HYPONATRAEMIAHYPONATRAEMIA

Dr. Mohammad Dr. Mohammad Rokun UddinRokun Uddin Medical Medical Officer Officer Dept. Of Medicine BBMH,USTC

A 65 year old women is brought to the A 65 year old women is brought to the emergency room for increasing emergency room for increasing confusion and lethargy over the past confusion and lethargy over the past week. She was recently diagnosed week. She was recently diagnosed with small cell cancer of lung. She has with small cell cancer of lung. She has not been febrile or had any other not been febrile or had any other recent illness. She is not taking any recent illness. She is not taking any medications. Her blood pressure is medications. Her blood pressure is 136/82 mm Hg, HR 84b/min and 136/82 mm Hg, HR 84b/min and respiratory rate 14b/min and respiratory rate 14b/min and unlabored. on examination she is an unlabored. on examination she is an elderly apearing woman who is elderly apearing woman who is difficult to arouse and reacts only to difficult to arouse and reacts only to painful stimuli. She is able to move painful stimuli. She is able to move her extremities without apparent her extremities without apparent motor deficits and her deep tendon motor deficits and her deep tendon reflexes are decrease symmetrically. reflexes are decrease symmetrically. The remainder of her examination is The remainder of her examination is normal ,with a normal jagular venous normal ,with a normal jagular venous pressure and no extremity odema.pressure and no extremity odema.

Laboratory test reveal the Laboratory test reveal the serum sodium 108 mmol/l , serum sodium 108 mmol/l , potassium 3.8mmol/l, potassium 3.8mmol/l, bicarbonate 24 mEq/l, BUN 5 bicarbonate 24 mEq/l, BUN 5 mg/dl, creatinine 0.5 mg/dl. mg/dl, creatinine 0.5 mg/dl. Serum osmolarity is 220 Serum osmolarity is 220 mOsm/kg and urine osmolality is mOsm/kg and urine osmolality is 400mOsm/Kg. A CT Scan of 400mOsm/Kg. A CT Scan of brain shows no masses or brain shows no masses or hydrocephalus.hydrocephalus.

What is the most likely What is the most likely diagnosis ?diagnosis ?

When the plasma sodium level is less than 135 mmol/L

(Normal plasma sodium 135-145mmol/L)

What is hyponatraemia ?What is hyponatraemia ?

Plasma osmolality=2[Na+]+2[k+]+[glucose]+Plasma osmolality=2[Na+]+2[k+]+[glucose]+[urea][urea]Normal plasma osmolality 280-295mmol/LNormal plasma osmolality 280-295mmol/L

Volume status and serum osmolalityVolume status and serum osmolality

are essential to determine etiology.are essential to determine etiology.    Hyponatraemia usually reflects Hyponatraemia usually reflects

excess excess

water retention relative to sodiumwater retention relative to sodium

rather than sodium deficiency.rather than sodium deficiency.     Hypotonic fluids commonly causeHypotonic fluids commonly cause

hyponatraemia in hospitalized hyponatraemia in hospitalized patients.patients.

PHYSIOLOGYPHYSIOLOGY

Serum sodium concentration Serum sodium concentration regulationregulation

Stimulation of thirstStimulation of thirst

Secretion of A.D.HSecretion of A.D.H

Feedback mechanism of renin Feedback mechanism of renin angiotensin aldosterone system.angiotensin aldosterone system.

Renal handling of filtered sodiumRenal handling of filtered sodium

ClassificationClassification

On OsmolalityOn Osmolality

On Volume statusOn Volume status

On Duration of On Duration of onsetonset

On OsmolarityOn Osmolarity

Pseudo HyponatraemiaPseudo Hyponatraemia

Spurious HyponatraemiaSpurious Hyponatraemia

True HyponatraemiaTrue Hyponatraemia

On Volume statusOn Volume status

Hypovolemic hyponatraemiaHypovolemic hyponatraemia

Euvolemic hyponatraemiaEuvolemic hyponatraemia

Hypervolemic hyponatraemiaHypervolemic hyponatraemia

On Duration On Duration

Acute HyponatraemiaAcute Hyponatraemia

Chronic hyponatraemiaChronic hyponatraemia

Pseudo HyponatraemiaPseudo Hyponatraemia

Causes :Causes : Severe Hyper triglyceridaemiaSevere Hyper triglyceridaemia Severe Hyperproteinaemia Severe Hyperproteinaemia

Serum osmolality is isotonic because Serum osmolality is isotonic because lipids and proteins do not affect lipids and proteins do not affect osmolality measurement.osmolality measurement.

