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Year 2 Medicine > Physiology of Thirst and Fluid Balance and it's Disorders > Flashcards

Physiology of Thirst and Fluid Balance and it's Disorders Flashcards

1
Q

Thirst and fluid balance - Physiology

  • Regulation of thirst and fluid balance
  • “…. homeostasis”
  • Featured hormone is … also known as …
A
  • Regulation of thirst and fluid balance
  • “water homeostasis”
  • Featured hormone is Anti-diuretic hormone (ADH) also known as Arginine vasopressin (AVP)
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2
Q

Thirst and fluid balance - Pathophysiology

  • poly… and poly… (DI)
  • Hypo… (syndrome of inappropriate ADH secretion (SIADH)
A
  • polyuria and polydispia (DI)
  • Hyponatraemia (syndrome of inappropriate ADH secretion (SIADH)
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3
Q

Physiology of water homeostasis: Importance

  • Regulation of water balance ensures plasma … (and extracellular fluid … )remains stable
  • Narrow range of plasma … (what is this?)
A
  • Regulation of water balance ensures plasma osmolality (and extracellular fluid osmalality) remains stable
  • Narrow range of plasma osmolality - 285-295mosmol/kg
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4
Q

Physiology of water homeostasis - 3 key determinants - what are they?

A
  1. ADH
    • osmotically stimulated secretion
    • acts on renal tubule to allow changes in water excretion
  2. Kidney
    • wide variation in urine output (0.5-20L/day)
  3. Thirst
    • osmoregulated
    • stimulates fluid intake
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5
Q

ADH is one of the 3 key determinants in water homeostasis. What does it do?

A
  • osmotically stimulated secretion
  • acts on renal tubule to allow changes in water excretion
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6
Q

The kidney is one of the 3 key determinants in water homeostasis. What is it’s urine output like?

A
  • a wide variation in urine output (0.5-20L/day)
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7
Q

Thirst is one of the 3 key determinants in water homeostasis. How is it regulated and stimulated?

A
  • osmoregulated
  • stimulates fluid intake
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8
Q

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
A
  • 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
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9
Q
  • 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?
A
  • 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
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10
Q

Anti-diuretic hormone (ADH)

  • water … hormone
  • human form is what?
  • like oxytocin - it is a …peptide
A
  • water conserving hormone
  • human form is arginine vasopressin (AVP)
  • like oxytocin - it is a Nonapeptide (9 AA peptide)
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11
Q
  • Where is vasopressin synthesised?
  • once synthesised, secretory granules migrate down where?
A
  • in neurons in supraoptic and paraventricular nuclei of the hypothalamus
  • secretory granules migrate down axons to posterior pituitary - where AVP is released
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12
Q

Where is vasopressin released?

A

Posterior pituitary

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13
Q

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
A
  • 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
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14
Q

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?
A
  • 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’
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15
Q

What relationship is shown here?

A
  • 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
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16
Q

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’
A
  • 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’
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17
Q

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
A
  • 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
18
Q

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?
A
  • 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
19
Q

Hypothalamic syndrome

  • Disordered … and Diabetes …
  • Disordered appetite, known as (…)
  • Disordered … regulation
  • Disordered … rhythm
  • Hypo…
A
  • Disordered thirst and Diabetes Insipidus
  • Disordered appetite (hyperphagia)
  • Disordered temperature regulation
  • Disordered sleep rhythm
  • Hypopituitarism
20
Q

Nephrogenic diabetes insipidus - what is it?

A

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

21
Q

Nephrogenic diabetes insipidus

  • Renal tubules resistant to …
    • Resulting in ​…
  • ​Thirst is stimulated
    • Resulting in ​…
A
  • Renal tubules resistant to AVP
    • Resulting in ​Polyuria
  • ​Thirst is stimulated
    • ​Polydipsia
22
Q

Nephrogenic diabetes insipidus - Causes

  • Idiopathic
  • …. (rare) Xr or Ar
    • mutations of … receptor gene / … gene
  • Metabolic
    • High … or low …
  • Drugs e.g …
  • Chronic … disease
A
  • 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
23
Q

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
A
  • 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
24
Q

Investigating polyuria and polydipsia

  • … history
  • Exclude what?
  • Document … hour fluid balance
    • urine output and fluid intake, day & night
  • Excluse hyper… / hypo…
  • … deprivation test
A
  • Medical history
  • Exclude diabetes mellitus
  • Document 24 hour fluid balance
    • urine output and fluid intake, day & night
  • Excluse hypercalcaemia / hypokalaemia
  • Water deprivation test
25
Q
  • What are causes of Nephrogenic diabetes insipidus?
  • Hyper… and Hypo…
A

Hypercalcaemia and hypokalaemia

26
Q

Water deprivation test

  • Period of …
  • Measure plasma and urine … & …
  • Injection of synthetic …
    • Known as … (DDAVP)
  • Measure plasma and urine …
A
  • Period of dehydration
  • Measure plasma and urine osmolalities & weight
  • Injection of synthetic vasopressin
    • Desmopressin (DDAVP)
  • Measure plasma and urine osmolalities
27
Q

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
A
  • 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
28
Q

Treatment for Cranial diabetes insipidus

  • DDAVP - what is this called?
  • Over-treatment can cause what?
A
  • DDAVP - desmopressin
  • Over-treatment can cause hyponatraemia
29
Q

Treatment for Nephrogenic diabetes insipidus

  • Correction of cause (… / … cause)
  • … diuretics / NSAID’s - what are these?
A
  • Correction of cause (metabolic / drug cause)
  • Thiazide diuretics / NSAID’s - Non-steroidal anti-inflammatory drugs
30
Q

Treatment for Primary Polydipsia

  • Explanation and …
  • … therapy
A
  • Explanation, persuasion
  • Psychological therapy
31
Q

Difference between Cranial diabetes insipidus and Nephrogenic diabetes insipidus?

A

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.

32
Q

Hyponatraemia

  • Definitions:
    • Sodium
    • Severe if
A
  • Sodium <135 mmol/L
  • Severe if <125 mmol/L
33
Q

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)
A
  • 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
34
Q

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
A
  • 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
35
Q

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)
A
  • 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)
36
Q

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
A
  • 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
37
Q

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?
A
  • 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
38
Q
  • 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…
A
  • 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
39
Q

Low plasma osmolality: particles diluted

  • AVP high or low?
  • Thirst high or low?
  • Urine osmolality high or low?
  • Urine volume high or low?
A
  • 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
40
Q

High plasma osmolality: particles concentrated

  • AVP high or low?
  • Thirst high or low?
  • Urine osmolality high or low?
  • Urine volume high or low?
A
  • 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
41
Q

Results of water deprivation test

  • High or low after each?
A

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

Year 2 Medicine (162 decks)

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