Dr. Sachin Verma is a young, diligent and dynamic physician. He did his graduation from IGMC Shimla and MD in Internal Medicine from GSVM Medical College Kanpur. Then he did his Fellowship in Intensive Care Medicine (FICM) from Apollo Hospital Delhi. He has done fellowship in infectious diseases by Infectious Disease Society of America (IDSA). He has also done FCCS course and is certified Advance Cardiac Life support (ACLS) and Basic Life Support (BLS) provider by American Heart Association. He has also done a course in Cardiology by American College of Cardiology and a course in Diabetology by International Diabetes Centre. He specializes in the management of Infections, Multiorgan Dysfunctions and Critically ill patients and has many publications and presentations in various national conferences under his belt. He is currently working in NABH Approved Ivy super-specialty Hospital Mohali as Consultant Intensivists and Physician.

1. ELECTROLYTE BALANCE :
SODIUM METABOLISM
Dr. Sachin Verma MD, FICM, FCCS, ICFC
Fellowship in Intensive Care Medicine
Infection Control Fellows Course
Consultant Internal Medicine and Critical Care
Web:- http://www.medicinedoctorinchandigarh.com
Mob:- +91-7508677495
References :
Harrison’s Principles of Internal Medicine 16th edn.
API Medicine update 2006.
Brenner & Rector – Diseases of Kidney.
Review of Medical physiology – Ganong 21st edn.

2. DEFINITION
 Sodium is the most abundant ion of the extra cellular
compartment.
 Water is the most abundant constituent of the body
50% of body weight in women & 60% of the body wt
in men is water, out of which 40% is intracellular and
20% is in extracellular compartment.
Total body water
(60% of body wt
I.C.F. (40 of E.C.F. (20% of
body wt) body wt)
Interstitial fluid
15% Intravascular 5%

3. IONIC COMPOSITION OF DIFFERENT
BODY FLUID COMPARTMENTS

4. How to measure the different
body compartments
 TBW – Measured by deuterium oxide (D2O)
 ECF – Measured by Insulin, mannitol, sucrose.
 ICF = TBW-ECF
 Plasma volume – by evans blue dye, serum albumin labeled with
radioactive iodine.
Plasma volume
 Total blood volume = ----------------------- x 100
100 – HCT
 Sodium placed in important rule in maintaining fluid balance of the
body.
 It is the main ion determining the osmolality of the ECF.
 Normal sodium concentration 135-145 meq/L.
 Normal plasma osmolality ranges from 275-290 mosm/L.
 Main ECF ions are Na+, Cl- and HCO3- main ICF ions or K+, Mg++ and
organic phosphates and protein.

5. UNDERSTANDING NORMAL
PHYSIOLOGICAL CONCEPTS
 Osmolarity – It is no of osmoles per litre of solution. It is affected by
volume of various solutes & temperature of the solution.
 Osmolality – It is the no. of osmoles per Kg of the solvent and it is not
effected by the temperature or the solutes.
 Osmosis – It is the movement of solvent molecules for the region low
solute concentration to high solute concentration.
Concept of effective and ineffective solute :
 Effective solute – are impermeable to cell membrane, e.g. Na +. mannitol.
 Ineffective solute – they are freely permeable to cell membranes e.g. urea,
ethanol, methanol.
 Glucose at normal physiological concentration is ineffective solute but in
case of insulin deficiency becomes an effective solutes.
 Osmolality of plasma = 2 x Na+ (meq/L) + glucose mg/dl /18+ blood
urea (mg/dl)/6

6. NORMAL SODIUM METABOLISM
 Sodium intake - normal typical western diet consists of 150 mmol
– of sodium chloride daily.
 Absorption of sodium from intestine is via two mechanisms first
by being freely permeable across the interstitial cell and secondly
by symport with glucose and aminoacids.
 Sodium excretion - the regulation of sodium excretion is the
major determinant of sodium balance. Mainly Na+ is absorbed at
3 main regions in the nephron.
1. PCT – 2/3 of Na+ reabsorbed.
2. TALH – 25-30% is reabsorbed via apical Na+ K+ 2Cl-
transporter.
3. DCT – 5% by thiazide sensitive Na+ Cl- cotransporter.
Finally Na+ reabsorption also occurs in cortical and
medullary collecting ducts.