Newer sodium assays using ion-specific Newer sodium assays using ion-specific electrodes will not produce electrodes will not produce pseudohyponatremia.pseudohyponatremia.

Treatment of ‘Hyponatraemia’ is Treatment of ‘Hyponatraemia’ is unnecessaryunnecessary..

Spurious Hyponatraemia/Hypertonic Spurious Hyponatraemia/Hypertonic HyponatremiaHyponatremia

Here Osmolality is high, total Here Osmolality is high, total sodium issodium is

normal. but concentration per dl is normal. but concentration per dl is low.low.

Diabetic KetoacidosisDiabetic Ketoacidosis

Chronic Mannitol infusionChronic Mannitol infusion

In both Diabetic ketoacidosis In both Diabetic ketoacidosis and chronic mannitol and chronic mannitol infusion,Glucose and mannitol infusion,Glucose and mannitol draws water from I.C.F to E.C.F draws water from I.C.F to E.C.F and there by dilute sodium and there by dilute sodium leading to fall in concentration leading to fall in concentration of sodium.Though total body of sodium.Though total body stores are normal.stores are normal.

True HyponatraemiaTrue Hyponatraemia

Both osmolality,sodium Both osmolality,sodium concentration and total sodium concentration and total sodium stores are low.stores are low.

Acute HyponatraemiaAcute Hyponatraemia

Develops in less than 48 hoursDevelops in less than 48 hours.

Rapidly developing Hyponatraemia Rapidly developing Hyponatraemia may kill a patient even if the value may kill a patient even if the value is only 125 Meq/L by causing water is only 125 Meq/L by causing water into ICF resulting cerebral oedemainto ICF resulting cerebral oedema.

Chronic HyponatraemiaChronic Hyponatraemia

>48 hours>48 hours

Patient may be asymptomatic even Patient may be asymptomatic even at 110 mmol /L, because brain at 110 mmol /L, because brain tissue gets time to correct oedema tissue gets time to correct oedema by excreting osmolites like by excreting osmolites like glucose, amino acids etc from the glucose, amino acids etc from the cell.cell.

So must be treated slowly.So must be treated slowly.

If rapid correction is done abrupt If rapid correction is done abrupt increase in extra cellular osmolality can increase in extra cellular osmolality can lead to water shifting out of cerebral lead to water shifting out of cerebral neurons, abruptly reducing their volume neurons, abruptly reducing their volume and risking detachment from their and risking detachment from their myelin sheaths resulting in myelin sheaths resulting in

Osmotic Demyelination syndrome

(CEREBRAL PONTINE MYELINOLYSIS) Which produces permanent structural Which produces permanent structural damage to mid brain structures and is damage to mid brain structures and is

fatal fatal .

CAUSESCAUSES

HYPOVOLAEMICHYPOVOLAEMIC

EUVOLAEMICEUVOLAEMIC

HYPERVOLAEMICHYPERVOLAEMIC

HYPOVOLAEMICHYPOVOLAEMIC

Sodium deficit with relatively smaller Sodium deficit with relatively smaller water deficitwater deficit..

Gastro Intestinal &Gastro Intestinal &other Sodium losses other Sodium losses VomitingVomiting DiarrhoeaDiarrhoea Skin Na lossesSkin Na losses BurnsBurns HaemorrhageHaemorrhage

Renal sodium losses Renal sodium losses Diuretic therapyDiuretic therapy (especially (especially

Thiazide )Thiazide ) Adrenocortical FailureAdrenocortical Failure,, Cerebral salt Cerebral salt

wasting syndromewasting syndrome Tubulo-interstitial Tubulo-interstitial

renal diseaserenal disease

EUVOLAEMICEUVOLAEMIC

Water retention alone.Water retention alone.

