检索问题
钾镁平衡、排水、高盐饮食、运动人群、生酮饮食 这些有什么关系？
人体的钾镁平衡、水分排泄、高盐饮食、运动以及生酮饮食，看似是几个独立的生活或生理片段，但它们在人体内部由一个共同的主轴串联起来：水和电解质（也就是身体里的“盐分”和矿物质）的动态平衡。它们相互制约、相互影响，任何一个环节发生剧烈变动，都会像推倒多米诺骨牌一样，引发心跳、血压、肌肉和神经的连锁反应。
为了让你轻松理解这些复杂的医学概念，我们先在大脑里建立一个小工厂的模型。
一、 认识几位核心“员工”和它们的办公室
在讲它们的关系之前，我们需要先认识几个关键角色，并了解它们的工作场所：
- 钾（K+）：它是细胞内部的“主力军”。你可以把它想象成细胞里的“电池液”，对于维持心脏跳动规律和肌肉收缩至关重要。如果血液里的钾太少（低钾血症），心脏会乱跳（心律失常）；如果太高（高钾血症），心脏可能会停跳 。
- 镁（Mg2+）：它是身体里的“全能润滑剂”和“指挥官”。镁参与了人体超过600种化学反应，包括产生能量和肌肉收缩 。它还在大脑、心脏和肌肉中起着关键的保护作用 。正常情况下，血液里的镁浓度被严格控制在一个很窄的范围内（0.7到1.1 mmol/L） 。
- 内部平衡：钾在身体里分为“细胞内”和“细胞外”（血液中）。钾可以在细胞内和细胞外来回穿梭，这种移动被称为“内部钾平衡”。比如，当你剧烈运动时，肌肉细胞会把钾释放到血液中；当你休息时，钾又被收回细胞内 。
- 肾脏：这是人体的“污水处理厂”和“盐分调节站”。它不仅负责排掉多余的水，还负责决定把哪些盐分（比如钠、钾、镁）留在身体里，把哪些扔进尿液排出去 。
二、 高盐饮食：打破平衡的“捣蛋鬼”
我们吃的盐主要成分是钠。高盐饮食就像往身体里强行塞入过多的钠，这会引发一系列麻烦：
- 升高血压：当身体里的钠太多时，为了冲淡这些盐分，身体会留住更多的水分，这会导致血管里的液体变多，压力变大，这就形成了高血压 。随着年龄增长，人体对盐越来越敏感，高盐饮食引发高血压的风险会急剧增加 。在全球范围内，有高达50%到60%的高血压患者属于“盐敏感性高血压”，也就是吃一点盐血压就飙升 。
- 连累钾和镁的流失：为了把多余的钠排出去，肾脏的“排污系统”会超负荷运转。在心衰等体内钠水潴留的情况下，肾脏在排钠的同时，往往会把钾和镁也一起排掉，导致身体缺钾、缺镁 。
- 引发炎症：高钠饮食还会导致身体产生有害物质（医学上叫氧化应激），并激活免疫系统，引起血管和肾脏的发炎，进一步推高血压 。
三、 运动人群：大量出汗带来的“水盐大考”
运动时，身体为了散热会大量出汗。汗水里不仅有水，还有钠、钾等电解质。
- 水分和盐分的流失：如果运动时间超过30分钟，尤其是长时间高强度运动，随着汗液的大量流失，人体的运动能力会下降，甚至危及健康 。身体为了适应长期大运动量，会进行自我调节。比如，经过连续几天的脱水训练，身体会储存更多的钠，导致血液中的水分相对增加（这叫血容量增加） 。
- 钾的剧烈波动：运动开始时，肌肉细胞会把钾释放到血液中，导致血液中钾浓度升高；而一旦停止运动，钾又迅速钻回细胞内，导致血液中的钾浓度骤降，甚至低于正常水平（低于3 mEq/l）。这种剧烈的忽高忽低，有时是导致运动中或运动后心脏出问题甚至猝死的原因之一 。不过，身体也有保护机制，运动时分泌的“儿茶酚胺”（一种能让心跳加快的激素）能保护心脏免受高钾的危害 。
- 补水有讲究：运动时如果只需要补水，水里最好带点葡萄糖和钠，且浓度不能太高（低渗或等渗），这样水才能最快进入血液 。运动后，补充钠和钾对于恢复体内的水盐平衡非常重要 。
四、 生酮饮食：燃烧脂肪的“副作用”
生酮饮食是一种极低碳水化合物（通常每天少于50克）、高脂肪的饮食方式 。它的核心原理是逼迫身体不去燃烧糖分，而是去燃烧脂肪，从而产生“酮体”作为能量来源（这被称为营养性酮症） 。这种饮食与水和电解质有着极其密切的关系：
- 疯狂排水与电解质流失：当身体开始生酮时，胰岛素水平下降，这会向肾脏发出信号，让它大量排出水分和钠。随着钠的流失，钾和镁也跟着一起从尿液里跑掉了。这就是为什么刚开始生酮饮食的人体重会迅速下降（其实是掉了水），并且经常会感到无力、抽筋，这就是所谓的“生酮流感”，本质上是缺水缺电解质了。
- 引发口渴的激素：生酮饮食会刺激身体分泌一种叫“FGF21”的激素。这种激素会让人非常想喝水 。这其实是身体在应对生酮带来的潜在脱水风险时的自我保护机制。
- 酸碱平衡的危机：生酮饮食会产生酮体，酮体偏酸性。如果严格控制不当，可能会导致血液变酸，引发严重的“代谢性酸中毒”（也就是血液里的酸性物质太多） 。另一方面，由于碳水摄入极少，身体在代谢脂肪时有时也会走向另一个极端，导致血液偏碱，引发“代谢性碱中毒” 。酸碱度的剧烈变化会直接干扰钾在细胞内外的分布（也就是前面提到的“内部钾平衡”） 。
- 影响运动表现：对于运动员来说，生酮饮食在燃烧脂肪方面表现出色（每分钟能多燃烧约1.5克脂肪），但它对运动表现的影响往往是中性或负面的 。特别是对于精英运动员，生酮饮食通常会导致运动成绩下降 。不过，在举重等力量训练方面，生酮饮食和普通饮食的效果差不多 。值得注意的是，社交媒体上经常吹捧生酮饮食，但运动员不应盲目跟风，必须在专业营养师指导下进行 。
五、 把拼图拼起来：全貌呈现
现在，我们把这几个元素连起来看，看看它们是如何在人体这台精密机器中相互作用的：
场景一：高盐饮食 + 缺钾缺镁 = 血压失控 当你吃得太咸，身体里钠太多，不仅会直接升高血压，还会在排钠的过程中把钾和镁排掉。钾和镁对血管是有保护作用的，特别是钾，多吃富含钾的食物可以帮助肾脏排掉多余的钠，从而降低血压 。所以，高盐饮食破坏了钾镁平衡，是导致高血压的罪魁祸首。
场景二：生酮饮食 + 水盐流失 = 身体失衡 生酮饮食像是一场人为制造的代谢危机。它强行改变了身体的供能方式，导致肾脏大量排水排钠。如果不注意补充，身体就会陷入缺水、缺钠、缺钾、缺镁的窘境。缺镁会让你肌肉抽筋、情绪不佳；缺钾会让你心慌心悸。更危险的是，它还可能引发血液酸碱度失衡，进一步打乱钾在细胞内外的正常分布 。
场景三：运动人群 + 生酮饮食 = 雪上加霜的挑战 有些运动员为了减脂尝试生酮饮食。但运动本身就会通过出汗流失水和电解质，还会让钾在血液中剧烈波动。如果再叠加生酮饮食带来的排水排盐效应，身体的水和电解质平衡就会面临巨大压力。这就解释了为什么刚开始生酮的运动员常常觉得没力气、成绩下降 。身体在一边努力应对运动带来的钾离子穿梭，一边又要处理生酮带来的缺水缺镁，很容易顾此失彼。
