Prepared by

DR.MUHAMMAD FAIZAN

Contents
Fluid compartment & Osmolality Sodium control Definition of hyponatremia Epidemiology Types clinical manifestation Diagnosis Treatment Definition of hypernatremia Clinical manifestation Diagnosis Treatment

Total body water

60% of lean body weight in men and 50% in women. 2/3 comprises ICF & 1/3 ECF. 25% of ECF is intravascular & 75% in interstitial spaces.Sodium is the main solute in Ecf where is potassium is main in Icf. Disturbances in TBW manifest primarily as changes in osmolality of fluid compartments.

Osmolality
Solute concentration is measured by osmolality i.e osmoles/kg water. 285-295 mosm/kg Tonicity osmolytes impermeable to cell membrane, they are effective osmolyte. e.g: Na, gluccose. Ineffective osmolytes permeate cell membrane. e.g: urea,ethanol.

Plasma osmolality= 2Na + glucose/18 +BUN/2.8 Effective plasma osm= 2Na

It is obvious that Na is intimately related to osmolality. Because of their relation to osmolality ,hyponatremia & hypernatremia are primarily disorders of water balance & water distribution across fluid compartment. Since 85-90% total body Na is in ECF,alterations manifest clinically as ECF volume depletion(hypotension,tachycardia) or ECF volume overload(peripheral/pulmonary edema).

Sodium control
Serum sodium conc is regulated by: 1. Stimulation of thirst 2. Secretion of ADH 3. Renin-Angiotensin-Aldosterone 4. Renal handling of Na.

Stimulation of thirst
Osmolality increases

Main driving force Only requires an increase of 2% - 3%

Blood volume or pressure is reduced

Requires a decrease of 10% - 15%

Thirst center is located in the anteriolateral center of the

hypothalamus Respond to NaCL and angiotensin II

Secretion of ADH
Synthesized by the neuroendocrine cells in the supraoptic

and paraventricular nuclei of the hypothalamus Triggers: Osmolality of body fluids A change of about 1% Volume and pressure of the vascular system Actions of ADH 1. Increases the water permeability of the collecting tubule 2. Mildly increases vascular resistance

Renin-Angiotensin-Aldosterone
Renin

Stimuli are perfusion pressure, sympathetic activity, and NaCl delivery

to the macula densa Increase in NaCl delivery to the macula decreases the GFR by decrease in the renin secretion Aldosterone Reduces NaCl excretion by stimulating its resorption Ascending loop of Henle Distal tubule Collecting duct

HYPONATREMIA
DEFINITION:
Defined as sodium concentration < 135 mEq/L Generally considered a disorder of water as opposed to disorder of salt Most often due to retention of free water 2ndary to impaired excretion of free water

Occ. due to Na loss exceeding water loss i.e. thiazide-induced hypoNa (elderly women)

EPIDEMIOLOGY
Hyponatremia is the most common electrolyte disorder incidence of approximately 1% prevalence of approximately 2.5%

Mortality/Morbidity
Acute hyponatremia (developing over 48 h or less) are

subject to more severe degrees of cerebral edema sodium level is less than 105 mEq/L, the mortality is over 50% Chronic hyponatremia (developing over more than 48 h) experience milder degrees of cerebral edema Brainstem herniation has not been observed in patients with chronic hyponatremia

TYPES

HYPOOSMOLAR Hypovolumic Renal or Non-Renal

Thiazide diuretics,cerebral salt wasting. Vomiting,diarrhea.

Euvolumic

SIADH, hypothyroidism, psychogenic polydipsia.

Hypervolumic

CHF,Hepatic cirrhosis,severe nephrotic syn.

HYPEROSMOLAR EUOSMOLAR PSEUDONATREMIA

Clinical manifestation
most patients with a serum sodium concentration exceeding 125

mEq/L are asymptomatic Patients with acutely developing hyponatremia are typically symptomatic at a level of approximately 120 mEq/L Most abnormal findings on physical examination are characteristically neurologic in origin and are related to osmotic intracellular water shift leading to cerebral edema. Depends on the severity of fall of plasma Na conc and rate of development. Acute (<48 hrz),chronic (>76 hrz)

Mild ( =125mEq/L): anorexia, nausea, lethargy Mod (115-125mEq/L): disoriented, agitated, neuro deficit Sev (<115mEq/L): seizures, coma, death

Algorithm for Diagnosis

Step 1 Sna > 145 => Hypernatremia Sna< 135 => Hyponatremia Step 2 Calculate Serum Osmolarity Hyponatremia = Is it Hypoosmolar, Isoosmolar or Hyperosmolar Step 3 Does calculated serum osmolarity agree with measured serum osmolarity to within 10 meq/l. Step 4 Determine ECV status euvolemic, hypovolemic, or hypervolemic (ECV status) Step 5 Obtain Urine Sodium and Urine Osmolarity. Is Urine sodium <or> 20 meq/l ? Is Urine osmolarity <or> 400 meq/l ?

