Search

Background: Potassium (K(+)) input occurs after meals or during ischemic exercise and is accompanied by a high concentration of L-lactate in plasma (P(L-lactate))., Methods: We examined whether infusing 100 μmol L-lactic acid/min for 15 min would lead to a fall in the arterial plasma K(+) concentration (P(K)). We also aimed to evaluate the mechanisms involved in normal rats compared with rats with acute hyperkalemia caused by a shift of K(+) from cells or a positive K(+) balance., Results: There was a significant fall in P(K) in normal rats (0.25 mM) and a larger fall in P(K) in both models of acute hyperkalemia (0.6 mM) when the P(L-lactate) rose. The arterial P(K) increased by 0.8 mM (p < 0.05) 7 min after stopping this infusion despite a 2-fold rise in the concentration of insulin in arterial plasma (P(Insulin)). There was a significant uptake of K(+) by the liver, but not by skeletal muscle. In rats pretreated with somatostatin, P(Insulin) was low and infusing L-lactic acid failed to lower the P(K)., Conclusions: A rise in the P(L-lactate) in portal venous blood led to a fall in the P(K) and insulin was permissive. Absorption of glucose by the Na(+)-linked glucose transporter permits enterocytes to produce enough ADP to augment aerobic glycolysis, raising the P(L-lactate) in the portal vein to prevent postprandial hyperkalemia., (Copyright © 2012 S. Karger AG, Basel.)

Purpose of Review: This review aims to illustrate why urea recycling may play an important role in potassium (K⁺) excretion and to emphasize its potential clinical implications., Recent Findings: A quantitative analysis of the process of intrarenal urea recycling reveals that the amount of urea delivered to the distal convoluted tubule is about two-fold larger than the quantity of urea excreted in the urine. As the number of osmoles delivered to the late cortical distal nephron (CCD) determines its flow rate when aquaporin 2 water channels have been inserted in the luminal membrane of principal cells, urea recycling may play an important role in regulating the rate of excretion of K⁺ when the distal delivery of electrolytes is not very high., Summary: Urea recycling aids the excretion of K⁺; this is especially important in patients with disorders or those who are taking drugs that lead to a less lumen-negative voltage in the CCD. As a large quantity of urea is reabsorbed daily in the inner medullary collecting duct, the assumption made in the calculation of the transtubular K concentration gradient that there is no appreciable reabsorption of osmoles downstream CCD is not valid.

Purpose of Review: Regulation of potassium (K) excretion was examined in an experimental setting that reflects the dietary conditions for humans in Paleolithic times (high, episodic intake of K with organic anions; low intake of NaCl), because this is when major control mechanisms were likely to have developed., Recent Findings: The major control of K secretion in this setting is to regulate the number of luminal K channels in the cortical collecting duct. Following a KCl load, the K concentration in the medullary interstitial compartment rose; the likely source of this medullary K was its absorption by the H/K-ATPase in the inner medullary collecting duct. As a result of the higher medullary K concentration, the absorption of Na and Cl was inhibited in the loop of Henle, and this led to an increased distal delivery of a sufficient quantity of Na to raise K excretion markedly, while avoiding a large natriuresis. In addition, because K in the diet was accompanied by 'future' bicarbonate, a role for bicarbonate in the control of K secretion via 'selecting' whether aldosterone would be a NaCl-conserving or a kaliuretic hormone is discussed., Summary: This way of examining the control of K excretion provides new insights into clinical disorders with an abnormal plasma K concentration secondary to altered K excretion, and also into the pathophysiology of calcium-containing kidney stones.

Control mechanisms for potassium (K(+)) excretion in humans developed in Palaeolithic times when diets were sodium poor and episodically K(+) rich. Nevertheless, our understanding of the regulation of K(+) excretion comes from experiments in rats with large sodium and K(+) intakes. Our objective was to identify how K(+) excretion was regulated when rats consumed a low NaCl diet to reflect Palaeolithic conditions. Rats that were given mineralocorticoids plus either NaCl, mannitol, or NaHCO(3) had a small kaliuresis. In contrast, KCl load induced a large kaliuresis and a near-maximal luminal [K(+)] in the terminal cortical collecting duct ([K(+)](CCD)). The time course of events was important. The rise in the [K(+)](CCD) was prompt, but the initial kaliuresis was only modest. Over the next 4 h, kaliuresis increased markedly due solely to a higher calculated distal flow rate, which appeared to be due to diminished reabsorption of NaCl in the loop of Henle; of note, the measured papillary [K(+)] rose. In summary, the increase in the [K(+)](CCD) in rats given KCl is likely to be due to an increase in the number of luminal K(+) channels rather than to mechanisms that are known to induce a lumen-negative voltage in cortical distal nephron segments. The higher distal flow rate might be due to a higher interstitial [K(+)], which inhibited NaCl reabsorption in the loop of Henle. Thus, to understand which of the potential control mechanisms are operating, one must look very closely at the conditions imposed by the experimental setting.

