POLYURIA
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Dr M du Plessis
Dept of Chemical Pathology
February 2002
1. DEFINITION OF POLYURIA:
 Polyuria is defined as a urinary volume >3 l/day or >4 m/lmin.
2. ANTIDIURETIC HORMONE (ADH):
 Arginine vasopressin.
 Synthesized and secreted: supraoptic and paraventricular
nuclei hypothalamus
 Stored in posterior pituitary lobe.
2.1 REGULATION OF SECRETION OF ADH:
1. Tonicity (Osmolality):
 Osmoreceptors (anterior HT) (changes of 1-2%)
 Direct relationship:  osmol   ADH
 osmol  ADH
 Osmotic threshold for ADH release > 280 mosmol/kg
2. Circulating blood volume:
 Baroreceptors (responds to changes in IVV > 10%)
 Inverse log-linear relationship:  IVV   ADH
 IVV   ADH
 Baroreceptors can override osmoreceptors in severe
hypovolemia (maintenance of IVV at expense of osmol
( IVV precedence over  osmol).
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3. Other non-osmotic stimuli for ADH release:
 Pain, stress, sleep, exercise
 Chemical stimuli: catecholamines, angiotensin II, opiates,
PG’s, anesthetics, nicotine, barbiturates.
4. Other non-osmotic inhibitors of ADH release:
 ANP (negative feedback during  IVV,  osmol)
 Alcohol, phenytion, glucocorticoids.
5. Thirst centre:
 Regulated by the same factors as ADH.
 Higher osmotic threshold of 290 mosmol/kg.
Responses involving ADH, thirst and the kidney are coordinated to
maintain plasma osmol within a narrow range (284-295
mosmol/kg).
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2.2 PHYSIOLOGICAL ACTIONS:
1. Regulation of water reabsorption by kidney and
concentration of urine:
 Normal urine concentration dependent on:
o ADH action ( AQP 2 channels in collecting tubules)
o Countercurrent mechanism responsible for
maintenance of concentration gradient.
2. Vasopressin: vasoconstriction and  BP
3. Augments action of CRH in stimulating ACTH-release
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3. DIFFERENTIAL DIAGNOSIS OF POLYURIA:
3.1
Water diuresis:
3.1.1 Water diuresis with intact ADH:
Overhydration with isotonic fluid (postoperatively/
resuscitation)  physiologically appropriate free water
diuresis.
3.1.2 Water diuresis without intact ADH:
Decreased ADH secretion/action = Diabetes insipidus
3.1.3 Psychogenic /primary polydipsia:
Chronic, excessive intake of water suppressing ADH
secretion and leading to washout of medullary solutes.
3.2
Osmotic diuresis:
Increased amounts of osmotically active material causing
diuresis:
3.2.1.Hyperglycemia (DM)
3.2.2 Myoglobinuria
3.2.3 Administration of mannitol or IV contrast
3.2.4 Renal tubular injury (CRF, postobstructive nephropathy,
post-ATN) ( urea)
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4. DEFINITION OF DIABETES INSIPIDUS:
Absence of an ADH effect causes:
 Failure to produce a maximally concentrated urine
 Polyuria and polydipsia
 Hypernatremia and hyperosmolality will develop when fluid
intake does not match losses ( mental alertness -  ability
to sense thirst or obtain access to fluids).
5. ETIOLOGY OF DIABETES INSIPIDUS:
5.1
Hypothalamic diabetes insipidus (HDI): (neurogenic,
central, cranial DI)
 Decreased ADH secretion.
 Destruction of 80% of ADH-secreting neurons required
for HDI.
 Causes:
i. Acquired: Hypothalamic disease: neoplastic
diseases, trauma, surgery, ischemia, infections,
granulomatous diseases.
ii. Hereditary: autosomal dominant trait.
iii. Idiopathic: 30%
 Importance in anaesthetic setting:
i. Emergencies in patients with established DI
ii. DI following neurosurgical procedures
iii. DI in the posttrauma setting
5.2
Nephrogenic diabetes insipidus (NDI) :
 Defective ADH action in the kidney (due to a defect in the
ADH receptor or AQP2 water channel).
 Causes:
i.
Hereditary: X-chromosome linked trait
ii.
Acquired:
 Metabolic disorders: Hypokalemia,
hypercalcemia, amyloidosis
 Drugs: Lithium, demeclocycline, barbiturates
 Renal diseases: Polycystic diseases, CRF.
iii.
Idiopathic.
