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Key Clinical Questions

  • image What are common causes of increased anion gap metabolic acidosis?

  • image How does measurement of the urinary anion gap help narrow the differential diagnosis of normal anion gap metabolic acidosis?

  • image What are the major types of renal tubular acidosis, and how are they diagnosed?

  • image How is urinary chloride used in the diagnosis of metabolic alkalosis?

  • image How is the delta gap used to diagnose complex acid-base disorders?

Acid-base disturbances occur frequently in the acutely ill hospitalized patient. Many physicians are intimidated by the complexity of acid-base analysis, as multiple, partially offsetting disorders can be challenging to diagnose. However, in the hospital setting, especially the critically ill, it is crucial that patients with acid-base disturbances be quickly identified and the abnormality be accurately interpreted. Swift intervention to treat the underlying causes is often necessary to avoid the often lethal consequences of severe acid-base disturbances.


A typical Western diet generates about 15,000 mmol of volatile acids, in the form of CO2, and ~70 mmol (1 mmol/kg) of fixed acid each day. CO2 is excreted by normal respiration. Fixed acids are buffered by intra- and extracellular buffers. New buffers, predominantly HCO3, must be continuously produced to replace buffers consumed in titrating fixed acids. Complex acid-base homeostasis mechanisms, which include chemical buffering in conjunction with the excretion of CO2 by the respiratory system and new HCO3 production by the kidneys, normally maintain the blood pH between 7.35 and 7.45.

Acid-base homeostasis requires complementary functions of the respiratory and the renal systems. The kidneys play a central role by reabsorbing filtered bicarbonate, approximately 4000 mmol/d, and generating new bicarbonate. The central nervous system and the respiratory systems control the arterial CO2 tension (PaCO2). Respiratory CO2 elimination is determined by alveolar ventilation. Kidneys generate new bicarbonate through the process of net acid excretion. Under normal conditions, net acid excretion balances fixed acid production. A disturbance of either respiratory CO2 elimination or the balance between fixed acid generation and renal net acid excretion results in an acid-base disorder.

PRACTICE POINT Glossary of terms for acid-base disorders

  • Acidemia: serum pH < 7.36

  • Alkalemia: serum pH > 7.44

  • Acidosis: pathophysiologic processes which favor development of acidemia

  • Alkalosis: pathophysiologic processes which favor development of alkalemia

  • Hypercapnia: underexcretion of CO2

  • Hypocapnia: overexcretion of CO2

  • Anion gap: unmeasured anions in plasma

  • Delta anion gap (ΔAG): prevailing minus normal AG

  • ΔHCO3: normal minus prevailing HCO3


These disorders involve only a single acid-base disorder, and include metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis. A key distinguishing feature is that the pH is always abnormal, as the compensation is never complete. Simple acid-base disorders can be classified as acute or chronic based ...

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