The molecular basis of many of the inherited disorders of potassium homeostasis has become much clearer in the last two decades. Despite these new insights into the physiology of renal potassium handling, a number of questions remain to be answered. The examples we use to illustrate these issues are Gordon's syndrome, Bartter's syndrome, and Gitelman's syndrome. Our objective is to integrate these new insights into an understanding of the pathophysiology of renal potassium handling. We also propose different ways to think about some of the unresolved issues in this area., (Copyright 2002 S. Karger AG, Basel)

In a logical, stepwise approach to patients presenting with hypokalaemia or hyperkalaemia the clinician must first recognise circumstances in which the dyskalaemia represents a clinical emergency because therapy then takes precedence over diagnosis. If a dyskalaemia has been present for a long time, there is an abnormal renal handling of K+. The next step to analyse is the rate of excretion of K+ and, if necessary, its two components (urine flow rate and K+ concentration in the cortical collecting duct [CCD]) analysed independently. If the K+ concentration in the CCD is not in the expected range, its basis should be defined at the ion-channel level in the CCD from clinical information that can be used to deduce the relative rates of reabsorption of Na+ and Cl- in the CCD. This analysis provides the basis for diagnosis and may indicate where non-emergency therapy should then be directed.

A deficit of K+ of close to 300 mmol develops in the first 2 wk of fasting, but little further excretion of K+ occurs, despite high levels of aldosterone and the delivery of ketoacid anions that are not reabsorbed in the distal nephron. Our purpose was to evaluate how aldosterone could have primarily NaCl-retaining, rather than kaliuretic, properties in this setting. To evaluate the role of distal delivery of Na+, four fasted subjects received an acute infusion of NaCl to induce a natriuresis. To assess the role of distal delivery of HCO3-, five fasted subjects were given an infusion containing NaHCO3. The natriuresis induced by an infusion of NaCl caused only a small rise in the rate of excretion of K+ (0.8 +/- 0.1 to 1.9 +/- 0.3 mmol/h); in contrast, when HCO3- replaced Cl- in the infusate, K+ excretion rose to 8.3 +/- 2.2 mmol/h, despite little excretion of HCO3- (urine, pH 5.8) and similar rates of excretion of Na+. The transtubular K+ concentration gradient was 19 +/- 3 with HCO3- and 6 +/- 2 with NaCl. We conclude that the infusion of NaHCO3 led to an increase in K+ excretion, likely reflecting an increased rate of distal K+ secretion. With a low distal delivery of HCO3-, aldosterone acts as a NaCl-retaining, rather than a kaliuretic, hormone.

Disorders of potassium (K+) homeostasis are frequently encountered in clinical medicine and may have serious sequelae, particularly cardiac arrhythmias. Since long-term K+ balance depends on regulation of renal excretion of K+, the focus of this paper is to provide a novel way to analyze the K+ excretory process at the bedside in a noninvasive fashion. A fundamental aim was to incorporate recent new advances in K+ physiology to the clinical analysis of K+ disorders. In so doing, we have tried to replace eponyms and largely descriptive terms with more specific, but hypothetical pathophysiologic diagnoses. The approach we used focuses on an assessment of the components of K+ excretion in vivo. If the rate of excretion of K+ differs from the "expected" value for the stimulus of hypokalemia or hyperkalemia, one should determine whether the fault is with the flow rate and/or the [K+] in the terminal cortical collecting duct. The former is influenced primarily by the rate of excretion of osmoles when antidiuretic hormone acts, whereas the [K+] in the cortical collecting duct is determined by factors that modulate rate of electrogenic reabsorption of Na+ in that segment and its conductance for K+. By examining the extracellular fluid (ECF) volume status, the plasma renin activity, and the renal response to the induction of ECF volume contraction, we attempted to deduce whether the change in electrogenic reabsorption of Na+ was due to an altered Na+ transport or apparent permeability to chloride in the cortical collecting duct. We believe that an approach which draws heavily on pathophysiology can be of practical use at the bedside and, in addition, indicate areas in which more research could be fruitful. To illustrate these points, two clinical cases with hypokalemia and two with hyperkalemia were analyzed. Nevertheless, it is important to emphasize that the approach provided is speculative.

