hynonatremia symptoms and management in cardiology practice

1. HYPONATREMIA
DIAGNOSIS AND MANAGEMENT

2. INTRODUCTION:PATHOPHYSIOLOGY
SYMPTOMS
WORK-UP
TREATMENT
CARDIOLOGIST`S PERSPECTIVE
AQUARETICS
OSMOTIC DEMYELINATION SYNDROME
TAKE HOME MESSAGE

3. INTRODUCTION
• Defined as sodium concentration < 135 mEq/L. mild 135-
130/moderate 130-120/severe <120.
• Generally considered a disorder of water as opposed to
disorder of salt i.e.it usually Results from increased water
retention
 Hyponatremia, the most common electrolyte disorder in
hospitalized patients present seen in 15%-22% patients at
admission

4. • Normal physiologic measures allow a person to excrete up
to 10 liters of water per day which protects against
hyponatremia
• Thus, in most cases, some impairment of renal excretion of
water is present
 Maximum concentrating ability of kidney is approximately
800-1600mOsm/kg
Verbalis et al Hyponatremia Treatment Guidelines 2007/The American Journal of Medicine (2007) Vol 120 (11A), S1–S21

5.  Because they impair distal tubule–diluting capacity without
affecting urinary concentration , thiazide drugs are the
predominant cause of diuretic induced hyponatremia(73%
cases)
 Furosemide-related hyponatremia tends to occur after many
months of therapy, often when an intercurrent illness
develops, whereas thiazide-related hyponatremia frequently
occurs within a few days or weeks after initiation of therapy.
Verbalis et al Hyponatremia Treatment Guidelines 2007/The American Journal of Medicine (2007) Vol 120 (11A), S1–S21

6.  Patients with thiazide-induced hyponatremia typically are
elderly women. In 1 study, the mean age was 76.4 +/- 9.6
years, 90% of those affected were aged 65years, and 70%
were women
 Serum uric acid levels, which typically rise with volume
depletion, were lower in patients with thiazide-induced
hyponatremia as compared with normonatremic patients
taking thiazides suggesting a role for abnormal thirst and
water intake
Verbalis et al Hyponatremia Treatment Guidelines 2007/The American Journal of Medicine (2007) Vol 120 (11A), S1–S21

7.  Max. ADH effect decreases urine output to approximately
500 cc/day
 No ADH release increases urine output to 15-20 Liters per
day. U osm = 40 – 80 mOsm/kg H2O
 The risk of death associated with hyponatremia appears to
be particularly strong in patients with cardiovascular
disease, cancer, and those undergoing orthopaedic
procedures

8. INTRODUCTION
PATHOPHYSIOLOGY:SYMPTOMS
WORK-UP
TREATMENT
CARDIOLOGIST`S PERSPECTIVE
AQUARETICS
OSMOTIC DEMYELINATION SYNDROME
TAKE HOME MESSAGE

9. Am J Cardiol 2005;95(suppl):8B–13B

11. Clinical Findings
Type I,
Hypervolemic
Type II,
Hypovolemic
Type IIIA,
Euvolemic
Type IIIB,
Euvolemic (SIAD)
CHF, cirrhosis, or nephrosis
Yes
No
No
No
Salt and water loss
No
Yes
No
No
ACTH–cortisol deficiency
and/or nausea and vomiting
No
No
Yes
No
Generalized edema, ascites
Yes
No
No
No
Postural hypotension
Maybe
Maybe
Maybea
No
BUN, creatinine
High-normal
High-normal
Low-normal
Low-normal
Uric acid
High-normal
High-normal
Low-normal
Low-normal
Serum potassium
Low-normal
Low-normalb
Normalc
Normal
Serum albumin
Low-normal
High-normal
Normal
Normal
Serum cortisol
Normal-high
Normal-highd
Lowe
Normal
Plasma renin activity
High
High
Lowf
Low
Urinary sodium (meq unit of
time)g
Low
Lowh
Highi
Highi
History
Physical examination
Laboratory

