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Patient with Bartter syndrome in whom chronic potassium depletion was considered one of the causes of hyponatremia
  1. Katsunobu Yoshioka
  1. Department of Internal Medicine, Shitennoji Hospital, Osaka, Japan
  1. Correspondence to Dr Katsunobu Yoshioka; kyoshioka{at}shitennoji-fukushi.jp

Abstract

A 53-year-old man was admitted to our hospital because of general fatigue and disorientation. He had been diagnosed with Bartter syndrome in his teens and had been taking potassium preparations since then. However, his serum potassium concentration (K+s) remained persistently low. Ten days before admission, he developed fever. He was diagnosed as having bronchitis and was treated with antibiotics. Although his fever subsided, general fatigue worsened. Laboratory examination showed hyponatraemia (127 mEq/L), while K+s was 2.3 mEq/L. C reactive protein was negative. On admission, laboratory examination revealed deterioration of hyponatraemia (125 mEq/L). Although his serum sodium concentration (Na+s) was refractory to electrolyte replacement, the level increased towards normal after spironolactone administration, following normalisation of K+s, suggesting that hyponatraemia was caused by K+ depletion. Physicians should be aware of the importance of the effects of exchangeable K+ (K+e) on Na+s.

  • fluid electrolyte and acid-base disturbances
  • medical management

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Background

According to the Edelman equation, serum sodium (Na+) concentration is approximated as the sum of exchangeable Na+ and potassium (K+) content divided by total body water (TBW).1 That is, Na+s = Embedded Image, in which Na+s is the serum Na+ concentration, Na+e is the exchangeable Na+ content and K+e is the exchangeable K+ content. As is evident from this equation, K+e content in the body plays an important role in the determination of Na+s. However, very few case reports have demonstrated K+e depletion as the main cause of hyponatraemia.2 3 This might be due to the low recognition of this condition by physicians because the effect of change in K+e on Na+s is intuitively less evident.

This report presents the development of hyponatraemia in a patient with Bartter syndrome, whose serum K+ concentration (K+s) remained persistently low. The cause of hyponatraemia was considered as chronic K+e depletion because Na+s increased towards normal after spironolactone therapy, following normalisation of K+s. This case suggests the importance of the effects of K+e on Na+s. Additionally, the mechanisms by which K+e depletion causes hyponatraemia are discussed.

Case presentation

A 53-year-old man (164 cm tall, weighing 57.1 kg) was admitted to our hospital because of general fatigue and disorientation. He had been diagnosed as having Bartter syndrome when he was a junior high school student and had been taking K+ supplements since then. His K+s was low (ranging from 2.3 to 3.4 mEq/L) at least for the previous 1 year, despite therapy with 900 mg of potassium l-aspartate. His Na+s was also slightly low (ranging from 134 to 135 mEq/L). Ten days before admission, he developed fever with a temperature of over 38°C, a stinging or tingling sensation on the head and general fatigue, for which he visited his family physician. Laboratory examination showed deterioration of Na+s (127 mEq/L), while K+s was 2.3 mEq/L. However, C reactive protein (CRP) levels were normal. He was diagnosed as having bronchitis and was treated with antibiotics. Although his fever and stinging/tingling sensation subsided, general fatigue worsened. He had no nausea or vomiting. Three days later, he revisited his family physician, complaining of worsening of fatigue and disorientation, including forgetting how to wear a necktie. At this time, since his hyponatraemia was found to have further deteriorated (Na+s 125 mEq/L), he was referred to our hospital for further examination and treatment.

On admission, his blood pressure was 99/73 mm Hg and pulse rate was 111 beats per minute. His body temperature was 36.6°C. Although he could respond normally to questionings, he appeared mildly confused and disoriented. He did not complain of headache. Inspection of his head did not disclose blisters suggestive of herpes zoster infection. His remaining physical examination was unremarkable.

Investigations

Laboratory results showed hyponatraemia, hypokalaemia and metabolic alkalosis. Serum calcium, phosphate and magnesium levels were normal (table 1). His CRP level was less than 0.05 mg/dL. Chest X-ray and whole body CT revealed no abnormal findings.

Table 1

Laboratory data on admission

Differential diagnosis

At first, ascribing the cause of hyponatraemia and hypokalaemia to poor Na+ and K+ intake due to the acute illness together with renal Na+ and K+ loss due to pre-existing tubular dysfunction, potassium chloride was given intravenously along with isotonic saline (0.9% sodium chloride + 40 mEq potassium chloride/L) for 24 hours. Furthermore, 1800 mg of potassium chloride was given orally. However, 2 days after admission, hyponatraemia and hypokalaemia deteriorated further (Na+s 122 mEq/L, K+s 2.7 mEq/L) (figure 1). By this time, his remaining laboratory test results were available, which showed excessive urinary excretion of Na+ (Na+u) and K+ (K+u). The trans-tubular potassium gradient value was high (16.6) for his K+s (3.0 mEq/L). Relative hypouricaemia prompted me consideration of the possibility of water excess as a cause of hyponatraemia. Hence, hypertonic saline (1.7% sodium chloride 500 mL +20 mEq potassium chloride) was given and water restriction was commenced, although without noticeable effects. At this point, the cause of hyponatraemia in the present case was speculated as chronic K+e depletion.

Figure 1

The patient’s clinical course.

