Nephrotic and Nephritic syndromes (7.7)

Question 1

Describe the normal glomerular structure and its possible responses to injury

Answer 1

Normal structure:

Tuft of capillaries enclosed within Bowman’s capsule. 3 layers (capillary endothelium, basement membrane and podocytes).

Possible responses to injury:

• Proliferation of endothelial cells
• Proliferation of mesangial cells/matrix
• Thickening of the glomerular basement membrane
• Changes in podocyte pedicles
• Capillary necrosis
• Crescent formation

Question 2

Describe the role of immune damage in glomerular disease

Answer 2

Deposition of circulating immune complexes at the basement membrane or mesangium.

Circulating antigen becomes trapped inducing subsequent binding of antibodies.

Anti-GBM antibodies: May lead to damage of the GBM

• All the above prompt infiltration of immune cells, complement activation and inflammation, leading to damage to the glomerulus and may induce sibsequent proliferation of component cells.
• Inflammation of the glomerulus → glomerular nephritis → Nephrotic/nephritic syndrome

Question 3

Describe the patterns of glomerular disease

Global, segmental, diffuse and focal

Answer 3

Global: Affecting the whole of one glomerulus

Segmental: Affecting part of one glomerulus

Diffuse: Affecting all glomeruli

Focal: Affecting some glomeruli

Tend to be

• Focal segmental
• Diffuse global

Global and segmental relate to the glomerulus.

Diffuse and focal relate to the kidney.

Question 4

Compare and contrast the morphological features and clinical manifestations of the nephrotic and nephritic syndromes

Answer 4

ADDITION: Podoctye effacement and eventual detachment may be seen in nephrotic syndrome

Question 5

Describe the clinical classification and manifestations of glomerular disease, including nephritic and nephrotic syndromes

Answer 5

Question 6

Describe an example of nephritic syndrome

Acute postinfectious glomerulonephritis

Answer 6

Mainly seen post strep. infection (of the throat) but also following infection with mumps and staph.

Morphological features:

• Diffuse
• Swelling and proliferation of endothelial and mesangial cells → occlusion of the lumen, RBC enter filtrate
• Infiltration of neutrophils and monocytes
• Immune complexes develop (IgG and C3) and become sub-epithelial deposits in the mesangium and basement membrane
  
  • Sub-epithelial = On the side of the GBM closest to the podocytes

Clinical manifestations

Most commonly seen in children

• Haematuria (cola coloured urine)
• Mild hypertension
• Oliguria
• Proteinuria

Question 7

Describe an example of nephrotic syndrome

Membranous glomerulonephritis

Answer 7

Morphological features:

• Diffuse global thickening of the GBM
• Antibodies bind antigens trapped in the glomerulus
• Increased GBM permeabilty
  
  • Deposits form but then ‘fall out’, creating a laced appearance
• Sub-epithelial deposits of immune complexes
• Podocyte effacement

Clinical manifestations

• Mostly idiopathic
• Presents in adulthood (30 - 50 yrs)

NOTE: Membranoproliferative glomerulonephritis

Also characterised as diffuse, global with immune complexes deposited within the basement membrane. The deposits are sub-endothelial. Also sees proliferation of mesangial cells

Question 8

Define sub-epithelial and sub-endothelial deposits

Answer 8

Sub-epithelial: Side of the basement membrane closest to the podocytes

Sub-endothelial: Side of the basement membrane closest to the capillary endothelium

Question 9

Outline the clinical classification of glomerular syndromes

TABLE

Answer 9