Editing Pathophysiology of Urinary Tract Obstruction (section)

== Pathologic changes of obstruction ==

* '''The histologic derangements associated with early obstruction are localized primarily to the tubulointerstitial compartment of the kidney and include:'''
*# '''Massive tubular dilation'''
*# '''Progressive tubulointerstitial fibrosis'''
*# '''Inflammatory cell infiltration'''
*#* One of the earliest pathologic findings associated with UUT obstruction
*# '''Apoptosis of tubular and interstitial cells'''
** '''The glomerulus is the renal structure that is best preserved in the presence of obstruction.'''
*** Glomerular changes are the last to occur with hydronephrosis
*** With long-term obstruction, other more distal components of the kidney are destroyed first.
* Long-standing obstruction ultimately results in glomerulosclerosis most likely as a result of chronic inflammation and/or hyperfiltration injury
* '''Molecular mechanisms of tubulointerstitial fibrosis'''
** '''Tubulointerstitial fibrosis is a major pathologic component of obstructive renal injury''' and is associated with a significant accumulation of matrix-producing fibroblasts
*** '''Fibroblasts are derived from (3):'''
***# '''Resident renal fibroblasts'''
***# '''Bone marrow–derived fibroblasts'''
***# '''Phenotypic transformation of renal tubular epithelial cells into matrix-producing fibroblasts''' (epithelial mesenchymal transition)
** One of the earliest histologic changes in the obstructed kidney is an increase in inflammatory cell infiltration into the interstitial compartment of the kidney.
** '''There is increased expression of TGF-β with obstruction that contributes to an increase in the extracellular matrix of the kidney and promotes inflammation.'''
* '''The release of TNF-α, a potent inflammatory cytokine, is stimulated by angiotensin, especially in the first few hours of renal obstruction.'''
** TNF-α can upregulate its own expression as well as that of other inflammatory mediators, such as interleukin-1, platelet-activating factor, nitric oxide, eicosanoids, and cell adhesion molecules.
* '''Caspases are known to mediate apoptotic cell death in obstructed kidneys'''
* '''The presence of increased collagen deposition in the renal parenchyma at the time of pyeloplasty and the presence of extensive glomerulosclerosis have both been shown to have a negative impact on recovery of renal function'''