Homeostasis of body fluids G. Ogweno. Alle Ding sind Gift, und nichts ohn Gift; allein die Dosis...

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