I1i: Determinants & Regulation of ECF
Definition
Extracellular fluid (ECF) is all the fluid compartments not existing inside cells. Consists of ISF, Plasma & Transcellular
Determinants
- ECF & ICF are separated by a semi-permeable membrane
- Water crosses freely down osmotic gradients
- Solutes = impermeable
- ECF volume determined by:
- Total body water
- [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