I1i: Determinants & Regulation of ECF

Definition

Extracellular fluid (ECF) is all the fluid compartments not existing inside cells. Consists of ISF, Plasma & Transcellular

Quantify

Determinants

  • ECF & ICF are separated by a semi-permeable membrane
  • Water crosses freely down osmotic gradients
  • Solutes = impermeable
  • ECF volume determined by:
    1. Total body water
    2. [Osmotically active solute] in ECF
  • Urea, glucose = ineffective osmoles (because more freely across membrane)
  • Na+ & Anions (Cl) = effective osmole → this is the definition of TONICITY = effective osmolality, the sum of solutes which have capacity to exert an osmotic force across a membrane
  • H2O always follows Na+
  • Na+ = 80% osmolality (particle, H1O ratio)

        = 93% tonicity (because other solutes like glucose, urea are ineffective)

  • ECF [Na+] = 135 – 145mmol/L
  • Normal daily intake 1 – 2 mmol/L = excretion (kidney, faeces)

Regulation

  • Changes in tonicity = life threatening
  • ∴Sensors & effectors to rapidly detect & correct

Sensor

OSMORECEPTORS

  • Located in anterior hypothalamus
  • Circumventricular organs
  • Organ vaculosum of lamina terminalis (OVLT)
  • Subfornical organ (SFO)
  • Very sensitive
  • Detects 1 – 2% ∆ osmolality

Effector

↑Osmolality

  • ADH release from PPG (produced in hypothalamus)
  • Released into blood
  • V1 (vessels) = VC
  • V2 (collecting duct) =
    • ↑GS,
    • ↑cAMP
    • Independent of Aquaporin 2 channels
    • ↑H2O reabsorption
    • ↓UO
  • V3 = stimulates thirst  

Sensor

VOLUME RECEPTORS

  • Low P BaroR in atria, vena cava, pulmonary veins
  • Detect 10% ↓ in blood volume

***Potent → override osmoreceptors because body will disregard tonicity if it helps maintain euvolaemia

Effector

↓ECF Volume

  • ↑symp stimulation
  • ↑RAAS
  • ↓GFR (mesangial cell constriction)
  • ↑Na, H2O reabsorption & thirst

↑ECF Volume

  • ↑RA ANP
  • ↑GFR (dilation of afferent arteriole)

↑H2O/Na excretion

Sensor

HIGH PRESSURE RECEPTORS

  • Carotid Sinus/Aortic Arch
  • Detect ∆ MAP
  • ∴ only activate if volume loss great enough to affect MAP

Effector

  • ↓MAP
  • ↓rate of BaroR firing
  • Removes basal inhibition in Vasomotor Centre
  • ↑symp + ↓parasymp output
  • ↑catecholamines
  • ↑RENIN
  • ↑AII
  • ↑Na+ reabsorption at PCT

Sensor

TUBULOGLOMERULAR FEEDBACK

  • Macula Densa = specialised cells in wall of thick asc. LoH
  • Detect [NaCl] → it associates ↑NaCl with ↑GFR & vice versa

** Intrinsic to kidney. No renal/hormonal influence. Alters its own GFR by afferent VC/VD depending on the Na load presented to M. Densa

Effector

  • ↓GFR
  • ↓NaCl to M.Densa
  • ↑PGE release
  • arteriole VD
  • Restore GFR
  • ↑GFR
  • ↑NaCl to M.Densa
  • ↑Adenosine
  • Afferent arteriole VC
  • Restores GFR

Sensor

GLOMERULAR TUBULAR BALANCE

  • Kidneys attempt to ensure 65% of Na+ load is always reabsorbed

**Another completely independent kidney mechanism

Effector

  • Not well understood but explained with oncotic pressures
  • ↑ECF
  • ↑GFR
  • ↑Na+ to kidneys
  • ↑p Peritubal caps
  • ↑Na+ reabsorption
  • ↑H2O reabsorption