Respiratory Acid-base Disturbances Research Articles

Physiological implications of ocean acidification for marine fish: emerging patterns and new insights.

Ocean acidification (OA) is an impending environmental stress facing all marine life, and as such has been a topic of intense research interest in recent years. Numerous detrimental effects have been documented in marine fish, ranging from reduced mortality to neurosensory impairment, and the prevailing opinions state that these effects are largely the downstream consequences of altered blood carbon dioxide chemistry caused by respiratory acid-base disturbances. While the respiratory acid-base disturbances are consistent responses to OA across tested fish species, it is becoming increasingly clear that there is wide variability in the degree of downstream impairments between species. This can also be extended to intraspecies variability, whereby some individuals have tolerant physiological traits, while others succumb to the effects of OA. This review will synthesize relevant literature on marine fish to highlight consistent trends of impairment, as well as observed interspecies variability in the responses to OA, and the potential routes of physiological acclimation. In all cases, whole animal responses are linked to demonstrated or proposed physiological impairments. Major topics of focus include: (1) respiratory acid-base disturbances; (2) early life survival and growth; (3) the implications for metabolic performance, activity, and reproduction; and (4) emerging physiological theories pertaining to neurosensory impairment and the role of GABAA receptors. Particular emphasis is placed on the importance of understanding the underlying physiological traits that confer inter- and intraspecies tolerance, as the abundance of these traits will decide the long-term outlook of marine fish.

Beyond bicarbonate: complete acid-base assessment in patients receiving intermittent hemodialysis.

Acid-base assessments in hemodialysis patients have been limited almost entirely to measurements of total CO 2 concentration, and assumptions have been made about the presence of acid-base disorders. To gain a fuller understanding of the acid-base status of stable hemodialysis patients, we analyzed measurements of pCO 2 , pH and HCO 3 - obtained in a cohort of chronic stable hemodialysis patients over a 5-year period. We reviewed acid-base measurements taken pre-dialysis from fistula blood in 53 outpatients receiving hemodialysis thrice weekly between 2008 and 2012. In these patients, pH and pCO 2 were measured using an onsite blood gas analyzer, and HCO 3 - was computed. Relevant clinical and laboratory data were obtained from medical records. Factors affecting serum HCO 3 - were identified. Simple and mixed acid-base disorders were diagnosed using accepted rules. Serum HCO 3 - was affected by age, normalized protein catabolic rate, interdialytic weight gain and length of interval between treatments. As expected, metabolic acidosis was the most common acid-base disorder, but respiratory acid-base disturbances, as simple or complex disorders, were found in 41% of the measurements. Respiratory alkalosis was seen more frequently than respiratory acidosis, but the latter disorder was more commonly associated with serious comorbidities. Respiratory acid-base disorders are an important component of the acid-base abnormalities seen in hemodialysis patients and are not identified by measuring total CO 2 concentration; hence, complete acid-base measurements are needed to determine the components of hemodialysis patients' acid-base status that are contributing to mortality risk.

Effect of water alkalinity on gill CO2 exchange and internal PCO2 in aquatic animals.

In addition to metabolic CO2 production and gill ventilatory flow rate, expired water PCO2 is very dependent on water acid-base balance in a complex way. This is particularly true in carbonated waters at low ambient PCO2 and high pH, where CO2 excreted in the gill water may be buffered by carbonate ions, leading to an increased CO2 capacitance coefficient. The higher the carbonate alkalinity (CA) and the lower the inspired PCO2 (i.e., the higher the inspired water pH), the stronger the carbonate buffering and the smaller the increase of PCO2 in the gill water during respiratory CO2 exchanges. As a consequence, as shown by a number of reported data, increasing the CA leads to blood hypocapnia and respiratory alkalosis at constant low, but not at high, inspired PCO2. In the low range of inspired PCO2, internal PCO2 becomes very sensitive to even small changes of water PCO2, which may explain at least in part the large variability of reported blood PCO2 values in gill breathers. Water CA also influences the amplitude of respiratory acid-base disturbances caused by changes of the gill ventilatory flow rate. Carbonate buffering of excreted CO2 and thus dependence of blood PCO2 on water alkalinity requires catalysis of CO2 hydration by carbonic anhydrase, that must be available from the water side of the gill epithelium.

Mechanisms of ion and acid-base regulation at the gills of freshwater fish.

