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WATER METABOLISM

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Title: WATER METABOLISM


1
WATER METABOLISM
Unregulated food social drink Insensible
and obligate loss
Regulated thirst AVP modulated water
output
2
THIRST
  • Hyperosmolar stimulus
  • hypothalamic osmoreceptors
  • threshold 1 to 4 above basal
  • Hypovolaemic stimulus
  • baroreceptors
  • threshold 10 - 15
  • ? absent in man (inconvenient with postural
    change!)
  • Normally inactive as unregulated input is in
    excess

3
BASAL
4
AVP secretion
  • Synthesized in hypothalamic SON and PVN nuclei
  • Stored and released from posterior pituitary (gt 1
    week store!)
  • Interacts via V2 receptors to insert aquaporin-2
    water channels
  • Osmolar threshold within normal range
  • High gain (i.e steep curve and high renal
    sensitivity)

5
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6
AVP secretion
  • Osmotic stimulus high sensitivity
  • Hypovolaemic stimulus high threshold (gt10)

7
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8
AVP secretion
  • Osmotic stimulus high sensitivity
  • Hypovolaemic stimulus high threshold (gt10)
  • Nausea most powerful known
  • Stress e.g. post-operative
  • Drugs SIADH

9
INTEGRATION OF THIRST AND AVP
  • Unregulated water intake supplies water in excess
    of need
  • Excess water is excreted
  • AVP secretion regulates free water clearance
  • AVP maintains osmolality within narrow limits
  • This avoids inconvenient thirst and
    water-seeking behaviour
  • Thirst kicks-in when deficiency reaches harmful
    levels

10
DIFFERENTIAL DIAGNOSIS OF HYPONATRAEMIA
HYPONATRAEMIA
Pseudo- hyponatraemia
YES
Lipaemia / hyperproteinaemia ?
NO
Compensatory hyponatraemia
Hyperglycaemia ?
YES
NO
Volume expanded
Volume depleted
Total body water
Renal loss
Extra-renal loss
No oedema
Oedema
Diuretics Addisons
Vomiting Diarrhoea
SIADH Hypothyroid
Nephrotic Cirrhosis CCF
UNa
gt20
lt10
lt10
gt20
Rx
Normal saline
Fluid restriction
11
Causes of hyponatraemia
HYPONATRAEMIA
Pseudo- hyponatraemia
YES
Lipaemia / hyperproteinaemia ?
NO
Compensatory hyponatraemia
Hyperglycaemia ?
YES
NO
Volume expanded
Volume depleted
Total body water
Renal loss
Extra-renal loss
No oedema
Oedema
Diuretics Addisons
Vomiting Diarrhoea
SIADH Hypothyroid
Nephrotic Cirrhosis CCF
UNa
gt20
lt10
lt10
gt20
Rx
Normal saline
Fluid restriction
12
Causes of hyponatraemia
HYPONATRAEMIA
Pseudo- hyponatraemia
YES
Lipaemia / hyperproteinaemia ?
NO
Compensatory hyponatraemia
Hyperglycaemia ?
YES
NO
Volume expanded
Volume depleted
Total body water
Renal loss
Extra-renal loss
No oedema
Oedema
Diuretics Addisons
Vomiting Diarrhoea
SIADH Hypothyroid
Nephrotic Cirrhosis CCF
UNa
gt20
lt10
lt10
gt20
Rx
Normal saline
Fluid restriction
13
Case 1
  • A 58-year old man presented with a history of
    general malaise and a persistant painful cough of
    three months duration
  • Serum
  • Sodium 116 mmol/L
  • Potassium 3.4 mmol/L
  • Urea 9.4 mmol/L
  • Bilirubin 12 umol/L
  • Alk phos 95 U/L
  • ALT 23 U/L
  • Albumin 20 g/L
  • Total protein 120 g/L

14
Causes of hyponatraemia
HYPONATRAEMIA
Pseudo- hyponatraemia
YES
Lipaemia / hyperproteinaemia ?
NO
Compensatory hyponatraemia
Hyperglycaemia ?
YES
NO
Volume expanded
Volume depleted
Total body water
Renal loss
Extra-renal loss
No oedema
Oedema
Diuretics Addisons
Vomiting Diarrhoea
SIADH Hypothyroid
Nephrotic Cirrhosis CCF
UNa
gt20
lt10
lt10
gt20
Rx
Normal saline
Fluid restriction
15
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16
Case 3
  • A 66-year old man was admitted for investigation
    of possible bronchogenic carcinoma
  • Serum Ref range
  • Sodium 121 mmol/L 133 143
  • Potassium 4.1 mmol/L 3.6 4.6
  • Urea 4.4 mmol/L 3.0 7.0

