Abstract
Blood lactate concentration predicts mortality in critically ill patients and is clinically used in the diagnosis, grading of severity, and monitoring response to therapy of septic shock. This paper summarizes available quantitative data to provide the first comprehensive description and critique of the accepted concepts of the physiology of lactate in health and shock, with particular emphasis on the controversy of whether lactate release is simply a manifestation of tissue hypoxia versus a purposeful transfer (“shuttle”) of lactate between tissues. Basic issues discussed include (1) effect of nonproductive lactate-pyruvate exchange that artifactually enhances flux measurements obtained with labeled lactate, (2) heterogeneous tissue oxygen partial pressure (Krogh model) and potential for unrecognized hypoxia that exists in all tissues, and (3) pathophysiology that distinguishes septic from other forms of shock. Our analysis suggests that due to exchange artifacts, the turnover rate of lactate and the lactate clearance are only about 60% of the values of 1.05 mmol/min/70 kg and 1.5 L/min/70 kg, respectively, determined from the standard tracer kinetics. Lactate turnover reflects lactate release primarily from muscle, gut, adipose, and erythrocytes and uptake by the liver and kidney, primarily for the purpose of energy production (TCA cycle) while the remainder is used for gluconeogenesis (Cori cycle). The well-studied physiology of exercise-induced hyperlactatemia demonstrates massive release from the contracting muscle accompanied by an increased lactate clearance that may occur in recovering nonexercising muscle as well as the liver. The very limited data on lactate kinetics in shock patients suggests that hyperlactatemia reflects both decreased clearance and increased production, possibly primarily in the gut. Our analysis of available data in health and shock suggests that the conventional concept of tissue hypoxia can account for most blood lactate findings and there is no need to implicate a purposeful production of lactate for export to other organs.
Highlights
Important clinical decisions are based on the observation that high blood lactate levels strongly correlate with mortality in patients with shock from any cause [1], including sepsis [2,3,4], trauma [5], and myocardial infarction [6]
While decreased cardiac output (CO) obviously must result in an overall decrease in tissue perfusion, we found no quantitative values in the literature as to how this decreased CO is distributed to the skeletal muscle and splanchnic tissues in human cardiogenic shock
Lactate was not commonly measured in clinical medicine until about 17 years ago when it was recognized that the blood level of lactate was a useful marker of the severity of disease, with regard to various forms of shock
Summary
Important clinical decisions are based on the observation that high blood lactate levels strongly correlate with mortality in patients with shock from any cause [1], including sepsis [2,3,4], trauma [5], and myocardial infarction [6]. Despite the immense literature on this topic, including many reviews [7,8,9,10,11,12,13,14], the pathophysiology underlying the correlation between lactate and mortality remains controversial In large part, this controversy reflects debate concerning the more fundamental question of what is the metabolic role of lactate in health and disease—is lactate a by-product of anaerobic metabolism or does it subserve a variety of important physiological functions, in particular as a shuttle delivering an energy source between organs? Proponents of the nutritive model have argued that the increased lactate metabolism in exercise might be representative of that in septic shock (i.e., a “hypermetabolic state”), there are marked differences between the exercise and shock states (discussed in Septic Shock and Hemorrhagic and Cardiogenic Shock) For such an important and well-studied field as shock and lactate, the experimental physiological data on this topic is limited and insufficient to definitively answer many important questions. We have attempted to summarize and evaluate all relevant information on the pathophysiology of lactate in shock
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