7. REGULATION OF SODIUM
EXCRETION
 Sodium excretion is regulated at 4 major steps :
1. Circulating levels of aldosterone – it primarily at on cortical
collecting ducts specially T cell to increase ENACs in apical membrane.
2. Circulating number of ANP & other natriuretic hormones – ANP
causes increase cGMP and this inhibits transport via ENAC.
3. Amount of AT-II, PGE2 levels in kidney – they causes increase
reabsorption of Na+ and HCO3 by action on PCT. PGE2 causes natriuresis
by inhibition of sodium transport via ENACs.
4. Rate of tubular secretion of K+ and H+ - Na+ reabsorption is coupled
with H+ and K+ secretion in tubules and play important role in acid
base metabolism.

8. JG APPARATUS

9. Hypertonicity Hypovolemia
Osmorecptors Barorecptors angiotensin -II
Hypothalamus
Thirst

10. DEFENSE OF ECF VOLUME AND
IONIC COMPOSITION OF THE BODY
Angiotensin
Renin
Angiotensin -I Hypovolemia
Adrenal cortex ACE
Angiotensin -II Hyperosmalarity
Aldosterone
Hypothalamus Vasoconstriction
Kidney Thirst
ADH
Na+, water
retention

12. HYPONATREMIA
ETIOLOGY
I. Pseudohyponatremia
A. Normal plasma osmolality
1. Hyperlipidemia
2. Hyperproteinemia
3. Posttransurethral resection of prostate/bladder tumor.
B. Increased plasma osmolality
1. Hyperglycemia
2. Mannitol
II. Hypoosmolal hyponatremia
A. Primary Na+ loss (secondary water gain) (Hypovolemia)
1. Integumentary loss: sweating, burns.
2. Gastrointestinal loss : tube drainage, fistula, obstruction,
diarrhoea.
3. Renal loss : Diuretics, osmotic diuresis, hypoaldosteronism,
salt-wasting nephropathy, postobstructive diuretics,
nonoliguric ATN.

13. HYPONATREMIA
ETIOLOGY
B. Primary water gain (secondary Na+ loss) (Euvolemic)
1. Primary polydipsia.
2. Decreased solute intake (e.g. beer potomania)
3. AVP release due to pain, nausea, drugs.
4. SIADH
5. Glucocorticoid deficiency
6. Hypothyroidism
C. Primary Na+ gain (exceeded by secondary water gain)
(Hypervolemic)
1. Heart failure
2. Hepatic cirrhosis
3. Nephrotic syndrome
Hyponatremia is the most common electrolyte imbalance in clinical
practice. Its incidence is 0.97% and prevalence of 2.42% in hospitalized
adult patients when 130 meq/L is the diagnostic criteria.

14. ABNORMAL ECF TONICITY AND CEREBRAL ADAPTATION

15. ETIOGENESIS OF SOME IMPORTANT
CAUSES OF HYPONATREMIA
 Factitious pseudohyponatremia – depends upon the methods use for S.
Na+ estimation.
1. Flamephotometry (older method)
2. Ion selective electrode method – newer, more accurate
 Pseudohyponatremia
- Every 100 mg/dl of increase in S. glucose causes S Na+ top
decrease by 1.6 meq/L but this correction factor should be 2.4
meq/L.
 Plasma TG (g/dl) x 0.002 = meq/L decrease in S. Na+.
 Plasma protein level -8 (g/dl) x 0.025 = meq/L decrease in S. Na+.
 Hyponatremia in hypothyroidism – Due to decrease C.O, GFR and
increase AVP secretion in response to hemodynamic stimuli.
 Hyponatremia in cortisol occurs due to hyper secretion of ADH.
 Premenopausal women are susceptible to develop severe cerebal edema in
association with acute hyponatremia due to inhibition of Na+ K+ ATPase
by estrogen and progesterone it may also cause hypothalamic and pituitary
infarction.
 Beer potomania – low protein diet and large consumption of beer may
cause renal excretory capacity to be overwhelmed and result in
hyponatremia.