Treatment

Although it could have potentially caused worsening of hyponatraemia, 25 mg of spironolactone was administered. Two days later, laboratory data revealed a slight increase in Na+s (126 mEq/L), with no change in K+s (2.7 mEq/L). At this time, he was discharged based on his strong request, under therapy with 50 mg of spironolactone together with 3600 mg of potassium chloride daily. Four days after discharge, laboratory data revealed a slight increase in K+s (3.3 mEq/L), with no change in Na+s (125 mEq/L). However, 12 days after discharge, laboratory data revealed improvement of both Na+s (131 mEq/L) and K+s (4.1 mEq/L). Additionally, his subjective symptoms, such as general fatigue and disorientation, had disappeared.

Outcome and follow-up

Thereafter, his Na+s and K+s remained within normal limits (Na+s: 137–139 mEq/L and K+s: 3.5–3.7 mEq/L) under daily therapy with 50 mg of spironolactone together with 3600 mg of potassium chloride.

Discussion

The diagnosis and treatment of hyponatraemia are challenging because there are a wide variety of causes of hyponatraemia.4 Hypovolemic hyponatraemia due to poor intake or extra-renal loss of Na+ was unlikely in the present case because urinary Na was high and the patient’s Na+s was refractory to electrolyte replacement therapy. Hypervolemic hyponatraemia, as with cardiac failure, renal failure and liver cirrhosis, was ruled out clinically. Additionally, the patient had no evidence of thyroid or adrenal disease.

Na+u levels (>20 mEq/L), urinary osmolality (>100 mOsm/kg), measurable arginine vasopressin level (0.8 pg/mL) and relatively low serum uric acid levels are findings that support the diagnosis of syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Before admission, the patient developed fever and a stinging/tingling sensation on the head. Therefore, it was important to consider the possibility of SIADH due to infectious diseases, such as meningitis, herpes zoster infection or bronchitis. However, these possibilities were ruled out by inspection of the head and laboratory and radiological findings. Furthermore, the diagnosis of SIADH is one of exclusion and cannot be considered in a patient with tubular dysfunction, such as Bartter syndrome, as in the present case.

Initially, the cause of hyponatraemia was considered as poor Na+ intake together with renal Na+ and K+ loss due to tubular dysfunction. However, this was ruled out because the patient’s Na+s was refractory to electrolyte replacement. Although it is possible that preceding acute illness might have caused poor Na+ and K+ intake and excessive water intake, thereby affecting Na+s, the possibility that hyponatraemia was caused mainly by chronic K+e depletion was considered, since Na+s increased towards normal after administration of spironolactone, following normalisation of K+s.

Bartter syndrome is characterised by a defect in the thick ascending limb of the loop of Henle, which results in hypokalaemia, metabolic alkalosis and normal to low blood pressure despite secondary hyperaldosteronism. These findings are similar to those seen with loop diuretic-induced tubular dysfunction. Loop diuretics mainly impair urinary concentrating ability and limit water retention. Therefore, hyponatraemia due to loop diuretics is rare unless they are administered together with spironolactone or in the presence of poor Na+ intake. Spironolactone inhibits mineralocorticoid receptors in the distal convoluted tubule, promoting Na+ excretion and K+ retention, which usually results in lowering of Na+s. However, in the present case, Na+s increased after administration of spironolactone, following normalisation of K+s.

Loss of potassium depletes intracellular K+ stores, which results in a shift of Na+ into the cell to compensate for the exit of K+ from the cell into the extracellular fluid.3 Furthermore, depletion of intracellular K+ stores results in hypotonicity, leading to a shift of water from the intracellular to the extracellular compartment, further lowering Na+s. The reverse occurs during K+ repletion. Replacement of K+ is more effective when it is administered in the form of potassium chloride rather than potassium L-aspartate, because the entry of both chloride ions and K+ into the cell increases intracellular hypertonicity, causing a shift of water from the extracellular to the intracellular compartment. Furthermore, potassium L-aspartate worsens metabolic alkalosis.

Laragh reported that oral administration of potassium chloride to patients with hyponatraemia resulted in small to rather striking increases in Na+s without the addition of exogenous Na+.3 Fichman et al reported that the great majority of their 25 patients with thiazide-induced hyponatraemia also had hypokalaemia, and hyponatraemia was corrected in four of them by K+ repletion despite continued diuretic use and Na+ restriction.2 It has been reported that failure to consider the effect of K+ replacement on Na+s has resulted in osmotic demyelination in many cases, not only in patients with hyponatraemia5 but also in patients with normal Na+s.6–8 This shows that potassium depletion predisposes to osmotic demyelination. Assuming that TBW accounts for 50% of body weight, retention of 3 mEq/kg body weight of K+e increases Na+s by as much as 6 mEq/L.

In summary, this report describes a case of hyponatraemia in a patient with Bartter syndrome, whose serum K+e remained persistently low. Although the patient’s Na+s was refractory to electrolyte replacement, Na+s levels increased towards normal after administration of spironolactone, following normalisation of K+s. Hence, the cause of hyponatraemia in this patient was considered as chronic K+e depletion. Physicians should be aware of the importance of the effects of K+e on Na+s levels.

Learning points

  • Serum sodium (Na+) concentration is approximated as the sum of exchangeable Na+ and potassium (K+) content divided by total body water.

  • Depletion of exchangeable K+ is an important cause of hyponatraemia.

  • Poorly controlled Bartter syndrome could be a model of chronic K+ depletion.

  • Physicians should be aware of the importance of the effects of exchangeable K+ on serum Na+ concentration.

References

Footnotes

  • Contributors KY contributed to the planning of the manuscript, reviewed the patient file, performed the literature review and wrote the first and final draft of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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