Dysnatremias
Case Presentation 1
19 year old female with a history of
depression is referred for polyuria and
polydipsia. Over the past 2 years she
developed polydipsia rather abruptly,
frequently drinking 5 gallons of water
per day. Medications included
fluoxetine 20 mg daily and famotidine
20 mg daily.
Case Presentation 1 Cont’d
Physical Exam Obese, depressed affect
BP 126/80 HR 100
Trace edema
24 hr urine volume 13 liters
Urine osm 80 mosm/kg
Serum
Sodium
144 Chloride
Potassium 4.4
CO2
BUN
5
Creat
Glucose
92
Osm
106
29
0.6
312
Polyuria
Urine output exceeding 3 L per day
 Etiology

» Water diuresis
– diabetes insipidus


central
nephrogenic
– primary polydipsia
» Solute diuresis
Evaluation of Polyuria
Urine Osmolality
< 250 mosm/kg
Water Diuresis
300-400 mosm/kg
Solute Diuresis
Water Restriction Test


No intake 2-3 hours prior to test
Measure:
» Hourly BP and weight
» Hourly urine volume and osmolality
» Plasma sodium and osmolality every 2 hour

Give dDAVP 5 mcg sc if no change in urine
osm despite rising serum osm or if plasma
osm > 295 mosm/kg
Case Presentation 1 Cont’d
Water Deprivation Test
dDAVP 5 u sc
TimeWt.
(hr)
(lb)
0
234
2
232
4
230
6
227
8
227
BP
(mmHg)
120/80
115/70
118/60
110/80
118/70
Sosm
Uosm
(mosm/kg)
305
87
313
113
325
125
323
138
305
655
Regulation of ADH Release
Posm
Effective Circulating Volume
Thirst
ADH
Water Excretion
Water Intake
Water Retention
Posm
Effective Circulating Volume
Plasma Vasopressin (pg/mL)
Sensitivities of Osmo- and Baroreceptor
Regulation of ADH Release
20
Pressure
Volume
Basal
Osmolality
15
10
5
0
-30
-15
0
+15
Percent Change
Figure 6
+30
Plasma Vasopressin (pg/ml)
Effects of Hemodynamic Variables on
the Osmo-regulation of ADH Release
10
Hypovolemia or
Hypotension
-20
5
-15
-10
Hypervolemia or
Hypertension
N
+10
+15
+20
0
260
300
340
Plasma Osmolality (mOsm/kg)
Figure 7
Figure 3
Regulation of ADH Release
Angiotensin
SFO
OVLT
PVN
SON
VLM
OC
Pituiatry
Osmolality
Baroreceptors
ADH
Central DI

Deficient secretion of ADH

Sudden onset of polyuria

Serum sodium tends to be > 142 mEq/L
Triphasic Changes in Water Balance after
Hypothalmic Surgery
DI
SIADH
5
4
3
2
DI
ADH release
from degenerating
posterior pituitary
Hypothalamic
Dysfunction
1
0
2
Urine
Output
(L/day)
4
6
8
10
12
Post-operative Day
14
16
Causes of Central DI







Idiopathic
Familial
Neurosurgery or trauma
Malignancy
Hypoxic encephalopathy
Sheehan’s syndrome
Infiltrative disorders
Treatment of Central DI

dDAVP
» Nasal spray 5-20 mcg every 12-24 hours
» Tablet 0.1-1.2 mg daily
» Follow serum Na+ and urine volume





Chlorpropamide 125-250 mg daily
Carbamezepine 100-300 mg BID
Clofibrate 500 mg QID
Thiazide diuretics
NSAIDs
Case Presentation 2
39 y.o. female with a history of schizophrenia and bipolar disorder is referred
for polyuria and polydipsia. Found to be
drinking out of bathtub and commode.
Had been treated with lithium in the past
(>1 year ago).
Case Presentation 2 Cont’d
Physical Exam BP 156/80 HR 92
Trace edema
24 hr urine volume 6000 ml
Urine osm 68 mosm/kg
Serum
Sodium
144 Chloride
Potassium 3.8
CO2
BUN
14
Creat
Glucose
98
Osm
100
24
1.5
292
Case Presentation 2 Cont’d
Water Deprivation Test
dDAVP 5 u sc
TimeWt.
(hr)
(lb)
0
196
2
195
4
194.5
6
194
8
193
BP
(mmHg)
148/80
145/85
145/80
140/80
138/70
Sosm
Uosm
(mosm/kg)
292
115
312
170
321
225
322
235
324
255
Factors Complicating the
Diagnosis of DI

Medullary washout

Central DI is often partial

Decrement in ADH activity in nephrogenic DI
is often partial

Elevated residual bladder capacity
Indirect Testing
Spontaneous Posm > 295
Spontaneous PNa+ > 143
Water Deprivation Test
Uosm > 500
U/Posm < 1.5
dDAVP 5 mcg sc
Primary Polydipsia
Uosm Rises > 150 mosm/kg
Uosm < 300 mosm/kg
Central DI
Nephrogenic DI
Plasma ADH (pg/ml)
ADH and Plasma Osmolality in Central
DI with 5% Saline Infusion
10
Normal
5
Central DI
0
280
295
Posm (mmol/kg)
310
Urine Osmolality (mosm/kg)
ADH and Urine Osmolality in Nephrogenic
DI with 5% Saline Infusion
1000
500
Normal
Nephrogenic DI
0
0
5
10
Plasma ADH (pg/ml)
Nephrogenic DI

