Renal Acid-Base Regulation
The kidney is one of the two organs — with the lungs — that defend the body's acid-base balance. It does so on two fronts: reabsorbing nearly all of the filtered bicarbonate so none is lost, and generating new bicarbonate while excreting the daily fixed-acid load as titratable acid and ammonium. These processes keep the body's buffer reserve replenished.
Definition
Renal acid-base regulation is the set of tubular processes by which the kidney reclaims filtered bicarbonate and excretes the net daily acid load — chiefly as ammonium and titratable acid — thereby generating new bicarbonate to maintain systemic acid-base equilibrium.
Scope
This topic covers the renal contribution to acid-base homeostasis: bicarbonate reabsorption, net acid excretion through titratable acid and ammoniagenesis, and the segmental basis of these functions. It is a physiological reference and does not provide criteria for diagnosing or treating acid-base disorders.
Core questions
- How does the kidney reabsorb the large filtered load of bicarbonate?
- How is new bicarbonate generated to replace that consumed buffering metabolic acid?
- What roles do titratable acid and ammonium play in net acid excretion?
- How does the kidney adjust acid excretion in response to acidosis?
Key concepts
- Bicarbonate reabsorption (proximal tubule)
- Net acid excretion
- Titratable acid (e.g. phosphate buffering)
- Ammoniagenesis and ammonium excretion
- Hydrogen ion secretion
- Carbonic anhydrase
- Renal compensation for respiratory disturbances
Mechanisms
The proximal tubule reabsorbs the great majority of filtered bicarbonate: secreted hydrogen ions combine with luminal bicarbonate to form carbon dioxide and water (a reaction accelerated by carbonic anhydrase), which are taken up and regenerate bicarbonate intracellularly for return to the blood. To excrete the daily metabolic acid load, the kidney secretes hydrogen ions that are buffered in the urine by phosphate and other buffers (titratable acid) and, importantly, generates and excretes ammonium; ammoniagenesis from glutamine in the proximal tubule yields new bicarbonate for the blood. In acidosis, ammoniagenesis is up-regulated, increasing net acid excretion and bicarbonate generation, which is the kidney's principal adaptive response and the slower component of compensation alongside the lungs (Hamm 2015; Curthoys 2014; Adrogué 1998; Guyton & Hall 2020).
Clinical relevance
Renal acid-base handling explains how the kidney sustains the body's bicarbonate buffer and compensates for chronic acid-base disturbances, and disorders of these processes underlie the renal tubular acidoses. This entry describes the normal physiology for reference and is not a basis for diagnosing or managing acid-base disorders in an individual.
Evidence & guidelines
The mechanisms summarized here are drawn from physiology reviews and reference texts. The entry is descriptive and does not present clinical management of acid-base disorders as recommendations.
History
Robert Pitts and colleagues established in the mid-twentieth century that the kidney excretes acid as titratable acid and ammonium and reabsorbs filtered bicarbonate, defining net acid excretion. Later work mapped the transporters and enzymes — carbonic anhydrase, the proximal glutamine pathway — that carry out bicarbonate reabsorption and ammoniagenesis (Hamm 2015; Curthoys 2014).
Key figures
- Robert Pitts
- L. Lee Hamm
- Norman Curthoys
- Donald Seldin
Related topics
Seminal works
- hamm-2015
- curthoys-2014
- adrogue-1998
Frequently asked questions
- How does the kidney differ from the lungs in defending acid-base balance?
- The lungs adjust acid-base status rapidly by changing carbon dioxide excretion, whereas the kidney acts more slowly, reabsorbing filtered bicarbonate and excreting the fixed metabolic acid load while generating new bicarbonate; together they provide fast and sustained regulation.
- Why is ammonium excretion important?
- Generating ammonium from glutamine lets the kidney excrete a large quantity of acid and, in the process, add new bicarbonate to the blood; this pathway is up-regulated during acidosis and is the main way the kidney increases net acid excretion.