Lactate và những thay đổi của nó

• 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]

Lactic Acid

Kinetics and Clinical Use

JOSHUA SOLOMON, MD

ASSOCIATE PROFESSOR OF MEDICINE NATIONAL JEWISH HEALTH

Outline

• Background

• History

• Kinetics

• Myths of lactate and lactic acidosis

• Types of lactic acidosis

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

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

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)

LACTATE FORMATION

Lactate Production at Rest

SKIN – 25% RBCs – 20%

CNS – 20% MUSCLE – 25%

Lactate Transport to Tissue

Myths

• Lactate production leads to acidosis

• Lactate is “bad” for cells and organs

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

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

Lactate production and tissue hypoxia

• Not correlated with tissue hypoxia or oxygen extraction

• Septic patients have increased oxygen

consumption, glucose utilization and

pyruvate production

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

Elevated lactate and

LACTATE UPTAKE IN

TISSUES LACTATE

PRODUCTION

LACTATE UPTAKE IN

TISSUES

LACTATE PRODUCTION

Metabolized by liver in to hours

Seheult et al Clin Chem Lab Med 2017; 55(3): 322–333

Systemic/local hypoperfusion Increased glycolysis

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

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)

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

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