12. The American Journal of Medicine, Vol 120 (11A), November 2007

13. The American Journal of Medicine, Vol 120 (11A), November 2007

14. INTRODUCTION
PATHOPHYSIOLOGY
SYMPTOMS:WORK-UP
TREATMENT
CARDIOLOGIST`S PERSPECTIVE
AQUARETICS
OSMOTIC DEMYELINATION SYNDROME
TAKE HOME MESSAGE

15. WHO HAS SYMPTOMS….?
 Depends on rate of development
 Symptoms universal if [Na] < 120 is acute
 Chronic hyponatremia is less likely to be
symptomatic
 Young and old are more likely to be symptomatic

16. WHAT ARE THE SYMPTOMS….?
ACUTE:
121-130 mEq/L
Nausea, malaise, headache, lethargy, muscle cramps,
disorientation, restlessness
<120 mEq/L
Obtundation, seizures, respiratory arrest, coma,death
CHRONIC: (developed over days)
Usually Asymptomatic / Non-Specific
Nausea, gait disturbance, forgetfulness, muscle cramps
confusion, lethargy, fatigue
Palmer, Biff F., John R. Gates, and Malcolm Lader. "Causes and Management of Hyponatremia." The Annals of
Pharmacotherapy 37 (2003): 1694-701.

17. INTRODUCTION
PATHOPHYSIOLOGY
SYMPTOMS
WORK-UP:TREATMENT
CARDIOLOGIST`S PERSPECTIVE
AQUARETICS
OSMOTIC DEMYELINATION SYNDROME
TAKE HOME MESSAGE

18. WORKUP FOR HYPONATREMIA
• 4 mandatory lab tests
– Serum Osmolality
– Urine Osmolality
– Urine specific gravity
– Urine Sodium Concentration
• Additional labs depending on clinical suspicion
– TSH, cortisol (Hypothryoidism or Adrenal insufficiency)
– Albumin, triglycerides (psuedohyponatremia, cirrhosis), MM
– Plasma urea and uric acid
– Acid base balance

19. HYPONATREMIA FLOW CHART
Urine Osmolality

20. PLASMA OSMOLALITY
 Distribution of water:- due to osmotic forces
 Serum osmol = 2(Na)+ BUN/2.8 + Gluc/18
 Normal:- 275 to 290 mosmol/kg
 reduced in most hyponatremic patients, because it is primarily
determined by the plasma [Na] and accompanying anion
 Mechanisms for regulation
 If osmol↑ → 1. thirst mechanism, 2. ADH↑
 ↓Effective circulating volume→ ADH↑
The American Journal of Medicine, Vol 120 (11A), November 2007

21.  NORMAL OSMOLALITY (ISO-OSMOLAR)
 aka Pseudohyponatremia with hyperlipidemia or
hyperproteinemia
 HYPEROSMOLAR HYPONATREMIA
 Gap
(measured - calculated) > 10 indicates osmotic
substance that is not Na, Glucose, or BUN
 Normal Serum Osm Gap is -14 to +10.
 Endogenous substances:-Acetone, Renal Failure,
Lactate
 Exogenous substances:-Methanol, Ethylene Glycol,
Ethanol, Glycine, Mannitol

23. URINE OSMOLALITY
o
used to distinguish between impaired water excretion (which is
present in almost all cases) and primary polydipsia
o
Remember: problem is too much water
o
normal response to hyponatremia is to completely suppress
ADH secretion
 results in
excretion of a maximally dilute urine with an osm
below 100 mosmol/kg and a SpG ≤1.003
 Most
hyponatremic patients have a relatively marked
impairment in urinary dilution that is sufficient to maintain
the urine Osm > or = 300 mosmol/k

