Use of Urine Electrolytes and Urine Osmolality in the Clinical Diagnosis of Fluid, Electrolytes, and Acid-Base Disorders.

We discuss the use of urine electrolytes and urine osmolality in the clinical diagnosis of patients with fluid, electrolytes, and acid-base disorders, emphasizing their physiological basis, their utility, and the caveats and limitations in their use. While our focus is on information obtained from measurements in the urine, clinical diagnosis in these patients must integrate information obtained from the history, the physical examination, and other laboratory data.

L-lactic acidosis: pathophysiology, classification, and causes; emphasis on biochemical and metabolic basis.

L-lactic acidosis (L-LA) is the most common cause of metabolic acidosis in the critical care setting, which has been associated with a large increase in mortality. The purpose of this article is to provide clinicians with an overview of the biochemical and metabolic background required to understand the different pathophysiological mechanisms that may lead to the development of L-LA. We propose a classification based on whether the pathophysiology of L-LA is due predominantly to increased production or decreased removal of L-lactic acid. In this article, we provide an overview of the biochemical and metabolic aspects of glucose oxidation, the production and removal of L-lactic acid, and a discussion of the pathophysiology of the various causes of L-LA.

Impact of Prolonged Fasting on the Risk of Calcium Phosphate Precipitation in the Urine: Calcium Phosphate Lithogenesis during Prolonged Fasting in a Healthy Cohort.

PURPOSE: Intermittent fasting and curtailing water intake for extended periods were likely common in Paleolithic times. Today it occurs for religious and dietary reasons. This restriction in intake should cause a decrease in the urine flow rate while raising the concentration of certain substances in urine to the point of precipitation. In this study we measured the risk of CaHPO4 precipitation following 18 hours of food and water deprivation. MATERIALS AND METHODS: Urine samples were periodically collected from 15 healthy subjects who fasted and abstained from drinking any liquid for 18 hours. The urine constituents Ca2+, HPO42- and pH involved in CaHPO4 formation were measured at various times throughout the fasting day. A comparison was made with control data, which consisted of diurnal urine collections taken throughout a separate nonfasting day prior to the fasting day. RESULTS: The mean ± SEM urine flow rate decreased significantly from 0.93 ± 0.1 ml per minute in the control group to 0.37 ± 0.05 ml per minute in the fasting group (p <0.05). Mean Na+ and Ca2+ excretion rates decreased significantly from 127 ± 12 to 54 ± 13 µmol per minute and from 3.2 ± 0.4 to 0.80 ± 0.21, respectively. Mean urinary Na+ and Ca2+ concentrations also decreased from 161 ± 11.6 to 122 ± 16.0 mmol/l and from 3.7 ± 0.5 to 2.0 ± 0.55, respectively. Urinary pH and the concentration of phosphate, citrate and magnesium were not significantly affected. CONCLUSIONS: Although the steady decrease in the urine flow rate was statistically significant during 18 hours of food and water deprivation, there was no evidence that the calculated risk of CaHPO4 precipitation in the healthy subjects had increased.

Renal potassium physiology: integration of the renal response to dietary potassium depletion.

We summarize the current understanding of the physiology of the renal handling of potassium (K+), and present an integrative view of the renal response to K+ depletion caused by dietary K+ restriction. This renal response involves contributions from different nephron segments, and aims to diminish the rate of excretion of K+ as a result of: decreasing the rate of electrogenic (and increasing the rate of electroneutral) reabsorption of sodium in the aldosterone-sensitive distal nephron (ASDN), decreasing the abundance of renal outer medullary K+ channels in the luminal membrane of principal cells in the ASDN, decreasing the flow rate in the ASDN, and increasing the reabsorption of K+ in the cortical and medullary collecting ducts. The implications of this physiology for the association between K+ depletion and hypertension, and K+ depletion and formation of calcium kidney stones are discussed.

Approach to the Treatment of Diabetic Ketoacidosis.

