Hypertensive nephropathy pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2] Nasrin Nikravangolsefid, MD-MPH [3]
Pathophysiology
- Hypertension can involve any compartment of the kidney [1] :
- Vessels
- Intimal thickening of small arterioles due to migration of myofibroblasts from media into intimal layer and secretion of collagen which leads to narrowing of the afferent arterioles.
- thining of media layer and hyalinosis of the afferent arteriole due to loss of smooth muscle cells, which have been changed into myofibroblasts, leads to a reduction in glomerular filtration rate (GFR).
- Glomerules
- Constriction of intraglomerular capillaries due to hyalinosis causes glomerular ischemia and reduced filtration which enhances the accumulation of Extracellular Matrix (ECM) in the periglomerular region resulting focal segmental glomerulosclerosis (FSGS) or Global glomerulosclerosis.
- Hypertrophy of the remaining healthy glomerules maintains filtration but increases intra-glomerular pressure and developing microalbuminuria.
- Podocyte loss due to hyperfiltration and glomerulosclerosis leads to destroying the filtration barrier and developing proteinuria.
- Tubulointerestitium
- Dilatation, flattening and loss of epithelial tubular cells
- Overexpression of fibrogenic and angiogenic factors such as transforming growth factor b1 (TGF-b1), Endothelin 1 (ET-1), and vascular endothelial growth factor (VEGF) results in disruption of tubular cells junction, transition of epithelial into mesenchymal cells, production of metalloproteinases, cell migration, production of collagen by myofibroblasts in the interstitial and subsequent tubulointerstitial fibrosis.
- Activation of Renin - Angiotensin - Aldosterone system further contributes to vasoconstriction, cell proliferation, reactive oxygen species production,inducing inflammation and ECM production.
- Angiotensin II induces differentiation of fibroblasts into myofibroblasts, which synthesize collagen in the periglomerular and peritubular regions.
- Dilatation, flattening and loss of epithelial tubular cells
- Vessels
| Changes of kidney compartments induced by Hypertension | |||
|---|---|---|---|
| Compartment | Changes | Final effects | |
| Vessels | Myofibroblasts migration from media into intimal layer
Collagen secretion by myofibroblasts Smooth muscle cells loss in the media layer |
Intimal thickening of small arterioles
Arteriolar narrowing Thining of media layer Arteriolar hyalinosis | |
| Glomerules | Intraglomerular capillaries constriction
Glomerular ischemia Reduced GFR Remained glomerules hypertrophy Podocyte loss |
ECM accumulation
Glomerulosclerosis, FSGS Increased Intraglomerular pressure Microalbuminuria
| |
| Tubulointerestitium | Transition of epithelial into mesenchymal cells
Dilatation and loss of epithelial tubular cells Collagen secretion by myofibroblasts RAAS activation |
Tubulointerstitial fibrosis
Inflammation induction ECM accumulation | |
Chronic hypoxia hypothesis
- Chronic hypoxia hypothesis by Fine et al. in 1998 revealed that hypertension-associated-changes in postglomerular peritubular capillaries cause decrease in blood flow and tubulointerstitial hypoxia, which induce inflammation and epithelial to mesenchymal differentiation. Proximal tubular epithelial cells that are more sensitive to oxygen deficiency than distal cells, are converted into myofibroblasts which produce collagens and inhibit degradation of ECM leading to tubulointerstitial fibrosis. [2][3]
- hypoxia also causes up-regulation of fibrogenic and angiogenic factors, which play a major role in fibrosis formation.
Benign versus Malignant Nephrosclerosis
- Kidney injury from benign and malignant hypertension results in benign and malignant nephrosclerosis, respectively.
Gross Pathology
- Benign Nephrosclerosis:
- The size of the kidneys is reduced or shrunken with loss of cortical mass and fine granularity.
- Malignant nephrosclerosis:
- Hemorrhages from surface capillaries gives the kidney a "flea-bitten" appearance.
Microscopic Pathology
- Benign nephrosclerosis:
- Afferent arterioles have eosinophilic fibrin deposits in the wall, causing hyaline arteriosclerosis
- Malignant nephrosclerosis:
- Fibrinoid necrosis in afferent arteriole
- Hyperplastic arteriosclerosis in inter-lobar arterioles
- Sclerosis in glomeruli and renal tubules
Figure 1. Fibrous intimal thickening in hypertensive nephropathy
Figure 2. Global glomerular collapse and filling of Bowman’s space with a lightly staining collagenous material
References
- ↑ Seccia, Teresa M.; Caroccia, Brasilina; Calò, Lorenzo A. (2017). "Hypertensive nephropathy. Moving from classic to emerging pathogenetic mechanisms". Journal of Hypertension. 35 (2): 205–212. doi:10.1097/HJH.0000000000001170. ISSN 0263-6352.
- ↑ Fine LG, Orphanides C, Norman JT (1998). "Progressive renal disease: the chronic hypoxia hypothesis". Kidney Int Suppl. 65: S74–8. PMID 9551436.
- ↑ Fine LG, Norman JT (2008). "Chronic hypoxia as a mechanism of progression of chronic kidney diseases: from hypothesis to novel therapeutics". Kidney Int. 74 (7): 867–72. doi:10.1038/ki.2008.350. PMID 18633339.