T. Addis

THE RELATION BETWEEN THE SERUM UREA CONCENTRATION AND THE PROTEIN CONSUMPTION OF NORMAL INDIVIDUALS

When a patient with renal disease is found to have a concentration of urea in his blood that is higher than usual we would like to be able to derive from the degree of increase in concentration some idea as to the degree of decrease in the urea-excreting function of his kidneys. In the individual patient this cannot safely be done. True, when we plot the blood urea concentrations of a large number of patients against their urea clearances, a general relation does emerge (1, 2). However, in any one of such a group of patients the prediction from concentration to clearance may fall dangerously far from the truth. This is inevitable because the concentration of urea in the body is determined not only by how much urea runs out of the system through the kidneys but also by how much urea runs into it from the liver. Whenmore runs out than runs in, the concentration falls to a lower level which is maintained as long as the discrepancy persists. When more runs in than runs out the concentration level rises and remains high as long as the excess of in-flow over out-flow continues. Unlike salt, the concentration of urea is confined within no narrow zone of variation by any regulatory mechanism. Urea is a substance to which the body is chemically and physically indifferent. It is an end product of protein metabolism and participates in no chemical reactions. Except in the kidney it has no osmotic effect because it is distributed evenly through the water of all organs and tissues. So we need not be surprised when we find, as we do, that there is a wide scatter in the urea concentrations in the blood of normal individuals (3, 4). In spite of wholly normal renal function we shall continue to find this high variability until we make measurements on normal subjects who are taking the same amounts of protein in their food; and in our patients, whose

Effect of Adrenalectomy on Spontaneous and Induced Proteinuria in the Rat.

Summary 1. Bilateral adrenalectomy abolishes or greatly reduces the types of experimentally produced proteinuria studied in the saline maintained rat. 2. The normal, spontaneous proteinuria of the male rat is significantly reduced by bilateral adrenalectomy. 3. Cortisone administration to bilaterally adrenalectomized male rats increases their spontaneous proteinuria to normal control levels. 4. Adrenal cortex extract, esoxycorticosterone acetate, and cortisone restore the ability of the salt-maintained, adrenalectomized rat to respond to renin injection with massive proteinuria.

The effect of intravenous injections of fresh human serum and of phosphated blood, on the coagulation time of the blood in hereditary hemophila

The coagulation time of the blood in hereditary hemophilia fluctuates in an irregular manner from day to day. Only very pronounced alterations are therefore of value as a guide to the effect of any particular method of treatment. The variations shown in Table I were observed in cases who were not subjected to any treatment. In many instances the changes observed are well beyond the error of the method which was used. Five cubic centimeters of blood were withdrawn from the median basilic vein through a short oiled needle into two or more test-tubes, and the average interval of time required until coagulation had advanced sufficiently to allow of the complete inversion of the tubes without spilling the contents was taken as the coagulation time. The temperature was 37° C. Normal blood requires about 13 minutes to coagulate under these conditions. Parallel observations with another method showed that reliable results could be obtained with blood from skin puncture when certain details in the manner of collecting the blood were observed. 1 Variations in coagulation time which were not greater than those illustrated in Table I were noted under the administration by mouth of calcium lactate, sodium chloride and of large quantities of raw beef juice. The removal from a vein of 60-70 c.c. of blood once a week had no effect. No immediate effect was produced by the intravenous injection of normal horse serum and of antidiphtheritic serum. These sera were all five or more weeks old. In one case a marked prolongation of coagulation time was found three weeks after an intravenous injection of horse serum, but since successive observations were not made during this interval, it is not certain that this was the result of the serum injection.

Age and the Rate of Venous Enlargement under Increased Venous Pressure.

Conclusions 1. After ligation of the vena cava above the entrance of the renal veins a plot of the logarithms of the percentage mortality on age seems to indicate that they are a linear function of the age at the time of operation. 2. It is suggested that the above relation may be the result of a decrease in the rate of venous enlargement under increased pressure as age advances.

Science and Practice in Bright's Disease

Excerpt There are in the main two sorts of men interested in Brights disease. We may call them the clinical scientists and the clinical practitioners. They are separated by a difference in their-a...