Mandatory Lab Test

Serum Osmolality

Urine Osmolality
Urine Sodium Concentration

Additional tests: TSH, cortisol (Hypothryoidism or Adrenal insufficiency) Albumin, BMP, triglycerides and SPEP (psuedohyponatremia, cirrhosis, MM)

Interpretation of Test

Serum Osmolality Can differentiate between true hyponatremia, pseudohyponatremia and hypertonic hyponatremia Urine Osmolality Can differentiate between primary polydipsia and impaired free water excretion Urine Sodium concentration Can differentiate between hypovolemia hyponatremia and SIADH

DIFFERENTIAL DIAGNOSIS

First test to obtain: serum osmolality Helps exclude two easier to remember causes of hyponatremia 1. Hyperosmolar hypoNa (osmo > 290) Hyperglycemia, mannitol 2. Iso-osmolar hypoNa (nl serum osmo) Severe hyperlipidemia or hyperproteinemia pseudohyponatremia not a true hypoNa

Ddx(contd)
2nd test to obtain: urine osmolality Plasma osmolality < 275 mosmol/kg+ urine osmolality

>100 mosm/l Increased volume, CHF, cirrhosis, nephrotic syndrome Euvolemic SIADH, hypothyroidism, psychogenic polydipsia, beer potomania, postoperative states Decreased volume GI loss, skin, 3rd spacing, diuretics

Ddx(contd)

3rd test:Urine sodium for dehydrated patients UNa < 20 ,i.e Na and water are lost other then via kidneys Diarrhea,vomiting,burns,trauma,heat exposure. UNa > 20 ,i.e Na is lost via kidneys Renal failure,diuretic excess,addisons disease.

Uric Acid Level

< 4 mg/dl consider SIADH

FeNa
Help to determine pre-renal from renal causes

Treatment
Four issues must be addressed Asymptomatic vs. symptomatic acute (within 48 hours) chronic (>48 hours) Volume status

Treatment (contd)
1st step is to calculate the total body water:
total body water (TBW) = 0.6 body weight

2nd step is to decide what our desired correction rate

should be: Symptomatic: 1. 1.5 to 2 mEq/L per hour for first 3-4 hours until symptoms resolve 2. Increase by no more than 10 mEq/L in first 24 hrs 3. Increase by no more than 18 mEq/L in first 48 hrs
The risks of correcting hyponatremia too rapidly are volume overload

and development of central pomtine myelinolysis(CPM),due to shrinkage of neuron away from their myelin sheaths.The risk of precipitaing cpm is increased with correction of Na >12 meq/l in 24 hrz. The absolute magnitude of correction in 24 hrz is more important then the rate.

Treatment(contd)
o

Na deficit = TBW x (desired [Na] - actual [Na]) (mmol)

Change in sodium from 1 litre of fluid: o Change in Na={(Na I)+(k i) (Na s)} /TBW

When do you need to Rx quickly?

Acute (<24h) severe (< 120 mEq/L) Hyponatremia Prevent brain swelling or Rx brain swelling Symptomatic Hyponatremia (Seizures, coma, etc.) Alleviate symptoms

Quickly: 3% NS, 1-2 mEq/L/h until:

Symptoms stop 3-4h elapsed and/or Serum Na has reached 120 mEq/L

Then SLOW down correction to 0.5 mEq/L/h with 0.9% NS or simply fluid restriction. Aim for overall 24h correction to be < 10-12 mEq/L/d to prevent myelinolysis

Treatment(contd)

When to Rx slowly (correct < 0.5 mEq/L/h, 1012 mEq/L/d)

Symptomatic/Acute: rapid Rx has resolved symptoms and

brought serum Na up to 120 mEq/L Asymptomatic, mild, chronic hyponatremia Want to prevent myelinolysis(Symptoms include: dysarthria, dysphagia, paraparesis, quadriparesis, lethargy, coma or even seizures)
Increased risk: Women, alcoholics, malnourished

Treatment (contd)

Treatment in asymptomatics:

Correct the underlying cause in the DDx Hypovolemic give volume Hypervolemic Na & water restriction Loop diuretics if CHF or nephrotic syndrome Euvolemic water restriction (because excretion cant match it) Specifics: if its hypothyroid give thyroxine Also use loops or, rarely, demeclocycline - causes opposite problem (diabetes insipidus

Treatment (contd)