SIADH SIADH (syndrome of inappropriate (syndrome of inappropriate anti diuretic hormone secretion)anti diuretic hormone secretion)

Primary polydipsiaPrimary polydipsia Excessive Electrolyte free water Excessive Electrolyte free water

InfusionInfusion HypothyroidismHypothyroidism Postoperative hyponatremiaPostoperative hyponatremia Adrenocorticotropin deficiencyAdrenocorticotropin deficiency

HYPERVOLAEMICHYPERVOLAEMIC

Sodium retention with relatively Sodium retention with relatively greater water retentiongreater water retention

Congestive cardiac failureCongestive cardiac failure

CirrhosisCirrhosis

Nephrotic syndromeNephrotic syndrome

Chronic renal Chronic renal failure failure (during free (during free water intake)water intake)

S.I.A.D.HS.I.A.D.H

CausesCauses Tumors .Tumors .Especially small cell lung cancerEspecially small cell lung cancer(75% of (75% of

cases of malignancy-associated cases of malignancy-associated SIADH)SIADH),colon cancer,colon cancer

CNS disordersCNS disordersLike stroke,trauma,infection,psychosisLike stroke,trauma,infection,psychosis

Pulmonary disordersPulmonary disordersLike pneumonia,TB,ostructive lung Like pneumonia,TB,ostructive lung

diseasedisease

DrugsDrugsLike:-Like:- - Anticonvulsants-- Anticonvulsants-

carbamazepinecarbamazepine - Psychotropics-haloperidol- Psychotropics-haloperidol - Anti depressants-amitriptyline- Anti depressants-amitriptyline - Cytotoxic-cyclophosphamide- Cytotoxic-cyclophosphamide - Hypoglycemics- Hypoglycemics -morphine-morphine Sustained pain,stress,nausea,Sustained pain,stress,nausea, Idiopathic.Idiopathic.

Diagnosis of SIADHDiagnosis of SIADH

Low plasma sodium concentration Low plasma sodium concentration

(typically<130 mmol/l(typically<130 mmol/l)) Low plasma osmolality Low plasma osmolality

( <270/mmol/kg)( <270/mmol/kg) Urine osmolality not minimally low Urine osmolality not minimally low

(>150mmol/kg)(>150mmol/kg)

Urine sodium concentration not minimally low Urine sodium concentration not minimally low ( > 30 mmol/L)( > 30 mmol/L)

Low-normal plasma urea, creatinine,uric acid.Low-normal plasma urea, creatinine,uric acid.

Exclusion of other causes of hyponatraemiaExclusion of other causes of hyponatraemia

Absence of heart, kidney, or liver disease and Absence of heart, kidney, or liver disease and normal thyroid and adrenal function .normal thyroid and adrenal function .

CLINICAL PRESENTATON OF CLINICAL PRESENTATON OF HYPONATRAEMIAHYPONATRAEMIA

Degree of cerebral symptomatology depends Degree of cerebral symptomatology depends more on the rate of development of the more on the rate of development of the electrolytes abnormamality than on its electrolytes abnormamality than on its severity.severity.

Early symptoms - anorexia, nausea, vomiting, Early symptoms - anorexia, nausea, vomiting, headacheheadache

Later -confusion, lethargy, brainstem Later -confusion, lethargy, brainstem herniation ,seizures and coma , death.herniation ,seizures and coma , death.

In acute hyponatremia symptom develop evan In acute hyponatremia symptom develop evan at Naat Na+ + ~~

125 mEq/L125 mEq/LIn chronic hyponatremia pt. may be In chronic hyponatremia pt. may be

asymptomatic until Naasymptomatic until Na+ + ~ 115 mEq/L or less.~ 115 mEq/L or less.Mild Hyponatremia (Na- 130–135 mmol/L) is usually asymptomatic.Mild Hyponatremia (Na- 130–135 mmol/L) is usually asymptomatic.