场景四：药物与疾病的干预 在某些疾病状态下，比如心力衰竭，医生会开出利尿剂（排水药）来排掉体内多余的水和钠，减轻心脏负担。但这不可避免地会导致钾和镁的大量流失 。为了保住救命药（比如某些能提高生存率但容易引起高钾的药物），医生又必须小心翼翼地监测钾浓度，有时甚至需要用到“钾结合剂”（一种能在肠道里把钾抓住排出去的药）来防止血钾过高 。在这个复杂的拉锯战中，维持钾镁平衡是重中之重。
六、 总结与建议
钾镁平衡、排水、高盐饮食、运动和生酮饮食，它们共同构成了人体水盐代谢和能量代谢的复杂网络：
- 高盐饮食是破坏者：它导致水钠潴留，血压升高，并加速钾镁的流失。
- 排水是双刃剑：无论是通过出汗（运动）、排尿（生酮或吃药），还是肾脏的正常排泄，排水的同时必然伴随着电解质的丢失。
- 钾镁是稳定器：它们在维持心脏跳动、肌肉收缩和血压稳定中起着决定性作用。任何导致它们大量流失的因素（如高盐、利尿剂、生酮初期）都会危及健康。
- 运动和生酮是变量：它们都能深刻改变身体的代谢状态和水盐分布。运动让钾在血液中穿梭，生酮则让身体大量排水排盐并改变血液酸碱度。两者结合需要极高的专业指导和营养补充。
给普通人的实用建议：
- 控盐补钾：少吃咸菜、加工肉等高盐食品。多吃新鲜蔬菜水果，它们富含天然的钾和镁，有助于对抗高盐带来的血压危害。
- 运动补水要带“盐”：如果是超过一小时的大量出汗运动，光喝白开水是不够的，最好喝点淡盐水或运动饮料，补充流失的钠和钾。
- 不要盲目跟风生酮：生酮饮食不仅仅是“不吃主食吃肥肉”，它对身体的内分泌和水盐代谢是巨大的冲击。如果确实需要尝试，必须提前了解其排水排电解质的副作用，并在专业人士指导下补充水分、钠、钾和镁，切忌只听信社交媒体上的片面之词 。
References
1Magnesium in man: implications for health and disease.PubMed
Jeroen H F de Baaij, Joost G J Hoenderop, René J M Bindels
Magnesium (Mg(2+)) is an essential ion to the human body, playing an instrumental role in supporting and sustaining health and life. As the second most abundant intracellular cation after potassium, it is involved in over 600 enzymatic reactions including energy metabolism and protein synthesis. Although Mg(2+) availability has been proven to be disturbed during several clinical situations, serum Mg(2+) values are not generally determined in patients. This review aims to provide an overview of the function of Mg(2+) in human health and disease. In short, Mg(2+) plays an important physiological role particularly in the brain, heart, and skeletal muscles. Moreover, Mg(2+) supplementation has been shown to be beneficial in treatment of, among others, preeclampsia, migraine, depression, coronary artery disease, and asthma. Over the last decade, several hereditary forms of hypomagnesemia have been deciphered, including mutations in transient receptor potential melastatin type 6 (TRPM6), claudin 16, and cyclin M2 (CNNM2). Recently, mutations in Mg(2+) transporter 1 (MagT1) were linked to T-cell deficiency underlining the important role of Mg(2+) in cell viability. Moreover, hypomagnesemia can be the consequence of the use of certain types of drugs, such as diuretics, epidermal growth factor receptor inhibitors, calcineurin inhibitors, and proton pump inhibitors. This review provides an extensive and comprehensive overview of Mg(2+) research over the last few decades, focusing on the regulation of Mg(2+) homeostasis in the intestine, kidney, and bone and disturbances which may result in hypomagnesemia.
2Role of the ketogenic diet in children with intractable seizures.PubMed
K B Tallian, M C Nahata, C Y Tsao
