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Approach to lactic acidosis

Dr Nikit
19/8/14

Lactate levels in clinical practice are


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