Decrease In HCO3 Research Articles

The conductance properties of Asp555 in the electrogenic Na/HCO3 cotransporter SLC4A4/NBCe1

The electrogenic Na/HCO3 cotransporter SLC4A4 (NBCe1) is important for HCO−3 reabsorption in the proximal tubules of the kidney. By sequence comparison between electrogenic transporters and electroneutral transporters, we previously identified Asp555 in NBCe1 as a residue that affects electrogenic HCO−3 current. In this study, we further characterized the HCO−3 conductance of the mutant transporter D555E (substitution of Asp555 with a Glu) using two‐electrode voltage clamp. In oocytes expressing D555E, the application of CO2/HCO−3 caused a negative shift of the reversal potential for HCO−3 current. However, the current progressively decreased at positive voltages that otherwise should be favorable for HCO−3 conductance. The current was larger at negative voltages. No inward current was produced at low [Na+]o that should reverse the direction of Na+/HCO−3 movement as in wild type NBCe1. In the steady state condition, which was achieved by superfusing oocytes with Na+‐free CO2/HCO−3 for 15 min, the application of a series of [Na+]o produced HCO−3 currents. The half maximum effective concentration of external Na+ was 2 mM for D555E, significantly smaller than 12 mM for wild type NBCe1. The substitution of Asp555 with an Asn (D555N) produced a progressive decrease in HCO−3 current at positive voltages and a negative shift of the reversal potential for the current. Reciprocal substitutions of Glu742 in the electroneutral Na/HCO3 cotransporter SLC4A7 (NBCn1) with Asp or Gln failed to produce electrogenic HCO−3 current. We conclude that the steric properties near Asp555 in NBCe1 likely contribute to ion translocation of the transporter.

The Glutamate Substitution of Aspartate555 of the Electrogenic Sodium/Bicarbonate Cotransporter NBCe1 Alters Bicarbonate Selectivity

To examine the structural requirements for electrogenicity of the sodium/bicarbonate cotransporter NBCe1, we mutated amino acid resides, in transmembrane domains, that are least conserved between electrogenic Na/HCO3 transporters and electroneutral Na/HCO3 transporters. Among these mutants, D555E (substitution of Asp555 with a Glu) had a significant decrease in HCO3 − conductance. Immunocytochemistry showed a strong fluorescence labeling in plasma membranes of oocytes expressing D555E. In 5% CO2/26 mM HCO3−, oocytes expressing D555E recovered intracellular pH from an acidification and produced an outward current comparable to ~25% of the current in oocytes expressing wild type NBCe1. Na+ removal in the continued presence of CO2/HCO3− reversed intracellular pH recovery and reduced the current. However, the current upon Na+ or HCO3− removal was no less than the initial current produced in CO2/HCO3−-free solution. The D555E-mediated conductance was significantly reduced by Cl− removal, indicating that D555E can transport Cl−. Anion substitution showed that oocytes expressing D555E had relatively weak HCO3−selectivity, producing currents with other monovalent anions. Substituting Asp555 with an Asn affected in the reversal potential of the HCO3−currents with negligible change in the conductance. We conclude that Asp555 is involved in anion selectivity of NBCe1.

Endothelin and nitric oxide mediate adaptation of the cortical collecting duct to metabolic acidosis