Diabetic ketoacidosis (DKA), a common cause of severe metabolic acidosis, remains a life-threatening condition due to complications of both the disease and its treatment. This Acid-Base and Electrolyte Teaching Case discusses DKA management, emphasizing complications of treatment. Because cerebral edema is the most common cause of mortality and morbidity, especially in children with DKA, we emphasize its pathophysiology and implications for therapy. The risk for cerebral edema may be minimized by avoiding a bolus of insulin, excessive saline resuscitation, and a decrease in effective plasma osmolality early in treatment. A goal of fluid therapy is to lower muscle venous Pco2 to ensure effective removal of hydrogen ions by bicarbonate buffer in muscle and diminish the binding of hydrogen ions to intracellular proteins in vital organs (such as the brain). In patients with DKA and a relatively low plasma potassium level, insulin administration may cause hypokalemia and cardiac arrhythmias. It is suggested in these cases to temporarily delay insulin administration and first administer potassium chloride intravenously to bring the plasma potassium level close to 4mmol/L. Sodium bicarbonate administration in adult patients should be individualized. We suggest it be considered in a subset of patients with moderately severe acidemia (pH<7.20 and plasma bicarbonate level < 12mmol/L) who are at risk for worsening acidemia, particularly if hemodynamically unstable. Sodium bicarbonate should not be administered to children with DKA, except if acidemia is very severe and hemodynamic instability is refractory to saline administration.

How Protective Mechanisms Interact to Prevent Overnight Calcium Phosphate Precipitation - An Observational Study to Determine Factors Against Calcium Phosphate Lithogenesis in a Healthy Cohort.

BACKGROUND/AIMS: As restful, non-interrupted sleep is essential for normal mental and physical functioning, the urine flow rate (UFR) overnight remains low. Due to this reduced UFR, the kidneys produce a lower urine volume, which may lead to supersaturation of lithogens in the renal collecting system. The protective mechanisms that prevent the rise in the concentration of the lithogenic substances in urine, such as calcium phosphate, are explored. METHODS: Urine samples were collected from 26 subjects every 2-3 h during daylight with one nocturnal collection; the UFR was calculated in the median time for each collection period. Urinary constituents for calcium phosphate precipitation including electrolytes, calcium, phosphate, citrate, and pH were measured. Comparisons within individuals were done by paired t test. RESULTS: The calcium excretion rate fell significantly overnight (from 2.4 ± 0.2 µmol/min during the daytime to 1.5 ± 0.3 µmol/min, p < 0.05), in parallel with sodium excretion (54 ± 16 µmol/min from its daytime 127 ± 12 µmol/min, p < 0.05), preventing nocturnal calcium concentration from increasing (3.0 ± 0.3 mmol/l daytime to 2.5 ± 0.5 mmol/l overnight), while citrate concentration did not change significantly. The total urine phosphate concentration rose significantly overnight (daytime 18.7 ± 1.4 µmol/min vs. nocturnal 20.9 ± 1.7 µmol/min), but the concentration of divalent phosphate did not increase in the overnight period. CONCLUSIONS: Although the UFR was lower overnight, there was no evidence that the risk of calcium phosphate precipitate formation in healthy subjects was increased.

Effect of improving the usability of an e-learning resource: a randomized trial.

Optimizing the usability of e-learning materials is necessary to reduce extraneous cognitive load and maximize their potential educational impact. However, this is often neglected, especially when time and other resources are limited. We conducted a randomized trial to investigate whether a usability evaluation of our multimedia e-learning resource, followed by fixing of all problems identified, would translate into improvements in usability parameters and learning by medical residents. Two iterations of our e-learning resource [version 1 (V1) and version 2 (V2)] were compared. V1 was the first fully functional version and V2 was the revised version after all identified usability problems were addressed. Residents in internal medicine and anesthesiology were randomly assigned to one of the versions. Usability was evaluated by having participants complete a user satisfaction questionnaire and by recording and analyzing their interactions with the application. The effect on learning was assessed by questions designed to test the retention and transfer of knowledge. Participants reported high levels of satisfaction with both versions, with good ratings on the System Usability Scale and adjective rating scale. In contrast, analysis of video recordings revealed significant differences in the occurrence of serious usability problems between the two versions, in particular in the interactive HandsOn case with its treatment simulation, where there was a median of five serious problem instances (range: 0-50) recorded per participant for V1 and zero instances (range: 0-1) for V2 (P < 0.001). There were no differences in tests of retention or transfer of knowledge between the two versions. In conclusion, usability evaluation followed by a redesign of our e-learning resource resulted in significant improvements in usability. This is likely to translate into improved motivation and willingness to engage with the learning material. In this population of relatively high-knowledge participants, learning scores were similar across the two versions.

