Intensive Care Medicine
Intens. Care Med. 5, 23-26 (1979)
9 by Springer-Verlag 1979
Hyponatraemia in Patients with Head Injury Michael D. Penney, Glyn Waiters, and David G. Wilkins Departments of ChemicalPathology and Anaesthetics, Bristol Royal Infirmary, Bristol
Abstract. Three patients with head injury are described t o illustrate certain features of the development, treatment and recovery of hyponatraemia. The hyponatraemia is initially due to water retention but true sodium depletion may develop because of an associated urine sodium loss. The mechanism of the latter is discussed.
encountered true sodium depletion as a contributory factor resulting from the renal sodium loss. The following three cases illustrate factors to be considered when assessing such hyponatraemia and the futility of attempts to correct secondary sodium depletion without first correcting the water overload.
Key words: Head Injury, Hyponatraemia, Antidiuretic hormone, Natriuresis.
Case Reports Case 1
Introduction Hyponatraemia and hypochloraemia are well recognised in patients with head injury, usually accompanied by loss of sodium and chloride in the urine [7]. These changes have also been observed in patients with other cerebral lesions [6]. Intravenous infusions of sodium chloride do not usually correct the hyponatraemia but merely increase the urinary excretion of sodium. At first it was thought that renal loss of sodium was the cause of the hyponatraemia, and Peters et al [13] postulated diminished tubular reabsorption of sodium, presumed to be mediated by renal nerves. A hypothalamic-renal pathway was suggested by Cort [4] on the basis of observations made on a patient with a posterior hypothalamic tumour. However, Carter et al. [1 ] studied the sodium balance in patients with cerebral hyponatraemia and concluded that hyponatraemia was the result of water retention, presumed to be due to prolonged and excessive secretion of antidiuretic hormone (ADH). Such water retention, result~mg in expansion of the extracellular fluid (ECF) volume, would be expected to cause the excretion of large amounts of sodium in the urine because reabsorption of sodium by the renal tubules is inhibited by ECF expansion [12]. We have seen a number of patients with head injury develop hyponatraemia and agree that the mechanism is generally one of water retention. However, we have also
A 21 year old male was admitted with multipe injuries after a motor-cycle accident. He was conscious on admission but gradually became comatose over the next five hours, with spasticity of the right side and dilatation of the left pupil. Burr holes and carotid angiography revealed no evidence of intracranial bleeding or cerebral contusion. Subsequently fat embolism was diagnosed. The plasma sodium fell progressively from the time of operation despite a sodium intake of 1400 mmol on the day of admission and 200 - 300 mmol/day thereafter (Fig. 1). By the tenth day after admission the plasma sodium was 125 mmol/1, and on the eleventh day 750 mmol of sodium chloride were given intravenously in the form of two litres of double strength saline and one litre of isotonic saline. During this 24-hour period the urinary excretion of sodium was about 300 mmol and although the plasma sodium did rise to 130 mrnol/1, this level was not sustained and hyponatraemia recurred within 24 h. The relevant biochemical changes at this stage are given in Table 1. On the basis of the plasma urea, the high urine specific gravity and high urine sodium concentration it was concluded that hyponatraemia was due to water retention and this was confirmed by the fluid balance charts which indicated a positive balance of 3.8 litres. The water intake was restricted to 800 ml/day, the sodium intake in the nasogastric feeds being about 50 mmol/day. It can be seen from Figure 1 that the urine output of sodium, which fell only slowly, exceeded the intake of sodium for four days. After this the output settled at about 50 mmol/day, 0342-4642/79/0005/0023/$ 01.00
24
PLASMA SOOIUM mmol/i
M.D. Penney et al.: Hyponatraemia
'4~I FLUIDRESTRICTION 800
7OO 800 SOOIUM 5OO INTAKE 400 mmo| /day 300
20O I00
SOOIUM OUTPUT
mmol
I day
'~ ......... Fig. 1.
