Louis G. Welt

The Concentration Dependence of Active Potassium Transport in the Human Red Blood Cell

The relation between the active potassium influx in the human red blood cell and the extracellular potassium concentration does not appear to be consistent with the Michaelis-Menten model, but is adequately described by a model in which two potassium ions are required simultaneously at some site or sites in the transport mechanism before transport occurs. The same type of relation appears to exist between that portion of the sodium outflux that requires the presence of extracellular potassium and the extracellular potassium concentration. Rubidium, cesium, and lithium, which are apparently transported by the same system that transports potassium, stimulate the potassium influx when both potassium and the second ion are present at low concentrations, as is predicted by the two-site model.

A STUDY OF THE OSMOTIC BEHAVIOR OF THE HUMAN ERYTHROCYTE

Despite many previous studies of the osmotic properties of erythrocytes, unequivocal answers have not been given to two important questions: 1) Is the erythrocyte in osmotic equilibrium with its normal surrounding fluid? 2) When the osmotic properties of the surrounding fluid are varied, does the erythrocyte gain or lose water to the extent necessary to remain in osmotic equilibrium with the new surroundings-that is, does the erythrocyte behave as a perfect osmometer over a wide range? Previous work related to these questions has been of two general types: measurements of changes of volume of the erythrocytes as the osmotic concentration of the extracellular phase was altered; and measurements of one or more of the colligative properties of the solutions involved. The present study is of the latter type. The osmotic behavior of the normal human erythrocyte has been investigated over a wide range of concentrations by a cryoscopic method and a method for measuring the melting point of microscopic samples. The results give affirmative answers to both of the above questions and illustrate some of the difficulties which may be expected in studies of osmotic properties of any tissues.

Phenacetin-induced Renal Disease in Rats

Excerpt There is a growing body of clinical evidence suggesting a relationship between the excessive ingestion of analgesic medication and the development of chronic renal disease. The evidence is ...

The effects of concentrated salt-poor albumin on the metabolism and excretion of water and electrolytes in nephrosis and toxemia of pregnancy.

Purified albumin was first prepared by Armstong and his co-workers (1) in 1940. It was hoped that it would provide a rational mode of therapy for the edema of hypoalbuminemia and serve as an experimental tool for the study of the formation of edema. Numerous investigators have described its use as a diuretic in nephrosis (2-6), cirrhosis of the liver (7-9), idiopathic hypoalbuminemia (10), and other conditions (10). In general the results have been extremely variable despite the fact that albumin induces the same initial hemodynamic events in all patients. Goodyer, Peterson, and Relman (11) have shown that normal subjects who experience similar changes in circulatory dynamics actually have a depression of salt excretion when concentrated albumin is administered intravenously. This has been confirmed by Welt and Orloff (12) under somewhat different conditions. However, the latter were able to augment urine flow profoundly when the albumin was introduced as an approximately iso-osmotic solution. In the past the diuresis which occurs in some patients had been ascribed to the expansion of plasma volume (10). More recently it has been

Further Evidence for a Humoral Natriuretic Factor

Experiments were performed in dogs, utilizing cross-circulation techniques, to examine the role of humoral factors in the production of the diminished net renal tubular reabsorption of sodium that is provoked by the expansion of the extracellular fluid volume. When the extracellular fluid volume of one of a pair of dogs (donor) was expanded by the intravenous infusion of isotonic saline, the rate of sodium excretion (UNaV) increased in the nonexpanded animal (recipient) as well as in the donor. Although the increase in UNaV of the recipients was statistically significant, its magnitude was approximately one-fifth of that of the donors. Modified cross-circulation experiments were designed in order to increase the blood flow from the donor dog to the kidneys of the recipient and from the recipient dog to the kidneys of the donor. This modification resulted in a greater increase in UNaV in the recipient and a lesser increase in UNaV in the donor when the donor was infused intravenously with isotonic saline so that the magnitudes of increase in UNaV in donor and recipient were not statistically significantly different. Neither dilution per se of the extracellular fluid of the donor nor passage of time resulted in an increased UNaV in donors and recipients. Expansion of the blood volume of the donors by the infusion of whole blood resulted in an increased UNaV in the donors but not in the recipients. It is concluded that a humoral factor is responsible, at least in part, for the natriuresis that accompanies the intravenous infusion of isotonic saline and that elaboration of the factor is not a consequence solely of either simple dilution of the extracellular fluid or expansion of the blood volume.