OBJECTIVE: To provide a review of the mechanism of action, clinical efficacy, adverse effects, drug interactions, and therapeutic considerations associated with the use of a ketogenic diet to manage patients with intractable seizures. DATA SOURCES: A MEDLINE search from January 1966 to the present and relevant articles from journals were reviewed. DATA SYNTHESIS: The ketogenic diet has been used as a treatment modality since the early 1920s to control intractable seizures. The exact mechanism of action is unknown. Overall, uncontrolled clinical studies have reported that approximately one-third of patients with intractable seizures have become seizure-free on the ketogenic diet. Common adverse events attributed to the diet include dehydration, gastrointestinal symptoms, hypoglycemia, as well as carnitine and vitamin deficiencies. Cognitive effects, hyperlipidemia, impaired neutrophil function, urolithiasis, optic neuropathy, osteoporosis, and protein deficiency may also occur in some patients. Carbohydrate content and drug formulation in the selection of medications while on the diet are important. Acetazolamide, phenobarbital, and valproic acid have been reported to interact with the ketogenic diet. Medications that cause carnitine deficiency or influence carbohydrate metabolism should also be used with caution. The carbohydrate content of drugs in various therapeutic classes is presented to aid in the selection of the most appropriate drug and formulation for patients on the ketogenic diet. The success of the diet in controlling intractable seizures is related to the patient's close adherence to the diet. Minimizing carbohydrate ingestion from medications along with a multidisciplinary team approach to the selection and monitoring of the diet are important to the success of the ketogenic diet in controlling seizures. CONCLUSIONS: The ketogenic diet has shown promising results in controlling intractable seizures; however, carefully controlled clinical trials are needed to better assess the efficacy of the diet during its use and after discontinuation.
3The Pressure of Aging.PubMed
Majd AlGhatrif, Mingyi Wang, Olga V Fedorova, et al.
Significant hemodynamic changes ensue with aging, leading to an ever-growing epidemic of hypertension. Alterations in central arterial properties play a major role in these hemodynamic changes. These alterations are characterized by an initial decline in aortic distensibility and an increase of diastolic blood pressure, followed by a sharp increase in pulse wave velocity (PWV), and an increase in pulse pressure (PP) beyond the sixth decade. However, the trajectories of PWV and PP diverge with advancing age. There is an increased prevalence of salt-sensitive hypertension with advancing age that is, in part, mediated by marinobufagenin, an endogenous sodium pump ligand.
