potassium-bicarbonate and Acidosis

Low-grade metabolic acidosis (LGMA), as induced by high dietary acid load or sodium chloride (NaCl) intake, has been shown to increase bone and protein catabolism. Underlying mechanisms are not fully understood, but from clinical metabolic acidosis interactions of acid-base balance with glucocorticoid (GC) metabolism are known. We aimed to investigate GC activity/metabolism under alkaline supplementation and NaCl-induced LGMA. Eight young, healthy, normal-weight men participated in two crossover designed interventional studies. In Study A, two 10-day high NaCl diet (32 g/d) periods were conducted, one supplemented with 90 mmol KHCO3/day. In Study B, participants received a high and a low NaCl diet (31 vs. 3 g/day), each for 14 days. During low NaCl, the diet was moderately acidified by replacement of a bicarbonate-rich mineral water (consumed during high NaCl) with a non-alkalizing drinking water. In repeatedly collected 24-h urine samples, potentially bioactive-free GCs (urinary-free cortisol + free cortisone) were analyzed, as well as tetrahydrocortisol (THF), 5α-THF, and tetrahydrocortisone (THE). With supplementation of 90 mmol KHCO3, the marker of total adrenal GC secretion (THF + 5α-THF + THE) dropped (p = 0.047) and potentially bioactive-free GCs were reduced (p = 0.003). In Study B, however, GC secretion and potentially bioactive-free GCs did not exhibit the expected fall with NaCl-reduction as net acid excretion was raised by 30 mEq/d. Diet-induced acidification/alkalization affects GC activity and metabolism, which in case of long-term ingestion of habitually acidifying western diets may constitute an independent risk factor for bone degradation and cardiometabolic diseases.

Topics: Acid-Base Equilibrium; Acidosis; Adult; Alkalies; Bicarbonates; Cortisone; Cross-Over Studies; Diet; Drinking Water; Glucocorticoids; Humans; Hydrocortisone; Male; Potassium Compounds; Sodium Chloride; Tetrahydrocortisol; Tetrahydrocortisone; Young Adult

Low-grade metabolic acidosis, consecutive to excessive catabolism of sulfur amino acids and a high dietary Na:K ratio, is a common feature of Western food habits. This metabolic alteration may exert various adverse physiological effects, especially on bone, muscle and kidneys. To assess the actual effects of various K salts, a model of the Westernised diet has been developed in rats: slight protein excess (20 % casein); cations provided as non-alkalinising salts; high Na:K ratio. This diet resulted in acidic urine (pH 5.5) together with a high rate of divalent cation excretion in urine, especially Mg. Compared with controls, K supplementation as KCl accentuated Ca excretion, whereas potassium bicarbonate or malate reduced Mg and Ca excretion and alkalinised urine pH (up to 8). In parallel, citraturia was strongly increased, together with 2-ketoglutarate excretion, by potassium bicarbonate or malate in the diet. Basal sulfate excretion, in the range of 1 mmol/d, was slightly enhanced in rats fed the potassium malate diet. The present model of low-grade metabolic acidosis indicates that potassium malate may be as effective as KHCO3 to counteract urine acidification, to limit divalent cation excretion and to ensure high citrate concentration in urine.

Topics: Acidosis; Amino Acids, Sulfur; Ammonia; Animals; Bicarbonates; Calcium; Diet; Dietary Supplements; Eating; Magnesium; Malates; Male; Potassium; Potassium Chloride; Potassium Compounds; Rats; Rats, Wistar; Sodium; Sulfates; Urination; Weight Gain