DAYOFADMISSION
Table 1. Urine sodium concentration and specific gravity in relation to plasma urea and electrolytes
Case 1 Case2 (Day 12) (Day 7) Plasma urea (mmol/1) Plasma sodium (mmol/1) Plasma potassium (mmol/1) Plasma chloride (mmol/1) Plasma bicarbonate (mmol/1) Plasma osmolality (mOsm/kg) Urine sodium (mmol/1) Urine specific gravity Urine osmolality (mOsm/kg)
Case 3 (Day 6)
5.0 127 3.5 96 24 258 120 1.022
2.8 120 4.2 89 23 254 135 1.019
2.5 120 3.2 88 25 249 not measured not measured
710
665
not measured
trarenal loss. By the seventh day the plasma sodium had fallen to 120 mmol/1. At this stage the low plasma urea and electrolyte concentrations and the high urine specific gravity and urine sodium concentration (Table 1) suggested water retention. This was corroborated by the fluid balance chart which showed a positive balance of 3 litres, which in a small woman (50 kg) was sufficient to account for such a fall in plasma sodium. Water restriction to 800 ml/day was imposed, and with it a reduction of the sodium intake, but the response was different from that in Case 1. Despite the maintenance of water restriction sufficient to reduce the positive cumulative water balance to less than one litre by day 12 there was little change in the plasma sodium concentration. In contrast to Case 1, the urine sodium concentration fell rapidly to very low levels indicating sodium depletion. The plasma concentrations of urea and potassium remained within the normal range, and the plasma osmolality reflected the sodium concentration. An intravenous infusion of 300 mmol of hypertonic sodium chloride was given and this caused the plasma sodium to rise dramatically to 140 mmol/1, around which level it was thereafter sustained. In contrast to Case 1, none of the infused sodium was excreted in the urine, and the urine sodium content remained low, more or less equalling the sodium intake. Thus, it appeared that the water restriction was an incomplete method of treatment in this patient but it can be seen from Fig. 2 that on the day that water restriction was begun and on the two preceding days the sodium excretion in the urine exceeded the intake. We interpret the changes as indicating initial natriuresis due to water overload with subsequent true sodium depletion as a re-
PLASMA SODIUM mmol/I
140I
1301 120L
i.e. it roughly equalled the intake. Yet despite the excretion of more sodium than the intake the plasma concentration rose to normal levels. This is a typical case in which simply restricting the water intake reversed the fall in plasma sodium concentration despite continuing loss of sodium in the urine. Case 2 A 38 year old woman was found unconscious in the road with left facial abrasions and bleeding from the left ear. The right pupil was fixed and dilated, the limbs were flaccid and all the tendon reflexes were absent. At operation an acute subdural haematoma in the right temporal and frontal region was drained. The patient remained unconscious. On the fifth day the plasma sodium concentration was found to be 125 mmol/1 despite an intake of sodium of 300-450 mmol/day since admission and no apparent ex-
SODIUM INTAKE
mmoi. /day
soo~~k~ 600~-
4ool-
[.~...~.~..~
300t 200~1000I
400~-
3~176
SODIUM 0UTPUTHot200F /day
2 4 6 8 1 0 1 2 1 4 1 8 1 8 2 0
Fig. 2.
DAY OF ADMISSION
M.D. Penneyet al.: I-Iyponatraemia
25
suit, despite which sodium excretion continued to exceed intake. Subsequently the plasma sodium remained within normal limits provided water restriction was maintained. For example, two months after admission water restriction was relaxed and the patient's sodium fell to 124 mmol/1. Thereafter water restriction was maintained until her death six months later; she had remained comatose thoughout her admission. At postmortem the brain was examined macroscopically only and showed extensive old damage to the right hemisphere and peduncle. Case 3 A 33 year-old woman was admitted with fractures of the left frontal sinus and orbit, and a Le Fort III fractured maxilla but no loss of consciousness. There was some CSF rhinorrhoea. On the sixth postoperative day the plasma sodium was found to be 120 mmol/1 (Table 1) having been normal three days previously; this had occured despite the intake of 1050 mmol of sodium since admission. Fluid balance charts showed a positive balance of 5.6 litres with no apparent abnormal sodium loss except for a little CSF rhinorrhoea. Following the administration of 650 rnmol sodium chloride in a mixture of normal saline and fifthnormal saline during 48 hours the plasma sodium rose to 130 mmol/1. At the end of this period, however, the patient passed two litres of urine in 7 h, with a specific gravity of 1.001. Diabetes insipidus was suspected and
PLASMA mmol/I
130/ 120L80O 70O
SODIUM
PITRESSIN TANNATE
60O
INTAKE mmol
5O0
/day
40O 300 20O 100 0
mmo[
/day
100[-
""~ 2
Fig. 3.