This review examines the branchial mechanisms utilized by freshwater fish to regulate internal acid-base status and presents a model to explain the underlying basis of the compensatory processes. Rainbow trout, Oncorhynchus mykiss, and brown bullhead, Ictalurus nebulosus, were examined under a variety of experimental treatments which induced respiratory and metabolic acid-base disturbances. Acid-base regulation was achieved by appropriate adjustments of Na+ and Cl- net fluxes across the gills which, in turn, were accomplished by variable contributions of three different branchial mechanisms: 1) differential changes in Na+ and Cl- diffusive effluxes, 2) changes in internal substrate (H+, HCO3-) availability, and 3) morphological adjustments to the gill epithelium. Differential diffusive efflux of Na+ over Cl- was involved only during periods of metabolic alkalosis. The importance of internal substrate availability was demonstrated using a two-substrate model. According to the model, ionic flux rates (J(in)Cl-, J(in)Na+) are determined not only by the concentration of the external ion (Na+, Cl-) but also by the concentration of the internal counterion (H+, HCO3-). This system provides for an "automatic negative feedback" to aid in the compensation of metabolic acid-base disturbances. Morphological alteration of the gill epithelia and the associated regulation of chloride cell (CC) fractional area is an essential third mechanism which is especially important during respiratory acid-base disturbances. Specifically, fish vary the availability of the CC associated Cl-/HCO3- exchange mechanism by physical covering/uncovering of CCs by adjacent pavement cells.

Brain pH in acute isocapnic metabolic acidosis and hypoxia: a 31P-nuclear magnetic resonance study

It is well known that brain pH changes rapidly in acute hypercapnia or hypocapnia. The effect of acute isocapnic metabolic acid-base change on brain pH is less certain. To study this problem, acute isocapnic metabolic acidosis was induced by HCl or lactic acid infusions in rats, and recovery from acidosis was accomplished by NaHCO3 infusion. Brain pH was measured by 31P-nuclear magnetic resonance. Despite decreases in blood pH of 0.34 and 0.36 units, respectively, in less than 1 h of acid infusion and rapid recovery during bicarbonate infusion, brain pH was unaffected (ranging between 7.08 and 7.11) and was uncorrelated with blood pH. The blood pH minus brain pH gradient was eliminated by the acidosis. By contrast, hypoxia-induced endogenous lactic acidosis lowered blood and brain pH equivalently, but the fall in brain pH preceded that in blood. During normoxic recovery, brain pH overshot and became alkaline when blood pH was still significantly reduced and blood lactate levels were markedly elevated. Presumably, this is due to stimulated active H+ transport. The results demonstrate that brain pH is affected differently in metabolic, respiratory, and endogenous acid-base disturbances. Thus brain pH cannot be predicted solely from blood pH values.

Effects of erythrocytes, bicarbonate, temperature and albumin on in vitro ionized calcium variations with pH

Using a heart lung machine as an in vitro model, the relation between ionized calcium (cCa2+) and pH has been shown to depend on several variables such as erythrocytes, temperature and albumin as well as the total calcium and bicarbonate concentrations. The respiratory acid-base disturbances were simulated by changing the gas flow between 1.0 and 2.4 1 min-1 by adding CO2 to the machine at a concentration of 0 to 17%. When pCO2 was used to alter pH, cCa2+ varied from 0.16 mmol l-1 per pH unit to 0.52 mmol l-1. The regression slope of cCa2+ on pH was made steeper by decreasing erythrocyte volume fraction and by increasing temperature and the concentrations of HCO-3, calcium or albumin. The metabolic acid-base alterations were produced by HC1 or NaHCO-3 at a constant gas flow. cCA2+ changes per pH unit were 0.70 mmol 1-1 in plasma and 1.04 mmol l-1 in whole blood. The different results found in plasma and in erythrocyte fluids may be explained by their different buffering capacity. Haemoglobin may buffer hydrogen ions, and the formation of HCO is catalysed by carbonic anhydrase from the red cells.

Ketoacid production in acute respiratory and metabolic acidosis and alkalosis in rats.

