Chapter 3 Hydrogen ion homoeostasis and blood gases
Introduction
Buffering of hydrogen ions
For every hydrogen ion buffered by bicarbonate, a bicarbonate ion is consumed (see Equation 3.2). To maintain the capacity of the buffer system, the bicarbonate must be regenerated. Yet, when bicarbonate is formed from carbonic acid (indirectly from carbon dioxide and water), equimolar amounts of hydrogen ions are formed simultaneously (see Equation 3.2). Bicarbonate formation can only continue if these hydrogen ions are removed. This process occurs in the cells of the renal tubules, where hydrogen ions are secreted into the urine, and where bicarbonate is generated and retained in the body.
Bicarbonate reabsorption and hydrogen ion excretion
The luminal surface of renal tubular cells is impermeable to bicarbonate and, therefore, direct reabsorption cannot occur. Within the renal tubular cells, carbonic acid is formed from carbon dioxide and water (Fig. 3.1). This otherwise rather slow reaction (see Equation 3.1) is catalysed in the kidneys by the enzyme carbonate dehydratase (carbonic anhydrase). The carbonic acid thus formed dissociates into hydrogen and bicarbonate ions. The bicarbonate ions pass across the basolateral borders of the cells into the interstitial fluid. The hydrogen ions are secreted across the luminal membrane in exchange for sodium ions, which accompany bicarbonate into the interstitial fluid (see Fig. 3.1). The formation of bicarbonate and hydrogen ions is promoted by their continuous removal and by the presence of carbonate dehydratase.
Clinical and Laboratory Assessment of Hydrogen Ion Status
By the law of mass action, it follows from the equations describing the dissociation of carbonic acid (Equations 3.1 and 3.2) that [H+] is directly proportional to Pco2 and inversely proportional to bicarbonate concentration; that is, it is determined by the ratio of Pco2 to bicarbonate:
The constant, K, embraces the dissociation constants for Equations 3.1 and 3.2 and the solubility coefficient of carbon dioxide, which governs the concentration of the gas in solution at a given partial pressure. When [H+] is measured in nmol/L, bicarbonate in mmol/L and Pco2 in kilopascals (kPa), the value of K is approximately 180 at 37°C; if Pco2 is measured in mm Hg, the value of K is 24.
Disorders of Hydrogen Ion Homoeostasis
Non-respiratory (metabolic) acidosis
The primary abnormality in non-respiratory acidosis is either increased production or decreased excretion of hydrogen ions other than from carbon dioxide. In some cases, both may contribute. Loss of bicarbonate from the body can also, indirectly, cause an acidosis. Causes of non-respiratory acidosis are given in Figure 3.6. Excess hydrogen ions are buffered by bicarbonate (Equation 3.2) and other buffers. The carbonic acid thus formed dissociates (Equation 3.1) and the carbon dioxide is lost in the expired air. This buffering limits the potential rise in hydrogen ion concentration, but at the expense of a reduction in bicarbonate concentration, which is a constant feature of non-respiratory acidosis.

Figure 3.6 Principal causes of non-respiratory (metabolic) acidosis. aAcidosis with normal anion gap.
The complete correction of a non-respiratory acidosis requires reversal of the underlying cause, for example rehydration and insulin for diabetic ketoacidosis (see Case history 11.2) and removal of salicylate in salicylate overdose. It is important to maintain adequate renal perfusion to maximize renal hydrogen ion excretion. The use of exogenous bicarbonate to buffer hydrogen ions is discussed below and on p. 193.
Decreased excretion of hydrogen ions
Acidosis occurs in renal glomerular failure (see Case history 4.2), when the decreased glomerular filtration causes a reduction in the amount of sodium that is filtered and, therefore, available for exchange with hydrogen ions. The amount of phosphate filtered and available for buffering also decreases. Renal tubular acidoses are discussed in Chapter 4.
Loss of bicarbonate
Loss of bicarbonate and retention of hydrogen ions can result in acidosis in patients losing alkaline secretions from the small intestine (e.g. through fistulae). In the stomach, bicarbonate generated from carbon dioxide and water diffuses into the blood and hydrogen ions are secreted into the lumen (Fig. 3.8). In the pancreas and small intestine, the movements of bicarbonate and hydrogen ions occur in the opposite directions (see Fig. 3.8); thus hydrogen ions that are secreted into the stomach lumen are neutralized by bicarbonate in the small intestine.
