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Narrative Review: Evolving Concepts in Potassium Homeostasis and Hypokalemia
Open accessAbstract
Humans are intermittently exposed to large variations in potassium intake, which range from periods of fasting to ingestion of potassium-rich meals. These fluctuations would abruptly alter plasma potassium concentration if not for rapid mechanisms, primarily in skeletal muscle and the liver, that buffer the changes in plasma potassium concentration by means of transcellular potassium redistribution and feedback control of renal potassium excretion. However, buffers have capacity limits, and even robust feedback control mechanisms require that the perturbation occur before feedback can initiate corrective action. In contrast, feedforward control mechanisms sense the effect of disturbances on the system's homeostasis. This review highlights recent experimental insights into the participation of feedback and feedforward control mechanisms in potassium homeostasis. New data make clear that feedforward homeostatic responses activate when decreased potassium intake is sensed, even when plasma potassium concentration is still within the normal range and before frank hypokalemia ensues, in addition to the classic feedback activation of renal potassium conservation when plasma potassium concentration decreases. Given the clinical importance of dyskalemias in patients, these novel experimental paradigms invite renewed clinical inquiry into this important area.
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“Fractional reabsorption of K+ in the proximal segment (proximal tubule and thick ascending limb) remains largely the same under low, normal, and high K+ intake conditions [7].”
From A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls (2022) · cites this paper as [7]
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“In a male rat, the proximal tubules consistently reabsorb about two-thirds of filtered K+ and then the loops of Henle reabsorb 20–25% more so that together these segments reabsorb around 90% of the filtered K+ [7].”
From A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls (2022) · cites this paper as [7]
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“During normal or high K+ intake, the distal tubular segments secrete 10% to 50% of filtered K+ [7].”
From A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls (2022) · cites this paper as [7]
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“Through upregulation of H+-K+-ATPase in the intercalated cells, the collecting duct can reabsorb up to 10% of filtered K+ [7, 9].”
From A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls (2022) · cites this paper as [7]
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“However, the distal tubule’s capacity to reabsorb K+ is limited (up to 3% of filtered K+ in male rats), meaning that in times of drastically low K+ intake, it is up to the downstream collecting duct to conserve K+ via reabsorption [7, 8].”
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“The rate of K+ secretion is regulated by dietary K+ intake, intracellular K+ concentration, Na+ uptake into the cells, urine flow rate, and hormones such as ALD and angiotensin II [7, 8].”
From A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls (2022) · cites this paper as [7]
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“The collecting duct both secretes and reabsorbs K+ through the function of principal and intercalated cells, respectively [7].”
From A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls (2022) · cites this paper as [7]
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Metadata
- Authors
- Greenlee, M., Wingo, C. S., McDonough, A. A., Youn, J.-H., & Kone, B. C.
- Affiliations
- University of Southern California (US)
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 2009-05-05
- Volume
- 150
- Issue
- 9
- Pages
- 619-625
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- PMC
- PMC4944758
- OpenAlex
- W1981036549
- Cited by
- 104
- References
- 43
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 6 · 2023: 5 · 2022: 9 · 2021: 1 · 2020: 10 · 2019: 5 · 2018: 4 · 2017: 10 · 2016: 7 · 2015: 12 · 2014: 3 · 2013: 9 · 2012: 5
- FWCI
- 0.83
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK034316, R01DK049750, R01DK047981, R01DK057678, R01DK075065, R21DK080233)
- Topics
- Health Sciences › Medicine › Nephrology › Potassium and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Health Sciences › Nursing › Nutrition and Dietetics › Magnesium in Health and Disease
- Keywords
- potassium homeostasis, hypokalemia, feedforward control, feedback control, renal potassium excretion, plasma potassium, potassium intake, dyskalemia
- MeSH terms
- Animals, Feedback, Homeostasis, Humans, Hypokalemia, Kidney, Liver, Potassium, Muscle, Skeletal
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