloma formation  Vasculitis of multiple organ systems.
  27. 27. Churg-Strauss  Incidence is estimated at 1 in 3 million.  Can occur at any age (not documented in infants).  Mean age is 48yrs.  M:F ratio= 1:1.2
  28. 28. Churg-Strauss  Granulomatous reaction and eosinophil infiltration can occur in any organ in the body, but the lungs predominate. Other areas involved include:  Skin  Cardiovascular system  Kidney  Peripheral nervous system  Gastrointestinal tract
  29. 29. Churg-Strauss  Presentation Pulmonary findings clearly dominate clinical picture  Severe asthma attacks and presence of pulmonary infiltrates.  Mononeuritis multiplex  Allergic rhinitis and sinusitis Heart disease (14%) = Most frequent cause of death.
  30. 30. Churg-Strauss  Presentation Skin involvement 51%  Include purpura in addition to cutaneous and subcutaneous nodules. Renal involvement 45%  Less common than seen in Wegener’s and MPA  Severe glomerulonephritis
  31. 31. Churg-Strauss  Biopsy of affected tissue (lung).  Microgranulomas, fibrinoid necrosis and throbosis of small arteries and veins (necrotizing vasculitis) with eosinophilic infiltrates.  Classification criteria (4 of 6 criteria is 85% Sensitive and 99.7% specific)  Asthma  Eosinophilia >10%  Mono- or polyneuropathy  Migratory or transitory pulm infiltrates  Paranasal sinus abnormality  Extravascular eosinophils on biopsy
  32. 32. Churg-Strauss  Treatment  Glucocorticoids; high dose.  Attempt to taper. Asthma makes tapering difficult, patients may need to be maintained on low-dose prednisone for years after clinical recovery from vasculitis to control asthma.  Patients who do not respond to glucocorticoids alone, can be treated with cyclophosphamide and prednisone (similar to Wegener’s treatment).
  33. 33. P-ANCA  MPO
  34. 34. Microscopic Polyangiitis.  Necrotizing vasculitis with few or no immune complexes affecting small vessels (capillaries, venules, or arterioles).  Glomerulonephritis and pulmonary capillaritis are common in Microscopic Polyangiitis. (NO pulmonary capillaritis in PAN).  Not associated with HBV like PAN  ABSENCE of granulomatous inflammation differentiates this disease from Wegener’s granulomatosis.
  35. 35. Microscopic Polyangiitis  Incidence not really established because it use to be included in PAN.  Age of onset is about 57 years.  Slightly more occurrence in males than females.
  36. 36. Microscopic Polyangiitis  Presentation Vascular lesion is a necrotizing inflammation of capillaries, venules, as well as small and medium-sized arteries. Rare immunoglobulin deposition seen in the vascular lesions. Renal lesion is identical to that of Wegener’s granulomatosis lesion.
  37. 37. Microscopic Polyangiitis  Renal involvement 90%  Glomerulonephritis, often rapidly progressive.  Can quickly lead to renal failure  Lung involvement 50%  Alveolar hemorrhage (12%)= hemoptysis  Mononeuritis multiplex  Gastrointestinal tract vasculitis  Cutaneous vasculitis.  (upper airway disease and pulmonary nodules are not typically found - if found: suggests Wegener’s)
  38. 38. Microscopic Polyangiitis  Diagnosis Biopsy of affected tissue.  Necrotizing pauci-immune inflammation of arterioles, capillaries and venules WITHOUT granulomas or eosinophilic infiltrates. ANCA positive
  39. 39. Microscopic Polyangiitis  Treatment Similar approach to that of Wegener’s. Relapse occurs in up to 34% of patients.
  40. 40. Differential Diagnosis for Pulmonary-Renal Syndrome Goodpasture’s Disease Systemic Vasculitis Wegener’s Granulomatosis Microscopic Polyangiitis Churg-Strauss syndrome Cryoglobulinemia Henoch-Schonlein Purpura Connective Tissue Disease Polymyositis/Dermatomyositis Progressive Systemic Sclerosis SLE Primary Glomerular Disease IgA nephropathy Post-Infectious GN Membranoproliferative GN Pleural effusions/Lupus Pneumonitis + SLE GN + ASO titer, can continue to have pulmonary symptoms by the time renal symptoms manifest.
  41. 41. References  Harrison et. al, (2005), Principles of Internal Medicine, 16th Edition, McGraw-Hill, NY  Jennette J. (1997), Small Vessel Vasculitis. New England Journal of Medicine; 21: 1512-1523.  PubMed: Renal-Pulmonary Syndrome. Retrieved on (9/1/09) from: http://www.ncbi.nlm.nih.gov/pubmed/15905974  Sabatine, Marc S,(2008) Pocket Medicine, 3rd Edition, Lippincott Williams &Wilkins, Philadelphia  Toy, et.al. (2007), Case Files: Internal Medicine, Second Edition, McGraw- Hill, NY

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