Rapidly Progressing Glomerulonephritis

Question 1

What are some general common characteristics of the Rapidly Progressing Glomerulonephritis syndromes (RPGN)?

Answer 1

Rapid loss of renal function
Nephritic syndrome, gross hematuria
Crescent

But the RPGNs have diverse pathogeneses

Question 2

What is the basic physiological function of tourniquets?

Answer 2

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.

Question 3

How does the function of crescents become pathological?

Answer 3

They stop the bleeding, but they compress the tuft and shut off filtration through the glomerulus entirely. This causes rapidly progressing renal failure

Question 4

List the tree types of RPGN and their basic classification

Answer 4

Type I - anti-glomerular basement membrane antibody

Type II - Circulating immune complex glomerulonephritis

Type III - “Pauci-immune”/ANCA associated glomerulonephritis

Question 5

RPGN Type I
What is the basic problem?
Where in the body is this problem caused?

Answer 5

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

Question 6

RPGN Type I

Typical Clinical Presentation

Answer 6

Gross hematura
Drop in urinary output (acute renal failure)
Hemoptysis (coughing up blood)

Question 7

RPGN Type I
Who most commonly acquires this?
What is the etiology/pathogenesis?

Answer 7

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

Question 8

RPGN Type I

What would you see on IF?

Answer 8

Linear stain due to antibodies binding the glomerular basement membrane

Question 9

RPGN Type I

What is the common antigen between the two most common sites of anti-GBM antibody action?

Answer 9

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

Question 10

RPGN Type I

What is the disease AKA?

Answer 10

Goodpasture Syndrome

Linear IgG deposits along glomerular and alveolar basement membranes

Question 11

RPGN Type I

Prognosis

Answer 11

Renal and pulmonary failure.

Question 12

RPGN Type I

Treatment

Answer 12

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

Question 13

RPGN Type II

What is the basic clinical presentation?

Answer 13

Gross hematuria

Drop in urinary output

Question 14

RPGN Type II

Basic pathological issue

Answer 14

Severe immune complex formation

More autimmunity with auto-antibody production leads to necrosis and breaks in the glomerular basement membrane

Question 15

RPGN Type II

In what patients might it be more likely to occur?

Answer 15

• Small % of people with postinfectious glomerulonephritis
• SLE patients
• Small % of IgA nephropathy pts
• Children, young adults

Question 16

RPGN Type II

If you suspect this, what clinical test MUST you get?

Answer 16

Kidney biopsy

You need to determine if this is Type I or II RPGN.

Question 17

RPGN Type II

What diagnostic characteristics will you see?

Answer 17

Crescents and whatever other clinical presentations are associated with its development (IgA nephropathy, SLE, postinfectious, etc)

Question 18

RPGN Type III

What is the typical clinical presentation?

Answer 18

Drop in urinary output (acute renal failure)
Gross hematuria
Hemoptysis
SOB

Question 19

RPGN Type III

What patients does this tend to happen more in?

Answer 19

Older patients

Question 20

RPGN Type III

Etiology/pathogenesis

Answer 20

Presence of ANCAs (anti-neutrophil cytoplasmic antibodies)

Question 21

RPGN Type III

What are ANCAs?

Answer 21

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)

Question 22

RPGN Type III

How would you test for this?

Answer 22

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)

Question 23

RPGN Type III

Why is it called “Pauci-immune”?

Answer 23

The IF and EM are essentially negative, as in there are no immune complex deposts

Question 24

RPGN Type III

Pathology

Answer 24

Crescents

NO immune complex deposits
NO electron dense deposits
NO anti-GBM antibodies

Question 25

RPGN Type III

Prognosis

Answer 25

Renal and pulmonary failure

Question 26

RPGN Type III

Treatment

Answer 26

Immunosuppression

Question 27

RPGN Type III

When the patient has a history of nasopharynx/sinusitis disease, what disease might you expect?

Answer 27

Wegener Granulomatosis

• Pulmonary angiitis and granulomatosis
• Due to c-ANCAs
• Involves ELK (ENT, Lung, Kidney)

Question 28

Churg-Strauss Syndrome

What is the basic clinical problem?

Answer 28

Small vessel necrotizing vasculItis with EOSINOPHILS

May also have skin purpura and vasculitis affecting the GI tract or myocardium

Question 29

Churg-Strauss Syndrome

What is the pathological origin?

Answer 29

p-ANCAs