A control engineering model of calcium regulation

Christie, Christopher R.; Achenie, Luke E.K.; Ogunnaike, Babatunde A.

doi:10.3182/20140824-6-za-1003.02826

Cited by 3 publications

(3 citation statements)

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“…If the kidney function starts to decline, a cascade of physiological processes eventually result in secondary hyperparathyroidism. Due to the complexity of the system, a growing number of mathematical models have been published with the aim to analyze the driving factors of calcium homeostasis, secondary hyperparathyroidism, and CKD-MBD [27,29,30,[35][36][37][38]. However these models did not include a detailed model of cinacalcet, a drug widely prescribed in patients with secondary hyperparathyroidism.…”

Section: Discussionmentioning

confidence: 99%

A Multi-Compartment Model Capturing the Pharmacokinetics of the Calcimimetic Cinacalce

Schappacher‐Tilp

Fuertinger

Kotanko

2019

Cell Physiol Biochem

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Section: Discussionmentioning

confidence: 99%

A Multi-Compartment Model Capturing the Pharmacokinetics of the Calcimimetic Cinacalce

Schappacher‐Tilp

Fuertinger

Kotanko

2019

Cell Physiol Biochem

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“…It accounts for the regulation of these exchanges by PTH, vitamin D 3 , as well as FGF23. The relatively recent discovery of the latter means that FGF23 was ignored in previous homeostasis models [18,61,66].…”

Section: Discussionmentioning

confidence: 99%

Coupling between phosphate and calcium homeostasis: a mathematical model

Granjon

Bonny

Edwards

2017

American Journal of Physiology-Renal Physiology

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We developed a mathematical model of calcium (Ca) and phosphate (PO) homeostasis in the rat to elucidate the hormonal mechanisms that underlie the regulation of Ca and PO balance. The model represents the exchanges of Ca and PO between the intestine, plasma, kidneys, bone, and the intracellular compartment, and the formation of Ca-PO-fetuin-A complexes. It accounts for the regulation of these fluxes by parathyroid hormone (PTH), vitamin D, fibroblast growth factor 23, and Ca-sensing receptors. Our results suggest that the Ca and PO homeostatic systems are robust enough to handle small perturbations in the production rate of either PTH or vitamin D The model predicts that large perturbations in PTH or vitamin D synthesis have a greater impact on the plasma concentration of Ca ([Ca]) than on that of PO ([PO]); due to negative feedback loops, [PO] does not consistently increase when the production rate of PTH or vitamin D is decreased. Our results also suggest that, following a large PO infusion, the rapidly exchangeable pool in bone acts as a fast, transient storage PO compartment (on the order of minutes), whereas the intracellular pool is able to store greater amounts of PO over several hours. Moreover, a large PO infusion rapidly lowers [Ca] owing to the formation of CaPO complexes. A large Ca infusion, however, has a small impact on [PO], since a significant fraction of Ca binds to albumin. This mathematical model is the first to include all major regulatory factors of Ca and PO homeostasis.

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“…Biological feedback control systems can be made with a similar structure, as illustrated by Figure 2, which shows the block diagram for the system used to maintain calcium homeostasis. 4 As discussed in ref 4, this diagram is obtained by organizing available information about the biological mechanisms subtending calcium regulation into the indicated functional module blocks.…”

Section: Engineering Of Biological Controlmentioning

confidence: 99%

110th Anniversary: Process and Systems Engineering Perspectives on Personalized Medicine and the Design of Effective Treatment of Diseases

Ogunnaike

2019

Ind. Eng. Chem. Res.

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The mammalian organism maintains stable, efficient, and “near-optimal” performance and homeostasis in the face of external and internal perturbations via distinct biological systems ranging from the large-scale physiological (nervous, endocrine, immune, cardiovascular, respiratory, etc.), to the cellular (growth and proliferation regulation, DNA damage repair, etc.), and the subcellular (gene expression, protein synthesis, metabolite regulation, etc.). A control engineering perspective of the function, organization, and coordination of these multiscale biological systems and the control mechanisms that enable them to carry out their functions effectively provides a framework for understanding the occurrence of diseases as a consequence of the malfunction of components of these biological control systems, with implications for the design of effective treatments and the prevention of diseases. This paper provides an overview of how physiological life is made possible by control and argues for the usefulness of a control engineering perspective of pathologies for diagnosis, design, and implementation of effective treatmentsespecially for personalized (precision) medicine for “optimizing health”. We present a control engineering perspective of this emerging approach to medical practice which we employ to make the case for the role that process systems engineering will play in enabling health care delivery of the future. The highlighted concepts and principles are illustrated with a modest clinical example from the literature involving platelet count control for an immune thrombocytopenic purpura (ITP) patient.

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A control engineering model of calcium regulation

Cited by 3 publications

References 25 publications

A Multi-Compartment Model Capturing the Pharmacokinetics of the Calcimimetic Cinacalce

A Multi-Compartment Model Capturing the Pharmacokinetics of the Calcimimetic Cinacalce

Coupling between phosphate and calcium homeostasis: a mathematical model

110th Anniversary: Process and Systems Engineering Perspectives on Personalized Medicine and the Design of Effective Treatment of Diseases

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