Concentration dependence of active potassium transport in the human red blood cell in the presence of inhibitors

The active potassium influx in the human red blood cell is inhibited by strophanthidin, ethacrynic acid, and MK-870 (a new diuretic), and the degree of inhibition is greater at low concentrations of extracellular potassium than at high. In the case of ethacrynic acid, potassium appears to diminish the rate of combination of the drug with the transport system. The kinetic behavior of the active potassium influx in the presence of the inhibitors strophanthidin and ethacrynic acid is consistent with a model in which the binding of potassium at one of the potassium-sensitive sites in the transport system reduces the affinity of the system for the drug, and binding of a second potassium ion further reduces the affinity. It is not possible to distinguish between the sites on the basis of the studies presented here.

RENAL LESIONS AND DISTURBANCE OF RENAL FUNCTION IN RATS WITH MAGNESIUM DEFICIENCY

Magnesium (Mg) deprivation in the rat results in the following biochemical alterations: hypomagnesemia, hypercalcemia, and azotoemia,l-“ as well as a coexisting small but significant decrement in muscle potassium content.44 The renal morphologic counterpart of these biochemical abnormalities has in past investigations been described by the general term “nephrocalcinosis,” affecting various regions of the renal ti~sues.7-l~ Microdissection studies have been carried out to define more precisely the morphologic characteristics and location of the renal lesion induced by Mg depletion.12J3 Initially, microliths appear in the thin limb of Henle’s Loop sometime during the second week of depletion (FIGURE 1 ) . These laminated microliths react positively with para-aminosalicylic acid (PAS), von Kossa and alizarin stains, indicating the presence of calcium as well as organic matrix. With repeated formation and accretion of new microliths, the lumen of the tubule becomes filled and distended by this composite mass, an intranephronic calculus (FIGURE 2). The structural disturbances exerted by these intraluminal aggregates are manifested locally as well as more generally. First, the local effects are illustrated in FIGURE 3. Note that a microspherolith has lodged in the “hairpin” turn of this portion of the loop. Proximal to the microlith the lumen is filled with PAS positive, von Kossa and Alizarin negative, material. Throughout the entire length of the proximal convolution up to the glomerulus, the epithelium of this first portion of the nephron appeared normal; specifically there was no dilatation of the tubule or Bowman’s Space. Distal to the calculus, scattered debris from erosion of the epithelial wall lies within the tubular lumen and extends throughout the remainder of the thin ascending limb and into the thick ascending portion of Henle’s Loop. This cellular debris, staining deeply with iron hematoxylin, was in part negative to alizarin. A conglomerate of calcareous salts was noted in the large scattered masses of cellular debris which distended and compressed the tubular wall (FIGURE 4); there was no evidence of the periodic pattern of mineral deposition (Liesegang rings) that characterized the original calculus. With increase of this amorphous accumulation, not only is the normal contour of the tubule destroyed but neighboring broad ascending tubules are similarly affected through lateral compression exerted by the enlarging calcareous mass (FIGURE 5) . The terminal portion of the

Severe hyperchloremic acidosis of unusual etiology

Summary The occurrence of severe hyperchloremic acidosis associated with depletion of potassium and with rickets in a child with an imperforate anus and a rectourethral fistula is reported. Data are presented suggesting that the primary cause of the acidosis was the loss of bicarbonate ions as the result of a change in the composition of the urine as it passed through the colon. Following reparative surgery, the ability of the patient to acidify the urine in response to ammonium chloride was normal. These considerations strongly suggest that the pathogenesis of the acidosis was entirely extrarenal.

Further Evidence for a Humoral Natriuretic Factor1

Publisher Summary This chapter provides biochemical evidences for a humoral natriuretic factor. The regulation of salt excretion is among the most important determinants that modifies the concentration of sodium in the extracellular fluid and, hence, its osmolality and that of the intracellular fluid; modifies the distribution of fluid between the major compartments; modifies the volume of the extracellular phase; and perhaps most significant of all, in turn, plays a vital role in the circulation of the blood and all the conditions attendant on this remarkable phenomenon. It is possible that the increased sodium excretion in the donor dogs might have been due to factors other than a humoral natriuretic substance. Thus, it seems quite clear that a highly significant natriuresis obtains in a nonexpanded dog when this particular cross circulation technique is employed. It is also possible that a natriuretic factor is elaborated but its effect on the kidney might not be seen in the absence of dilution of the extravascular fluid.