approach to lactic acidosis

7/24/2019 Approach to Lactic Acidosis

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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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approach to lactic acidosis

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