Endothelin (ET) and nitric oxide (NO) modulate ion transport in the kidney. In this study, we defined the function of ET receptor subtypes and the NO guanylate cyclase signaling pathway in mediating the adaptation of the rabbit cortical collecting duct (CCD) to metabolic acidosis. CCDs were perfused in vitro and incubated for 3 h at pH 6.8, and bicarbonate transport or cell pH was measured before and after acid incubation. Luminal chloride was reversibly removed to isolate H(+) and HCO(3)(-) secretory fluxes and to raise the pH of beta-intercalated cells. Acid incubation caused reversal of polarity of net HCO(3)(-) transport from secretion to absorption, comprised of a 40% increase in H(+) secretion and a 75% decrease in HCO(3)(-) secretion. The ET(B) receptor antagonist BQ-788, as well as the NO synthase inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME), attenuated the adaptive decrease in HCO(3)(-) secretion by 40%, but only BQ-788 inhibited the adaptive increase in H(+) secretion. There was no effect of inactive d-NAME or the ET(A) receptor antagonist BQ-123. Both BQ-788 and l-NAME inhibited the acid-induced inactivation (endocytosis) of the apical Cl(-)/HCO(3)(-) exchanger. The guanylate cyclase inhibitor LY-83583 and cGMP-dependent protein kinase inhibitor KT-5823 affected HCO(3)(-) transport similarly to l-NAME. These data indicate that signaling via the ET(B) receptor regulates the adaptation of the CCD to metabolic acidosis and that the NO guanylate cyclase component of ET(B) receptor signaling mediates downregulation of Cl(-)/HCO(3)(-) exchange and HCO(3)(-) secretion.

Cyclosporin A produces distal renal tubular acidosis by blocking peptidyl prolyl cis-trans isomerase activity of cyclophilin.

Cyclosporin A (CsA), a widely used immunosuppressant, causes distal renal tubular acidosis (dRTA). It exerts its immunosuppressive effect by a calcineurin-inhibitory complex with its cytosolic receptor, cyclophilin A. However, CsA also inhibits the peptidyl prolyl cis-trans isomerase (PPIase) activity of cyclophilin A. We studied HCO(3)(-) transport and changes in beta-intercalated cell pH on luminal Cl(-) removal in isolated, perfused rabbit cortical collecting tubules (CCDs) before and after exposure to media pH 6.8 for 3 h. Acid incubation causes adaptive changes in beta-intercalated cells by extracellular deposition of hensin (J Clin Invest 109: 89, 2002). Here, CsA prevented this adaptation. The unidirectional HCO(3)(-) secretory flux, estimated as the difference between net flux and that after Cl(-) removal from the lumen, was -6.7 +/- 0.2 pmol.min(-1).mm(-1) and decreased to -1.3 +/- 0.2 after acid incubation. CsA in the bath prevented the adaptive decreases in HCO(3)(-) secretion and apical Cl(-):HCO(3)(-) exchange. To determine the mechanism, we incubated CCDs with FK-506, which inhibits calcineurin activity independently of the host cell cyclophilin. FK-506 did not prevent the acid-induced adaptive decrease in unidirectional HCO(3)(-) secretion. However, [AD-Ser](8) CsA, a CsA derivative, which does not inhibit calcineurin but inhibits PPIase activity of cyclophilin A, completely blocked the effect of acid incubation on apical Cl(-):HCO(3)(-) exchange. Acid incubation resulted in prominent "clumpy" staining of extracellular hensin and diminished apical surface of beta-intercalated cells [smaller peanut agglutinin (PNA) caps]. CsA and [AD-Ser](8) CsA prevented most hensin staining and the reduction of apical surface; PNA caps were more prominent. We suggest that hensin polymerization around adapting beta-intercalated cells requires the PPIase activity of cyclophilins. Thus CsA is able to prevent this adaptation by inhibition of a peptidyl prolyl cis-trans isomerase activity. Such inhibition may cause dRTA during acid loading.

Metabolic Acidosis in a Pediatric Patient Receiving Topiramate

Topiramate is an anticonvulsant that is labeled for the management of several seizure types in children >2 years of age. With the exception of cognitive dysfunction, nephrolithiasis, weight loss, and paresthesia, adverse effects in children are similar to other those noted with other anticonvulsants. We describe a 33-month-old child with complex partial seizures and secondary generalization who received topiramate 45 mg orally twice daily (6.2 mg/kg/d) for approximately 4 weeks before admission. He developed asymptomatic metabolic acidosis that was evidenced by a decrease in HCO(3) (-), which was unresponsive to treatment with sodium bicarbonate. The child was weaned off topiramate and the metabolic acidosis resolved 48 hours after its discontinuation.

