osmoregulation (control)

• what does osmotic force determine?

  • the distribution of water between ECF & ICF compartments
• what are the homeostatic mechanisms for maintaining fluid balance?

  • ADH release and its action on the kidney regulate water balance
  • plasma sodium concentration influences ECF osmolality
  • imbalances can lead to hypo or hypernatremia (e.g SIADH, diabetes insipidus)
• how is water distributed between ICD and ECF?

  • osmotic forces determine water movement between compartments
  • adding pure water to ECF creates an osmotic gradient, expanding ECF and ICF
• what are the typical daily inputs and outputs for water balance?

  • input:
  • drink (1000ml)
  • food (700ml)
  • metabolism (300ml)
  • output:
  • gut (100ml)
  • insensible loss [lungs/skin] (900ml)
  • renal excretion (1000ml)
  • total intake = total loss (2000ml)
• what happens with water excess or deficit?

  • water excess: decreases body fluid osmolality, large volume of dilute urine
  • water deficit: increased osmolality, small volume of concentrated urine
• where is water loss regulated in the body?

  • the renal tubule is the only site of regulated water loss
  • the kidney varies solute-free water excretion to maintain osmolality
• what role does ADH play in water regulation?

  • ADH controls water permeability in the CD
  • low ADH: CD impermeable to water -> dilute urine (50mOsm/kg)
  • high ADH: CD permeable to water -> concentrated urine (up to 1200mOsm/kg)
• how does ADH affect kidney function?

  • ADH binds to V2 receptors on principal cells of the CD -> inserts aquaporin-2-channels into membrane -> increases water reabsorption
  • V1 receptors on vascular smooth muscle cause vasoconstriction at high ADH levels
• what regulates ADH release?

  • osmoreceptors in the anterior hypothalamus detect changes in plasma osmolality
  • normal range: 285-295mOsm/kg
  • ADH release threshold: 280-285mOsm/kg
  • large blood volume/pressure decreases (10-15%) also trigger ADH
• maintaining osmolality: ADH

  • net water loss increases ECF osmolarity
  • normal range = 285-295mOsm/kg
  • changes detected by osmoreceptors in anterior hypothalamus
  • project to magnocellular neurones of paraventricular and supraoptic nuclei of hypothalaum
  • PVN and SON neurones release ADH from their axon terminals in posterior pituitary
  • threshold for ADH release is 280-285mOsm/kg
  • above this range small changes in osmolality produce large chages in ADH secretion
• maintaining osmolality: thirst

  • net water loss increases ECF osmolarity
  • changes detected by osmoreceptors in anterior hypothalaum
  • project to centres mediating thirst, drinking
  • strong desire to drink when plasma osmolarity >=295mOsm/kg
  • oropharyngeal and upper GI receptors reduce thirst on drinking
  • thirst also stim by:
  • large (10-15%) drops in BV/P
  • angiotensin 2 acting on hypothalamus
• how does sodium affect ECF osmolality?

  • Na+ is the main extracellular cation (135-145mmol/L)
  • plasma osmolality estimate: 2[Na+] + 2[K+] + [glucose] + [urea]
• how are disturbances in water balance present?

  • hypernatremia (Na+>145mmol/L) = water deficit -> hyperosmolality
  • hyponatremia (Na+<135mmol/L) = water excess -> hypoosmolality
• what are the causes of hypernatremia?

  • gain of sodium (rare): latrogenic, XS mineralocorticoid activity (Conn's syndrome)
  • loss of water (common): dehydration, infection, diabetes insipidus
• what is diabetes insipidus (DI)?

  • Inability to concentrate urine due to ADH deficiency or resistance.
  • lack oF effective ADH:
  • Central DI: ADH secretion failure.
  • Nephrogenic DI: Kidney unresponsive to ADH.
  • Presents with polydipsia and polyuria.
  • Hypernatremia develops if water access is restricted.
• how does ADH contribute to hyponatremia?

  • XS ADH leads to continued water retenion -> dilutional hyponatremia
  • SIADH: Hyponatremia + high urine osmolality (causes include CNS disorders, ectopic ADH production by tumors)
• what happens to ADH secretion in hypovolemia?

  • low BV/P overrides osmotic signals
  • ADH secretion remains high -> water retention -> ECF dilution
• what are the key learning points from this topic?

  • Mechanisms of fluid balance regulation.
  • ADH’s role in kidney function and osmoregulation.
  • Relationship between plasma sodium and ECF osmolality.
  • Causes and consequences of hypo- and hypernatremia.