Physiology of Thirst and Fluid Balance and it's Disorders Flashcards
Thirst and fluid balance - Physiology
- Regulation of thirst and fluid balance
- “…. homeostasis”
- Featured hormone is … also known as …
- Regulation of thirst and fluid balance
- “water homeostasis”
- Featured hormone is Anti-diuretic hormone (ADH) also known as Arginine vasopressin (AVP)
Thirst and fluid balance - Pathophysiology
- poly… and poly… (DI)
- Hypo… (syndrome of inappropriate ADH secretion (SIADH)
- polyuria and polydispia (DI)
- Hyponatraemia (syndrome of inappropriate ADH secretion (SIADH)
Physiology of water homeostasis: Importance
- Regulation of water balance ensures plasma … (and extracellular fluid … )remains stable
- Narrow range of plasma … (what is this?)
- Regulation of water balance ensures plasma osmolality (and extracellular fluid osmalality) remains stable
- Narrow range of plasma osmolality - 285-295mosmol/kg
Physiology of water homeostasis - 3 key determinants - what are they?
-
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
ADH is one of the 3 key determinants in water homeostasis. What does it do?
- osmotically stimulated secretion
- acts on renal tubule to allow changes in water excretion
The kidney is one of the 3 key determinants in water homeostasis. What is it’s urine output like?
- a wide variation in urine output (0.5-20L/day)
Thirst is one of the 3 key determinants in water homeostasis. How is it regulated and stimulated?
- osmoregulated
- stimulates fluid intake
Osmoreceptors
- they are groups of specialised cells which detect changes in plasma … (Especially …)
- they are located in the … wall of the … ventricle
- … in the blood-brain barrier allow circulating solutes (osmoles) to influence brain osmoreceptors
- they are groups of specialised cells which detect changes in plasma osmolality (Especially sodium)
- they are located in the anterior wall of the 3rd ventricle
- fenestrations in the blood-brain barrier allow circulatig solutes (osmoles) to influence brain osmoreceptors

- How do osmoreceptor cells alter their volume? (in response to changes in plasma osmolality?)
- What does this initiate? what is synthesised? what happens as a result?
- 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)
- water … hormone
- human form is what?
- like oxytocin - it is a …peptide
- water conserving hormone
- human form is arginine vasopressin (AVP)
- like oxytocin - it is a Nonapeptide (9 AA peptide)
- Where is vasopressin synthesised?
- once synthesised, secretory granules migrate down where?
- in neurons in supraoptic and paraventricular nuclei of the hypothalamus
- secretory granules migrate down axons to posterior pituitary - where AVP is released

Where is vasopressin released?
Posterior pituitary
ADH action in the kidney
- ADH action mediated via … receptors
- ADH sensitive water channel (…) normally stored in cytoplasmic …, moves to & … with the luminal membrane
- … water permeability of renal collecting tubules, promoting water …
- When ADH cleared - water channels removed from the luminal surface (…) and returned to cytoplasm
- 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/Thirst
- AVP and the kidney:
- Low plasma osmolality
- AVP is …
- urine is …
- … urine output
- Thirst?
- High plasma osmolality
- AVP secretion is …
- urine is …
- … urine output
- Thirst?
- Low plasma osmolality
- AVP and the kidney:
- Low plasma osmolality
- AVP is Undetectable
- urine is dilute
- high urine output
- no thirst
- High plasma osmolality
- AVP secretion is high
- urine is concentrated
- low urine output
- yes - increased thirst sensation - but drinking immediately transiently suppresses AVP secretion and thirst - avoids an ‘overshoot’
- Low plasma osmolality
What relationship is shown here?

- relationship between plasma AVP and plasma osmolality/urine osmolality
- Left - As plasma osmolality rises, vasopressin rises, thirst triggered
- Right - vasopressin up, osmolality of urine up
Polyuria and Polydipsia
- Exclude what first?
- Three other main causes are:
- ?
- lack of osmoregulated AVP secretion
- ?
- lack of response of the renal … to AVP
- ?
- psychogenic polydipsia, social/cultural
- ?
- all may be ‘partial’
- Exclude diabetes mellitus first
- Three other main causes are:
-
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’
-
Cranial (Central) diabetes insipidus

