The pH (the negative logarithm of [H+]) is maintained at 7.4 (normal range 7.35-7.45). The metabolism of food and endogenous body tissues produces about 70-100 mmol of H+ each day, which is excreted by the kidneys. Bicarbonate (HCO3-) is the main plasma and extracellular fluid buffer. It mops up free H+ ions and prevents increases in the H+ concentration (Fig. 8.4). Bicarbonate is filtered at the glomerulus but is then reabsorbed in the proxi-mal and distal renal tubule. The lungs also constantly regulate acid-base balance through the excretion of CO2. Between production and excretion of H+ ions there is an extremely effective buffering system maintaining a con-stant H+ ion concentration inside and outside the cell. Buffers include hae-moglobin proteins, bicarbonate and phosphate.
Fig. 8.4 The carbonic anhydrase reaction.
Acid-base disturbances may be caused by:
■ Abnormal carbon dioxide removal in the lungs ('respiratory' acidosis and alkalosis)
■ Abnormalities in the regulation of bicarbonate and other buffers in the blood (‘metabolic' acidosis and alkalosis).
In general, the body compensates to some extent for changes in pH by regu-lating renal bicarbonate excretion and altering the respiratory rate. For instance, metabolic acidosis causes hyperventilation (via medullary chemo-receptors), leading to increased removal of CO2 in the lungs and partial compensation for the acidosis. Conversely, respiratory acidosis is accompa-nied by renal bicarbonate retention, which could be mistaken for primary metabolic alkalosis.
Measurement of pH, Paco2 and [HCO3-] will reveal which type of distur-bance is present (Table 8.8). These measurements are made on an arterial blood sample using an automated blood gas analyser. Clinical history and examination usually point to the correct diagnosis. In complicated patients, the Flenley acid-base nomogram can be used to identify the acid-base disorder that is present when arterial hydrogen ion concentration and Paco2 are known (Fig. 8.5).
This is usually associated with ventilatory failure, with retention of carbon dioxide (p. 584). Treatment is of the underlying cause.
Hyperventilation results in increased removal of carbon dioxide, resulting in a fall in PaCO2 and [H+].
Table 8.8 Changes in arterial blood gases
Normal or reduced
Normal or reduced
Normal or reduced
Normal or increased
Normal or increased
Normal or increased
The pH may be at the limits of the normal range if the acidosis or alkalosis is compensated, e.g. respiratory compensation (hyperventilation) of a metabolic acidosis.
The clue to the abnormality from the blood gases will be the abnormal PaCO2 and HCO3-
Fig. 8.5 The Flenley acid-base nomogram.
This is the result of the accumulation of any acid other than carbonic acid. The most common cause is lactic acidosis following shock or cardiac arrest.
These include hyperventilation, hypotension caused by arteriolar vaso-dilatation and the negative inotropic effect of acidosis, and cerebral dys-function associated with confusion and fits.
Differential diagnosis (the anion gap)
The first step is to identify whether the acidosis is the result of retention of HCl or of another acid. This is achieved by measurement of the anion gap. The main electrolytes measured in plasma are sodium, potassium, chloride and bicarbonate. The sum of the cations, sodium and potassium normally exceeds that of chloride and bicarbonate by 6-12 mmol/L. This anion gap is usually made up of negatively charged proteins, phosphate and organic acids. If the anion gap is normal in the presence of acidosis, it can be concluded
|Table 8.9 Causes of metabolic acidosis with a normal anion gap|
|Increased gastrointestinal HCO3- loss
− renal loss
Proximal (type 2) renal tubular acidosis
Tubular damage, e.g. drugs, heavy metals
Decreased renal H+ excretion
Distal (type 1) renal tubular acidosis
Type 4 renal tubular acidosis
Increased HCl production
Ammonium chloride ingestion
Increased catabolism of lysine, arginine
that HCl is being retained or NaHCO3 is being lost. The causes of a normal anion gap acidosis are given in Table 8.9.
If the anion gap is increased (i.e. >12 mmol/L), the acidosis is the result of an exogenous acid, e.g. salicylates or one of the acids normally present in small unmeasured quantities, such as lactate. Causes of a high anion gap acidosis are given in Table 8.10.
Increased production of lactic acid occurs when cellular respiration is abnor-mal, resulting from either lack of oxygen (type A) or a metabolic abnormality (type B). The most common form in clinical practice is type A lactic acidosis, occurring in septicaemic or cardiogenic shock.
This is a high anion gap acidosis caused by the accumulation of acetoacetic and hydroxybutyric acids.
Renal tubular acidosis
Renal tubular acidosis may occur in the absence of chronic kidney disease and is a normal anion gap acidosis. There is failure of the kidney to acidify the urine adequately. This group of disorders is uncommon and only rarely a cause of significant clinical disease. There are four types of which type 4 (also known as hyporeninaemic hypoaldosteronism) is the most common. Typical features are acidosis and hyperkalaemia occurring in the setting of mild chronic kidney disease, usually caused by tubulointerstitial disease or
|Table 8.10 Causes of metabolic acidosis with a high anion gap|
Renal failure (sulphate, phosphate)
diabetes. Plasma aldosterone and renin levels are low and do not respond to stimulation. Treatment is with fludrocortisone, diuretics, sodium bicarbonate and ion exchange resins for the reduction of serum potassium.
Reduction of the capacity to secrete H+ and NH4+, in addition to bicarbonate wasting, contributes to the acidosis of chronic kidney disease. Acidosis occurs particularly when there is tubular damage, such as reflux and chronic obstructive nephropathy. It is associated with hypercalciuria and renal osteodystrophy because H+ ions are buffered by bone in exchange for calcium. Treatment is with calcium or sodium bicarbonate, although acidosis in end-stage renal failure is only usually fully corrected by adequate dialysis.
This is much less common than acidosis and is often associated with potas-sium or volume depletion. The main causes are persistent vomiting, diuretic therapy or hyper-aldosteronism. Vomiting causes alkalosis both by causing volume depletion and through loss of gastric acid.
Cerebral dysfunction is an early feature of alkalosis. Respiration may be depressed.
This includes fluid replacement, if necessary, with replacement of sodium, potassium and chloride. The bicarbonate excess will correct itself.
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