Anthony Sebastian

Chronic Low-Grade Metabolic Acidosis in Normal Adult Humans: Pathophysiology and Consequences

Normal adult humans eating modern-day diets have a chronic low-grade metabolic acidosis whose severity is determined in part by the net rate of endogenous acid production (NEAP). NEAP varies mainly with diet composition. The greater the quantity of organic and sulfuric acids produced from metabolism of animal foods, and the lower the amounts of potassium salts metabolizable to bicarbonate, which come mainly from fruits and vegetables, the greater the production rate of acid. It had previously been thought that “healthy” kidneys were capable of excreting any excess acid produced by the body’s metabolism [1]; the authors’ research suggests that the normally occurring slow decline in renal function with age allows the kidneys to merely mitigate the degree of severity of the acidosis, and with increasing age, the steady-state levels of acidity in the body slowly rise [2– 3].

States of Aldosterone Deficiency or Pseudodeficiency

Sodium, chloride, potassium, and acid-base homeostasis in humans is dependent in part on the “mineralocorticoid activity” of steroid hormones secreted by the adrenal cortex and is reflected in the electrolyte and acid-base composition of the extracellular fluid and in the volume of the arterial blood. Aldosterone is the only adrenal steroid known to participate in the physiologic feedback regulation of electrolyte and volume homeostasis. Thus, primary or secondary disorders of the adrenal cortex that result in subnormal rates of aldosterone production are characterized by abnormalities in extracellular fluid volume, blood pressure, and electrolyte and acid-base composition. In addition, rare disorders in which signs and symptoms of aldosterone deficiency are present despite normal or elevated levels of aldosterone (so-called pseudohypoaldosteronism) also result in major alterations in mineral homeostasis. This chapter will review the pathophysiology and treatment of disorders due to aldosterone deficiency and pseudodeficiency in the context of our current understanding of the physiologic effects of mineralocorticoid hormones, summarized in Section I.