24. o Values
above this level indicate an inability to
normally excrete free water (i.e. continued secretion
of ADH)
o
Normal urine osmolality: 400-500 mM
 Maximal dilution 50-100 mM (USG 1.002-1.003)
 Maximal concentration 900-1200 mM (USG 1.0301.040)
Concentrated Urine: > 500 mM (at least!), USG > 1.017
o
Thus, UOSM > POSM is not enough to R/O Diabetes Insipidus
o

25. o
Urine Osm < 100 with hyponatremia is seen in conditions
o Psychogenic Polydipsia
o Massive H2O intake overwhelms H2O excretion
o
Beer Drinkers Potomania (aka Tea & Toast diet),
malnutrition
o dietary solute intake such as Na, K, protein is
decreased
o therefore solute excretion is so low that the rate of
H2O excretion is markedly diminished even though
urinary dilution is intact
o
Reset osmostat

26.  Increased urine osmolality:






Addison's disease (rare)
Congestive heart failure
Dehydration
Glycosuria
Renal artery stenosis
Shock
Syndrome of inappropriate ADH secretion
 Decreased urine osmolality:





Aldosteronism (very rare)
Diabetes insipidus (rare)
Excess fluid intake(psychogenic polydipsia)
Kidney failure
Renal tubular necrosis
Severe pyelonephritis

27. URINE SPECIFIC GRAVITY USG
 Estimates solute concentration of urine on basis of weight
as compared with an equal volume of distilled water

Normal Posm is 0.8-1.0% heavier than water so PSG = 1.0081.010
 Each ↑ in UOSM 30-35 mM ↑ USG by 0.1% (0.001)
 Therefore, USG of 1.010 ~ UOSM 300-350 mM
 Larger Molecular Weight urinary OSM (glucose, radio
contrast, carbenicillin) if present will falsely elevate USG
 Nothing falsely lowers USG

28. URINE SODIUM CONCENTRATION
• used to distinguish b/n hypovolemic and euvolemic hyponatremia.
 UNa < 30 implies hypovolemic or reduced effective circulation
volume
 Kidneys reabsorb solutes to retain water and volume
 unless there is renal salt-wasting:


diuretic therapy(most often )
adrenal insufficiency (infrequently)
cerebral salt-wasting
 UNa > 30 seen in the euvolemic types

usually above 40 meq/L in patients with the SIADH who are
normovolemic and whose rate of sodium excretion is
determined by sodium intake, as it is in normal subjects.

29. o
Most hyponatremic patients have a relatively marked
impairment in urinary dilution that is sufficient to maintain
the urine Osm > or = 300 mosmol/k
o
serial monitoring of the urine [Na] may be helpful in
selected cases in which the correct diagnosis may not be
apparent

If hypovolemic, isotonic saline should suppress the
hypovolemic stimulus to ADH release

If SIADH urine osmolality remains high but urine Na
excretion is promoted by volume expansion and often
rises above 40 mEq/L

30. ADDITIONAL LAB TESTS
• FeNA
• PLASMA URIC ACID
o
initial water retention and volume expansion in the SIADH is
frequently associated with hypouricemia (due to increased uric acid
excretion in the urine).
o
Uric acid is increased in patients with hypovolemia
• PLASMA UREA
o
Hypervolemia also increases urea clearance such that hyponatremia
of SIADH usually is associated with a BUN of < 5 mg/dL (1.8
mmol/L).
 caution in older patients as BUN is seldom this low secondary to
decreased FeBUN that occurs with aging.
 i.e the absence of a low BUN cannot be used to exclude SIADH
in older patients

31. • ACID-BASE AND POTASSIUM BALANCE,
• E.g:
o
Metabolic alkalosis and hypokalemia
 Diuretic use or vomiting
o
Metabolic acidosis and hypokalemia
 Diarrhea or laxative abuse,
o
Metabolic acidosis and hyperkalemia
 Adrenal insufficiency
• BRAIN NATRIURETIC PEPTIDE:• elevation of BNP provides useful lab evidence of
hypervolemia

