manjil

1. APPROACH TO HYPONATREMIA
Ashish Jha
Resident (3rd year)
Internal Medicine
Patan Academy of health Sciences

2.  Hyponatremia is defined as a plasma [N a + ]
< 135 mEq/ L
 Usually caused by a failure to excrete water
normally
 In healthy individuals, the ingestion of water
does not lead to hyponatremia because
suppressed release of antidiuretic hormone
(ADH), also called vasopressin, allows excess
water to be excreted in a dilute urine

3. Degree of hyponatremia
 Severe hyponatremia – <120 mEq/L
 Complications of untreated hyponatremia
and complications from overcorrection of
hyponatremia are most common among
patients with severe hyponatremia.

4.  Moderate hyponatremia – 120 to 129 mEq/L i
 Mild hyponatremia - 130 to 134 mEq/L

5. General Principles
 To maintain a normal [Na + ] the ingestion of
water must be matched with an equal volume
of water excretion.
 Any process that limits the elimination of
water or expands the volume around a fixed
Na + content may lead to a decrease in Na +
concentration.

6. Expansion of the space
1.
 Pseudohyponatremia refers to a laboratory
anomaly in which high levels of plasma
proteins and/or lipids expand the nonaqueous
portion of the plasma sample and result in an
errant report of a low ECF [Na + ]

7. 2.
 Hyperosmolar hyponatremia refers to
circumstances in which an osmotically active
solute other than Na + accumulates in the
ECF, drawing water into the ECF and diluting
the Na + content
 Hyperglycemia results in fall in plasma [Na +
] of 1.6–2.4 mEq/L for every 100 mg/dL rise in
plasma glucose

8.  Glycine, mannitol, or sorbitol, can be
absorbed into the ECF during bladder
irrigation, leading to the transient
hyponatremia seen in post–transurethral
resection of the prostate syndrome( post
TURP syndrome)

9. 3.
 psychogenic polydipsia, water intoxication,
beer potomania, and the so-called “tea and
toast” diet
 ECF water content rises simply because the
ingested quantity of water exceeds the
physiologic capacity of water excretion in the
kidney

10.  Urine cannot be diluted to an osmolality less
than approximately 50 mOsm/L, meaning
that a small amount of solute is required in
even the most dilute urine.
 So there is a limit to renal water clearance.

11. “Appropriate” ADH secretion
 With fall in effective circulating volume
 Thirst and water retention are stimulated,
protecting volume status at the cost of the
osmolar status
1. Hypovolemic hyponatremia may result from
any cause of net Na + loss, such as in thiazide
use and cerebral salt wasting

13. 2. Hypervolemic hyponatremia occurs in
edematous states such as congestive heart
failure (CHF), hepatic cirrhosis, and severe
nephrotic syndrome.
 Despite the expanded interstitial space, the
circulating volume is reduced (that stimulates
ADH)
 Alterations in Starling forces contribute to
this apparent paradox, shifting fluid from the
intravascular to interstitial space

14. “Inappropriate” secretion of ADH
 activation of water-conserving mechanisms
despite the absence of osmotic- or volume-
related stimuli
 most common form of this SIADH
 Pharmacologic agents may also stimulate
inappropriateADH secretion-
antidepressants (particularlySSRIs),
narcotics, antipsychotic agents,
chlorpropamide, and NSAIDs

15. SIADH
 nonphysiologic release of vasopressin from the
posterior pituitary or an ectopic source
Causes:
 neuropsychiatric disorders (e.g., meningitis,
encephalitis, acute psychosis, cerebrovascular
accident, head trauma)
 pulmonary diseases (e.g., pneumonia,
tuberculosis, positive-pressure ventilation, acute
respiratory failure)
 malignant tumors (most commonly, small cell
lung cancer)

16.  Diagnosis
1. Hypo-osmotic hyponatremia
2. Urine osmolality >100 mOsm/L
3. Euvolemia
4. Absence of conditions that stimulate ADH
secretion, including volume contraction,
nausea, adrenal dysfunction, and
hypothyroidism

17. Reset osmostat
 set point for plasma osmolality is reduced
 ADH and thirst responses, although
functional, maintain plasma osmolality at this
new, lower level
 occurs in almost all pregnant women and
occasionally in those with a chronic
decreased effective circulating volume

18. Diagnosis
 Clinical features are related to the osmotic
intracellular water shift leading to cerebral
edema
 So symptoms are primarily neurologic

19.  In acute hyponatremia (i.e., developing in <=
2 days ) patients complain of nausea and
malaise with Na at 125 mEq/L
 As the plasma [Na + ] falls further, symptoms
may progress to include headache, lethargy,
confusion, and obtundation.
 Stupor, seizures, and coma do not usually
occur unless the plasma [Na + ] falls acutely
below 115 mEq/L

20.  In chronic hyponatremia (>2 days in
duration), adaptive mechanisms designed to
defend cell volume occur and tend to
minimize the increase in ICF volume and its
symptoms.

