Definition of Clinically Relevant Lactic Acidosis in Patients with Internal Diseases

Luft, D; Deichsel, Guntram; Schmülling, R. M.; Stein, Wolfgang; Eggstein, M.

doi:10.1093/ajcp/80.4.484

Cited by 131 publications

(78 citation statements)

References 13 publications

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“…In this study, we found that during hibernation, a depressed O 2 consumption rate was not compensated for by increased glycolysis, as plasma lactate levels did not increase in winter samples, in agreement with previous measurements (17). Levels of plasma lactate found in winter (3.05 Ϯ 1.32 mM) were comparable to normal human values (22,30,41). The higher variation of plasma lactate concentration in the summer samples may reflect a more variable activity of the individual bears at the time of sampling ( Table 2).…”

Section: Discussionsupporting

confidence: 91%

Decrease in the red cell cofactor 2,3-diphosphoglycerate increases hemoglobin oxygen affinity in the hibernating brown bearUrsus arctos

Revsbech

Malte

Fröbert

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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consumption rate to ϳ25% compared with the active state, while body temperature decreases moderately (to ϳ30°C), suggesting a temperature-independent component in their metabolic depression. To establish whether changes in O 2 consumption during hibernation correlate with changes in blood O2 affinity, we took blood samples from the same six individuals of hibernating and nonhibernating free-ranging brown bears during winter and summer, respectively. A single hemoglobin (Hb) component was detected in all samples, indicating no switch in Hb synthesis. O 2 binding curves measured on red blood cell lysates at 30°C and 37°C showed a less temperature-sensitive O2 affinity than in other vertebrates. Furthermore, hemolysates from hibernating bears consistently showed lower cooperativity and higher O2 affinity than their summer counterparts, regardless of the temperature. We found that this increase in O2 affinity was associated with a significant decrease in the red cell Hb-cofactor 2,3-diphosphoglycerate (DPG) during hibernation to approximately half of the summer value. Experiments performed on purified Hb, to which DPG had been added to match summer and winter levels, confirmed that the low DPG content was the cause of the left shift in the Hb-O 2 equilibrium curve during hibernation. Levels of plasma lactate indicated that glycolysis is not upregulated during hibernation and that metabolism is essentially aerobic. Calculations show that the increase in Hb-O2 affinity and decrease in cooperativity resulting from decreased red cell DPG may be crucial in maintaining a fairly constant tissue oxygen tension during hibernation in vivo. metabolic suppression; body temperature; oxygen binding curves; heat of oxygenation; hibernation A DISTINCT TRAIT OF MAMMALIAN hibernation is the highly controlled decrease in body temperature and metabolic rate. A hibernating brown bear (Ursus arctos) routinely spends 5-7 mo per year in continuous dormancy with no food or water intake, no urination, and no defecation (19,36). During this time, bears appear to be resistant to loss of muscle mass, strength, or bone density (18,24,29,43,14,44). During hibernation bear body temperature is downregulated only slightly, fluctuating from ϳ37°C to a minimum of 30°C, as found in brown and in black bears (Ursus americanus) (17,26,27,36,43), whereas O 2 consumption rate is downregulated by 75% (43). In comparison, in most smaller hibernators, such as ground squirrels and marmots, body temperature drops dramatically to values close to ambient temperatures (32, 37, 48), with a consequent strong Q 10 -induced depression of metabolic rate (where Q 10 is the rate coefficient for a 10°C change in temperature). In spite of substantial downregulation of ventilation and heart rate, most hibernators likely experience only slight or no hypoxia and in some ground squirrels arterial O 2 tension (PO 2 ) is normal during torpor (16). As opposed to smaller hibernators that exhibit periods of spontaneous arousals back to normothermic temperature and metabolic rate (33...

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Section: Discussionsupporting

confidence: 91%

Decrease in the red cell cofactor 2,3-diphosphoglycerate increases hemoglobin oxygen affinity in the hibernating brown bearUrsus arctos

Revsbech

Malte

Fröbert

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Our patient satisfied the Luft criteria for lactic acidosis, namely, pH < 7·35 and lactate > 45mg/dL. 5 Metformin levels could not be measured, but since all other causes of increased lactate were ruled out, MALA was diagnosed. Surprisingly, the pH and lactate levels do not correlate with worse prognosis.…”

Section: Discussionmentioning

confidence: 81%

Metformin-associated lactic acidosis: it really happens!

