Pathophysiology of Clinical Disorders of Urine Concentration and Dilution

A Clinical Diagnosis of Disorders in Concentration and Dilution DEFECT IN THE ABILITY to concentrate or dilute the urine can be easily rec­ ognized by the maximum or minimum urine concentration the patient is able to achieve. Maximum concentrating ability (Umax) is determined by the urine osmolality reached after a fixed period of dehydration and maximal diluting ability (Umin) by the minimum osmolality of the urine after the oral inges tion of a fixed water-load. These indices, however, do not allow an understanding of the pathophy­ siological alterations leading to the pres­ ence of the defect. Inability to maximally concentrate the urine can be attributed to one or both of two basic tubular defects: first, a failure of maximal free-water generation by the diluting segment in the ascending limb of Henle's loop and second, a failure of the distal tubular epithelium to achieve maxi­ mum permeability to water during water deprivation. These changes singly or com­ bined are capable of reducing maximum concentrating ability. The first brings about the reduction in Umax by diminish­ ing the cortico-papillary solute gradient and thus reducing the gradient for free­ water reabsorption from collecting duct lumen to interstitium. The second re­ duces Umax by preventing osmotic equi­ libration of collecting duct Huid with the medullary interstitium (1-3). Inability to produce a maximally dilute urine may likewise be attributed to one or both of two basic tubular defects: first, the failure of maximal free-water generation by the diluting segment, and second, an in­ appropriately high permeability to water of the distal tubular epithelium during water diuresis. The former, while reducing maxi­ mal concentrating ability, also diminishes maximal diluting' ability by resulting in a less than normal dilution of tubular fluid. The second results in the inappropriate re­ absorption of water from the collecting duct in response to the interstitial solute gradient generated by solute reabsorption in the ascending limb. It is readily apparent that a failure of the ascending limb and other diluting seg­ ments to generate normal amounts of free water can result, at low tubular flow rates, in a diminution of both maximal concen· trating and maximal diluting ability. Nevertheless, a comparison of Umax and Umin may be utilized to distinguish be­ tween a permeability defect and a defect in free-water generation. If both concentrat­ ing and diluting ability are reduced, a de­ fect in free-water generation is suggested. Such a defect must involve the active solute reabsorption process in the medullary por­