Acid-Base Homeostasis

Abstract

Acid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. The importance of this regulation is evidenced by a variety of physiologic derangements that occur when plasma pH is either high or low. The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance. This function of the kidneys has two components: reabsorption of virtually all of the filtered HCO 3 2 and production of new bicarbonate to replace that consumed by normal or pathologic acids. This production or generation of new HCO 3 2 is done by net acid excretion. Under normal conditions, approximately one-third to one-half of net acid excretion by the kidneys is in the form of titratable acid. The other one-half to two-thirds is the excretion of ammonium. The capacity to excrete ammonium under conditions of acid loads is quantitatively much greater than the capacity to increase titratable acid. Multiple, often redundant pathways and processes exist to regulate these renal functions. Derangements in acid-base homeostasis, however, are common in clinical medicine and can often be related to the systems involved in acid-base transport in the kidneys.

Integrated compensatory network is activated in the absence of NCC phosphorylation

“…Ammonium excretion has been proposed to be stimulated in states of potassium deficiency as an adaptive mechanism to reduce urinary potassium loss (59,91). If accompanied by an increase in α-KG signaling, activation of bicarbonate aldosterone, angiotensin II, and alkalosis (46,47), can be elevated in Gitelman syndrome, as well as in NCC-and SPAK KO mice, and likely work with α-KG to maximize pendrin-mediated transport.…”

Lactic Acidosis in a Patient with Type 2 Diabetes Mellitus

“…At first blush, this is somewhat unexpected, given the conventional wisdom that efflux of cellular potassium, with consequent hyperkalemia, accompanies mineral (hyperchloremic) acidosis but not organic acidosis, like lactic or ketoacidosis (58). Of note, however, is Fulop's original case series (59), which is widely cited in support of this contention, revealed that some patients with organic acidoses did develop hyperkalemia.…”

Urine Ammonium, Metabolic Acidosis and Progression of Chronic Kidney Disease

“…The NH 4 + thus reabsorbed dissociates into NH 3 (ammonia) and H + due to the less acidic milieu. The ammonia is then secreted into the lumen of the collecting duct, where it is trapped as an ammonium ion (NH 4 + ) by H + secreted through intercalated cells via H + -ATPase (and H + /K + ATPase) [21,22].…”

“…The renal excretion of acid (H + ) is achieved by titratable acidity and ammonium (NH 4 + ) excretion, with the latter playing a critical role in acid-base balance, specifically when endogenous acid production is enhanced [3]. Metabolic acidosis is generated consequent to either enhanced production of endogenous acid or decreased excretion of acid by the kidney [4]. One major pathophysiologic state associated with metabolic acidosis is the chronic kidney disease (CKD), which is characterized by a gradual reduction in the number of functioning nephrons and impairment in acid excretion, eventually culminating in significant retention of endogenous acid [5,6].…”