GoodPasture Syndrome

…named after the American pathologist, Ernest Goodpasture.

Introduction…

Goodpasture syndrome (GPS) also known as Goodpasture’s disease is a rare autoimmune disease in which antibodies attack the basement membrane in lungs and kidneys, leading to bleeding from the lungs and to kidney failure

Some forms of the disease involve just the lung or the kidney, most times, both.

Men are eight times more likely to be affected than women. The disease most commonly occurs in early adulthood.

What would cause this…?!As an autoimmune disorder, it occurs when the immune system mistakenly attacks and destroys healthy body tissue & develop substances that attack collagens(t4a3) in the tiny air sacs in the lungs and the glomeruli of the kidneys (the basement membranes).

These substances are called anti-glomerular basement membrane (anti-GBM) antibodies.

The immune system's faulty response causes bleeding in the air sacs of the lungs and inflammation in the kidney's filtering units.

As idiopathic as it has remained, an initial insult(injury) to the pulmonary vasculature is required for exposure of the alveolar capillaries to the anti-GBM antibodies.

Predisposing factors for such exposure include the following:

• Exposure to organic solvents (e.g. chloroform) or hydrocarbons.

• Exposure to tobacco smoke.

• Certain gene mutations (human leukocyte antigen HLA-DR15).

• Infection(viral), such as influenza A.

• Cocaine inhalation.

• Metal dust inhalation.

• Bacteremia.

• Sepsis.

• High-oxygen environments.

• Anti-lymphocytic treatment (especially monoclonal antibodies) such as alemtuzumab.

PathoPhysiology…The abnormal production of anti-GBM antibodies are by the plasma cells of the blood. The anti-GBM antibodies attack the alveoli and glomeruli basement membranes. These antibodies bind their reactive epitopes to the basement membranes and activate the complement cascade, leading to the death of tagged cells, resulting in tissue injury.

Although basement membranes are ubiquitous, only the alveolar and glomerular basement membranes are affected clinically.

Under normal conditions, the alveolar endothelium is a barrier to the anti–basement membrane antibodies. However, with increased vascular permeability, antibody binding to the basement membrane occurs in the alveoli. Therefore, for the deposition of antibody, an additional nonspecific lung injury that increases alveolar-capillary permeability is required (aforesaid etiology).

T cells are also implicated. They enhance B-cell function and antibody production and may play a direct pathogenic role in kidney and lung injury. (Re fe r t o A u t o re a c t i ve T c e l l s )

It is generally considered a type II hypersensitivity reaction.

Signs and SymptomsSymptoms may occur very slowly over months or even years, but they often develop very quickly over days to weeks. As much as it attacks the lungs and kidneys (in that order), there are Generalized symptoms such as: Loss of appetite, fatigue, fever, joint pain and weaknesswhich are common early signs preceding what’s to come.Lung symptoms may include:•Coughing up blood•Dry cough•Chest pain•Shortness of breath

Kidney and other symptoms include:•Blood in urine

•Protein in urine

•Edema in any area of the body, especially in the legs

•Burning sensation when urinating

•High amounts of urea in blood

•Nausea and vomiting

•Pale skin

•High blood pressure

Diagnosis• A physical examination may reveal signs of high blood pressure and fluid overload.

• Abnormal heart and lung sounds on auscultation.

• Urinalysis results are usually abnormal, and show blood and protein in the urine. Abnormal red blood cells and cytoplasmic anti neutrophilic cytoplasmic antibodies in the bloodstream may be seen.

The following tests may also be done:

• Anti-glomerular basement membrane test

• Arterial blood gas

• Blood urea nitrogen (BUN) test

• Chest x-ray

• Creatinine (serum)

• Lung biopsy

• Kidney biopsy

• Direct Immunofluorescence

Treatment

Plasmapheresis removes whole blood from the body & replaces the plasma with fluid, protein, or donated plasma thus removing harmful antibodies with old plasma. This may reduce inflammation in the kidneys and lungs.

Corticosteroid medications (such as prednisone) and other drugs that suppress the immune system may be used.

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) to control blood pressure.

Dialysis at chronic kidney failure.

Kidney transplant at loss of kidney function. A transplant is not done until the level of harmful antibodies drops.

Autopsy of consolidated lung from extensive bleeding, which led to asphyxiation.

Autopsy of consolidated lung from extensive bleeding, which led to asphyxiation. Close-up view

Cytoplasmic anti neutrophilic cytoplasmic antibodies (c-ANCA)

Perinuclear anti neutrophilic cytoplasmic antibodies (p-ANCA)

The renal biopsy revealing crescentic glomerulonephritis.

Direct immunofluorescence showing smooth linear staining of the basement membrane

X-Ray of a 35-year-old man who previously smoked cigarettes heavily, depicting massive hemoptysis.

Possible Complications•Chronic kidney disease

•End-stage kidney disease

•Lung failure

•Rapidly progressive glomerulonephritis

•Severe pulmonary hemorrhage (lung bleeding)

PreventionNever sniff glue or siphon gasoline with your mouth, which expose the lungs to hydrocarbon solvents and can cause the disease.

Alternative Names• Anti-glomerular basement membrane antibody disease.

• Rapidly progressive glomerulonephritis with pulmonary hemorrhage.

• Pulmonary renal syndrome.

• Glomerulonephritis - pulmonary hemorrhage.

I appreciate your attention.

Adighibenma S.O.S