A New Perspective on Hypernatremia

Taipei Veterans General Hospital, Hsin-Chu branch

Director of Nephrology

Steve Chen

Na

SodiumSodium

Reference Range:136 – 145 meq/L

SodiumSodium

Hypernatremia is Na+ > 150 meq/L

Pathophysiology(1)Pathophysiology(1)

– Primary MechanismsPrimary Mechanisms Renal response to ADHRenal response to ADH

– Conservation of free waterConservation of free water– ↓↓ Urine output with osmolality > 1000 mosm/kgUrine output with osmolality > 1000 mosm/kg

Failure of ADH responseFailure of ADH response– Inability to excrete NaInability to excrete Na++ properly properly– Urine osmolality 200-300 mosm/kgUrine osmolality 200-300 mosm/kg– Urinary NaUrinary Na++ 60-100 meq/kg 60-100 meq/kg

Pathophysiology(2)Pathophysiology(2)

– Rapid hypertonicity Rapid hypertonicity Loss of 10% of body weight Loss of 10% of body weight

– “ “Doughy” skin turgorDoughy” skin turgor CNS cellular dehydrationCNS cellular dehydration

– Hemorrhage: ICH/SAHHemorrhage: ICH/SAH– Tearing of cerebral blood vessels, then 2° brain Tearing of cerebral blood vessels, then 2° brain

shrinkageshrinkage– Gradual hypertonicityGradual hypertonicity

Idiogenic osmoles prevent brain shrinkageIdiogenic osmoles prevent brain shrinkage

Etiology of Etiology of HypernatremiaHypernatremia

Etiology(1)Etiology(1)– Excessive sodium intakeExcessive sodium intake

Iatrogenic NaIatrogenic Na++ administration administration Sea water ingestionSea water ingestion Mineralocorticoid or glucocorticoid excessMineralocorticoid or glucocorticoid excess

– Pure water lossPure water loss Inability to swallow, bedridden, comatoseInability to swallow, bedridden, comatose

Etiology of Etiology of Hypernatremia Hypernatremia

Etiology(2)Etiology(2)– Loss of waterLoss of water

RenalRenal– Central Diabetes InsipidusCentral Diabetes Insipidus– Impaired renal concentrating abilityImpaired renal concentrating ability

DrugsDrugs– Alcohol, Lithium, Phenytoin, Propoxyphene, Alcohol, Lithium, Phenytoin, Propoxyphene,

SulfonylureasSulfonylureas

Etiology of Etiology of Hypernatremia Hypernatremia

Etiology (3)Etiology (3)– Loss of water > NaLoss of water > Na++

Skin loss: Burns, sweatingSkin loss: Burns, sweating Peritoneal dialysisPeritoneal dialysis GI loss: Vomiting, diarrhea GI loss: Vomiting, diarrhea

Symptoms & Signs Symptoms & Signs

Clinical Features: mainly CNSClinical Features: mainly CNS– Acute symptoms at Acute symptoms at NaNa++ > 158 meq/L > 158 meq/L

OsmolOsmol– Restless, irritabilityRestless, irritability 350-375350-375– Tremulousness, ataxiaTremulousness, ataxia 375-400375-400– Hyperreflexia, twitching, spasticityHyperreflexia, twitching, spasticity

400-430400-430– Seizures and deathSeizures and death > 430> 430

TypesTypes of Hypernatremia of HypernatremiaHypernatremia with low body sodium

content

Hypernatremia with normal body sodium content

Hypernatremia and increased body sodium content

Hypernatremia with Hypernatremia with lowlow total total body sodium contentbody sodium content

Water loss in excess of sodium loss

Osmotic diuresis Diarrhea Sweating Vomiting

Hypernatremia with Hypernatremia with normalnormal total total body sodium contentbody sodium content

Due to water loss

Diabetes insipidus Central diabetes insipidus Nephrogenic diabetes

insipidus

Hypernatremia and Hypernatremia and increasedincreased total body sodium contenttotal body sodium content

Following administration of large quantities of hypertonic saline solutions

Iatrogenic Na administration: FFP… Sea water intake Mineralocorticoid or glucocorticoid

excess

Flow chart of DDFlow chart of DD ECF volume Increased Hypertonic Na

Not increased

Minimun volume of maximum concentrated urine

Yes

Extra-renal Insensible water loss GI

No Urine osmole excretion rate > 750 mosmol/day

Osmotic diureticDiuretics

YesNo

Renal response to DDAVP Urine osmolality↑

CDIYes

No

NDI

Hypernatremia Hypernatremia Q1: What is the ECF volume?

