L10 - Physiology of thirst and fluid balance and its disorders Flashcards
Featured hormones in the physiology of thirst and fluid balance
- Anti-diuretic hormone (ADH)
- Arginine vasopressin (AVP)
Examples of pathophysiology - thirst and fluid balance
- Polyuria and polydipsia - diabetes insipidus
- Hyponatraemia - syndrome of inappropriate ADH secretion (SIADH)
Why is regulation of water balance important
- Regulation of water balance ensures plasma osmolality(and extracellular fluid osmolality) remains stable
- Narrow range of plasma osmolality - 285-295 mosmol/kg
3 key determinants involved in the regulation of water balance
- Antidiuretic hormone - osmotically stimulated secretion
- Kidney - wide variation in urine output (0.5-20 L/day)
- Thirst - osmoregulated, stimulates fluid intake
What are osmoreceptors
- Groups of specialised cells which detect changes in plasma osmolality (esp sodium)
Location of osmoreceptors
- Located in the anterior wall of 3rd ventricle
- Fenestrations in the blood-brain barrier allow circulating solutes(osmoles) to influence brain osmoreceptors
What do osmoreceptors respond to
- Osmoreceptor cells alter their volume by a transmembrane flux of water in response to changes in plasma osmolality
- This initiates neuronal impulses that are transmitted to the hypothalamus to synthesise ADH, and to the cerebral cortex to register thirst
What is arginine vasopressin
- Human form of ADH
- Nonapeptide - 9 amino acid peptide
Where is vasopressin synthesised
- In neurons in supraoptic and paraventricular nuclei of the hypothalamus
- Secretory granules migrate down axons to posterior pituitary from where AVP is released ww
Where are AVP and copeptin released
- AVP and copeptin are released into capillaries of the portal system that transport copeptin to the anterior pituitary
Where are AVP and copeptin stored
- AVP and copeptin storage occurs in axons in the posterior pituitary
What does AVP stimulate the release of
- AVP stimulates endocrine cells to release ACTH from anterior pituitary
Receptors that mediate ADH action in the kidney
- V2 receptors
Where are ADH-sensitive water channels (aquapprins) normally stored
- In cytoplasmic vesicles, moves to and fuses with the luminal membrane
Effect of ADH
- Increases water permeability of renal collecting tubules, promoting water reabsorption
- When ADH cleared, water channels removed from the luminal surface (endocytosis) and returned to cytoplasm
Effects of low plasma osmolality on osmoregulation
- AVP undetectable
- Dilute urine
- High urine output
- No thirst
Effects of high plasma osmolality on osmoregulation
- High AVP secretion
- Concentrated urine
- Low urine output
Effect of high osmolality on thirst
- Increased thirst sensation
- Drinking immediately transiently suppresses AVP secretion and thirst (avoids overshoot)
Relationship between plasma AVP and plasma osmolality/urine osmolality
- Direct correlation
- Plasma vasopressin levels increase with plasma osmolality
Link between urine osmolality and plasma vasopressin levels
- Urine osmolality increases with plasma vasopressin levels
Three other main causes of polyuria and polydipsia
- Cranial (central) diabetes insipidus (DI) - lack of osmoregulated AVP secretion
- Nephrogenic diabetes insipidus (DI) - lack of response of the renal tubule to AVP
- Primary polydipsia - psychogenic polydipsia, social/cultural
All may be ‘partial’
What is primary polydipsia
Is characterised by excessive fluid intake in the absence of physiological stimuli to drink
- Driven by primary stimulation of the thirst centre in the hypothalamus
What is diabetes insipidus
Diabetes insipidus (DI) is caused by a problem with either the production, or action, of the hormone vasopressin (AVP).
If you have DI your kidneys are unable to retain water. This leads to the production of large volumes of urine and, in turn, greatly increased thirst
What can cause diabetes insipidus
- Lack of vasopressin production by the pituitary
What is nephrogenic diabetes insipidus
- Nephrogenic diabetes insipidus (also known as renal diabetes insipidus) is a form of diabetes insipidus primarily due to pathology of the kidney (kidney is resistant to vasopressin)
- This is in contrast to central/neurogenic diabetes insipidus, which is caused by insufficient levels of antidiuretic hormone
Percentage of cases of cranial diabetes insipidus that are idiopathic and genetic
- Idiopathic - 27%
- Genetic - <5%
Genes implicated in cranial diabetes insipidus
- Familial (AD) mutation of AVP gene
Secondary causes of cranial diabetes insipidus
• Post-surgical (pituitary / other brain operations)
• Traumatic (head injury, including closed injury)
• Rarer causes
○ Tumours, histiocytosis, sarcoidosis, encephalitis, meningitis, vascular insults, autoimmune
What is polyuria
- Excessive or an abnormally large production or passage of urine (greater than 2.5 or 3 L over 24 hours in adults).
