The Extrarenal Response to Acute Acid-Base Disturbances of Respiratory Origin 1

Giebisch, Gerhard; Berger, Lawrence R.; Pitts, Robert F.; Parks, Mary Ellen; MacLeod, Martha B.

doi:10.1172/jci103076

Cited by 204 publications

(54 citation statements)

References 27 publications

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“…This is a result of increased cell buffering. In addition, the bicarbonate distribution space increases when extracellular buffering capacity is lowered by inducing either a metabolic acidosis (39,40) or a respiratory alkalosis (41 (41), and the fall in Pco2 from 32 to 20 mm Hg accounts for at least part of the drop in the muscle bicarbonate concentration after acid infusion. The observed change in muscle cell bicarbonate is less than that predicted from previous estimates of muscle buffering capacity (14).…”

Section: Discussionmentioning

confidence: 99%

An Extrarenal Role for Parathyroid Hormone in the Disposal of Acute Acid Loads in Rats and Dogs

Fraley¹,

Adler²

1979

J. Clin. Invest.

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A B S T R A C T Acid infusion studies were performed in nephrectomized rats and dogs with either intact parathyroid glands (intact) or after thyroparathyroidectomy (thyroparathyroidectomized [TPTX]) to determine the role of parathyroid hormone (PTH) in extrarenal disposal and buffering of acutely administered acid. 29 intact rats given 5 mM/kg HCI and 6 intact dogs given 7 mM/kg HC1 developed severe metabolic acidosis but all survived. However, each of 12 TPTX rats and 4 TPTX dogs given the same acid loads died. Intact rats and dogs buffered 39 and 50% of administered acid extracellularly, respectively, whereas extracellular buffering of administered acid was 97 and 78% in TPTX rats and dogs, respectively. 17 TPTX rats and 6 TPTX dogs given synthetic PTH 2 h before acid infusion survived. The blood bicarbonate and extracellular buffering in these animals, measured 2 h after acid infusion, was similar to intact animals. Changes in liver, heart, and skeletal muscle pH determined from [14C]5,5-dimethyl-2,4 oxazolidinedione distribution seemed insufficient to account for the increased cell buffering of PTH-replaced animals. Indeed, muscle pH in TPTX dogs given PTH and acid was only 0.06 pH units lower than in control dogs given no acid, suggesting that another tissue, presumably bone, was the target for PTH-mediated increased cell buffering. This conclusion was supported by the observation that PTH did not alter the pH of intact rat diaphragms in vitro. These results indicate that PTH is necessary for the optimal buffering of large, acute acid loads presumably by increasing bone buffering.

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Section: Discussionmentioning

confidence: 99%

An Extrarenal Role for Parathyroid Hormone in the Disposal of Acute Acid Loads in Rats and Dogs

Fraley¹,

Adler²

1979

J. Clin. Invest.

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“…Neutralization as bicarbonate of retained carbon dioxide (5)(6)(7)(8) also indicates the role of intracellular buffers when acid loading overwhelms respiratory and renal regulations of acid-base equilibriumi. While intracellular buffers might be-expected to participate in neutralizing excess alkali, studies of the distribution of administered bicarbonate in cat muscle (9) and in the whole body of man (10) do not allocate to intracellular buffers a significant role in neutralizing administered alkali.…”

mentioning

confidence: 99%

Distribution of Sodium Bicarbonate Infused Into Nephrectomized Dogs 1

Swan¹,

Axelrod²,

Seip³

et al. 1955

J. Clin. Invest.

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The participation of intracellular buffers in stabilizing hydrogen ion concentration in body fluids (1) is suggested by studies in which mineral acid has been administered at rates in excess of renal excretion of acid (2-4). Neutralization as bicarbonate of retained carbon dioxide (5-8) also indicates the role of intracellular buffers when acid loading overwhelms respiratory and renal regulations of acid-base equilibriumi. While intracellular buffers might be-expected to participate in neutralizing excess alkali, studies of the distribution of administered bicarbonate in cat muscle (9) and in the whole body of man (10) do not allocate to intracellular buffers a significant role in neutralizing administered alkali.The extent to which blood and tissue buffers participate in neutralizing alkali infused as sodium bicarbonate has been studied by measuring changes in the total quantity of extracellular and erythrocyte sodium, potassium, bicarbonate, and chloride following infusion of sodiuim bicarbonate into nephrectomnized dogs. Prelimninary reports (11,12) three-fourths of the added sodium and two-thirds of the added bicarbonate remain in extracellular fluid, while one-fourth of the added sodium probably exchanges for intracelltular hydrogen ion.EXPERIMENTAL PLAN Dogs w-ere neplhrectomized immediately before each experiment to eliminate renal excretion of water and ions and to permit more accurate measurement of the volume of distribution of radiosulfate. Control values for sodium, potassium, bicarbonate, and chloride in extracellular fluid and in the circulating erythrocyte mass were established three and four hours after nephrectomy. One and two hours after the production of severe metabolic alkalosis by infusioni of sodium bicarbonate (0.6 normal in the first group of four experiments, 0.3 normal in the second group of four experiments) the total amounts of each of these ions in extracellular fluid and in the erythrocyte mass w-ere re-established. Ion transfers to and from extracellular fluid and into and out of circulating erythrocytes were calculated from the differences in mean ion contents observed in the two control and two alkalosis observations. Results of four control experiments performed under comparable conditions have been reported previously (4). EXPERIMENTAL PROCEDUREHealthy, moderately lean, adult male dogs were lightly anesthetized w ith sodium pentobarbital, weighed and nephrectomized bilaterally. Radiosulfate (S'3O4) and (in three of eight experiments) radiochloride (Cl36) were infused as previously described (13). Two and one-half, three, three and one-half and four hours after infusion of radioisotopes arterial blood samples were drawn for measurement of plasma radiosulfate concentration and plasma specific gravity. Additional samples were obtained at three and four hours for measurement of plasma and whole blood sodium, potassium, CO2, chloride, and for plasma radiochloride concentrations, plasma pH, whole blood water content, hematocrit and, in the second group of experiments, for plasma in...

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“…Metabolic alkalosis has occurred during breathing of CO2 mixtures in unanesthetized man (4) and dog (1,5) and in dogs anesthetized with pento-. barbital (3). The same response hgs beeR;.…”

Section: Resultsmentioning

confidence: 67%