4
k 8
10
DAY OF ADMISSION
12
14
1 mg of pitressin tannate in oil was given. Liberal fluids were also given and as a result the following morning the plasma sodium was once again 120 mmol/1. The water intake was therefore restricted and no more pitressin was given. The plasma sodium rapidly returned to normal levels and there was no further problem with fluid and electrolyte balance. Data on urine sodium excretion are scanty and were not collected until the day the plasma sodium rose to normal. However it is noteworthy that on the day of the largest sodium infusion less than half of it was excreted during that 24 h period and that three days later, although the plasma sodium was normal, the urine sodium excretion was exceedingly low. Evidently a sodium depletion was being corrected. It seems likely that the sequence of events in this case was as follows. Hyponatraemia due to water retention developed between the third and sixth days, followed by spontaneous recovery as evidenced by the large volume of dilute urine and the restoration of the plasma sodium concentration; subsequently hyponatraemia recurred due to pitressin-induced water retention. The sodium balance at the end indicated some degree of sodium depletion.
Discussion All three cases illustrate the development of hyponatraemia despite the previous administration of large amounts of sodium in excess of any extrarenal loss. The plasma urea and electrolytes showed a dilutional pattern, i.e. normal or low urea concentration and reduction of sodium and chloride concentration in the same proportions, as indicated by the normal level of bicarbonate. In the first two cases the urine was concentrated relative to the plasma while in Case 3 the urine concentration at the relevant time is not known. It is noteworthy that the administration of pitressin to this patient followed by hypotonic sodium chloride solutions resulted in a recurrence of hyponatraemia accompanied by the excretion of large amounts of sodium in the urine, exactly as occurred spontaneously in the other two patients. Secretion of anti-diuretic hormone is affected by changes in both plasma osmolality and blood volume [ 11 ], and increased secretion forms part of the metabolic response to injury. In the latter circumstance however the period of water retention generally lasts for less t h a n 48 h so that other factors, as yet unknown, must account for the prolonged tendency to water retention in some patients with head injury; whether they are associated with anatomical lesions in the hypothalamus has not been determined. The mechanism of the urinary sodium loss is complex. There is little doubt that it is related to expansion of the ECF volume, as the administration of pitressin followed by a water load in normal subjects produces hyponatraemia with renal sodium wasting [12], as seen in Case 3. Expansion of the ECF volume increases the glomerular Filtration rate but this appears not to be the main cause of the associated renal excretion of sodium [8]. Aldosterone
26
secretion, and hence reabsorpfion of sodium in the distal renal tubule, is usually inhibited by expansion of the ECF volume, and low levels of aldosterone have been found in some cases of hyponatraemia due to water retention [14]. In others however, including one case of head injury [ 10], the levels were normal or raised despite the presence of renal sodium loss. Recently, Cohen et al [2] have suggested that hyponatraemia is itself a stimulus to aldosterone secretion and that it may over-ride the inhibitory effect on aldosterone secretion of volume expansion. Most of the sodium in the glomerular filtrate is reabsorbed in the proximal tubule, the regulatory factor being the so-called natriuretic hormone or "third factor" [9]. If sodium is rejected at this site the amount reaching the distal segment may exceed the latter's capacity for sodium reabsorption even when aldosterone secretion is high [5]. The continued urinary loss of sodium in the presence of high levels of aldosterone is therefore probably due to this mechanism, and as the administration of isotonic or hypertonic saline will further expand the ECF volume, it serves only to increase the urinary excretion of sodium. If