Plasma Citrate Homeostasis: How It Is Regulated; And Its Physiological and Clinical Implications. An Important, But Neglected, Relationship in Medicine

The homeostatic maintenance of a normal plasma citrate concentration is an important factor in humans and in animals; and is required for many normal physiological activities. Dysregulation of normal plasma citrate presents pathophysiological hypocitricemic or hypercitricemic conditions. This can lead to clinical consequences in many areas of medicine; such as impaired blood clotting, altered acid/base status, impaired neuromuscular/cardiac activities, hypocitraturia and stone formation, bone disorders with loss of bone strength and increased fractures, hypocitricemia of surgical stress. These important implications of citrate relationships have been largely ignored by the contemporary clinical and biomedical community; to the extent that it is not even described in most current textbooks and review papers. This review describes the physiological, endocrine, and metabolic relationships in the normal regulation and maintenance of plasma citrate; and presents some important clinical consequences of its dysfunctional maintenance. The importance of bone, kidney and liver activities in the maintenance of normal plasma citrate is described along with the citricemic roles of parathyroid hormone, calcitonin and vitamin D. These factors and relationships are presented as the contemporary understanding of the integrated regulation of plasma citrate as the basis for its clinical importance in medicine. The exclusion of these citrate relationships leads to misunderstanding and misrepresentation of physiological and clinical conditions in many issues in medicine and paramedicine areas. The intent of this review is to revive the interest and support for research to address the many unknown and speculative issues of plasma citrate regulation and its important clinical implications. This is in the best interest of the medical community and the public-at-large.