The oliguria of acute renal failure has been attributed to tubular obstruction (1-12), "leakage" of the glomerular filtrate through rents in the tubular wall (13)(14)(15)(16)(17)(18)(19), and vascular mechanisms of various types (20)(21)(22)(23)(24)(25). In a previous paper, it was shown that the oliguria of mercury-induced acute renal failure in the rat reflects a primary decrease in glomerular filtration rate and cannot be attributed to tubular mechanisms (26). The applicability of these findings to most types of acute renal failure occurring in humans may be questioned, however, because of the very dissimilar etiologies and the known effect of large doses of mercury on the renal circulation (27). The present study concerns hours before glycerol injection. They lost an average of 8% of body weight in the period of dehydration, during which time their food intake was one-third less than that of nondehydrated animals. Blood samples were obtained by cardiac puncture from a number of glycerolinjected animals and dehydrated control rats that were exempted from micropuncture studies to determine the change in their blood urea nitrogen (BUN) occurring over a 48-hour period. BUN was measured on 0.2-ml samples by a modification of the urease method of Gentzkow (28). Urinary osmolalities were determined with an Advanced osmometer.Acute renal failure was induced by injecting 50%o glycerol in water into the muscle of both hind limbs at a total dose of 10 ml per kg of body weight. Within 2 hours after this injection, the urine was found to be burgundy red in color due to the presence of heme pigments.The animals were subjected to micropuncture experiments at times ranging from 30 minutes to 26 hours after glycerol injection. They were anesthetized with sodium pentobarbital given intraperitoneally at a dose of 40 to 50 mg per kg body weight. Their blood pressure was monitored as described earlier (26) either by a tail cuff microphone method or intra-arterial manometry. Although hypotension typically did not occur, animals whose mean arterial blood pressure was less than 85 mm Hg were excluded from micropuncture study. The left kidney was exposed through an abdominal incision and carefully dissected free of the perirenal fat. The renal hilus was disturbed as little as possible, and the renal capsule was left intact. The kidney was placed in a Lucite holder to minimize its displacement with respiration. Its surface was covered with warm mineral oil to prevent drying and to aid in visualization of the renal structures.Micropuncture methods were those described in an earlier paper (26). In short, proximal tubular hydrostatic pressure was measured by a modification of the manometric method of Wirz (29), using a water manometer to obtain maximal definition of the end point. The manometer was calibrated at zero pressure before each measurement. Glomerular filtration rate and fractional water absorption were determined at least 30 minutes after the injection of 40 ,uc of "C-labeled inulin 1 in 0.3 to 0.5 ml of 140 mM NaCl. Labele...

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A B S T R A C T The concentration of serum albumin in proximal tubule fluid of normal rats and animals with aminonucleoside nephrosis was studied using renal micropuncture techniques. Albumin was quantitated by an ultramicrodisc electrophoresis method capable of measuring 3 X 10'" g of albumin, in 10 nl volumes. With this sensitivity., only small samples of tubule fluid were required for analysis. Collectifn times could be kept short, therefore decreasing the opportunity for sample contamination with extraneous serum albumin. The measured mean concentration of albumin in proximal tubule fluid (1 mg/100 ml in females and 0.7 mg/ 100 ml in males) was somewhat lower than values reported by others, but even these values are apt to have been artifactually high as a result of animal preparation and trace contamination of samples during micropuncture. Rats injected with aminonucleoside of puromycin 4 days earlier, showed a significant increase in tubulefluid albumin concentration coincident with a fall in serum albumin concentration and a 43-fold increase in urine albumin concentration. Tubular absorption of albumin was small relative to that of water. Although albumin filtration was significantly increased over that in normal animals, the glomerular basement membrane still served as a highly efficient barrier to albumin transfer.

