Hematuria pathophysiology

Template:Pathophysiology Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Adnan Ezici, M.D[2]

Pathophysiology

Pathogenesis

It is understood that glomerular hematuria is caused by either the dysfunction or damage of the glomerular filtration barrier(GFB).

• Major components of GFB include:
  • Endothelial surface layer (composed of glycosaminoglycans)
  • Endothelial cells
  • Glomerular basement membrane (GBM)
  • Slit diaphragms
  • Subpodocyte space

The pathophsiologic mechanism of glomerular hematuria might be further classified into 6 subtype depends on the primary and histopathologic localization.

• Injuries of the glomerular endothelial cell and surface layer
• Primary and secondary GBM disorders
• Diseases that can cause mesangial deposition
• Diseases that can cause subendothelial and subepithelial deposition
• Podocyte-associated disorders
• Miscellaneous

Genetics

Molecular defects involved in the pathogenesis of glomerular hematuria include:

Diseases with structural GBM damage

• In the pathogenesis of alport syndrome:
  • COL4A5 (X linked)
  • COL4A3/COL4A4 (autosomal recessive)
• In the pathogenesis of thin basement membrane disease:
  • COL4A3/COL4A4
• In the pathogenesis of hereditary angiopathy, nephropathy, aneurysms, and muscle cramps syndrome:
  • COL4A1

Diseases with structural podocyte damage

• In the pathogenesis of MYH9-related disorder:
  • Non muscle myosin IIA heavy chain

Storage disorders

• In the pathogenesis of fibronectin glomerulonephritis:
  • Fibronectin
• In the pathogenesis of fibrillary glomerulonephritis:
  • 10-30 nm fibrils
• In the pathogenesis of fabry’s disease:
  • lysosomal storage
• In the pathogenesis of immunotactoid glomerulonephritis:
  • Fibrils that are > 30 nm

Autoimmune disorders

• In the pathogenesis of ANCA (antineutrophil cytoplasmic antibodies):
  • Antibodies against endothelium
• In the pathogenesis of anti-GBM:
  • Antibodies against COL4

Complement mediated disorders

• In the pathogenesis of C3 glomerulopathy:
  • Alternative pathway

Infectious (endocapillary) diseases

• In the pathogenesis of IgA nephritis:
  • Galactose-deficient IgA1