Alterations of Red-Cell Glycolytic Intermediates and Oxygen Transport as a Consequence of Hypophosphatemia in Patients Receiving Intravenous Hyperalimentation

Travis, Susan F.; Sugerman, Harvey J.; Ruberg, R.L.; Dudrick, Stanley J.; Delivoria‐Papadopoulos, Maria; Miller, Leonard D.; Oski, Frank A.

doi:10.1056/nejm197109302851402

Cited by 280 publications

(82 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Hypophosphatemia has been found to associate with lower RBC levels of 2,3-DPG in previous studies (13,14). Extracellular phosphate and RBC intracellular phosphate concentrations are linked through at least three phosphate transporters in RBC membranes: band 3, Na/phos cotransporter, and sodium-independent transport (15).…”

Section: Discussionmentioning

confidence: 91%

Reductions in Red Blood Cell 2,3-Diphosphoglycerate Concentration during Continuous Renal Replacment Therapy

Brugnara

Betensky

et al. 2015

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Background and objectives Hypophosphatemia is a frequent complication during continuous renal replacement therapy (CRRT), a dialytic technique used to treat AKI in critically ill patients. This study sought to confirm that phosphate depletion during CRRT may decrease red blood cell (RBC) concentration of 2,3-diphosphoglycerate (2,3-DPG), a crucial allosteric effector of hemoglobin's (Hgb's) affinity for oxygen, thereby leading to impaired oxygen delivery to peripheral tissues.Design, setting, participants, & measurements Phosphate mass balance studies were performed in 20 patients with severe AKI through collection of CRRT effluent. RBC concentrations of 2,3-DPG, venous blood gas pH, and oxygen partial pressure required for 50% hemoglobin saturation (P50) were measured at CRRT initiation and days 2, 4, and 7. Similar measurements were obtained on days 0 and 2 in a reference group of 10 postsurgical patients, most of whom did not have AKI. Associations of 2,3-DPG with laboratory parameters and clinical outcomes were examined using mixed-effects and Cox regression models.Results Mean 2,3-DPG levels decreased from a mean (6SD) of 13.463.4 mmol/g Hgb to 11.063.1 mmol/g Hgb after 2 days of CRRT (P,0.001). Mean hemoglobin saturation P50 levels decreased from 29.764.4 mmHg to 26.764.0 mmHg (P,0.001). No significant change was seen in the reference group. 2,3-DPG levels after 2 days of CRRT were not significantly lower than those in the reference group on day 2. Among patients receiving CRRT, 2,3-DPG decreased by 0.53 mmol/g Hgb per 1 g phosphate removed (95% confidence interval 0.38 to 0.68 mmol/g Hgb; P,0.001). Greater reductions in 2,3-DPG were associated with higher risk for death (hazard ratio, 1.43; 95% confidence interval, 1.09 to 1.88; P=0.01).Conclusions CRRT-induced phosphate depletion is associated with measurable reductions in RBC 2,3-DPG concentration and a shift in the O 2 :Hgb affinity curve even in the absence of overt hypophosphatemia. 2,3-DPG reductions may be associated with higher risk for in-hospital death and represent a potentially avoidable complication of CRRT.

show abstract

Section: Discussionmentioning

confidence: 91%

Reductions in Red Blood Cell 2,3-Diphosphoglycerate Concentration during Continuous Renal Replacment Therapy

Brugnara

Betensky

et al. 2015

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…Adequate total body phosphorus and phosphate are necessary for glucose utilization, glycolysis, ATP synthesis, numerous biochemical reactions, 2,3-diphosphoglycerate synthesis and function (which are necessary for oxygen release from hemoglobin and delivery to tissues), neurologic function, and muscular function (especially the myocardium and diaphragm). 24,25,27,28,[121][122][123][124] Hypophosphatemia. Hypophosphatemia (serum phosphorus concentration of <2.7 mg/dL) can lead to severe clinical sequelae, including 30,121,122,[125][126][127][128] Given the potential adverse effects of hypophosphatemia, serum phosphorus concentrations in critically ill patients should be maintained within the normal range.…”

Section: Phosphorusmentioning

confidence: 99%

“…24,25,27,28,[121][122][123][124] Hypophosphatemia. Hypophosphatemia (serum phosphorus concentration of <2.7 mg/dL) can lead to severe clinical sequelae, including 30,121,122,[125][126][127][128] Given the potential adverse effects of hypophosphatemia, serum phosphorus concentrations in critically ill patients should be maintained within the normal range. Treatment of hypophosphatemia depends on the magnitude of hypophosphatemia and whether or not the patient is symptomatic.…”

