Disorders of sodium balance
BMJ 2006; 332 doi: https://doi.org/10.1136/bmj.332.7543.702 (Published 23 March 2006) Cite this as: BMJ 2006;332:702All rapid responses
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Being in agreement with your review about the importance of proper
diagnosis and treatment of "dysnatremias" and
far from criticizing a good job, I´d just like to suggest
calling them what they are, that is disorders of "plasma sodium
concentration" and not of "sodium balance".
Everyone in the nephrology field knows that, but for general practitioners and
students I think it would be better to use the proper name, mentioning
that "the disorders of sodium concentration mostly reflect disorders in
water balance". In that way it is easier to understand the pathophysiology
and treatment.
I know that I´m saying an obvious thing, but sometimes it is good to remember what we were taught.
Sincerely yours.
Gerardo O. Mogni.
Staff physician, Nephrology Division, Hospital Posadas, Buenos Aires,
Argentina
Competing interests:
None declared
Competing interests: No competing interests
It was interesting to see that none of your correspondents have
commented on the shift in the use of the word 'Balance' in the recent
article on Sodium abnormalities [1]. The authors apply the balance word to
shifts in the concentration of plasma Sodium rather than relating it
conventionally to total body Sodium, for which they harness 'Volaemia' of
various degrees.
Generations of medical students and trainees have confounded conventional
sodium balance and sodium concentration, to the detriment of bedside
clinical physiology and safe clinical management.
The problem seems to develop from the occurrence of Hyponatraemia in
Addison's Disease, where sodium wasting is also present. The fact that the
Hyponatraemia may come from the secretion of vasopressin, responding to a
hypovolaemic rather than an osmotic stimulus, is not widely enough
considered. The Hyponatraemia is then easily attributed to sodium losses
rather than dilution by retained water.
The common disorders of Sodium Concentration (Balance?) are largely the
result of disordered Water Balance, however that may have developed.
Sodium (conventional) balance is manifest through blood pressure, weight
and signs of the congested state, at whatever concentration of plasma
Sodium that is determined by current water balance. The authors structure
this usefully in Table form.
If Balance is used for shifts in concentration, what term shall we use for
the variation of total body Sodium, when concentration is not at all the
issue? Nephrotic Syndrome comes to mind. Most nephrosis occurs with
elevated total body sodium (positive conventional balance), normal plasma
Sodium and little or no evidence of central volume disturbance, so that
reliance on a derivative of volaemia to express Sodium status would be
unhelpful. Was it the intention of the authors to reform the clinical
vocabulary in this way? If so, they may create as much confusion as they
aimed to dispel, with clinical physiology redefined without proper notice
and some flaws.
1. Rebecca M Reynolds, Paul L Padfield, and Jonathan R Seckl
Disorders of sodium balance
BMJ 2006; 332: 702-705
Competing interests:
None declared
Competing interests: No competing interests
Reynolds et al.[1] make a useful contribution to the literature on
sodium disturbances. However, they make scant mention of cerebral salt
wasting syndrome (CSWS). Hyponatraemia occurs in 1-15% of hospital
inpatients[2] but is most common in the inpatient neurological
population[3], in whom a significant proportion of hyponatraemia is caused
by CSWS. This is a poorly understood phenomenon thought to be caused by
raised atrial and brain natriuretic peptide levels, and characterised by
renal loss of sodium in the presence of intracranial disease, leading to
hyponatraemia and hypovolaemia. CSWS is predominantly associated with
subarachnoid haemorrhage but has also been described in conjunction with
traumatic brain injury, glioma, and tuberculous or carcinomatous
meningitis[4].
