Lactic acidosis: Its more than JUST lactic acidosis

Summary of Lactic Acidosis:
Major sites of Lactate production includes the skin, muscles, brain and RBCs (Placenta in pregnant women)
In the absence of oxygen (or in the case of RBC), energy is derived from glycolysis of glucose
Lactate is produced in this process with 2 ATP
(pyruvate to lactate with NADH --> NAD+. NAD+ regeneration is important for further glycolysis)
With the reestablishment of oxygen, lactate is oxidized into water and carbon dioxide or undergoes gluconeogenesis (only liver and kidney have enzymes for gluconeogenesis)
Liver (60%) and kidneys (30%) are important metabolizers of lactate
50% are converted to glucose (gluconeogenesis) and 50% metabolized to water and carbon dioxide in the citric acid cycle

If the oxidation rxn is absent, lactate accumulates resulting in lactic acidosis:
- the balance of blood lactate depends on release into bloodstream and hepatorenal uptake
- these mechanisms maintain blood lactate at 1 mmol/L
- renal threshold for lactate is around 5-6mmol/L, i.e. if blood lactate levels exceed 5-6 mmol/L ==> lactate will be excreted in the urine

Common causes:

1. Medication: Phenformin (like metformin, it is a biguanide and causes weight loss. It is no longer in use due to lactic acidosis being its S/E) and anti-retrovirals (mitochondrial toxicity). Catecholamines and Cocaine cause lactic acidosis by increasing lactate production.
2. poisons: CO, cyanide
3. Diabetic ketoacidosis
4. Liver disease
5. Convulsions, severe exercise

Typically, they present with:
1. abdominal pain and vomiting
2. rapid and deep breathing (Kussmauls?)

Sounds like GE isnt it?

Definition:
Normal lactate ~ 1mmol/L
Hyperlactaemia ~2-5mmol/L
Severe lactic acidosis >5mmol/L (thus lactate in urine?)

Classification of Lactic acidosis:
Lactic acidosis is divided into types A and B
They differ with regards to adequacy of tissue oxygen delivery

Type A: decreased perfusion or oxygenation (anaerobic metabolism), mitochondria assumed to be normal and intact, most common clinical situation. Examples"
- severe respiratory failure
- anaemia (poor oxygen delivery)
- CO poisoning
- hypoperfusion of tissues (e.g. hypovolaemia(e.g. DKA) hypotension)
- convulsions and sprinting (anaerobic muscular activity)
- mesenteric ischaemia (compromised regional oxygen delivery)

Type B:
- B1: underlying diseases (e.g. Liver disease, renal disease, lymphoma, leukaemia, DKA, AIDS)
- B2: intoxication, medication (e.g. phenformin, anti-retroviral, catecholamines, cocaine, cyanide)
- B3: inborn errors of metabolism

Special attention is paid in the discussion of liver's role:
- the liver has immense capacities for lactate metabolism
- pathologies like sepsis, hypovolaemia, hypotension, cirrhosis, hypothermia result in decreased hepatic capacity for lactate metabolism


Notes:
Causes of HAGMA:
- uraemic acidosis
- lactic acidosis
- ketoacidosis

Why bicarbonate does not work in lactic acidosis:
- metabolic acidosis (intracellular) inhibits PFK, the RDS enzyme in glycolysis
- on administration of IV bicarb, there is intracellular metabolic alkalosis, as such removes the inhibition of PFK resulting in further lactate production