33. INTRODUCTION
PATHOPHYSIOLOGY
SYMPTOMS
WORK-UP
TREATMENT:CARDIOLOGIST`S PERSPECTIVE
AQUARETICS
OSMOTIC DEMYELINATION SYNDROME
TAKE HOME MESSAGE

34. THERAPY
ADVANTAGES
DISADVANTAGES
Fluid restriction
Generally effective; inexpensive
Noncompliance
Demeclocycline
Consistently effective
Reversible azotemia and
nephrotoxicity; polyuria
Lithium
Effective in some patients
Inconsistent effectiveness;
significant adverse effects
Loop diuretics (e.g. furosemide)
plus increased salt intake
Effective in some patients
Imbalance between diuretic
action and salt ingestion
can lead to volume
depletion or overload
Urea
Consistently effective
Poor palatability; gastrointestinal
adverse effects;
development of azotemia at
higher doses
Hypertonic (3% or 5%) saline
with or without coadministration of loop
diuretics
Corrects serum [Na+]
Rate of correction is variable and
difficult to control; overly
rapid correction is
associated with
myelinolysis
VAPTANS
Corrects sodium consistently
Expensive, no long term
mortality benefit

35. GENERAL GUIDELINES
 Na deficit = 0.6 x wt(kg) x (desired [Na] - actual [Na]) (mmol)
 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
 Initially treat“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

36. Rx Hyponatremia (Example)
 Na deficit (mmol) = 0.6 x wt(kg) x (desired [Na] - actual [Na])
 60 kg woman, serum Na 107, seizure and other symptoms
 Na deficit = 0.6 x (60) x (120 – 107) = 468 mEq
 Want to correct at rate 1.5 mEq/L/h: 13/1.5 = 8.7h
 468 mEq / 8.7h = 54 mEq/h
 3% NaCl has 513 mEq/L of Na
 54 mEq/h =
513 mEq
x
1L
 x = rate of 3% NaCl = 105 cc/h over 8.7h to correct serum Na to 120 mEq/h
 Note: Calculations are always at best estimates, and anyone getting
hyponatremia corrected by IV saline (0.9% or 3%) needs frequent serum
electrolyte monitoring (q1h if on 3NS).

37. ADROGUE MADIAS FORMULA
 Ratio of actual to expected rise in sodium is calculated using the
Adrogue-Madias formula.
 A value of 1 indicates that the entire increase in serum sodium
concentration can be accounted for by the administered
hypertonic saline.
 In 74.2% of the patients with preinfusion sodium 120 mEq/L, the
ratio was >1, indicating that the actual increase exceeded the
predicted increase.

38.  The Adrogue -Madias formula underestimates increase in sodium
concentration after hypertonic saline therapy esp.in patients with
ECF depletion and psychogenic polydipsia
 Hypertonic saline should be infused at rates lower than those
predicted by formulas with close monitoring of serum sodium and
urine output.
 Total body water is estimated as total body weight
 X 0.6 in children and nonelderly men,
 X 0.5 in nonelderly women and elderly men
 X 0.45 in elderly women.
 Other formulas are Barsoum-Levine and the Nguyen-Kurtz

39.  Total body water can be determined using Flowing
afterglow mass spectrometry FA-MS measurement of
.
deuterium abundance in breath samples from individuals
after ingestion of D2O
 Another method of determining total body water
percentage (TBW%) is via Bioelectrical Impedance
Analysis (BIA). . BIA has emerged as a promising
technique because of its simplicity, low cost, high
reproducibility and non-invasiveness

40. Karen E. Yeates, Michael Singer, CMAJ • FEB. 3, 2004; 170 (3)

41. Adrogue: NEJM, Volume 342(21).May 25, 2000.1581-1589

42. INTRODUCTION AND PATHOPHYSIOLOGY
SYMPTOMS
WORK-UP
TREATMENT
CARDIOLOGIST`S PERSPECTIVE:AQUARETICS
OSMOTIC DEMYELINATION SYNDROME
TAKE HOME MESSAGE

