• In sepsis, lactate isn’t increased because of tissue hypoxia alone. • Lactate levels are good at prognosticating but lactate-guided therapy in sepsis needs more study.[r]
(1)Lactic Acid
Kinetics and Clinical Use
JOSHUA SOLOMON, MD
ASSOCIATE PROFESSOR OF MEDICINE NATIONAL JEWISH HEALTH
(2)Outline
• Background
• History
• Kinetics
• Myths of lactate and lactic acidosis
• Types of lactic acidosis
(3)(4)Lactate
• By-product of anaerobic metabolism or
increased glycolysis
• Primarily produced when there is not enough
oxygen present to oxidise pyruvate in Krebs Cycle and ETC (in Mitochondria)
• Lactate can be transported in blood, lactic acid can’t
(5)Lactate
• Every organ in the body can produce it
• The body produces 1500 mmol/day
• The liver (60%) and kidneys (30%) are the main organs in lactate disposal
• Resting blood lactate levels are ~ mmol/L but during exercise this can increase to ~30 mmol/L
(6)(7)Lactate History
• 1930s to 1970s – “dead end waste product”
◦ Dead end metabolite from glycolysis from muscle hypoxia
◦ Primary cause of slow component of oxygen debt
• 1980s – lactate shuttle was discovered
◦ During exercise, muscle is the main producer of lactate
◦ During recovery, muscle (and heart and brain) takes up lactate and use as fuel source (spares glucose for use elsewhere)
(8)(9)LACTATE FORMATION
(10)Lactate Production at Rest
SKIN – 25% RBCs – 20%
CNS – 20% MUSCLE – 25%
(11)(12)(13)Lactate Transport to Tissue
(14)(15)Myths
• Lactate production leads to acidosis
• Lactate is “bad” for cells and organs
(16)Lactate alone doesn’t lead to acidosis
• Lactic acid disassociates to produce H+
• Pyruvate is converted to LACTATE, not lactic acid
◦ This consumes H+ intracellularly and mitigates acidosis
• Lactate is associated with acidosis
◦ Lactate reduces strong ion difference ☛ disassociation of water and weak acids
(17)Lactate is GOOD
• Brain and cardiac oxidation of lactate increase during exercise and shock
• Lactate removal during stress is associated with cardiovascular collapse
• Infusion of lactate increases cardiac output in cardiogenic shock and sepsis
(18)(19)(20)(21)(22)Lactate production and tissue hypoxia
• Not correlated with tissue hypoxia or oxygen extraction
• Septic patients have increased oxygen
consumption, glucose utilization and
pyruvate production
(23)Lactate production and tissue hypoxia
• Septic patients have decreases in pyruvate dehydrogenase activity
• Buildup in pyruvate leads to more lactate production
• Epinephrine stimulates release of lactate from muscles through
B-adrenoceptors
(24)(25)(26)(27)(28)(29)Elevated lactate and
(30)LACTATE UPTAKE IN
TISSUES LACTATE
PRODUCTION
(31)LACTATE UPTAKE IN
TISSUES
LACTATE PRODUCTION
Metabolized by liver in to hours
(32)Seheult et al Clin Chem Lab Med 2017; 55(3): 322–333
Systemic/local hypoperfusion Increased glycolysis
(33)(34)(35)Lactate-guided therapy
• First trail looking at lactate as a marker of resuscitation
• Randomized to either for hours:
1 CVP>8, MAP > 65 and Scvo2 of at least 70%
2 CVP>8, MAP > 65 and lactate clearance of 10%
• No difference in mortality when using
lactate instead of ScvO2
(36)Lactate-guided therapy
• Open label randomized
study looking at lactate as a marker of resuscitation
• When controlling for other factors, significant
reduction in mortality (HR 0.61, CI 0.43 – 0.87)
(37)Lactate-guided therapy
• Lactate is good at prognosticating
◦ Meta-analysis concluded that initial lactate and
changes over time are good at identifying sick patients
◦ They conclude that lactate-guided resuscitation needs more studies
Kruse et al Scand J Trauma, Resus and EM 2011; 19: 74
• Lactate-guided therapy needs more studies
• Experts in the field (e.g Paul Marik) argue that lactate is from the stress response, increasing oxygen delivery may be harmful and ‘lactate clearance’ shouldn’t be an endpoint of
(38)Conclusions
• Lactate is a byproduct of glycolysis
• Lactate is utilized by organ systems
• Lactate production doesn’t directly cause acidosis
• In sepsis, lactate isn’t increased because of tissue hypoxia alone