Normal ADH secretion, but renal
resistance to ADH activity

Gradual onset

Serum sodium tends to be > 142 mEq/L
Effect of ADH on Principle Cells
in the Collecting Ducts
Tubular
Lumen
ADH
V2 Receptor
cAMP
Aquaporin-2
H2O
PKC
PKA
H2O
Aquaporins-3 and 4
H2O
Hypertonic
Medulla
Figure 4
Causes of Nephrogenic DI








Hereditary X-linked V2 receptor defect
Hereditary AR Aquaporin-2 defect
Lithium toxicity
Hypercalcemia
Hypokalemia
Cidofovir and Foscarnet
Advanced age
Renal failure
Aquaporin-2 Excretion
Aquaporin-2 excretion is several-fold
higher in normals compared with those
with central DI
 Aquaporin-2 excretion increases with
exogenous ADH in patients with central
DI and not in patients with nephrogenic
DI

Treatment of Nephrogenic DI

Diuretics
» thiazides
» amiloride (lithium)


Low salt, low protein diet
NSAIDS
» prostaglandins normally antagonize ADH
activity

dDAVP
Water Clearance (L/day)
Relationship Between Solute
Intake and Urine Output
Solute intake
(mosm/day)
8
6
900
4
600
2
300
0
100
130
140
110
120
Urine Osmolarity (mosm/kg)
Case Presentation 3
47 year old female referred for polyuria. She
initially presented to her urologist for urinary
incontinence. A bladder neck suspension
was performed, and the patient was
subsequently found to have large post-void
residuals of 300-400 ml. She denied
nocturia, history of head trauma, and was on
no medications.
Case Presentation 3 Cont’d
Physical Exam Normal blood pressure and pulse. No
edema.
24 hr urine volume 5000 ml
Urine osm 178 mosm/kg
Serum
Sodium
141 Chloride
104
Potassium 4
CO2
26
BUN
10
Creat
0.8
Glucose
77
Osm
288
Case Presentation 3 Cont’d
Water Deprivation Test
Time
(hr)
0
1
2
3
4
Wt.
BP
UVol. Sosm Uosm
(lb)
(mmHg) (L)
(mosm/kg)
118
110/60 .15 285 335
118
98/65 .1 288 450
117
102/60 .125 289 550
117.5 102/70 .075 290 580
117.25 112/70 .1
297 600
ADH
(pg/ml)
< 2.5
< 2.5
Radioimmunoassay of ADH



Assay is cumbersome
High incidence of falsely low values
Sample preparation
»
»
»
»
»
»
Collect in chilled 7 ml EDTA tubes
Centrifuge 1000 g X 20 min
Freeze at -20oC
Extract in acetone and petrol-ether
Freeze at -80oC
Dessicate and store at -20oC
Mechanisms of Thirst Regulation
1. Cerebral cortex
Nonessential
drinking
Thirst
3. Hypothalamic
Osmoreceptors
2. Oropharnygeal
mechanoreceptors
Stimulated by imbibing large volumes
of water
Plasma ADH (pg/ml)
Osmotic Regulation of Thirst and
ADH Release
6
Thirst
3
0
275
280
290
285
Plasma Osmolality (mosm/kg)
295
Primary Polydipsia

Central defect in thirst regulation
» osmotic threshold thirst < ADH
» continue to drink until the plasma osm is
less than the threshold

Neuroleptic therapy
Treatment of Primary Polydipsia

Clozapine may correct the central
disturbance in thirst regulation

Limit use of drugs that cause dry mouth

ACE inhibitors
Urine and Plasma Osmolality in
Disorders of Water Balance
1000
Normal
Water
Deprivation
dDAVP
800
Primary polydipsia
600
Central DI
400
Nephrogenic DI
200
280
285
290
295
Posm(mosm/kg)
300
Case Presentation 4
29 y.o. female with a 31 week intrauterine
pregnancy admitted with a 2 week
history of polyuria and polydipsia. She
reported 6-8 liters of daily fluid intake
and voided urine every 30 minutes to an
hour.
Case Presentation 4 Cont’d
Physical exam BP 130/80, HR 150, trace
pretibial edema
24 hr urine volume 7000 ml
Urine osm 162 mosm/kg
Serum
Sodium
168
Potassium 3.6
BUN
5
Glucose
77
Chloride
CO2
Creat
133
21
2.8
Osm
348
Polyuria in Pregnancy

Vasopressinases are released from the
placenta resulting in a four-fold rise in
ADH catabolism
» May be treated with dDAVP which is
resistant to vasopressinase
» Polyuria often seen in patients with
decreased ADH secretory reserve

Central DI in Sheehan’s syndrome
Case Presentation 5
A 16 y.o. male was treated for the “flu” at
home. Despite improvement in his fever
and cough, worsening lethargy prompted
his mother to bring him to the E.R.
Physical Exam
Afebrile BP 140/85 no edema
Disoriented No focal neurologic deficits
Case Presentation 5 Cont’d
Laboratory data
24 hr urine volume 4000 ml
Urine osm 400 mosm/kg
Serum
Sodium
170
Potassium 3.9
BUN
8
Glucose
85
Chloride
CO2
Creat
128
29
0.8
Osm
360
Solute (Osmotic) Diuresis

Etiology
» Glucose
» High-protein feedings (urea)
» Expanded ECF volume
» Release of urinary tract obstruction
Urine osm > 300 mosm/kg
 Osmolar excretion > 900 mosm per day

Postobstructive Diuresis
Urine output after release of obstruction
may initially exceed 500-1000 ml/hr
 This solute diuresis is appropriate
 Administer normal replacement fluids
(e.g. 1/2 NS at 75 ml/hr)
 Replacing fluids at a rate greater than
replacement level will only exacerbate
the solute diuresis