volume expansion due to the administration of hypotonic solutions is prolonged it is clearly possible for a negative sodium balance to develop. Water restriction alone may then not restore the plasma sodium level to normal and indeed, in some such patients, a rise in the plasma urea indicates the development of a subnormal circulating volume before the hyponatraemia is corrected. Hyponatraemia results in a shift of water into the cells. In conscious patients this causes apathy, headache, anorexia, nausea and vomiting and, in severe cases, coma, convulsions and death. Focal neurological signs, and changes in the EEG [3] may lead to a misdiagnosis of a cerebro-vascular disorder. Clearly, such misleading effects of hyponatraemia in head injuries are to be avoided by careful attention to the patient's water balance. Should hyponatraemia develop, restriction of water intake to about 800 ml per day will reverse the positive water balance; but the possibility of sodium depletion and the need for sodium supplements must be borne in mind. However, it is pointless to infuse even hypertonic sodium solutions before restricting the water intake, because the additional sodium will not be retained if the extracellular fluid volume remains expanded. Acknowledgements. We thank Mr. B.H. Cummins and Mr. H.B. Griffith for permission to publish details of these patients who were under their care.
M.D. Penney et al.: Hyponatraemia
References 1. Carter, N.W., Rector, F.C., Seldin, D.W.: Hyponatraemia in cerebral disease resulting from the inappropriate secretion of antidiurefic hormone. N. Engl. J. Med. 264, 67 (1961) 2. Cohen, J.J., Hulter, H.N., Smithline, N., Melby, J . C ' Schwartz, W.B.: The critical role of the adrenal gland in the renal regulation of acid-base equilibrium during chronic hypotonic expansion. J. Clin. Invest. 58, 120 (1976) 3. Cohn, S.H.: Electroencephalographic changes induced by water intoxication. J. Nerv. Meat. Dis. 106, 513 (1947) 4. Cort. J.H.: Cerebral salt wasting. Lancet 1954 I, 752 5. Fichman, M.P., Bethune, J.E.: The role of adrenocorticoids in the appropriate antidiuretic hormone syndrome. Ann. Intern. Med. 68, 806 (1968) 6. Goldberg, M., Handler, J.S.: Hyponatraemia and renal wasting of sodium in patients with malfunction of the central nervous system. N. Engl. J. Med. 263, 1037 (1960) 7. Higgins, G., Lewin, W., O'Brien, J.R.P., Taylor, W.H.: Metabolic disorders in head injury. Lancet 1954 I, 61 8. Jones, N. F., Barraclough, M.A. and Mills, I.H.: The mechanism of increased sodium excretion during water loading with 2.5 per cent dextrose and vasopressin. Clin. Sci. 25,449 (1963) 9. Klahr, S., Rodriguez, H.J.: Natriuretic hormone. Nephron 15,387 (1975) 10. Knochel, J.P., Osborn, J.R., Cooper, E.B.: Excretion of aldosterone in inappropriate secretion of antidiuretic hormone following head trauma. Metabolism 14,715 (1965) 11. Kurtzman, N.A., Boonjarern, S.: Physiology of antidiuretic hormone and the interrelationship between the hormone and the kidney. Nephron 15,167 (1975) 12. Leaf, A., Bartter, F.C., Santos, R.F., Wrong, O.: Evidence in man that urinary electrolyte loss induced by pitressin is a function of water retention. J. Clin. Invest. 32, 868 (1953) 13. Peters, J.P., Welt, L.G., Sims, E.A.H., Orloff, J., Needham, J. : A salt wasting syndrome associated with cerebral disease. Trans. Assoc. Am. Physicians 63, 57 (1950) 14. Schwartz, W.B., Bennett, W., Curelop, S., Bartter, F.C.: A syndrome of renal sodium loss and hyponatraemia probably resulting from inappropriate secretion of antidiuretic hormone. Am. J. Med. 23,592 (1957) Dr. Michael Penney Bristol Royal Infirmary Bristol BS2 8 HW England
Intens. Care Med. 5, 23-26 (1979)
9 by Springer-Verlag 1979
Hyponatraemia in Patients with Head Injury Michael D. Penney, Glyn Waiters, and David G. Wilkins Departments of ChemicalPathology and Anaesthetics, Bristol Royal Infirmary, Bristol
Abstract. Three patients with head injury are described t o illustrate certain features of the development, treatment and recovery of hyponatraemia. The hyponatraemia is initially due to water retention but true sodium depletion may develop because of an associated urine sodium loss. The mechanism of the latter is discussed.
