Physiology of thirst/fluid balance and its disorders Flashcards
Why is water homeostasis important?
What is it mainly determined by?
Ensures plasma osmolality (and extracellular fluid osmolality) remains stable
- ADH/ AVP(against diuresis)
- Osmotically stimulated secretion
- Acts on kidney tubule to allow changes in H2O secretion - Kidneys- allow large variation in urine output (0.5-20L/day)
- Thirst - important in osmoregulation, stimulates fluid intake
What are osmoreceptors?
Groups of specialised cells which detect changes in plasma osmolality (especially Na)
- located in anterior wall of third ventricle
- alter the 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
- Fenestrations in BBB allow circulating solutes to influence brain osmoreceptors
How is ADH like oxytocin?
How are they different?
- Non-peptide (Contain 9 AA’s, 7 of which are identical)
- Vasopressin is synthesised in neurons in supraoptic and paraventricular nuclei of the hypothalamus
- Secretory granules migrate down axons to post.pituitary gland, from where AVP’s releases
AVP stimulates endocrine cells to release ACTH. Oxytocin inhibits ACTH secretion
Explain the action of ADH in the kidney.
- Action mediated by V2 receptors
- ADH sensitive water channel (aquaporins) stored in cytoplasmic vesicles, move to and fuse with the luminal membrane
- This increases water permeability of renal collecting duct, promoting H20 reabsorption
(when ADH is cleared, aquaporins removed from luminal surface by endocytosis)
V2 receptor + vasopression –> Stimulates adenylate cyclase –> ATP conversion to cAMP–> PKA –> Protein phosphorylation –> membrane fusion
How are collecting duct cells joined?
By tight junctions (can become leaky)
Outline the physiological differences between a state of high and low plasma osmolality
LOW PLASMA OSMOLALITY (Lots of water in blood)
- No thirst
- AVP undetectable
- Dilute urine
- High urine output
HIGH PLASMA OSMOLALITY
- High thirst sensation (drinking immediately suppresses AVP seecretion and thirst - avoids ‘overshoot’)
- High AVP secretion
- Concentrated urine
- Low urine output
Define polyuria and polydipsia
Now consider the pathophysiology of polyuria and polydipsia.
What are the 3 main causes?
Polyuria: excessive or an abnormally large production or passage of urine. May be accompanied by increased frequency of urination
Polydipsia: excess drinking in absence of physiological stimulus-thirst, often accompanied by dry mouth
- Cranial (central) diabetes insipidus
- 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
What are the causes of cranial DI?
- Idiopathic (27%)
- Genetic (<5%): Familial (AD) mutation of the AVP gene, DIPMOAD (Wolfram) - Ar, incomplete penetrance
Secondary (commonest)
- Post surgical (pituitary/other brain areas)
- Traumatic (head injury including closed injury)
- Tumours, histiocytosis, sarcoidosis, encephalitis, meningitis, vascular insults, AI
What are the causes of nephrogenic DI?
- Idiopathic
- Genetic (RARE) - Xr or Ar, mutations of V2 gene/aquaporin gene
- Metabolic - High [Ca], Low [K]
- Drugs - Lithium
- Chronic kidney disease
Outline the pathophysiology of cranial DI
- Insufficient AVP secretion, excess solute free renal water secretion (polyuria)
- Thirsts sensation intact and readily accessible fluid, thirst stimulated to maintain stable, normal plasma osmolality (polydipsia)
Outline the pathophysiology of nephrogenic DI
- Renal tubules resistant to AVP (polyuria)
- Thirst stimulated (polydipsia)
How is hypothalamic syndrome characterised?
- Disordered thirst and DI
- Disordered appetite (hyperphagia)
- Disordered temperature regulation
- Disordered sleep rhythm
- Hypopituitarism
Characterise psychogenic primary polydipsia
- High fluid intake without physiological stimulus -thirst (polydipsia)
- Lower plasma osmolality (high water content in blood)
- Low urine osmolality, high urine output (polyuria)
- Suppressed AVP secretion
- Loss of renal interstitial solute and renal concentrating ability
CLINICAL APPLICATION
What investigation would be appropriate for suspected polydipsia/polyuria?
- Medical Hx (ex. DM)
- Document 24 hour fluid balance (urine output and fluid intake, day and night)
- Exclude hypercalcaemia/ hypokalaemia
- Water deprivation test
CLINICAL APPLICATION
What is a water deprivation test?
What would be the results of a water deprivation test in
a) Healthy patient
b) Patient with Cranial DI
c) Nephrogenic DI
Water deprivation test: period of dehydration, measure plasma and urine osmolalities and weight, inject synthetic ADH (Desmopressin) and repeat measurements
a) Normal plasma osmolality, high urine osmolality (low water content)
b) Poor urine concentration after dehydration, higher urine osmolality after desmopressin
c) Poor urine concentration after dehydration, no rise in in urine osmolality after desmopressin
