Metabolic acidosis

See also: Acidosis

Metabolic acidosis refers to any one of numerous pathological conditions affecting systemic acid-base physiology, conditions that manifest as an abnormal chemical compositional state 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 references 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 compartment (ICF) as well.

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 due to insufficient rates of excretion of carbon dioxide (exhalation by the lungs) relative to 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.

Thus, abnormally increased acidity characterizes both metabolic acidosis and respiratory acidosis, but an 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.

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 lactic acid production, often due to reduced oxygen delivery to body tissues; prolonged exercise; liver failure;
• 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.

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. That homeostatic target makes sense from a biological chemistry perspective for the following reasons: Hydrogen ions, protons, in aqueous solution bind to water molecules, molecules of H₂O, forming so-called hydronium ions, H₃O⁺. By hopping from one water molecule to an adjacent one, 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 — protons diffuse along their concentration gradients through the solution very rapidly. 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 disrupt 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, 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.