4Potassium and the heart.PubMed
P A Poole-Wilson
The electrical stability of the heart is more sensitive to the extracellular than to the intracellular potassium concentration. During exercise, extracellular potassium varies rapidly. Catecholamines also modulate the plasma potassium concentration. Hypokalaemia of any cause can precipitate arrhythmias. Ischaemic myocardium loses potassium into the extracellular space within seconds and the cell becomes depolarized. The rise of the extracellular potassium ion concentration accounts for many of the early electrophysiological changes. Abrupt changes of plasma potassium concentration in normal myocardium and a high potassium concentration in ischaemic myocardium can set up electrical forces which initiate arrhythmias. The same phenomenon can account for changes on the electrocardiogram early after the cessation of an exercise test in a patient with ischaemic heart disease. Accumulation of potassium between cells in response to an increase of heart rate is a possible mechanism for false positive exercise tests and Syndrome X.
5International society of sports nutrition position stand: ketogenic diets.PubMed
Alex Leaf, Jeffrey A Rothschild, Tim M Sharpe, et al.
POSITION STATEMENT: The International Society of Sports Nutrition (ISSN) provides an objective and critical review of the use of a ketogenic diet in healthy exercising adults, with a focus on exercise performance and body composition. However, this review does not address the use of exogenous ketone supplements. The following points summarize the position of the ISSN. UNLABELLED: 1. A ketogenic diet induces a state of nutritional ketosis, which is generally defined as serum ketone levels above 0.5 mM. While many factors can impact what amount of daily carbohydrate intake will result in these levels, a broad guideline is a daily dietary carbohydrate intake of less than 50 grams per day. UNLABELLED: 2. Nutritional ketosis achieved through carbohydrate restriction and a high dietary fat intake is not intrinsically harmful and should not be confused with ketoacidosis, a life-threatening condition most commonly seen in clinical populations and metabolic dysregulation. UNLABELLED: 3. A ketogenic diet has largely neutral or detrimental effects on athletic performance compared to a diet higher in carbohydrates and lower in fat, despite achieving significantly elevated levels of fat oxidation during exercise (~1.5 g/min). UNLABELLED: 4. The endurance effects of a ketogenic diet may be influenced by both training status and duration of the dietary intervention, but further research is necessary to elucidate these possibilities. All studies involving elite athletes showed a performance decrement from a ketogenic diet, all lasting six weeks or less. Of the two studies lasting more than six weeks, only one reported a statistically significant benefit of a ketogenic diet. UNLABELLED: 5. A ketogenic diet tends to have similar effects on maximal strength or strength gains from a resistance training program compared to a diet higher in carbohydrates. However, a minority of studies show superior effects of non-ketogenic comparators. UNLABELLED: 6. When compared to a diet higher in carbohydrates and lower in fat, a ketogenic diet may cause greater losses in body weight, fat mass, and fat-free mass, but may also heighten losses of lean tissue. However, this is likely due to differences in calorie and protein intake, as well as shifts in fluid balance. UNLABELLED: 7. There is insufficient evidence to determine if a ketogenic diet affects males and females differently. However, there is a strong mechanistic basis for sex differences to exist in response to a ketogenic diet.
6Magnesium biology.PubMed
Jana L Kröse, Jeroen H F de Baaij
Magnesium (Mg2+) is essential for energy metabolism, muscle contraction and neurotransmission. As part of the Mg-ATP complex, it is involved in over 600 enzymatic reactions. Serum Mg2+ levels are tightly regulated between 0.7 and 1.1 mmol/L by interplay of intestinal absorption and renal excretion. In the small intestine, Mg2+ is absorbed paracellularly via claudin-2 and -12. In the colon, transcellular absorption of Mg2+ is facilitated by TRPM6/7 and CNNM4. In the kidney, the proximal tubule reabsorbs only 20% of the filtered Mg2+. The majority of the filtered Mg2+ is reabsorbed in the thick ascending limb, where the lumen-positive transepithelial voltage drives paracellular transport via claudin-16/-19. Fine-tuning of Mg2+ reabsorption is achieved in the distal convoluted tubule (DCT). Here, TRPM6/7 tetramers facilitate apical Mg2+ uptake, which is hormonally regulated by insulin and epidermal growth factor. Basolateral Mg2+ extrusion is Na+ dependent and achieved by CNNM2 and/or SLC41A3. Hypomagnesemia (serum Mg2+ <0.7 mmol/L) develops when intestinal and/or renal Mg2+ (re)absorption is disturbed. Common causes include alcoholism, type 2 diabetes mellitus and the use of pharmacological drugs, such as proton-pump inhibitors, calcineurin inhibitors and thiazide diuretics. Over the last decade, research on rare genetic and acquired Mg2+ disorders have identified Mg2+ channel and transporter activity, DCT length, mitochondrial function and autoimmunity as mechanisms explaining hypomagnesemia. Classically, treatment of hypomagnesemia depended on oral or intravenous Mg2+ supplementation. Recently, prebiotic dietary fibers and sodium-glucose cotransporter 2 inhibitors have been proposed as promising new therapeutic pathways to treat hypomagnesemia.
7The Hormone FGF21 Stimulates Water Drinking in Response to Ketogenic Diet and Alcohol.PubMed
Parkyong Song, Christoph Zechner, Genaro Hernandez, et al.