43.  Approximately 5% of CHF patients have hyponatremia.
 Predominantly dilutional hyponatremia
 Total extracellular sodium is higher than normal
 Predicted as 1 of the predictors of mortality in OPTIME-
CHF Study as also in ACTIV-CHF.
 In the OPTIMIZE-HF registry, the risk of death during
follow-up of 60 to 90 days increased by 10% for each 3mmol/L decrease in baseline serum sodium 140
mmol/L.3
 Marker of neurohormonal activation

44. Am J Cardiol 2005;95(suppl):8B–13B

45. Am J Cardiol 2005;95(suppl):8B–13B

46. AJCVOL. 95 (9A) MAY 2, 2005

47. Am J Cardiol 2009;103:405– 410

48. MANAGEMENT
 Improvement in cardiac function
 Control of factors causing exacerbation of cardiac
dysfunction
 Fluid restriction
 Controlled use of diuretics causing free water
clearance/avoidance of thiazides
 Use of hypertonic saline and aquaretics as indicated

50. MAJOR TRIALS OF VAPTANS
 ACTIV IN CHF:-(319 pts),Tolvaptan(doses 30/60/90 mg)
produced weight reduction and correction of hyponatremia
without electrolyte imbalance and worsening of renal function.
No effect on heart failure outcomes at 60 days.
 METEOR:-(240 pts)Showed no beneficial effects of tolvaptan
on LV remodeling
 EVEREST:-(4133 pts)Tolavaptan had no significant mortality
benefit and decrease of hospitalization if drug is continued after
discharge.However dyspnoea ,body weight and edema were
decreased

51.  SALT1/2:-multicentre placebo controlled trial on 448 pts
with conivaptan in euvolemic/hypervolemic hyponatremia
demonstrated benefit
 ADVANCE:-343 PTS in NYHA class 2-4 were given
conivaptan for 12 weeks. Quality of life and exercise capacity
of the pts did not improve
 VICTOR:-83 pts in NYHA class 2-3 with signs of congestion
were given Tolvaptan in addition to furosemide. Euvolemia
and normonatremia was better achieved in pts given
Tolavaptan
 BALANCE:-650 pts multicenter RCT in pts with
decompensated Heart Failure. study completed.results not
published as yet

52. Circulation. 2008;118:410-421.)

53. Circulation. 2008;118:410-421.

56. INTRODUCTION AND PATHOPHYSIOLOGY
SYMPTOMS
WORK-UP
TREATMENT
CARDIOLOGIST`S PERSPECTIVE
AQUARETICS:OSMOTIC DEMYELINATION SYNDROME
TAKE HOME MESSAGE

57. THINGS TO KNOW ABOUT VAPTANS
 Vasopressin receptor antagonists can cause an electrolyte-
free aquaresis, reduce urine osmolality, & raise serum Na
 Use in euvolemic/hypervolemic hyponatremia
 Contraindicated in hypovolemic hyponatremia
 Vaptans are not suitable for hyponatremia due to cerebral
salt wasting and psychogenic polydipsia where the ADH
level is appropriate.

58.  Avoid in pregnant women
 Aquaresis delayed 1-2 h
 Promotes slow aquaresis/Risk of overly rapid correction of
hyponatremia seems low
 Adverse Effects:  Thirst 8-16%; dry mouth 4-13%
 Hypernatremia develops in 5%
 Correction rate > 12 mmol/L/24h-3%

59.  If rate of correction too rapid use water or DDAVP
 Not studied in acute hyponatremia
 Not studied in patients with sNa < 115 mmol/L
 Role in hyponatremia due to over treated DI?
 No reduction in Mortality/Morbidity with long term use in
heart failure

60.  Possibility of hypotension & variceal bleeding in
cirrhotics if given a V1aR blocker
 ? Bleeding complications from V2R inhibition in vascular
endothelium
 Metabolized by CYP3A4
 Tachyphylaxis does not seem to occur
 Heart failure decreases clearance
 Risks v/s benefit?