The Cl(-)/HCO(3)(-) exchanger AE2 is believed to be involved in transcellular bicarbonate reabsorption that occurs in the thick ascending limb of Henle's loop (TAL). The purpose of this study was to test whether chronic changes in acid-base status and sodium intake regulate AE2 polypeptide abundance in the TAL of the rat. Rats were subjected to 6 d of loading with NaCl, NH(4)Cl, NaHCO(3), KCl, or KHCO(3). AE2 protein abundance was estimated by semiquantitative immunoblotting in renal membrane fractions isolated from the cortex and the outer medulla of treated and control rats. In the renal cortex, AE2 abundance was markedly increased in response to oral loading with NH(4)Cl or with NaCl. In contrast, AE2 abundance was unchanged in response to loading with KCl or with NaHCO(3) and was decreased by loading with KHCO(3). The response of AE2 in the outer medulla differed from that in the cortex in that HCO(3)(-) loading increased AE2 abundance when administered with Na(+) but had no effect when administered with K(+). Immunohistochemistry revealed that NaCl loading increased AE2 abundance in the basolateral membrane of both the cortical and the medullary TAL. In contrast, NH(4)Cl loading increased AE2 abundance only in the cortical TAL but not in the medullary TAL. These results suggest that regulation of the basolateral Cl(-)/HCO(3)(-) exchanger AE2 plays an important role in the adaptation of bicarbonate absorption in the TAL during chronic acid-base disturbances and high sodium intake. The present study also emphasizes the contribution of cortical TAL adaptation in the renal regulation of acid-base status.

Topics: Acid-Base Equilibrium; Acidosis; Administration, Oral; Alkalosis; Ammonium Chloride; Animals; Anion Transport Proteins; Antiporters; Bicarbonates; Down-Regulation; Immunohistochemistry; Kidney Cortex; Kidney Medulla; Loop of Henle; Male; Potassium Chloride; Potassium Compounds; Rats; Rats, Sprague-Dawley; SLC4A Proteins; Sodium; Sodium Bicarbonate; Sodium Chloride

Topics: Acidosis; Bicarbonates; Calcium, Dietary; Female; Humans; Hypocalcemia; Male; Osteoporosis; Osteoporosis, Postmenopausal; Potassium Compounds; Risk Factors; Vitamin D

CO2 chemoreception may be mediated by the modulation of certain ion channels in neurons. Kir4.1 and Kir5.1, two members of the inward rectifier K+ channel family, are expressed in several brain regions including the brainstem. To test the hypothesis that Kir4.1 and Kir5. 1 are modulated by CO2 and pH, we carried out experiments by expressing Kir4.1 and coexpressing Kir4.1 with Kir5.1 (Kir4.1-Kir5. 1) in Xenopus oocytes. K+ currents were then studied using two-electrode voltage clamp and excised patches. Exposure of the oocytes to CO2 (5, 10 and 15 %) produced a concentration-dependent inhibition of the whole-cell K+ currents. This inhibition was fast and reversible. Exposure to 15 % CO2 suppressed Kir4.1 currents by approximately 20 % and Kir4.1-Kir5.1 currents by approximately 60 %. The effect of CO2 was likely to be mediated by intracellular acidification, because selective intracellular, but not extracellular, acidification to the measured hypercapnic pH levels lowered the currents as effectively as hypercapnia. In excised inside-out patches, exposure of the cytosolic side of membranes to solutions with various pH levels brought about a dose-dependent inhibition of the macroscopic K+ currents. The pK value (-log of dissociation constant) for the inhibition was 6.03 in the Kir4.1 channels, while it was 7.45 in Kir4.1-Kir5.1 channels, an increase in pH sensitivity of 1.4 pH units. Hypercapnia without changing pH did not inhibit the Kir4.1 and Kir4.1-Kir5.1 currents, suggesting that these channels are inhibited by protons rather than molecular CO2. A lysine residue in the N terminus of Kir4.1 is critical. Mutation of this lysine at position 67 to methionine (K67M) completely eliminated the CO2 sensitivity of both the homomeric Kir4. 1 and heteromeric Kir4.1-Kir5.1. These results therefore indicate that the Kir4.1 channel is inhibited during hypercapnia by a decrease in intracellular pH, and the coexpression of Kir4.1 with Kir5.1 greatly enhances channel sensitivity to CO2/pH and may enable cells to detect both increases and decreases in PCO2 and intracellular pH at physiological levels.

