Hyponatreamia Re-visited

Dr. Ng Butt Chin, Consultant Physician

Is a very common electrolyte disturbance and is not well addressed. This arises from an inadequate understanding of the aetiologies and often patients are given saline infusion when they are already grossly overloaded just because they are hyponatreamic.

Basic fluid and electrolyte physiology-60% of body weight is made up of water.2/3 of water content is intracellular, 1/3 is extracellular. Extracellular compartment is subdivided into intravascular and interstitial.2/3 of ECF is interstitial while 1/3 is intravascular. The main intravascular cation is Na while intracellular cation is K. Even though there is a huge concentration gradient for potassium and sodium across the cellular membrane, there is no shift of sodium into the cells or shift of potassium out of cells because of the Na/K ATPase pump on the cell membrane. Plasma osmolarity is calculated by total of 2xNa, 2xK, glucosand urea.

Normal plasma osmolarity is 285 mosmol/kg to 295 mosmol/kg.

Osmolarity is regulated by ADH or vasopressin, produced by supraoptic and paraventricular nuclei of hypothalamus and stored in the posterior lobe of pituitary. Vasopressin acts on V2 receptors on P (principle) cells of collecting ducts rendering it permeable to water thus absorbing water from the collecting ducts. This will dilute and reduce plasma osmolarity and concentrates urine. Increase in osmolarity will increase vasopressin release, above 285 mosmol/kg, vasopressin release is linearly related to osmolarity.Increase in osmolarity is sensed by osmoreceptors in hypothalamus. Which is very sensitive.1-2% change in osmolarity is enough to trigger the receptors.

The other factor which stimulates vasopressin is hypovolaemia.This is not sensitive; need at least 5% loss of intravascular volume to activate the baroreceptors which are carotid sinus and aortic arch. But it is a powerful stimulant, it overrides the osmoreceptors.It is important to note that Na concentration do not give us any clue as to the total sodium content in our body. It merely reflects the ratio between sodium content and water content in our body. Thus hyponatreamia do not equate to sodium depletion while hypernatreamia do not equate to sodium overload. In reality, most cases of hyponatreamia or hypernatreamia is due to change in t he water component.

Hyponatreamia may be classified as 1) hypovolaemic hyposmolar hyponatreamia 2) normovolaemic hyposmolar hyponareamia 3) hypervolaemic hyposmolar hyponatreamia.

Hypovolaemic hyponatreamia is due to true salt and water depletion. It occurs with diuretics especially thiazides and loop diuretics. Other causes are Addison’s disease, salt loosing nephritis.Extrarenal losses are diarrhoea, vomiting and perspiration. Clinical presentations include loss of skin turgor, dry mucous membrane and postural hypotension. Treatment is salt and water replacement.

Normovolaemic hyponatreamia are spurious hyponatreamia which occurs with grossly elevated lipid or protein like myeloma. Other causes are SIADH, hypothyroidism and hypopituitarism with impaired ACTH causing secondary hypocortisolaemia.SIA.DH is defined as inability to maximally dilute urine in presence of hyponatreamia .It is highly suspicious when plasma osmolarity is <275 mosmol/kg and urine osmolarity is >100 mosmol/kg.Clinically there is no hypertension or oedema. Renal, adrenal and thyroid dysfunction must be ruled out before diagnosing SIADH.Causes of SIADH are bronchogenic carcinoma, subarachnoid haemorrhage, traumatic brain injury and drugs like SSRI, tricyclic antidepressants and antiepileptics.

Clinical presentations depend more on rapidity of onset than actual sodium level. If onset is gradual over weeks etc, our brain can adjust by releasing active osmotic agent known as LMW inorganic osmolytes.This will reduce the intracellular osmolarity to keep pace with extracellular osmolarity.Thus the osmotic gradient is abolished and osmosis cannot take place.

Treatment is fluid restriction if mild. Lithium and demeclocycline which induces diuresis may be used. If urgent correction is required, 3% hypertonic saline may be used.1 ml/kg/hour may be used. I tend to err on the conservative side and I give 30 ml/hour. To prevent pulmonary oedema in elderly patients, concomitant IV frusemide may be given.Frusemide also induces free water clearance and helps to increase sodium concentration by haemoconcentration.The rule is not to exceed an increase of 8-10 mosmol/kg in 24 hours. Too rapid correction cause central pontine myelinosis.

Hypervolaemic hyposmolar hyponatreamia or dilutional hyponatreamia occurs in cases of gross water and salt retention. Such examples are CCF, nephrotic syndrome and liver cirrhosis. The water overload overwhelms the salt overload; hence the hyponatreamia.Treatment is fluid and salt restriction. Never advise patient with CCF to have supplementary and good food intake. This will increase their water and solute content and make thing worse. Loop diuretics like frusemide promotes free water clearance and will correct hyponatreamia by haemoconcentration effect.

I would like to share an interesting case of hyponatreamia which I managed 10 years ago.A 60 year old Chinese man was referred by the oncologist for incidental finding of hyponatreamia. He was on radiotherapy for NPC.Clinically; he has pallor not consistent with anaemia as his conjunctiva was pink. On suspicion of hypopituitarism, I directly asked him when he last shaved. He replied that he forgotten as it came to his realisation that he had not shaved for a long time. Test showed that he had secondary hypothyroidism and secondary hypocortisolaemia due to impaired TSH and ACTH respectively. I started him on hydrocortisone and thyroxine replacement. I presumed that his hypopituitarism may be due to radiation effect. Notice that I did not give fludrocortisone as is needed in Addison’sdisease.His mineralcorticoid is not affected as aldosterone release is not regulated by the pituitary. Aldosterone release is regulated by volume status which is sensed by baroreceptors i.e. carotid sinus and aortic arch. Shortly after, he came back with a complain of polyuria and polydipsia.I checked his RBS and BUNSE which were normal. I expected this and without further investigation like water deprivation test, I started him on vasopressin which stopped his polyuria.In fact when he first saw me, he was already having cranial diabetes insipidus. As free water clearance requires glucocorticoid,and he did not had cortisol then, his diabetes insipidus could not be manifested. But the moment his cortisol was replaced, free water clearance occurred and his so called occult cranial DI was unmasked. Another interesting point was that his BUNSE was normal. We were taught that DI typically gives hypernatreamia and hyperosmolarity because of haemoconcentration effect. In reality this does not happen because of our thirst mechanism.1 to 2 % increase in osmolarity will trigger our thirst centre and we will drink water to compensate.Haemoconcentration with resultant hypernatreamia and hyperosmolarity happens only in elderly and sick patients who cannot request for water or in children who are denied free access to water.