10. Physiology of Thirst and Fluid Balance and its Disorders Flashcards
What hormone is featured in regulating thirst and fluid balance?
Anti-diuretic hormone (ADH) aka arginine vasopressin (AVP)
Why is water homeostasis important?
Regulating water ensures plasma osmolality and extracellular fluid osmolality remains stable.
There is a very narrow range of plasma osmolality - 285-295mosmol/kg
What are the 3 key determinants of water balance?
ADH - osmotically stimulated secretion, acts on renal tubule to allow changes in water excretion.
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, especially Sodium.
Located in the anterior wall of the third ventricle. Fenestrations in the blood brain barrier allow circulating solutes aka osmoles, to influence brain osmoreceptors
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 a diuresis - water conserving
Human form of ADH is arginine vasopressin (AVP)
Like oxytocin:
nonapeptide (9 aa)
Vasopressin synthesised in neurons in supraoptic and paraventricular nuclei of hypothalamus
Secretory granules migrate down axons to posterior pituitary from where AVP is released
What is AVP
AVP (arginine vasopressin) is human ADH
AVP = ADH
ADH = AVP=vasopressin
same thing
stops u peeing
desmopressin = synthetic vasopressin/AVP
Where are oxytocin and AVP synthesised?
In supraoptic and paraventricular nuclei of hypothalamus
Secretory granules migrate down axons to posterior pituitary, where AVP is releases from
ADH action in the kidney
ADH action is mediated via V2 receptors
Aquaporins (ADH-sensitive water channel) are normally stored in cytoplasmic vesicles but move to and fuse with luminal membrane in response to ADH
ADH increases water permeability of renal collecting tubules, promoting water reabsorption
When ADH is cleared, water channels are endocytosed from the luminal surface and return to the cytoplasm
Low plasma osmolality
(lots of water little osmoles) AVP is undetectable Dilute urine High urine output No thirst
High plasma osmolality
(little water lots of osmoles) High AVP secretion Concentrated urine low urine output Increased thirst sensation
Drinking immediately transiently suppresses AVP secretion and thirst to avoid overshoot
Polyuria and polydipsia (diabetes insipidus)
Exclude diabetes mellitus
Three main causes:
Cranial (central) diabetes insipidus (DI): lack of osmoregulated AVP secretion/lack of vasopressin
Nephrogenic diabetes insipidus:
lack of response of renal tubule to AVP
Primary polydipsia: psychogenic polydipsia, social/cultural (e.g. drinking too much/too little water), loss of thirst centre stimulation
All may be partial
Primary causes of cranial diabetes insipidus
27% idiopathic
<5% genetic - familial (AD) mutation of AVP gene, DIDMOAD (Wolfram) (Ar, incomplete penetrance)
Secondary causes of causal diabetes insipidus
Post-surgical (pituitary/other brain operations)
Traumatic (head injury, including closed injury)
Rarer causes - tumours, histiocytosis, sarcoidosis, encephalitis, meningitis, vascular insults, autoimmune
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
Hypothalamic 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
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)
increased 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
What is polydipsia
Excessive thirst or drinking
Investigating polyuria and polydipsia
Medical history Exclude diabetes mellitus Document 24 hour fluid balance Urine output and fluid intake, day & night Exclude hypercalcaemia,hypokalaemia Water deprivation test
What is a water deprivation test?
Period of dehydration
Measure plasma and urine osmolalities & weight
Injection of synthetic vasopressin - desmopressin (DDAVP)
Measure plasma and urine osmolalities
What are the different responses in a water deprivation test?
Normal response to dehydration - normal plasma, osmolality, high urine osmolality
Cranial diabetes insipidus - poor urine concentration after dehydration, rise in urine osmolality after desmopressin
Nephrogenic diabetes insipidus - poor urine concentration after dehydration, no rise in urine osmolality after desmopressin
so basically if normal get conc pee, if cranial DI dont get conc pee but do with desmopressin (because problem is lack of AVP) and if nephrogenic doesnt get better even with desmopressin because can;t respond to it at kidney level anyway
Treatment of DI
Cranial:
DDAVP (desmopressin) but over-treatment can cause hyponatraemia
Nephrogenic:
Correction of cause (metabolic/drug cause)
Thiazide diuretics/NSAIDs
Primary polydipsia:
Explanation, persuasion
Psychological therapy
Hyponatraemia definition
[Sodium] < 135mmol/L
Severe [Na] <125 mmol/L
Symptoms of hyponatraemia
May be asymptomatic
Depends on rate of fall as well as absolute value
Brain adapts if chronic
Non-specific: headache, nausea, mood change, cramps, lethargy
Severe/sudden: confusion, drowsiness, seizures, coma
Classification of hyponatraemia
Exclude drug causes e.g. thiazide diuretics
Exclude high concentrations of glucose, plasma lipids or proteins
Classify by extracellular fluid volume status:
hypovalaemia: renal loss, non-renal loss (D&V, burns, sweating)
Normovalaemia (euvolaemia): hypoadrenalism, hypothyroidism, SIADH
Hypervolaemia: renal failure, cardic failure, cirrhosis, excess IV dextrose
SIADH
Clinically euvolaemic patient, with low plasma sodium and low plasma osmolality
inappropriately high urine sodium concentration and high urine osmolality (normal volume of blood with low sodium, but lots of sodium in pee)
Assess renal, adrenal and thyroid function
Many causes: neoplasias, neurological disorders (CNS), lung disease, drugs, endocrine (hypothyroid/hypoadrenalism)
SIADH treatment
Identify and treat underlying cause
Fluid restriction (<100ml daily)
Induce negative fluid balance 500ml
Aim for a low-normal sodium
Demeclocycline - drug that induces mild nephrogenic DI
Vasopressin (V2R) antagonists - vaptans that 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
