Good Pasture Syndrome and Hemosiderosis Flashcards
What is it?
A disease affecting kidneys and lungs that is caused by circulating Ab’s to Type IV Collagen
Specifically it is rapidly progressive glomerulonephritis
Specific domain involved in Goodpasture’s and what genetic deffect is thought to cause it?
The non-collagenous domain: alpha-3 chain
Genetic defect in: HLA DRB1-1501 and 1502
Possible causes for Goodpasture’s?
Unknown but could be environmental insult:
Viral
Hydrocarbon exposure
Smoking
**Epitopes on anti-collagen Ab’s are hidden inside insulting molecule
These epitopes found in 90% of pt’s with anti-GBM nephritis
General information on what GPS (goodpasture syndrome) does
Destroys the Basement Membrane (BM) in alveoli and glomeruli
What is the distribution pattern of GPS?
6:1 male to female ratio
2 peaks
1 at ages 5-40ad the other in the 6th decade
Those of the 6th decade usually do NOT have pulmonary hemorrhage and the disease shows an equal distribution among the sexes
Clinical Renal Presentations of GPS
Hematuria
Subnephrotic proteinuria (<3.5 g/24 hrs)
Nephritis-induced urinary sediment: dysmorphic RBC and RBC casts
Rapidly progressive renal failure (glomerulonephritis): weeks
Clinical Sx: respiratory
Hemoptysis/pulmonary hemorrhage
Fluffy pulmonary infiltrates and focal pulmonary consolidation⇒fatal pulmonary hemorrhage
Treatment for GPS
- Plasma exchange: removes circulating Ab’s and chemical mediatours of immunologic immunity
- Immunosuppressive therapy: prevents further Ab production
What gross pattern is seen in GPS?
Heavy with areas of red-brown consolidation
GPS histologically?
Focal necrosis of alveolar walls
▪Intra-alveolar hemorrhages
▪Hemosiderin-laden macrophages
§Fibrous thickening of septae
§Hypertrophy of type II pneumocytes
§Organizing thrombi in alveolar spaces
Testing for GPS?
Direct Immunofluorescence for IgG Abs
Linear Staining Pattern
What is Hemosiderosis?
Rare genetic disorder
Intermittent diffuse alveolar damage
Most commonly in children
Clinical presentation of Hemosiderosis
Productive cough
Hemoptysis
Anemia
Weight Loss
Diffuse pulmonary infiltrates
**Insidious onset
Gross pattern of hemosiderosis
Moderately increased weight
Red-brown to red foci of consolidation
Treatment of hemosiderosis
Immunosuppression: prednisone/azathioprine
Some ppl develop other autoimmune disorders
Wegener Granulomatosis: what is it?
Autoimmune disease involving the upper respiratory tract
What does Wegener’s granulomatosis cause?
- Acute necrotizing granulomas upper respiratory areas (ears, nose, sinuses, throat) and lower respiratory areas (lung).
- Necrotizing or granulomatous vasculitis: small and medium sized vessels like capillaries, venules, arterioles, arteries
- Renal disease: focal necrotizing, often crescenteric, glomerulitis
Epidimiology of Wegeners?
Male>females
40 years of age
Wegener’s clinical presentation
Hemoptysis
Persistent pneumonitis with bilateral nodular and cavity lesions (95%)
Chronic sinusitis (90%)
Mucosal ulcerations (nasopharynx) (75%)
Renal disease (80%)
Prognosis of Wegener’s?
If untreated-80% mortality w/in a year
What is detectable in serum in pt’s with Wegeners?
C-ANCA: marker of disease activity
Pathogenesis of Wegeners
Hypersensitivity reaction
Inhaled infectious or environmental agent
Diagnosis of Wegener’s?
Transbronchial lung biopsy will reveal necrosis and granulomatous vasculitis
What is the respiratory pathophysiology of Wegeners?
Upper Respiratory Tract:
Inflammatory sinusitis
Mucosal granulomas
Ulcerative lesions, nose, palate, pharynx
Granulomas: geographic necrosis with surrounding lymphocytes, plasma cells, macrophages, and giant cells.
Renal pathophysiology of Wegener’s?
Mild:
Acute focal proliferation and necrosis (focal necrotizing glomerulonephritis)
Hematuria with proteinuria
Advanced:
Diffuse necrosis, proliferation, cresecent formation
Rapidly progressing renal failure
