Membrane Physiology Body Fluids: 1) Water: (universal solvent) Body water varies based on of age, sex, mass, and body composition H 2 O ~ 73% body weight Low body fat; Low bone mass H 2 O ( ) ~ 60% body weight H 2 O ( ) ~ 50% body weight = body fat / muscle mass H 2 O ~ 45% body weight 1
Plasma membrane Body Fluids: 1) Water: (universal solvent) Total Body Water Volume = 40 L (60% body weight) Intracellular Fluid (ICF) Volume = 25 L (40% body weight) Interstitial Fluid Volume = 12 L Plasma Volume = 3 L Extracellular Fluid (ECF) Volume = 15 L (20% body weight) Body Fluids: 2) Solutes: Urea A) Non-electrolytes (do not dissociate in solution neutral) Mostly organic molecules (e.g., glucose, lipids, urea) Carbonic acid Units for measuring [solute]: A) moles / liter (mol / L) In biological systems, [solute] are usually quite low and are expressed in millivolumes (10-3 ) mole = 6.02 x 10 23 molecules A glucose concentration of 1 mol / L has 6.02 x 10 23 glucose molecules in 1 L of solution B) osmoles / liter (osmol / L) osmole = # of particles into which a solute dissociates in solution 1 mol / L of NaCl is equal to 2 osmol / L because NaCl dissociates into two particles C) equivalents / liter (Eq / L) B) Electrolytes (dissociate into ions in solution charged) Inorganic salts Inorganic / organic acids Proteins equilavent = # of moles x valence 1 mol / L of CaCl 2 equates to 2 Eq / L of Ca ++ and 2 Eq / L of Cl - in solution D) ph (used to express H + concentration) ph = -log 10 [H + ] A [H + ] of 6.5 x 10-8 Eq / L equates to a ph of 7.19 2
Body Fluids: 2) Solutes: The solute composition varies greatly between the ECF and ICF HOWEVER Substance ECF ICF Na + (meq/l) 140 14 K + (meq/l) 4 120 Ca 2+ (meq/l) 2.5 1 x 10-4 Cl - (meq/l) 105 10 HCO - 3 (meq/l) 24 10 ph 7.4 7.1 Osmolarity (mosm/l) 290 290 * Each body fluid compartment has the same concentration, in meq/l, of positive ions (cations) and negative ions (anions) (Principle of Macroscopic Electroneutrality) & The total solute concentration (osmolarity) is the same in ICF and ECF (water moves freely across cell membranes) Marieb & Hoehn (Human Anatomy and Physiology, 9 th ed.) Figure 26.2 The differences in solute concentration across cell membranes are created and maintained by mechanisms in cell membranes 3
Cell Membrane Structure: Fluid mosaic model A) Phospholipids (amphipathic) Functional barrier B) Integral proteins Anchored via electrostatic interactions Transport proteins Pore / channel proteins Anchor proteins (CAMs) Receptor proteins Anchored via hydrophobic interactions Removal = lipid disruption (e.g., detergents) Guyton & Hall (Textbook of Medical Physiology, 12 th ed.) Figure 2.3 C) Peripheral proteins Anchor proteins Enzymes Transport Mechanisms: Downhill Simple Diffusion: Substances diffuse directly through membrane or through channel (no interaction with protein) (no metabolic Factors affecting net diffusion (flux): 1) Concentration (C A C B ) concentration = flux 2) Partition coefficient (K) [solute] in oil K = ----------------------- [solute] in water 3) Thickness of membrane ( x) thickness = flux K = flux 4) Size of solute molecule size = flux 5) Viscosity of medium viscosity = flux 6) Surface area (A) surface area = flux Diffusion coefficient (D) 4
Transport Mechanisms: Downhill Simple Diffusion: Substances diffuse directly through membrane or through channel (no interaction with protein) (no metabolic Determining rate of net diffusion: J = PA (C A C B ) * J = Net rate of diffusion (mmol / sec) P = Permeability (cm / sec) A = Surface area for diffusion (cm 2 ) C A = Conc. of solution A (mmol / L) C B = Conc. of solution B (mmol / L) * Includes K, D, and membrane thickness Transport Mechanisms: Facilitated Diffusion: Substances interact with carrier proteins (conformational / chemical changes) Downhill (no metabolic Characteristics of carrier-mediated : Saturation Stereospecificity: Recognize specific molecular isomers Competition: Recognize chemically-related solutes mirror image D-glucose L-glucose D-glucose D-galactose 5
