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Approach to lactic acidosis
Dr Nikit
19/8/14
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Lactate levels in clinical practice areoften used as surrogate for illness severity
gauge response to therapeuticinterventions
Type A: related to tissue
hypoperfusion Type : not related to tissue
hypoperfusion
!igh lactate: "4 ##ol/L
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+ iso#ers: L,lactate / D,lactate
!u#ans have LD! to #eta-olise Liso#er
D iso#er produced -y -acteria.Lacto-acillilus 0hich reuires renale2creation solely
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La- #easure#ent
L lactate
Arterial sa#ple
To -e processed in 1*,)3 #in f delay then transport on ice
n conditions other than tissue
hypoperfusion venous lactatecorrelates 0ell 0ith arterial
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%athophysiology of lactate
Lactate: end product of anaero-icglycolysis and is produced -y thereduction of pyruvate
Nor#al lactate:pyruvate ratio: +3:1
skeletal #uscle5 -rain5 675 renal#edulla: responsi-le for #aority ofthe production
T0o fates: conversion -ack to pyruvate
e2cretion -y the kidney
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Nor#ally less than + is e2creted inthe urine
ven in the setting of e2peri#entalhyperlactate#ia.-lood lactate 13##ol/L: 13 , 1+ of lactatee2creted
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;2idativephosphorylation
LD!
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%D!: rate li#iting #itochondrialen: rate li#iting en
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under conditions of hypo2ia5 pyruvateis una-le to enter #itochondria and isconverted to lactate instead(
The increase in NAD!/NAD$ ratio andthe pyruvate -oth favor continuedproduction of lactate
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The anaero-ic #eta-olis# of glucose producesonly lactate5 AT%5 and 0ater
No protons are produced
Acidosis occurs 0hen AT% is hydroly
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!o#eostatic #echanis#s
?,phosphofructokinase:key en
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Type A LA
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Type LA
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Drugs causing lacticacidosis
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Approach to lactic acidosis
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Treat#ent of lactic acidosis
Na!7;)
7ar-icar-
T!AE Tri-onate
Dicloroacetate
6enal replace#ent therapy
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7ar-icar-
ui#olar #i2ture of Na!7;) and Na+7;)
This agent is uniue in that it does notgenerate 7;+ and therefore does not have
the potential to 0orsen intracellular acidosis Beveral ani#al studies have sho0n
i#prove#ents in acid,-ase -alance5 includingintracellular p!5 lactate production5 and
cardiac he#odyna#ic para#eters ;nly one study in hu#ans has -een pu-lished
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T!AE
Tris,hydro2y#ethyl a#ino#ethane
t is a -iologically inert a#ino alcohol that -u@ers
car-on dio2ide and Acids
ecause it has the capacity to -u@er and notgenerate 7;+5 T!AE is e@ective in a closed syste#
Approved in the Fnited Btates as T!AE acetate foruse in prevention and treat#ent of #eta-olicacidosis
6enally e2creted Bide e@ects: respiratory depression5hypoglyce#ia5
and hyperkale#ia
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Tri-onate
t is a #i2ture of T!AE5 Na!7;)5acetate5 and phosphate
Tri-onat appears to have a #orefavora-le e@ect on intracellular p!-ecause there is less 7;+ generation
t also has -een sho0n to increaseintracellular calciu#5 0hich #ay-eneCt #yocardial contractility
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Dicloroacetate
ncreases activity of %D! and helps inclearing lactate
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