17
Case 3
  • A 66-year old man was admitted for investigation
    of possible bronchogenic carcinoma
  • Serum Ref range
  • Sodium 121 mmol/L 133 143
  • Potassium 4.1 mmol/L 3.6 4.6
  • Urea 4.4 mmol/L 3.0 7.0
  • Glucose 5.2 mmol/L

18
Case 3
  • A 66-year old man was admitted for investigation
    of possible bronchogenic carcinoma
  • Serum Ref range
  • Sodium 121 mmol/L 133 143
  • Potassium 4.1 mmol/L 3.6 4.6
  • Urea 4.4 mmol/L 3.0 7.0
  • Glucose 5.2 mmol/L
  • Osmolality 250 mmol/Kg 275 - 295
  • Urine
  • Osmolality 614 mmol/Kg

19
SYNDROME OF INAPPROPRIATE ADH
  • Hyponatraemia is very common
  • up to15 hospitalised patients
  • affects 50 of nursing home residents each year
  • gt30 acutely ill nursing home patients have
    hyponatramia
  • SIADH accounts for about 50 of all chronic
    hyponatraemias

20
SYNDROME OF INAPPROPRIATE ADH
  • Bartter and Schwartz criteria (1967)
  • hyponatraemia with hypotonicity of plasma
  • urine osmolality inappropriately high
  • ongoing renal sodium excretion
  • absence of oedema or volume depletion
  • normal renal and adrenal function
  • i.e. normovolaemic hyponatraemia

21
SYNDROME OF INAPPROPRIATE ADH
Symptoms relate to rate of fall as well as
severity
  • Sodium lt120 mmol/L
  • Lethargy
  • Anorexia
  • Nausea and vomiting
  • Irritability
  • Headache
  • Muscle weaknes
  • Cramps
  • Sodium lt110 mmol/L
  • Drowsiness
  • Confusion
  • Depressed reflexes
  • Extensor plantar responses
  • Seizures
  • Coma
  • Death

No oedema because water distributed in both
compartments
22
SIADH - pathogenesis
  • Inappropriately high AVP levels
  • Ongoing (unregulated) water intake
  • Blood volume rises
  • gt10 expansion inhibits aldosterone and triggers
    natriuresis

23
Causes of SIADH
  • Neoplasia
  • Carcinoma of lung, pancreas, bladder
  • Leukaemia
  • Thymoma
  • Lymphoma
  • Sarcoma
  • Mesothelioma
  • Neurological disorders
  • Meningitis
  • Encephalitis
  • Brain tumour
  • Subarachnoid haemorrhage
  • Cerebral and cerebellar atrophy
  • Guillain-Barré syndrome
  • Acute intermittent porphyria
  • Shy-Drager syndrome
  • Head injury
  • Lung disease
  • Pneumonia
  • TB
  • Pneumothorax
  • Asthma
  • IPPV

24
Causes of SIADH
  • Drugs
  • Vasopressin
  • Oxytocin
  • Vinca alkaloids
  • Cisplatin
  • Chlorpropamide
  • Carbamazepine
  • Phenothiazines
  • Thiazides
  • MAOIs
  • SSRIs
  • Tricyclics
  • Nicotine
  • Ecstacy
  • Miscellaneous
  • Acute psychosis
  • Post-operative state
  • AIDS
  • Glucocorticoid deficiency
  • Severe hypothyroidism
  • Idiopathic

25
The impact of ageing on water metabolism
  • Rise in osmotic sensitivity of ADH release
  • Delayed ability to excrete water load
  • Thirst mechanism diminishes
  • Decrease in maximal urinary concentrating ability
  • Decreased renal mass
  • Impaired responsiveness to sodium balance
  • Multiple drug therapy
  • A lifetime of accumulated disease and
    comorbidities

26
The impact of ageing on water metabolism
  • Rise in osmotic sensitivity of ADH release
  • Delayed ability to excrete water load
  • Thirst mechanism diminishes
  • Decrease in maximal urinary concentrating ability
  • Decreased renal mass
  • Impaired responsiveness to sodium balance
  • Multiple drug therapy
  • A lifetime of accumulated disease and
    comorbidities