Hasan¹,

Vidyasagar²

2017

J Clin Sci Res

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Metformin-associated lactic acidosis (MALA) in the absence of other risk factors, is extremely rare. A 60-year-old male presented to the emergency department feeling tired and breathless for the preceeding 3 days. He had a 10 year history of type 2 diabetes mellitus (T2DM) and was receiving treatment with metformin. There was no history of fever, cough or orthopnoea. Physical examination was unremarkable. Arterial blood gas analysis showed an increased anion gap metabolic acidosis and raised lactate. Mild pre-renal impairment was also present. There was no evidence of sepsis, heart or liver failure, anaemia or history of alcohol abuse. He received intravenous fluids with resultant normalisation of renal function but lactate levels remained elevated and bicarbonate remained low. At this point a diagnosis of MALA was considered. Metformin was stopped and within 24 hours lactate and bicarbonate levels returned to normal limits. This case highlights the possibility of metformin-treated patients developing lactic acidosis in the absence of other risk factors. Any unwell patient taking metformin should undergo measurement of serum lactate and bicarbonate. Key words: Metformin, Lactic Acidosis

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“…La acidosis láctica tipo B es definida como niveles de acido láctico mayores de 5mmol/L y pH menor a 7,30 en sangre (Luft et al, 1983), considerada, una complicación metabólica de mal pronóstico si no es reconocida rápidamente, la cual, debe ser tratada con quimioterapia de urgencia. Otras modalidades de tratamiento incluyen, la terapia dialítica, bicarbonato, administración de tiamina intravenosa (Ruiz et al, 2011) (Carella et al, 2015) (Claudino et al, 2015).…”

Section: Rol De Lactato En El Paciente Critico Con Cáncerunclassified

Utilidad clínica del lactato en el paciente oncológico

Páez¹,

Villagómez²,

Montero³

et al. 2017

prosciences

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Resumen: Acorde a la hipótesis de Warburg, las células cancerígenas, seleccionan la glucólisis aerobia, como la principal forma de metabolizar la glucosa en lugar de la fosforilación oxidativa (House et al., 1956), (Jiang, 2017), debido a ello las células tumorales captan más moléculas de glucosa, para generar acido láctico, necesario para mantener el micro ambiente celular (Jiang, 2017). Hoy en día, los procesos de reprogramación metabólica, han llevado al estudio de diversos oncogenes y genes supresores, que se encargan en las células proliferantes de la reprogramación del metabolismo mitocondrial (Alonso Remedios et al., 2016). Así, la acidosis láctica tipo B, los fenómenos metabólicos de reprogramación (Kroemer and Pouyssegur, 2008), la sobre expresión de hexoquinasa II y alteraciones en la pirofosfato de tiamina, (PPT) entre otras, causan elevaciones del lactato, que han sido pobremente descritas. Con lo antes mencionado, intentamos adentrarlos, en esta revisión, al conocimiento del lactato y el cáncer.Palabras Clave-Glucólisis aeróbica, Acidosis láctica tipo B, Reprogramación celular, Neoplasias hematológicas.Abstract: According to the Warburg hypothesis, the cancer cells select aerobic glycolysis, as the main way to metabolize glucose instead of oxidative phosphorylation (House et al., 1956), (Jiang, 2017), due to which the tumor cells capture more glucose molecules, to generate lactic acid, necessary to maintain the cellular micro-environment (Jiang, 2017). Nowadays, the processes of metabolic reprogramming have led to the study of various oncogenes and suppressor genes, which are responsible for the proliferating cells of the reprogramming of mitochondrial metabolism (Alonso Remedios et al., 2016). Thus, lactic acidosis type B, the metabolic phenomena of reprogramming (Kroemer and Pouyssegur, 2008), the over-expression of hexokinase II and alterations in thiamine pyrophosphate, (PPT) among others, cause lactate elevations, which have been poorly described. With the aforementioned, we try to introduce them, in this review, to the knowledge of lactate and cáncer.Keywords-Aerobic glycolysis, Type B lactic acidosis, Cell reprogramming, Hematological neoplasms. Fisiopatología:La glucólisis, es el proceso que involucra 10 pasos iniciales, para generar, a partir de una molécula de glucosa, dos molécu-las de piruvato, formadas de 3 carbonos; en los organismos con respiración celular, la glucólisis es la primera etapa del proceso, esta no requiere oxígeno, por lo que también la realizan otros organismos anaerobios (Costello and Franklin, 2005). Así la glucólisis se puede dar tanto en ausencia de oxígeno, donde se produce lactato, como en presencia de este, donde se puede metabolizar el piruvato a acetil-CoA y pasar a su oxidación completa: CO2 y agua, produciendo una gran cantidad de energía en la fosforilación oxidativa (Gatenby and Gillies, 2004 Las células adultas normales bien diferenciadas, tienen un bajoíndice de divisiones, y metabolizan glucosa para CO2 y H2O a través de glucólisis y ciclo de acido trica...

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Definition of Clinically Relevant Lactic Acidosis in Patients with Internal Diseases

Cited by 131 publications

References 13 publications

Decrease in the red cell cofactor 2,3-diphosphoglycerate increases hemoglobin oxygen affinity in the hibernating brown bearUrsus arctos

Decrease in the red cell cofactor 2,3-diphosphoglycerate increases hemoglobin oxygen affinity in the hibernating brown bearUrsus arctos

Metformin-associated lactic acidosis: it really happens!

Utilidad clínica del lactato en el paciente oncológico

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