Alcohol and ketogenic diets increase water consumption. Here, we show that the hormone FGF21 is required for this drinking response in mice. Circulating levels of FGF21 are increased by alcohol consumption in humans and by both alcohol and ketogenic diets in mice. Pharmacologic administration of FGF21 stimulates water drinking behavior in mice within 2 hr. Concordantly, mice lacking FGF21 fail to increase water intake in response to either alcohol or a ketogenic diet. The effect of FGF21 on drinking is mediated in part by SIM1-positive neurons of the hypothalamus and is inhibited by β-adrenergic receptor antagonists. Given that FGF21 also is known to suppress alcohol intake in favor of pure water, this work identifies FGF21 as a fundamental neurotropic hormone that governs water balance in response to specific nutrient stresses that can cause dehydration.
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Ariel Jaitovich, Alejandro M Bertorello
Chronic hypertension is characterized by a persistent increase in vascular tone. Sodium-rich diets promote hypertension; however, the underlying molecular mechanisms are not fully understood. Variations in the sodium content of the diet, through hormonal mediators such as dopamine and angiotensin II, modulate renal tubule Na(+),K(+)-ATPase activity. Stimulation of Na(+),K(+)-ATPase activity increases sodium transport across the renal proximal tubule epithelia, promoting Na(+) retention, whereas inhibited Na(+),K(+)-ATPase activity decreases sodium transport, and thereby natriuresis. Diets rich in sodium also enhance the release of adrenal endogenous ouabain-like compounds (OLC), which inhibit Na(+),K(+)-ATPase activity, resulting in increased intracellular Na(+) and Ca(2+) concentrations in vascular smooth muscle cells, thus increasing the vascular tone, with a corresponding increase in blood pressure. The mechanisms by which these homeostatic processes are integrated in response to salt intake are complex and not completely elucidated. However, recent scientific findings provide new insights that may offer additional avenues to further explore molecular mechanisms related to normal physiology and pathophysiology of various forms of hypertension (i.e. salt-induced). Consequently, new strategies for the development of improved therapeutics and medical management of hypertension are anticipated.
9Fluid and electrolyte loss and replacement in exercise.PubMed
R J Maughan
Prolonged exercise leads to a progressive water and electrolyte loss from the body as sweat is secreted to promote heat loss. The rate of sweating depends on many factors and is increased in proportion to the work rate and the environmental temperature and humidity. Sweat rate is highly variable between individuals, and can exceed 21 h-1 for prolonged periods. Since it is established that dehydration will impair exercise capacity and can pose a risk to health, the intake of fluid during exercise to offset sweat loss is important. Fluid intake is also aimed at providing a source of substrate, usually in the form of carbohydrate. The availability of ingested fluids may be limited by gastric emptying or by intestinal absorption. Gastric emptying of liquids is slowed by the addition of carbohydrate in proportion to the carbohydrate concentration and osmolality of the solution. With increasing glucose concentration, the rate of fluid delivery to the small intestine is decreased, but the rate of glucose delivery is increased. Water absorption in the small intestine is a passive process and is stimulated by the active absorption of glucose and sodium. The optimum fluid for rehydration during exercise depends on many factors, particularly the intensity and duration of the exercise, the environmental conditions, and the individual physiology of the athlete. There is no advantage to fluid intake during exercise of less than 30 min duration. The composition of fluids to be used will depend on the relative needs to replace water and to provide substrate. Where rehydration is a priority the solution should contain some glucose and sodium and should not exceed isotonicity: this will require the glucose concentration to be low (20-309 g l-1) or the substitution of glucose polymers, and the sodium content to be high (perhaps as much as 60 mmol l-1). Where substrate provision is more important, a more concentrated solution, incorporating large amounts of glucose polymers in concentrations of 150-200 g l-1, is to be preferred. To minimize the limitation imposed by the rate of gastric emptying, the volume of fluid in the stomach should be kept as high as is comfortable by frequent ingestion of small amounts of fluid. Addition of sodium, and perhaps also of potassium, may be important for rehydration after exercise.
10Effect of Social Media on Diet, Lifestyle, and Performance of Athletes: A Review of Current Evidence.PubMed
Santanu Nath, Sangita Bhattacharya, Vani Bhushanam Golla, et al.
PURPOSE OF REVIEW: Social media (SM) plays an important role in providing diet and health advice to athletes, but it also carries with it a risk of credibility in the information sought for and received. The objective of this review is to assess the knowledge gap on how SM influences dietary and lifestyle practices in athletes. RECENT FINDINGS: For this, relevant literature was searched in three leading databases with appropriate keywords, which were subjected to proper scrutiny that led to inclusion of 22 articles (original research papers, reviews, viewpoints, and commentaries). The current era of digitalization has seen an over-reliance on internet and SM for nutrition and lifestyle advice for an athlete. SM has become a powerful tool in athlete's choice of food, nutrition information, healthy living, and performance, with merits and demerits. Their role in choosing dietary supplements and particular food types (e.g., ketogenic diet), body image, self-esteem and eating disorders, and in lifestyle and performance are discussed. SM should be used with caution and should not be used alone as a source of information for nutrition related pieces of advise by athletes. Any food type and supplements trending in SM should be discussed with a sports nutritionist before consumption. SM influencers having a big follower base may not always be disseminating the right knowledge on food and nutrition, thus caution should be exercised. For optimal benefit to the athlete, SM information should be in alignment with recommendations provided by sports nutrition and coaches.
