Cellular Physiology Membrane Physiology Body Fluids: 1) Water: (universal solvent) Body water varies based on of age, sex, mass, and body composition H2O ~ 73% body weight Low body fat; Low bone mass H2O (♂) ~ 60% body weight H2O (♀) ~ 50% body weight ♀ = body fat / muscle mass H2O ~ 45% body weight Cellular Physiology Cellular Physiology In biological systems, [solute] are usually quite low and are expressed in millivolumes (10-3) Body Fluids: Body Fluids: Units for measuring [solute]: 1) Water: (universal solvent) 2) Solutes: A) moles / liter (mol / L) Total Body Water Urea mole = 6.02 x 1023 molecules Volume = 40 L A glucose concentration of 1 mol / L has (60% body weight) 6.02 x 1023 glucose molecules in 1 L of solution A) Non-electrolytes (do not dissociate in solution – neutral) B) osmoles / liter (osmol / L) Plasma • Mostly organic molecules osmole = # of particles into which a (e.g., glucose, lipids, urea) solute dissociates in solution Intracellular Fluid (ICF) Interstitial 1 mol / L of NaCl is equal to 2 osmol / L Fluid 3 = Volume Carbonic because NaCl dissociates into two particles Volume = 25 L acid Volume = 12 L (40% body weight) C) equivalents / liter (Eq / L) Plasma membrane Plasma equilavent = # of moles x valence L B) Electrolytes ++ 1 mol / L of CaCl2 equates to 2 Eq / L of Ca (dissociate into ions in solution – charged) and 2 Eq / L of Cl- in solution • Inorganic salts D) pH (used to express H+ concentration) Extracellular Fluid (ECF) • Inorganic / organic acids + pH = -log10 [H ] Volume = 15 L • Proteins A [H+] of 6.5 x 10-8 Eq / L equates to a pH of 7.19 (20% body weight) Cellular Physiology Cellular Physiology Substance ECF ICF Body Fluids: Na+ (mEq/L) 140 14 2) Solutes: K+ (mEq/L) 4 120 • The solute composition varies greatly Ca2+ (mEq/L) 2.5 1 x 10-4 between the ECF and ICF Cl- (mEq/L) 105 10 - HCO3 (mEq/L) 24 10 * pH 7.4 7.1 HOWEVER Osmolarity (mOsm/L) 290 290 The differences in solute concentration across Each body fluid compartment has the cell membranes are created and maintained by same concentration, in mEq/L, of positive transport mechanisms in cell membranes 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, 9th ed.) – Figure 26.2 1 Cellular Physiology Cellular Physiology Simple Diffusion: Cell Membrane Structure: Transport Mechanisms: Substances diffuse directly through membrane or through channel (no interaction with protein) Fluid mosaic model Downhill transport Chemical gradient Lipid bilayer A) Lipid bilayer • Phospholipids (amphipathic) • Functional barrier (no metabolic energy required) B) Integral proteins Factors affecting net diffusion (flux): • Transport proteins • Anchored via • Pore / channel proteins 1) Concentration gradient (CA – CB) 4) Size of solute molecule electrostatic • concentration gradient = flux • size = flux interactions • Anchor proteins (CAMs) Diffusion coefficient • Receptor proteins 2) Partition coefficient (K) 5) Viscosity of medium (D) [solute] in oil • viscosity = flux C) Peripheral proteins K = ----------------------- • K = flux [solute] in water • Anchored via hydrophobic interactions • Anchor proteins 6) Surface area (A) (e.g., detergents) 3) Thickness of membrane (x) • surface area = flux • Removal = lipid disruption • Enzymes Guyton & Hall (Textbook of Medical Physiology, 12th ed.) – Figure 2.3 • thickness = flux Cellular Physiology Cellular Physiology Simple Diffusion: Facilitated Diffusion: Transport Mechanisms: Substances diffuse directly through Transport Mechanisms: Substances interact with carrier membrane or through channel proteins (conformational / chemical changes) (no interaction with protein) Downhill Downhill transport transport Chemical Chemical gradient gradient Lipid bilayer Lipid bilayer (no metabolic (no metabolic energy required) energy required) Determining rate of net diffusion: Characteristics of carrier-mediated transport: Saturation Stereospecificity: Competition: J = Net rate of diffusion (mmol / sec) Recognize specific molecular isomers Recognize chemically-related solutes * P = Permeability (cm / sec) A = Surface area for diffusion (cm2) J = PA (CA – CB) CA = Conc. of solution A (mmol / L) mirror image CB = Conc. of solution B (mmol / L) * Includes K, D, and membrane thickness D-glucose L-glucose D-glucose D-galactose Cellular Physiology Cellular Physiology Primary Active Transport: Transport Mechanisms: Diabetes mellitus Transport Mechanisms: Energy derived from the breakdown (“sweet urine”) of ATP is directly coupled to Saturation: the transport process (metabolic energy required) Simple diffusion Other examples: 2+ Chemical Ca pump gradient H+ / K+ pump Increase # of Lipid bilayer V carrier proteins max Two sub-units: V Process takes Uphill max time transport • α subunit Facilitated diffusion • β subunit Rate ofDiffusion Rate Can function Na+ / K+ Pump: in reverse! Outside Inside Na+ 142 mEq/L 10 mEq/L Anchor Concentration of Substance Transport maximum (T ) Max K+ 4 mEq/L 140 mEq/L Ultimately, all carriers actively WHY? involved in shuttling substances Guyton & Hall (Textbook of Medical Physiology, 12th ed.) – Figure 4.8 Guyton & Hall (Textbook of Medical Physiology, 12th ed.) – Figure 4.11 2 Cellular Physiology Cellular Physiology Primary Active Transport: Secondary Active Transport: Transport Mechanisms: Energy derived from the breakdown Transport Mechanisms: Energy derived from concentration of ATP is directly coupled to gradient established by primary the transport process active transport (metabolic (metabolic energy required) energy required) Chemical Chemical gradient gradient 2 1 Lipid bilayer Lipid bilayer ATP Uphill Uphill transport transport How much energy is required for active transport? It depends on strength of concentration gradients being established… A) Cotransport (symport) Cotransport Solutes transported in the same Energy (cal / osmole) = 1400 log (C1 / C2) direction across membrane 10x = 1400 cal Both solutes required for transporter to function 100x = 2800 cal May require 60 – 90% of cell’s energy! Costanzo (Physiology, 4th ed.) – Figure 1.7 Cellular Physiology Cellular Physiology Secondary Active Transport: Transport Mechanisms: Energy derived from concentration Prescription Drug: gradient established by primary active transport Cardiac glycosides are a class of drugs that (metabolic + + energy required) inhibit Na / K pumps Chemical gradient + 2 1 Na Lipid bilayer ATP K+ Na+ / K+ pump Uphill transport Cardiac muscle + cell Na Digitalis ++ A cornerstone for the Ca (antiport) Cotransport B) Countertransport treatment of heart failure cardiac contractility Solutes transported in opposite ( cardiac contractility) directions across membrane Na+ / Ca++ countertransporter Both solutes required for transporter to function Common + foxglove Na Costanzo (Physiology, 4th ed.) – Figure 1.8 Digitalis purpurea Cellular Physiology Cellular Physiology Low [solute] to high [solute] concentration Osmosis: Osmosis: Osmosis: Movement of water across a semi-permeable membrane due to differences Osmosis: Movement of water across a semi-permeable membrane due to differences in solute concentrations in solute concentrations Osmosis depends on the osmolarity of the two solutions in question: Osmotic Pressure: The amount of pressure Osmolarity = g C necessary to stop osmosis (mOsm / L) g = # of particles per mole in solution (Osm / mol) • Takes into account whether there is complete or Pressure difference driving partial dissociation force for osmotic water flow C = concentration (mmol / L) ( osmotic pressure = rate of osmosis) van’t Hoff Isosmotic Hyperosmotic Hyposmotic = g C R T equation Solutions with same osmolarity Solution with osmolarity Solution with osmolarity Osmotic pressure () depends on: = Osmotic pressure (atm) 1) Concentration of osmotically active particles g = # of particles per mole in solution (Osm / mol) C = Concentration (mmol / L) 2) Ability of solute to cross membrane H2O = Reflection coefficient (varies from 0 – 1) R = Gas constant (0.082 L – atm / mol – K) 25.5 L – atm / mol T = Absolute temperature (K) Guyton & Hall (Textbook of Medical Physiology, 12th ed.) – Figure 4.10 Guyton & Hall (Textbook of Medical Physiology, 12th ed.) – Figure 4.10 3 Costanzo (Physiology, 4th ed.) – Figure 1.10 Cellular Physiology = g C R T Osmosis: Reflection coefficient: Ease at which a solute crosses a membrane = 1 = 0 = 0 to 1 Membrane Membrane Membrane is impermeable freely permeable partially permeable to solute to solute to solute (e.g., albumin) (e.g., urea) (most solutes) Tonicity: The effective osmotic pressure between two solutions Net water movement from a hypotonic solution to a hypertonic solution 10 10 Isotonic 10 5 effective effective osmotic = osmotic Sol. Sol. pressure pressure 1 2 Sol. Sol. 1 2 No net water movement Hypertonic Hypotonic between solutions Higher effective Lower effective osmotic pressure osmotic pressure 4 .