Integration of the response to a dietary potassium load: a paleolithic perspective.

Our purpose is to integrate new insights in potassium (K(+)) physiology to understand K(+) homeostasis and illustrate some of their clinical implications. Since control mechanisms that are essential for survival were likely developed in Paleolithic times, we think the physiology of K(+) homeostasis can be better revealed when viewed from what was required to avoid threats and achieve balance in Paleolithic times. Three issues will be highlighted. First, we shall consider the integrative physiology of the gastrointestinal tract and the role of lactic acid released from enterocytes following absorption of sugars (fruit and berries) to cause a shift of this K(+) load into the liver. Second, we shall discuss the integrative physiology of WNK kinases and modulation of delivery of bicarbonate to the distal nephron to switch the aldosterone response from sodium chloride retention to K(+) secretion when faced with a K(+) load. Third, we shall emphasize the role of intra-renal recycling of urea in achieving K(+) homeostasis when the diet contains protein and K(+).

Bolus administration of intravenous glucose in the treatment of hyperkalemia: a randomized controlled trial.

BACKGROUND: Hyperkalemia is a common medical emergency that may result in serious cardiac arrhythmias. Standard therapy with insulin plus glucose reliably lowers the serum potassium concentration ([K(+)]) but carries the risk of hypoglycemia. This study examined whether an intravenous glucose-only bolus lowers serum [K(+)] in stable, nondiabetic, hyperkalemic patients and compared this intervention with insulin-plus-glucose therapy. METHODS: A randomized, crossover study was conducted in 10 chronic hemodialysis patients who were prone to hyperkalemia. Administration of 10 units of insulin with 100 ml of 50% glucose (50 g) was compared with the administration of 100 ml of 50% glucose only. Serum [K(+)] was measured up to 60 min. Patients were monitored for hypoglycemia and EKG changes. RESULTS: Baseline serum [K(+)] was 6.01 ± 0.87 and 6.23 ± 1.20 mmol/l in the insulin and glucose-only groups, respectively (p = 0.45). At 60 min, the glucose-only group had a fall in [K(+)] of 0.50 ± 0.31 mmol/l (p < 0.001). In the insulin group, there was a fall of 0.83 ± 0.53 mmol/l at 60 min (p < 0.001) and a lower serum [K(+)] at that time compared to the glucose-only group (5.18 ± 0.76 vs. 5.73 ± 1.12 mmol/l, respectively; p = 0.01). In the glucose-only group, the glucose area under the curve (AUC) was greater and the insulin AUC was smaller. Two patients in the insulin group developed hypoglycemia. CONCLUSION: Infusion of a glucose-only bolus caused a clinically significant decrease in serum [K(+)] without any episodes of hypoglycemia.

An efficient approach to improve the usability of e-learning resources: the role of heuristic evaluation.

Optimizing the usability of e-learning materials is necessary to maximize their potential educational impact, but this is often neglected when time and other resources are limited, leading to the release of materials that cannot deliver the desired learning outcomes. As clinician-teachers in a resource-constrained environment, we investigated whether heuristic evaluation of our multimedia e-learning resource by a panel of experts would be an effective and efficient alternative to testing with end users. We engaged six inspectors, whose expertise included usability, e-learning, instructional design, medical informatics, and the content area of nephrology. They applied a set of commonly used heuristics to identify usability problems, assigning severity scores to each problem. The identification of serious problems was compared with problems previously found by user testing. The panel completed their evaluations within 1 wk and identified a total of 22 distinct usability problems, 11 of which were considered serious. The problems violated the heuristics of visibility of system status, user control and freedom, match with the real world, intuitive visual layout, consistency and conformity to standards, aesthetic and minimalist design, error prevention and tolerance, and help and documentation. Compared with user testing, heuristic evaluation found most, but not all, of the serious problems. Combining heuristic evaluation and user testing, with each involving a small number of participants, may be an effective and efficient way of improving the usability of e-learning materials. Heuristic evaluation should ideally be used first to identify the most obvious problems and, once these are fixed, should be followed by testing with typical end users.

Response of the renal inner medulla to hypoxia: possible defense mechanisms.

