PubMed Health⌕ Search

PubMed · 8202051

Acidosis and bone.

Abstract

Acidosis has important effects on the bone mineral which can be investigated utilizing neonatal mouse calvariae in organ culture. When calvariae are cultured for 3 h in physiologically acidic medium produced by a reduction of the bicarbonate concentration, a model of acute metabolic acidosis, there is net calcium efflux from bone in addition to net proton influx into bone which lessens the severity of the acidosis. Utilizing a high resolution scanning ion microprobe to study the bone during acidosis we have found that the protons exchange for sodium and potassium on the bone surface. In acute experiments the calcium efflux is the result of mobilization of carbonated apatite through an alteration in the physicochemical driving forces for bone mineral accretion and dissolution. In the more chronic cultures (greater than 48 h) metabolic acidosis induces calcium efflux by stimulating osteoclastic bone resorption and inhibiting osteoblastic bone formation. When calvariae are cultured for 3 h in acidic medium produced by an increase in the partial pressure of carbon dioxide, a model of respiratory acidosis, there is also calcium efflux; however, at the same decrement in pH the net flux is far less than that observed during metabolic acidosis. During acute respiratory acidosis there is no measurable influx of protons into bone and during chronic studies there is no measurable calcium efflux.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

D A Bushinsky. 1994. Acidosis and bone.. https://pubmed.ncbi.nlm.nih.gov/8202051/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Grave acidosis after severe anaphylactic bronchospasm: friend or foe?

In a 20-year-old woman with known asthma, anaphylactic bronchospasm induced a grave combined respiratory and metabolic acidosis (pH(a) 6.66) with marked hypoxaemia (S(a)O(2) 45%). The beneficial effects of the rightward shift of the oxyhaemoglobin dissociation curve on tissue O(2) unloading at such pH was more than offset by the negative effect on S(a)O(2) at the reduced P(a)O(2) (7.0 kPa) found in this patient. This case illustrates the detrimental effect of grave acidosis on arterial blood oxygen content at subnormal P(a)O(2) values, the beneficial effect of a supranormal P(a)O(2) on the S(a)O(2) in such patients, and the rapid remission rate of life-threatening acidosis and blood lactate after adequate ventilation and tissue oxygenation were secured. The initial treatment of the patient and clinically relevant considerations are discussed.

Acidosis↗

[Isoniazid intoxication].

HISTORY AND ADMISSION FINDINGS: A 55-year-old woman presented with sustained convulsions after the ingestion of an at first unknown amount of isoniazid, rifampin, ethambutol and alcohol. INVESTIGATION: At admission the patient had a severe metabolic acidosis. Blood tests showed changes caused by the hepatotoxicity of isoniazid. TREATMENT AND COURSE: Because diazepam was not efficacious in controlling the convulsions the patient was intubated. In response to the therapautic measures the convulsions stopped and metabolic acidosis was quickly compensated. Pyridoxine was given intravenously as an antidote. CONCLUSION: The rare intoxication with isoniazid demands immediate administration of pyridoxine and aggressive treatment of the convulsions.

Acidosis↗

Mitogen-activated protein kinase-dependent activation of the Na+/H+ exchanger is mediated through phosphorylation of amino acids Ser770 and Ser771.

We investigated regulation of the type 1 isoform of the Na(+)/H(+) exchanger by phosphorylation. Four specific groups of serine and threonine residues in the regulatory carboxyl-terminal tail were mutated to alanine residues: group 1, S693A; group 2, T718A and S723A/S726A/S729A; group 3, S766A/S770A/S771A; and group 4, T779A and S785A. The proteins were expressed in Na(+)/H(+) exchanger-deficient cells, and the activity was characterized. All of the mutants had proper expression, localization, and normal basal activity relative to wild type NHE1. Sustained intracellular acidosis was used to activate NHE1 via an ERK-dependent pathway that could be blocked with the MEK inhibitor U0126. Immunoprecipitation of (32)P-labeled Na(+)/H(+) exchanger from intact cells showed that sustained intracellular acidosis increased Na(+)/H(+) exchanger phosphorylation in vivo. This was blocked by U0126. The Na(+)/H(+) exchanger activity of mutants 1 and 2 was stimulated similar to wild type Na(+)/H(+) exchanger. Mutant 4 showed a partially reduced level of activation. However, mutant 3 was not stimulated by sustained intracellular acidosis, and loss of stimulation of activity correlated to a loss of sustained acidosis-mediated phosphorylation in vivo. Mutation of the individual amino acids within mutant 3, Ser(766), Ser(770), and Ser(771), showed that Ser(770) and Ser(771) are responsible for mediating increases in NHE1 activity through sustained acidosis. Both intact Ser(770) and Ser(771) were required for sustained acidosis-mediated activation of NHE1. Our results suggest that amino acids Ser(770) and Ser(771) mediate ERK-dependent activation of the Na(+)/H(+) exchanger in vivo.

Acidosis↗