Physiology of thirst, fluid balance and its disorders

Question 1

What are the 3 key determinants of water homeostasis?

Answer 1

ADH (AVP) - osmotically stimulated secretion, acts on renal tubule to allow changes in water excretion
Kidney - wide variation in urine output
Thirst - osmoregulated, stimulates fluid intake

Question 2

What are osmoreceptors and where are they found?

Answer 2

groups of specialised cells which detect changes in plasma osmolality (esp sodium). located in anterior wall of 3rd ventricle.

Question 3

What is the function of osmoreceptors?

Answer 3

fenestrations in blood-brain barrier allow circulating solutes 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

Question 4

Outline ADH action on the kidneys

Answer 4

mediated via V2 receptors.
aquaporin is normally stored in cytoplasmic vesicles, moves to and fuses with luminal membrane.
increases water permeability of renal collecting tubules, promoting water reabsorption.
when ADH cleared – water channels removed from luminal surface (endocytosis) and returned to cytoplasm.

Question 5

Outline osmoregulation in the kidneys when there is high and low plasma osmolality

Answer 5

Low: AVP undetectable, dilute urine, high urine output.
High: high AVP secretion, concentrated urine, low urine output.

Question 6

Outline the osmoregulation of thirst when there is high and low plasma osmolality

Answer 6

Low: no thirst
High: increased thirst sensation, drinking immediately transiently suppresses AVP secretion and thirst - avoids ‘overshoot’

Question 7

Excluding diabetes mellitus, what are the other main causes of polyuria and polydipsia?

Answer 7

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 - social/cultural.
All may be ‘partial’

Question 8

What are the causes of cranial diabetes insipidus?

Answer 8

Idiopathic
Genetic: familial mutation of AVP gene, Wolfram syndrome
Secondary (commonest causes): post-surgical (pituitary / other brain operations), traumatic (head injury, including closed injury), rarer: tumours, histiocytosis, sarcoidosis, encephalitis, meningitis, vascular insults, autoimmune.

Question 9

What is cranial diabetes insipidus?

Answer 9

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.

Question 10

What are the potential consequences of hypothalamic syndrome?

Answer 10

Disordered thirst and DI
Disordered appetite (hyperphagia)
Disordered temperature regulation
Disordered sleep rhythm
Hypopituitarism

Question 11

What is nephrogenic diabetes insipidus?

Answer 11

Renal tubules resistant to AVP - polyuria

Thirst stimulated - polydipsia

Question 12

What are the causes of nephrogenic diabetes insipidus?

Answer 12

Idiopathic
Genetic (rare) - mutations of V2 receptor gene / aquaporin gene
Metabolic - high [calcium] or low [potassium]
Drugs - lithium
Chronic kidney disease

Question 13

What is primary polydipsia (psychogenic)?

Answer 13

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

Question 14

How is polyuria and polydipsia investigated?

Answer 14

Medical History
Exclude diabetes mellitus
Document 24 hour fluid balance - urine output and fluid intake, day and night
Exclude hypercalcaemia / hypokalaemia
Water deprivation test

Question 15

Outline the water deprivation test

Answer 15

Period of dehydration
Measure plasma and urine osmolalities and weight
Injection of synthetic vasopressin -desmopressin (DDAVP)
Measure plasma and urine osmolalities

Question 16

What are the results of the water deprivation test for a normal response to dehydration and for diabetes insipidus?

Answer 16

Normal: normal plasma osmolality, high urine osmolality.
Cranial DI: poor urine concentration after dehydration, rise in urine osmolality after desmopressin.
Nephrogenic DI: poor urine concentration after dehydration, no rise in urine osmolality after desmopressin.

Question 17

How is DI and primary polydipsia treated?

Answer 17

Cranial DI: DDAVP (desmopressin), over-treatment can cause hyponatraemia.
Nephrogenic DI: correction of cause (metabolic / drug cause), thiazide diuretics / NSAIDs.
Primary polydipsia: explanation, persuasion, psychological therapy.

Question 18

What are the symptoms of hyponatraemia?

Answer 18

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

Question 19

How is hyponatraemia classified?

Answer 19

Exclude ‘drug’ causes - thiazide diuretics, others.
Exclude high concentrations of glucose, plasma lipids or proteins.
Classify by extracellular fluid volume status:
Hypovolaemia - due to renal loss, non-renal loss (D&V, burns, sweating).
Normovolaemia (euvolaemia) - hypoadrenalism, hypothyroidism, SIADH.
Hypervolaemia - due to renal failure, cardiac failure, cirrhosis, excess IV dextrose.

Question 20

How is SIADH diagnosed?

Answer 20

Clinically euvolaemic patient.
Low plasma sodium and low plasma osmolality.
Inappropriately high urine sodium concentration and high urine osmolality.
Assess renal, adrenal and thyroid function.

Question 21

What are the causes of SIADH?

Answer 21

Many causes: neoplasias, neurological disorders (CNS), lung disease, drugs, endocrine (hypothyroid/hypoadrenalism)

Question 22

How is SIADH treated?

Answer 22

Identify and treat 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 antagonists - “Vaptans” induces a water diuresis, but is expensive, has variable responses and some attenuation, lacks clinically significant outcome data.

Question 23

How is hyponatraemia treated?

Answer 23

Correct severe hyponatraemia slowly.
Rapid correction risks oligodendrocyte degeneration and CNS myelinolysis (osmotic demyelination) - severe neurological sequelae, may be permanent. alcoholics and malnourished particularly at risk.