- Frequent urination is usually an accompanying symptom
Features of hypothalamic syndrome
- Disordered thirst and DI
- Disordered appetite (hyperphagia)
- Disordered temperature regulation
- Disordered sleep rhythm
- Hypopituitarism
Genes implicated in nephrogenic diabetes insipidus
- Genetic (rare) Xr or Ar
- Mutations of V2 receptor gene/aquaporin gene
Cranial vs nephrogenic diabetes insipidus
cranial diabetes insipidus – where the body doesn’t produce enough AVP, so excessive amounts of water are lost in large amounts of urine
nephrogenic diabetes insipidus – where AVP is produced at the right levels but, for a variety of reasons, the kidneys don’t respond to it in the normal way
Most common cause of acquired nephrogenic diabetes insipidus
- Lithium
What is the water deprivation test
- Period of dehydration
- Measure plasma and urine osmolalities and weight
- Injection of synthetic vasopressin - desmopressin
- Measure plasma and urine osmolalities
Normal response to water deprivation test
- Normal plasma osmolality, high urine osmolality
Water deprivation test response - cranial diabetes insipidus
- Poor urine concentration after dehydration
- Rise in urine osmolality after desmopressin
Water deprivation test response - nephrogenic diabetes insipidus
- Poor urine concentration after dehydration
- No rise in urine osmolality after desmopressin
Treatment - cranial diabetes insipidus
- DDAVP (desmopressin)
- Over-treatment can cause hyponatraemia
Treatment - nephrogenic diabetes insipidus
- Correction of cause (metabolic/drug cause)
- Thiazide diuretics/NSAIDs
Treatment - primary polydipsia
- Explanation, persuasion
- Psychological therapy
Hyponatraemia - definitions
- [Sodium] < 135 mmol/L
- Severe [Na] <125 mmol/L
Symptoms of hyponatraemia
- May be asymptomatic
- Depends on rate of fall as well as absolute value (brain adapts - chronic)
- Non-specific - headache, nausea, mood change, cramps, lethargy
- Severe/sudden - confusion, drowsiness, seizures, coma
What do you exclude when classifying hyponatraemia
- Exclude ‘drug’ causes
- Thiazide diuretics, others
- Exclude high concentrations of
- Glucose, plasma lipids or proteins
Classifying hyponatraemia by extracellular fluid volume status
• Hypovolaemia
- Renal loss, non-renal loss (D&V, burns, sweating)
• Normovolaemia (euvolaemia)
- Hypoadrenalism, hypothyroidism
- Syndrome of inappropriate ADH secretion (SIADH)
• Hypervolaemia
- Renal failure, cardiac failure, cirrhosis, excess IV dextrose
What is SIADH
The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is defined by the hyponatremia and hypo-osmolality resulting from inappropriate, continued secretion or action of the antidiuretic hormone arginine vasopressin (AVP) despite normal or increased plasma volume, which results in impaired water excretion
SIADH - diagnosis
• Clinically euvolaemic patient
• Low plasma sodium and low plasma osmolality
Inappropriately high urine sodium concentration and high urine osmolality
Assessment - SIADH
Assess renal, adrenal and thyroid function
Causes of SIADH
- Neoplasias, neurological disorders (CNS), lung disease, drugs, endocrine (hypothyroid/hypoadrenalism)
SIADH treatment
- Identify and treat the underlying cause
- Fluid restriction (<1000 ml daily)
- Induce negative fluid balance 500 ml
- Aim ‘low normal’ sodium
- Demeclocycline
- Drug that induces mild nephrogenic DI
- Vasopressin (V2 receptor) antagonists
- “Vaptans” – induce a water diuresis
- Expensive, variable responses, some attenuation
- Lack of clinically significant outcome data
Hyponatraemia treatment
- Correct severe hyponatraemia slowly
- Rapid correction risks oligodendrocyte degeneration and CNS myelinolysis (osmotic demyelination)
- Severe neurological sequelae, may be permanent
- Alcoholics & malnourished particularly at risk