Acute renal failure in man may result from such factors as trauma, transfusion accidents, sepsis, burns, and acute poisoning with carbon tetrachloride, ethylene glycol, or mercury. Regardless of the etiology and despite marked variability in the histologic appearance of the kidneys of individual cases, most patients with acute renal failure develop oliguria or anuria together with evidence of impaired tubular function. The cause of this decrease in urine volume, however, has not been well defined. Some theories commonly conjured to explain the oliguria of acute renal insufficiency stem largely from pathological findings rather than from functional studies in vivo. Of these findings, three have been stressed as possibly being responsible for oliguria: tubular obstruction by cellular debris (1-3), tubular compression by interstitial edema (4-7), and "passive backflow" of glomerular filtrate through holes in the wall of the tubule (6,8,9). We have attempted to determine the possible role of these factors in mercury-induced acute renal failure in the rat. perimentation. Their food and fluid intake and urine volume were measured; animals whose water intake was less than 10 ml during this period received supplementary fluids intraperitoneally in the form of 75 mM saline. Mercuric chloride, 12 mg per ml 140 mM NaCi, was injected intramuscularly at a dose of 12 mg per kg, control animals receiving a comparable volume of saline alone. Micropuncture experiments were performed at times ranging from 2 to 27 hours after mercury injection, and the fluid intake and output in the intervening period were recorded. Urine osmolalities, measured cryoscopically with a Fiske osmometer, were obtained routinely in early experiments to rule out hypovolemia due to a redistribution of body water and a resultant ADH effect as the sole cause of oliguria. Since urine osmolalities in mercury-treated animals were consistently less than 610 mOsm per kg, these measurements later were discontinued. MethodsAnimals were anesthetized with sodium pentobarbital, 35 mg per kg body weight, supplementary pentobarbital being added as necessary. They were placed supine and warmed from above with an infrared lamp to maintain body temperature at 400 C. The left kidney was exposed through an abdominal-flank incision and gently dissected from the perirenal fat. The renal capsule was left intact, but in dissecting the kidney from its bed collateral circulation through capsular vessels was virtually abolished. The kidney was placed in a Lucite holder as gently as possible, care being taken to avoid distortion of the renal vessels and ureter. The surface of the kidney was illuminated with a 25-w zirconium arc lamp and covered with warm mineral oil to prevent surface evaporation and facilitate visualization of the renal architecture. The blood pressure of each animal was monitored with either a tail microphone apparatus or direct aortic manometry. When the tail microphone was used, a 1-cm occluding cuff was placed at the base of the tail and the pickup positioned ...

A questionnaire and interviews were used to study the policies of 219 physicians about "telling" cancer patients. Ninety per cent indicated a preference for not telling. Although clinical experience was cited by three-quarters as the major policy determinant, the data bear no relation to experience or age. Instead, inconsistencies, opinionatedness, and resistance to change and to research were found which indicated emotion-laden a priori personal judgments as the real determinants. Feared reactions to telling

Inulin and mannitol clearances, BUN concentrations and renal morphologic alterations were studied in rats 24 h after the injection of low doses of mercuric chloride. Water drinking rats given 4.7 mg/kg body weight of HgCl₂ developed renal failure and severe tubular necrosis. Their clearance of inulin was decreased to the same degree as their simultaneously determined mannitol clearance. Any significant change in tubular permeability should have resulted in a greater loss of mannitol than inulin, and it is suggested that tubular permeability to neither molecule was greatly increased. This is supported by the fact that rats drinking one percent saline in place of tap water for a month prior to receiving the same dose of HgCl₂ showed insignificant changes in inulin clearance and minimal elevations in BUN concentration. Nevertheless, histologic sections of their kidneys showed frank tubular necrosis that was equally severe as, but slightly less extensive than that observed in the water drinking rats whose inulin clearance was 6 % of normal. In view of these findings, it seems unlikely that alterationin tubular permeability per se are responsible for the development of acute renal failure in low dose mercury poisoning. The protective effect of salt loading does not depend on the prevention of tubular injury, and may well reflect inhibition of pre-glomerular vasoconstriction by suppression of the renin-angiotensin axis.

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Stopped flow microperfusion technique ( Am. J. Physiol. 195: 563, 1958) was used to study water movement across the proximal tubular wall of Necturus kidney. In 23 experiments, net water movement was measured from perfusion solutions containing 50, 62.5, 75 and 100 mEq. NaCl/1. which were made isosmotic with Necturus plasma by addition of mannitol. Water movement was shown to depend upon luminal NaCl concentration. Studies of the relationship between net solute flux and water flux demonstrated a linear relationship: net water flux (mµl/sec.) = 9.4 x net solute flux + 0.003. Net water flux is statistically zero when net solute flux is zero. Under these experimental conditions no force is important for water movement other than that arising from solute movement. It is concluded that net movement of Na has taken place up an electrochemical potential gradient, indicating active transport of this ion. Furthermore, movement of water from the tubule is considered to be passive since net water flux may be accounted for quantitatively in terms of osmotically induced forces arising from net solute movement.