Cranial Diabetes Insipidus - Causes
- Idiopathic causes - what % ?
- Genetic - what% ?
- familial (AD) mutation of … gene
- DIDMOAD (Wolfram) (Ar, incomplete penetrance)
- Secondary (commonest causes)
- post-… (pituitary / other brain operations)
- … (head injury, including closed injury)
- … causes
- tumours, histiocytosis, acoidosis, encephalitis, meningitis, vascular insults, autoimmune
- Idiopathic (27%)
- Genetic (<5%)
- familial (AD) mutation of AVP gene
- DIDMOAD (Wolfram) (Ar, incomplete penetrance)
- Secondary (commonest causes)
- post-surgical (pituitary / other brain operations)
- traumatic (head injury, including closed injury)
-
rarer causes
- tumours, histiocytosis, acoidosis, encephalitis, meningitis, vascular insults, autoimmune
Cranial Diabetes Insipidus
- … osmoregulated AVP secretion
- Leads to excess solute-free renal water excretion
- known as what?
- Provided thirst sensation remains intact and there is ready access to fluids, thirst is stimulated to maintain a stable, normal plasma osmolality
- known as what?
- 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 … and Diabetes …
- Disordered appetite, known as (…)
- Disordered … regulation
- Disordered … rhythm
- Hypo…
- Disordered thirst and Diabetes Insipidus
- Disordered appetite (hyperphagia)
- Disordered temperature regulation
- Disordered sleep rhythm
- Hypopituitarism