Water Diuresis Promotes Urine Acidification with Decreases in HCO3- Concentration

It is known that the reabsorption of filtered HCO3-depends on the tubular flowrate in the proximal uniferous tubule. In animal experiments, studies have demonstratedthat, when diuresis was induced, the pH of the collecting duct urine decreased, resulting from the decrease in HCO3-concentration with no change in the pCO2 level.The present study was designed to examine changes in urine acidification in humansunder a water diuretic state. Urine pH, pCO2 levels, and HCO3-concentration weremeasured before and after the drinking of water. In 120 minutes after hydration, theurine pH level fell about 0.5 pH unit from that before the intake of water. The urine HCO3-concentration coincidentally decreased significantly. However, pCO2 values remainedunchanged. These results indicated that also in humans, water diuresis promotesurine acidification, resulting from a decrease in HCO3-concentration with nochange in the pCO2 level, which may contribute to the prevention of the loss of plasmaHCO3-into the urine when the urine flow rate increases.

Topiramate and metabolic acidosis in pediatric epilepsy.

Topiramate (TPM) has been widely used as an adjunctive therapy for treating epilepsy. TPM is reported to have multiple mechanisms of action, including inhibition of carbonic anhydrase, which may result in metabolic acidosis from decreased serum bicarbonate (HCO3-). Clinical data from 30 children who received TPM as adjunctive therapy for medically refractory epilepsy were reviewed at Children's Hospital, Boston. Serum HCO3- levels were assessed before, during, and after discontinuing TPM (n = 9). When multiple data were available, mean values were used for analysis. Of the 30 patients, 21 had a >10% decrease in HCO3- levels. The mean decrease in HCO3- among the 21 patients was 4.7 mEq/L, and maximum was 10 mEq/L. No clinical symptoms occurred, and HCO3- supplement was not needed, except for one patient who developed tachypnea from worsened acidosis after prolonged status epilepticus during a suspected viral illness. Among the 21 patients, TPM was discontinued in seven children because of a lack of efficacy, and in two because of anorexia. After discontinuing TPM, the serum HCO3- returned to the previous level before starting TPM in all nine. Decreased HCO3- levels occurred in the majority of patients reviewed, usually only to a small to moderate extent, but by 8 and 10 mEq/L in two cases. In patients at risk for acidosis, the decrease in HCO3- may cause significant consequences, such as severe acidosis or renal calculi. Monitoring HCO3- levels before and during TPM therapy may be indicated, especially with conditions that predispose to acidosis.

Plasticity of Intercalated Cell Polarity: Effect of Metabolic Acidosis

The cortical collecting duct (CCD) is capable of secreting H⁺ or HCO^–₃ depending on the acid-base status in vivo. Transport is a function of two types of intercalated cells in the CCD: A-intercalated cells secrete H⁺ and B-intercalated cells secrete HCO^–₃. Metabolic acidosis results in a decrease in HCO^–₃ secretion and an increase in H⁺ secretion by the respective cells. Using a model of metabolic acidosis in vitro, we have shown that the down-regulation of HCO^–₃ secretion occurs by endocytosis of apical anion exchangers in B-intercalated cells. The finding of basolateral anion exchangers in some adapted B-intercalated cells is consistent with a reversal of functional epithelial polarity. Plasticity of polarity is also observed in cultured intercalated cells: high-density plating results in converting B- to A-intercalated cells via the deposition of the novel protein hensin in the extracellular matrix. A key problem in renal physiology is to investigate the role of hensin in mediating the adaptation of the CCD to acidosis in vitro and in vivo.

