water balance and vasopressin disorders Flashcards
What does the brain monitor to maintain water balance?
Body fluid osmolality (osmostat)
This monitoring leads to appropriate thirst and vasopressin release.
What is Vasopressin also known as?
Anti-diuretic Hormone (ADH)
It is made in the hypothalamus and released from the posterior pituitary.
What is the primary action of Vasopressin?
Reabsorb water and concentrate urine
This action is mediated through V2 receptors in the kidneys.
What are the two types of Vasopressin Deficiency?
- Vasopressin Deficiency (VpD) in pituitary/hypothalamus (Cranial Diabetes Insipidus)
- Vasopressin Resistance (VpR) in kidney (Nephrogenic Diabetes Insipidus)
What results from Vasopressin Deficiency or Resistance?
Deficient water reabsorption and excessive urine volume (polyuria)
This leads to dilute urine (insipid) and excess water wasting.
What does SIADH stand for?
Syndrome of Inappropriate ADH
It results in excessive water reabsorption and concentrated urine.
What are the clinical consequences of excessive Vasopressin action?
- Excess water retention
- Dilute body fluids
- Low plasma sodium (hyponatraemia)
What is the normal water intake for an adult in a temperate climate?
0.9 to 2-2.5 litres
This intake is necessary to match urinary losses.
What is a cause of excessive water loss leading to polyuria?
Vasopressin Deficiency or Resistance
Other causes may include primary polydipsia or osmotic diuresis.
What is the definition of polyuria?
Passing excessive urine volumes, defined as >2ml/kg/hr
For a 70kg person, this equates to >3.36 litres.
What are the key components needed for proper ADH function?
- Adequate ADH production
- Kidney responsive to ADH
- Effective feedback stopping ADH release
What can cause loss of thirst (adipsia)?
Hypothalamic damage
This condition can be difficult to treat.
What are the roles of V1 and V2 receptors for Vasopressin?
- V1a: Vasopressor effects, maintain blood volume
- V2: Appropriate water retention, maintain osmolality
What factors can stimulate non-osmotic release of Vasopressin?
- Low blood pressure
- Low extracellular fluid volume
- Pain
- Nausea
What is the effect of excessive water retention on plasma sodium levels?
It leads to low plasma sodium (hyponatraemia)
This can cause symptoms like confusion, drowsiness, and nausea.
What is the normal range for plasma sodium levels?
135-145mmol/L
A level of 140 ± 5 is considered normal.
What is the significance of the osmostat in water balance?
It drives thirst and ADH release in response to body fluid osmolality changes.
What is the action of Vasopressin on the distal nephron?
Increases water permeability and apical AQP2 expression
This enhances water reabsorption.
What is the clinical presentation of polyuria due to Vasopressin Deficiency?
Inappropriate high urine output and persistent thirst
This can lead to negative fluid balance.
What is the role of the thirst center in the hypothalamus?
It integrates signals to drive water intake when body water is low.
What physiological condition can lead to hypernatraemia?
Inadequate fluid intake due to loss of thirst
This is particularly dangerous in severe cases.
What are the consequences of high insensible losses of water?
Increased risk of hypernatraemia
This is especially a concern for individuals in extreme conditions.
What is the impact of renal impairment on polyuria?
It can lead to inappropriately high urine output
This is considered unusual.
What are the key steps in the investigation of polyuria?
- Accurate fluid balance and plasma [Na+]
- Check glucose, urea, eGFR, K+, Ca2+
- Distinguish between Vasopressin Deficiency/Resistance and primary polydipsia
What are the two primary causes of polyuria?
- Vasopressin Deficiency/Resistance (VpD/VpR)
- Primary polydipsia
What is osmotic diuresis?
A condition caused by substances like glucose leading to increased urine output
What is the urine volume threshold for polyuria diagnosis?
Urine volume >2ml/kg/hr
What plasma sodium concentration indicates potential polyuria?
[Na+] > 145mmol/L
What is the significance of urine osmolality >600mosmol/kg?
Excludes Vasopressin Deficiency/Resistance (VpD/VpR)
What does a water deprivation test assess?
