9th February 2024

Metabolic component

Normal physiology

The kidneys are the main organs that control metabolic acid-base balance. It achieves this by manipulating the body’s bicarbonate and hydrogen ion levels. As a reminder, here is the primary reaction between CO2 and water within the body.

CO2 (carbon dioxide) + H2O (water) ⇌ H2CO3 (carbonic acid) ⇌ HCO3- (bicarbonate) + H+ (hydrogen ion)

The kidneys can reabsorb nearly all of the HCO3- excreted within the urine when needed. The reabsorption rate of HCO3- can be controlled depending on the levels of acidaemia or alkalosis. It can also produce new HCO3- by effectively exploiting the reversible reaction above by excreting more H+ ions and shifting the equilibrium to produce more HCO3- ions. 

Metabolic acidosis and alkalosis

Metabolic acidosis can be seen as low pH, low HCO3- and normal CO2 on an ABG. Metabolic acidosis is common as many of the body’s metabolic reactions produce acids as by-products. Imbalance occurs in the following situations:

• The rate of acid production is increased
• The rate of acid excretion is reduced
• Acid is ingested
• Increased loss of bicarbonate via the kidneys or gastrointestinal tract

Causes of metabolic acidosis can be split into two categories: those with a normal anion gap (raised chloride) and those that cause an increased anion gap (normal chloride and exogenous acid). To calculate the gap, the following equation can be used: 

Anion gap = Na + K + (Cl- + HCO3-)

A normal anion gap between 10-18 mmol/L represents the negative charge on albumin, phosphate, sulphate and other organic acids. 

Causes of metabolic acidosis with normal anion gap:

• Diarrhoea – due to loss of alkaline lower GI secretions and potassium
• Renal tubular acidosis – reduced urinary acid secretion via reduced secretion of hydrogen ions into the urine (Type 1 RTA), reduced reabsorption of bicarbonate from filtrate (Type 2 RTA) or reduced ammonia production due to reduced aldosterone levels or renal resistance to aldosterone (Type 4 RTA)
• Hypoaldosteronism
• Partially treated ketoacidosis

Causes of metabolic acidosis with raised anion gap can be usefully remembered using the mnemonic CAT-MUDPILES:

• Carbon monoxide/Cyanide
• Alcohol ketoacidosis
• Theophylline/Toluene
• Methanol
• Uraemia
• Diabetic ketoacidosis/Starvation ketoacidosis
• Paracetamol/Paraldehyde
• Iron/Isoniazid/Inborn errors of metabolism
• Lactic acidosis
• Ethanol/ethylene glycol
• Salicylates.

Metabolic alkalosis is seen as high pH, HCO3- and normal pCO2 levels on an ABG. This is often accompanied by hypokalaemia. In normal circumstances, the kidneys are very efficient at secreting excess bicarbonate to maintain equilibrium, making states of metabolic alkalosis less common. High bicarbonate ions will react with circulating H+ ions, reducing free H+ ions. 

Causes of metabolic alkalosis:

• GI hydrogen ion loss (vomiting, pyloric stenosis, excess NG suction)
• Hypokalaemia (compensatory intracellular shift of hydrogen ions)
• Renal hydrogen ion loss 
  • loop/thiazide diuretics
  • mineralocorticoid excess
  • Post hypercapnia – with mechanical ventilation, CO2 levels fall quicker than the renal compensatory mechanism can switch off, resulting in excess bicarbonate.
  • milk-alkali syndrome – secondary to excess calcium carbonate ingestion
• Oral alkali therapy
• Contractional alkalosis (volume depletion)

The respiratory system compensates for metabolic acid-base abnormalities. This is achieved by adjusting pCO2 in the circulation. The lungs will either increase ventilation to blow off CO2 or decrease ventilation to retain CO2 in response to stimulation from the medulla. This can occur quickly in order to restore equilibrium. As before, compensation occurs as the pH returns towards the normal pH range, with partial compensation as a partial pH correction.