Plasma tCO2 Research Articles

Superficial distal and deep nephrons in correction of metabolic alkalosis

Chloride is necessary and sufficient to correct alkalosis induced by dialysis vs. 0.15 M NaHCO3. To determine the contribution of the cortical (SC) distal convolution (DCT) and juxtamedullary (JM) nephrons to correction, we examined Cl and total CO2 (tCO2) transport in alkalotic Sprague-Dawley rats infused with 5% dextrose (group DM) or with 5% dextrose and 80 mM Cl (group CC); in papillary studies in alkalotic Munich-Wistar rats, 6% albumin was added to the infusate. In cortical studies, changes in plasma Cl and tCO2 were 4.9 +/- 0.7 vs. 0.7 +/- 0.9 and -6.0 +/- 0.8 vs. 0.4 +/- 0.9 meq/l and in tCO2 excretion (133 +/- 28 vs. -8 +/- 10 mueq/min) in groups CC and DM, respectively; results in papillary studies were similar. Delivery of tCO2 out of late SC DCT (CC 146 +/- 20 and DM 146 +/- 23 pmol/min) and Henle's loop (CC 145 +/- 18 and DM 202 +/- 56 pmol/min) and reabsorption within DCT (CC 15 +/- 24 and DM 45 +/- 19 pmol/min) did not differ. During correction of chloride-depletion alkalosis, the increment in bicarbonate excretion does not emanate from DCT of SC nephrons or JM nephrons but rather from the collecting duct.

Total CO2 absorption in the distal tubule of the rat

By use of in vivo microperfusion methodology, we assessed proton secretion (acidification) in the superficial distal tubule of the rat by determining the rate of total CO2 (tCO2) absorption (JtCO2). In these studies, we compared the JtCO2 in rats fed a diet that increased urine pH to the JtCO2 in rats fed a high-protein diet that reduced urine pH. The effect of amiloride added to the perfusate, used in rats fed the high-protein diet, was also examined. In rats, Group 1, fed a commercial diet, urine pH was 6.9; plasma tCO2 was 30.0 mM, and JtCO2 was 15.5 +/- 5.3 pmol X mm-1 X min-1. Following the ingestion of a high-protein diet the night before study, the urine pH fell to 5.6 and the plasma tCO2 to 28.2 mM. The JtCO2 in this group, Group 2, 41.1 +/- 4.8 was significantly greater than Group 1, P less than 0.05. The late distal transepithelial potential difference was comparable in both groups, -50.3 +/- 4.3 vs. -45.2 +/- 3.1 mV, P not significant. In a third group, Group 3, amiloride (10(-4) M) was added to the perfusate of rats prepared as in Group 2. JtCO2 was 23.4 +/- 0.4 pmol X mm-1 X min-1, significantly less than Group 2, P less than 0.05. The transepithelial potential difference was reduced to -4.0 +/- 2.3 mV, P less than 0.01 vs. Group 2. We conclude that the superficial distal tubule of the rat responds to subtle stimuli to increase proton secretion and contributes to urinary acidification. The rate of acidification can be influenced by alterations in the electrical profile across the acidifying epithelium.

Distal tubule bicarbonate accumulation in vivo. Effect of flow and transtubular bicarbonate gradients.

We have performed microperfusion studies on distal tubules of normal and alkalotic rats in an attempt to demonstrate in vivo bicarbonate secretion. All perfusion solutions were free of phosphate and other nonbicarbonate buffers. In both normal and alkalotic rats, distal perfusions elicited significant tCO2 entry only at high flow (24 nl/min). Even when perfusate tCO2 concentration closely matched plasma tCO2 concentration (30 mM tCO2), significant tCO2 entry again occurred at high flow. This was associated with a rise of the perfusate tCO2 concentration, which indicated net entry of tCO2 against a concentration gradient. In this "symmetrical" perfusion situation, acetazolamide blockade prevented tCO2 entry. Accordingly: distal tubule tCO2 entry is demonstrable in both alkalotic and normal rats at high flow rates; increasing perfusate tCO2 concentration can suppress tCO2 entry; and entry can occur in the absence of a gradient and this effect can be blocked by acetazolamide.

Effect of metabolic acidosis on proximal tubular total CO2 absorption.

In vivo microperfusion studies of the proximal convoluted tubule of the rat were performed to determine the effect of metabolic acidosis on total CO2 (tCO2) absorption. In series I, tubular perfusion was performed in control and acidotic rats in a manner by which similar mean total CO2 concentrations in the proximal tubule were maintained. Comparable ranges of perfusion rate were studied in both groups. Following 3 days of HCl ingestion, plasma tCO2 was 20.0 +/- 0.9 mM in the acidotic rats whereas it was 29.6 +/- 0.53 mM in control rats. The arterial blood pH values were 7.25 +/- 0.02 vs. 7.43 +/- 0.01. Starting tCO2 perfusate concentrations were identical in both groups, 29.3 and 29.7 mM, as were the concentrations at the end of the perfused segments, 21.2 and 21.9 mM. The absorption of tCO2 (JtCO2, pmol X mm-1 X min-1) was significantly greater in the acidotic rats than in the controls, 576 +/- 39 vs. 256 +/- 21. At all perfusion rates studied, proximal tubular JtCO2 was higher in the acidotic than in the control rats. In series II, similar lengths of the late proximal tubule were perfused at the same rate in control and acidotic rats. Again, JtCO2 was higher in the acidotic rats, 352 +/- 19 vs. 198 +/- 13. The results indicate that at comparable luminal tCO2 concentration and tubular fluid flow rates, tCO2 absorption is significantly increased in the acidotic state. Although other mechanisms cannot be excluded, the finding of an increase in proximal tCO2 absorption in the acidotic rats is in agreement with the presence of an accelerated Na+/H+ exchange rate in brush border membrane vesicles obtained from the renal cortex of animals with metabolic acidosis.