Metabolic acidosis inhibits and alkalosis enhances ketoacid production in ketotic humans and animals. To compare these effects with those of superimposed respiratory acid-base disturbances, ketone output was evaluated in awake ketotic rats during metabolic (intravenous infusions of HCl or NaHCO3) or respiratory (hyper or hypocapnia) disorders. With decreases in blood pH of 0.1-0.2 units over 3 h, blood ketone concentrations significantly decreased an average of 1.9 mM (metabolic) and 1.1 mM (respiratory) and urinary ketone excretion rates significantly decreased by 1.3 mumol/min (metabolic). With increases in systemic pH, blood ketone concentrations and urinary ketone excretion rates were significantly increased. Changes in blood pH correlated with changes in urinary ketone excretion rates in both metabolic (r = 0.87) and respiratory (r = 0.67) acid-base disturbances. The alterations occurred promptly and were rapidly reversible. These findings indicate that modest changes in systemic pH from metabolic or respiratory acid-base disturbances modify net ketoacid production in ketotic rats, confirm pH control of endogenous acid output as an acid-base regulator, and show that systemic pH, not bicarbonate concentration, mediates the process.

Effects of erythrocytes, bicarbonate, temperature and albumin on in vitro ionized calcium variations with pH.

Using a heart lung machine as an in vitro model, the relation between ionized calcium (cCa2+) and pH has been shown to depend on several variables such as erythrocytes, temperature and albumin as well as the total calcium and bicarbonate concentrations. The respiratory acid-base disturbances were simulated by changing the gas flow between 1.0 and 2.41 min-1 by adding CO2, to the machine at a concentration of 0 to 17%. When pCO2 was used to alter pH, cCa2+ varied from 0.16 mmol l-1 per pH unit to 0.52 mmol l-1. The regression slope of cCa2+ on pH was made steeper by decreasing erythrocyte volume fraction and by increasing temperature and the concentrations of HCO3, calcium or albumin. The metabolic acid-base alterations were produced by HCl or NaHCO3 at a constant gas flow, cCA2+ changes per pH unit were 0.70 mmol l-1 in plasma and 1.04 mmol l-1 in whole blood. The different results found in plasma and in erythrocyte fluids may be explained by their different buffering capacity. Haemoglobin may buffer hydrogen ions, and the formation of HCO3- is catalysed by carbonic anhydrase from the red cells.

Epileptiform activity induced by alkalosis in rat neocortical slices: Block by antagonists of [formula omitted

The effects of changing extracellular pH on epileptiform activity induced by the removal of magnesium ions from the perfusing medium were studied. The proportion of bicarbonate in the artificial cerebrospinal fluid and of CO 2 in the gas mixture were altered to mimic metabolic and respiratory acid base disturbances. Changes in pH of 0.2 unit from control produced marked effects. Epileptiform activity was enhanced by alkalosis and diminished by acidosis. In normal magnesium-containing medium metabolic alkalosis (pH > 7.8) induced spontaneous epileptiform activity that was blocked by selective N- methyl- d-aspartate antagonists. The relevance of these findings to acid/base changes in clinical epilepsy is discussed.

Skeletal muscle oxygen availability during respiratory acid-base disturbances in cats

Respiratory acid-base disorders elicit physiological responses that alter O 2 delivery to various tissues. We have used a near infrared (NIR) optical technique to monitor cytochrome a, a 3 oxidation state, tissue O 2 store (relative hemoglobin plus myoglobin oxygenation), and regional blood volume in intact resting skeletal muscle during respiratory acid-base disturbances in anesthetized cats. Hypercapnic acidosis of hypercapnic alkalosis were produced in separate groups of animals by ventilation with increasing concentrations of CO 2 (n = 13) or hyperventilation (n = 8). Respiratory acidosis decreased oxygen availability to hindlimb muscle while respiratory alkalosis did not change tissue oxygenation. Inspired CO 2 progressively decreased muscle blood volume, cytochrome a, a 3 oxidation level, and muscle oxygen store. These optical responses were greatly attenuated both by pre-treatment with bretylium and by hemorrhagic hypotension, suggesting mediation through sympathetic vasoconstriction. Metabolic acidosis, produced by intravenous HCl infusion (n = 8), did not reproduce the hindlimb optical responses mediated by Co 2. These experiments demonstrate that hypercapnic acidosis significantly decreases oxygen supply to resting skeletal muscle in the anethetized cat, probably via neuroregulatory responses to CO 2 which do not depend on changes in arterial [H +] in tested pH range.