Section: Phosphorusmentioning

confidence: 99%

Treatment of electrolyte disorders in adult patients in the intensive care unit

Kraft

Btaiche²,

Sacks³

et al. 2005

American Journal of Health-System Pharmacy

241

202

View full text Add to dashboard Cite

Purpose. The treatment of electrolyte disorders in adult patients in the intensive care unit (ICU), including guidelines for correcting specific electrolyte disorders, is reviewed. Summary. Electrolytes are involved in many metabolic and homeostatic functions. Electrolyte disorders are common in adult patients in the ICU and have been associated with increased morbidity and mortality, as has the improper treatment of electrolyte disorders. A limited number of prospective, randomized, controlled studies have been conducted evaluating the optimal treatment of electrolyte disorders. Recommendations for treatment of electrolyte disorders in adult patients in the ICU are provided based on these studies, as well as case reports, expert opinion, and clinical experience. The etiologies of and treatments for hyponatremia hypotonic and hypernatremia (hypovolemic, isovolemic, and hypervolemic), hypokalemia and hyperkalemia, hypophosphatemia and hyperphosphatemia, hypocalcemia and hypercalcemia, and hypomagnesemia and hypermagnesemia are discussed, and equations for determining the proper dosages for adult patients in the ICU are provided. Treatment is often empirical, based on published literature, expert recommendations, and the patient's response to the initial treatment. Actual electrolyte correction requires individual adjustment based on the patient's clinical condition and response to therapy. Clinicians should be knowledgeable about electrolyte homeostasis and the underlying pathophysiology of electrolyte disorders in order to provide the optimal therapy to patients. Conclusion. Treatment of electrolyte disorders is often empirical, based on published literature, expert opinion and recommendations, and patient's response to the initial treatment. Clinicians should be knowledgeable about electrolyte homeostasis and the underlying pathophysiology of electrolyte disorders to provide optimal therapy for patients.

show abstract

“…These studies suggest that INTRODUCTION Hypophosphatemia and intracellular deficiency of inorganic phosphate result in dysfunction of a wide range of organ systems in man and experimental animals. Erythrocyte hemolysis (1-3), derangements in the mechanical and phagocytic properties of leukocytes (1, 4), decreased survival and abnormal function of platelets (1,5), central nervous system abnormalities compatible with metabolic encephalopathy (1,6,7), abnormalities in renal function (1,8), and cardiac (1,(9)(10)(11)13), and skeletal myopathy (1,(12)(13)(14)(15)(16)(17) have been described in patients or animals with phosphate deficiency.…”

mentioning

confidence: 99%

“…The mechanisms proposed include shifts in the hemoglobin-02 dissociation curve leading to tissue hypoxia (6,18,19), inhibition of glycolysis and glycogenolysis (3,6,20), impaired calcium metabolism (8,10,17), alterations in phospholipid content of cellular membranes (17), diminished intracellular ATP stores secondary to a defect in ATP synthesis (1, 8, 11-13, 16-18, 21, 22), and disruption of energy transport from the mitochondria to the myofibril via the creatine phosphate (CP)' shuttle (11,13). The latter two mechanisms, i.e., a defect in ATP synthesis and a defect in energy utilization, may be of particular relevance in explaining the muscle dysfunction observed in phosphate deficiency, since both energy production in the form of ATP synthesis in the mitochondria and energy use in the form of CP transfer to ADP at the myofibril increase manyfold during vigorous muscle contraction (23,24).…”

mentioning

confidence: 99%

Defective adenosine triphosphate synthesis. An explanation for skeletal muscle dysfunction in phosphate-deficient mice.

Hettleman¹,

Sabina²,

Drezner³

et al. 1983

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T The basis for skeletal muscle dysfunction in phosphate-deficient patients and animals is not known, but it is hypothesized that intracellular phosphate deficiency leads to a defect in ATP synthesis. To test this hypothesis, changes in muscle function and nucleotide metabolism were studied in an animal model of hypophosphatemia. Mice were made hypophosphatemic through restriction of dietary phosphate intake. Gastrocnemius function was assessed in situ by recording isometric tension developed after stimulation of the nerve innervating this muscle. Changes in purine nucleotide, nucleoside, and base content of the muscle were quantitated at several time points during stimulation and recovery.Serum concentration and skeletal muscle content of phosphorous are reduced by 55 and 45%, respectively, in the dietary restricted animals. The gastrocnemius muscle of the phosphate-deficient mice fatigues more rapidly compared with control mice. ATP and creatine phosphate content fall to a comparable extent during fatigue in the muscle from both groups of animals; AMP, inosine, and hypoxanthine (indices of ATP catabolism) appear in higher concentration in the muscle of phosphate-deficient animals. Since total ATP use in contracting muscle is closely linked to total developed tension, we conclude that the comparable drop in ATP content in association with a more rapid loss of tension is best explained by a slower rate of ATP synthesis in the muscle of phosphate-deficient animals. During the period of recovery after muscle stimulation, ATP use for contraction is minimal, since the muscle is at rest. In the recovery period, ATP content returns to resting levels more slowly in the phosphate-deficient than in the control animals. In association with the slower rate of ATP repletion, the precursors inosine monophosphate and AMP remain elevated for a longer period of time in the muscle of phosphate-deficient animals. The slower rate of ATP repletion correlates with delayed return of normal muscle contractility in the phosphate-deficient mice. These studies suggest that the slower rate of repletion of the ATP pool may be the consequence of a slower rate of ATP synthesis and this is in part responsible for the delayed recovery of normal muscle contractility.

show abstract

Alterations of Red-Cell Glycolytic Intermediates and Oxygen Transport as a Consequence of Hypophosphatemia in Patients Receiving Intravenous Hyperalimentation

Cited by 280 publications

References 21 publications

Reductions in Red Blood Cell 2,3-Diphosphoglycerate Concentration during Continuous Renal Replacment Therapy

Reductions in Red Blood Cell 2,3-Diphosphoglycerate Concentration during Continuous Renal Replacment Therapy

Treatment of electrolyte disorders in adult patients in the intensive care unit

Defective adenosine triphosphate synthesis. An explanation for skeletal muscle dysfunction in phosphate-deficient mice.

Contact Info

Product

Resources

About