11Metabolic Alkalosis Pathogenesis, Diagnosis, and Treatment: Core Curriculum 2022.PubMed
Catherine Do, Pamela C Vasquez, Manoocher Soleimani
Metabolic alkalosis is a widespread acid-base disturbance, especially in hospitalized patients. It is characterized by the primary elevation of serum bicarbonate and arterial pH, along with a compensatory increase in Pco consequent to adaptive hypoventilation. The pathogenesis of metabolic alkalosis involves either a loss of fixed acid or a net accumulation of bicarbonate within the extracellular fluid. The loss of acid may be via the gastrointestinal tract or the kidney, whereas the sources of excess alkali may be via oral or parenteral alkali intake. Severe metabolic alkalosis in critically ill patients-arterial blood pH of 7.55 or higher-is associated with significantly increased mortality rate. The kidney is equipped with sophisticated mechanisms to avert the generation or the persistence (maintenance) of metabolic alkalosis by enhancing bicarbonate excretion. These mechanisms include increased filtration as well as decreased absorption and enhanced secretion of bicarbonate by specialized transporters in specific nephron segments. Factors that interfere with these mechanisms will impair the ability of the kidney to eliminate excess bicarbonate, therefore promoting the generation or impairing the correction of metabolic alkalosis. These factors include volume contraction, low glomerular filtration rate, potassium deficiency, hypochloremia, aldosterone excess, and elevated arterial carbon dioxide. Major clinical states are associated with metabolic alkalosis, including vomiting, aldosterone or cortisol excess, licorice ingestion, chloruretic diuretics, excess calcium alkali ingestion, and genetic diseases such as Bartter syndrome, Gitelman syndrome, and cystic fibrosis. In this installment in the AJKD Core Curriculum in Nephrology, we will review the pathogenesis of metabolic alkalosis; appraise the precipitating events; and discuss clinical presentations, diagnoses, and treatments of metabolic alkalosis.
12A Case of Severe Metabolic Acidosis in the Setting of a Strict Ketogenic Diet.PubMed
Kerrie E Ward, Jay Ramsay, Bao Joseph Vu
Patients with metabolic acidosis often present with obscure, multifactorial etiologies, making efficient diagnosis and treatment key to preventing poor clinical outcomes. This case report describes a patient with severe metabolic acidosis in which the underlying cause was not immediately apparent. After a thorough work-up and history taking, the patient's strict ketogenic diet was identified as the most likely source of his illness. Over multiple days, the patient improved as he resumed a normal diet and was treated for refeeding syndrome. This case highlights the importance of taking a comprehensive social and diet history when assessing a patient with metabolic acidosis. It also highlights the need for physicians to understand and be ready to counsel on the possible effects of fad diets, such as the ketogenic diet.
13Integrated mechanisms linking sodium-potassium imbalance to salt-sensitive hypertension.PubMed
Chileleko Siakabanze, Emmanuel Luwaya, Lweendo Muchaili, et al.
Salt-sensitive hypertension (SS-HT) represents a clinically heterogeneous and mechanistically distinct phenotype of blood pressure dysregulation in which sodium intake disproportionately elevates blood pressure. SS-HT affects up to 50%-60% of individuals with hypertension globally, with an even greater burden among individuals of African ancestry, postmenopausal women, and those with obesity or metabolic syndrome. SS-HT arises from multifactorial dysregulation of renal, vascular, and immune systems. Central to its pathophysiology is aberrant activation of the epithelial sodium channel (ENaC), which drives sodium reabsorption in the distal nephron. ENaC activity is enhanced by both aldosterone-dependent and -independent mechanisms. Concurrently, high dietary sodium induces oxidative stress through NADPH oxidase-mediated reactive oxygen species (ROS) production, disrupts nitric oxide (NO) signaling, and activates antigen-presenting dendritic cells, triggering T-cell-mediated vascular and renal inflammation. This review proposes a systems-level framework in which SS-HT reflects the convergence of ENaC hyperactivation, immunometabolic priming, and hormonal modulation, shaped by sex, race, and dietary sodium-potassium imbalances. Understanding SS-HT as a multifaceted systems disorder opens new avenues for personalized prevention and treatment. Population-specific interventions, such as ENaC-targeting therapies, potassium-enriched diets, and sex and ancestry-informed modulation of the renin-angiotensin-aldosterone system (RAAS), represent promising strategies for precision medicine.