Nephrogenic diabetes insipidus - what is it?
Nephrogenic diabetes insipidus (NDI) is an inability to concentrate urine due to impaired renal tubule response to vasopressin (ADH), which leads to excretion of large amounts of dilute urine
Nephrogenic diabetes insipidus
- Renal tubules resistant to …
- Resulting in …
- Thirst is stimulated
- Resulting in …
- Renal tubules resistant to AVP
- Resulting in Polyuria
- Thirst is stimulated
- Polydipsia
Nephrogenic diabetes insipidus - Causes
- Idiopathic
- …. (rare) Xr or Ar
- mutations of … receptor gene / … gene
- Metabolic
- High … or low …
- Drugs e.g …
- Chronic … disease
- Idiopathic
-
Genetic (rare) Xr or Ar
- mutations of V2 receptor gene / aquaporin gene
- Metabolic
- High calcium or low potassium
- Drugs e.g lithium
- Chronic kidney disease
Primary polydipsia (psychogenic)
- Increased … intake
- polydipsia
- … plasma osmolality
- Suppressed … secretion
- low or high ? - urine osmolality and urine output
- polyuria
- Also lose renal interstitial solute, reducing renal concentrating ability
- Increased fluid intake
- polydipsia
- Low 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
- … history
- Exclude what?
- Document … hour fluid balance
- urine output and fluid intake, day & night
- Excluse hyper… / hypo…
- … deprivation test
- Medical history
- Exclude diabetes mellitus
- Document 24 hour fluid balance
- urine output and fluid intake, day & night
- Excluse hypercalcaemia / hypokalaemia
- Water deprivation test
- What are causes of Nephrogenic diabetes insipidus?
- Hyper… and Hypo…
Hypercalcaemia and hypokalaemia
Water deprivation test
- Period of …
- Measure plasma and urine … & …
- Injection of synthetic …
- Known as … (DDAVP)
- Measure plasma and urine …
- Period of dehydration
- Measure plasma and urine osmolalities & weight
- Injection of synthetic vasopressin
- Desmopressin (DDAVP)
- Measure plasma and urine osmolalities
Water deprivation test
- What response?
- Normal plasma osmolality, after desmopressin = high urine osmolality
- … diabetes insipidus
- Poor urine concentration after dehydration
- Rise in urine osmolality after desmopressin
- … diabetes insipidus
- Poor urine concentration after dehydration
- No rise in urine osmolality after desmopressin
-
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
Treatment for Cranial diabetes insipidus
- DDAVP - what is this called?
- Over-treatment can cause what?
- DDAVP - desmopressin
- Over-treatment can cause hyponatraemia
Treatment for Nephrogenic diabetes insipidus
- Correction of cause (… / … cause)
- … diuretics / NSAID’s - what are these?
- Correction of cause (metabolic / drug cause)
- Thiazide diuretics / NSAID’s - Non-steroidal anti-inflammatory drugs
Treatment for Primary Polydipsia
- Explanation and …
- … therapy
- Explanation, persuasion
- Psychological therapy
Difference between Cranial diabetes insipidus and Nephrogenic diabetes insipidus?
Cranial diabetes insipidus is a condition in which the hypothalamus does not produce enough anti-diuretic hormone. Nephrogenic diabetes insipidus is a condition in which the kidneys fail to respond to anti-diuretic hormone.
Hyponatraemia
- Definitions:
- Sodium
- Severe if
- Sodium <135 mmol/L
- Severe if <125 mmol/L
Hyponatraemia symptoms:
- May be …
- Depends on … of fall as well as absolute value
- … adaps - chronic
- Non-specific symptoms include… (5)
- Severe/ sudden symptoms include… (4)
- May be asymptomatic
- Depends on rate of fall as well as absolute value
- Brain adaps - chronic
- Non-specific
- Headache, nausea, mood change, cramps, lethargy
- Severe/ sudden
- Confusion, drowsiness, seizures, coma
Classification of hyponatraemia
- Exclude ‘drug’ causes
- … diuretics, others
- Exclude high concentrations of … (3)
- Classify by extracellular fluid volume status
- …volaemia
- renal loss, non-renal loss (D&V, burns, sweating)
- …volaemia (euvolaemia)
- hypoadrenalism, hypothyroidism
- SIADH - what does this stand for?
- …volaemia
- renal failure, cardiac failure, cirrhosis, excess IV dextrose
- …volaemia
- Exclude ‘drug’ causes
- thiazide diuretics, others
- Exclude high concentrations of
- glucose, plasma lipids or proteins
- Classify 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
-
hypovolaemia
Syndrome of inappropriate ADH secretion (SIADH)
- Diagnosis:
- clinically … patient
- … plasma sodium and … plasma osmolality
- inappropriately high urine … concentration and high urine …
- Assess what functions? (3)
- Many causes
- neoplasias, neurological disorders (CNS), lung disease, drugs, endocrine (hypothyroid/hypoadrenalism)
- Diagnosis:
- 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
- Many causes
- neoplasias, neurological disorders (CNS), lung disease, drugs, endocrine (hypothyroid/hypoadrenalism)
Syndrome of inappropriate ADH secretion (SIADH) - treatment
- Identity and treat the underlying …
- Fluid … (<1000ml daily)
- Induce negative fluid balance 500ml
- Aim ‘low normal’ sodium
- …
- drug that induces mild nephrogenic DI
- … (V2 receptor) antagonists
- “Vaptans” - induce a water …
- Expensive, variable responses, some attenuation
- Lack of clinically significant outcome data
- Identity and treat the underlying cause
- Fluid restriction (<1000ml daily)
- induce negative fluid balance 500ml
- 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 slow or fast? - why?
- Who is particularly at risk for this happening if the treatment is done too slowly/fast?
- 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
- ADH release is regulated by where?
- ADH is synthesised where?
- ADH is released from?
- ADH acts where?
- ADH acts via?
- ADH results in insertion of…
- ADH release is regulated by plasma osmolality
- ADH is synthesised where - hypothalamus
- ADH is released from - posterior pituitary
- ADH acts where - kidney (distal convoluted tubule (DCT) and collecting ducts (CD)
- ADH acts via - V2 receptors
- ADH results in insertion of aquaporins
Low plasma osmolality: particles diluted
- AVP high or low?
- Thirst high or low?
- Urine osmolality high or low?
- Urine volume high or low?
- AVP high or low? - low - undetectable
- anti diuretic - stops you weeing - low levels = more urine excreted (dilute urine)
- Thirst high or low? - no thirst
- Urine osmolality high or low? - low
- Urine volume high or low? - high
High plasma osmolality: particles concentrated
- AVP high or low?
- Thirst high or low?
- Urine osmolality high or low?
- Urine volume high or low?
- AVP high or low? - high
- anti diuretic - stops you weeing - high levels = less urine
- Thirst high or low? - high - but drinking suppresses AVP secretion and thirst immediately
- Urine osmolality high or low? - high
- Urine volume high or low? - low
Results of water deprivation test
- High or low after each?

1. Normal response:
- Dehydration - Normal plasma osmolality
- After desmopressin = High urine osmolality
2. Cranial diabetes insipidus:
- Poor urine concentration after dehydration
- Rise in urine osmolality after desmopressin
3. Nephrogenic diabetes insipidus:
- Poor urine concentration after dehydration
- No rise in urine osmolality after desmopressin