Diabetes insipidus & SIADH Flashcards

1
Q

Two mechanisms that regulate body water balance

A

(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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the 3 vasopressin receptors and their actions?

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is Diabetes insipidus?

A
  • deficiency of ADH action (hypotonic polyuria)
  • inappropriately dilute urine & high urine volume
  • may lead to hypernatraemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the 3 causes of diabetes insipidus?

A

Cranial
Nephrogenic
Gestational

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is cranial DI?

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is nephrogenic DI?

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is gestational DI?

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What would be the result of a hypertonic saline test in someone with DI?

A

Normal - blood ADH rises

DI - blood ADH does not rise as steeply

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the treatment for cranial DI?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the treatment for nephrogenic DI?

A

= 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Treatment in partial DI?

A

Occasionally treatment which can promote SIADH are tried:

- Chlorpropamide may up regulate renal ADH receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Normal plasma Na levels

A

Plasma Na = 135-145 mmol/l

HyperNa - >145 mmol/l
HypoNa <135 mmol/l

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is an inappropriate Na loss in urine?

Possible causes

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

When would a hyponatraemia be due to SIADH?

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the treatment for SIADH

A
  • 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 well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How to investigate patient with polyuria

A

(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

17
Q

Possible causes of polyuria

A

DI (cranial or nephrogenic)

Habitual / psychogenic polydipsia

Osmotic diuresis - glucose, mannitol, hypercalcaemia

Renal impairment

18
Q

Water deprivation test

A
  • 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

19
Q

Symptoms of excess water loss

A

Collapse, confusion

BP decreases

20
Q

Symptoms of excess water retention

A

Usually little symptoms initially.

Later [Na] and plasma osmolality fall
Confusion, drowsiness, nausea, fits

21
Q

What is SIADH?

A
  • 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
22
Q

Causes of SIADH

A

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

23
Q

Possible causes:

HypoNa, dehydrated, Urine [Na+] >20 mmol/l

A

Renal Na+/ water loss

Addisons
Diuretic excess
Renal disease
Osmotic diuresis (glucose, Ca2+, urea)

24
Q

Possible causes:

HypoNa, dehydrated, Urine [Na+] <20 mmol/l

A

Non-renal Na+/water loss

Gut losses - diarrhea, fistula, small bowel obstruction, villous cancer rectum

Skin: burns, trauma

Cystic fibrosis

25
Q

Possible causes:

HypoNa, NOT dehydrated, oedematous

A

Oedematous disorder

Cardiac failure
Liver failure (nephrotic syndrome)
26
Q

Possible causes:
HypoNa, NOT dehydrated, NOT oedematous

Urine osmolality >2x plasma osmolality or >500 mmol/l

A

SIADH

27
Q

Possible causes:
HypoNa, NOT dehydrated, NOT oedematous

Urine osmolality NOT >2x plasma osmolality or >500 mmol/l

A

Non - SIADH retained water excess

Low GFR
ACTH/GC deficient
Severe hypothyroidism