Effects Of Acid-base Disturbances Research Articles

Intracellular pH regulation by acid-base transporters in mammalian neurons

Intracellular pH (pHi) regulation in the brain is important in both physiological and physiopathological conditions because changes in pHi generally result in altered neuronal excitability. In this review, we will cover 4 major areas: (1) The effect of pHi on cellular processes in the brain, including channel activity and neuronal excitability. (2) pHi homeostasis and how it is determined by the balance between rates of acid loading (JL) and extrusion (JE). The balance between JE and JL determine steady-state pHi, as well as the ability of the cell to defend pHi in the face of extracellular acid-base disturbances (e.g., metabolic acidosis). (3) The properties and importance of members of the SLC4 and SLC9 families of acid-base transporters expressed in the brain that contribute to JL (namely the Cl-HCO3 exchanger AE3) and JE (the Na-H exchangers NHE1, NHE3, and NHE5 as well as the Na+- coupled HCO3− transporters NBCe1, NBCn1, NDCBE, and NBCn2). (4) The effect of acid-base disturbances on neuronal function and the roles of acid-base transporters in defending neuronal pHi under physiopathologic conditions.

Effect of acid-base disturbances on aldosterone secretion in man.

The present study was carried out to elucidate whether changes in blood pH induced by administration of alkalinizing and acidifying agents influence aldosterone secretion in man. Since aldosterone secretion is known to be regulated by various factors such as the renin-angiotensin system, adrenocorticotropic hormone (ACTH), and serum potassium concentration, these indices were simultaneously measured during manipulation. Oral administration of tris hydroxymethyl aminomethane (THAM) resulted in a moderate but not significant decrease in serum aldosterone together with an increase in blood pH, whereas plasma renin activity (PRA) remained unchanged and serum potassium was elevated. ACTH and cortisol decreased significantly. Following CaCO3 ingestion, blood pH, serum potassium concentration, and hormones did not change significantly compared with before ingestion. NH4Cl ingestion showed a significant fall of blood pH and serum cortisol, on the other hand, aldosterone increased significantly compared with CaCO3 ingestion. Following NaHCO3 ingestion, serum aldosterone decreased with an increase in blood pH compared with before ingestion, while serum cortisol and PRA did not change significantly. The overall results of experiments using THAM, CaCO3, NaHCO3, and NH4Cl led to the conclusion that under acid-base disturbances a change in aldosterone can not be induced by either renin-angiotensin or ACTH. We suggest that under acid-base disturbances blood pH may be related, at least, in part to changes in aldosterone in humans.

Na+/H+ exchange in human lymphocytes and platelets in chronic and subacute metabolic acidosis.

The effect of acid-base disturbances on sodium/proton (Na+/H+) exchange has been examined in animal models; however, few data are available from human studies. To test the effect of metabolic acidosis on Na+/H+ exchange in man, as well as to examine the relationship between Na+/H+ exchange and cytosolic calcium ([Ca2+]i), we measured both variables in patients with decreased renal function with mild metabolic acidosis (pH 7.34 +/- 0.06), in normal control subjects (pH 7.41 +/- 0.02), and in subjects before (pH 7.40 +/- 0.01), and after (pH 7.26 +/- 0.04) ammonium chloride (NH4Cl) 15 g for 5 d. Lymphocytes and platelets were loaded with the cytosolic pH (pHi) indicator 2'-7'-bis(carboxyethyl)-5,6-carboxyfluorescein and acidified to pH approximately 6.6 with propionic acid. To quantitate Na+/H+ exchange, dpHi/dt was determined at 1 min. [Ca2+]i was measured with fura-2. Na+/H+ exchange was significantly increased only in lymphocytes of patients with renal insufficiency. Neither intracellular pH (pHi) nor [Ca2+]i was different from controls. NH4Cl resulted in a significant increase in Na+/H+ exchange in lymphocytes, but not in platelets of normal subjects. Values of pHi and [Ca2+]i in either cell type remained unaffected. Since metabolic acidosis influenced Na+/H+ only in lymphocytes, but not in platelets, it is possible that protein synthesis may be involved in increasing Na+/H+ exchange.

Effects of acid-base disturbances caused by differences in dietary fixed ion balance on kinetics of calcium metabolism in ruminants with high calcium demand.