INVESTIGATIONSINVESTIGATIONS

Serum Electrolytes- Including Mg Serum Electrolytes- Including Mg (as decrease potassium & Magnesium potentiates ADH (as decrease potassium & Magnesium potentiates ADH

release)release) Plasma osmolarity- Plasma osmolarity- - Increase in Psaeudo hyponitraemia- Increase in Psaeudo hyponitraemia - Decrease in spurious hyponitraemia- Decrease in spurious hyponitraemia Urinary OsmolarityUrinary Osmolarity Urinary SodiumUrinary Sodium TSH and CortisolTSH and Cortisol Calcium, Albumin, Glucose, LFTCalcium, Albumin, Glucose, LFT

Urine Na and osmolality in the differential Urine Na and osmolality in the differential diagnosis of hyponatraemiadiagnosis of hyponatraemia

Urine Na (mmol/L) Urine osmolality (mmol/kg)

Possible diagnoses

Low (< 30)Low (< 30) Low (< 100)Low (< 100) Primary polydipsiaPrimary polydipsiaMalnutritionMalnutritionBeer excessBeer excess

LowLow High (> 150)High (> 150) Salt depletionSalt depletionHypovolaemiaHypovolaemia

High (> 40)High (> 40) LowLow Diuretic action (acute Diuretic action (acute phase)phase)

HighHigh HighHigh SIADHSIADHAdrenal insufficiencyAdrenal insufficiencyCerebral salt-wastingCerebral salt-wasting

TREATMENTTREATMENT

Treatment of Hyponatraemia is Treatment of Hyponatraemia is depend on rate of development, depend on rate of development, severity and underlying causesseverity and underlying causes

If Hyponatraemia developed If Hyponatraemia developed rapidly- generaly it is safe to rapidly- generaly it is safe to correct rapidly with 3% NaClcorrect rapidly with 3% NaCl

If Development is slow, it is safe to If Development is slow, it is safe to correct slowly.correct slowly.

Symptomatic Hyponatraemia Symptomatic Hyponatraemia with Neurological featureswith Neurological features

Manage in HDUManage in HDU Increase Na- by as little as 3-7 Increase Na- by as little as 3-7

mmol/L will usually treat symptomsmmol/L will usually treat symptoms

In acute HyponatraemiaIn acute Hyponatraemia

Hypertonic (3%) sodium chloride Hypertonic (3%) sodium chloride solutions, especially when the solutions, especially when the patient is convulsing.patient is convulsing.

Aim for increase Na >1-2 mmol/L Aim for increase Na >1-2 mmol/L /hour untill asymptomatic - in the /hour untill asymptomatic - in the first 4 hoursfirst 4 hours

Do not correct > 10 mmol/L/dayDo not correct > 10 mmol/L/day Should not be corrected > 125-130 Should not be corrected > 125-130

mmol/Lmmol/L Monitor every 2-4 hr.Monitor every 2-4 hr.

In Chronic HyponatraemiaIn Chronic Hyponatraemia

Aim for increase Na > Aim for increase Na > 0.5mmol/L /hour untill 0.5mmol/L /hour untill asymptomaticasymptomatic

Correct <8-10 mmol/L/day ,Correct <8-10 mmol/L/day , <18 mmol/L/48hr.<18 mmol/L/48hr.

Hypovoluamic Hypovoluamic HyponatraemiaHyponatraemia Primary causes should be treated Primary causes should be treated

firstfirst Oral Electrolyte glucose mixtureOral Electrolyte glucose mixture Increase salt intake sodiumIncrease salt intake sodium 60-80 mmol/day60-80 mmol/day ( 1 tab NaCl= 10 mmol)( 1 tab NaCl= 10 mmol) If vomiting and severe If vomiting and severe volume depletion-volume depletion- IV fluid with 0.9% NaCl.IV fluid with 0.9% NaCl.

Euvoluamic Euvoluamic HyponatraemiaHyponatraemia

Fluid restriction (500-1000 ml Fluid restriction (500-1000 ml /day)/day)

NaCl 4-8 tab daily ± frusemide NaCl 4-8 tab daily ± frusemide (20-40mg daily)(20-40mg daily)

SIADH-SIADH- - Demeclocycline 600-900 - Demeclocycline 600-900

mg/daymg/day - Oral Urea 30-45 gm/day - Oral Urea 30-45 gm/day - Oral vasopressin receptor - Oral vasopressin receptor

antagonist (Vaptan).antagonist (Vaptan).

Hypervoluamic Hypervoluamic HyponatraemiaHyponatraemia

Treatment of Primary Treatment of Primary causecause

Fluid restriction (<1000 Fluid restriction (<1000 ml /day)ml /day)

FurosemideFurosemide Potassium sparing Potassium sparing

Diuretics.Diuretics.