A gain of Na is rarely the sole cause of hypernnatremia

Q2: Has the body weight changed? Water shift with convulsion or rhabdomyolysis rarely : 10-15meq/L

Q3: Is the thirst response to hypernatremia normal? ↑1% Na is powerful urge to drink ﹝ ﹞

Q4: Is the renal response to hypernatremia normal? Urine osmolarity > 1000mOsm/KgH2O Urine volume=20mL/H unless there is a high rate of excretion of effective osmoles

Goals of therapyGoals of therapy

To correct water deficit

To stop ongoing water loss

Principles of therapyPrinciples of therapyCorrection should be done over

48 to 72 hours

Hypotonic solution like 5% dextrose

Plasma Na should be lowered by 0.5 meq/L/hr or not more than 12meq/L/ 24 hrs

Total Water Deficit = A+B+CTotal Water Deficit = A+B+CIf it results only from water loss, then Current

total body osmoles = Normal total body osmoles CBWa x plasma Na = NBWa x 140 ﹝ ﹞Water deficit (A)

= NBWa - CBW a = CBWa x

plasma Na /140- 1﹛ ﹝ ﹞ ﹜ Estimated insensible loss (B) = 30-50ml/HRenal water loss, ongoing (C)

Guidelines of therapyAdministration of IV Fluids

– (Isotonic Salt ~ Free)Encourage foods: low in Na+

Push P.O. FluidsMonitor Neurological statusMonitor for Arrhythmias

PolyuriaPolyuria

Polyuria based on an unexpectedly low urine osmolality (UO)

If renal medulla is damaged, UO is close to that of plasma when ADH acts( 300mOsm/Kg)

If ADH fails, UO is below 300 mOsm/Kg

Urine Specific GravityUrine Specific Gravity

USG defined as weight of solution compared with that of an equal volume of distilled water

USG ∞ particle weight X particle number Urine osmolality ∞ particle number

Normally(neither glucose nor protein in urine), ↑SG 0.001=↑UO 30-35mosmol/Kg SG (1.010) = UO( 300-350)

Polyuria Polyuria

Polyuria as a function of osmole excretion rate= urine osmolality x urine volume (UV)

Normally, osmole excretion rate = 900mOsm/D if urine osmolality is 900, UV is 1 L

In osmotic diuresis, osmole excretion rate =1800mOsm/D , which is exogenous(Glucose) if urine osmolality is 900, UV is 2L in fact, urine osmolality is 450, UV is 4L

Polyuria Polyuria Appropriate Inappropriate

Water diuresis(Uosm<250mosmol/Kg)

IV dilutionPrimary hypodipsia

CDINDI

Solute diuresis(Uosm>300mosmol/Kg)

Saline loadingPost-obstructive

HyperglycemiaHigh-protein tube feedingNa-wasting nephropathy

Urine osmolatity (mosmol/Kg)

Clinical settings Response to ADH

<300 CDINDI

+--

300 to 800 Osmotic diuresisCDI, partialNDI, partialVolume depletion in CDI

--+--+

>800 Non-renal water loss primary hypodipsia Na overload

----

Variable Essential hypernatremia

Variable

Renal water loss in NDIRenal water loss in NDILithium-induced NDI with hypernatremia

150ml/H of isosmotic urine(=325mosmol/Kg)Urine urea/amonium is ineffective particle

Urine Na+K con. affect plasma Na con. ﹙ ﹚Urine Na+K =60meq/L﹙ ﹚ ;

Plasma Na+K =150meq/L ﹙ ﹚ Effective urine osmolarity=40% that of plasma

Renal water loss= 150ml/H x 60%

Hypernatremia-Na gainHypernatremia-Na gain

Half normal saline in lithium-induced NDI Normal saline in glucose-induced osmotic diuresis

Hypertonic NaHCO3 in cardiac arrest Dialysis error( hypertonic dialysate) Salt poisoning in infants Ingestion of sea water FFP plus Lasix in burned patients Combination of above and thirst center defect

Reset HyponatremiaReset Hyponatremia Normal osmoreceptor response to change in

plasma osmolarity: plasma Na 125﹝ ﹞ ～ 130meq/L

Clinical settings: Hypovolemic states: baroreceptor stimulus Quadriplegia: ↓ effective volume Psychosis Defective cellular metabolism: TB meningitis Pregnancy: hCG

Reset Hypernatremia Reset Hypernatremia Inhibition of ADH release and excretion of a dilute

urine after water loading Stimulation of ADH release and excretion of a

concentrated urine after water deprivation Maintenance of new normal plasma Na within ﹝ ﹞

narrow limits(±1-2%): 140±2.8meq/L( 137 ～ 143) Clinical setting: Primary hyper-aldosteronism reset

Na > 145meq/L﹝ ﹞ , restored by hormone manipulation or lowering the effective volume with diuretic

Essential hypernatremiaEssential hypernatremiaPrimary hypo-dipsia (thirst center defect)

plus inhibition of ADH (osmoreceptor defect) New normal plasma Na : wide variation ﹝ ﹞

between 150 and 180meq/LOsmoreceptor relatively insensitive

rather than being reset at a higher level; selectively damaged ; normal response to volume

Chlorpropamide: ↑ ADH effect

SIADH: drug related SIADH: drug related ADH ↑ ADH ↑ADH preparations:

DAVdP(Desmopressin), Aqueous vasopressin, Lysine-vasopressin in nasal spray, Vasopressin tannate in oil

Potentiate ADH effect Chlopropamide, Cabamazepine, NSAIDs

Increase ADH secretion Clofibrate

Drug not requiring ADH Thiazide ± Amiloride