Reynolds et al. correctly state that plasma and urine osmolalities
are rarely helpful in diagnosing the cause of hyponatraemia and that
clinical examination is the key to diagnosis. However, in their assessment
flowchart for hyponatraemia they erroneously state that, in the context of
hypovolaemic hyponatraemia, urine sodium will be <30 mmol/l but may be
>30 if intravenous saline has already been administered and associate a
urine sodium>30 mmol/l with a euvolaemic state requiring treatment by
fluid restriction. CSWS and syndrome of inappropriate antidiuretic hormone
secretion are both associated with a high urine sodium[5], often greatly
elevated above 30 mmol/l, but the treatment of these two conditions is
diametrically opposed. It is not correct to say, as did the authors, that
the treatment of asymptomatic hyponatraemia, even if chronic, is fluid
restriction. If the diagnosis is CSWS, fluid restriction will worsen the
hypovolaemic state and lead to serious complications. The treatment of
CSWS is always fluid and sodium resuscitation using 0.9% saline in the
first instance.
We advocate an expectant and supportive management strategy in
asymptomatic hyponatraemic patients, with treatment reserved for those
developing symptoms. We have recently published simple algorithms to aid
assessment[5] and would strongly counsel against a blanket policy of fluid
restriction, even in chronic asymptomatic cases, stressing instead that
treatment must always be guided by clinical examination of volaemic
status.
1. Reynolds RM, Padfield PL, Seckl JR. Disorders of sodium balance.
BMJ 2006;332(7543):702-5.
2. Fried LF, Palevsky PM. Hyponatremia and hypernatremia. Med Clin
North Am 1997;81(3):585-609.
3. Reeder RF, Harbaugh RE. Administration of intravenous urea and
normal saline for the treatment of hyponatremia in neurosurgical patients.
J Neurosurg 1989;70(2):201-6.
4. Betjes MG. Hyponatremia in acute brain disease: the cerebral salt
wasting syndrome. Eur J Intern Med 2002;13(1):9-14.
5. Tisdall M, Crocker M, Watkiss J, Smith M. Disturbances of sodium
in critically ill neurologic patients: a clinical review. J Neuro Anesth
2006;18(1):57-63.
Competing interests:
None declared
Competing interests: No competing interests
Like some of your other correspondents, we enjoyed reading the
article by Reynolds et al (1). However, we felt that their text-book
presentation of the classification of hyponatraemia does not make for easy
learning. As Robert Lord pointed out in his response, keeping it as
simple as possible is key to remembering facts at the bedside. In
addition, it is important to remember that common things happen commonly,
a maxim we all need to reinforce in our teaching. In this respect, we felt
the article failed to emphasise this point.
In March this year, our department analysed 13,080 inpatient samples
for sodium. Of these, the mean sodium was 137 mmol/L, with a standard
deviation of 5 mmol/L. 24.4% were less than 135 mmol/L and 0.22% were less
than 120 mmol/L. The commonest cause we see for sodium in the range 120-
135 mmol/L is fluid replacement therapy, which receives only a brief
mention in Reynold et al’s article.
Severe hyponatraemia (<_120 mmol="mmol" l="l" is="is" rare.="rare." crook="crook" et="et" al="al" _2="_2" have="have" previously="previously" found="found" that="that" the="the" commonest="commonest" causes="causes" of="of" severe="severe" hyponatraemia="hyponatraemia" in="in" hospital="hospital" patients="patients" are="are" chest="chest" infection="infection" diuretics="diuretics" cardiac="cardiac" failure="failure" post-="post-" operative="operative" stress="stress" carcinoma="carcinoma" and="and" selective="selective" serotonin="serotonin" re-uptake="re-uptake" inhibitors.="inhibitors." p="p"/> In our experience, the commonest cause of hyponatraemia in primary
care patients is diuretics, though a few cases of Addison’s have been
picked up from a low sodium result.
As Reynolds et al (1) stated, hypernatraemia is seen less commonly
than hyponatraemia; 3.8% of our sodiums analysed in March were greater
than 145 mmol/L. In our experience, hypernatraemic patients are often on
ITU and ventilated, with increased insensible losses.
We would also like to point out that the Clinical Biochemistry
Department is there to offer advice to hospital doctors and GP’s on the
possible causes and appropriate laboratory investigation of hypo- and
hypernatraemia, if required!
1.Reynolds RM, Padfield PM, Seckl JR. Disorders of sodium balance.
BMJ 2006;332:702-705.
