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
compartment
%body wt
Vol(L) barrier
Total Body water
60% 42
ICF 40% 28 Cell membrane
ECF(ISF/plasma)
20(15&5)
14(10.5&3.5)
Capillary 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 transportersWater channels: aquaporinsIon channels: Na+,K+,Ca++,Cl-,Anion,CatSolute carriers:• Uniport:glucose(Glut2),Fructose(Gluts),Urea(UT-A),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 Gibbs-Donnan 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 techniquesQualities 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