Lactic acidosis and hyperlactataemia

Question 1

Write the equation for Glycolysis

Answer 1

Gluc + 2 ADP + 2NAD+ –> 2Pyruvate + 2ATP + 2 NADH

Question 2

List the possible pathways that pyruvate can follow once formed by glycolysis

Answer 2

1. TCA cycle (mitochondria) –> Acetyl CoA + CO2
2. Cori cycle –> Lactate –> Liver –> Gluconeogenesis
3. Cahill cycle –> Alanine –> Liver –> Gluconeogenesis

The conversion of pyruvate to lactate is reserved primarily for excess pyruvate levels

Question 3

Under what conditions is pyruvate converted to lactate

Answer 3

Pyruvate + NADH + H+ Lactate + NAD+

The equation is in equilibrium and under normal conditions the ratio of lactate to pyruvate is 10:1

The ratio of NADH to NAD+ by the law of mass action determines the balance between lactate and pyruvate

The conversion of pyruvate to lactate is favoured hypoxic conditions and several other clinically relevant conditions

Question 4

What maintains a normal lactate level of 1 mmol/L

Answer 4

The balance between release into the bloodstream and hepatorenal uptake

Question 5

List the conditions favouring the conversion of pyruvate to lactate

Answer 5

1. Systemic hypoperfusion necessitating anaerobic metabolism
2. Regional hypoperfusion and microcirculatory dysfxn
3. Increased aerobic glycolysis (Pyruvate production exceeds pyruvate dehydrogenase capacity)
   a) Cytokines
   b) Increased Catecholamines
   c) Leucocytes at site of inflammation
4. Mitochondrial dysfunction (sepsis / drug toxicity)
5. Impaired Pyruvate Dehydrogenase
   a) Alcohol use (thiamine deficiency)
   b) Cofactor deficiency states

Question 6

What ultimately determines the lactate concentration

Answer 6

The lactate concentration reflects the balance between net lactate production and net lactate consumption/clearance

Question 7

Classify severity of hyperlactataemia

Answer 7

Normal: 0.6 - 1.8

Hyperlactataemia: 2 - 5

Severe hyperlactataemia: > 5

High mortality rate: > 8

Question 8

Where is lactate metabolized

Answer 8

Liver 60%
Kidneys 30%
Heart 10%

Question 9

What does the liver and kidneys to with lactate

Answer 9

Liver
- Produce glucose (and glycogen) via the Cori cycle

Kidney

• Also uses lactate in gluconeogenesis
• Renal threshold is 5 mmol/L (does not excrete lactate in the normal range)
• Severe kidney injury –> impaired lactate excretion