2.Crook MA, Velauthar U, Moran L, Griffiths W. Review of investigation and
management of severe hyponatraemia in a hospital population. Ann Clin
Biochem 1999;36:158-162.
Competing interests:
None declared
Competing interests: No competing interests
When the duration of hypernatraemia is unknown, and the patient has
only mild to moderate neurological symptoms but unable to drink, there is
no justification for using hypotonic saline or any dextrose iv infusion.
0.9% (normal) saline would suffice. Its sodium concentration at 150mmols
per litre, is still lower than the serum sodium concentration in such
patients. As the vascular volume expands there would be gradual correction
of intravascular and cellular osmolality, followed by renal sodium
excretion
One of the dangers of rapid intravascular osmolar dilution is the
risk of developing cerebral oedema. In younger patients with bigger
physiological reserve, this may not matter much. However, in older
patients, rapid haemodilution is often followed by neurological
deterioration.
Thank you
Competing interests:
None declared
Competing interests: No competing interests
Thank you for the well written and easily understandable review about
dysnatraemias! Many junior doctors will benefit from this.
I would like to add that there is some help available to estimate the
correction of dysnatraemias by intravenous fluids. In 2000 HJ Androuge and
NE Madias published their reviews about dysnatraemias in the NEJM (1,2).
They included a formula to predict what effect a given intravenous
solution will have on the serum-sodium level. The aim was to use this
formula to avoid too rapid changes and therefore complications of sodium
correction.
In January 2006 G Liamis et al. published a paper where it was verified
that this formula (Adrogue-Madias formula) is indeed useful in the real
world and can fairly accurately predict the effect of intravenous fluids
(though it tends to underestimate the result by a few milimol)(3). Care
has to be taken to use an adequate total body weight. The formula was not
very good to estimate sodium correction in patients with hypernatraemia,
severe dehydration and marked renal impairment.
(1) Androgue HJ, Madias NE. Hyponatremia. N Engl J Med 2000;342; 1581
-1589
(2) Androgue HJ, Madias NE. Hypernatremia. N Engl J Med 2000;342; 1493-
1499
(3) Liamis G et al. Therapeutic approach in patients with dysnatemias.
Neprol Dial Transplant 2006; doi:10.1093/ndt/gfk090
Competing interests:
None declared
Competing interests: No competing interests
Professor John Wildsmith suggests that 3 litres of fluid a day is too
high an intake and may lead to frequency of micturition. Whilst urine
output certainly is commensurate with fluid ingestion, I would challenge
the premise that a high (but not excessive) daily intake is likely to be
harmful in any way for healthy adults with healthy kidneys. Most of us
consume far more sodium than we need - government figures suggest that
most adults consume about 10 grams a day, whilst our daily requirement is
actually only about 0.5 grams a day. I am sure a high fluid intake helps
flush out some of this surplus and harmful sodium. The risks of
hyponatremia are low as the kidneys are very effective at retaining
sodium. Of course, most of us who practice this simple form of "detox"
have learned to ingest fluids early in the day rather than late at night.
Competing interests:
None declared
Competing interests: No competing interests
Reynolds et al provide a very useful overview of the causes and
treatment of hypo-and hypernatraemia.1 However, the not uncommon
artefactual causes of abnormal serum sodium levels might have had greater
representation. In particular, the authors state: “Pseudohyponatraemia ...
should no longer be seen with the measurement of sodium by ion specific
electrodes” needs to be interpreted with caution. The authors dismiss
pseudohyponatraemia, but in our view this remains an important cause of
apparently abnormal levels.
Whilst Ion Selective Electrodes (ISEs) are almost universal now,
there are two types namely direct and indirect ISEs. The distinction is
important as the indirect ISEs are affected by pseudohyponatraemia. In the
latest round of the National External Quality Assurance Scheme (NEQAS),
534 (397 from UK labs) respondents employed indirect compared to only 31
(30 from UK) employing direct ISE measurement. (Source: Finlay MacKenzie,
UKNEQAS, personal communication). With more than 90% of labs still
potentially experiencing pseudohyponatraemia, we believe that this issue
should not be forgotten!