Anchor Rate of Diffusion Transport Mechanisms: Saturation: Diabetes mellitus ( sweet urine ) Simple diffusion Increase # of carrier proteins V max V max Process takes time Facilitated diffusion Concentration of Substance WHY? Transport maximum (T Max ) Ultimately, all carriers actively involved in shuttling substances Guyton & Hall (Textbook of Medical Physiology, 12 th ed.) Figure 4.8 Transport Mechanisms: Primary Active Transport: Energy derived from the breakdown of ATP is directly coupled to the process (metabolic Other examples: Ca 2+ pump H + / K + pump Uphill Two sub-units: α subunit β subunit Na + K + Na + / K + Pump: Outside Inside 142 meq/l 4 meq/l 10 meq/l 140 meq/l Can function in reverse! Guyton & Hall (Textbook of Medical Physiology, 12 th ed.) Figure 4.11 6
Transport Mechanisms: (metabolic Primary Active Transport: Energy derived from the breakdown of ATP is directly coupled to the process Uphill How much energy is required for active? It depends on strength of concentration s being established Energy (cal / osmole) = 1400 log (C 1 / C 2 ) 10x = 1400 cal 100x = 2800 cal May require 60 90% of cell s energy! Transport Mechanisms: Secondary Active Transport: Energy derived from concentration established by primary active (metabolic 2 1 ATP Uphill A) Co (symport) Solutes ed in the same direction across membrane Co Both solutes required for er to function Costanzo (Physiology, 4 th ed.) Figure 1.7 7
Transport Mechanisms: Secondary Active Transport: Energy derived from concentration established by primary active (metabolic 2 1 ATP Uphill B) Counter (antiport) Solutes ed in opposite directions across membrane Co Both solutes required for er to function Costanzo (Physiology, 4 th ed.) Figure 1.8 Prescription Drug: Cardiac glycosides are a class of drugs that inhibit Na + / K + pumps Na + K + Na + / K + pump Cardiac muscle cell Na + Digitalis A cornerstone for the treatment of heart failure ( cardiac contractility) Ca ++ cardiac contractility Na + / Ca ++ counterer Common foxglove Digitalis purpurea Na + 8
Osmosis: Low [solute] to high [solute] concentration Osmosis: Movement of water across a semi-permeable membrane due to differences in solute concentrations Osmosis depends on the osmolarity of the two solutions in question: Osmolarity = g C (mosm / L) g = # of particles per mole in solution (Osm / mol) Takes into account whether there is complete or partial dissociation C = concentration (mmol / L) Isosmotic Solutions with same osmolarity Hyperosmotic Solution with osmolarity Hyposmotic Solution with osmolarity H 2 O Guyton & Hall (Textbook of Medical Physiology, 12 th ed.) Figure 4.10 Osmosis: Osmosis: Movement of water across a semi-permeable membrane due to differences in solute concentrations Osmotic Pressure: The amount of pressure necessary to stop osmosis Pressure difference driving force for osmotic water flow ( osmotic pressure = rate of osmosis) Osmotic pressure ( ) depends on: 1) Concentration of osmotically active particles 2) Ability of solute to cross membrane 25.5 L atm / mol = g C R T = Osmotic pressure (atm) g = # of particles per mole in solution (Osm / mol) C = Concentration (mmol / L) = Reflection coefficient (varies from 0 1) R = Gas constant (0.082 L atm / mol K) T = Absolute temperature (K) van t Hoff equation Guyton & Hall (Textbook of Medical Physiology, 12 th ed.) Figure 4.10 9
Costanzo (Physiology, 4 th ed.) Figure 1.10 Osmosis: = g C R T Reflection coefficient: Ease at which a solute crosses a membrane = 1 Membrane impermeable to solute (e.g., albumin) = 0 Membrane freely permeable to solute (e.g., urea) = 0 to 1 Membrane is partially permeable to solute (most solutes) 10 10 Sol. 1 Tonicity: The effective osmotic pressure between two solutions effective osmotic pressure Isotonic = effective osmotic pressure Sol. 2 Sol. 1 Hypertonic No net water movement between solutions Higher effective osmotic pressure Net water movement from a hypotonic solution to a hypertonic solution 10 5 Sol. 2 Hypotonic Lower effective osmotic pressure 10