ELECTROLYTE BALANCE : ELECTROLYTE BALANCE : SODIUM METABOLISMSODIUM 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.

DEFINITIONDEFINITION 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 body wt)

E.C.F. (20% of body wt)

Interstitial fluid 15% Intravascular 5%

IONIC COMPOSITION OF DIFFERENT

BODY FLUID COMPARTMENTS

How to measure the different How to measure the different body compartmentsbody 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.

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

UNDERSTANDING NORMAL UNDERSTANDING NORMAL PHYSIOLOGICAL CONCEPTSPHYSIOLOGICAL CONCEPTS

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.

REGULATION OF SODIUM REGULATION OF SODIUM EXCRETIONEXCRETION

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.

JG APPARATUS

Hypertonicity

Osmorecptors

Hypovolemia

Barorecptors angiotensin -II

Thirst

Hypothalamus

DEFENSE OF ECF VOLUME AND DEFENSE OF ECF VOLUME AND IONIC COMPOSITION OF THE BODYIONIC COMPOSITION OF THE BODY

Angiotensin

Angiotensin -I

Angiotensin -II

Hypothalamus

ADHThirst

Hypovolemia

Hyperosmalarity

Vasoconstriction

Adrenal cortex

Aldosterone

Kidney

Na+, water retention

Renin

ACE

HYPONATREMIAHYPONATREMIAETIOLOGYI. Pseudohyponatremia

A. Normal plasma osmolality1. Hyperlipidemia2. Hyperproteinemia3. Posttransurethral resection of prostate/bladder tumor.

B. Increased plasma osmolality1. Hyperglycemia2. Mannitol

II. Hypoosmolal hyponatremiaA. 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.

HYPONATREMIAHYPONATREMIAETIOLOGY

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. SIADH5. Glucocorticoid deficiency6. Hypothyroidism

C. Primary Na+ gain (exceeded by secondary water gain) (Hypervolemic)

1. Heart failure2. Hepatic cirrhosis3. 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.

ABNORMAL ECF TONICITY AND CEREBRAL ADAPTATION

ETIOGENESIS OF SOME IMPORTANT ETIOGENESIS OF SOME IMPORTANT CAUSES OF HYPONATREMIACAUSES 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.

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

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.

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, disoreintation, nausea, anorexia, agitation

Altered sensorium, decrease DTR, cheyne stokes respiration, hypothermia, pseudobulbar palsy, seizures.

DIAGNOSIS AND MANAGEMENTDIAGNOSIS 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 osmolalaity3. 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.

Plasma osmolality

High Normal Low

Hyperglycemia mannitol

Hyperproteinemia hyperlipidemia bladder irrigation

Maximal volume of maximally dilute urine (<100 mosmol/kg

ECF volume Primary polydipsia reset osmostat

Increased Normal Decreased

Heart failure hepatic cirrhosis nephrotic

syndrome renal insufficiency

SIADH Hypothyroidism

adrenal insufficiency

Urine Na+ concentration

< 10 mmol/L > 20 mmol/L

Extrarenal Na+ loss remote diuretic use remote vomiting

Na+ wasting nephropathy hypoaldosteronism diuretic vomiting

TREATMENT OF HYPONATREMIATREATMENT 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 equationWater 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.

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.

TREATMENT OF SEVERE HYPONATREMIA TREATMENT OF SEVERE HYPONATREMIA

Symptomatic Asymptomatic

Chronic Duration >48 hr or unknown

Chronic Rarely < 48 hr

Acute Duration < 48 hr

Some immediate correction needed

• Hypertonic saline 1-2 mL/kg/hr

• Coadministration of forosemide

• Change to water restriction upon 10% increase of [Na], or if symptoms resoive

Perform frequent measurement of serum and urine electrolytes

Do not exceed 12 mEq/L/day

No immediate correction needed

Emergency correction needed

• Hypertonic saline (3%) at 1-2mL/kg/hr

• Coadministration of furosemide

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.

SODIUM REPLACEMENT SODIUM REPLACEMENT

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.

(ODS) OSMOTIC DEMYELINATION SYNDROME (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.

HYPERNATREMIAHYPERNATREMIA 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 evaporation2. GI loss : Diarrhoeas 1. Osmotic – Lactulose, sorbitol, malabsorption, viral gastroenteritis, - in all these conditions water loss > Na+ loss – Hypernatremia2. 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.

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.

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.

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

Clinical featuresClinical 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.

DIAGNOSIS AND MANAGEMENT OF DIAGNOSIS AND MANAGEMENT OF HYPERNATREMIAHYPERNATREMIA

Complete history and physical examination often provide clues to the underlying cause of hypernatremia.

Measurement of urine volume and osmolality. Calculating :

Plasma Na+ Concentration - 140Water 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)

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.

CLINICAL APPROACH TO HYPERNATREMIACLINICAL APPROACH TO HYPERNATREMIA

ECF volume

Increased Not increased

Administration of hypertonic NaCl or NAHCO3

Minimum volume of maximal concentrated urine

Urine osmole excretion rate >750 mosm/day

Insensible water less gastrointestinal water less remote renal water loss.

Renal response to desmopressin Diuretic osmotic diuresis

Urine osmolality increase Urine osmolality unchanged

CDI NDI

No Yes

YesNo