Good Pasture Syndrome and Hemosiderosis

Question 1

What is it?

Answer 1

A disease affecting kidneys and lungs that is caused by circulating Ab’s to Type IV Collagen

Specifically it is rapidly progressive glomerulonephritis

Question 2

Specific domain involved in Goodpasture’s and what genetic deffect is thought to cause it?

Answer 2

The non-collagenous domain: alpha-3 chain

Genetic defect in: HLA DRB1-1501 and 1502

Question 3

Possible causes for Goodpasture’s?

Answer 3

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

Question 4

General information on what GPS (goodpasture syndrome) does

Answer 4

Destroys the Basement Membrane (BM) in alveoli and glomeruli

Question 5

What is the distribution pattern of GPS?

Answer 5

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

Question 6

Clinical Renal Presentations of GPS

Answer 6

Hematuria

Subnephrotic proteinuria (<3.5 g/24 hrs)

Nephritis-induced urinary sediment: dysmorphic RBC and RBC casts

Rapidly progressive renal failure (glomerulonephritis): weeks

Question 7

Clinical Sx: respiratory

Answer 7

Hemoptysis/pulmonary hemorrhage

Fluffy pulmonary infiltrates and focal pulmonary consolidation⇒fatal pulmonary hemorrhage

Question 8

Treatment for GPS

Answer 8

1. Plasma exchange: removes circulating Ab’s and chemical mediatours of immunologic immunity
2. Immunosuppressive therapy: prevents further Ab production

Question 9

What gross pattern is seen in GPS?

Answer 9

Heavy with areas of red-brown consolidation

Question 10

GPS histologically?

Answer 10

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

Question 11

Testing for GPS?

Answer 11

Direct Immunofluorescence for IgG Abs

Linear Staining Pattern

Question 12

What is Hemosiderosis?

Answer 12

Rare genetic disorder

Intermittent diffuse alveolar damage

Most commonly in children

Question 13

Clinical presentation of Hemosiderosis

Answer 13

Productive cough

Hemoptysis

Anemia

Weight Loss

Diffuse pulmonary infiltrates

**Insidious onset

Question 14

Gross pattern of hemosiderosis

Answer 14

Moderately increased weight

Red-brown to red foci of consolidation

Question 15

Treatment of hemosiderosis

Answer 15

Immunosuppression: prednisone/azathioprine

Some ppl develop other autoimmune disorders

Question 16

Wegener Granulomatosis: what is it?

Answer 16

Autoimmune disease involving the upper respiratory tract

Question 17

What does Wegener’s granulomatosis cause?

Answer 17

1. Acute necrotizing granulomas upper respiratory areas (ears, nose, sinuses, throat) and lower respiratory areas (lung).
2. Necrotizing or granulomatous vasculitis: small and medium sized vessels like capillaries, venules, arterioles, arteries
3. Renal disease: focal necrotizing, often crescenteric, glomerulitis

Question 18

Epidimiology of Wegeners?

Answer 18

Male>females

40 years of age

Question 19

Wegener’s clinical presentation

Answer 19

Hemoptysis

Persistent pneumonitis with bilateral nodular and cavity lesions (95%)

Chronic sinusitis (90%)

Mucosal ulcerations (nasopharynx) (75%)

Renal disease (80%)

Question 20

Prognosis of Wegener’s?

Answer 20

If untreated-80% mortality w/in a year

Question 21

What is detectable in serum in pt’s with Wegeners?

Answer 21

C-ANCA: marker of disease activity

Question 22

Pathogenesis of Wegeners

Answer 22

Hypersensitivity reaction

Inhaled infectious or environmental agent

Question 23

Diagnosis of Wegener’s?

Answer 23

Transbronchial lung biopsy will reveal necrosis and granulomatous vasculitis

Question 24

What is the respiratory pathophysiology of Wegeners?

Answer 24

Upper Respiratory Tract:

Inflammatory sinusitis

Mucosal granulomas

Ulcerative lesions, nose, palate, pharynx

Granulomas: geographic necrosis with surrounding lymphocytes, plasma cells, macrophages, and giant cells.

Question 25

Renal pathophysiology of Wegener’s?

Answer 25

Mild:

Acute focal proliferation and necrosis (focal necrotizing glomerulonephritis)

Hematuria with proteinuria

Advanced:

Diffuse necrosis, proliferation, cresecent formation

Rapidly progressing renal failure