Changes in the levels of various substrates of nitrogen metabolism and tricarboxylic acid cycle during experimental acidosis in calves

The effect of experimental metabolic acidosis and its correction for nitrogen and energy metabolism was studied in new-born calves. It was discovered that a change in the acid-base balance towards acidosis causes a sharp increase in "ammoniogenesis", urea formation and inhibition of the tricarboxylic acid cycle, which is also observed in calves suffering from dyspepsia with symptoms of acute diarrhea. Alongside with the use of therapeutic measures for treating dyspepsia of new-born calves, it is necessary to control the acid-base balance of blood in the calves and in case of revealing the acidosis state to use means of its correction.     

Basis for indicators of acid-base status of blood and metabolic processes in rats under hibernation and under trivial analgesia for foreleg amputation

The article deals with some data on investigation of the blood acid-base balance main blood indices and metabolic processes in the rats organism under the artificial hibernation and trivial anesthesia at the foreleg amputation. This model of the artificial hibernation was shown as capable to be promising the hard and complicated operative intrusions in the organism.     

Carbonic anhydrase 5 regulates acid-base homeostasis in zebrafish

The regulation of the acid-base balance in cells is essential for proper cellular homeostasis. Disturbed acid-base balance directly affects cellular physiology, which often results in various pathological conditions. In every living organism, the protein family of carbonic anhydrases regulate a broad variety of homeostatic processes. Here we describe the identification, mapping and cloning of a zebrafish carbonic anhydrase 5 (ca5) mutation, collapse of fins (cof), which causes initially a collapse of the medial fins followed by necrosis and rapid degeneration of the embryo. These phenotypical characteristics can be mimicked in wild-type embryos by acetazolamide treatment, suggesting that CA5 activity in zebrafish is essential for a proper development. In addition we show that CA5 regulates acid-base balance during embryonic development, since lowering the pH can compensate for the loss of CA5 activity. Identification of selective modulators of CA5 activity could have a major impact on the development of new therapeutics involved in the treatment of a variety of disorders.     

Acid-base balance and urinary acidification in birds

This essay will treat, first, the defended parameters of acid-base status in avian blood and their modification under conditions pertinent to the life of birds, and, second, urinary acidification and its role in maintenance of acid-base balance. Of the two topics, urinary acidification is of particular interest to the author, has received less sustained attention experimentally and has been infrequently reviewed (Sykes, 1971), so it will receive attention here. The reports cited in the essay concern primarily adult birds outside periods of egg-laying.     

Acid-base status of the blood and adenine nucleotide metabolism in ruminant erythrocytes during early post-natal development]

It has been established that data of acid-base balance in cows' and newborn calves' blood closely correlate with physiological status of animals during their initial days of postnatal ontogenesis and depend on the peculiarities of metabolism in fetus and newborn organisms. Data on the acid-base balance in blood of newborn calves under diarrhea syndrome are discussed from the point of view of the influence of rehydration therapy and "Namacit" preparation on clinical status of animals.     

Concept of the "physiological age" of animals and its application to ixodid ticks

The definition "physiological age" of animals has been revised. A new definition has been formulated on the basis of V. N. Beklemishev's (1962) and Ju. S. Balashov's (1962) theses as follows: physiological age of animals (= biological) is an extent of general irreversible morphophysiological change of organism during its whole life and determined by the accumulation of irreversible changes as a result of its normal vital activity. This definition is equivalent to that of "biological ages" of man. The contents of this definition is enlarged and the possibility of its use for different animals including their males is unified. On the basis of the general concept this definition is specified in regard to ixodid ticks: physiological age of hungry ixodid tick is an extent of general irreversible morpholophysiological change of its organism during the whole life and determined by the state of reserve nutrient and excretory substances. According to the amount of reserve and excretory substances in the organism of ixodid tick we distinguish 4 main physiological ages: new-born, young, mature and old which reflect general biological regularity of age development of animals.     

Physiological role of carbonic anhydrase isozymes and their distribution in ruminant gastrointestinal tract

New data on physical-chemical characteristics, biochemical properties and functional specificity of carbonic anhydrase isozymes of human and animals are reviewed. The recent literature information about the tissue composition and regional distribution of isozymes of carbonic anhydrase in the ruminant gastrointestinal tract is generalized. The participation of carbonic anhydrase isozymes in the regulation of acid-base balance in the organism of ruminants is considered.     

