hypernatremia topic for residents/fellows

1. Disorders of Water Handling:
HYPERNATREMIA
JAN MELVIN M. ZAPANTA, MD

2. Take note:
Disorders of water
handling = Hyponatremia
& Hypernatremia
Disorders of sodium
handling = Hypovolemia
& Hypervolemia

3. Sodium is different…and HARD!
 Most ions must be regulated because of
direct effects of the ion.


 Arrhythmias from high (or low) potassium
Weakness from high magnesium
Tetany from low calcium
 Sodium is not like that.

 The problems with high or low sodium have little
to do with direct effects of the ion.
Disregulation of sodium causes changes in cell
volume.

4. Osmosis: the thought experiment

5. The movement of water in the body
 The movement of water into and out of cells
is analogous to the beaker experiment:
intracellular compartment extracellular compartment
When tonicity
outside of the
cells increases,
cells shrink

6.  If the concentration of solute in the cells
increases the result is predictable:
The movement of water in the body
When the tonicity inside of
cells increases, cells swell.

7. Why we care about osmolality?
 Alterations in cell size disrupt tissue
function.

8. Tonicity versus Osmolality
 Osmolality
 Total concentration of
all particles in solution.
 Tonicity

 Concentration of only
the osmotically active
particles.
Only impermeable
particles contribute to
tonicity.
Only impermeable particles
cause changes in cell volume.

9. Tonicity versus Osmolality

10. Osmolarity vs Osmolality vs Tonicity
 Osmolarity = [osmoles] in a volume of solvent (mOsm/L)
 Osmolality = [osmoles] in a mass of solvent (mOsm/kg)
*in dilute systems, they are the same
 Tonicity = effective osmolality and is equal to the sum of the
concentrations of the solutes which have the capacity to exert
an osmotic force across the membrane.
Serum osmolality = 2[Na+K] + glucose + BUN
[mEq/L] [mEq/L]
NV = 275 – 290 mOsm/kg

11. Sodium is an indicator of Osmolality& Tonicity
 The clinically important variable is TONICITY.
We are interested in sodium because it gives a
good clue to the tonicity.

12. Summary
 We are interested in plasma tonicity
because:

 When elevated, water leaves the cells causing
dysfunction.
When decreased water moves into the cells
causing dysfunction.
 We are interested in sodium because it
usually tells us the plasma tonicity.

13. Renal Water Excretion
Formula 1:
Formula 2: 
V = Urine Volume
Cosm = isotonic portion urine Posm= serum osmolality
Cwater = free water
Formula 3:
.

14. Renal Water Excretion
Cwater= V (1– Uosm)
Posm
1. In hypotonic urine (Uosm <Posm), Cwater is positive.
2. In isotonic urine (Uosm = Posm), Cwater is zero.
3. In hypertonic urine (Uosm >Posm), Cwater is negative (i.e., water is
retained).

15. Renal Water Excretion
Limitation of the previous equation:
- UREA is included in computing for urine osmolality!
- ineffective osmole, does not influence serum Na+ concentration or the
release of AVP
Electrolyte Free Water clearance [ Cwater(e)]
Better predicts changes in serum Na+
1. If UNa + UK < PNa, then Cwater(e) is positive and serum [Na+] ↑
2. If UNa + UK > PNa, then Cwater(e) is negative and serum [Na+] ↓

17. HYPERNATREMIA
1. Serum sodium > 145 mmol/L
2. Always represents hyperosmolality
[water loss or sodium retention]
3. Never seen in an alert adult with access to water unless
there is abnormal thirst mechanism
4. Normal TBW = 45 – 60% lean body wt.
In water-depleted pxs = 40 – 50% lean body wt.

19. Approach to Diagnosis
Thorough HISTORY to determine possible cause/s of hypernatremia
1. Decreased water intake in a patient with diminished physical or mental
capacity
2. Osmotic diarrhea
3. Neurologic problems that may cause central diabetes insipidus
4. Use of drugs which may be associated with hypernatremia:
 Lithium, cisplatin, aminoglycosides, demeclocycline, and amphotericin B which
may lead to nephrogenic diabetes insipidus;
 mannitol which can cause osmotic diuresis,
 lactulose or sorbitol which can cause hypotonic gastrointestinal losses
(osmotic diarrhea)
 hypertonic bicarbonate or NaCl solutions

20. Approach to Diagnosis
 Physical Examination
recognize signs/symptoms of hypernatremia
assess volume status
check for ongoing losses
 Laboratory examinations
serum electrolytes
urine electrolytes
others as needed