16.  Hyponatremia in AIDS -May occur due to multiple cuases
such as administration of I/V fluids, CMV adrenalitis,
mycobacterial infections and SIADH caused by CNS and
pulmonary infection.
 Diuretics specially thiazide diuretic lead to Na+, K+
depletion and ADH related water retention.
 Loop diuretics decrease medullary interstitial tonicity and
impair maximal urinary concentrating ability and risk limits
the ability of ADH to promote water retention.
 SIADH - Most common cause of evolemic hypoosmolality.
 20-40% of prevalence among all cases of hypoosmolal
patients

17.  Diagnostic criteria for SIADH.
1. Decreased effective osmolality of ECF (plasma osmolality of
<275 mosmol/kg.
2. Inappropriate urinary concentration (urine osmolality >100 mosm/kg
with hyponatremia.
3. Clinical euvolemia (hypouricemia <4 mg%, low BUN <10mg%
4. Increased urinary Na+ but <40 mEq/L despite normal salt intake.
5. Absence of other causes of euvolemic hypoosmolality.
6. Normal renal, pituitary, acid basedand K+ balance.
ETIOLOGY
 Neoplasm – carcinomas – lungs, duodenum, ovary bladder
 Infection – abscess, cavitation, pneumonias, TB, AIDS, meningitis.
 Vascular – CVA, cavernous sinus thrombosis.
 Neurological – GBS, MS, ALS, Hydrocephalus.
 Respiratory–PPV, pneumothorax, asthma.
 Drugs – Chlorpropamide, SSRI, MAOi, oxytocin, desmopressin,
carbamazepine.

18. CLINICAL FEATURES
 The clinical manifestation of hyponatremia are related to osmotic
water shift leading to increased ICF volume, brain cell swelling
and cerebral edema. Symptoms progressively occurs as Na+
conc. Decreases less than 130 meq/L.
Symptoms Signs
Lethargy, apathy, Altered sensorium, decrease
disoreintation, nausea, DTR, cheyne stokes
anorexia, agitation respiration, hypothermia,
pseudobulbar palsy,
seizures.

19. DIAGNOSIS AND MANAGEMENT
 Hyponatremia is not a disease but a manifestation of
a variety of disorders and requires accurate history
physical examination and lab investigations for
diagnosis.
 Important investigation for the diagnosis of
hyponatremia are –
1. Plasma osmoalality
2. Urinary osmolalaity
3. Urine sodium concentration
 Therapeutic strategy in hyponatremia is dictated by
the underlined disorder as well as 1. presence or
absence of symptoms. 2. Duration of the disorder 3.
The risk of neurological complications.

20. Plasma osmolality
High Normal Low
Hyperglycemia Hyperproteinemia hyperlipidemia Maximal volume of maximally
mannitol bladder irrigation dilute urine (<100 mosmol/kg
ECF volume Primary polydipsia reset
osmostat
Increased Normal Decreased
Heart failure hepatic SIADH Urine Na+
cirrhosis nephrotic Hypothyroidism concentration
syndrome renal adrenal insufficiency
insufficiency
< 10 mmol/L > 20 mmol/L
Extrarenal Na+ loss remote Na+ wasting nephropathy
diuretic use remote vomiting hypoaldosteronism diuretic vomiting

21. TREATMENT OF HYPONATREMIA
 The underlying treatment of hyponatremia depends upon presence or
absence of symptoms.
 Goals of treatment -
1. To increase plasma sodium concentration. Restricting water
(if <120 mEq/L) to <500-1000 ml/day intake and promoting water
loss.
2. Correction of underlying disorder.
 ECF volume should be restored in hypovoleumic patients which can be
calculated according to the following equation
Water excess =Total body water x (125/plasma Na+) - 1
 The rate of plasma Na+ concentration should not be >0.5 to 1 mmol/L/hr
in asymptomatic patients.
 In severe symptomatic patients plasma Na+ concentration should be
raised by 1 to 2 mmol/L/hr for first 3 for hours or until seizures subside
 In both conditions plasma Na+ concentration should not be raised > than
12 mmol/L in 24 hrs.

22. Treatment of underlying disorders
 Adrenal insufficiency – I/V glucocorticoid administration
(100-200 gm) hydrocortisone 1 L of 5% DNS over 4 hours –
for acute conditions.
 ACE inhibitor and loop diuretic are given in volume expanded
states with increase RAAS activity such as CHF & nephrotic
syndrome.
 In correctable conditions like metastatic lung cancer (SIADH)
treated with demeclocycline (900-1200 mg/day).
 Stop I/V hypotonic solutions, offending drugs.
 Treatment of SIADH - severe water restriction, upto 25-50%
of maintenance of water intake is required and correction if
possible of underlying disorder.

