This document discusses hypernatremia, including its pathophysiology, etiology, symptoms, diagnosis and treatment. Hypernatremia is defined as a sodium level above 150 meq/L. It can be caused by excessive sodium intake, water loss, or both. Symptoms range from restlessness to seizures depending on the severity of sodium elevation. Treatment involves identifying the cause, stopping ongoing water loss, and slowly correcting the sodium level over 1-2 days to avoid cerebral complications. Accurate diagnosis depends on assessing water balance, renal function and response to ADH.

1. A New Perspective
on Hypernatremia
Taipei Veterans General Hospital, Hsin-Chu branch
Director of Nephrology
Steve Chen
Na

2. SodiumSodium
Reference Range:
136 – 145 meq/L

3. SodiumSodium
Hypernatremia is Na+
> 150 meq/L

5. 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++
properlyproperly
– Urine osmolality 200-300 mosm/kgUrine osmolality 200-300 mosm/kg
– Urinary NaUrinary Na++
60-100 meq/kg60-100 meq/kg

6. Pathophysiology(2)Pathophysiology(2)
– Rapid hypertonicityRapid hypertonicity
 Loss of 10% of body weightLoss 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 shrinkageTearing of cerebral blood vessels, then 2° brain shrinkage
– Gradual hypertonicityGradual hypertonicity
 Idiogenic osmoles prevent brain shrinkageIdiogenic osmoles prevent brain shrinkage

7. Etiology of HypernatremiaEtiology of Hypernatremia
 Etiology(1)Etiology(1)
– Excessive sodium intakeExcessive sodium intake
 Iatrogenic NaIatrogenic Na++
administrationadministration
 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

8. Etiology of HypernatremiaEtiology of 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, SulfonylureasAlcohol, Lithium, Phenytoin, Propoxyphene, Sulfonylureas

9. Etiology of HypernatremiaEtiology of 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, diarrheaGI loss: Vomiting, diarrhea

10. Symptoms & SignsSymptoms & Signs
 Clinical Features: mainly CNSClinical Features: mainly CNS
– Acute symptoms atAcute 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

12. TypesTypes of Hypernatremiaof Hypernatremia
Hypernatremia with low body sodium
content
Hypernatremia with normal body
sodium content
Hypernatremia and increased body
sodium content

13. Hypernatremia withHypernatremia with lowlow totaltotal
body sodium contentbody sodium content
Water loss in excess of sodium loss
Osmotic diuresis
Diarrhea
Sweating
Vomiting

14. Hypernatremia withHypernatremia with normalnormal total bodytotal body
sodium contentsodium content
Due to water loss
Diabetes insipidus
Central diabetes insipidus
Nephrogenic diabetes insipidus

15. Hypernatremia andHypernatremia and increasedincreased totaltotal
body sodium contentbody sodium content
Following administration of large
quantities of hypertonic saline solutions
Iatrogenic Na administration: FFP…
Sea water intake
Mineralocorticoid or glucocorticoid excess

16. 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 diuretic
Diuretics
Yes
No
Renal response to
DDAVP
Urine osmolality↑
CDI
Yes
No
NDI

17. HypernatremiaHypernatremia
 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

19. Goals of therapyGoals of therapy
To correct water deficit
To stop ongoing water loss

20. Principles of therapyPrinciples of therapy
Correction 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

21. Total Water Deficit = A+B+CTotal Water Deficit = A+B+C
If 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/H
Renal water loss, ongoing (C)

22. Guidelines of therapy
Administration of IV Fluids
– (Isotonic Salt ~ Free)
Encourage foods: low in Na+
Push P.O. Fluids
Monitor Neurological status
Monitor for Arrhythmias

24. 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

25. 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)

26. PolyuriaPolyuria
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

27. PolyuriaPolyuria
Appropriate Inappropriate
Water diuresis
(Uosm<250
mosmol/Kg)
IV dilution
Primary hypodipsia
CDI
NDI
Solute diuresis
(Uosm>300
mosmol/Kg)
Saline loading
Post-obstructive
Hyperglycemia
High-protein
tube feeding
Na-wasting
nephropathy

28. Urine osmolatity
(mosmol/Kg)
Clinical settings Response to
ADH
<300 CDI
NDI
+
--
300 to 800 Osmotic diuresis
CDI, partial
NDI, partial
Volume depletion in
CDI
--
+
--
+
>800 Non-renal water loss
primary hypodipsia
Na overload
--
--
Variable Essential
hypernatremia
Variable

29. Renal water loss in NDIRenal water loss in NDI
Lithium-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%

31. 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

33. 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


34. Reset HypernatremiaReset 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

36. Essential hypernatremiaEssential hypernatremia
Primary hypo-dipsia (thirst center defect)
plus inhibition of ADH (osmoreceptor defect)
 New normal plasma Na : wide variation﹝ ﹞
between 150 and 180meq/L
Osmoreceptor relatively insensitive
rather than being reset at a higher level;
selectively damaged ; normal response to
volume
 Chlorpropamide: ↑ ADH effect

37. SIADH: drug relatedSIADH: 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