Lactate Acidosis
9/5/10
PY
OH
- hyperlactaemia: a level from 2 to 5 mmol/L
- severe lactic acidosis: > 5 mmol/L (mortality very high)
- high mortality with lactate > 8mmol/L
PHYSIOLOGY
Daily production
- normal production = 20mmols/kg/day) -> blood -> hepatic and renal metabolism (Cori cycle)
- all tissues can produce lactate under anaerobic conditions.
Relationship of lactate to pyruvate
Pyruvate + NADH + H+ <=> Lactate + NAD+
- catalysed by lactate dehydrogenase
- pyruvate and lactate are in equilibrium
- lactic acid has a pK value of about 4 so it is fully dissociated into lactate and H+ at body pH
Tissues Producing Excess Lactate
- at rest, the tissues which normally produce excess lactate are:
(i) skin - 25% of production
(ii) red cells - 20%
(iii) brain - 20%
(iv) muscle - 25%
(v) gut - 10%
- during heavy exercise, the skeletal muscles contribute most of the muchincreased circulating lactate.
- during pregnancy, the placenta is an important producer of lactate (can pass to fetus as well).
Lactate metabolism and elimination
- lactate is metabolised predominantly in the liver (60%) and kidney (30%).
- 50% -> glucose (gluconeogenesis) and 50% -> CO2and water (citric acid cycle)
- this results in no net acid accumulation but requires the aerobic metabolism
- the small amount of lactate that is filtered(180mmol/day) is fully reabsorbed.
PATHOPHYSIOLOGY
- lactic acidosis can occur due to:
(i) excessive tissue lactate production
(ii) impaired hepatic metabolism of lactate (large capacity to clear)
- clinically there is often a combination of the above to produce a persistent lactic acidosis
CAUSES(Cohen& Woodsclassification)
Type A - Inadequate Oxygen Delivery
(i) anaerobic muscular activity (sprinting, generalised convulsions)
(ii) tissue hypoperfusion (shock, cardiacarrest, regional hypoperfusion -> mesenteric ischaemia)
(iii) reduced tissue oxygen delivery (hypoxaemia, anaemia) or utilisation (CO poisoning)
Type B - No Evidence of Inadequate Tissue Oxygen Delivery
B1: associated with underlying diseases
- LUKE: leukaemia, lymphoma
- TIPS: thiamine deficiency, infection, pancreatitis, short bowel syndrome
- FAILURES: hepatic, renal, diabetic failures
B2: associated with drugs & toxins
- phenformin
- cyanide
- beta-agonists
- methanol
- adrenaline
- salicylates
- nitroprusside infusion
- ethanol intoxication in chronic alcoholics
- anti-retroviral drugs
- paracetamol
- salbutamol
- biguanides
- fructose
- sorbitol
- xylitol
- isoniazid
B3: associated with inborn errors of metabolism
- congenital forms of lactic acidosis withvarious enzyme defects (eg pyruvate dehydrogenase deficiency)
DIAGNOSIS
- plasma lactate level
- once documented the cause must be found and treated appropriately
- D lactate = isomer of lactate produced by intestinal bacterial and not by humans ->a bed side test may be able to be developed to help with diagnosis of mesenteric ischaemia.
MANAGEMENT
(i) diagnose and correct the underlying condition
(ii) restore adequate tissue oxygen delivery
(iii) ensure appropriate compensatory hyperventilation where possible
Use of bicarbonate
- two randomised controlled studies of bicarbonate in lactic acidosis and shock found no beneficial effects on cardiac function or any other effects of pH correction.
- types available: NaHCO3, carbicarb, dichloroacetate, Tris/THAM
- only real justification in the treatment of acidosis: severe pulmonary hypertension and right heart failure to optimized right ventricular function and severe IHD where lactic acidosis is thought to be an arrythmogenic risk.
Adverse effects:
- acute hypercapnia
- ionised hypocalcaemia
- intracellular acidosis due to CO2 crossing cell membranes rapidly
- acute intravascular overload
- bicarbonate increases lactate production by increasing the activity of the rate limitingenzyme phosphofructokinase, shifts Hb-O2 dissociation curve, increased oxygen affinityof haemoglobin and thereby decreases oxygen delivery to tissues
Indications:
(i) patients with pulmonary hypertension in whom pulmonary vasoconstriction may be worsened by acidosis
(ii) patients with significant ischaemic heart disease in whom severe acidosis lowers thethreshold for arrhythmia
Dialysis/haemofiltration
- peritoneal dialysis is not useful in removing lactate when using bicarbonate buffered
- haemofiltration: it remains a useful marker of clinical disease progressionin patients on bicarbonate buffered haemofiltration
Jeremy Fernando (2010)