L10 - Physiology of thirst and fluid balance and its disorders Flashcards
What is the physiology?
Regulation of thirst and fluid balance
Water homeostasis
Featured hormone:
-ADH aka arginine vasopressin (AVP)
What is the pathophysiology?
Polyuria and polydipsia
-Diabetes Insipidus (DI)
Hyponatraemia
-Syndrome of inappropriate ADH secretion (SIADH)
Physiology of water homeostasis: Importance
Regulation of water balance ensures plasma osmolality (and extracellular fluid osmolality) remains stable
Narrow range of plasma osmolality
-285-295 mosmol/kg
Physiology of water homeostasis: 3 key determinants
ADH
- osmotically stimulated secretion
- acts on renal tubule to allow changes in water excretion
Kidney
-wide variation in urine output (0.5-20L/day)
Thirst
- osmoregulated
- stimulates fluid intake
What are osmoreceptors?
Osmoreceptors are groups of specialised cells which detect changes in plasma osmolality (esp sodium)
Where are osmoreceptors located?
Located in the anterior wall of 3rd ventricle
-Fenestrations in the blood-brain barrier allow circulating solutes (osmoles) to influence brain osmoreceptors
How do osmoreceptors work?
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
Anti-diuretic hormone (ADH)
ADH = ‘against diuresis’ - water conserving
Human form of ADH is arginine vasopressin AVP
Like oxytocin
- Nonapeptide - 9 amino acid peptide
- 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
ADH action in the kidney
ADH action mediated via V2 receptors
ADH-sensitive water channel (aquaporin) normally stored in cytoplasmic vesicles, moves to & fuses with the luminal membrane
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
Osmoregulation: AVP and the kidney
Low plasma osmolality
- AVP undetectable
- Dilute urine
- High urine output
High plasma osmolality
- High AVP secretion
- Concentrated urine
- Low urine output
Osmoregulation: Thirst
Low plasma osmolality
-No thirst
High osmolality
- Increased thirst sensation
- Drinking immediately transiently suppresses AVP secretion and thirst
- avoids overshoot
Relationship between plasma AVP and plasma osmolality/urine osmolality
positive, when one increases so does the other
What do polyuria and polydipsia exclude?
diabetes mellitus
3 main causes of polyuria and polydipsia
Cranial (central) diabetes insipidus (DI)
-lack of osmoregulated AVP secretion
Nephrogenic diabetes insipidus
-lack of response of the renal tubule to AVP
Primary polydipsia
-psychogenic polydipsia, social/cultural
all may be ‘partial’
Causes of cranial diabetes insipidus
Idiopathic (27%)
Genetic (<5%)
- familial (AD) mutation of AVP gene
- DIDMOAD (wolfram) (Ar, incomplete penetrance)
Secondary (comments causes)
- post-surgical (pituitary/other brain operations)
- traumatic (head injury, including closed injury)
- rarer causes (tumours, histiocytosis, sarcoidosis, encephalitis, meningitis, vascular insults, autoimmune)
What is cranial diabetes insipidus?
Decreased osmoregulated AVP secretion
Excess solute-free renal water excretion
-polyuria
Provided thirst sensation remains intact and there is ready access to fluids, thirst is stimulated to maintain a stable, normal plasma osmolality
-polydipsia
Hypothalamus syndrome
Disordered thirst and DI
Disordered appetite (hyperphagia)
Disordered temperature regulation
Disordered sleep rhythm
Hypopituitarism
Nephrogenic diabetes insipidus
Renal tubules resistant to AVP
-polyuria
Thirst stimulated
-polydipsia
Causes of nephrogenic diabetes insipidus
Idiopathic
Genetic (rare) Xr or Ar
-mutations of V2 receptor gene/aquaporin gene
Metabolic
-high calcium or low potassium
Drugs
-lithium
Chronic kidney disease
Primary polydipsia (psychogenic)
Increases fluid intake
-polydipsia
Lower plasma osmolality
Suppressed AVP secretion
Low urine osmolality, high urine output
-polyuria
Also lose renal interstitial solute, reducing renal concentrating ability
Investigating polyuria and polydipsia
Medical history
Exclude diabetes mellitus
Documents 24hr fluid balance
-urine output and fluid intake, day and night
Exclude hypercalcaemia/hypokalaemia
Water deprivation test
Water deprivation test
Period of dehydration
Measure plasma and urine osmolalities & weight
Injection of synthetic vasopressin
-desmopressin (DDAVP)
Measure plasma and urine osmolalities
Water deprivation test: normal response to dehydration
normal plasma osmolality, high urine osmolality
Water deprivation test: cranial diabetes insipidus
poor urine concentration after dehydration
rise in urine osmolality after desmopressin
