9th February 2024

Acid-Base Balance

Overview of acid-base balance

Introduction

Acid-base balance is the balance between the intake, production and elimination of hydrogen ions to maintain a pH between 7.35 and 7.45. Acidosis, a low pH under 7.35, refers to a raised hydrogen ion concentration and alkalosis, or a high pH over 7.45, refers to a low hydrogen ion concentration. pH is a negative logarithm of hydrogen ions; therefore, a slight change in pH results in a significant change in the concentration of hydrogen ions. To maintain this tight control, compensatory mechanisms occur within the kidneys and lungs.

Typical values on arterial blood gases are as follows:

pH 7.35 – 7.45

pO2 (on room air) >11.3 kPa

pCO2 4.7 – 6.0

HCO3- 22-28 mmol/l

It is essential to cite the percentage of inspired oxygen when documenting arterial blood gases.

Respiratory component

Normal physiology

The respiratory system helps control the acid-base balance within the body by adjusting the concentration of carbon dioxide within the body. Carbon dioxide is a by-product of metabolism. Carbon dioxide dissolves in blood to form carbonic acid during the following chemical reaction:

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

The transport of carbon dioxide in the form of bicarbonate predominates within the body. However, the body can also transport bicarbonate by carbaminohaemoglobin and deoxyhaemoglobin. These processes account for a small fraction of carbon dioxide transported. At the level of the alveolus, this is expelled from the body via its reverse process. 

Image Source: Wikimedia Commons (2013). 2319 Fig23, Licensed under a creative commons licence. Available for free at: https://upload.wikimedia.org/wikipedia/commons/2/28/2319_Fig_23.19.jpg  (Accessed: 4 January 2024).

Hypoventilation results in failure of the lungs to adequately remove CO2, causing hypercapnia. The excess carbon dioxide leads to an increase in carbonic acid and, hence, respiratory acidosis. Causes of this include chronic lung disease, acute on chronic lung disease, neuromuscular disease (GBS, Myasthenia gravis, etc.), decreased chest wall compliance (kyphoscoliosis, flail chest, etc.), sleep apnoea, reduced GCS (coma, intoxication, etc.).

When too much CO2 is lost through hyperventilation, blood becomes more alkalotic as carbonic acid levels drop. Causes include anxiety, pain, fever, severe anaemia, pregnancy (normal)

Respiratory component

The first and easiest thing to assess is whether the patient is in respiratory failure. A pO2 <10kPa on room air indicates hypoxaemia, but a pO2 of <8kPa on room air represents severe hypoxaemia and respiratory failure.

When assessing for respiratory failure on an ABG, it is crucial to consider the patient’s clinical state. 

• If the patient looks well, but the pO2 is very low on the gas, consider that the sample may be venous. 
• If the patient is on a large amount of oxygen, you would expect the pO2 to be raised; therefore, a normal pO2 indicates respiratory failure. To calculate the expected pO2, subtract 10kPa from the percentage of inspired concentration FiO2 (e.g. on 60% FiO2, you would expect a pO2 of 50kPa)

Next, is to consider the CO2 to establish whether the patient has type one or two respiratory failure. 

• Type 1 Respiratory failure – pO2 <8kPa with a normal pCO2 <6kPa. 
  • This occurs due to a mismatch between airflow in and out of the lungs and blood flow to the lungs. The lungs can still remove carbon dioxide but cannot adequately provide oxygen due to differences in the dissociation curves. 
  • Causes of Type 1 respiratory failure include pulmonary embolism, pulmonary oedema, and bronchoconstriction.
• Type 2 Respiratory failure – pO2 <8kPa with a raised pCO2 >6kPa. 

Respiratory acidosis is characterized by reduced pH, high pCO2 and normal HCO3- levels. Respiratory alkalosis is characterized by high pH, low pCO2 and normal HCO3- levels.

HCO3- levels are normal as the change in HCO3- requires the kidneys to adjust the bicarbonate levels within the circulation. The kidneys play a huge role in maintaining acid-base balance by reabsorbing bicarbonate from filtrate and excreting hydrogen ions. In acidosis, more bicarbonate is reabsorbed, more hydrogen ions are secreted, and more ammonia buffer (NH3) is formed. Conversely, alkalosis results in increased bicarbonate excretion. Neither response is rapid – metabolic compensation implies that the acid-base imbalance has been present for several days.

When metabolic compensation is present, the pH will normalize to neutral pH with partial compensation as the pH improves but has not returned to normal pH levels. 

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. 

Mixed respiratory and metabolic derangement

It is possible to have derangement in both respiratory and metabolic acid-base mechanisms simultaneously. In these cases, CO2 and HCO3- will move in opposite directions on blood gases.

Mixed respiratory and metabolic acidosis:

• pH low
• CO2 high
• Bicarbonate low

Causes include cardiac arrest and multi-organ failure

Mixed respiratory and metabolic alkalosis:

• pH high
• CO2 low
• Bicarbonate high

Causes include hyperemesis gravidarum, excessive ventilation in COPD and diuretic use in liver cirrhosis.

References

Hall, J. E., & Guyton, A. (2011). Guyton and Hall textbook of medical physiology. Saunders/Elsevier.

Costanzo, L. S. (2010). Physiology (4th ed.). Saunders/Elsevier.

Sherwood, L. (2010). Human physiology: From cells to systems (7th ed.). Brooks/Cole, Cengage Learning.