B/ 70 Pathogenesis of Glomerular diseases

Question 1

Aspect of glomerular disease

Answer 1

Immunological aspect, Morphological aspect, Clinical aspects.

Question 2

Immunological aspect of glomerular diseases. Three forms of antibody associated injuries

Answer 2

1. An injury resulting from deposition of soluble circulating antigen-antibody complexes in the glomerulus.
2. Injury by antibodies reacting in situ within the glomerulus either with fixed (intrinsic) glomerular antigens or with molecules planted within the glomerulus.
3. Injury by antibodies directed against glomerular cell components.

Question 3

Glomerulonephritis caused by circulating immune complexes (Type 3 hypersensitivity reaction)

Answer 3

Antigen may be endogenous or exogenous. The immune complexes become trapped within the glomerulus. The compliment system becomes activated and recruits leukocytes which are responsible for the tissue injury.

Complexes can be trapped within the mesangium, the sub endothelium or the sub epithelium.

Question 4

In situ immune complex glomerulonephritis

Answer 4

In this case the complex is generated within the glomerulus. There are 2 main theories.

1. Anti basement membrane glomerulonephritis (antigens are intrinsic): Antibodies are directed against fixed antigens within the glomerular basement membrane. This can be the non-collagenous domain of the alpha3 chain of collagen type IV. These anti-GBM antibodies can cross react with the lung and lead to the formation of Goodpasture syndrome (lung+ kidney lesions).
2. Antibodies against planted non-glomerular antigens (extrinsic): such as DNA, bacterial antigens, large aggregated proteins.

Question 5

Heymann´s nephritis

Answer 5

An experimental model of membranous glomerulonephritis. A brush border antigen is taken out of a rabbit and injected into a rat. The rat then produces anti-brush border antibodies which are extracted from the rat and reintroduced into the rabbit. The anti-brush border antibodies will react with the antigens of podocytes within the rabbit leading to membranous glomerulonephritis.

Question 6

Morphological aspects of glomerulonephritis

Answer 6

Hypercellularity, basement membrane thickening, hyalinization

Question 7

Hypercellularity

Answer 7

Related to the proliferation of the endothelial, epithelial and mesangial cells. Most likely it is a compensatory mechanism in response to cellular injury.
Also infiltration of inflammatory cells can be seen: Monocytes, neutrophils, lymphocytes.

Question 8

Basement membrane thickening

Answer 8

May be diffused, linear or granular. Granular can either be subepithelial or a subendothelial thickening.

Question 9

Hyalinization

Answer 9

Capillary system is replaced by a hyalin-like sclerotic tissue. It is an end-stage disease which is most likely due to glomerulonephritis. Loss of barrier function leads to leakage of proteins which become trapped within the glomeruli.

Question 10

Types of hyalinization

Answer 10

Segmental - one segment of one glomerulus
Global - whole glomerulus is affected
Focal - some of the glomeruli are affected
Diffused - all the glomeruli are affected

Question 11

Clinical aspects

Answer 11

Acute nephritic syndrome, rapidly progressive, nephrotic syndrome, asymptomatic haematuria/oligosymptmatic disease, chronic glomerulonephritis

Question 12

Acute nephritis syndrome

Answer 12

Sudden appearance of macroscopic hematuria + mild proteinuria along with an elevated blood pressure.

Question 13

Rapidly progressive glomerulonephritis

Answer 13

Loss of renal function within days or weeks. Manifests as anuria/oliguria, hematuria, proteinuria. If it is left untreated it can progress to acute renal failure.

Question 14

Nephrotic syndrome

Answer 14

Characterized by:
Heavy proteinuria, meaning excretion of over 3.5g/day
Hypoalbuminemia, meaning less than 3mg/dL
Compensatory mechanism of the liver, producing increased amounts of proteins, including lipoproteins, leading to hyperlipidemia, lipiduria
Severe edema
Immune deficiency due to loss of Ig

Question 15

Chronic glomerulonephritis

Answer 15

Characterized by prolonged symptoms and signs or uremia.