14Water and electrolyte requirements during exercise.PubMed
D L Costill
These studies demonstrate the body's capacity to minimize electrolyte losses during acute and repeated bouts of exercise and dehydration. Although there are marked shifts in water and selected ions in the exercising muscle, only during prolonged exertion is the ratio of intramuscular to extramuscular potassium significantly altered, suggesting that some modifications of the muscle cell membrane may occur. Muscle tissue not engaged in the exercise seems unaffected by the sweat loss during prolonged activity but relinquishes intracellular water shortly after work is terminated. Blood, muscle, sweat, and urine measurements before and following varied levels of dehydration demonstrate that body water loss during exercise in the heat is accomplished at the expense of larger water losses from extracellular and intracellular compartments. Moreover, the loss of ions in sweat and urine have little effect on the potassium content of either plasma or muscle. With repeated days of dehydration and heavy exercise, plasma volume increases in proportion to an increase in body sodium storage. Since red blood cells and hemoglobin are confined to the vascular space, both may decrease significantly as a function of the hemodilution induced by repeated days of exercise and dehydration. This may, in part, explain the apparent anemia reported by sports physicians among athletes undergoing intensive training. It is also possible that such hemodilution may produce low concentrations of plasma potassium, which might be falsely interpreted as suggestive of hypokalemia. In any event, some caution should be used in the clinical interpretation of plasma concentrations of various constituents among endurance-trained athletes. In general, it seems that the large sweat losses incurred during training and competition are adequately tolerated by the athlete, with concomitant adjustments in the water and electrolyte distribution of their fluid compartments. Despite the sizable excretion of ions and sweat, the athlete's large caloric intake and renal conservation of sodium minimize the threat of chronic dehydration or electrolyte deficits, or both.
15Water and electrolyte homeostasis during decongestion in heart failure.PubMed
Jef Van den Eynde, Frederik H Verbrugge
In heart failure, sodium retention generally occurs out of proportion to water retention and may occur disproportionate to chloride retention, requiring excretion of other cations (i.e. potassium, magnesium, and hydrogen). Renal homeostatic mechanisms keep chloride levels in balance, making it the primary regulator of intravascular tonicity. Excess total body sodium stores and potassium depletion increase the vulnerability to dehydration, especially in the intracellular compartment. With decompensation, extracellular volume expansion with sodium and chloride overload occurs, further enhancing potassium losses. While diuretics are vital to treat fluid overload, they derange important electrolyte and water balances. Diuretic therapies in heart failure produce disproportionate electrolyte-free water excretion, further exacerbate potassium depletion, and cause chloride losses disproportionate to natriuresis. This can be mitigated by allowing liberal electrolyte-free water intake, providing aggressive potassium and chloride supplementation, and using upfront proximal diuretics to preserve the chloride balance.
16Fluid-electrolyte homeostasis requires histone deacetylase function.PubMed
Kelly A Hyndman, Joshua S Speed, Luciano D Mendoza, et al.
Histone deacetylase (HDAC) enzymes regulate transcription through epigenetic modification of chromatin structure, but their specific functions in the kidney remain elusive. We discovered that the human kidney expresses class I HDACs. Kidney medulla-specific inhibition of class I HDACs in the rat during high-salt feeding results in hypertension, polyuria, hypokalemia, and nitric oxide deficiency. Three new inducible murine models were used to determine that HDAC1 and HDAC2 in the kidney epithelium are necessary for maintaining epithelial integrity and maintaining fluid-electrolyte balance during increased dietary sodium intake. Moreover, single-nucleus RNA-sequencing determined that epithelial HDAC1 and HDAC2 are necessary for expression of many sodium or water transporters and channels. In performing a systematic review and meta-analysis of serious adverse events associated with clinical HDAC inhibitor use, we found that HDAC inhibitors increased the odds ratio of experiencing fluid-electrolyte disorders, such as hypokalemia. This study provides insight on the mechanisms of potential serious adverse events with HDAC inhibitors, which may be fatal to critically ill patients. In conclusion, kidney tubular HDACs provide a link between the environment, such as consumption of high-salt diets, and regulation of homeostatic mechanisms to remain in fluid-electrolyte balance.
17Internal potassium balance and the control of the plasma potassium concentration.PubMed
R H Sterns, M Cox, P U Feig, et al.
The plasma potassium concentration is determined both by external potassium balance and by the distribution of potassium between extracellular and intracellular fluid compartments, i.e., "internal potassium balance." Whenever external potassium balance is altered, the resultant change in the plasma potassium concentration is strongly influenced by concomitant alterations in internal potassium balance. Several factors alter internal potassium balance independently of changes in external balance. Acid-base disturbances produce shifts of potassium into or out of cells, but attempts to quantify these effects are not likely to be clinically useful. Hypertonicity produces a shift of potassium out of cells. Several hormones (insulin, aldosterone, catecholamines, glucagon, and growth hormone) may have roles in internal potassium balance. Digitalis and succinylcholine, by producing efflux of potassium from cells, may cause hyperkalemia. Potassium is released from skeletal muscle during exercise, causing an increase in the plasma potassium concentration. The periodic paralyses are associated with well-defined transient alterations in internal potassium balance.