23. Approach to management (RiCH-
RELATE)
1. Anticipate Risk of hypernatremia
2. Compute for Corrected serum Sodium
3. Review History and PE: chronicity and volume status
4. Determine need for volume Resuscitation
5. Compute for estimated water deficit (Edelman)
6. Add ongoing Losses and free water clearance
7. Compute for rate of correction (Adrogue-Madias)
8. Select Type of fluid regimen
9. Monitor and re-Evaluate fluid prescription

24. Anticipate Risk
 Hypernatremia occurs in predictable clinical settings
 opportunity for PREVENTION
 Deranged/abnormal THIRST MECHANISM
 At risk patients:
1. Elderly, infants
2. Critically ill (intubated, comatose, sedated)
3. Certain clinical situations
 recovery from acute kidney injury, catabolic states, therapy with
hypertonic solutions, uncontrolled diabetes, and burns

25. Corrected Sodium
Correct serum Na+ in the presence of HYPERGLYCEMIA
 Serum sodium is generally reduced in hyperglycemia due to
loss of sodium ions by polyuria and vomiting (DKA), and
because severe hyperglycemia shifts intracellular water into
interstitial compartment
 Increase serum Na+ by 1.6 mmol/L for every 100 mg/dl
increase in serum glucose above 100 mg/dl
 If serum glucose is > 400 mg/dl, increase serum Na+ by 2.4
mmol/L for every 100 mg increase in serum
glucose (Hillier Method)

26. History and PE
1. CHRONICITY: whether hypernatremia is acute or
chronic
 Acute hypernatremia: developed < 48 hrs
 Chronic hypernatremia: developed > 48 hrs
 If unsure, use chronic
2. VOLUME STATUS:
 Hypovolemic hypernatremia (loss of hypotonic solution)
 Euvolemic hypernatremia (loss of free water)
 Hypervolemic hypernatremia (gain of hypertonic solution)

27. Resuscitate
 VOLUME over SODIUM always!!
 In hypovolemic hypernatremia – use sodium-containing
solutions (PNSS/PLRS) until euvolemia is achieved
 May give D5W or oral water once hemodynamically stable

28. Estimate water deficit
 Serves as a guide in INITIAL therapy
 May use either of the two formula
1. Edelman Formula
Water deficit* = current TBW x (serum Na - 1)
140
*assumes no ongoing fluid/electrolyte losses
*assumes baseline Na of 140 is the target
Total Body Water (TBW) = 60% of lean body weight
• 60% LBW Young Men (65 yrs old)
• 50% LBW Young Women (65 yrs old)
• 50% LBW Elderly Men (>65 yrs old)
• 45% LBW Elderly Women (>65 yrs old)

29. Estimate water deficit
2. Relationship of [Na+] with TBW
Water deficit = TBW1 – TBW2
[Na+
1] x TBW1 = [Na+
2] x TBW2
*Assuming no ongoing losses, number of osmoles of Sodium is
always equal (concentration x volume)
[Na+
1] = 140 mmol/L (if there is no previous Na level to compare with)
TBW1 = previous total body water (TBW) (if previous weight of the patient is
unknown)
[Na+
2] = present plasma sodium concentration
TBW2 = present total body water ( based on the present weight of the
patient in kg

30. Estimate water deficit
Example: 70 kg male, present [Na+] = 165, present wt 50kg
1. Edelman Equation:
Water deficit = (50 x 0.5) x [(165/140)-1] = 4.46L
2. Na and TBW relationship:
140 x TBW1 = 165 x (50 x0.5)
TBW1 = 4125 / 140 = 29.46L
Water deficit = 25 – 29.46 = 4.46L

31. Ongoing Losses and Cwater(e)
1. Add ongoing losses (urine, stool, etc) to deficit
2. Add insensible losses
 800 ml/day (minimum in an unstressed adult)
 Transepidermal diffusion (400ml/day)
 Evaporative water loss in respiratory tract (400ml/day)
 Fever: Add 200ml/degree above 37C/day
 Metabolic water production from carbohydrates and fatw
(400ml/day) – can account for the insensible respiratory water
losses (1:1)
 NO insensible losses in mechanically ventilated patients due to a
closed system and presence of humidifier

32. Ongoing Losses and Cwater(e)
1. Add ongoing losses (urine, stool, etc) to deficit
2. Add insensible losses
3. Calculate Free water clearance [Cwater(e)]
 In presence of hypernatremia, target Cwater(e) should be
negative
 If Cwater(e) is positive, hypernatremia will worsen
 If Cwater(e) is 0, hypernatremia remains unchanged

33. Ongoing Losses (quick method)
 If patients have modest urine output, it is not so important to consider the
correction of hypernatremia
 As the UO rises => more and more important to include it in replacement.
 Topf Method:
1. 0-1 L: ignore
2. 1-3 L: replace half
3. >3 L: replace all
 Example for UO of 6 liters = 0 + 1 + 3 = 4 L