encountered true sodium depletion as a contributory factor resulting from the renal sodium loss. The following three cases illustrate factors to be considered when assessing such hyponatraemia and the futility of attempts to correct secondary sodium depletion without first correcting the water overload.
Key words: Head Injury, Hyponatraemia, Antidiuretic hormone, Natriuresis.
Case Reports Case 1
Introduction Hyponatraemia and hypochloraemia are well recognised in patients with head injury, usually accompanied by loss of sodium and chloride in the urine [7]. These changes have also been observed in patients with other cerebral lesions [6]. Intravenous infusions of sodium chloride do not usually correct the hyponatraemia but merely increase the urinary excretion of sodium. At first it was thought that renal loss of sodium was the cause of the hyponatraemia, and Peters et al [13] postulated diminished tubular reabsorption of sodium, presumed to be mediated by renal nerves. A hypothalamic-renal pathway was suggested by Cort [4] on the basis of observations made on a patient with a posterior hypothalamic tumour. However, Carter et al. [1 ] studied the sodium balance in patients with cerebral hyponatraemia and concluded that hyponatraemia was the result of water retention, presumed to be due to prolonged and excessive secretion of antidiuretic hormone (ADH). Such water retention, result~mg in expansion of the extracellular fluid (ECF) volume, would be expected to cause the excretion of large amounts of sodium in the urine because reabsorption of sodium by the renal tubules is inhibited by ECF expansion [12]. We have seen a number of patients with head injury develop hyponatraemia and agree that the mechanism is generally one of water retention. However, we have also
A 21 year old male was admitted with multipe injuries after a motor-cycle accident. He was conscious on admission but gradually became comatose over the next five hours, with spasticity of the right side and dilatation of the left pupil. Burr holes and carotid angiography revealed no evidence of intracranial bleeding or cerebral contusion. Subsequently fat embolism was diagnosed. The plasma sodium fell progressively from the time of operation despite a sodium intake of 1400 mmol on the day of admission and 200 - 300 mmol/day thereafter (Fig. 1). By the tenth day after admission the plasma sodium was 125 mmol/1, and on the eleventh day 750 mmol of sodium chloride were given intravenously in the form of two litres of double strength saline and one litre of isotonic saline. During this 24-hour period the urinary excretion of sodium was about 300 mmol and although the plasma sodium did rise to 130 mrnol/1, this level was not sustained and hyponatraemia recurred within 24 h. The relevant biochemical changes at this stage are given in Table 1. On the basis of the plasma urea, the high urine specific gravity and high urine sodium concentration it was concluded that hyponatraemia was due to water retention and this was confirmed by the fluid balance charts which indicated a positive balance of 3.8 litres. The water intake was restricted to 800 ml/day, the sodium intake in the nasogastric feeds being about 50 mmol/day. It can be seen from Figure 1 that the urine output of sodium, which fell only slowly, exceeded the intake of sodium for four days. After this the output settled at about 50 mmol/day, 0342-4642/79/0005/0023/$ 01.00
24
PLASMA SOOIUM mmol/i
M.D. Penney et al.: Hyponatraemia
'4~I FLUIDRESTRICTION 800
7OO 800 SOOIUM 5OO INTAKE 400 mmo| /day 300
20O I00
SOOIUM OUTPUT
mmol
I day
'~ ......... Fig. 1.
