Role of acidosis in regulating hepatic nitrogen metabolism during fasting in conscious dog

E. Cersosimo, P. E. Williams, D. O'Donovan, D. B. Lacy, N. N. Abumrad

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


This study was designed to investigate the role that acidosis plays in the metabolic responses to fasting. Eighteen conscious dogs with surgically implanted catheters in the femoral artery and in the hepatic, portal, and renal veins were studied. Six were fasted for 24 h and 12 were fasted for 4 days (96 h). On the day of the study, six 4-day fasted dogs were infused intravenously with NaHCO3 (10 μmol·kg-1·min-1) for 3 h, while the rest received saline and acted as controls. Splanchnic balances of glutamine, alanine, blood urea nitrogen, ammonia, lactate, β-hydroxybutyrate, and acetoacetate were estimated using the Fick principle. Blood flow to the splanchnic and renal beds were estimated using indocyanine green and p-aminohippurate extraction methods, respectively. The infusion of NaHCO3 nearly abolished the base deficit associated with fasting and normalized arterial bicarbonate levels but did not alter blood pH. It suppressed but did not abolish hepatic glutamine output by 60%. This was associated with a shift in cytoplasmic and mitochondrial redox potentials of the hepatocyte as evident by a decrease in hepatic production of β-hydroxybutyrate and an increase in hepatic production of acetoacetate and a decrease in hepatic lactate utilization. Concomitantly, renal glutamine uptake decreased. Glutamine release of skeletal muscle was unchanged. The data suggest that hepatic glutamine synthesis and release seen with 4-day fasting has two components: 1) a bicarbonate-dependent component that is influenced by the redox potential of the hepatocyte and 2) a bicarbonate-independent component, the nature of which is not yet clear. The studies also indicate that the kidneys decrease their uptake of glutamine with alkalinization, whereas the muscle is resistant to any changes in the acid-base milieu of the animal.

Original languageEnglish (US)
Pages (from-to)E313-E319
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number3 (15/3)
StatePublished - Jan 1 1987
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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