Zinc toxicity in the fish Cnesterodon decemmaculatus in the Paraná River and Río de La Plata Estuary

Acute static tests were performed to assess Zn toxicity on adults of Cnesterodon decemmaculatus (not sexed), a neotropical fish of wide distribution in the Río de la Plata basin. Tests were carried out with ZnCl 2 dissolved in natural waters from the Lower Paraná River, the Río de la Plata Estuary, reconstituted waters of similar composition, tap and distilled waters. Median lethal concentration at 24 h was positively correlated to conductivity and the concentrations of Ca 2+, Mg 2+, and HCO − 3 ( r = 0.99, 0.96, 0.97, 0.99, p < 0.05, respectively), being higher at the Río de la Plata Estuary (61.2 mg l −1) than at the Lower Paraná River (35.3 mg l −1). Contaminant load in the natural waters tested was similar at both sites, being Zn concentration 40 and 44 μg l −1, respectively. An assay with reconstituted water of similar alkalinity to the estuary showed a simultaneous decrease in HCO − 3 and dissolved Zn, while the Zn speciation, predicted with a computer program, suggested that Zn 2+ precipitated as ZnCO 3. The effect of Ca 2+ on Zn toxicity is also discussed. Zn toxicity was higher in the Río de la Plata Estuary water than in synthetic water of similar ionic composition (24-h LC50 = 93.2 mg l −1), suggesting the synergistic effect of other toxic pollutants such as metals, present in the former which were absent in the later.

Maps of hco+ Emission in c/1995 o1 (Hale–Bopp)

On-the-Fly maps of emission from the HCO+ J = 3-2 transition at 267.6 GHz were obtained of C/1995 O1 (Hale-Bopp) on 1997 Mar 15.6 UT using the NRAO 12-m telescope with high spatial resolution. Unlike the relatively symmetric and centralized maps of the neutral species CO, HCN and H2CO, the spatial extent of HCO+ emission is very diffuse with a complex structure characterized by at least two physically different regions. The bulk of the HCO+ emission peaks in intensity ∼175,000 km anti-sunward from the nuclear position. This peak emission does not fall directly along the anti-sunward direction, but is rotated by ∼10 degrees toward the east from the anti-sunward direction. A substantial void, or decrease, of HCO+ emission is observed within ∼ 55,000 km of the nucleus. The HCO+ emission in this void is roughly half the intensity of the emission observed 100,000 km away. This decrease of HCO+ emission near the nucleus may indicate that production or excitation of HCO+ is inhibited, or perhaps that HCO+ is easily destroyed in the inner coma, especially within ∼50,000 km of the nucleus. This void roughly coincides with the approximate location and size of the so-called “diamagnetic cavity” in the coma and may mark a significant transition region in the inner coma of Hale-Bopp

Respiratory, acid-base and ion status during voluntary immersion of the air-breathing crab Cardisoma carnifex assessed in situ

The respiratory haemolymph gas and acid-base state of the crab Cardisoma carnifex during submersion were investigated in situ on the Cocos (Keeling) Islands. Crab burrows less than 90 cm deep contained no water. Burrow water was brackish, between 60 and 370 mOsm osmotic pressure but C. carnifex was observed to voluntarily immerse in 50% seawater. Post-pulmonary haemolymph O 2 partial pressure and content were reduced after 30 min submergence. The internal hypoxia was accompanied by a severe hypercapnic acidosis exacerbated by a lactacidosis after 30 min in water. This haemolymph acidosis caused a decrease in Hc-O 2 affinity such that the in vivo P 50 increased from 6 to 18 torr, which further decreased O 2 transport. During submersion C. carnifex released minimal amounts of air from the branchial chambers. A trapped air-bubble represents a finite O 2 source and CO 2 sink and could thus account for the hypercapnic hypoxia. The haemolymph osmotic pressure of C. carnifex taken from burrows among the trees and sand flat margins ranged from 699 to 803 mOsm whereas those sampled on the sand flats on their way to immerse in saltwater had lower osmotic pressure, between 678 to 687 mOsm. While there was no correlation between burrow water osmotic pressure and that of the haemolymph it is possible that the crabs make periodic forays to salt water to replenish haemolymph ions. C. carnifex occasionally immerses itself but it is an air-breather and not a truly amphibious crabs. C. carnifex do not require water for respiratory and acid-base homeostasis and thus, further studies must examine in more detail ionic and water balance in field situations.

