PubMed · 13846652
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
T M YOUNG, D MENDEL. 1959. Acidotic coma.. https://doi.org/10.1111/j.1365-2044.1959.tb02457.x
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
It is widely appreciated that inflammatory responses in peripheral tissues are usually associated to the development of acidic microenvironments. Despite this, there are few studies aimed to analyze the effect of extracellular pH on immune cell functions. We analyzed the impact of acidosis on the behavior of dendritic cells (DCs) derived from murine bone marrow. We found that extracellular acidosis (pH 6.5) markedly stimulated the uptake of FITC-OVA, FITC-dextran, and HRP by DCs. In fact, to reach similar levels of endocytosis, DCs cultured at pH 7.3 required concentrations of Ag in the extracellular medium almost 10-fold higher compared with DCs cultured at pH 6.5. Not only the endocytic capacity of DCs was up-regulated by extracellular acidosis, but also the expression of CD11c, MHC class II, CD40, and CD86 as well as the acquisition of extracellular Ags by DCs for MHC class I-restricted presentation. Importantly, DCs pulsed with Ag under acidosis showed an improved efficacy to induce both specific CD8(+) CTLs and specific Ab responses in vivo. Our results suggest that extracellular acidosis improves the Ag-presenting capacity of DCs.
In this study, we investigated the effect of acute metabolic acidosis on tissue protein synthesis. Groups of rats were made acidotic with intragastric administration of NH(4)Cl (20 mmol/kg body wt every 12 h for 24 h) or given equimolar amounts of NaCl (controls). Protein synthesis in skeletal muscle and a variety of different tissues, including lymphocytes, was measured after 24 h by injection of l-[(2)H(5)]phenylalanine (150 micromol/100 g body wt, 40 moles percent). Results show that acute acidosis inhibits protein synthesis in skeletal muscle (-29% in gastrocnemius, -23% in plantaris, and -17% in soleus muscles, P < 0.01) but does not affect protein synthesis in heart, liver, gut, kidney, and spleen. Protein synthesis in lymphocytes is also reduced by acidosis (-8%, P < 0.05). In a separate experiment, protein synthesis was also measured in acidotic and control rats by a constant infusion of l-[(2)H(5)]phenylalanine (1 micromol.100 g body wt(-1).h(-1)). The results confirm the earlier findings showing an inhibition of protein synthesis in gastrocnemius (-28%, P < 0.01) and plantaris (-19%, P < 0.01) muscles but no effect on heart and liver by acidosis. Similar results were also observed using a different model of acute metabolic acidosis, in which rats were given a cation exchange resin in the H(+) (acidotic) or the Na(+) (controls) form. In conclusion, this study demonstrates that acute metabolic acidosis for 24 h depresses protein synthesis in skeletal muscle and lymphocytes but does not alter protein synthesis in visceral tissues. Inhibition of muscle protein synthesis might be another mechanism contributing to the loss of muscle tissue observed in acidosis.
BACKGROUND: Chronic metabolic acidosis (CMA) in normal adults results in complex endocrine and metabolic alterations including growth hormone (GH) insensitivity, hypothyroidism, hyperglucocorticoidism, hypoalbuminaemia and loss of protein stores. Similar alterations occur in chronic renal failure, a prototypical state of CMA. We evaluated whether metabolic acidosis contributes to the endocrine and metabolic alterations characteristic of end-stage renal disease. METHODS: We treated 14 chronic haemodialysis patients with daily oral Na-citrate for 4 weeks, yielding a steady-state pre-dialytic plasma bicarbonate concentration of 26.7 mmol/l, followed by 4 weeks of equimolar Na-chloride, yielding a steady-state pre-dialytic plasma bicarbonate of 20.2 mmol/l. RESULTS: Blood pressure, body weight and dialysis adequacy were equivalent in the two protocols. Na-citrate treatment corrected CMA, improved GH insensitivity, increased and normalized plasma free T(3) concentration, and improved plasma albumin. Correction of CMA had no significant effect on measured cytokines (interleukin-1 beta and -6, tumour necrosis factor-alpha) or acute phase reactants (C-reactive protein, serum amyloid A, alpha(2)-macroglobulin). CONCLUSION: CMA contributes to the derangements of the growth and thyroid hormone axes and to hypoalbuminaemia, but is not a modulator of systemic inflammation in dialysis patients. Correcting CMA may improve nutritional and metabolic parameters and thus lower morbidity and mortality.