Editing Pathophysiology of Urinary Tract Obstruction (section)

== Effects of obstruction on tubular function ==

* Normal urine concentrating ability depends on
*# A hypertonic medullary interstitial gradient
*#* Established by active sodium transport out of the tubule and the countercurrent exchange mechanism
*# Variable permeability of the tubules to water
*#* Mediated by aquaporin water channels.
* '''Mechanisms of nephropathy secondary to obstruction leading to disrupted electrolyte and acid/base balance:'''
*# '''Decreased concentrating ability, due to (3):'''
*## '''Disruption of the medullary hypertonic interstitial gradient leads to a loss of the osmotic driving force for water to move into the interstitium'''
*## '''Decreased sodium transport after release of obstruction, resulting in salt wasting''' and also contributes to the concentrating defect observed in response to obstruction
*## '''BUO leads to a''' '''decrease in the expression of aquaporins''' (1, 2 and 3) that are important in the absorption of water; a decreased expression of aquaporin 1 can persist after 30 days from relief of obstruction
*##* '''Primary cause of persistent concentrating defect after relief of BUO'''
*# '''Impaired urinary acidification''', due to:
*#* impaired H+ excretion and bicarbonate transport within the tubule
*#** The cumulative evidence shows a major acidification defect in the distal nephron. Release of obstruction does not result in bicarbonaturia, indicating that proximal reclamation remains intact. There is a defect in the proximal handling and breakdown of glutamine, which means that a higher proportion of protons are buffered as titratable acid. The best evidence indicates a '''defect in the expression of H+-ATPase in the collecting duct'''
*# '''BUO prevents excretion of potassium, phosphate and magnesium. In cases of UUO the overall balance of these electrolytes is maintained by compensation from the contralateral kidney.'''
*# '''Urinary dilution is not affected by chronic unilateral ureteral obstruction'''.