Photolysis of glyoxal at 193, 248, 308 and 351 nm

The UV photochemistry of glyoxal in nitrogen has been investigated by employing excimer laser photolysis at 193, 248, 308 and 351 nm in combination with cavity ring-down spectroscopy. The HCO radical was a photofragmentation product with yields of 0.42 ± 0.21, 0.53 ± 0.24, 0.69 ± 0.29, and 1.5 ± 0.6 at 193, 248, 308 and 351 nm. The larger than unity HCO yield at 351 nm suggests the photolysis channel (CHO) 2 + hv (351 nm) → 2 HCO. The decrease in HCO yields at higher photolysis photon energies is attributed to the opening up of additional glyoxal photolysis pathways.

Acute mild hypothermia in awake unrestrained rats induces a mixed acid-base disorder.

The interactions between components that contribute to acid-base homeostasis were studied in the first steps of acute hypothermia [body temperature (Tb) 37-31 degrees C] in awake unrestrained rats as an experimental model of accidental hypothermia in mammals. The concurrent changes in blood gases, plasma ions, and plasma protein concentrations in arterial blood were analyzed. Acute decreases in Tb decreased PCO2 and increased pH. The ratio of Na+ concentration to Cl- concentration increased at 35-33 degrees C Tb, leading to an increase in the plasma strong ion difference ([SID]). These increases were transient, and levels returned to baseline at lower Tb (31 degrees C). Lack of change in hematocrit, hemoglobin, plasma osmolality, or plasma protein concentration indicated stability in plasma volume. Therefore, [SID] changes were related to ionic shifts with respect to the extravascular space and not to ionic depletion. A feasible role in this ionic exchange for contracting skeletal muscle during shivering thermogenesis is given. Significant decrease in HCO3- concentration at lower Tb (31 degrees C) was related to an apparent increase in relative ventilation (lung ventilation per unit of CO2 removed). It is concluded that, during the first stages of body cooling, the blood acid-base status of conscious hypothermic rats is affected by PCO2 changes, apparently because of uncoupled changes between ventilation and metabolism, but it is also affected by a transitory metabolic disorder due to ion imbalance.

Renal tubular acidosis in the Silver-Russell syndrome.

Several patients with the Silver-Russell syndrome (SRS) attending our Genetics Clinic were diagnosed as having persistent metabolic acidosis. Since this abnormality has not been reported previously in the SRS, we reexamined 33 SRS patients to evaluate the frequency and type of metabolic acidosis, the clinical and laboratory findings, and the growth pattern in SRS patients with and without metabolic acidosis. Among them, 14 had a consistent decrease in HCO3- levels. Renal studies in acidotic patients showed urine pH of 5.8 and 24 h urine calcium of < 2.4 mg/kg/24 h; serum creatinine, excretion of glucose, and amino acids were normal, as were renal ultrasound and excretory urography findings. These data supported the diagnosis of renal tubular acidosis, probably type II; the patients were treated with oral bicarbonate and acidosis was corrected successfully. Clinical manifestations were similar in acidotic and non-acidotic patients. The nutritional indices at diagnosis and at last evaluation (at least 8 months after diagnosis) were abnormally low in all patients; however, acidotic patients, treated with bicarbonate, showed an improvement of nutritional status particularly in the weight/height index, although the difference between groups after follow-up did not reach statistical significance. We suggest that metabolic acidosis due to renal tubular acidosis, probably type II, may occur in children with the SRS and should be looked for and treated in all patients.