Skeletal muscle oxygen availability during respiratory acid-base disturbances in cats

Respiratory acid-base disorders elicit physiological responses that alter O 2 delivery to various tissues. We have used a near infrared (NIR) optical technique to monitor cytochrome a,a 3 oxidation state, tissue O 2 store (relative hemoglobin plus myoglobin oxygenation), and regional blood volume in intact resting skeletal muscle during respiratory acid-base disturbances in anesthetized cats. Hypercapnic acidosis and hypocapnic alkalosis were produced in separate groups of animals by ventilation with increasing concentrations of CO 2 (n = 13) or hyperventilation (n = 8). Respiratory acidosis decreased oxygen availability to hindlimb muscle while respiratory alkalosis did not change tissue oxygenation. Inspired CO 2 progressively decreased muscle blood volume, cytochrome a,a 3 oxidation level, and muscle oxygen store. These optical responses were greatly attenuated both by pre-treatment with bretylium and by hemorrhagic hypotension, suggesting mediation through sympathetic vasoconstriction. Metabolic acidosis, produced by intravenous HCl infusion (n = 8), did not reproduce the hindlimb optical responses mediated by CO 2. These experiments demonstrate that hypercapnic acidosis significantly decreases oxygen supply to resting skeletal muscle in the anesthetized cat, probably via neuroregulatory responses to CO 2 which do not depend on changes in arterial [H +] in the tested pH range.

Effect of systemic pH, PCO2 and bicarbonate concentration on biliary bicarbonate secretion in the rat.

The effect of acute metabolic or respiratory acid-base disturbances on biliary bicarbonate secretion was examined in bile fistula rats. Animals were infused with ursodeoxycholate at a rate that stimulates bicarbonate secretion (1 mumole . min-1 X 100 gm-1), in control conditions and during acute acid-base disturbances. Metabolic acidosis or alkalosis were induced by HCl or NaHCO3 infusions, and respiratory acidosis or alkalosis were created respectively by adding CO2 to the inspired gas or by hyperventilation in artificially ventilated animals. Biliary bicarbonate concentration was always higher than plasma bicarbonate concentration. During metabolic disturbances, changing the plasma bicarbonate concentration from 9.2 to 30.2 mM stimulated biliary bicarbonate secretion by 113%. During respiratory disturbances, changing the plasma PCO2 from 25.5 to 59.8 mm Hg also increased biliary bicarbonate secretion by 89%. Biliary bicarbonate output was thus independent of plasma pH. When all animals were considered, bile flow was positively correlated with biliary bicarbonate concentration (r = 0.71, p less than 0.001). Acetazolamide significantly decreased ursodeoxycholate-induced bile flow and bicarbonate secretion by 20 and 22%, respectively. These results support the hypothesis that there is a relationship between ursodeoxycholate-induced bicarbonate secretion and bile flow. They are also consistent with the view that ursodeoxycholate-stimulated biliary bicarbonate secretion in the rat is strongly affected by plasma bicarbonate and PCO2, but not by plasma pH, and involves carbonic anhydrase.

Der Säuren-Basen-Haushalt in der Anästhesiologie und operativen Intensivmedizin. Physiologie, Pathophysiologie und Klinik der Alkalosen und gemischten Störungen

This review details basic and clinical aspects of metabolic and respiratory alkalosis and mixed acid-base disturbances. New experimental results show that NH4Cl and arginine-HCl should no longer be used in antialkalotic therapy because they increase intracellular pH and have no effect on intracellular bicarbonate concentration. Appropriate HCl solutions should be employed in severe metabolic alkalosis because they reduce pH and the bicarbonate concentrations in both body compartments.

Acid-Base Regulation and Ion Transfers in the Carp (Cyprinus Carpio) During and After Exposure to Environmental Hypercapnia

