Diabetes insipidus & SIADH Flashcards
Two mechanisms that regulate body water balance
(1) Thirst
- Increased plasma osmolarity leads to increased thirst, higher CNS -> seek and drink water
- Loss of thirst (adipsia) can occur with hypothalamic damage
(2) ADH
- released from pituitary
- acts on kidney (V2 receptors)
- match urinary water loss to requirements
- inadequate ADH action = Diabetes insipidus
What are the 3 vasopressin receptors and their actions?
V1a
- via IP3 + Ca
- maintain blood volume and circulation
- role at high [ADH] concentrations
- expressed in vascular smooth muscle, heart
- effect - vasoconstriction
V1B
- via IP3 + Ca
- ?role in ACTH release and stress response
V2
- via cAMP
- appropriate retention of water, maintain osmolality
- expression: distal nephron (DCT2-CD, TAL)
- increased water permeability, increased NaCl, increased interstitial osmolality
What is Diabetes insipidus?
- deficiency of ADH action (hypotonic polyuria)
- inappropriately dilute urine & high urine volume
- may lead to hypernatraemia
What are the 3 causes of diabetes insipidus?
Cranial
Nephrogenic
Gestational
What is cranial DI?
- inadequate ADH release
- usually from pituitary or hypothalamic disease
- can follow surgical treatment for disease, head injury, intracranial infection, major hemorrhage (Sheehan’s syndrome), aneurysm
- Genetic: isolated AVP gene (AD, secondary loss of posterior pituitary cells) / DIDMOAD - DI, DM, optic atrophy, deafness
What is nephrogenic DI?
Renal insensitivity to ADH
- rarely congenital
Inherited:
- Majority - V2R - X-linked
- Others: AQP2 - chromosome 12
Usually acquired from:
- hyperCa, hypokalemia
- accompanying obstructive uropathy
- chronic renal failure
- treatment with lithium or demeclocycline
What is gestational DI?
Vasoressinases (produced by placenta)
- Degrade AVP, little effect on DDAVP
- Becomes a problem if a woman has deficiency in AVP
- Problem resolves 1 week post partum
What would be the result of a hypertonic saline test in someone with DI?
Normal - blood ADH rises
DI - blood ADH does not rise as steeply
What is the treatment for cranial DI?
Give DDAVP (peptide) - may be nasal, rhinal, tablets (desmopressin)
Long acting - can give just twice daily
More selective for renal V2R
SAME TREATEMENT FOR GESTATIONAL DI
REMEMBER to always treat other hypothalamo-pituitary deficiencies e.g. cortisol, thyroxine, sex steroids
What is the treatment for nephrogenic DI?
= Measures to decrease polyuria
- Thiazide (bendorfluazide) and/or amiloride diuretics paradoxically reduce urine output
- +/- indomethacin - lowers intrarenal prostaglandins (that oppose ADH) can limit urine volume
- Lower salt diet - lower urinary osmoles –> less urine lost
- lower protein diet
Treatment in partial DI?
Occasionally treatment which can promote SIADH are tried:
- Chlorpropamide may up regulate renal ADH receptors
Normal plasma Na levels
Plasma Na = 135-145 mmol/l
HyperNa - >145 mmol/l
HypoNa <135 mmol/l
What is an inappropriate Na loss in urine?
Possible causes
Urinary Na+ >20mmol/l
Possible causes:
- Adrenal insufficiency
- salt wasting renal disease
- diuretic excess
- hypomagnesaemia
Na loss may be from elsewhere e.g. GI tract, burns
When would a hyponatraemia be due to SIADH?
Consider if patient is neither dehydrated nor oedematous
- Demonstrate inappropriately concentrated urine (urine osmolality >500mosmol/l or >2x plasma osmolality) coexisting with hyponatreamie (Na <135 mmol/l) and/or low plasma osmolarity (<280 mosmol/l)
EXCLUDE adrenal and thyroid insufficiency.
What is the treatment for SIADH
- restrict fluid intake to 1l/day, then to 800ml if persisting
- occasionally demeclocyline is used (induces partial nephrogenic DI)
- Soon may be role for AVP receptor blockers - aquaretics e.g. tolvaptan - not for use >30 days, not in significant liver disease
care must be taken to avoid rapid correction of hyponatraemia and it is best if plasma Na+ rises towards normal range at <10mmol/l/day
How to investigate patient with polyuria
(1) document accurate fluid balance to determine if really polyuria (>2ml/kg/hour or 3l/day)
(2) Check glucose, Ca2+, urea and creatinine to identify osmotic diuresis or renal impairment
(3) Check urine never normally concentrated
- Random urine samples and early morning urine - urine osmolality <600 mosmol/kg
- if >600mosmol /kg –> exclude DI
(4) Water deprivation test - show if unable to concentrate urine
- Plasma osmolality and [Na+] rise as negative water balance
- DI if urine osmolality still <600 mosmol/kg when plasma osmolality >300 mosmol/kg or [Na] plasma>145 mmol/l
Possible causes of polyuria
DI (cranial or nephrogenic)
Habitual / psychogenic polydipsia
Osmotic diuresis - glucose, mannitol, hypercalcaemia
Renal impairment
Water deprivation test
- 12 hours to prior to test - can have fluids overnight and at breakfast
- during test (8 hours) - no fluids, only dry snacks
- patient supervised
- hourly weight, BP, urine samples (volume + osmolality)
- 2 hourly bloods - Na+, osmolality, +/- ADH
Stop test if urine osmolality reaches >600 or if danger (weight loss >3%, hypotensive, dizzy)
When water depleted (plasma osmolality >296 or [Na]>145 - give DDAVP
Symptoms of excess water loss
Collapse, confusion
BP decreases
Symptoms of excess water retention
Usually little symptoms initially.
Later [Na] and plasma osmolality fall
Confusion, drowsiness, nausea, fits
What is SIADH?
- concentrated urine and moderate body water excess with hyponatraemia
Caused
- Non-osmotic “appropriate release” - severe hypotension or hypovolaemia e.g. hemorrhage
- physiologically inappropriate excessive ADH release
Causes of SIADH
intracranial lesions/disease
intrathoracic disease - infections
neoplasms - esp. lung, mediastinal
Drugs
- antipsychotics - phenothiazines
- sedatives - morphine, barbiturates
- 5 C’s = chlorpropamide, clofibrate, chlorpromazine, carbamezapine, chlorthiazide
- Other thiazides - bendrofluazide
Nicotine
pain - esp. post-op
Severe ACTH or thyroid hormone deficiency
Possible causes:
HypoNa, dehydrated, Urine [Na+] >20 mmol/l
Renal Na+/ water loss
Addisons
Diuretic excess
Renal disease
Osmotic diuresis (glucose, Ca2+, urea)
Possible causes:
HypoNa, dehydrated, Urine [Na+] <20 mmol/l
Non-renal Na+/water loss
Gut losses - diarrhea, fistula, small bowel obstruction, villous cancer rectum
Skin: burns, trauma
Cystic fibrosis
Possible causes:
HypoNa, NOT dehydrated, oedematous
Oedematous disorder
Cardiac failure Liver failure (nephrotic syndrome)
Possible causes:
HypoNa, NOT dehydrated, NOT oedematous
Urine osmolality >2x plasma osmolality or >500 mmol/l
SIADH
Possible causes:
HypoNa, NOT dehydrated, NOT oedematous
Urine osmolality NOT >2x plasma osmolality or >500 mmol/l
Non - SIADH retained water excess
Low GFR
ACTH/GC deficient
Severe hypothyroidism