Pitting Corrosion of Pipeline Steel in Dilute Bicarbonate Solution with Chloride Ions

Abstract Corrosion behavior of grade 550 (X-80) pipeline steel with coating disbondments was studied in a range of bicarbonate (HCO3−) solutions using a potentiodynamic polarization technique. Corrosion morphology of the steel was examined using optical and scanning electron microscopy. The shape of the polarization curves and the sensitivity of the steel to pitting corrosion varied with HCO3− concentration. Increases in HCO3− concentration resulted in a wider passive region and a more noble breakdown potential (Eb), resulting in greater resistance to pitting corrosion. Surface morphology showed no pit formation in solutions with HCO3− concentration > 0.05 M, but pits developed at a concentration of 0.05 M. Size and density of corrosion pits increased with further decreases in HCO3− concentration. The graph of corrosion potential (Ecorr) vs HCO3− concentration showed a peak at 0.05 M, whereas the corrosion current density increased monotonically with increased HCO3− concentration. Low concentrations of ch...

Effects of Acute Hyperventilation on Serum Potassium in the Dog

The effects of increasing respiratory rates on arterial pH, PaCO2, HCO3, and potassium (K) were measured in normal anesthetized dogs. Hyperventilation resulted in increased pH, decreased PaCO2, decreased HCO3, and decreased K compared with those parameters in spontaneously breathing dogs. The changes were related quantitatively: each 10 mmHg decrease in PaCO2 was associated with a pH increase of 0.1, a HCO3 decrease of 2.0 mEq/L, and a K decrease of 0.4 mEq/L. There were no cardiac arrhythmias or clinical signs of hypokalemia. After termination of hyperventilation, serum K was slower to return to control values than PaCO2. The ratio of the duration of hyperventilation to the time required for return of serum K to control was 0.67.

Hydrochemical evolution of regional groundwaters to playa brines in central Australia

A large-scale groundwater system in central Australia discharges to a chain of playas. Recharge in calcrete and fractured rock aquifers gives rise to relatively low-salinity HCO 3 Cl SO 4 groundwaters, which evolve through regional saline groundwaters, to highly saline playa brines. The hydrochemical evolution of the groundwaters follows the anionic sequence HCO 3 Cl SO 4 → ClbHCO 3SO 4 → ClSO 4HCO 3 → ClSO 4 → Cl. With increasing salinity, there is a relative increase in Na, K, Mg, Cl and SO 4; however, there is a relative decrease in HCO 3, Ca, and SiO 2 owing to the precipitation of carbonate, sulphate and silicate minerals, and the resultant brines are depleted in these ions. Significant chemical variation in the composition of playa brines is a result of complex processes of solution, evaporative concentration, precipitation and mineralogical change, including dolomitisation. Thermodynamic calculations based on the Pitzer equations have enabled a general model to be developed for these evolutionary processes in saline groundwaters up to the stage of halite saturation. At an early stage the regional groundwaters are saturated with respect to the carbonate minerals, dolomite first, then calcite. With increasing salinity, sulphate minerals begin to precipitate: saturation with respect to gypsum is attained at a chlorinity of 19‰, and saturation with respect to anhydrite is attained at 122‰. The playa brines attain saturation with respect to halite at a chlorinity of 144‰. Solute budgets based on a chloride concentration factor show that final playa brines are 178 times more concentrated than recharge groundwaters, and confirm the virtually complete loss of HCO 3, Ca and SiO 2 through precipitation. There are subtle differences in the hydrochemistry of different central Australian playa brines and also vis-à-vis playa brines described from other parts of the world. Most Australian playas have brines of the ClNa type with SO 4 and Mg also important. The generally accepted Hardie-Eugster model for brine evolution and mineral precipitation sequences has therefore been modified and extended. Three pathways are defined, following calcite precipitation, on the basis of the ratio of molar Ca to alkalinity; these pathways lead to saline waters with different compositions. Subsequent evolution of the brines depends on the ratios between molar SO 4, Mg, Ca and alkalinity.