21. Diagnostic Testing
 Accurate history and physical examination,
including an assessment of ECF volume
status and the effective circulating volume.
 Three laboratory analyses:
(1) the plasma osmolality
(2) urine osmolality
(3) the urine [Na + ]

22. Plasma osmolality
 Most patients with hyponatremia have a low
plasma osmolality ( <275mOsm/L)
 If this is not low then pseudohyponatremia
and hyperosmolar hyponatemia must be
ruled out
[Calculated plasma osmolality = 2 x Na +
glucose/18 + BUN / 2.8]

23. Urine osmolality
 appropriate renal response to hypo-
osmolality is to excrete a maximally dilute
urine (urine osmolality <100 mOsm/L and
specific gravity < 1.003)
 urine sample that is not dilute suggests
impaired free water excretion due to
appropriate or inappropriate secretion of the
ADH

24. Urine [Na +]
 Bedside assessment of effective circulating
volume and can discriminate between
extrarenal and renal losses of Na +
 Appropriate response to decreased effective
circulating volume is to enhance tubular Na +
reabsorption such that urine [Na + ] is less
than 10 mEq/L

25.  A urine [Na + ] of >20 mEq/L suggests a
normal effective circulating volume or a Na +
-wasting defect
 Occasionally, the excretion of a
nonreabsorbed anion obligates loss of the Na
+ cation despite volume depletion (ketonuria,
bicarbonaturia).

28. Treatment:Rate of correction
 In chronic hyponatremia, the target rate of
correction should not exceed 8 mEq/L over 24
hours ( ideally 4-6 mEq/L as usual therapy
increases Na at a greater rate)
 The risk of iatrogenic injury is increased in
patients with chronic hyponatremia because
cells gradually adapt to the hypo-osmolar
state

29.  The primary risk of overcorrection is the
development of central pontine myelinolysis
(CPM) or osmotic demyelination syndrome
(ODS)
 High risk for ODS – serum sodium
concentrations of less than or equal to 105
mEq/L and those with hypokalemia,
alcoholism, malnutrition, and liver disease

30.  CPM results from damage to neurons due to
rapid osmotic shifts
 In its most overt form, it is characterized by
flaccid paralysis, dysarthria, and dysphagia
 Confirmed by CT scan or MRI of the brain
 The risk of precipitating CPM is increased
with correction of the [Na + ] by 10–12 mEq/L
in a 24-hour period

31.  In symptomatic hyponatremia, the serum
[Na + ] should again be corrected cautiously.
 A targeted rise in serum [Na + ] by 4–6
mEq/L within the first 4–6 hours is generally
sufficient to reverse the neurologic sequelae
and avoid overcorrection.
 The total daily correction should not exceed 8
mEq/day

32. Type of intervention
 In symptomatic hyponatremia, hypertonic
saline should be used to achieve the brisk
correction described above (4–6 mEq/L in the
first 6 hours).
 Hypertonic saline can be given in 100 mL
boluses (up to 3 doses as needed).

33.  Can also be given as an infusion
 Traditional approach is:
Na deficit = 0.6(males) / o.5 (females) x body
weight x ( target plasma Na – starting plasma
Na)
• 1 L 3% NaCl = 513 mEq Na
• 1 L NS (0.9% NaCl) = 154 mEq Na

34. Example
 A 60 kg female patient with Na of 120
 Na deficit = 0.5 x 60 x (126-120) = 180 mEq Na
 Amount of fluid required=
1. 3% NaCl = 180/513 = 0.35 L = 350 ml
2. NS = 180/154 = 1.16 L = 1160 ml

35.  No algorithm or equation can replace the
importance of rechecking laboratory data to
ensure correction at an appropriate rate and
adjust fluid administration
 If the desired rate of correction is exceeded,
hypertonic fluids should be discontinued and
either hypotonic fluids or desmopressin can
be given to re-lower the serum Na + to
achieve a 24 hour correction less than 8
mEq/day

36.  In asymptomatic hyponatremia treatment
should be targeted to the cause of the
disorder :
1.Hypovolemic hyponatremia:
In patients with asymptomatic hypovolemic
hyponatremia, isotonic saline can be used to
restore the intravascular volume

37. 2. Hypervolemic hyponatremia
• Hyponatremia in CHF and cirrhosis often
reflects the severity of the underlying disease
• The hyponatremia itself is typically
asymptomatic
• Because the effective circulating volume is
decreased, the administration of fluid may
worsen the volume-overloaded state

38. • Management of the underlying condition is
the treatment
• Although restriction of water intake and
increasing water diuresis may help to
attenuate the degree of hyponatremia and
hypervolemia

39. 3. SIADH
• This disorder should be distinguished from
the previously listed conditions that stimulate
vasopressin secretion
• Standard first-line therapy is water restriction
and correction of any contributing factors
(nausea, pneumonia, drugs, etc.)

40. • Water restriction: amount of fluid restriction
necessary depends on the extent of water
elimination
• If (Urine Na + + Urine K+ )/Serum Na + < 0.5
restrict to 1 L/day
• If (Urine Na + + Urine K+ )/Serum Na + is 0.5–
1.0, restrict to 500 mL/d

41.  If (Urine Na + + Urine K+ )/Serum Na + is >1,
the patient has a negative renal free water
clearance, and any amount of ingested water
may be retained
 In such situations, the following options may
be required:
a) A high dietary solute load (using salt or urea
tablets) increases the capacity for water
excretion

42. b) Loop diuretics impair the urinary
concentrating mechanism and can enhance
free water excretion
c) Vasopressin antagonists promote water
diuresis ; IV (conivaptan) and oral (tolvaptan)
d) Lithium and demeclocycline interfere with
the collecting tubule’s ability to respond to
ADH

43. References
 TheWashington Manual of Medical
Therapeutics 36th Edition 2020
 UpToDate – accessed on 16th December 2020
 HARRISON Principles of Internal Medicine
20th Edition

44. Thank you for listening!!
 Questions ???