The Renal Reabsorptive Mechanism for Inorganic Phosphate in Normal and Acidotic Dogs

Abstract

Phosphate plays a role in a number of body functions: calcium phosphat'e is a prominent constituent of skeletal structures; organic phosphate complexes are of importance in energy transformations within cells; and, as the chief buffer component of the urine, inorganic phosphate aids the body in balancing its acid base requirements. Since the urine is the major portal of exit for excess phosphate of dietary origin, the renal mechanisms controlling loss or conservation of the body's stores of inorganic phosphate are of prime interest. Recent investigators (2, 7, 12, 19, 22) concede that phosphate is filtered through the glomeruli, a part is reabsorbed by the renal tubules and the excess is excreted. Upon the characteristics of the reabsorptive process, which fundamentally determine the balance between conservation and elimination, there is less agreement. Harrison and Harrison (7) claim that the capacity of the renal tubules to reabsorb phosphate is limited in the same sense as Shannon and Fisher (16) had previously shown glucose reabsorption to be limited. Thus, if phosphat'e is presented to t,he renal tubules in the glomerular filtrate in amounts exceeding their capacity to reabsorb, the excess appears in the urine. The limited range of plasma phosphate concentration in their studies, i.e., from 3 to 10 mgm. of phosphate phosphorus per 100 cc., is insufficient to establish their conclusion definitely. Smith, Ollayos and Winkler (19) reinvestigated the problem and arrived at the opposite conclusion, namely: that the capacity of the tubules to reabsorb phosphate increases progressively with increasing plasma concentration over a range from 3 to 40 mgm. per 100 cc. Their experiments were complicated by rapid falls in plasma concentration and by sharply declining rates of glomerular filtration. Coupled with their few experiments, these factors render their conclusion unconvincing. As a preliminary to a study of the renal mechanisms for the regulation of acid base balance, we have found it necessary to determine the properties of the renal tubular reabsorptive mechanism for phosphate. Our results indicate that the capacity of the renal tubules to reabsorb inorganic phosphate is limited and that the mechanism is relatively st,able and unaffected by considerable shifts in electrolyte and acid base balance of the organism. METHODS. Our experiments have been carried out on 5 trained female dogs loosely restrained on a comfortable animal board. Water, in amounts of 50 cc. per kilo, was administered by stomach tube at the start of the experiment to ensure adequate hydration of the animal. Urines were collected by catheter and the bladder washed out with distilled water at the end of each 10 minute 648

The Renal Regulation of Acid-Base Balance in Man. Ii. Factors Affecting the Excretion of Titratable Acid by the Normal Human Subject 1

“…There appears from our limited data to be no difference between this maximum rate of reabsorption in acidosis and under conditions of normal acid-base balance. In this respect, results on man and dog (12) are in agreement. In contrast, at normal plasma concentrations of phosphate the reabsorption of phosphate is significantly less complete in acidosis than under conditions of normal acid-base balance.…”

“…Accordingly, the spontaneous rate of excretion of phosphate is higher in acidosis, a factor no doubt of major importance in explaining the phosphaturia in man. In our experience dogs show much less phosphaturia and no appreciable change in reabsorption of phosphate at normal plasma levels in acidosis (12). In these observations on man there appeared to be no significant effect of acidosis on plasma phosphate concentration, the range of variation being about the same in acidosis as in the normal.…”

“…The excess urinary phosphate is derived in large part from stores of non-diffusible organic acid soluble phosphorus within the cells, hydrolysis of which liberates inorganic phosphate into the plasma (11). According to 1 view, the renal reabsorptive mechanism for phosphate is unaltered in acidosis and the elevation of plasma phosphate which results from hydrolysis of the esters adequately explains the increased rate of phosphate excretion (12). On the other hand, it has been claimed that the plasma phosphate concentration is below normal in acidosis and that the phosphaturia results from a depression in the capacity of the renal tubules to reabsorb phosphate (13).…”

The Parathyroid Glands and Phosphorus Homeostasis 12

“…Certain published data, however, fail to support this thesis (27,34,35) and in our own studies we have been unable to detect any significant change in the various moieties of total blood phosphorus either in sivo or in vitro as a consequence of parathyroid extract administration. Harrison and Harrison (27) and Pitts and associates (36,37) have suggested that a renal tubular maximal capacity for phosphorus reabsorption (TmP) exists. This maximal capacity or "threshold" value is presumed to be directly under the influence of the parathyroid glands.…”

Mechanisms of Edema Formation in Chronic Experimental Pericarditis With Effusion 1

“…Then either isotonic (0.9%) or hypertonic (2.5% or 5%) saline was used. Sodium clearances were calculated from plasma sodium levels, glomerular filtration rates and urinary sodium excretion rates (23). Plasma and urine sodium concentrations were determined by the methods of Bradbury (24) and Butler and Tuthill (25), respectively.…”