The purpose of this report is to apply recent advances in the understanding of the physiology of the excretion of potassium to a patient who had hyperkalemia due to a low rate of excretion of potassium. The defect was first suspected during therapy for diabetic ketoacidosis, when the concentration of potassium in plasma was unusually high (7.3 mmol/l) on admission and the deficit of potassium, as judged from the quantity of potassium infused to maintain normokalemia (40 mmol/24 h), was much less than expected. After recovery from diabetic ketoacidosis, hyperkalemia persisted despite near-normal values for creatinine and glucose in plasma. Excretion of potassium was low, considering the stimulus of hyperkalemia, and did not rise appreciably after the acute or chronic administration of a mineralocorticoid. The transtubular potassium concentration gradient (TTKG) did not exceed 6 after a large dose of fludrocortisone (200 micrograms) was administered. Notwithstanding, the TTKG rose to 14.4 following the intake of acetazolamide. We speculate that the basis for the hyperkalemia was type II hypoaldosteronism.

In animals, secretion of potassium (K) in the cortical collecting duct (CCD) is modulated by the properties of the accompanying anion. In humans, results are inconclusive as previous studies have not differentiated between a kaliuresis due to a rise in the concentration of K from one due to an increase in the volume of urine. Our purpose was to study the effects of chloride (Cl) and bicarbonate on the secretion of K in the CCD in humans using the transtubular K concentration gradient (TTKG), a semi-quantitative index of secretion of K in the terminal CCD. After control blood and urine samples were obtained, all subjects ingested 0.2 mg fludrocortisone to ensure that mineralocorticoids were not limiting the secretion of K. The anionic composition of the urine was varied using three protocols: Normal subjects (N = 11) ingested cystine and methionine to induce sulfaturia; nine subjects with a contracted ECF volume (to lower the concentration of Cl in the urine) were also studied during sulfaturia following the ingestion of cystine and methionine; 13 normovolemic subjects were studied during bicarbonaturia following the ingestion of acetazolamide. When the concentration of Cl in the urine was greater than 15 mmol/liter, sulfate had no effect on the TTKG. With lower concentrations of Cl in the urine, the TTKG rose 1.5-fold. The TTKG rose 1.8-fold in the presence of bicarbonaturia despite concentrations of Cl in the urine that were greater than 15 mmol/liter, suggesting that bicarbonate has additional effects on this K secretory process. At comparable concentrations of sulfate and bicarbonate in the urine, the TTKG was increased only with bicarbonaturia.(ABSTRACT TRUNCATED AT 250 WORDS)

It is advantageous to make an independent assessment of the potassium (K) secretory process and the luminal flow rate in the renal cortex to evaluate K handling by the kidney during hypokalemia or hyperkalemia. The transtubular potassium concentration gradient (TTKG) is a semiquantitative index of the activity of the K secretory process. The purpose of this study was to define expected values for the TTKG in normal subjects with hypokalemia or following an acute K load. During hypokalemia of non-renal origin, the TTKG was 0.9 +/- 0.2; in contrast, the TTKG was significantly higher during the hypokalemia of hyperaldosteronism, 6.7 +/- 1.3. The TTKG was 11.8 +/- 3.6, 2 hours after normokalemic subjects received 0.2 mg 9 alpha-fludrocortisone (9 alpha-F). To obtain expected values during hyperkalemia, normal subjects ingested 50 mmol potassium chloride; 2 hours later, the TTKG was 13.1 +/- 3.8. Therefore, the expected value for the TTKG must be interpreted relative to the concentration of K in the plasma. Circumstances were also defined where the TTKG is low despite hyperaldosteronism, namely, during a water diuresis and pre-existing hypokalemia.