Potential difference responses to secretory K +, Na + and HCO 3− changes in secreting and resting states of frog stomach in Cl −-free media

The effects of changes in secretory concentrations of K +, Na + and HCO 3 − on transmucosal potential difference (PD) and resistance in Cl −-free (SO 4 2−) solutions were compared for secreting fundus and resting fundus of Rana pipiens. In the resting fundus experiments, histamine was not present in the nutrient solution and cimetidine was primarily used to obtain acid inhibition. Increase of K + from 4 to 80 mM, decrease of Na + from 156 to 15.6 mM and decrease of HCO 3 − from 25 to 5 mM gave, 10 min after the change, in the secreting fundus Δ PD values of 39.7, −11.9 and 3.2 mV, respectively. In the resting fundus, 1.5 to 2 h after the addition of cimetidine, the same changes in secretory ion concentration gave Δ PD values of 12.2, −5.6 and 1.5 mV, respectively. Replacement of cimetidine with SCN and without histamine yielded a Δ PD somewhat lower than that in cimetidine, namely 9 mV for a K + change from 4 to 80 mM. Subsequent addition of histamine with SCN present gave a Δ PD of about 21 mV. The change in PD was attributed to histamine increasing the secretory membrane area, leading to an increase in K + conductance. Another possibility is that histamine increases the K + conductance per se.

Axial heterogeneity and filtered-load dependence of proximal bicarbonate reabsorption

A theoretical model was developed to examine the role of physical and chemical factors in the control of bicarbonate reabsorption in the renal proximal tubule. Included in the model were axial and radial variations in the concentrations of HCO3-, CO2 and related chemical species in the tubule lumen and epithelial cells. Relations between these concentrations and the solute fluxes across the brush border and basolateral membranes were also included, as were reaction rate and equilibrium expressions to describe the various buffering processes in the lumen and cells. The two most critical membrane parameters, the rate constant for H+ secretion at the brush border and the effective permeability of HCO3- at the basolateral membrane, were evaluated by comparing model predictions with available free-flow micropuncture data in the rat. It was found that the experimental observations could be explained only by decreasing one or both of these membrane parameters with axial position, suggesting a progressive decrease in HCO3- reabsorptive capacity along the tubule. For single nephron filtered loads of HCO3- up to about 1,400 pmol/min, absolute bicarbonate reabsorption was predicted to increase nearly in proportion to filtered load, whereas it was calculated to be relatively constant at higher filtered loads, irrespective of how filtered load was assumed to be varied. These predictions are in excellent agreement with most of the available micropuncture data in rats, as is the prediction that HCO3- reabsorption should change in parallel with CO2 partial pressure in the filtrate, at a given filtered load of HCO3-. Certain discrepancies between the model predictions and experimental observations are evident at very high filtered loads, and the implications of these are discussed in terms of possible adaptive responses of the tubule.

Changes in Blood Acid-Base Equilibrium in Mice Exposed to Carbon Monoxide

The changes in blood acid-base equilibrium in mouse during and after exposure to carbon monoxide (CO) were studied with special reference to the relationship to carboxyhemoglobin (HbCO) content in blood. Acid-base parameters investigated were pH, pCO2, HCO3- and base excess (BE).The results obtained were as follows:1. The changes in blood acid-base equilibrium during CO exposure took place in two phases depending strongly upon HbCO content in blood.2. The decrease in pCO2 and increase in pH, i. e., a respiratory alkalosis was observed in the first phase which appeared when HbCO content in blood reached 50-60%. Little change in HCO3- and BE was observed.3. The decrease in HCO3-, BE and pH, i. e., a metabolic acidosis was observed in the second phase which appeared when HbCO content in blood increased more than 60-70%. The decrease in pCO2 was also remarkable.4. The metabolic acidosis caused by CO exposure remained unchanged for a while after discontinuing the exposure, although rapid decrease in HbCO content in blood was observed.5. All the blood acid-base parameters began to improve when HbCO content in blood fell to 30-40%. Metabolic acidosis disappeared when HbCO content in blood became approximately 20%. On the other hand, at this time, pCO2 increased beyond the upper limit of normal value and a state of respiratory acidosis developed.6. The results so far obtained indicate that shift in blood acid-base equilibrium must be carefully taken into consideration in the diagnosis of CO poisoning and its treatments.