Hematuria pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Adnan Ezici, M.D[2]
Overview
The pathophysiology of hematuria depends on the underlying etiology. It is understood that glomerular hematuria is caused by either the dysfunction or damage of the glomerular filtration barrier(GFB). Molecular defects (COL4A5, COL4A3/COL4A4, COL4A1, Non muscle myosin IIA heavy chain, Fibronectin, etc.) might be involved in the pathogenesis of glomerular hematuria. Gross pathology and microscopic pathology might differ depending on the underlying etiology of hematuria. The pathophysiology of non-glomerular hematuria might be depending on the underlying etiology. It is thought that non-glomerular hematuria is caused by either polycystic kidney disease, sickle cell disease and papillary necrosis, nephrolithiasis, trauma, leukemia, tumors, strenuous exercise, or infection. The pathophysiology of non-renal hematuria might be depending on the underlying etiology. It is thought that non-renal hematuria is the result of either stone, infection, tumor, trauma, urinary tract infection (UTI), irritation, or foreign body which might be originating from either the ureter, bladder, or urethra. It may also be caused by prostatic bleeding, vaginal bleeding, and endometriosis.
Pathophysiology
Pathogenesis
- It is understood that glomerular hematuria is caused by either the dysfunction or damage of the glomerular filtration barrier(GFB).[1]
- Major components of GFB include:
- Endothelial surface layer (composed of glycosaminoglycans)
- Endothelial cells
- Glomerular basement membrane (GBM)
- Slit diaphragms
- Subpodocyte space
- Major components of GFB include:
- The pathophysiologic mechanism of glomerular hematuria might be further classified into 6 subtype depending on the primary and histopathologic localization.[1]
- 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
- The pathophysiology of non-glomerular hematuria might be depending on the underlying etiology. It is thought that non-glomerular hematuria is caused by either polycystic kidney disease, sickle cell disease and papillary necrosis, nephrolithiasis, trauma, leukemia, tumors, strenuous exercise, or infection.[2]
- The pathophysiology of non-renal hematuria might be depending on the underlying etiology. It is thought that non-renal hematuria is the result of either stone, infection, tumor, trauma, urinary tract infection (UTI), irritation, or foreign body which might be originating from either the ureter, bladder, or urethra. It may also be caused by prostatic bleeding, vaginal bleeding, and endometriosis.[2]
Genetics
Molecular defects involved in the pathogenesis of non-glomerular hematuria include:
- In the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD):[3]
- PKD1 and PKD2 genes
- In the pathogenesis of autosomal recessive polycystic kidney disease (ARPDK):[4]
- PKHD1 gene
Molecular defects involved in the pathogenesis of glomerular hematuria include:[1]
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
Gross Pathology
Gross pathology might differ depending on the underlying etiology of hematuria.
- On gross pathology,
- Multiple cyst formation and kidney enlargement are characteristic findings of autosomal dominant polycystic kidney disease (ADPKD)[5]
- Solid yellow/golden lesions (because of the cells with lipid-rich cytoplasma), internal necrosis, cystic degeneration, and hemorrhage are characteristic findings of clear cell renal cell carcinoma
Microscopic Pathology
Microscopic pathology might differ depending on the underlying etiology of hematuria.
- On microscopic histopathological analysis,
- Diffuse thinning of the glomerular basement membrane (GBM) is characteristic finding of thin basal membrane disease[6]
- Lobular appearance with massive fibronectin deposits and the absence of immunoglobulin/complement deposition are characteristic findings of fibronectin nephropathy[7]
- Randomly aligned fibrillar deposits that measure 12-24 nm is characteristic finding of fibrillary nephropathy[8][9]
References
- ↑ 1.0 1.1 1.2 Yuste C, Gutierrez E, Sevillano AM, Rubio-Navarro A, Amaro-Villalobos JM, Ortiz A, Egido J, Praga M, Moreno JA (May 2015). "Pathogenesis of glomerular haematuria". World J Nephrol. 4 (2): 185–95. doi:10.5527/wjn.v4.i2.185. PMC 4419128. PMID 25949932.
- ↑ 2.0 2.1 Ingelfinger JR (July 2021). "Hematuria in Adults". N Engl J Med. 385 (2): 153–163. doi:10.1056/NEJMra1604481. PMID 34233098 Check
|pmid=value (help). - ↑ Tan YC, Blumenfeld J, Rennert H (October 2011). "Autosomal dominant polycystic kidney disease: genetics, mutations and microRNAs". Biochim Biophys Acta. 1812 (10): 1202–12. doi:10.1016/j.bbadis.2011.03.002. PMID 21392578.
- ↑ Bergmann C (2017). "Genetics of Autosomal Recessive Polycystic Kidney Disease and Its Differential Diagnoses". Front Pediatr. 5: 221. doi:10.3389/fped.2017.00221. PMC 5811498. PMID 29479522.
- ↑ Akbar S, Bokhari S. PMID 30422529. Vancouver style error: initials (help); Missing or empty
|title=(help) - ↑ Foster K, Markowitz GS, D'Agati VD (May 2005). "Pathology of thin basement membrane nephropathy". Semin Nephrol. 25 (3): 149–58. doi:10.1016/j.semnephrol.2005.01.006. PMID 15880325.
- ↑ Lusco MA, Chen YP, Cheng H, Dong HR, Najafian B, Alpers CE, Fogo AB (November 2017). "AJKD Atlas of Renal Pathology: Fibronectin Glomerulopathy". Am J Kidney Dis. 70 (5): e21–e22. doi:10.1053/j.ajkd.2017.09.001. PMID 29055354.
- ↑ Klomjit, Nattawat; Alexander, Mariam Priya; Zand, Ladan (2020). "Fibrillary Glomerulonephritis and DnaJ Homolog Subfamily B Member 9 (DNAJB9)". Kidney360. 1 (9): 1002–1013. doi:10.34067/KID.0002532020. ISSN 2641-7650.
- ↑ Rosenstock JL, Markowitz GS (July 2019). "Fibrillary Glomerulonephritis: An Update". Kidney Int Rep. 4 (7): 917–922. doi:10.1016/j.ekir.2019.04.013. PMC 6611949 Check
|pmc=value (help). PMID 31317113.