Homeostasis of body fluids
G. Ogweno
Alle Ding sind Gift, und nichts ohn Gift; allein die
Dosis macht, daß ein Ding kein Gift ist
"All substances are poisons; there is none which
is not a poison. The right dose differentiates a
poison and a remedy.”
Paracelsus (1493-1541)
(Philippus Theophrastus Aureolus Bombastus
von Hohenheim )
Fluid compartments
compart
ment
Total
Body
water
ICF
%body
wt
60%
Vol(L)
40%
28
ECF(IS 20(15&
F/plasm 5)
barrier
42
Cell
membra
ne
14(10.5 Capillar
&3.5)
y wall
Ionic composition
ion
units
ECF
ICF
Na+
mEq/L
135-147 10-15
K+
mEq/L
3.5-5.0
120-150
Cl-
mEq/L
95-105
20-30
HCO3
mEq/L
22-28
12-16
Ca++
Mmol/L
2.1-2.8
10-7
Pi
Mmol/L
1.0-1.4
0.5-0.7
Fluid exchange between ICF and
ECF
• Free movement of water
• Direction by hydrostatic pressure and
osmotic pressure balance determined by
osmolality
• Water channels(aquaporins)
• Ionic movement determined by membrane
transporters
Mechanisms creating ionic
gradients
• predominantly Na+&Cl- extracellular,
K+,Prot&Pi intracellular
• Result of active transport e.g Na+/K+
ATPase
• Specific channels e.g K+leakage
• Presence of large organic osmolytes
• Membrane characteristics
Membrane transporters
Water channels: aquaporins
Ion channels: Na+,K+,Ca++,Cl-,Anion,Cat
Solute carriers:
• Uniport:glucose(Glut2),Fructose(Gluts),Urea(UTA),Fe++(ferroportin)
• Symport:Na+-glucose(SGLT2),2Na+-amino acid,Na+-Cl-,Na+K+,Na+-Pi,Na-3HCO3,K+-Cl etc
• Antiport: Na+-H+,Cl- -HCO3,3Na+-Ca++
Transport ATPase:
• P-Type: Na+,K+
• H+,K+
• H+,Ca++(PMCA)
• V-Type:H-ATPase
• ABC transporters:cystic fibrosis transmembrane regulator
(CFTR),multidrug resistance protein (MRP-1),Organic anion
Role of ionic gradients
• Optimal enzymatic pH
• Membrane potential for excitable tissues
• Regulation of cell volume/turgor/shape
Effect of exogenous fluid tonicity on
ECF
• Isotonic NaCl to ECF-increase vol by
same amount, ICF unaffected
• Hypotonic NaCl to ECF-osmotic
equilibration, both ECF&ICF increase,
equal but lower osmolality
• Hypertonic NaCl-osmotic equilibration,
shift from ICF to ECF
Regulation of cell volume:isotonic
• Water freely permeable, depends on osmotic
pressure/osmolality gradient
• Function of balance of active ion transporters and GibbsDonnan effect
• Can be modified by reduced ATP synthesis or metabolic
inhibitors e.g oubain
• Steady state determined by impermeant solutes
• Permeant solutes only cause transient changes in
volume
• The greater the permeability of membrane to permeant
solutes, the more the rapidity of time-cause of transient
changes
Response to hypotonic solution
Response to hypertonic solution
Regulation of cell
volume:nonisotonic
• ECF normally isotonic
• Certain regions non-isotonic e.g renal medulla, brain
• Regulation by organic osmolytes e.g sorbitol,
myoinositol, methylamines,tarine, glutamate, β-Alanine
• Ionic transporters e.g Na+/K+; Na+/H+;
• Specific ion channels e.g K+,Cl-,
• Cell size monitored by cytoskeleton, macromolecular
crowding, ionic strength, stimuli like stretching, second
mesengers, neurotransmitters e.g glutamate
Measurement of fluid volumes:
principles
Indicator dilution techniques
Qualities of dye:
• Easy to detect conc,
• equal equilibration rapidly, Complete mixing
• Not adsorbed onto cells or constituents
• nil disturbance of compartment
• Stays in compartment
• Can account for elimination e.g by metabolism
or excretion
• Non toxic
Measurement of fluid
volumes:agents
• Plasma volume:tagged plasma proteins e.g
Evans blue(T-1824) or iodine (131I) on albumin
• Total blood volume=plasma volX 100/(100-Ht)
• Red cell vol=TBV-plasma vol;tagged RBC space
e.g by 51 Cr,59Fe, 32 p
• ECF: inulin, mannitol, substraction from TBW
• Interstitial: indirectly
• ISF=ECF-plasma volume
• ICF=TBW-ECF
• TBW: deuterium(D2O),tritium oxide, aminopyrine
Importance of water in life
• Cell life-cell turgor and shape
• medium for Chemical and metabolic
reactions
• Transport of nutrients
• Body temperature regulation
• Elimination of waste
• Lubricant finctions