Topics: Acidosis; Animals; Bicarbonates; Brain Chemistry; Carbon Dioxide; Female; Gene Expression; Hydrogen-Ion Concentration; Hypercapnia; Ion Channel Gating; Lysine; Membrane Potentials; Mutagenesis, Site-Directed; Neurons; Oocytes; Patch-Clamp Techniques; Potassium Channels; Potassium Channels, Inwardly Rectifying; Potassium Compounds; Protons; Xenopus laevis

Previously we demonstrated that low grade chronic metabolic acidosis exists normally in humans eating ordinary diets that yield normal net rates of endogenous acid production (EAP), and that the degree of acidosis increases with age. We hypothesize that such diet-dependent and age-amplifying low grade metabolic acidosis contributes to the decline in skeletal muscle mass that occurs normally with aging. This hypothesis is based on the reported finding that chronic metabolic acidosis induces muscle protein breakdown, and that correction of acidosis reverses the effect. Accordingly, in 14 healthy postmenopausal women residing in a General Clinical Research Center and eating a constant diet yielding a normal EAP rate, we tested whether correcting their "physiological" acidosis with orally administered potassium bicarbonate (KHCO3; 60-120 mmol/day for 18 days) reduces their urinary nitrogen loss. KHCO3 reduced EAP to nearly zero, significantly reduced the blood hydrogen ion concentration (P < 0.001), and increased the plasma bicarbonate concentration (P < 0.001), indicating that pre-KHCO3, diet-dependent EAP was significantly perturbing systemic acid-base equilibrium, causing a low grade metabolic acidosis. Urinary ammonia nitrogen, urea nitrogen, and total nitrogen levels significantly decreased. The cumulative reduction in nitrogen excretion was 14.1 +/- 12.3 g (P < 0.001). Renal creatinine clearance and urine volume remained unchanged. We conclude that in postmenopausal women, neutralization of diet-induced EAP with KHCO3 corrects their preexisting diet-dependent low grade metabolic acidosis and significantly reduces their urinary nitrogen wasting. The magnitude of the KHCO3-induced nitrogen-sparing effect is potentially sufficient to both prevent continuing age-related loss of muscle mass and restore previously accrued deficits.

Topics: Acidosis; Aged; Bicarbonates; Female; Humans; Hydrogen-Ion Concentration; Middle Aged; Nitrogen; Postmenopause; Potassium Compounds; Quaternary Ammonium Compounds; Urea; Urine

Topics: Acidosis; Bicarbonates; Bone and Bones; Female; Humans; Hydrogen-Ion Concentration; Male; Osteoporosis; Osteoporosis, Postmenopausal; Potassium Compounds

The partial replacement of casein by a mixture of gelatin, fish protein and soy protein in cholesterol-free semipurified diets of rabbits reduced the hypercholesterolemic response. The partial replacement of casein by the protein mixture also increased the feed intake and alleviated or reversed the weight loss observed from the casein diet. The data indicate that casein alone is not an ideal protein source for rabbits probably because of the imbalance of the amino acid composition. When KCl in the semipurified diets was replaced by KHCO3, a higher feed intake and a better growth were obtained, irrespective of the protein source in the diet. In addition, the feeding of semipurified diets containing KCl resulted in acidosis, which could be prevented by its replacement with KHCO3. A semipurified diet containing casein and KCl produced a more severe acidosis and higher serum cholesterol levels than the diet containing the protein mixture. Nevertheless, the correction of the acidosis by the replacement of KCl in the diet by KHCO3 did not lead to an abrogation of the casein-induced hypercholesterolemia.

Topics: Acidosis; Amino Acids; Animals; Bicarbonates; Body Weight; Caseins; Diet; Dietary Proteins; Eating; Fishes; Gelatin; Glycine max; Hypercholesterolemia; Male; Potassium Chloride; Potassium Compounds; Rabbits

Topics: Acidosis; Animals; Bicarbonates; Caseins; Dietary Proteins; Fat Emulsions, Intravenous; Lipids; Male; Potassium Chloride; Potassium Compounds; Rabbits