Faculty Bibliography

Disorders of systemic acid-base balance have recently been shown to markedly alter intestinal electrolyte transport. These studies were based on earlier acid balance studies in humans and animals, data suggesting the presence of intestinal mucosal Na+-H+ and Cl-HCO-3 exchange processes and the reported effects of acid-base variables on other epithelia. In vivo studies have shown that intestinal net sodium and chloride absorption is markedly affected by systemic pH and carbon dioxide tension (Pco2). Specifically, systemic acidemia (in the rat ileum) and hypercapnia (in the rat colon) increase sodium and chloride absorption, while alkalemia and hypocapnia decrease absorption. In addition, net bicarbonate secretion (in both segments) varies directly with the plasma HCO3 concentration. The rabbit ileum has been studied both in vivo and in vitro and is affected in a similar way. The rat jejunum and rabbit distal colon and gallbladder do not respond to changes in blood pH and Pco2, consistent with the apparent absence of a mucosal Na+-H+ exchange process in these segments. Evidence suggests important roles for cellular carbonic anhydrase activity and the intracellular concentrations of hydrogen, bicarbonate, and calcium ions and calcium-calmodulin in mediating or modulating the effects of the systemic acid-base disorders. In addition, systemic pH may alter the effects of the neural and humoral mediators of intestinal transport

To determine the relative effects of systemic pH, PCO2, and bicarbonate concentration on colonic electrolyte transport, states of acute metabolic acidosis and alkalosis were created in Sprague-Dawley rats by gavage feeding (NH4)2SO4 and NaHCO3, respectively. During in situ perfusion of the distal colon in pentobarbital-anesthetized animals, electrolyte transport was measured before and after respiratory compensation of the systemic pH. Acute respiratory acidosis and alkalosis also were studied by ventilating animals with 0, 3, or 8% CO2. When animals in all groups were considered, net sodium absorption correlated well with blood PCO2 (r = 0.99) but not with blood pH. Net bicarbonate secretion correlated with the plasma (r = 0.95) and luminal (r = -0.63) bicarbonate concentrations but not with blood pH or PCO2. Net chloride absorption correlated with both blood PCO2 (r = 0.92) and the plasma bicarbonate concentration (r = 0.80). These results suggest that systemic PCO2 affects a sodium chloride absorptive process and that the plasma bicarbonate concentration affects a chloride absorptive-bicarbonate secretory exchange process in the rat colon

To examine the nature of the electroneutral sodium chloride absorptive process affected by arterial carbon dioxide tension (PCO2), we measured the effects of amiloride on colonic sodium absorption at concentrations (0.75 mM) known to inhibit cell membrane sodium-hydrogen ion exchange. During sequential in situ perfusions of distal colon with amiloride-free and amiloride-containing solutions, water and electrolyte transport was measured in anesthetized, mechanically ventilated rats during normocapnia, respiratory alkalosis, or respiratory acidosis. During amiloride-free perfusions, alkalosis decreased and acidosis increased net water, sodium, and chloride absorption without changing the transmural potential difference. Perfusion of amiloride (0.75 mM) caused a similar fractional decrease in net sodium absorption in alkalotic (-53.3 +/- 10.2%), normocapnic (-46.3 +/- 6.5%), and acidotic rats (-57.2 +/- 5.2%). Net water (-43%) and chloride absorption also exhibited equivalent fractional reductions in the three acid-base states during amiloride perfusion, although net chloride absorption was reduced only about 20%. These results suggest that the specific colonic sodium absorptive process affected by arterial PCO2 is an amiloride-sensitive, sodium-hydrogen ion exchange process. Arterial PCO2 probably also affects a mucosal chloride-bicarbonate exchange process that results in its overall effect on electroneutral sodium chloride absorption by the distal colon

The mechanism of the increase in luminal CO2 tension (PCO2) that accompanies jejunal HCO-3 absorption is unknown. One possibility is that mucosal metabolism and the reaction of absorbed HCO-3 with blood buffers in mucosal capillaries govern luminal PCO2. To evaluate this possibility, jejunal segments of anesthetized adult male Sprague-Dawley rats were perfused in vivo with modified Ringer solutions with varying PCO2 levels (0-141 mmHg). Arterial PCO2 was varied by mechanical ventilation (20-70 mmHg). The net flux of CO2 gas into bulk luminal fluid varied directly with the transmucosal PCO2 gradient both in the absence (r = 0.98, P less than 0.001) and presence of net HCO-3 absorption (r = 0.97, P less than 0.001). The apparent permeability coefficient for CO2 gas across the jejunal mucosa was relatively low (2 X 10(-4) cm3 X s-1 X cm length -1) and was not affected by net HCO-3 absorption. Under conditions of equal arterial blood and perfusate PCO2 levels (40 mmHg), the PCO2 in mucosa and effluent was 51 and 44 mmHg, respectively, in the absence and 62 and 48 mmHg, respectively, in the presence of net HCO-3 absorption. These results suggest that CO2 diffuses from the mucosal region into bulk liminal fluid during net HCO-3 absorption in the rat jejunum. In addition, we found in vitro that the elevation of mucosal PCO2 above arterial PCO2 during net HCO-3 absorption can be quantitatively accounted for by metabolism and the admixture of absorbed HCO-3 with blood buffers

Acute respiratory alkalosis and acidosis alter rat ileal and colonic but not jejunal electrolyte transport. To examine the role of altered intracellular pH, pHi, and HCO3 concentration, (HCO3)i, we measured pHi in mucosa scraped from the jejunum, ileum, and colon of anesthetized, mechanically ventilated Sprague-Dawley rats. During states of respiratory alkalosis (Pco2 24.9 +/- 0.8 mmHg, pH 7.586 +/- 0.014), respiratory acidosis (Pco2 67.8 +/- 1.2 mmHg, pH 7.228 +/- 0.007), and normocapnia (Pco2 41.1 +/- 0.7 mmHg, pH 7.401 +/- 0.006), pHi was measured by determining the distribution of 5,5-dimethyl[2-14C]oxazolidine-2,4-dione, using [3H]inulin as a marker of extracellular space. (HCO3)i was calculated using portal vein Pco2. In the ileum, the pHi of 6.901 +/- 0.029 was similar in alkalosis [(HCO3)i 5.4 +/- 0.3 mM], acidosis [(HCO3)i 12.4 +/- 0.6 mM], and normocapnia [(HCO3)i 8.6 +/- 0.8 mM). In both the jejunum and colon, pHi was increased in alkalosis [pHi 6.998 +/- 0.038, (HCO3)i 6.7 +/- 0.6 mM] and decreased in acidosis [pHi 6.789 +/- 0.024, (HCO3)i 10.4 +/- 0.6 mM] as compared with normocapnia [pHi 6.915 +/- 0.026, (HCO3)i 8.9 +/- 0.7 mM] (colon data given). Net electrolyte transport measured by in vivo perfusion revealed that ileal and colonic, but not jejunal, net Na and Cl absorption was decreased during alkalosis and increased during acidosis. These data suggest that, during respiratory acidosis and alkalosis, pHi is maintained in a qualitatively similar way in the jejunum, ileum, and colon with quantitatively greater or lesser changes in (HCO3)i.(ABSTRACT TRUNCATED AT 250 WORDS)