DAYOFADMISSION
Table 1. Urine sodium concentration and specific gravity in relation to plasma urea and electrolytes
Case 1 Case2 (Day 12) (Day 7) Plasma urea (mmol/1) Plasma sodium (mmol/1) Plasma potassium (mmol/1) Plasma chloride (mmol/1) Plasma bicarbonate (mmol/1) Plasma osmolality (mOsm/kg) Urine sodium (mmol/1) Urine specific gravity Urine osmolality (mOsm/kg)
Case 3 (Day 6)
5.0 127 3.5 96 24 258 120 1.022
2.8 120 4.2 89 23 254 135 1.019
2.5 120 3.2 88 25 249 not measured not measured
710
665
not measured
trarenal loss. By the seventh day the plasma sodium had fallen to 120 mmol/1. At this stage the low plasma urea and electrolyte concentrations and the high urine specific gravity and urine sodium concentration (Table 1) suggested water retention. This was corroborated by the fluid balance chart which showed a positive balance of 3 litres, which in a small woman (50 kg) was sufficient to account for such a fall in plasma sodium. Water restriction to 800 ml/day was imposed, and with it a reduction of the sodium intake, but the response was different from that in Case 1. Despite the maintenance of water restriction sufficient to reduce the positive cumulative water balance to less than one litre by day 12 there was little change in the plasma sodium concentration. In contrast to Case 1, the urine sodium concentration fell rapidly to very low levels indicating sodium depletion. The plasma concentrations of urea and potassium remained within the normal range, and the plasma osmolality reflected the sodium concentration. An intravenous infusion of 300 mmol of hypertonic sodium chloride was given and this caused the plasma sodium to rise dramatically to 140 mmol/1, around which level it was thereafter sustained. In contrast to Case 1, none of the infused sodium was excreted in the urine, and the urine sodium content remained low, more or less equalling the sodium intake. Thus, it appeared that the water restriction was an incomplete method of treatment in this patient but it can be seen from Fig. 2 that on the day that water restriction was begun and on the two preceding days the sodium excretion in the urine exceeded the intake. We interpret the changes as indicating initial natriuresis due to water overload with subsequent true sodium depletion as a re-
PLASMA SODIUM mmol/I
140I
1301 120L
i.e. it roughly equalled the intake. Yet despite the excretion of more sodium than the intake the plasma concentration rose to normal levels. This is a typical case in which simply restricting the water intake reversed the fall in plasma sodium concentration despite continuing loss of sodium in the urine. Case 2 A 38 year old woman was found unconscious in the road with left facial abrasions and bleeding from the left ear. The right pupil was fixed and dilated, the limbs were flaccid and all the tendon reflexes were absent. At operation an acute subdural haematoma in the right temporal and frontal region was drained. The patient remained unconscious. On the fifth day the plasma sodium concentration was found to be 125 mmol/1 despite an intake of sodium of 300-450 mmol/day since admission and no apparent ex-
SODIUM INTAKE
mmoi. /day
soo~~k~ 600~-
4ool-
[.~...~.~..~
300t 200~1000I
400~-
3~176
SODIUM 0UTPUTHot200F /day
2 4 6 8 1 0 1 2 1 4 1 8 1 8 2 0
Fig. 2.
DAY OF ADMISSION
M.D. Penneyet al.: I-Iyponatraemia
25
suit, despite which sodium excretion continued to exceed intake. Subsequently the plasma sodium remained within normal limits provided water restriction was maintained. For example, two months after admission water restriction was relaxed and the patient's sodium fell to 124 mmol/1. Thereafter water restriction was maintained until her death six months later; she had remained comatose thoughout her admission. At postmortem the brain was examined macroscopically only and showed extensive old damage to the right hemisphere and peduncle. Case 3 A 33 year-old woman was admitted with fractures of the left frontal sinus and orbit, and a Le Fort III fractured maxilla but no loss of consciousness. There was some CSF rhinorrhoea. On the sixth postoperative day the plasma sodium was found to be 120 mmol/1 (Table 1) having been normal three days previously; this had occured despite the intake of 1050 mmol of sodium since admission. Fluid balance charts showed a positive balance of 5.6 litres with no apparent abnormal sodium loss except for a little CSF rhinorrhoea. Following the administration of 650 rnmol sodium chloride in a mixture of normal saline and fifthnormal saline during 48 hours the plasma sodium rose to 130 mmol/1. At the end of this period, however, the patient passed two litres of urine in 7 h, with a specific gravity of 1.001. Diabetes insipidus was suspected and
PLASMA mmol/I
130/ 120L80O 70O
SODIUM
PITRESSIN TANNATE
60O
INTAKE mmol
5O0
/day
40O 300 20O 100 0
mmo[
/day
100[-
""~ 2
Fig. 3.