IV Fluids
One liter of Lactated Ringer's Solution contains: 130 mEq of sodium ion = 130 mmol/L 109 mEq of chloride ion = 109 mmol/L 28 mEq of lactate = 28 mmol/L 4 mEq of potassium ion = 4 mmol/L 3 mEq of calcium ion = 1.5 mmol/L One liter of Normal Saline contains: 154 mEq/L of Na+ and Cl (total osm=308) One liter of 3% saline contains: 514 mEq/L of Na+ and Cl (total osm=1028)

Example

60 kg woman with sodium level of 116 How much sodium will bring him up to 124 in the next 24 hours? Sodium needed = 0.5 x 60 x (124-116) = 240 Hypertonic saline contains 500 mEq/L of sodium Normal saline contains 154 mEq/L of sodium The patient needs 240 mEq in next 24 hours That averages to 10 mEq per hour or 20 mL of hypertonic saline per hour However, this will only raise the serum sodium by 0.33 per hour therefore, increasing the rate 60 mL to 90 mL will produce the desired rate of serum sodium increase of 1.0 to 1.5 mEq per hour until symptoms resolve

Take Home Points

If asked to work-up hypoNa, first: H&P History of fluid loss (vomit/diarrh) or diuretics. On exam: mucous membranes, skin turgor, peripheral edema/ascites (CHF or cirrhosis) Labs: ask for serum osmolality FIRST Rule out the hyper & iso-osmolar forms #2: assess volume status if hypo-osmolar Determine if its Hyper- / Eu- / Hypovolemic form Ask for urine osmolality & urine sodium Identify the cause of hypoNa, then treat

Treatment is based on symptoms

Severe symptoms = Hypertonic Saline Mild or no symptoms = Fluid restriction

HYPERNATREMIA
DEFINITION
Hypernatremia is defined as sa plasma Na >145 mEq/L and represents a state of hyperosmolality.

TYPES

May be caused by a primary water deficit or Na gain.

Primary water deficit: 1. Impaired thirst response 2. Non renal water losses( diarrhea,sweating,burns) 3. Renal water loss( osmotic diuresis or diabetes inspidus). Na gain: 1. Mineralocortecoid excess 2. NaHco3 excess

CLINICAL MANIFESTATION

Initial symptoms include lethargy, weakness and irritability Can progress to twitching, seizures, obtundation or coma Resulting decrease in brain volume can lead to rupture of cerebral veins leading to hemorrhage Severe symptoms usually occur with rapid increase to sodium concentration of 158 mEq or more Sodium concentration greater than 180 mEq are associated with high mortality

ALGORITHM FOR DIAGNOSIS

First asses Ecf volume Second to asses urine volume. Third to measure the urine osmolality If urine osmolality >800,then 4th test to do Urine Na level if urine osmolality 300-800 ,then 4th to measeure Urine osmole excretion per day If urine osmolality <300,then 4th to do Response to dDAVP

DIFFERENTIAL DIAGNOSIS
First check Ecf volume. Hypervolemic Helps exclude 2 common causes: 1. Hypertonic Na load 2. Cushing syndrome

Ddx (contd)
1. 2. 3. 4.

1. 1. 2.

If hypovolemic or euvolemic then check urine volume and measure urine osmolality: If urine volume <800 and urine osmolality >800 mosm/l Insensible losses Gi losses Loop diuretic Primary hupodipsia If urine volume >1000 ml and urine osmolality 300-800 Urine osmole excretion per day > 900 mosm/day Osmotic diuresis( glucosuria,mannitol,high solute loads,) If urine volume >1000ml and urine osmolality <300 and response to dDAVP : Complete CDI(if +) Partial CDI(if-)

TREATMENT

Therapeutic goals are: Reduce serum sodium concentration to 145 mmol/L Determine rate of correction Correct the water deficit Correct the underlying disorder

1. 2. 3.

4.

TREATMENT (CONTD)

Hypernatremia that developed over a period of hours (accidental loading) Rapid correction improves prognosis without cerebral edema Accumulated electrolytes in brain rapidly extruded Reducing Na+ by 1 mmol/L/hr appropriate Hypernatremia of prolonged or unknown duration a slow pace of correction prudent full dissipation of brain solutes occurs over several days maximum rate 0.5 mmol/L/hr to prevent cerebral edema A targeted fall in Na+ of 10 mmol/L/24 hr

TREATMENT (CONTD)

Administration of Fluids: Preferred route: oral or feeding tube

IV fluids if oral not feasible Except in cases of frank circulatory compromise, isotonic saline is unsuitable Only hypotonic fluids are appropriate-pure water, 5% dextrose, 0.2 % saline, 0.45% saline-the more hypotonic the infusate, the lower the infusion rate required

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