18Hyperkalemia in Heart Failure with Reduced Ejection Fraction: Implications and Management.PubMed
Craig J Beavers, Stephen J Greene
Hyperkalemia is a potentially life-threatening electrolyte imbalance that has traditionally posed significant challenges in the management of heart failure (HF). This review explores the complex interplay between hyperkalemia and the use of guideline-directed medical therapies (GDMT), such as renin-angiotensin-aldosterone system inhibitors (RAASi) and steroidal mineralocorticoid receptor antagonists (sMRAs), including spironolactone and eplerenone, which are currently recommended in guidelines for improving outcomes in heart failure with reduced ejection fraction (HFrEF). While these therapies reduce mortality and hospitalizations in HFrEF, their benefit in patients with heart failure with left ventricular ejection fraction (LVEF) ≥ 40% remains less conclusive. Nevertheless, their use in clinical practice is often limited by the risk of hyperkalemia, potentially leading to dose reduction or discontinuation of life-saving treatments. The prevalence of hyperkalemia in HF patients is notably higher compared to the general population, particularly in those with comorbid chronic kidney disease (CKD) and diabetes mellitus, further complicating management. This review emphasizes the importance of regular potassium monitoring, the potential benefits of combining therapies such as sodium-glucose cotransporter 2 (SGLT2) inhibitors with RAASi to reduce the risk of hyperkalemia, and the emergence of the newer non-steroidal MRA (nsMRA), finerenone, which may have a lower risk of hyperkalemia. Additionally, potassium binders such as patiromer and sodium zirconium cyclosilicate (SZC) are highlighted for their role in managing and preventing hyperkalemia, allowing patients to continue optimal RAASi and MRA therapy without interruption. By synthesizing current evidence on the incidence, risks, and management strategies of hyperkalemia in HF, this review aims to provide a comprehensive guide for clinicians to optimize patient outcomes while mitigating the risks associated with hyperkalemia.
19How Does Dietary Potassium Influence BP?PubMed
Adrienne M Assmus, Lena K Rosenbaek, Robert A Fenton
Hypertension is a global burden and a major contributor to cardiovascular disease and premature death. Public health guidelines for the management of high BP contain numerous dietary recommendations, of which one is a reduction in salt (NaCl) intake. In addition, the modern diet is also characterized by low potassium (K + ) content and recent guidelines propose increasing K + intake as an alternative or complementary measure to reducing salt intake for lowering of BP. Most beneficial effects of K + supplementation on BP involve a homeostatic response of the kidney to dietary-induced changes in extracellular K + concentrations, particularly decreased reabsorption of NaCl in the distal convoluted tubule. However, the effects of greater K + intake on BP are not linear, and the ideal K + supplementation or intake for management of BP remains unclear. This article covers the mechanisms in the kidney by which changes in K + translate to alterations in BP, the effects of altered K + intake in animal models and human populations, and the importance of concurrent salt intake and what constitutes K + supplementation.
20Potassium regulation during exercise and recovery in humans: implications for skeletal and cardiac muscle.PubMed
M I Lindinger
This review summarizes the main cellular mechanisms involved in potassium regulation in plasma and skeletal muscle during exercise. The effects of exercise-induced hyperkalemia and post-exercise hypokalemia on the cardiac action potential are reviewed in light of recent research on Na+ and K+ channel activity. Specific consideration is given to K+ release from contracting skeletal muscle, K+ uptake by contracting skeletal muscle, K+ uptake by non-contracting tissues during the period of exercise, and K+ uptake by skeletal muscle recovering from contractile activity. The onset of exercise is associated with a net release of K+ from contracting skeletal muscle that results in an increase in plasma [K+]. Resultant decreases in intracellular [K+] and increases in interstitial [K+] in contracting skeletal muscle have been implicated in the fatigue process. The rate and magnitude of increase in plasma [K+] is dependent on exercise intensity, trained state of the individual, and on drugs such as beta-adrenoceptor blockers and caffeine. During exercise, the uptake of K+ from the blood by non-contracting tissues may be important in preventing plasma [K+] from rising to excessive levels that will impair skeletal muscle and myocardial excitability and contractility. Cessation of exercise results in a rapid decrease in plasma [K+], often to 3 mEq/l or less with intense exercise, that may be maintained for prolonged periods. The rapid increases and decreases in plasma [K+] with onset and cessation of exercise, respectively, has been implicated in altered myocardial function and sudden cardiac death. Recent studies suggest that increases in catecholamines during exercise are cardioprotective to the arrhythmogenic effects of hyperkalemia.