FORMULAFORMULA

Amount of sodium to be given per day Amount of sodium to be given per day

eg(X)=Target sodium –Patient Sodium ×× body weight in kg × × 0.6 (in case of males) or

0.5 ( in case of females)For example, a nonedematous,severely For example, a nonedematous,severely

symptomatic 70 kg woman with a symptomatic 70 kg woman with a serum sodium of 122 mEq/L should serum sodium of 122 mEq/L should have her Na 132 mEq/L in the first 24 have her Na 132 mEq/L in the first 24 hours. Her sodium deficit is hours. Her sodium deficit is calculated as:calculated as:

1 mL/kg of 3% sodium chloride 1 mL/kg of 3% sodium chloride will raise will raise the plasma sodium by the plasma sodium by 1mmol/L.1mmol/L. X=513-Patients Sodium /Body weight in kg X=513-Patients Sodium /Body weight in kg × 0.6+1× 0.6+1

Na deficit = 70 kg × 0.5 × (132 Na deficit = 70 kg × 0.5 × (132 mEq/L – 122 mEq/L)mEq/L – 122 mEq/L)= 350 mEq= 350 mEq

3% NaCl 514 mEq/1000 mL. 3% NaCl 514 mEq/1000 mL. Delivery rate = Sodium deficit/514 Delivery rate = Sodium deficit/514

mEq/1000mL/24 hoursmEq/1000mL/24 hours = 350 mEq/514 mEq/1000 mL/24 = 350 mEq/514 mEq/1000 mL/24

hourshours =680mL/24hrs=680mL/24hrs = 28 mL/hour.= 28 mL/hour.

Osmotic Demyelination SyndromeOsmotic Demyelination Syndrome

Patients with chronic hyponatremia are most susceptible to the Patients with chronic hyponatremia are most susceptible to the development of ODS, since their brain cell volume has returned to development of ODS, since their brain cell volume has returned to near normal as a result of the osmotic adaptive mechanisms near normal as a result of the osmotic adaptive mechanisms described above. Therefore, administration of hypertonic saline to described above. Therefore, administration of hypertonic saline to these individuals can cause sudden osmotic shrinkage of brain cells. these individuals can cause sudden osmotic shrinkage of brain cells. Caused by correcting hyponatremia too rapidly . Caused by correcting hyponatremia too rapidly .

Risk factors for ODS include prior cerebral anoxic injury, Risk factors for ODS include prior cerebral anoxic injury, hypokalemia, and malnutrition, especially secondary to alcoholismhypokalemia, and malnutrition, especially secondary to alcoholism

Neurologic disorder characterized by flaccid paralysis, dysarthria, Neurologic disorder characterized by flaccid paralysis, dysarthria, and and

dysphagia ataxia,fluctuating level of conciousness,diplopiadysphagia ataxia,fluctuating level of conciousness,diplopia..

Suspected clinically and can be confirmed by neuroimaging studies.Suspected clinically and can be confirmed by neuroimaging studies. [CT/ MRI ][CT/ MRI ] hypointense lesions on T1-weighted images and hypointense lesions on T1-weighted images and

hyperintense on T2- hyperintense on T2- weighted images on MRI.weighted images on MRI.

No specific treatment . Associated with significant morbidity and No specific treatment . Associated with significant morbidity and mortality. mortality.

Magnetic resonance imaging (MRI) of patient Magnetic resonance imaging (MRI) of patient showing lesions typical of central pontine showing lesions typical of central pontine myelinolysis, with high T2-weighted MRI signal.myelinolysis, with high T2-weighted MRI signal.

Diagnosis ?Diagnosis ?

Diagnosis : Diagnosis : Severe Severe hyponatraemia hyponatraemia most likely a most likely a tumor-related tumor-related SIADHSIADH.

ReferencesReferences

Davidson’s Principles & Practice of Davidson’s Principles & Practice of MedicineMedicine

Kumar and Clarks Clinical MedicineKumar and Clarks Clinical Medicine CURRENT Medical Diagnosis and CURRENT Medical Diagnosis and

Treatment 2013Treatment 2013 Oxford Handbook of Nephrology.Oxford Handbook of Nephrology.

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