B/ 73 Systemic disease associated with glomerular damage

Question 1

Glomerulopathies secondary to systemic diseases such as:

Answer 1

SLE
Diabetic nephropathy
Amyloidosis
Secondary to lymphoplasmacytic disorders
Goodpasture syndrome
Microscopic polyangitis
Wegeners granulomatosis
Henoch-Scönelin pupura
Bacterial endocarditis-related GN
Secondary extra renal infection
Thrombotic angiopathy

Question 2

Diabetic glomerulo-sclerosis: three renal lesions in diabetes

Answer 2

Glomerular lesions - most relevant for this topic
Renal vascular lesions, principally arteriolosclerosis
Pyelonephritis

Question 3

Characteristics for the glomerular lesions in diabetes

Answer 3

1. Thickening of the basement membrane
2. Diffuse mesangial sclerosis: sclerotic hyalinic precipitate. When the glomerulosclerosis becomes marked, the patient manifests with Nephrotic syndrome.
3. Nodular glomerulosclerosis: ball-like deposits of laminated matrix situated in the periphery of the glomerulus. Called Kimmelstiel-Wilson lesions.

Question 4

Causes of glomerular lesions in diabetes

Answer 4

Non enzymatic glycosylation: when glucose chemically binds to free amino groups of proteins without the aid of enzymes. Leads to formation of Advanced glycosylation end products (AGE) which can cause cross-links between polypeptides and form a net for the entrapment of proteins. This thickens the BM.
Hypercalcemia destroys the filtration ability of the glomerulus.
Increased synthesis of collagen type IV, leading to thickening of the BM.

Question 5

Amyloidosis of the kidney

Answer 5

Deposits of amyloid within the glomeruli. Found within the mesangial matrix and capillary BM - eventually obliterates the capillary lumen.
Corticosteroid cause progression of the disease.

Question 6

Wegener granulomatosis - General

Answer 6

Necrotizing vasculitis which is characterized by a triad of:

1. Acute necrotizing granulomas in the upper or lower respiratory tract.
2. Acute necrotizing granulomas affecting small to medium sized vessels.
3. Renal disease in the form of focal necrotizing glomerulonephritis.

Question 7

Wegener granulomatosis - pathogenesis

Answer 7

Cell-mediated hypersensitivity. C-ANCA are present 95% of the time.
Focal and segmental necrotizing GN - leakage of plasma from the necrotic segment- segment is replaced by sclerotic tissue.
Hematuria and proteinuria which is non-responsive to therapy.

Question 8

SLE

Answer 8

Deposition of DNA/anti-DNA complexes within the glomeruli.
inflammatory reaction - proliferation of mesangial, endothelial and epithelial cells. Sometimes also necrosis of the glomeruli.

Question 9

Five patterns of glomerular damage in SLE

Answer 9

Class I: No kidney involvement
II: Mesangial lupus GN. Precipitation in the mesangium.
III: Focal proliferative GN. Lass than 50% of glomeruli affected. Only part of the glomeruli are affected. Affected portions show swelling and proliferation of endothelial and mesangial cells.
IV: Diffuse proliferative GN. Most glomeruli show proliferation which affect the entire glomerulus.
V: Membranous - thickening of the basement membrane