27
Patterns of AVP release in SIADH
28
Diagnosis of SIADH
  • Essential criteria
  • True plasma hypo-osmolality (lt275 mOsm/Kg)
  • Inappropriate urine osmolality (gt100 mOsm/Kg)
  • Euvolaemia no oedema, ascites or intravascular
    hypovolaemia
  • Urine sodium not low (gt30 mmol/L during normal
    intake)
  • Normal renal, adrenal, and thyroid function
  • Supplemental criteria
  • Low serum urea and urate
  • Unable to excrete gt80 of water load (20mL/Kg) in
    4h and/or failure to achieve urine osmolality
    lt100 mOsm/Kg
  • No significant rise in serum Na after volume
    expansion but improvement with fluid restriction

29
Treatment of SIADH
  • Identification and treatment of underlying cause
  • Clearance of excess water
  • not necessary in asymptomatic chronic
    hyponatraemia
  • fluid restriction to 500 - 1000 mL/24h
  • Demeclocycline
  • 600 to 1,200 mg daily
  • may take three weeks to reach maximal effect
  • caution in renal or hepatic insufficiency
  • Specific V2 receptor antagonists (OPC-31260)

30
Treatment of SIADH
  • Hypertonic saline
  • Only if significantly symptomatic or duration lt3
    day
  • Calculate sodium required
  • Na req. (mmol) (125 Na) x 0.6 x body
    weight (kg)
  • Also measure and re-infuse urinary sodium output
  • Rate of increase not usually gt0.5 mmol/L/h
  • ? combine with i.v. furosemide
  • Stop saline when sodium reaches 120 - 125 mmol/L

31
Treatment of SIADH
Na req. (mmol) (125 Na) x 0.6 x body
weight (kg)
  • Example symptomatic patient with sodium 105
    mmol/L
  • Body weight 60 Kg
  • Available hypertonic saline 2.7 (3 normal)
  • Sodium requirement (125-105) x 0.6 x 60 720
    mmol
  • 2.7 saline Na 462 mmol/L
  • Correction at 0.5 mmol/L/hr ? correction over 25
    hrs
  • 2.7 saline requirement 720/462 L 1.56 L
  • Infusion rate 1.56/25 62 mL/hr (plus extra for
    ongoing urinary Na output)

32
Other causes of euvolameic hyponatraemia
  • Psychogenic hyponatraemia
  • Massive water intake (20 - 30 L/day)
  • Urine osmolality lt100 mOsm/kg
  • Beer-drinkers potomania
  • High volume low solute drinks impair ability to
    excrete water
  • Hypothyroidism
  • Reset osmostat
  • Pure glucocorticoid deficiency
  • Cortisol is required for renal free water
    excretion

33
Cerebral salt wasting
  • SIADH
  • 1º increase in AVP
  • Inappropriate urine hyperosm.
  • Volume-expansion
  • Suppressed aldosterone
  • Appropriate natriuresis
  • Decreased urea and urate
  • Treatment fluid restriction
  • CSW
  • Cerebral damage
  • Reduced SNS efferents /- BNP
  • Inappropriate natriuresis
  • Volume-depletion
  • Volume mediated AVP release
  • Appropriate urine hyperosm.
  • Treatment Normal saline infusion

34
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35
Case 4
  • A 53-year old bachelor was brought to the AE
    department having been found semi-comatose. He
    was known to be a heavy drinker of alcohol. On
    examination he was jaundiced. His abdomen was
    distended there was hepatomegaly and evidence of
    ascites. He had ankle oedema.
  • Serum Ref range
  • Creatinine 84 µmol/L 75 120
  • Urea 10.0 mmol/L 3.0 7.0
  • Sodium 111 mmol/L 133 143
  • Potassium 4.9 mmol/L 3.6 4.6
  • Bilirubin 166 µmol/L lt 17
  • Alk phos 175 U/L 21 - 92
  • ALT 450 U/L 5 40
  • Albumin 24 g/L 35 55
  • Total protein 72 g/L 62 80
  • Globulin 48 g/L 22 - 36

36
Oedematous hyponatraemia
  • Splanchnic arterial underfilling / vasodilatation
  • ?
  • Non-osmotic release of AVP
  • ?
  • Impaired renal water retention
  • ?
  • Dilutional hyponatraemia
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