4
k 8
10
DAY OF ADMISSION
12
14
1 mg of pitressin tannate in oil was given. Liberal fluids were also given and as a result the following morning the plasma sodium was once again 120 mmol/1. The water intake was therefore restricted and no more pitressin was given. The plasma sodium rapidly returned to normal levels and there was no further problem with fluid and electrolyte balance. Data on urine sodium excretion are scanty and were not collected until the day the plasma sodium rose to normal. However it is noteworthy that on the day of the largest sodium infusion less than half of it was excreted during that 24 h period and that three days later, although the plasma sodium was normal, the urine sodium excretion was exceedingly low. Evidently a sodium depletion was being corrected. It seems likely that the sequence of events in this case was as follows. Hyponatraemia due to water retention developed between the third and sixth days, followed by spontaneous recovery as evidenced by the large volume of dilute urine and the restoration of the plasma sodium concentration; subsequently hyponatraemia recurred due to pitressin-induced water retention. The sodium balance at the end indicated some degree of sodium depletion.
Discussion All three cases illustrate the development of hyponatraemia despite the previous administration of large amounts of sodium in excess of any extrarenal loss. The plasma urea and electrolytes showed a dilutional pattern, i.e. normal or low urea concentration and reduction of sodium and chloride concentration in the same proportions, as indicated by the normal level of bicarbonate. In the first two cases the urine was concentrated relative to the plasma while in Case 3 the urine concentration at the relevant time is not known. It is noteworthy that the administration of pitressin to this patient followed by hypotonic sodium chloride solutions resulted in a recurrence of hyponatraemia accompanied by the excretion of large amounts of sodium in the urine, exactly as occurred spontaneously in the other two patients. Secretion of anti-diuretic hormone is affected by changes in both plasma osmolality and blood volume [ 11 ], and increased secretion forms part of the metabolic response to injury. In the latter circumstance however the period of water retention generally lasts for less t h a n 48 h so that other factors, as yet unknown, must account for the prolonged tendency to water retention in some patients with head injury; whether they are associated with anatomical lesions in the hypothalamus has not been determined. The mechanism of the urinary sodium loss is complex. There is little doubt that it is related to expansion of the ECF volume, as the administration of pitressin followed by a water load in normal subjects produces hyponatraemia with renal sodium wasting [12], as seen in Case 3. Expansion of the ECF volume increases the glomerular Filtration rate but this appears not to be the main cause of the associated renal excretion of sodium [8]. Aldosterone
26
secretion, and hence reabsorpfion of sodium in the distal renal tubule, is usually inhibited by expansion of the ECF volume, and low levels of aldosterone have been found in some cases of hyponatraemia due to water retention [14]. In others however, including one case of head injury [ 10], the levels were normal or raised despite the presence of renal sodium loss. Recently, Cohen et al [2] have suggested that hyponatraemia is itself a stimulus to aldosterone secretion and that it may over-ride the inhibitory effect on aldosterone secretion of volume expansion. Most of the sodium in the glomerular filtrate is reabsorbed in the proximal tubule, the regulatory factor being the so-called natriuretic hormone or "third factor" [9]. If sodium is rejected at this site the amount reaching the distal segment may exceed the latter's capacity for sodium reabsorption even when aldosterone secretion is high [5]. The