Metabolic system of acid-base homeostasis in the human and animal body

Peculiarities of carbohydrate, lipid, amino acid nucleotide metabolism, of the tricarboxylic acid cycle functioning and of the oxidative phosphorylation have been studied in man and animals under conditions of changes in the acid-base equilibrium (ABE) state in the organism. The results of studies are analyzed and generalized. Strictly defined peculiarities of changes in the mentioned aspects of metabolism depending on the ABE state in the organism are revealed. Basing on a new interpretation of the experimental data and detected regularities in the metabolism, the author has drawn a conclusion on the existence of the previously unknown system of acid-base homeostasis in tissues. The physiological sense of this system functioning is the regulation of the intracellular acid-base equilibrium stability. The regulation mechanisms promoting functioning of this system are discussed. The system is shown to be of great applied significance for improvement of methods to cure a number of human and animal diseases as well as for an increase of the productivity of animals.     

Intracellular pH regulation and metabolic interactions in hepatic tissues.

Intracellular pH (pHi) regulation in the vertebrate liver relies heavily on ionic transport mechanisms. Liver, in common with many tissues, has plasma membrane Na(+)-H+ and Cl(-)-HCO3- electroneutral exchangers which work in opposition to tightly control pHi. Mammalian livers also possess electrogenic Na(+)-HCO3- exchangers, capable of base uptake, which, when coupled to pHi-mediated changes in membrane potential, probably confer an additional measure of pHi control, compared to fish livers, where the transporter appears to be functionally absent. It is suggested that this may be a fundamental difference between aquatic and aerial breathing. pHi regulation has barely been examined in invertebrate hepatic tissues, but already some interesting differences are apparent. Notably, an electrogenic 2Na(+)-1H+ acid-extrusion system is present in apical membranes of crustacean hepatopancreas. Despite these ionic control systems, complex acid-base disturbances (e.g., "metabolic" acidosis) have been known for some time to influence hepatic metabolism in vertebrates, but few studies have carefully examined the independent effects of the acid-base variables involved. Thus mechanistic explanations for the effects of acid-base disturbances are scarce. Ureogenesis in mammals has been well studied, and several pH-related mechanisms are evident. In contrast, the pH-insensitivity of ureogenesis in fish liver may represent a second difference between aquatic and terrestrial species. In summary, by virtue of its metabolic diversity, liver represents a potentially important organ in acid-base balance, and an interesting study tissue for interrelationships between metabolism and acid-base balance.     

Acid-base regulation in fishes: cellular and molecular mechanisms

The mechanisms underlying acid-base transfers across the branchial epithelium of fishes have been studied for more than 70 years. These animals are able to compensate for changes to internal pH following a wide range of acid-base challenges, and the gill epithelium is the primary site of acid-base transfers to the water. This paper reviews recent molecular, immunohistochemical, and functional studies that have begun to define the protein transporters involved in the acid-base relevant ion transfers. Both Na(+)/H(+) exchange (NHE) and vacuolar-type H(+)-ATPase transport H(+) from the fish to the environment. While NHEs have been thought to carry out this function mainly in seawater-adapted animals, these proteins have now been localized to mitochondrial-rich cells in the gill epithelium of both fresh and saltwater-adapted fishes. NHEs have been found in the gill epithelium of elasmobranchs, teleosts, and an agnathan. In several species, apical isoforms (NHE2 and NHE3) appear to be up-regulated following acidosis. In freshwater teleosts, H(+)-ATPase drives H(+) excretion and is indirectly coupled to Na(+) uptake (via Na(+) channels). It has been localized to respiratory pavement cells and chloride cells of the gill epithelium. In the marine elasmobranch, both branchial NHE and H(+)-ATPase have been identified, suggesting that a combination of these mechanisms may be utilized by marine elasmobranchs for acid-base regulation. An apically located Cl(-)/HCO(3)(-) anion exchanger in chloride cells may be responsible for base excretion in fresh and seawater-adapted fishes. While only a few species have been examined to date, new molecular approaches applied to a wider range of fishes will continue to improve our understanding of the roles of the various gill membrane transport processes in acid-base balance.     

Channels, pumps, and exchangers in the gill and kidney of freshwater fishes: their role in ionic and acid-base regulation

In freshwater fishes, the gill and kidney are intricately involved in ionic and acid-base regulation owing to the presence of numerous ion channels, pumps, or exchangers. This review summarizes recent developments in branchial and renal ion transport physiology and presents several models that integrate epithelial ion and acid-base movements in freshwater fishes. At the gill, three cell types are potentially involved in ionic uptake: pavement cells, mitochondria-rich (MR) PNA(+) cells, and MR PNA(-) cells. The transfer of acidic or basic equivalents between the fish and its environment is accomplished largely by the gill and is appropriately regulated to correct acid-base imbalances. The kidney, while less important than the gill in overall acid or base excretion, has an essential role in regulating systemic acid-base balance by controlling HCO(3) (-) reabsorption from the filtrate.     

