often used as surrogate for illness severity gauge response to therapeutic interventions
Type A: related to tissue
hypoperfusion Type B: not related to tissue hypoperfusion High lactate: >4 mmol/L
2 isomers: L-lactate / D-lactate
Humans have LDH to metabolise L isomer D isomer produced by bacteria (Lactobacillilus) which requires renal excreation solely
Lab measurement
L lactate Arterial sample To be processed in 15-30 min If delay then transport on ice In conditions other than tissue hypoperfusion venous lactate correlates well with arterial
Pathophysiology of lactate Lactate: end product of anaerobic glycolysis and is produced by the reduction of pyruvate Normal lactate:pyruvate ratio: 20:1 skeletal muscle, brain, RBC, renal medulla: responsible for majority of the production Two fates: conversion back to pyruvate excretion by the kidney
Normally less than 2% is excreted in
the urine Even in the setting of experimental hyperlactatemia(blood lactate 10 mmol/L): 10 - 12% of lactate excreted
LDH
Oxidative phosphorylation
PDH: rate limiting mitochondrial
enzyme in the oxidation of pyruvate PFK: rate limiting enzyme in gylcolysis liver and kidney are important lactate consuming organs: under normal conditions use approximately 60% of the circulating lactate
under conditions of hypoxia, pyruvate
is unable to enter mitochondria and is converted to lactate instead. The increase in NADH/NAD+ ratio and the pyruvate both favor continued production of lactate
The anaerobic metabolism of glucose produces
only lactate, ATP, and water No protons are produced Acidosis occurs when ATP is hydrolyzed to ADP and Pi releasing a hydrogen ion 1 mole of glucose produces 2 moles of lactate and 2 moles of hydrogen These hydrogen ions are then titrated by bicarbonate and non-bicarbonate buffers When oxygen is available, hydrogen ions can enter mitochondria and are used for oxidative phosphorylation
Homeostatic mechanisms 6-phosphofructokinase: key enzymes in glucose metabolism, is inhibited by intracellular acidosis kidney plays a more important role in lactate disposal Specifically gluconeogenesis in the renal cortex is enhanced by increased activity of the rate-limiting enzyme phosphoenolpyruvate carboxykinase Even in the setting of marked renal hypoperfusion, lactate can still be removed by the kidney through this pathway
Type A LA
Type B LA
Drugs causing lactic
acidosis
Approach to lactic acidosis
Treatment of lactic acidosis
NaHCO3 Carbicarb THAM Tribonate Dicloroacetate Renal replacement therapy
Carbicarb Equimolar mixture of NaHCO3 and Na2CO3 This agent is unique in that it does not generate CO2 and therefore does not have the potential to worsen intracellular acidosis Several animal studies have shown improvements in acid-base balance, including intracellular pH, lactate production, and cardiac hemodynamic parameters Only one study in humans has been published
THAM Tris-hydroxymethyl aminomethane It is a biologically inert amino alcohol that buffers carbon dioxide and Acids Because it has the capacity to buffer and not generate CO2, THAM is effective in a closed system Approved in the United States as THAM acetate for use in prevention and treatment of metabolic acidosis Renally excreted Side effects: respiratory depression,hypoglycemia, and hyperkalemia
Tribonate It is a mixture of THAM, NaHCO3, acetate, and phosphate Tribonat appears to have a more favorable effect on intracellular pH because there is less CO2 generation It also has been shown to increase intracellular calcium, which may benefit myocardial contractility
Dicloroacetate Increases activity of PDH and helps in clearing lactate