continued urinary loss of sodium in the presence of high levels of aldosterone is therefore probably due to this mechanism, and as the administration of isotonic or hypertonic saline will further expand the ECF volume, it serves only to increase the urinary excretion of sodium. If volume expansion due to the administration of hypotonic solutions is prolonged it is clearly possible for a negative sodium balance to develop. Water restriction alone may then not restore the plasma sodium level to normal and indeed, in some such patients, a rise in the plasma urea indicates the development of a subnormal circulating volume before the hyponatraemia is corrected. Hyponatraemia results in a shift of water into the cells. In conscious patients this causes apathy, headache, anorexia, nausea and vomiting and, in severe cases, coma, convulsions and death. Focal neurological signs, and changes in the EEG [3] may lead to a misdiagnosis of a cerebro-vascular disorder. Clearly, such misleading effects of hyponatraemia in head injuries are to be avoided by careful attention to the patient's water balance. Should hyponatraemia develop, restriction of water intake to about 800 ml per day will reverse the positive water balance; but the possibility of sodium depletion and the need for sodium supplements must be borne in mind. However, it is pointless to infuse even hypertonic sodium solutions before restricting the water intake, because the additional sodium will not be retained if the extracellular fluid volume remains expanded. Acknowledgements. We thank Mr. B.H. Cummins and Mr. H.B. Griffith for permission to publish details of these patients who were under their care.
M.D. Penney et al.: Hyponatraemia
References 1. Carter, N.W., Rector, F.C., Seldin, D.W.: Hyponatraemia in cerebral disease resulting from the inappropriate secretion of antidiurefic hormone. N. Engl. J. Med. 264, 67 (1961) 2. Cohen, J.J., Hulter, H.N., Smithline, N., Melby, J . C ' Schwartz, W.B.: The critical role of the adrenal gland in the renal regulation of acid-base equilibrium during chronic hypotonic expansion. J. Clin. Invest. 58, 120 (1976) 3. Cohn, S.H.: Electroencephalographic changes induced by water intoxication. J. Nerv. Meat. Dis. 106, 513 (1947) 4. Cort. J.H.: Cerebral salt wasting. Lancet 1954 I, 752 5. Fichman, M.P., Bethune, J.E.: The role of adrenocorticoids in the appropriate antidiuretic hormone syndrome. Ann. Intern. Med. 68, 806 (1968) 6. Goldberg, M., Handler, J.S.: Hyponatraemia and renal wasting of sodium in patients with malfunction of the central nervous system. N. Engl. J. Med. 263, 1037 (1960) 7. Higgins, G., Lewin, W., O'Brien, J.R.P., Taylor, W.H.: Metabolic disorders in head injury. Lancet 1954 I, 61 8. Jones, N. F., Barraclough, M.A. and Mills, I.H.: The mechanism of increased sodium excretion during water loading with 2.5 per cent dextrose and vasopressin. Clin. Sci. 25,449 (1963) 9. Klahr, S., Rodriguez, H.J.: Natriuretic hormone. Nephron 15,387 (1975) 10. Knochel, J.P., Osborn, J.R., Cooper, E.B.: Excretion of aldosterone in inappropriate secretion of antidiuretic hormone following head trauma. Metabolism 14,715 (1965) 11. Kurtzman, N.A., Boonjarern, S.: Physiology of antidiuretic hormone and the interrelationship between the hormone and the kidney. Nephron 15,167 (1975) 12. Leaf, A., Bartter, F.C., Santos, R.F., Wrong, O.: Evidence in man that urinary electrolyte loss induced by pitressin is a function of water retention. J. Clin. Invest. 32, 868 (1953) 13. Peters, J.P., Welt, L.G., Sims, E.A.H., Orloff, J., Needham, J. : A salt wasting syndrome associated with cerebral disease. Trans. Assoc. Am. Physicians 63, 57 (1950) 14. Schwartz, W.B., Bennett, W., Curelop, S., Bartter, F.C.: A syndrome of renal sodium loss and hyponatraemia probably resulting from inappropriate secretion of antidiuretic hormone. Am. J. Med. 23,592 (1957) Dr. Michael Penney Bristol Royal Infirmary Bristol BS2 8 HW England
