Metabolic acidosis

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See also: Acidosis

In the health sciences, metabolic acidosis refers to a pathological state of systemic acid-base physiology, a state that manifests as an abnormal chemical composition of the body, a state that, when uncomplicated by masking acid-base pathophysiological conditions, clinicians characterize as abnormally increased acidity — measured as decreased pH or increased hydrogen ion concentration (the concentration symbolized as [H+]) — accompanied by abnormally decreased bicarbonate concentration (the concentration symbolized as [HCO3]) — the abnormalities of composition judged by comparison with reference values in persons judged in 'normal' health, the abnormalities detectable in the extracellular fluid (ECF) compartment of the body, usually through measurements on samples taken from the blood compartment, the clinicians acknowledging that, with few notable exceptions, a similar paired pH and [HCO3] compositional abnormality exists in the intracellular fluid (ICF) compartment as well.

The pathological conditions that cause metabolic acidosis categorize as follows:

  • habitual consumption of a diet who metabolism by the body yields a net load of non-carbonic acids as end-products (e.g., a ketogenic diet used in the treatment of certain types of epilepsy ;
  • conditions that cause the body's metabolic processes to produce abnormally increased amounts of non-carbonic acids (e.g., β-hydroxybutyric acid in diabetic ketoacidosis);
  • diseases of the kidneys that abnormally decrease generation, and delivery to the systemic circulation, of bicarbonate, in amounts over and above that filtered from, and reabsorbed back into, the circulation, amounts sufficient to neutralize the non-carbonic acids produced by habitual consumption of a diet whose metabolism by the body yields a net load of non-carbonic acids as end-products (e.g., certain disorders of the renal tubules);
  • conditions that cause the body to abnormally increased amounts of bicarbonate through the feces (e.g., diseases causing diarrhea);

Overview

Clinicians distinguish between metabolic acidosis and respiratory acidosis. In the latter, the acid, carbonic acid, or H2CO3, deriving from the hydration reaction with the metabolic waste product, carbon dioxide (CO2),

CO2 + H20 = H2CO3 = H+ + HCO3

tends to accumulate in body fluids when the rates of excretion of carbon dioxide (exhalation by the lungs) falls below the rates of carbon dioxide production by cellular metabolism. Abnormally increased acidity results from dissociation of carbonic acid, which occurs rapidly spontaneously, yielding hydrogen ions, the bicarbonate concentration also increasing to abnormally increased levels, inasmuch as the dissociation of carbonic acid also yields bicarbonate. Under ordinary physiological conditions, metabolism produces on the order of 15,000 mmol carbon dioxide per day, which in the healthy steady-state the lungs exhale.

Abnormally increased acidity characterizes both metabolic acidosis and respiratory acidosis, but an accompanying abnormally reduced bicarbonate concentration characterizes only metabolic acidosis. Some clinicians define metabolic acidosis in terms of a primary decrease in blood plasma or serum bicarbonate concentration [HCO3 ]p.

Metabolic acidosis involves only non-carbonic acids, of which numerous such acids can underlie the compositional abnormality characteristic of metabolic acidosis. In healthy adult humans consuming typical American diets, net production of non-carbonic acids ranges between 20 and 120 mmol per day, matched by kidney excretion of an equal amount of net acid per day.

Common examples of metabolic acidosis include:

  • Diabetic ketoacidosis, caused by abnormally high rates of liver production of ketoacids, ultimately due to severe insulin deficiency;
  • Lactic acidosis, caused by abnormally high rates of hydrogen ion and lactate anion production, often due to reduced oxygen delivery to body tissues; prolonged exercise; liver failure;[1]
  • Renal acidosis, caused by diseased kidneys that fail to deliver sufficient renally-generated bicarbonate to the body in the circumstances of bicarbonate losses due to:
    • titration of bicarbonate by non-carbonic acids produced during metabolism foods from diets that consist of more acid-producing than base-producing foods;
    • down-setting of the plasma bicarbonate concentration threshold at which the kidneys return to the body all the bicarbonate filtered by the kidneys from the blood;
    • defects of renal tubules impairing hydrogen ion secretion into the tubule lumens.

Acid-Base homeostasis

Homeostatic mechanisms regulating the acid-base status of the ECF and ICF appear to target the concentration of the positively charged hydrogen ion [H+], a proton, the concentration often expressed in terms of the common acidity index, pH.[2] That homeostatic target makes sense from a biological chemistry perspective for the following reasons: Hydrogen ions, protons, in aqueous solution bind weakly to water molecules, molecules of H2O, forming so-called hydronium ions, H3O+. Through thermal agitation, the protons diffuse along their concentration gradients through the solution very rapidly by hopping from one water molecule to an adjacent one, in the process electrically kicking a proton off the adjacent molecule, which repeats the hop, which kicks another proton on — a kind of concerted transport through water, similar to the way electrons conduct along a copper wire.

In their attachment to the tiny water molecule — tiny by comparison to the numerous macromolecules (proteins, nucleic acids, lipids) present in body fluids — they jiggle and swirl vigorously, driven by the thermal (heat) energy of the body fluids. Accordingly, they frequently encounter a macromolecule, their small size giving them access to the interstices of the macromolecule as well as their outer surfaces, and their charged status giving them the ability to interact with the charges on the macromolecules, charges that importantly help maintain the convoluted structure of the macromolecule critical for its normal biological/biochemical function. Small changes in pH can exert large or small functional disruptions of proteins, potentially leading to acute serious biological disturbances in such activities as enzyme catalysis, cell signaling, gene regulation, and many others, very many more in the ICF than in the ECF.[2]


References

  1. Robergs RA, Ghiasvand F, Parker D. (2004)Biochemistry of exercise-induced metabolic acidosis. Am J Physiol Regul Integr Comp Physiol 287:R502-R516.
  2. 2.0 2.1 Bevensee MO, Boron WF. (2008) Control of Intracellular pH. Volume 2. Chapter 51. Page 1429. In: Alpern RJ, Hebert SC, Seldin DW, Giebisch GH. (editors) (2008) Seldin and Giebisch's The Kidney: Physiology & Pathophysiology. 2 volumes. Elsevier Inc., Academic Press: Amsterdam. ISBN 9780120884896. 2871 pages