23. TREATMENT OF SEVERE HYPONATREMIA
Symptomatic Asymptomatic
Acute Duration < Chronic Duration >48 hr or Chronic Rarely <
48 hr unknown 48 hr
Emergency correction Some immediate correction needed No immediate correction
needed • Hypertonic saline 1-2 mL/kg/hr needed
• Hypertonic saline (3%) at • Coadministration of forosemide
1-2mL/kg/hr
• Change to water restriction upon 10%
• Coadministration of increase of [Na], or if symptoms resoive
furosemide
Perform frequent measurement of
serum and urine electrolytes
Do not exceed 12 mEq/L/day
Long-Term management
• Identification and treatment of reversible etiologies
• Water restriction
• Demoeclocycline 300 to 600 mg bid- Allow 2 weeks for full effect, or
• Urea 15 g to 60 g gd - Immediate effect
• V2 receptor antagonist – Under investigation, conivaptan, VPA-925.

24. SODIUM REPLACEMENT
Sodium Replacement :
 When corrective therapy requires the infusion the isotonic saline or
hypertonic saline, the replacement therapy can be guided by the
calculated sodium deficit. This is determined as follow (using a plasma
Na+ of 130 mEq/L as the desired end – point of replacement therapy).
 Sodium derficit (mEq.)= Normal T.B.W x (130-current Plasma Na +)
 Example : For a 60 Kg. Male with plasma Na+ 120 meq/L. Sodium
deficit=0.60X60X(130-120)meq., =360 meq.
 Because 3% N.S. contain 513 meq of Na+/L, the vol. Of hypertonic
saline needed to correct Na+ deficit of 360 meq will be 360/513=700 ml.
 Using a max. rate of rise of 0.5 meq/L/hour. For plasma Na + the Na+
concentration deficit of 10 meq/liter in the example – should be corrected
over at least 20 hours.

25. (ODS) OSMOTIC DEMYELINATION SYNDROME
 This is a neurological disorder characterized by flaccid
paralysis, dysarthria & dysphagia. It occurs due to rapid
correction of hyponatremia.
 Other features of that may occur in this disorder are
quadriparesis weakness of lower face and tongue overfew
days to weeks.
 The lesion may extend dorsally to involve sensory tract and
leave patients in locked in syndrome.
 Risk factors for ODS –Malnutrition due to chronic alcoholic
liver disease, hypokalemia, cerebral anoxic injury.
 Water restriction in primary polydipsia and intravenous
saline therapy in ECF volume contracted patients may also
lead to rapid correction of hyponatremia as a result of ADH
suppression and brisk water diuresis.

26. HYPERNATREMIA
 It is defined as plasma Na+ concentration >145mmol/L.
 Hypernatremia is generally mild unless thirst mechanism is
abnormal or access to water is limited e.g. infants, physically
challanged, impaired mental status, postop patient, intubated
patients in ICU.
 May be due to - Primary Na+ gain
- Primary water deficit
1. Free water loss – may be renal or extra renal
 Extra renal – 1. Skin & respiratory tract (Insensible water loss)
due to evaporation
2. GI loss : Diarrhoeas 1. Osmotic – Lactulose, sorbitol,
malabsorption, viral gastroenteritis, - in all these conditions
water loss > Na+ loss – Hypernatremia
2. Secretory – Cholera, carcinoid syndromes, ViPomas- in
these conditions fecal osmolality is similar to plasma osmolality
so plasma Na+ concentration remain same or decreases with
ECV contraction.

27. RENAL LOSS
 Most common cause of hypernatremias.
1. Drug induced
- Loop diuretics – interfere with counter current mechanism
and produces isoosmotic, solute diuresis,
2. Osmotic diuresis
- Due to presence of non reabsorbed organic solutes in the
tubular lumen osmotic diuresis in which water loss > Na+ K+
loss e.g. hyperglycemia, I/V mannitol increased urea in body.
DIABETES INSIPIDUS
 It is a syndrome characterized by production abnormally large volume
of dilute urine. The 24 hours urine volume is >50 ml /kg body weight
and the osmolarity is <300 mosmol/L.
 Causes non osmotic water loss. It is of two types :
1. Central diabetes insipidus – due to impaired ADH secretion.
2. NDI nephrogenic diabetes insipidus – due to end organ resistance
to the action of ADH.

