In recent years, physiology of hypothermia has received a great deal of attention by many medical scientists. However, renal functions in hypothermia have received relatively little attention as compared to ethers and, consequently, there are many
problems yet to be solved. One of the most important problems to be solved in this field is concerned with the process of urinary acidification inasmuch as acidosis is known to develop in hypothermia (Fleming, 1954 ; Axelrod et at., 1956 : Kanter,1963).
Eggleton has shown in 1947 that the hydrogen ion excretion is diminished whileothers (Segar, 1956: Hernandez et al., 1957) showed a reduction in the urinary excretion of ammonia, in hypothermia. On the other hand, the urinary concentration of phosphate is also markedly reduced in hypothermia (Segar, 1958 : Hernandez and Coulson, 1959). Recently, Kanter(1963) reported that, in hypothermia, the urinary acidification process as a whole is depressed while the tubular reabsorption of bicarbonate is inhibited in proportion to the reduction in the glomerular filtration rate.
As evident from these literature surveys, available informations concerning the problem of urinary acidification in hypothermia are rather fragmentary and thus a systematic, quantitative approach is needed. Hence, this investigation was
undertaken to study in hypothermia, 1) the extent of urinary acidification along with the urinary excretions of ammonia, titratable acid, bicarbonate and phosphate, 2) the effect of acetazolamide on the urinary acidification and, finally, 3) the maximal reabsorptive capacity of bicarbonate and phosphate. In a final analysis of the data, all the factors related to the urinary acidification are correlated and a general scheme for the urinary acidification in hypothermia is proposed.
Experiments were carried out in 37 anesthetized female dogs, weighing approximately 10kg. Unless stated otherwise, metabolic acidosis was induced by administration of HCI (10 mEq/kg) by stomach tubing 15 to 18 hrs prior to the onset of experiment, in order to activate the urinary acidification process. Having fasted for 15 hrs prior to the experiment, the dog was anesthetized with Nembutal (27mg/kg, i.v.) and an endotracheal tube was inserted. A femoral artery was cannulated for blood sampling and a femoral vein for infusion. Urinary bladder was
catheterized. A telethermometer probe was inserted approximately 20 cm into the rectum for continuous reading of deep body temperature.
30 to 40 minutes after the surgical procedures, 2M urea in 0.15 M NaCl was infused at a rate of 5ml/min/kg fellowing which a priming dose of inulin (50 mg/kg) was given intravenously. Sustaining dosers of inulin (1mg/min/kg) were contained in the above solution. After a 30 minute period of equilibration blood and urine samples were collected every 10 minutes for 30 minutes following which the infusion was stopped and the dog was immersed in an ice water bath until the rectal temperature reached approximately 27-28 C. At this point, the animal was removed from the water bath. Body temperature continued to decrease, but leveled off after 40-60 minutes at 24-26 C. During this steady state of hypothermia, collections of blond and urine were resumed for three periods as above. During hypothermia, infusion was continued at a rate of 3ml/min/kg and the dose of inulin was reduced to one-half of the euthermic dose. In addition to the above procedure, acetazolamide was intravenously administered in 10 dogs. In this case, 7mg/kg was given as a priming dose which was followed by a sustaining dose of 7mg/kg/hr. In those experiments in which the maximal reabsorptive capacity (Tm) of bicarbonate or phosphate was determined, 0.3M NaHC0^^3 or 0.11 M sodium phosphate (pH 7.4) was infused instead of urea in saline at a rate of 5ml/min/kg to those animals in which metabolic acidosis was not induced.
Results and Discussion
(1) The glomerular filtration rate as measured by the inulin clearance was reduced by 59% in hypothermia. Although blood pH tended to be lowered from 7.25 in euthermia to 7.21 in hypothermia, urine pH tended to increase from 6.35 to 6.53.
However, the titratable acidity of urine was not altered while the excretion of titratable acid was reduced by 40% in hypothermia. These indicate that the hydrogen ion secretion by the renal tubule per unit time is diminished at lower body temperature.
(2) The urinary concentration of both bicarbonate and phosphate increased while the excretion of ammonia diminished in hypothermia. Moreover, the fractional excretion of the filtered bicarbonate and phosphate increased by 50 to 100% in hypothermia. These results indicate that the tubular reabsorption of bicarbonate and phosphate is depressed.
(3) In both euthermia and hypothermia, administration of acetazolmide increased urine pH and decreased the excretion of ammonia and the titratable acid. Moreover, the excretion of both bicarbonate and phosphate increased by nearly 2-fold after acetazolamide. These indicate that carbonic anhydrase is still active even in hypothermia.
(4) The tubular maxima for bicarbonate reabsorption was 1.21 mM/min/100gm kidney in euthermia, but was reduced to 0.78 mM/min/100gm kidney in hypothermia. The temperature coefficient(Q^^10) for bicarbonate reabsorption was 1.41. However, the tubular maxima for phosphate reabsorption was 146 and 51μM/min/100gm kidney in euthermia and hypothermia, respectively, and the value of Q^^10 was 2.35. These indicate that, of the two substances which play a very important role in acidifying the urine, the phosphate reabsorption is far more sensitive to changes in temperature than bicarbonate.
On the basis of above findings, the following scheme for the urinary acidification in hypothermia is proposed: In hypothermia, the glomerular filtration rate is reduced. However. the active reabsorption of bicarbonate and phosphate is also inhibited in hypothermia and thus the concentration of these substances in the tubular lumen would increase. Since these substances, especially phosphate, are main buffer substances in the urine, an increase in the concentration of bicarbonate and phosphate would buffer hydrogen ions which are continuously secreted into the lumen, whereby preventing the reduction in urine pH. Moreover, carbonic anhydrase is still active even in hypothermia and hence thin increase in buffer substances in the lumen would continuously stimulate hydrogen ion secretion without provoking the ammonia secretion. However, the excretion of titratable acid is still less in hypothermia than in euthermia because of a greater reduction in the glomerular filtration rate at lower body temperature.