61. AJC VOL. 95 (9A) MAY 2, 2005

63. The AJC Vol 96 (12A) December 19, 2005

64. PHARMACOKINETICS
“The Vaptans”
Conivaptan
Tolvaptan
Convenience
Mech Of Action
IV
non-selective(10:1)
PO
Selective(29:1)
Efficacy/Onset
Mean Increases:
40 mg/day: 6.3mEq/L
80 mg/day: 9.4 mEq/L
Lost effect at end of tx
As early as 10 hr in the 80mg
arm, increase >=4mEq/L
Mean increases
~6.2 mEq/L
(end of 30 day treatment)
Lost effect at end of tx
At day 4,~4mEq/L increase
was achieved
Safety
Infusion site reactions,
phlebitis, cardiac effects
Limited to v2 antagonism
Rash
Drug Interactions
Strong CYP3A4
Inhibitor/substrate
P-glycoprotein Substrate

65. OTHER USES OF VAPTANS
 POLYCYSTIC KIDNEY DISEASE
 polycystin defects may promote cyst development b/c they 
increases in intracellular cAMP (a second messenger for AVP acting
at the V2R) – therefore, V2R antagonists may  reduced cyst
volume
 CONGENITAL NEPHROGENIC DIABETES INSIPIDUS
 type 2 V2R mutations cause misfolding & interfere w/ trafficking of
the receptor from the ER to the cell membrane – VRA can bind to
misfolded intracellular V2R & improve transport to the cell
membrane

66. INTRODUCTION
PATHOPHYSIOLOGY
SYMPTOMS
WORK-UP
TREATMENT
CARDIOLOGIST`S PERSPECTIVE
AQUARETICS
OSMOTIC DEMYELINATION SYNDROME:TAKE HOME MESSAGE

67. OSMOTIC DEMYELINATION SYNDROME
OR CENTRAL PONTINE MYELINOLYSIS
 First described by Adams et al. in 1959
 RISK FACTORS: alcoholism
 chronically ill patients
 Elderly/malnourished
 Cirrhosis predisposes to demyelination (due to depletion of
intracellular organic solutes)
 Hypokalemia is a strong predictor

68.  Demyelination can be diffuse and not involve the pons
 Symptom onset can be delayed for weeks
• Rate of correction over 24 hours more important than rate of
correction in any one particular hour
• More common if sodium increases by more than 20 mEq/L in
24 hours

69. • Very uncommon if sodium increases by 12 mEq/L or less in 24
hours
• CT but preferably MRI to diagnose demyelination if suspected,
though imaging studies may not be positive for up to 4 weeks
after initial correction
• Symptoms generally occur 2-6 days after elevation of sodium
and usually either irreversible or only partially reversible
The AJM, Vol 120 (11A), November 2007

70. PRESENTATION







Dysarthria
Dysphagia
Parkinsonism
Catatonia (2 case reports)
Locked-in syndrome
Lethargy and coma
Seizures








Nystagmus
Ataxia
emotional lability
akinetic mutism
gait disturbance
myoclonus
Behavioral disturbances
Paraparesis or
quadriparesis

71. PATHOPHYSIOLOGY
 Exact pathophysiology unknown.
 Possibly due to disturbance of blood brain barrier and damage
by cytokines
 Or due to influx of potassium triggering apoptosis
 brain regions that are slowest to recover osmolytes are the
most severely affectedby myelinolysis
 Uremia protects against myelinolysis

72. EVALUATION
 MRI may not show changes for weeks
 Appears as symmetric area of myelin disruption
 Extrapontine areas include:
 cerebellar and neocortical white/gray junctional areas
 thalamus
 subthalamus
 amygdala
 globus pallidus
 Putamen
 Caudate and lateral geniculate bodies