28.  In complete CDI – after water deprivation test maximal urinary
osmalality <300 mosmol.L which increases substantially with
ADH.
 In partial CDI maximal urinary osmolality is between 300 –800
mosmol/L which increases >10% after ADH administration.
 In NDI maximal urinary osmolality is between 300 –500
mosmol/L and does not rises with ADH administration.
CDI - Etiology
 Congenital – genetic causes AVP – neurophysin gene mutation.
– Malformation e.g. holoprosencephaly, craniofacial
defects.
 Acquired – head trauma
Neoplasm e.g. craniopharyngioma, pituitary adenoma.
Granulomas e.g. neurosarcoid, histiocytosis.
Infections e.g chronic meningitis, viral encephalitis.
Inflammatory e.g.SLE, Scleroderma, Wegener’s granulomatosis.
Vascular e.g. aneurysm, HIE.

29. NDI - etiology
 Genetic – X-linked recessive, AR, AD, AVP receptor,
aquaporin gene defects.
 Acquired –
drugs – Li, Cisplatin, Rifampin, demeclocycline.
Metabolic – hypercalcemia, hypokalemia
Vascular – sickle cell disease, ATN.
Granulomas and Neoplasm
pregnancy

30. Clinical features
 Clinical features of hypernatremia are primarily neurological.
Major neurological –symptoms include :
- Nausea, Muscular weakness, altered mental status,
neuromuscular irritability, focal neurological deficit and
occasionally coma or seizures and they depend upon the rapidly
of outset, its duration and its magnitude.
 In severe acute hypernatremia brain shrinkage may be substantial,
exerting traction on the venous causing intra cerebral and SAH.
 The patients may also complain of polyuria or excessive thirst. The
signs and symptoms of volume depletion are often present in
patient with history of excessive sweating, diarrhea or osmotc
diuresis.
 In chronic hypernatremia brain cell initially take up Na+ and K+
later accumulates organic osmolytes such as inositol to restore the
brain ICF volume.

31. DIAGNOSIS AND MANAGEMENT OF
HYPERNATREMIA
 Complete history and physical examination often provide clues
to the underlying cause of hypernatremia.
 Measurement of urine volume and osmolality.
 Calculating :
Plasma Na+ Concentration - 140
Water deficit = ----------------------------------- x total body water
140
 Rapid correction of hypernatremia is dangerous because
sudden decrease in osmolality can cause rapid shift of water
into the cells resulting in swelling of brain cells.
 Treatment of hypovolemic hypernatremia – is by restoring
volume by I/V NS.
 Treatment of hypervolemic hypernatremia is by removing
sodium excess by diuresis.
 Sodium excess (mEq) = 0.6xwt in Kg x (patient’s serum
sodium – 140)

32.  In cases of volume disturbances D-5%, DNS are given as
preferred solutions.
 In hypovolemic patients Ist colloid & 0.9% NS is given before
hypotonic solutions or free water is administrated.
TREATMENT OF DIABETES INSIPIDUS
 In the treatment of CDI desmopression intranasally plays
important role. It can be given 1-2 µg qd or bid injection or 10-
20 µg by bid or tid by nasal spray.
 Besides chlorpropamide, clofibrate carbamazepine can also be
given for treatment of CDI. Thiazide diuretic and low Na+ diet
is given for management of NDI.
 Besides in the management of NDI - NSAIDs amiloride and
lithium can also be given in selected patients.

33. CLINICAL APPROACH TO HYPERNATREMIA
ECF volume
Increased Not increased
Administration of Minimum volume of maximal
hypertonic NaCl or NAHCO3 concentrated urine
No Yes
Urine osmole excretion rate >750 Insensible water less gastrointestinal
mosm/day water less remote renal water loss.
No Yes
Renal response to desmopressin Diuretic osmotic diuresis
Urine osmolality increase Urine osmolality unchanged
CDI NDI