ABSTRACT Acid-base balance and ion transfers were studied in the carp, Cyprinus carpio L., during and after 48 h of exposure to environmental hypercapnia ( Torr). Plasma pH, [HCO3−], and net transfers of HCO3−, NH4+, Cl− and Na+ between the fish and the environmental water were measured periodically throughout the experiment. Over the first 8 h of hypercapnia, plasma increased by 7·6 Torr with a concurrent decrease in plasma pH of 0·28 units. Plasma [HCO3−] was slowly elevated from about 14 to 22 mm after 48 h, at which point 50% of the pH depression expected at constant bicarbonate concentration had been compensated. The net amount of H+ transferred to the water was 3 ·3 mmol kg−1 fish, representing a 115 % increase in the rate of cumulative H+ efflux, and inducing an elevation of both intracellular and extracellular [HCO3−]. Cl− transfer was reversed from a net uptake to a net efflux, while net Na+ influx was increased slightly. Following hypercapnia, plasma pH returned to control values within 1 h, while the plasma [HCO3−], which was elevated during hypercapnia, fell continuously to reattain pre-hypercapnic control values after 20 h. The [HCO3−] decrease was due to the net gain of H+ ions from the water during this period. Cl− transfer returned to a net uptake, while the original Na+ influx was reversed to a net loss. Acid-base regulatory responses in the carp are qualitatively similar to those observed in other fish, though the time required for compensatory pH adjustment is longer. It is concluded that alterations in the rates of Cl −/HCO3− and Na+/H+ exchanges during hypercapnia and Na+/H+ exchange following hypercapnia, play a significant role in the compensation of respiratory acid-base disturbances in these animals.

Clinical Approach to Patients with Acid-Base Disorders

Simple relationships that hold during compensation for metabolic or respiratory acid-base disturbances have been emphasized. When considered by the physician, they should allow for the interpretation and diagnosis of both simple and mixed disturbances. Since the correct diagnosis of an acid-base disturbance is central to initiation of correct therapy, these considerations are not merely academic exercises but are essential steps to follow in careful management. Table 6 summarizes the stepwise approach to diagnosis of an acid-base disorder. Application of these principles in a routine fashion combined with a careful history and physical examination often results in the successful diagnosis of complicated disturbances. Understanding of the pathophysiologic derangements in each specific disorder is necessary for full appreciation of acid-base balance in disease.

Effect of ischemia, hypertrophy, hypoxia, acidosis, and alkalosis on canine defibrillation.

Our purpose was to assess the effect of myocardial ischemia, left ventricular hypertrophy, and systemic hypoxia and acid-base abnormalities on the energy requirements for defibrillation. We determined the defibrillation threshold (DFT), the minimum energy required to defibrillate. DFT was not significantly elevated after left anterior descending coronary occlusion, nor was there a relationship between the size of the occluded coronary distribution area (coronary risk area) and the change in DFT in individual animals. Renal hypertension and left ventricular hypertrophy were induced by unilateral nephrectomy and contralateral renal artery stenosis. DFT in left ventricular hypertrophy dogs was not significantly higher than in dogs without hypertrophy. Finally, we induced systemic hypoxia and acid-base abnormalities. Neither respiratory nor metabolic acid-base disturbances affected DFT, but during systemic hypoxia (O2 tension 45 +/- 2) DFT fell from 83 +/- 49 to 58 +/- 28 J (P less than 0.01). Thus in dogs, myocardial ischemia, left ventricular hypertrophy, and acid-base abnormalities do not elevate defibrillation energy requirements, whereas hypoxia reduces the energy needed to defibrillate.

Influence of steady-state alterations in acid-base equilibrium on the fate of administered bicarbonate in the dog.

Previous workers have shown that metabolic acidosis increases the apparent space through which administered bicarbonate is distributed. This finding has been ascribed to the accompanying acidemia and to the consequent availability of a large quantity of hydrogen ion that accumulates on nonbicarbonate tissue buffers during the development of acidosis. To test this hypothesis, bicarbonate space was measured in dogs with a broad range of steady-state plasma [HCO-3] in association with alkalemia as well as with acidemia. Appropriate combinations of pH and plasma [HCO-3] were achieved by pretreating the animals to produce graded degrees of each of the four cardinal, chronic acid-base disorders. Metabolic acidosis (n = 15) was produced by prolonged HCl-feeding; metabolic alkalosis (n = 17) by diuretics and a chloride-free diet; and respiratory acidosis (n = 9) and alkalosis (n = 8) by means of an environmental chamber. Animals with normal acid-base status (n = 4) were also studied. Sodium bicarbonate (5 mmol/kg) was infused over 10 min to the unanesthetized animals; observations were carried out over 90 min. The results obtained from animals with metabolic acid-base disturbances demonstrated an inverse relationship between bicarbonate space and initial plasma pH, confirming the previous findings of others. By contrast, the results obtained in animals with respiratory acid-base disturbances demonstrated a direct relationship between bicarbonate space and initial plasma pH. The pooled data revealed that bicarbonate space is, in fact, quite independent of the initial pH but is highly correlated with the initial level of extracellular [HCO-3]; dogs with low extracellular [HCO-3] (congruent to 10 meq/liter) whether acidemic or alkalemic, have a bicarbonate space that is 25% larger than normal and some 50% larger than in dogs with high extracellular [HCO-3] (congruent to 50 meq/liter). We conclude from these results that the increased bicarbonate space in metabolic acidosis (and respiratory alkalosis) does not reflect the availability of more hydrogen ions for release during bicarbonate administration, but merely evidences the wider range of titration (delta pH) of nonbicarbonate buffers that occurs during alkali loading whenever plasma [HCO-3] is low.