Effects of subclinical metabolic acid-base disturbances, caused by dietary fixed ion imbalances on kinetics of calcium (Ca) metabolism were examined in eucalcemic caprine does (period 1) and does during simulated lactational Ca loss (period 2). In both experiments, Ca balance data and serial blood, fecal and urine samples were collected after an iv injection of 45Ca. In period 2, lactational Ca loss was simulated by continuous infusion of ethylene glycol-bis (beta-amino ethyl ether)N,N,N'N'-tetraacetic acid (EGTA) to standardize the loss of Ca among goats. The data were fit to a four-compartment model of Ca metabolism. In period 1, fixed anion excess, [sodium + potassium - chloride] = -2 meq/100 g diet dry matter (ANEX) increased urinary Ca excretion relative to fixed cation excess, [sodium + potassium - chloride] = 71 meq/100 g diet dry matter (CATEX). Consequently, rates of Ca absorption and resorption were elevated in goats made acidotic by dietary fixed anion excess. During period 2 (EGTA infusion), urinary Ca loss was elevated to similar levels in goats fed ANEX and CATEX, but Ca absorption remained higher in goats fed ANEX. Consequently, size of the exchangeable Ca pool, accretion rate and balance across bone were higher in these goats. Fixed anion excesses (found in corn silage and grains) cause subclinical metabolic acidosis, which elevates rates of Ca absorption but does not affect size of the exchangeable Ca pool. Fixed cation excesses (associated with diets containing alfalfa and buffers) cause subclinical metabolic alkalosis, which diminishes Ca absorption and urinary Ca excretion. Acidosis-induced hypercalciuria is the metabolic cost of maintaining high prepartum Ca absorption rates and high flux of Ca through the exchangeable Ca pool that may aid in adjustment to sudden Ca losses at parturition.

Effect of Acidosis and Alkalosis on Divalent Ion Transport across the Proximal Straight Tubule of the Rabbit

In vitro microperfusion experiments were performed on the cortical proximal straight tubule of the rabbit to examine the effect of acid base disturbances on calcium and magnesium transport by this segment of the nephron. During acidosis (pH 7.22 +/- 0.01) net calcium reabsorption was reduced, whereas during alkalosis (pH 7.82 +/- 0.02) net calcium reabsorption was increased. Our flux experiments with 45Ca indicate that the efflux of Ca from the lumen to the bath remained the same during acidosis; however, the back-flux (bath to lumen) of calcium increased. On the other hand, during alkalosis the efflux of calcium rose and the influx of calcium remained unchanged. These changes in fluxes during acid-base disturbances can be accounted for mainly by changes in ionized calcium as a result of pH changes. We failed to observe any effect of acid-base changes on net magnesium transport by the superficial proximal straight tubule.

Effects of acid-base disturbances on renal handling of magnesium in the dog.

Clearance and micropuncture studies were performed in four groups of acutely thyroparathyroidectomized animals to study the effects of alkalosis and acidosis on the renal handling of magnesium. Our results indicate that chronic metabolic acidosis reduces, whereas acute metabolic alkalosis enhances, magnesium reabsorption. The site within the nephron where absorption of magnesium increases or decreases during acid-base disturbances was beyond the late proximal tubule. Tubular fluid bicarbonate was also measured in these experiments, and the results indicated that magnesium reabsorption in the distal tubule correlated to bicarbonate delivery. However, whether this was a direct or an indirect effect of bicarbonate on magnesium transport could not be delineated.

Effects of acid base disturbances on basolateral membrane potential and intracellular potassium activity in the proximal tubule of Necturus.

The effects of extracellular acid-base disturbances on intracellular potential (Em) and potassium activity (aiK) in the early proximal tubule of Necturus were examined. Using conventional and double barreled potassium ion selective microelectrodes it was possible to measure both the transient and steady-state responses to various states of extracellular acidosis and alkalosis. The results show that (i) when extracellular [HCO-3] is varied at constant pCO2, Em and aiK decrease in acidosis and increase in alkalosis. The greatest sensitivity in Em is between pH 7.6 and 6.8 with apparent saturation above and below these extremes; (ii) decreased [HCO-3] at constant pH = 7.6 also causes a depolarization of Em and reduces aiK, suggesting a major effect of extracellular [HCO-3] on intracellular potential and aiK; (iii) rapid perfusions and transient delta Em analysis suggest a high basolateral conductance for K+ and HCO-3 and a low Cl- conductance; (iv) increasing extracellular [K+] decreases the response of both Em and aiK to reduced [HCO-3] at constant pCO2. The results of this study demonstrate the important role of extracellular pH and/or [HCO-3] on the maintenance of cellular K+ homeostasis.