34. Rate of correction
 Avoid rapid correction to avoid CEREBRAL EDEMA
 What exact rate? CONTROVERSIAL
 Maximum rate of correction of the serum sodium should be 10-
12 mmol/l/day in patients with hypernatremia for at least
24 hours
 Based on chronicity:
• for acute hypernatremia: 0.5 – 1.0 mmol/L/hr
• for chronic hypernatremia: not more than 0.5 mmol/L/hr

35. Rate of IVF fluid replacement
 Adrogué-Madias formula
• Determines the change in the serum Na+ when 1L of a certain infusate is
given
△ serum Na+ per liter = infusate Na+ – serum Na+
of infusate TBW + 1
• If infusate has K+:
△ serum Na+ per liter = (infusate Na+ + Infusate K) – serum Na+
of infusate TBW + 1

36. Rate of IVF fluid replacement
Example: 70kg male, Na 165, wt 50kg
What will be the change in serum Na if
1L of 0.3 NaCl solution is given?
△Na = 51 – 165 = -4.38mmol per liter of
25 +1 infusate
What if 1L of PLRS solution is given?
△Na = (130+4) – 165 = -1.19mmol per liter of
25 +1 infusate

37. Rate of IVF fluid replacement
 Determine the volume needed to achieve target serum Na level and
correct fluid deficit.
Volume needed = Desired change in Serum Na+
△ Na+ per liter of infusate
Example:
1. If we want to use 0.3 NaCl to cause a decrease in serum Na+ by 10
mmol/24 hrs, we need to give (10/4.38) = 2.3L of 0.3NaCl in 24h or
96cc/hr
2. If we will give PLRS, we need to give (10/1.19) = 8.4L of PLRS in 24hrs
or 350cc/hr

38. Fluids
a. oral/enteral free water
b. D5W = considered free water
b. 0.3% NaCl, 0.45% NaCl
> use if with concomitant Na depletion
c. 0.9% NaCl (pNSS)
> if patient is initially hypotensive
(VOLUME over SODIUM!!)
Appropriate Type of Fluids

39. HYPERNATREMIA
HYPERNATREMIA
Sodium & Water Loss
(more water lost)
Low Total Sodium
Renal Loss Extra-Renal Loss
Osmotic Diuresis
Mannitol
Glucose
Excess Sweating
UNa+ > 20 UNa+ < 20
Isotonic/Hypotonic Urine Hypertonic Urine
Hypotonic Saline

40. HYPERNATREMIA
HYPERNATREMIA
Pure Water Loss
Normal Total Sodium
Renal Loss Extra-Renal Loss
Diabetes Insipidus Respiratory Losses
Variable UNa+ Variable UNa+
Variable Variable
Water Replacement

41. HYPERNATREMIA
HYPERNATREMIA
Sodium Addition
High Total Sodium
Primary Hyperaldosteronism
Cushing’s Syndrome
Iatrogenic
Na+
HCO3-
Hypertonic HD
Na+
Cl-
Mineralocorticoids
UNa+ > 20
Isotonic/Hypertonic Urine
Diuretics + Water/Hypotonic

42.  Monitor response
• Serum sodium monitoring q6-8 hours, or more often if necessary)
• Other serum electrolytes (especially K+)
• Urine electrolytes to check for Cwater(e)
• WOF for complications of rapid correction
 Adjust fluid prescription accordingly
Monitoring and Re-evaluate

43. Case1: 40/F hypertensive and diabetic; chronic intake of thiazides; fell
and had a skull fracture. Urine output is 175 mL/hr.
Weight = 70 kg, comatose, BP 130/70, HR 98, afebrile, clear breath
sounds, no peripheral edema
Insensible losses ~ 1000 mL/day.
Na = 168 mEq/L Posm = 350 mOsm/kg UK = 4 meq/L
K = 4 mEq/L Uosm = 80 mOsm/kg
Hgt = 290 mg/dL UNa = 10 mEq/L
QUESTION 1 : What’s causing his hypernatremia?
A. Thiazides
B. Central Diabetes Insipidus
C. Decreased Water Intake (coma)
D. A & B
E. B & C

44. THIAZIDES
1. Inhibit Na-Cl reabsorption at the DCT
2. Not as potent as loop diuretics
3. Do not affect Na-Cl reabsorption at the
medullary interstitium.
a. no effect on medullary tonicity
b. no effect on urine concentration
c. may lead to hyponatremia (presence of ADH)
4. Steady state levels after 1 week.

