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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 (\u201cshuttle\u201d) of lactate between tissues. Basic issues discussed include (1) effect of nonproductive lactate\u2010pyruvate 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\u2009mmol\/min\/70\u2009kg and 1.5\u2009L\/min\/70\u2009kg, 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\u2010studied physiology of exercise\u2010induced 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.<\/jats:p>","DOI":"10.1155\/2020\/2608318","type":"journal-article","created":{"date-parts":[[2020,10,24]],"date-time":"2020-10-24T07:45:03Z","timestamp":1603525503000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Quantitative Assessment of Blood Lactate in Shock: Measure of Hypoxia or Beneficial Energy Source"],"prefix":"10.1155","volume":"2020","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3757-4716","authenticated-orcid":false,"given":"David G.","family":"Levitt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph E.","family":"Levitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Levitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,23]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-016-1403-5"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000000742"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-017-4683-6"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201812-2342OC"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0000000000001156"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.260"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2014.05.007"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.03.008"},{"key":"e_1_2_12_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00421-017-3795-6"},{"key":"e_1_2_12_10_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.058701"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ccx.0000235208.77450.15"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/cc3526"},{"key":"e_1_2_12_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-014-0503-3"},{"key":"e_1_2_12_14_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201708712"},{"key":"e_1_2_12_15_2","doi-asserted-by":"publisher","DOI":"10.2147\/CEG.S260600"},{"key":"e_1_2_12_16_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.48.2.334"},{"key":"e_1_2_12_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature24057"},{"key":"e_1_2_12_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2015.00022"},{"key":"e_1_2_12_19_2","volume-title":"Lactate, not pyruvate, is the end product of glucose metabolism via glycolysis, Carbohydrate","author":"Schurr A.","year":"2017"},{"key":"e_1_2_12_20_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3430281"},{"key":"e_1_2_12_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1999.276.5.E843"},{"key":"e_1_2_12_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1218099"},{"key":"e_1_2_12_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1218530"},{"key":"e_1_2_12_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2014.10.008"},{"key":"e_1_2_12_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)85942-2"},{"key":"e_1_2_12_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2017.04.004"},{"key":"e_1_2_12_27_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00009.2004"},{"key":"e_1_2_12_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101177"},{"key":"e_1_2_12_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.2010.02122.x"},{"key":"e_1_2_12_30_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1987.252.3.E439"},{"key":"e_1_2_12_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(92)90199-K"},{"key":"e_1_2_12_32_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1995.268.5.E880"},{"key":"e_1_2_12_33_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1994.266.3.E334"},{"key":"e_1_2_12_34_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1988.254.4.E532"},{"key":"e_1_2_12_35_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1994.267.1.E174"},{"key":"e_1_2_12_36_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1995.78.2.483"},{"key":"e_1_2_12_37_2","doi-asserted-by":"publisher","DOI":"10.3109\/07853899009147263"},{"key":"e_1_2_12_38_2","first-page":"54","article-title":"Isotopic evaluation of the metabolism of pyruvate and related substrates in normal adult volunteers and severely burned children: effect of dichloroacetate and glucose infusion","volume":"110","author":"Wolfe R. 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