Rapidly Progressing Glomerulonephritis Flashcards
What are some general common characteristics of the Rapidly Progressing Glomerulonephritis syndromes (RPGN)?
Rapid loss of renal function
Nephritic syndrome, gross hematuria
Crescent
But the RPGNs have diverse pathogeneses
What is the basic physiological function of tourniquets?
After severe glomerular basement membrane damage, presence of RBCs, fibrin, and macrophages in urinary space gives a potent stimulus for parietal epithelial cells to proliferate and form a crescent.
Crescents form to stop the bleeding into the renal tubules and into urine.
How does the function of crescents become pathological?
They stop the bleeding, but they compress the tuft and shut off filtration through the glomerulus entirely. This causes rapidly progressing renal failure
List the tree types of RPGN and their basic classification
Type I - anti-glomerular basement membrane antibody
Type II - Circulating immune complex glomerulonephritis
Type III - “Pauci-immune”/ANCA associated glomerulonephritis
RPGN Type I
What is the basic problem?
Where in the body is this problem caused?
Anti-glomerular basement membrane (anti-GBM) antibody is formed (Hypersensitivity Type II)
Acts in the glomerular basement membrane and the pulmonary capillaries to cause injury
RPGN Type I
Typical Clinical Presentation
Gross hematura
Drop in urinary output (acute renal failure)
Hemoptysis (coughing up blood)
RPGN Type I
Who most commonly acquires this?
What is the etiology/pathogenesis?
Young men
The formation of anti-GBM antibodies may be induced by exposure to viruses, smoking, solvents (stains, dyes), drugs. Could also be due to a genetic predisposition to autoimmunity
RPGN Type I
What would you see on IF?
Linear stain due to antibodies binding the glomerular basement membrane
RPGN Type I
What is the common antigen between the two most common sites of anti-GBM antibody action?
Noncollagenous Protein (NC1) Present in both pulmonary capillaries and glomerular basement membrane, but it normally does not elicit an antibody response and is not exposed to the immune system
RPGN Type I
What is the disease AKA?
Goodpasture Syndrome
Linear IgG deposits along glomerular and alveolar basement membranes
RPGN Type I
Prognosis
Renal and pulmonary failure.
RPGN Type I
Treatment
Plasmaphoresis (removing pathogenic antibodies from circulation) must occur ASAP to save the lungs, as most mortality from this disease occurs from pulmonary complications. Renal failure may be treated with dialysis
RPGN Type II
What is the basic clinical presentation?
Gross hematuria
Drop in urinary output
RPGN Type II
Basic pathological issue
Severe immune complex formation
More autimmunity with auto-antibody production leads to necrosis and breaks in the glomerular basement membrane
RPGN Type II
In what patients might it be more likely to occur?
- Small % of people with postinfectious glomerulonephritis
- SLE patients
- Small % of IgA nephropathy pts
- Children, young adults
RPGN Type II
If you suspect this, what clinical test MUST you get?
Kidney biopsy
You need to determine if this is Type I or II RPGN.
RPGN Type II
What diagnostic characteristics will you see?
Crescents and whatever other clinical presentations are associated with its development (IgA nephropathy, SLE, postinfectious, etc)
RPGN Type III
What is the typical clinical presentation?
Drop in urinary output (acute renal failure)
Gross hematuria
Hemoptysis
SOB
RPGN Type III
What patients does this tend to happen more in?
Older patients
RPGN Type III
Etiology/pathogenesis
Presence of ANCAs (anti-neutrophil cytoplasmic antibodies)
RPGN Type III
What are ANCAs?
Anti-neutrophil cytoplasmic antibodies
React with PMN antigens, particularly those in the granules, to cause premature degranulation and release of PMN enzymes
May have c-ANCA (cytoplasmic) or p-ANCA (perinuclear)
RPGN Type III
How would you test for this?
IF on neutrophils
Smear neutrophils on a glass slide and add the patient’s serum (which may or may not bind depending on ANCA presence)
RPGN Type III
Why is it called “Pauci-immune”?
The IF and EM are essentially negative, as in there are no immune complex deposts
RPGN Type III
Pathology
Crescents
NO immune complex deposits
NO electron dense deposits
NO anti-GBM antibodies
RPGN Type III
Prognosis
Renal and pulmonary failure
RPGN Type III
Treatment
Immunosuppression
RPGN Type III
When the patient has a history of nasopharynx/sinusitis disease, what disease might you expect?
Wegener Granulomatosis
- Pulmonary angiitis and granulomatosis
- Due to c-ANCAs
- Involves ELK (ENT, Lung, Kidney)
Churg-Strauss Syndrome
What is the basic clinical problem?
Small vessel necrotizing vasculItis with EOSINOPHILS
May also have skin purpura and vasculitis affecting the GI tract or myocardium
Churg-Strauss Syndrome
What is the pathological origin?
p-ANCAs