BACKGROUND/AIMS: Owing to the precarious blood supply to the renal medulla and the high metabolic requirement of the medullary thick ascending limb of Henle's loop, this nephron segment should be especially vulnerable when its supply of O(2) declines. METHODS: Rats were exposed to 8 or 21% O(2) at different time points up to 5 h, and samples were collected for urine flow rate, urine (U(osm)) and renal papillary (RP(osm)) osmolality, urinary excretion of Na(+), Cl(-), K(+) and Mg(2+), blood gases, erythropoietin and vasopressinase activity in plasma. Other groups of rats were pretreated with desmopressin acetate (dDAVP) or underwent bilateral nephrectomy (BNX) 1 h prior to the exposure. RESULTS: Hypoxic rats had water diuresis (WD) within 2.5 h, as evidenced by lower U(osm) (333 ± 42 mosm/l) and RP(osm) (869 ± 57 mosm/l), thus suggesting that hypoxia led to a failure to achieve osmotic equilibrium within the renal papilla. Circulating vasopressinase activity increased, which was partially renal in origin because it was lower after BNX. The renal concentrating ability during hypoxia was maintained with dDAVP pretreatment, suggesting that dDAVP may have improved O(2) delivery and the active reabsorption of Na(+) in the renal medullary region. CONCLUSIONS: WD or high vasopressinase activity may be valuable diagnostic tools to assess renal medullary hypoxia. Pretreatment with dDAVP may prevent these changes during hypoxia.

Non-natriuretic doses of furosemide: potential use for decreasing the workload of the renal outer medulla with minimal magnesium wasting in the rat.

BACKGROUND/AIMS: Since furosemide (FS) inhibits active Na(+) reabsorption by medullary thick ascending limb (mTAL) in the renal outer medulla, it may decrease its work during periods of low O2 supply to deep in the renal outer medulla. This study was designed to demonstrate that there may be a dose of FS would reduce its metabolic work while preventing the excessive loss of magnesium (Mg(2+)). Mg(2+) is important because the ATP needed to perform work must have bound Mg(2+) to it. METHODS: Rats were injected intraperitoneally with a range of doses of FS. The measured outcomes were urine flow rate and parameters of functions of the mTAL (i.e. urine and renal papillary osmolality and urinary excretion of Na(+), Cl(-), K(+) and Mg(2+), and concentrations of Mg(2+) in serum). RESULTS: The urine flow rate increased significantly starting at 2.4 mg FS/kg. The renal papillary osmolality decreased at ≥0.4 mg FS/kg, and the large detectable natriuresis started at 1.6 mg FS/kg. At this latter dose, the urinary excretion of Mg(2+) rose significantly. CONCLUSION: In rats, the non-natriuretic dose of FS may reduce the work of the mTAL. The earliest indicator of reduced work in the mTAL appears to be a decrease in urine osmolality rather than a rise in urine flow rate. Higher doses of FS should be avoided, as they induce high rates of Mg(2+) excretion, which can deplete the body of this essential electrolyte.

Development and evaluation of a multimedia e-learning resource for electrolyte and acid-base disorders.

This article reports on the development and evaluation of a Web-based application that provides instruction and hands-on practice in managing electrolyte and acid-base disorders. Our teaching approach, which focuses on concepts rather than details, encourages quantitative analysis and a logical problem-solving approach. Identifying any dangers to the patient is a vital first step. Concepts such as an "appropriate response" to a given perturbation and the need for electroneutrality in body fluids are used repeatedly. Our Electrolyte Workshop was developed using Flash and followed an iterative design process. Two case-based tutorials were built in this first phase, with one tutorial including an interactive treatment simulation. Users select from a menu of therapies and see the impact of their choices on the patient. Appropriate text messages are displayed, and changes in body compartment sizes, brain size, and plasma sodium concentrations are illustrated via Flash animation. Challenges encountered included a shortage of skilled Flash developers, budgetary constraints, and challenges in communication between the authors and the developers. The application was evaluated via user testing by residents and specialists in internal medicine. Satisfaction was measured with a questionnaire based on the System Usability Scale. The mean System Usability Scale score was 78.4 ± 13.8, indicating a good level of usability. Participants rated the content as being scientifically sound; they liked the teaching approach and felt that concepts were conveyed clearly. They indicated that the application held their interest, that it increased their understanding of hyponatremia, and that they would recommend this learning resource to others.

Intrarenal urea recycling leads to a higher rate of renal excretion of potassium: an hypothesis with clinical implications.

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.