1. Reynolds RM, Padfield PL, Seckl JR. Disorders of sodium balance.
BMJ 2006;332:702-705.
Competing interests:
None declared
Competing interests: No competing interests
I enjoyed this review but was struck that no mention was made of the
role of prescribed medication, particullarly under the mantle of
'iatrogenic causes', (and indeed illict drug use), despite the references
to the former in the article, 1,2.
A Large numbers of drugs are implicated in inappriate ADH secretion,
including most of the Selective Serotonin Re-uptake Inhibitors (Prozac
like drugs), which can present with life threatening seizures. It would
have been usefull to gently remind a general readership of this, and the
need to take a drug history.
1. Adrogué, HJ, Madias NE. Hyponatraemia. N Engl J Med 2000;342: 1581
-9.
2.Matthai SM, Davidson DC, Sills JA, Alexandrou D. Cerebral oedema
after ingestion of MDMA ("ecstasy") and unrestricted intake of water. BMJ
1996;312:1359.
Competing interests:
None declared
Competing interests: No competing interests
Re: disorders of sodium concentration
"Dysnatremias" are "disorders of "plasma sodium concentration" and
not of "sodium balance" and "disorders of sodium concentration mostly
reflect disorders in water balance", writes Gerardo O. Mogni in his rapid
response to this article (1).
If the intercompartmental movement of sodium is accompanied by an
osmotic equivalent of water then dysnatremias and disorders of water
balance may both be disorders of pH balance which in turn may be a
reflection of energy balance or Daniel Atkinson enrgy charge. An
intracellular acidosis, which is commonly a reflection of anerobiosis, has
as its dominant intracellular pH regulator the Na(+)/H(+) antiport which
increases intracellular [Na+]..and its osmotic equivalent of water. This
might be inhibited when the interstitial pH falls to abnormally low levels
or perhaps more accurately when the interstitial pH falls below the
intracellular pH. If so this is likely to be a largely passive process
certainly in the short term (2) but clearly one that has an active
component, one possibly (3) activated by the generation of cAMP (4). The
generation of cAMP from ATP is increasingly unlikely to occur as the pH
falls in accordances with the Daniel Atkinson energy charge hypothesis
(5).
The inference is that plasma [Na+], and the movement of its osmotic
equvalent of water, is influenced by the energy charge, the pH, and the
pH gradient between intraceullar and interstitial fluid. To determine the
quantitative significance of these possibilities it would seem necessary
to perturb normal balances by clamping plasma pH at different levels,
possibly by means of the pH-stat technique (2), and inducing changes in
the energy charge and Na(+)/H(+) antiport activity possibly with EGF.
The notion that, "disorders of sodium concentration mostly reflect
disorders in water balance" might be a gross oversimplification especially
in pathologic circumstances in which an energy deficit is likely to be
present.
2. Fiddian-Green RG, Silen W.Mechanisms of disposal of acid and
alkali in rabbit duodenum.
Am J Physiol. 1975 Dec;229(6):1641-8.
3. Nylander-Koski O, Mustonen H, Puolakkainen P, Kiviluoto T,
Kivilaakso E. Epidermal Growth Factor Enhances Intracellular pH Regulation
via Calcium Signaling in Acid-Exposed Primary Cultured Rabbit Gastric
Epithelial Cells.
Dig Dis Sci. 2006 Jul 11;
4. Chaturvedi D, Edwin F, Sun H, Patel TB. Analysis of EGF receptor
interactions with the alpha subunit of the stimulatory GTP binding protein
of adenylyl cyclase, Gs.
Methods Mol Biol. 2006;327:49-59.
5. Hardie DG, Hawley SA. AMP-activated protein kinase: the energy
charge hypothesis revisited.
Bioessays. 2001 Dec;23(12):1112-9.
6. Noakes TD, Speedy DB. Case proven: exercise associated
hyponatraemia is due to overdrinking. So why did it take 20 years before
the original evidence was accepted?
Br J Sports Med. 2006 Jul;40(7):567-72.
unreversed ATP hydrolysis is neutralized in part by the
Competing interests:
None declared
Competing interests: No competing interests