Ability to concentrate urine and diagnose Vp disorders (VpD/VpR)
What is the dosage of DDAVP used in diagnosis?
2µg IM
If urine osmolality rises >600mosmol/kg after DDAVP, what does this indicate?
Vasopressin Deficiency (VpD)
If urine osmolality remains <600mosmol/kg after DDAVP, what does this indicate?
Vasopressin Resistance (VpR)
What is Copeptin used for in the investigation of Vp disorders?
To differentiate between VpD and VpR
What Copeptin level indicates Vasopressin Resistance?
[Copeptin] >21.4 pmol/L
What Copeptin level suggests Vasopressin Deficiency?
[Copeptin] <4.9 pmol/L
List some acquired causes of Vasopressin Resistance (VpR)
- Hypercalcaemia
- Hypokalaemia
- Secondary effect of psychogenic polydipsia
- Lithium therapy
- Demeclocycline
What are some inherited causes of Vasopressin Resistance (VpR)?
- V2R mutations (X-linked)
- AQP2 mutations (Autosomal Recessive or Dominant)
What is the first line treatment for Vasopressin Deficiency (VpD)?
Desmopressin (DDAVP)
What should be treated in cases of Vasopressin Resistance (VpR)?
Underlying causes such as electrolyte imbalances or medication effects
What is the consequence of chronic hyponatraemia treatment?
Must be normalized slowly ([Na+] <8-10mmol/l/day)
What are the major categories of causes for SIADH?
- Intracranial lesions/disease
- Intrathoracic disease
- Neoplasms
- Drugs
What is the treatment approach for SIADH?
- Fluid restriction
- Increase solute intake
- Hypertonic saline (if urgent)
What is the role of vasopressin-antagonists in the treatment of SIADH?
New treatment options for managing hyponatraemia
What is the initial fluid restriction for treating hyponatraemia?
1000ml/d, then < 800ml/d if needed
What may be increased to help treat hyponatraemia?
Solute intake, such as salt supplements
What is a potential intravenous treatment for urgent moderate hyponatraemia?
Hypertonic saline
How must chronic hyponatraemia be normalized?
Slowly, with [Na+] < 8-10mmol/l/day
What rare treatment may be used for hyponatraemia?
Demeclocycline
What are the new options for treating hyponatraemia mentioned?
Vasopressin-antagonists: ‘vaptans’
What is an example of an aquaretic drug?
Tolvaptan
What are combined V2-V1a antagonists used for?
Treatment of SIADH, heart failure, etc.
What was the outcome of early trials of aquaretics?
Follow-up for 2+ years (Saltwater trial)
What effect does Tolvaptan have on chronic SIADH?
It successfully lowers Na+
What condition makes it harder to treat low sodium levels?
Cirrhosis
What effect did Tolvaptan have on the decline in GFR in PKD?
Reduced the rate of decline by over 30%
For how long is Tolvaptan approved for use?
Not for use >30 days
What percentage of patients experienced deranged liver function tests on Tolvaptan?
4.9% vs. 1.2%
What is the definition of hyponatraemia?
[Na+] < 135 mmol/L
What indicates renal Na+/water loss?
Urine [Na+] > 20 mmol/L
What conditions can cause renal Na+/water loss?
- Addison’s
- Diuretic excess
- Renal disease (salt wasting)
- Osmotic diuresis (glucose, Ca2+, urea)
What are non-renal causes of Na+/water loss?
- Gut losses (diarrhoea, fistula, small bowel obstruction, villous Ca rectum)
- Skin (burns, trauma)
- Cystic fibrosis
What indicates an oedematous disorder?
Yes, the patient is oedematous
What conditions are associated with oedematous disorders?
- Cardiac Failure
- Liver Failure
- Nephrotic syndrome
What does πu > 2x πp indicate?
SIADH
What is a condition that can lead to ‘non SIADH retained water excess’?
Low GFR
What deficiency can cause severe hyponatraemia?
ACTH/GC deficiency
What hormonal deficiency can also contribute to severe hyponatraemia?
Severe hypothyroidism