75. TREATMENT
 No effective therapy
 Case reports of improvement with aggressive plasmapheresis
immediately after diagnosis
 Case reports of treatment with thyrotropin-releasing hormone
 infusion of myoinositol (a major osmolyte lost in the adaptation
to hyponatremia)protects against mortality and myelinolysis
from rapid correctionof hyponatremia
Am J Med. 2006;119(suppl 1):S12–S16

76. PROGNOSIS
 Changes can be irreversible
 Old statistics shows 50% mortality
 Milder cases now diagnosed more often

77. INTRODUCTION
PATHOPHYSIOLOGY
SYMPTOMS
WORK-UP
TREATMENT
CARDIOLOGIST`S PERSPECTIVE
AQUARETICS
OSMOTIC DEMYELINATION SYNDROME
TAKE HOME MESSAGE:-

78. TAKE HOME MESSAGE
 Hyponatremia needs to be taken seriously in patients
with heart failure being a marker of neurohormonal
activity
 Do not ascribe muscle cramps always to Hypokalemia.
Think about hyponatremia as well!!
• WORK UP:-4 mandatory lab tests
– Serum Osmolality
– Urine Osmolality
– Urine specific gravity
– Urine Sodium Concentration

79.  CORRECTION FORMULA: Na deficit = 0.6 x wt(kg) x (desired [Na] - actual [Na])
(mmol)
 Use of aquaretics is a relatively safe and effective method
for hyponatremia correction with no long term mortality
benefit
 Thiazide diuretics cause hyponatremia much more
commonly than loop diuretics. Onset is earlier and is
predominantly seen in elderly females.

80.  Overzealous correction of hyponatremia needs to be
avoided lest CPM develops
 Pontine myelinolysis not necessarily involves pons
 MRI change may take upto 4 weeks to occur
 Less severe forms of CPM are much more common
 Essentially CPM has no t/t

82. Neoplasms
Carcinomas
Lung
Duodenum
Pancreas
Ovary
Bladder, ureter
Other neoplasms
Thymoma
Mesothelioma
Bronchial adenoma
Carcinoid
Gangliocytoma
Ewing's sarcoma
Head trauma (closed and penetrating)
Infections
Pneumonia, bacterial or viral
Abscess, lung or brain
Cavitation (aspergillosis)
Tuberculosis, lung or brain
Meningitis, bacterial or viral
Encephalitis
AIDS
Vascular
Cerebrovascular occlusions, hemorrhage
Cavernous sinus thrombosis
Neurologic
Guillain-Barré syndrome
Multiple sclerosis
Delirium tremens
Amyotrophic lateral sclerosis
Hydrocephalus
Psychosis
Peripheral neuropathy
Congenital malformations
Agenesis corpus callosum
Cleft lip/palate
Other midline defects
Metabolic
Acute intermittent porphyria
Pulmonary
Asthma
Pneumothorax
Positive-pressure respiration
Drugs
Vasopressin or desmopressin
Chlorpropamide
Oxytocin, high dose
Vincristine
Carbamazepine
Nicotine
Phenothiazines
Cyclophosphamide
Tricyclic antidepressants
Monoamine oxidase inhibitors
Serotonin reuptake inhibitors

83. http://www.accessmedicine.com.proxy.westernu.edu/content.aspx?aID=10935&searchStr=hyponatremia

84. Syndrome of Inappropriate ADH
Release (Bartter’s Criteria)
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Hyponatremia and true hypoosmolality bydefinition
Euvolemia clinical
Urine less than maximally dilute (urinary
osmolality usually > 200 mOsm/kg of H2O)
Normal renal, cardiac, hepatic, adrenal, pituitary,and
thyroid function
No history of antidiuretic drugs
No emotional or physical stress
Urinary sodium > 20 mEq/litera
a Urinary sodium may be <20 mEq/liter if the patient
is volume depleted or on low sodium intake.