Effects of acute acid-base disturbances on K+ delivery to the juxtamedullary end-descending limb

Effects of acute-base disturbances on fractional delivery of potassium to the juxtamedullary end-descending limb were examined by micropuncture in the rat to test the hypothesis that potassium is reabsorbed from the collecting duct and is secreted in juxtamedullary pars recta or descending limb in the renal medulla. In metabolic acidosis, fractional potassium delivery was only slightly reduced compared with control values and was a function of potassium excretion, as the hypothesis predicts. Fractional potassium delivery was sharply reduced both in respiratory acidosis and metabolic alkalosis and was no longer a function of potassium excretion. Although seemingly inconsistent with the recycling hypothesis, the latter finding may be reconciled by the following observations. In respiratory acidosis, vasa recta blood flow nearly doubled, which would lead to vascular washout of interstitial potassium. In metabolic alkalosis, flow rate in the pars recta or descending limb was reduced by 28%, which would limit transepithelial potassium addition. The results indicate complex effects of acid-base disturbances on fractional potassium delivery to the end-descending limb, which can be unified by postulated changes in transepithelial potassium concentration differences across the juxtamedullary pars recta or descending limb. An unexpected observation emerged--fractional delivery of water to the end-descending limb declined as a function of plasma bicarbonate concentration when all groups were combined.

Effect of acute metabolic acidosis on plasma phosphorus concentration.

The effects of acid-base disturbances on plasma phosphorus concentration remain poorly defined. In a previous study, we infused anesthetized mongrel dogs with several mineral and non-mineral acids for one to three hours. HCl and NH4Cl infusions were not associated with changes in plasma phosphorus in contrast to the findings with the organic acids lactic (LA) and beta-hydroxybutyric which increased, and methylmalonic which decreased phosphorus levels. To evaluate these observations further and to gain insight into the mechanism(s) involved we measured plasma phosphorus concentration and renal phosphorus handling in dogs infused with 0.45% NaCl (control), HCl and LA for six hours. In the control group there was no significant change in phosphorus levels whereas the increase in phosphorus concentration for LA was significant after hour four. Although with HCl, phosphorus concentration decreased in the first hour, there was a tendency for an elevation by five hours. Cumulative six hour UpV was significantly lower with HCl than with either LA or NaCl and the data suggest that the infusion of both acids may have blunted the augmentation of phosphorus excretion associated with mild volume expansion. Plasma glucose and insulin measured for three hours showed no significant differences between the groups.

The effects of acid-base disturbances on cardiovascular and pulmonary function

Disturbances in acid-base balance are commonly met problems in clinical medicine and decisions about their treatment are of great importance in patients with cardiopulmonary problems, in whom acid-base disturbances may be especially critical.Similarly, cardiopulmonary function may be significantly compromised even in patients with no intrinsic heart or lung disease, in the face of acid-base disturbances.It is essential, therefore, to understand the physiological consequences of these disturbances on the cardiovascular and pulmonary system. Of major importance is the effect of acid-base disturbances on the delivery of to the various tissue cells of the body.In order to understand all the pathophysiological mechanisms involved it is necessary to review the effects of acid-base changes on the heart, the peripheral vessels, the lungs, and the diffusion of between air, blood, and tissues. The requirement for by the various tissue cells of the body is met by the combined cardiovascular and pulmonary systems, which function as a unit termed the oxygen transport system of the body.The movement of from the ambient air to the tissue cells involves ventilation, pulmonary perfusion, diffusion, oxygen-carrying capacity of hemoglobin, cardiac output (including cardiac muscle performance), systemic distribution of flow, and finally the delivery capacity of hemoglobin.It is important to understand the effects of changes in pH on each of these steps in the chain.