Stephen L Gluck
Acid-base disorders are common clinical problems resulting from a wide variety of pathophysiological conditions, including newly recognised acquired and genetic causes. The history and physical examination and measurement of blood and urinary indices allow identification of the underlying cause of these disorders in mostcases. Treatment directed at correction of electrolyte abnormalities and the underlying cause for the disorder is essential for preventing the acute and long-term metabolic consequences of acid-base derangements.
The extracellular fluid (ECF) contains about 350 mmol of bicarbonate buffer. Every day metabolism produces acid (as H+) to a total of about 70 mmol (1 mmol/kg) asnon-volatile sulphuric acid (25 mmol) from aminoacid catabolism, non-metabolised organic acids (40 mmol) and phosphoric and other acids. The kidney reabsorbs all of the filtered bicarbonate (HCO3–) and generates new bicarbonate in the collecting duct. The proximal tubule reabsorbs some 85% (3800 mmol) daily of filtered HCO3– and the thick ascending limb reabsorbs 10% (450 mmol).1,2 In thecollecting duct, proton secretion titrates the remaining luminal HCO3–, and buffering of secreted protons by non-bicarbonate buffers in the tubular lumen, mainly phosphate and ammonia, enables the cells to generate new HCO3–.3 The rate of secretion of hydrogen ions (H+, protons) is affected by several factors, including luminal pH, systemic pCO2, mineralocorticoids, and the potential difference acrossthe collecting duct.4 The renal cortical segment of the collecting duct normally has a potential difference of 30 to 60 mV, arising largely from sodium reabsorption, and this is an important driving force for H+ secretion.4 The amount of ammonium ion (NH4+) accumulating in the collecting duct increases as urinary pH becomes more acidic. Urinary ammonia is generated in mitochondria of the proximaltubule by deamination of glutamine.5 Ammonia production is subject to physiological regulation, adding a mechanism for control of nett acid excretion independent of the rate of distal H+ secretion; the rate of ammonia production per nephron is increased by metabolic acidosis, potassium (K+) depletion, glucocorticoids, loss of functional renal mass, and other factors, and is suppressed byhyperkalaemia.6 Under normal steady-state conditions, the nett quantity of acid secreted and the consequent renal generation of new bicarbonate equals the rate of metabolic proton generation, preserving H+ balance). When that balance is disturbed the consequence is acidosis or alkalosis.
Lancet 1998; 352: 474–79
Departments of Medicine and Cell Biology and Physiology, Washington University School ofMedicine, St Louis, MO, USA (Prof S L Gluck MD) Correspondence to: Dr Stephen L Gluck, Renal Division, Washington University School of Medicine, 660 South Euclid Avenue, Box 8126, St Louis, MO 63110, USA (e-mail: firstname.lastname@example.org)
Metabolic effects of H+ retention
In metabolic acidosis non-volatile acid accumulates or HCO3– is lost at a rate that induces pathophysiologicalresponses, and this can happen even when the plasma [HCO3–] is normal. “Non-volatile acid” refers to acids other than carbonic acid or CO2, and I shall use the term acid interchangeably with non-volatile acid unless otherwise stated. Nett retention of H+, which occurs either by increased intake or generation of acid or by loss of HCO3–, activates three adaptive physiological responses—namely,buffering, increased ventilation, and increased renal reabsorption and generation of HCO3–. Retained acid is titrated by both extracellular HCO3– and “cellular” buffers (mainly bone mineral7 and skeletal muscle8). If the retention of acid is great enough, ventilation is stimulated within minutes, principally by increasing ventilatory volume (Kussmaul respirations). The kidney responds to nett...