Body Fluids — Water Balance

H₂O

Body H₂O content (or TBW state) is determined by the body’s H₂O balance (daily H₂O
intake vs loss) → normally, it is balanced (as per table below):

• Note: Abnormal TBW states arise when an imbalance in body H₂O exists:
  • ↓ TBW (“H₂O deficit” → due to H₂O loss > intake) → results in ↑ plasma osmolality due to a relative ↑ plasma [Na⁺] → associated with ↓ ECFV (and PV)
  • ↑ TBW (“H₂O excess” → due to H₂O intake > loss) → results in ↓ plasma osmolality due to a relative ↓ plasma [Na⁺] → associated with ↑ ECFV (and PV)

Control of TBW

TBW state is controlled via –ve feedback system as follows:

Sensors

• Osmoreceptors (anterior hypothalamus)
  • Responds to ↑ plasma osmolality. Very sensitive (detects 1% change) → threshold for stimulation is 280 mosm/kg (near lower normal limit) → steep linear rise in response > 290 mosm/kg
• Low-pressure baroreceptors (right atrium and great vessels)
  • Responds to ↓ plasma volume indirectly by ↓ CVS PHYDROSTATIC (↓ MAP) → ↓ sensitive cf. osmoreceptors (detects 5-10% ∆ in PV)
• High-pressure baroreceptors (carotid sinus and aortic arch)
  • Responds to ↓ plasma volume indirectly by ↓ CVS PHYDROSTATIC (↓ MAP) → Even ↓ sensitive cf. osmoreceptors (detects > 10% ∆ in PV → large H₂O deficits) → BUT its response overrides that of the osmoreceptors!

Effectors

Hypothalamus integrates afferent signals from these sensors and modulates an
appropriate effector response that includes:

• Thirst response → triggered by:
  • ↑ plasma osmolality
  • ↓ plasma volume (or ↓ MAP)
  • AT-II (acting on circumventricular organs (SFO/OVLT)
• ADH
  • 9 a.a peptide hormone synthesised in hypothalamus (SON/PVN) → transported to posterior pituitary where it is secreted by:
    • ↑ plasma osmolarity (main trigger)
    • ↓ plasma volume (or ↓ MAP) → note that LARGE ∆ in PV (> 10%) can override response by osmoreceptors (Ie. ADH is secreted irrespective of plasma osmolality)
    • Other stimuli: AII, pain, nausea/vomiting, exercise
• Effects:
  • Via V1 receptor (GPCR via Gq → activates PLC to ↑ IP3 → ↑ IC [Ca²⁺] → SM contraction) → causes ↓ GFR to ↓ glomerular filtration (and loss of) H₂O → via:
    • Renal afferent arteriolar constriction
    • Renal mesangial cell contraction
  • Via V2 receptor (GPCR via Gs → activates AC to ↑ cAMP → activates PKA) → this causes:
    • Upregulates insertion of luminal AQP2 (stored in vesicles) in all parts of CD → ↑ H₂O permeability → ↑ H₂O reabsorption into hypertonic medullary interstitium
    • Upregulates “urea transporters” in inner MCD → ↑ permeability to urea → ↑ urea absorption to maintain ↑ medullary osmolality (strengthens CCM) → promotes ↑ H₂O reabsorption
    • ↑ Na⁺ reabsorption and K⁺ secretion by principal cells of CCD

Bianca 2016

Answer by Bianca