Regulatory processes of metabolic and respiratory acid-base disturbances in embryos.

First, preliminary experiments were designed in the 16-day-old individual chick embryo to elucidate the effect of electrolyte infusion and blood samplings on hemodilution, which might influence the acid-base balance. Three kinds of hemodilution were observed: 1) hemodilution caused by four repetitive samplings, which had no influence on acid-base balance; 2) hypervolumic hemodilution caused by infusion of solution whose volume equaled about 5-6% of total blood volume, which induced dilution acidosis; and 3) hypertonic hemodilution caused by hypertonic electrolyte infusion, which also induced dilution acidosis. The embryo recovered from the hypertonic dilution acidosis in 6 h after infusion, but it did not recover from hypervolumic acidosis. Second, the time course of changes in metabolic and respiratory acid-base disturbances was studied in the individual embryo. Metabolic acid-base disturbances made by hypertonic NaHCO3 infusion were restored to control state in 6 h. Respiratory acid-base disturbances were also regulated in terms of changes in plasma[HCO-3] and pH. The renal function and redistribution of HCO-3 may in part be responsible for the regulation.

Interregional differences in brain intracellular pH and water compartmentation during acute normoxic and hypoxic hypocapnia in the anesthetized dog

Interregional differences in intracellular pH (pH i) in brain tissue, and its regulation following 1 and 5 h of respiratory alkalosis (with and without hypoxemia) were determined in N 2O anesthetized dogs. Two techniques for pH i estimation were used (T co 2 and 14C-DMO) and included corrections for measured extracellular fluid ( 35SO 4 2−) space (ECS). Cortical pH i by the two techniques agreed closely in control and in 3 of the 4 experimental conditions, suggesting: (a) our estimation of extracellular fluid (ECF) [HCO 3 −] from measured CSF [HCO 3 −] was a valid ssumption; and (b) our method had sufficient resolution to determine the magnitude of brain pH i regulation during respiratory acid-base disturbances. When moderate normoxic respiratory alkalosis (PaCO 2 ≈ 25 mm Hg) was imposed for 5 h, pH i (in most brain regions) was well regulated and always exceeded the incomplete regulation noted in bulk CSF. When moderate hypoxemia (PaO 2 ≈ 45 mm Hg) accompanied hypocapnia, pH i was more closely regulated during the early phase (1 h) of respiratory alkalosis. Increased levels of metabolic acids (especially lactic acid) were critical to brain pH i regulation during the initial hour of respiratory alkalosis and accounted for much of the independent effect of hypoxemia on pH i regulation. However, these metabolic acids remained unchanged as pH i was more completely regulated between 1 and 5 h of continued hypocapnia or hypoxic hypocapnia. This time-dependent tregulation of pH i may involve some regulatory role for changed transmembrane fluxes of H + and/or HCO 3 −. Significant interregional differences were observed in both pH i and in ECS; with tendencies toward more alkaline pH i and lower ECS in brain stem and white matter. With respiratory alkalosis ECS fell and intracellular fluid increased in both cortex and caudate nucleus, possibly reflecting an osmotic effect of increased metabolic acid levels or reduction in cell membrane ion pumping.

Compensation of diffusive respiratory disturbances of the acid-base balance in the chick embryo

1. 1. Blood buffer line and time course of the change in respiratory acid-base disturbances of chick embryos were determined. 2. 2. At 10–30 min of disturbances, the acid-base status of arterialized blood shifted along the buffer line. Then, it moved along a pCO 2 isopleth to a direction to compensate for pH. 3. 3. In the respiratory alkalosis, plasma [HCO 3 −] was decreased in excess of that accounted for by blood buffer value, and in the acidosis it was increased. 4. 4. Compensation was incomplete: its end value was attained within 3 hr after onset of the disturbances. 5. 5. Allantoic fluid pCO 2 was changed in parallel with a change in blood pCO 2.