Role of acid-base balance in the chemoreflex control of breathing.

This paper uses a steady-state modeling approach to describe the effects of changes in acid-base balance on the chemoreflex control of breathing. First, a mathematical model is presented, which describes the control of breathing by the respiratory chemoreflexes; equations express the dependence of pulmonary ventilation on Pco(2) and Po(2) at the central and peripheral chemoreceptors. These equations, with Pco(2) values as inputs to the chemoreceptors, are transformed to equations with hydrogen ion concentrations [H(+)] in brain interstitial fluid and arterial blood as inputs, using the Stewart approach to acid-base balance. Examples illustrate the use of the model to explain the regulation of breathing during acid-base disturbances. They include diet-induced changes in sodium and chloride, altitude acclimatization, and respiratory disturbances of acid-base balance due to chronic hyperventilation and carbon dioxide retention. The examples demonstrate that the relationship between Pco(2) and [H(+)] should not be neglected when modeling the chemoreflex control of breathing. Because pulmonary ventilation controls Pco(2) rather than the actual stimulus to the chemoreceptors, [H(+)], changes in their relationship will alter the ventilatory recruitment threshold Pco(2), and thereby the steady-state resting ventilation and Pco(2).     

Relation between pH and the strong ion difference (SID) in body fluids

Acid-base balance evaluation according to the Henderson-Hasselbalch equation enable us to assess the contribution of respiratory (pCO2) and/or non-respiratory (metabolic, HCO3(-)) components to the acid-base balance status. A new approach to acid-base balance evaluation according to Stewart-Fencl, which is based on a detailed physical-chemical analysis of body fluids shows that metabolic acid-base balance disorders are characterized not only by [HCO3(-)]. According to this concept independent variables must be taken into an account. The abnormality of concentration of one or more of the independent variable(s) determines the pH of a solution. The independent variables are: 1. strong ion difference (SID); 2. total concentration of nonvolatile weak acids [A(tot)]; 3. in agreement with the Henderson-Hasselbalch concept also pCO2. Traditional evaluation of acid-base balance disorders is based on the pH of body fluids (though pH may be within normal range if several acid-base balance disturbances are present). In order to maintain this view and simultaneously to respect the Stewart-Fencl principle, we invented a new equation, which uses only the independent variables to define the pH of body fluids. This analysis shows that for a given value of pCO2, the pH of body fluids is determined by a difference between SID and [A(tot)-]. pH = 6.1 + log((SID - [A(tot)-])/(0.03pCO2)) or in itemized form: pH = 6.1 + log((([Na+] + [K+] + [Ca2+] + [Mg2+] - [Cl-] - [UA-]) - (k1[Alb] + k2[P(i)]))/(0.03 x pCO2)). Evaluation of the individual components of this equation enables us to detect, which of the independent variable (or a combination of independent variables) deviates from the normal range and therefore which one or ones is a cause of the acid-base balance disorder. At the end of this paper we give examples of a practical application of this equation.     

Decrease in N-ethylmaleimide-sensitive ATPase activity in collecting duct by metabolic alkalosis

Changes in systemic acid-base balance are known to influence acidification in the collecting duct. The H+ secretion in the collecting duct has been shown to be an electrogenic process and it has been suggested that an H-ATPase sensitive to inhibition by N-ethylmaleimide (NEM) is responsible for H+ secretion. This study was designed to determine the effect of metabolic alkalosis on NEM-sensitive ATPase activity in the microdissected segments of the distal nephron. Metabolic alkalosis was produced by giving NaHCO3 to normal rats for 7 days. The plasma total CO2 concentration in the experimental group was 31.5 +/- 1.8 mM compared with 23.4 +/- 1.0 mM in the control group. NEM-sensitive ATPase activity was significantly lower in the cortical collecting duct and in the outer and inner medullary collecting ducts of alkali-loaded rats than those of control rats. There was no significant difference in the enzyme activity between the two groups of animals in the other nephron segments examined. Our results suggest that NEM-sensitive H-APTase activity in all three segments of the collecting duct is modulated by the acid-base status of the animal.     

Co-expression of pendrin, vacuolar H+-ATPase alpha4-subunit and carbonic anhydrase II in epithelial cells of the murine endolymphatic sac.