45. ADH
1. Appropriately shut off
a. normovolemia
b. hypoosmolality
2. Inappropriately shut off
a. central diabetes insipidus
3. Resistance to ADH
a. nephrogenic diabetes insipidus

46. Case 1 : 40/F hypertensive and diabetic; chronic intake of thiazides; fell
and had a skull fracture. Urine output is 175 mL/hr.
Weight = 70 kg, comatose, BP 130/70, HR 98, afebrile, clear breath
sounds, no peripheral edema
Insensible losses ~ 1000 mL/day.
Na = 168 mEq/L Posm = 350 mOsm/kg UK = 4 meq/L
K = 4 mEq/L Uosm = 80 mOsm/kg
Hgt = 290 mg/dL UNa = 10 mEq/L
Question 2 : What IVF will you use to
treat the patient?
A. Isotonic saline at 100 cc/hr
B. 0.3%NaCl at 200 cc/hr
C. 0.3%NaCl at 170 cc/hr
D. D5W at 200 cc/hr
E. D5W at 170 cc/hr

47. Approach
1. Anticipate Risk of patient: comatose, polyuric state
2. Corrected Na+ = Na+ + 0.016 x (Glu-100) = 168 + 0.016 x (300-100) = 171
3. Hx, PE: euvolemic, assume chronic
4. Resuscitation not needed
5. Water deficit:
 Edelman: deficit = (70 x 0.5) x [(171/140)-1] = -7.75L
 140 x TBW1 = 171 x 35 -> TBW1 = 42.75 -> deficit = 35-42.75 = -7.75L
6. Losses:
 insensible 1000mL/day
 Free water clearance: UNa + UK < PNa, hence positive, renal losses of free water worsening the situation

48. Approach
7. Rate of Correction: not more than 0.5mmol/L/h or 12mmol/day max, choose 10 mmol/day
change
8. Choose fluid and rate of replacement: D5 0.3NaCl 1L (ideally D5W but due to thiazide use, may
need to give additional sodium)
△Na = 51 – 171 = -3.33mmol per liter of D5 0.3 NaCL
35 +1
volume of solution needed in a day = 10 /3.33 = 3L or 3000mL
Rate of IVF: 3000ml/24 = 125cc/h but + insensible losses 42cc/hr = 167cc/h
*May start adding free water thru enteral feeding
*start Desmopressin for the CDI
9. Monitor frequently and revise fluids accordingly

49. Case 2 : 67/M came due to increased sleeping time; he is a chronic
alcoholic with signs of chronic liver disease. He was on lactulose 30cc 3-
4x/day as treatment for his hepatic encephalopathy. He has asterixis, with
note of ascites. Wt 60kg, BP 90/50, HR 110, afebrile, pale looking
Insensible losses ~ 800 mL/day, stools ~250cc/episode 4x/day, UO
50ml/hr
Na = 160 mEq/L Posm = 330 mOsm/kg UK = 15 meq/L
K = 2.5 mEq/L Uosm = 100 mOsm/kg
Hgt = 92 mg/dL UNa = 12 mEq/L
Question 3 : What is causing the
hypernatremia?
A. pure water renal loss
B. pure water extrarenal loss
C. hypotonic fluid renal loss
D. hypotonic fluid extrarenal loss
E. hypertonic fluid gain

50. Approach
1. Anticipate Risk of patient:
2. Corrected Na?
3. Hx/PE – volume? Chronicity?
4. Resuscitation?
5. After resuscitation, bP 110/70 HR 87, rpt Na stil 160. Water deficit?
6. Losses? Cwater(e)?
7. Rate of correction?
8. What Fluid of choice? What IVF rate? Anything else to do?
9. Monitor and reevaluate

51. LAST WORDS ON SODIUM
1. Treat the cause, not the electrolyte.
2. Don’t correct too aggressively.
a. Overcorrection of hypoNa  CPM
b. Overcorrection of hyperNa  cerebral edema
3. MAINTENANCE OF CIRCULATION / PERFUSION
TAKES PRECEDENCE OVER
OSMOLALITY/TONICITY
a. When hypotensive, give pNSS/LR/colloids
b. Worry about the electrolytes later.
4. No formula is perfect, but they can guide us
a. many assumptions
b. fails to account ongoing losses, other variables

52. REFERENCES
 Adrogue, HJ and Madias, NE. Primary Care: Hypernatremia, NEJM 2000
 Harrison’s Principle of Internal Medicine. 19th edition
 Brenner and Rector’s The Kidney. 11th Edition
 Comprehensive Nephrology, 5th Edition
 Lecture Notes: UP-PGH Nephrology Fluid and Electrolytes Postgraduate
course
 Lecture Slides from Dr. Joel Topf
 Notes from Dr. Elizabeth Montemayor, Dr. Raymond Alonso