The implications of the hypocitricemic response to surgery and the role of liver function and hepatocyte metabolism: An important, but neglected, clinical relationship

Abstract

Reported studies more than forty years ago established that all surgery patients exhibit a marked postoperative hypocitricemia within one day following surgery and persists for seven days and longer. Animals also exhibit the postoperative hypocitricemia. The hypocitricemia results from increased liver clearance of plasma citrate, in which the hepatocytes become capable of transporting and utilizing citrate from plasma. This represents a physiologic/metabolic response during the patient recovery from surgery. The extensive hypocitricemia in response to surgery is not manifested by known citricemic hormones, but is initiated via an unidentified putative endocrine hypocitricemic hormone. In addition to the importance relating to surgery patients, the surgical hypocitricemic effects, along with the liver and hepatic cell effects, will impact virtually all human and animal clinical and experimental studies that include surgical intervention; including the conclusions and translational clinical implications.Unfortunately, the hypocitricemic response to surgery has been ignored for the past forty years, and most contemporary clinicians and biomedical investigators are not aware of this clinical relationship. The intent of this review is to inform members of the medical community of the established hypocitricemic response to surgery and the important role of liver clearance and hepatocyte metabolism of plasma citrate; which, hopefully, will generate interest and research that should be integrated into contemporary issues that involve surgical intervention.

Understanding the Central Role of Citrate in the Metabolism of Cancer Cells and Tumors: An Update

“…Interestingly, citrate concentrations of up to 5 mM can stimulate lipid synthesis and histone acetylation in HepG2 cells, but higher concentrations (10 mM or more) decreased both acetylation and ACLY expression [ 132 ]. Factors influencing the blood concentration of citrate (which is normally around 100–150 µM [ 133 ]) have not been well characterized up to now. In theory, it likely depends on the daily intake, the secretion of citrate by body reserves (approximately 90% of citrate is located in mineralized tissues), and the citrate consumption in various biological processes, particularly bone formation [ 134 ].…”

Targeting Longevity Gene SLC13A5: A Novel Approach to Prevent Age-Related Bone Fragility and Osteoporosis

“…Furthermore, modelling of plasma citrate flux into the liver based on pharmacokinetic data from healthy human subjects suggested that the liver is the major organ of citrate clearance from plasma in humans [40]. Other studies showed that hepatic clearance can be further increased under certain conditions such as surgery causing hypocitricemia [41]. However, the closely related transporters SLC13A2 and SLC13A3, mainly expressed in the kidney, may also contribute to citrate clearance.…”