The endolymph in the endolymphatic sac (ES) is acidic (pH 6.6-7). Maintaining this acidic lumen is believed to be important for the normal function of the ES. The acid-base regulation mechanisms of the ES are unknown. Here we investigated the expression patterns of acid-base regulators, including vacuolar (v)H+-ATPase (proton pump), carbonic anhydrase (CA) II, and pendrin in the murine ES epithelium by immunohistochemistry (IHC) and compared their expression patterns by double immunostaining. We found that pendrin and vH+-ATPase were co-localized in the apical membrane of a specific type of ES epithelial cell. Pendrin- and vH+-ATPase-positive cells also expressed cytoplasmic CA II. Co-expression of pendrin, vH+-ATPase, and CA II in the same subgroup of ES cells suggests that this specific type of ES cell is responsible for the acid-base balance processes in the ES and pendrin, vH+-ATPase, and CA II are involved in these processes.     

Interactions Between Transcutaneous Ion Transfer Processes and Carbon Dioxide Excretion in Amphibians

SYNOPSIS. The amphibian skin possesses a wide variety of physiologicalfunctions in that it constitutes not only the major organ forrespiratory CO₂ exchange but also plays important roles forionic as well as osmotic balance. Apart from the simple transcutaneousdiffusion of CO₂ down its partial pressure gradient, acid-baserelevant ion exchange mechanisms in the skin may also be importantin overall pH regulation in these animals. The skin of somefrogs, for example, contains mechanisms for the exchange ofNa^$/H^$ and HCO₃^–/Cl^– in which NaCl is actively transportedinto the animal in exchange for H^$ and HCO₃^–. While suchexchange mechanisms have often been studied in the context ofosmoregulation in freshwater environments, their potential importancein acid-base regulation have been largely unexplored. The presentpaper reviews the evidence for participation of cutaneous iontransfer mechanisms in the overall regulation of CO₂ excretionand acid-base balance in amphibians.     

CO2 mass transfer and acid-base balance under conditions of muscular activity at sea level and in the mountains

The state of the blood acid-base balance and dynamics of carbonic acid gas mass transfer were studied in sportsmen at the sea level and in mountains. It is shown that at the sea level due to an intensive muscular activity large amounts of CO2 are formed and excreted; the mass transfer of this gas is multiply accelerated, simultaneously, a pronounced decompensated metabolic acidosis is observed which in some cases is complicated respiratory acidosis. The similar exercises in mountains are followed by a more pronounced disturbance in the acid-base balance and a more intensified mass-transfer of CO2. After 12-day acclimatization and training in mountains the buffer blood capacity increases, the metabolic acidosis under conditions of muscular activity is less pronounced.     

A comparison between the effects of cold exposure in vivo and of noradrenaline in vitro on the metabolism of the brown fat of new-born rabbits

1. Exposure of new-born rabbits to the cold leads to an increase in the incorporation of [(14)C]glucose into the glycerol of brown-fat triglyceride, but has no effect on [(14)C]glucose incorporation into triglyceride of white fat or liver. The effect of cold exposure on brown-fat triglyceride is abolished by cutting the cervical sympathetic nerve. 2. Brown fat incorporates very little [(14)C]glucose into triglyceride fatty acids, either in vivo or in vitro. 3. Noradrenaline added to incubations of brown fat from new-born rabbits stimulates O(2) consumption, CO(2) output and incorporation of glucose into triglyceride glycerol. The effects of noradrenaline in vitro are therefore consistent with the hypothesis that noradrenaline mediates the response of the brown fat of new-born rabbits to cold exposure. 4. Glycerokinase is present in the brown fat of new-born rabbits, but its activity is much less than that of the glycerokinase in the brown fat of adult rats. 5. Insulin has no effect on O(2) consumption, CO(2) output or glucose uptake in brown fat of new-born rabbits. 6. It is concluded that the thermogenic response of new-born rabbits to cold exposure is accompanied by a selective acceleration of the triglyceride cycle in brown fat. However, resynthesis of triglyceride would not account for more than 1% of the O(2) consumed in vitro by new-born rabbit brown fat in the presence of noradrenaline if respiration remains coupled to phosphorylation.     

The oxygen regime and acid-base status of the blood in the irradiated body

Radiation-induced changes in the oxygen regime and acid-base balance in the blood are a direct function of radiation dose. Superlethal doses have been shown to cause the development of tissue hypoxia and metabolic acidosis at early times after irradiation.