Metabolic acidosis

See also: Acidosis

Metabolic acidosis refers to an abnormal chemical compositional state of the body that clinicians characterize as abnormally increased acidity — measured as pH reduction or hydrogen ion concentration [H⁺] increase — accompanied by abnormally reduced bicarbonate (HCO₃^-) concentration in the extracellular fluid (ECF) compartment of the body, acknowledging that few notable exceptions similar compositional abnormalities exist 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^– — accumulates in body fluids due to insufficient rates of excretion (exhalation by the lungs). Abnormally increased acidity results from dissociation of carbonic acid, yielding hydrogen ions, but the bicarbonate concentration increases to abnormally increased levels as the dissociation of carbonic acid also yields bicarbonate. Abnormally increased acidity characterizes both metabolic acidosis and respiratory acidosis, but an abnormally reduced bicarbonate concentration characterizes only metabolic acidosis. Metabolic acidosis involves only noncarbonic acids, of which numerous such acids can underlie the condition.

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 due to reduced oxygen delivery to body tissues; prolonged exercise; liver failure;
• Renal acidosis, caused by diseased kidneys that fail to deliver sufficient bicarbonate to the body in the circumstances of bicarbonate losses due to:
  • titration of bicarbonate by noncarbonic 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.