The function of the kidneys under strain in uranium nephritis and the relationship between anatomy and function under these conditions

Rabbits were injected subcutaneously with uranium nitrate in doses which varied from those which produced marked anatomical and functional changes to those which led to no certain effect. A strain was placed on the urea-excreting function of the kidneys by the administration of urea by stomach tube. While the kidneys were under the influence of this strain, the volume of urine, the rate of urea excretion, and the concentration of urea in the urine and blood were determined before and after the injection of uranium. The most marked and constant functional change produced by the uranium was found to be a depression of the ratio between the rate of urea excretion and the concentration of urea in the blood. The degree of depression in this ratio was fairly closely parallel to the degree of anatomical damage, as judged from the extent and intensity of the necrosis or of the degenerative changes found in the terminal portion of the proximal convoluted tubule.

Influence of Age on Degree of Renal Hypertrophy Produced by High Protein Diets.

Three adequate diets which contained 18 per cent, 31 per cent and 70 per cent of protein in the form of casein, which differed only in respect to a replacement of cornstarch and lard by casein, were fed to three groups of male albino rats from the time they were 26 days old until they were 70 days of age. The animals were then killed and the kidney weights ascertained. Table I shows that as the amount of protein increased there was a considerable increase in the weight of the kidney. The same diets were also given to adult rats from the time they were 346 days of age until they were 400 days old. Table II shows that the increase in the consumption of protein had little effect on the weight of the kidney in these older rats.

Metabolism of Intraperitoneally Injected Serum Protein.

Two groups of 10 albino rats with identical average body weights were selected. For 2 days they were given no food. On the morning and evening of each day 12 cc of 6.4% dextrose in 0.9% sodium chloride was injected into the peritoneal cavities of the controls while to the experimental group an injection of 12 cc of freshly separated serum obtained from normal rats was given. Both groups were anesthetized 48 hours after the first injection and 18 hours after the last. All the blood that could be obtained from the cut abdominal aorta while the heart was still beating was centrifuged at high speed for half an hour and the serum separated from the clot. The quantity thus drawn represents about 75% of the total blood volume. The liver, kidneys and heart were then removed, weighed and prepared for the protein determinations. The contents of the alimentary tract were removed after boiling in 0.5 M acetate buffer at pH 5. and the protein content of the tract determined with the carcass. 1 In the experimental group the abdominal cavities contained on an average nearly 5 cc of a fluid that had a somewhat higher protein concentration than the serum that had been injected. This fluid was collected and its protein is not included in the total protein given in Table I. Since the original body weights of the two groups were identical the quantities found after 48 hours may be directly compared. It is evident that in all the organs examined serum injection is associated with a higher protein content than is found after dextrose injection. But the only important question is whether this greater protein content is a part of the rats protein or is only the serum protein that we had injected.

An Error in the Urease Method for the Determination of Urea.

Estimates of the urea concentration of the blood, muscle and liver tissue of rats were carried out in connection with a study of the effects of high protein diets. The urease method was used. A typical result is given in Table I. The high concentration of urea shown here for the rats liver is at variance with the observation of Marshall 1 who found an approximate equality of urea concentration in the blood, muscle and liver of other animals. In obtaining the results shown in Table I the rats were anesthetized with ether, and bled to death by cutting the abdominal aorta. The tissues were removed immediately, weighed, ground in a mortar and quantitatively transferred with water to large aeration tubes. The method used has been described in detail elsewhere. 2 The only changes made were those which were necessitated by the fact that the tissues and blood were made up with water to a volume of 30 cc. This method is simply a special adaptation of the aeration method described by Marshall. 1 The urea is calculated from the amount of additional ammonia formed after incubation of the tissue with the filtrate from a suspension in water of freshly ground jack beans. When the liver was heatcd before adding the jack bean filtrate an entirely different result was obtained, the previous high level of urea concentration in the liver was no longer found, and the estimates showed an approximate equallity of concentration in blood, muscle, and liver, in accordance with the conclusion reached by Nf arshall. (Table 11.) A linear relation is attained ktween the quantities of urea produced and the quantities of “urease” used when the ratio between liver and urease is neither too small nor too large. Fig. 1 shows the result of an experiment in which the liver was held constant at 2.26 gm. and the urease was varied from 0.2 to 1.0 gm. The mixtures were incubated for 2 hours at a temperature of 37” C. The reaction was maintained at pH 7.2 by phosphate.

Do High Protein Diets Increase Weight of Kidney Because They Increase Nitrogen Excretion

The experiments cited in the preceding note 1 served as controls for experiments in which the same order of magnitude of increase in nitrogen consumption was obtained by the administration of urea instead of protein. The results given in Table I suggest that the simple hypothesis of a work hypertrophy may be inadequate as an explanation for the increased kidney weight in young rats, and demonstrate that in adult rats a marked increase in nitrogen consumption may have no effect on the weight of the kidney.