Serum/plasma potassium concentration in health and disease – a detailed comprehensive review

The Core Curriculum series of the American Journal of Kidney Disease (AJKD), which was initiated in 2003, is intended to provide nephrology trainees with a strong knowledge base for an up-to-date understanding of a range of core topics in renal medicine. This highlighted paper, the latest in the Core Curriculum series, focuses on potassium homeostasis.

Authored by two distinguished US medical/nephrology teachers with an established interest in the causes and consequences of disturbed potassium homeostasis, this article is an authoritative, nicely structured didactic review of potassium physiology and pathophysiology, presented under three main headings: “Normal Potassium Homeostasis”; “Hypokalemia”; and “Hyperkalemia”. The educative nature of the article is enhanced by insertion of four illustrative case history presentations; the authors pose clinically pertinent questions related to each case history that allow readers to test their understanding of the text. In line with the format and educative ethos of all articles in the Core Curriculum series, the authors offer “further reading lists” at the end of each of the three main headings.

Under the first of the three main headings – Normal Potassium Homeostasis – the authors first discuss the distribution of potassium in the body revealing that of the 3000 to 4000 mEq in the human body, just 60-80 mEq (~2 %) is present in the extracellular fluid (ECF) compartment at an approximate concentration of 3.5-5.3 mEq/L (3.5-5.3 mmol/L). They go on to detail the mechanisms involved in the shift of potassium between ECF and cells that help ensure maintenance of ECF concentration within these tight limits. The roles of insulin, the adenosine triphosphatase sodium/potassium pump (Na⁺/K – ATPase) and catecholamines in these mechanisms are discussed. The authors describe how acid-base disturbance can affect this physiological internal shift of potassium between ECF and cells.

A substantial portion of the Normal Potassium Homeostasis section of the article is devoted to the essential role of the kidney in regulating urinary potassium excretion and thereby ECF potassium concentration. Here the molecular complexities of potassium handling along the length of the renal tubule are detailed with the aid of clear diagrams. The authors describe how five major determinants of potassium excretion – plasma potassium concentration, renal tubule sodium concentration/flow rate, the hormones aldosterone and arginine vasopressin, and acid-base status – operate synergistically to ensure regulation of potassium excretion by specific cell types of the distal nephron under normal conditions, and those of high dietary potassium intake and disturbance of acid-base/fluid balance.

Having discussed in considerable detail the physiological (renal and non-renal) mechanisms required to maintain ECF (plasma) potassium within the approximate normal range 3.5-5.3 mEq/L, the authors turn attention to disturbance of this state of health by considering first hypokalemia (reduced plasma potassium concentration) and then hyperkalemia (raised plasma potassium concentration).

The many causes of hypokalemia are discussed by the authors under three broad etiological headings: “Decreased Potassium Intake”, “Cellular Distribution” (i.e. increased movement of potassium from ECF to cells) and “Decreased Total Body Potassium” (i.e. hypokalemia resulting from increased loss of potassium from the body via either renal or non-renal routes). The authors detail the pathophysiological mechanisms of hypokalemia under each of these headings and provide the rationale for the use of supplementary testing (including urine potassium-creatinine ratio, serum bicarbonate, serum renin and aldosterone) to help elucidate the cause. The authors provide a useful flow diagram for application of these tests in the investigation of hypokalemic patients.

The authors then discuss the consequences of hypokalemia in terms of its clinical presentation, and finally, treatment of hypokalemia.

A similar format is used to discuss hyperkalemia, the final topic of this review article. The many causes of hyperkalemia are discussed under the following etiological headings: “Pseudohyperkalemia” (i.e. falsely increased potassium due to poor sample collection/handling); “Increased Dietary Intake”; “Cell Shift” (i.e. increased plasma potassium resulting from increased shift of potassium from cells to ECF); and “Impaired Renal Excretion” (i.e. increased potassium resulting from acute kidney injury (AKI) and chronic kidney disease (CKD). Once again, the authors discuss the pathophysiological mechanism of hyperkalemia under each of these headings; particularly detailed discussion is reserved for hyperkalemia due to AKI and CKD. This discussion includes consideration of several commonly prescribed drugs that potentiate hyperkalemia in patients with CKD. The final section of the article focuses on the clinical features and treatment of hyperkalemia.