Role of the kidneys in maintaining normal blood pH

The maintenance of blood pH within normal limits (7.35-7.45), called acid-base homeostasis, is a complex synergy involving three organs (lungs, kidneys and brain) as well as chemical buffers in blood and blood cells (erythrocytes). This vital physiologic process is the subject of a recent expert review article, authored by three academic/research nephrologists that focuses principally, although not exclusively, on the role of the kidney. 

The article begins with a broad overview of acid-base homeostasis, its pathophysiological importance and some familiar basic concepts such as bicarbonate buffering system and the related Henderson- Hasselbalch equation. The concept of metabolic/respiratory components of acid-base balance allows brief discussion of the integrated role of brain, lungs and kidneys. 

This introduction paves the way for the central focus of the article, which is the authors’ research interest: the role of the kidneys in acid-base homeostasis. In broad terms this role has two aspects that both relate to maintenance of normal blood bicarbonate (the metabolic component) concentration. 

The two aspects are: reabsorption to blood of virtually all bicarbonate filtered from blood by the kidneys; and generation of new bicarbonate that has been lost in buffering acid produced during normal cell metabolism. Most of this authoritative article is devoted to describing the complex detail of what is currently known about the multiple pathways involved in reabsorption and regeneration of bicarbonate, as well as secondary regulatory pathways. 

Although the main focus of the article is a detailed physiological description of these pathways and their regulation, there are also frequent references to the pathological significance, and the precise ways in which disturbance of pathways contribute to the development of metabolic alkalosis or metabolic acidosis. 

There is also discussion of the way these pathways contribute to compensation for pathological disturbance of acid-base homeostasis, and help return abnormal blood pH towards normal limits. The authors highlight recent research that continues to reveal further complexity of the mechanisms involved in bicarbonate reabsorption and regeneration. 

For example, they discuss previously unsuspected roles for Rh proteins and the protein pendrin. The article, which is littered with visually friendly schematics that complement and helpfully clarify the text, draws on 84 references to provide a very detailed and up-to-date account of the role of the kidney in acid-base homeostasis.