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6. LABORATORY EVALUATION OF POLYURIA:
6.1 Determination of Serum and urine osmol and UKE.
 U-Osmol:
o Osmotic diuresis: U-osmol similar to serum ( 50
mosm/kg)
o Water diuresis (+/- intact ADH): U-osmol < 200
mosm/kg
 S-Na and S-Osmol:
o Water diuresis with intact ADH: S-Na and S-Osmol
normal/
o Water diuresis with defective ADH: S-Na and S-Osmol
normal/
6.2 Exclude osmotic diuresis:
P-Glucose
S-Urea
S/U-Myoglobin
6.3 Water deprivation test:
6.3.1 Indications:
o If DI is suspected in a patient with normal S-Na and
Osmol (to exclude water diuresis due to fluid
overload/PP)
o Hypernatremia ( 145 mmol/l) and hyperosmolality
( 295 mosm/kg) in the presence of polyuria
confirms the diagnosis of DI, and obviates the
need for performing a water deprivation test.
6.3.2 Criteria for interpretation:
o Normal ADH with fluid overload/PP:
 N S-Na and S-Osmol (< 295 mosm/kg)
 Concentrated U-Osmol (> 400 mosm/kg) (often
> 850 mosm/kg)
 Ratio of U/S-Osmol > 1.5
o DI:
  S-Na (>145 mmol/l) and S-Osmol (> 295
mosm/kg)
 U-Osmol  400 mosm/kg (often < 200)
 Ratio U/S Osmol < 1.5 (often < 1)
 Response to DDAVP:
 HDI: Increase in U-Osmol  10% (often >
50%)
 NDI: Increase in U-Osmol < 10%
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7. TREATMENT OF DI:
7.1 Fluids:
 Hypernatremia and hyperosmolality develop if inability to
maintain oral fluid intake.
 Preferred fluid for IV use: dextrose in water (hypotonic)
 Inappropriate fluid: Normal saline  added renal solute load 
 osmotic diuresis and dehydration.
7.2 DDAVP: (1-desamino 8-D-arginine vasopressin)
 Analogue with
  duration of action (6-24 h)
  pressor and uterotonic effects
  antidiuretic properties.
 Administration:
 parenteral (IV/IM/SC): 1-2 ug
 intranasally: 10-20 x parenteral dose (metered dose spray of
10ug).
7.3 ARGININE VASOPRESSIN:
 Significant pressor and uterotonic activity, in addition to
antidiuretic effects.
 Administration:
 Continuous infusion: short duration of action allows safe
management of rapid fluctuations in osmol.
 Dosage: 1-2 mU/kg/hour
CARE MUST BE TAKEN NOT TO CONTINUE EXCESS
HYPOTONIC FLUID WHILE PRODUCING ANTIDIURESIS WITH
DDAVP  HYPONATREMIA:
 Measure hourly urine output and osmolality.
 Allow some return of hypotonic polyuria before readministering
DDAVP.
 Be aware of syndrome of triphasic diabetes insipidus.
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8. TRIPHASIC DIABETES INSIPIDUS:
(Following neurosurgical procedures or head trauma)
8.1 FIRST PHASE: Diabetes insipidus:
 Hours to days after injury
 Impaired ADH release due to axonal shock (not neuron death)
8.2 SECOND PHASE: Inappropriate antidiuresis:
 2-14 days post-injury
 Uncontrolled vasopressin release due to leakage out of
damaged neurons
 HYPONATREMIA if high fluid intake continues
8.3




THIRD PHASE: Diabetes insipidus:
After 14 days
ADH deficiency recurs as neuronal granules are depleted
Temporary or prolonged
Depending on proximity of lesion to neuronal cell body.
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CONCLUSION:
The abrupt onset of hypertonic polyuria and hypernatremia, in the
post-neurosurgery or posttrauma setting, may reflect new onset DI.
Established DI becomes an emergency and leads to severe
hyperosmolality and dehydration when there is impairment in
mental status (eg due to anaesthesia) that precludes compliance
with a previous medical regimen and impairs the ability to sense
and act on thirst.
Postoperative patients, especially after neurosurgery or head
trauma, are at particular risk of complicated DI.
Correct and prompt diagnosis and appropriate treatment are of
equal importance in prevention of complications.
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LABORATORY EVALUATION OF POLYURIA:
POLYURIA
U-Osmol
U-Osmol ~ S-Osmol
( 50) (ratio ~ 1)
U-Osmol < 200
S-Na
S-Osmol
Water
diuresis
due to
fluid
overload
Normal
after fluid
deprivation
 S-Na (> 145)
S-Osmol (>295)
U/S-Osmol < 1.0
N S-Na
S-Osmol
Fluid
deprivation
N S-Osmol + Na
U-Osmol > 400
U/S-Osmol > 1.5
Normal
Fluid
Overload
 S-Osmol + Na
U-Osmol  400
U/S-Osmol < 1.0
Dx of DI
P-Glucose
DM
S-Urea
Renal disease
Mioglobin
Mioglobinuria
DDAVP
Response:
HDI
No response:
NDI