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Anatomy & Physiology 101-805 Unit 4 Transport Across The Cell Membrane Paul Anderson 2017 METHODS OF MEMBRANE TRANSPORT • Simple Diffusion • Facilitated Diffusion • Osmosis Passive Transport No ATP needed • Dialysis • Active Transport • Vesicle Transport (Exo & Endocytosis) ATP required Simple Diffusion • A sample of dye dissolves in water then spreads by simple diffusion throughout the water. • Simple Diffusion is the tendency for molecules or ions to randomly distribute because of their kinetic (heat) energy. Martini & Bartholomew Figure 3.4 Stages of Simple Diffusion-1 • SIMPLE DIFFUSION of molecules/ions occurs in all directions. • NET DIFFUSION is the overall movement down a CONCENTRATION GRADIENT. STAGE 1 Maximum Concentration Gradient & Net Diffusion A A B A B = 4 - 0 = 4 mols/t Net Diffusion Maximum rate of net diffusion Maximum Concentration gradient B Stages of Simple Diffusion-2 Reduced CONCENTRATION GRADIENT causes a reduced rate of NET DIFFUSION STAGE 2 Reduced Concentration Gradient & Net Diffusion A A A B B = 3 - 1 = 2 mols/t Net Diffusion Reduced rate of net diffusion Reduced Concentration gradient B Stages of Simple Diffusion-3 LAW OF DIFFUSION Substances show a NET DIFFUSION down their CONCENTRATION GRADIENT until they reach a DIFFUSION EQUILIBRIUM STAGE 3 Diffusion Equilibrium No Net Diffusion A A A B B No Concentration Gradient B = 2 - 2 = 0 mols/t • Net Diffusion ceases but • Simple Diffusion continues to maintain a dynamic equilibrium. Summary of Simple Diffusion • Simple Diffusion is the tendency for molecules or ions to randomly distribute because of their kinetic (heat) energy. • Simple Diffusion occurs in all directions. • in Simple Diffusion substances obey the Law of Diffusion: • Simple Diffusion does not require a membrane or a carrier. • Simple Diffusion does not use ATP so is Passive Transport. Molecules Simple Diffusion through a membrane Membrane Concentration Gradient Net Diffusion Reduced Concentration Gradient Reduced Net Diffusion Diffusion Equilibrium Simple Diffusion across the Cell Membrane Cell Membrane SIMPLE DIFFUSION occurs across the cell membrane in two ways: • HYDROPHOBIC MOLECULES diffuse through the membrane lipids, e.g. O2, CO2, lipids. • SMALL HYDROPHILIC POLAR MOLECULES or IONS diffuse through channels in membrane proteins, e.g. H2O, Na+, K+, Cl-. Concentration gradient Law of Diffusion & Gas Exchange In body fluids each molecule or ion shows a NET DIFFUSION down its own concentration gradient until it reaches a DIFFUSION EQUILIBRIUM. In the lungs • O2 shows a net diffusion into blood from alveoli. • CO2 shows a net diffusion out of blood into alveoli. O2 CO2 Conc gradient air Air sac& Reece fig 7.11 Campbell (alveolus) blood Pulmonary capillary Glucose Enters Cells by Facilitated Diffusion • FACILITATED DIFFUSION is the diffusion of molecules cross the cell membrane using a specific membrane CARRIER PROTEIN. • Glucose enters most cells from the IF by this method. • The rate of Facilitated Diffusion depends on the number of carriers. • Insulin increases the number of glucose carriers in target cells which increases the rate of glucose uptake. Glucose molecule attaches to receptor site Receptor site INTERSTITIAL FLUID Carrier protein Martini & Bartholomew Figure 3.8 Change in shape of carrier protein CYTOPLASM Glucose released into cytoplasm Facilitated Diffusion: Carrier Mediated Transport Cell Membrane Carrier protein Carrier protein Carrier protein Carrier protein Net diffusion down Concentration gradient • Unlike simple diffusion Facilitated Diffusion only occurs across cell membranes and requires a membrane carrier protein. • Molecules crossing by Facilitated Diffusion are transported using kinetic (heat) energy so they obey the LAW of DIFFUSION. • Facilitated Diffusion does NOT use ATP so is PASSIVE TRANSPORT. Cell Membrane ATP Carrier protein ATP Carrier protein Active Transport • Unlike Diffusion ACTIVE TRANSPORT moves molecules or ions in one direction up their concentration gradient opposing net diffusion. • Like Facilitated Diffusion Active Transport requires a specific carrier protein. • The carrier is like an enzyme but catalyses the physical process of membrane transport. • Unlike Diffusion Active Transport is a form of biological work and so requires energy in the form of ATP. Concentration gradient • Energy from ATP is used to change the shape of the carrier so that the molecules/ions can only be transported up their concentration gradient . Comparison of 3 Methods of Membrane Transport Channel protein Carrier protein ATP Cell Membrane Simple Diffusion Facilitated Diffusion Active Transport Three Examples of Active Transport in the Body 1. The Na+/K+ pump is a carrier protein in all body cells that moves Na+ out of cells and moves K + into cells. 2. Amino acids enter all cells by active transport. 3. Glucose enters intestinal cells from the GI tract by secondary active transport (co-transported with Na) indirectly dependent on the ATP- driven Na pump. Intestinal lumen Na+ Common carrier for Na & glucose Intestinal epithelial cell Interstitial fluid ATP Na+ glucose • Na moves into intestinal cells by facilitated diffusion down its concentration gradient created by the Na pump. • Glucose moves up its concentration gradient by active transport using the same carrier. Na/K pump The Na+/K+ Pump Moves Na Out & K Into Cells The Na+/K+PUMP is a protein carrier which moves Na+ out of cells and moves K+ into cells by ACTIVE TRANSPORT opposing net diffusion for each ion. Na+ INTERSTITIAL + Na FLUID Na+3 Na+ Sodium– Potassium Exchange Pump 2 K+ K+ K+ ATP ADP CYTOPLASM Martini & Bartholomew, fig 3-9 Functions of The Na+/K+PUMP The Na+/K+pump has two important functions. 1. It concentrates Na+ in the ECF and concentrates K+ in the ICF. 2. It helps create a polarized membrane in which the external cell surface is positively charged with respect to the inside of the membrane. The Na+/K+ Pump Helps Create a Polarized Cell Membrane • The Na/K pump moves 3 Na+ out of cells for every 2 K+ moved in so adding more positive charge to the ECF than to the ICF. • ACTIVE TRANSPORT of Na+, K+ helps create a POLARIZED CELL. • In a polarized cell the exterior has a slight excess of positive charge and the interior an excess of negative charge. • This is called the cell’s Resting Membrane Potential, important for nerve & muscle cell function. K+ K+ ICF -- Carrier ATP Protein Na K pump Cell Membrane + + + + + Na+ Na+ Na+ ECF Figure 3.5 Summary of Methods for Crossing Cell Membrane Hydrophobic molecules can diffuse through membrane lipids. INTERSTITIAL FLUID cell membrane INTRACELLULAR FLUID Steroids, fats O2 CO2 • Glucose • amino acids • Na+ & K+ (via pump) Hydrophilic molecules/ions may cross membrane using a membrane protein carrier. Martini & Bartholomew, fig 3-5 Channel protein • Na+ • K+ • Cl• H2O Small hydrophilic Molecules/ions can diffuse through membrane channels. Vesicle Transport Large molecules or particles move in or out of cells via Vesicle Transport. - Endocytosis requires ATP: three types exist 1. Receptor Mediated Endocytosis: specific uptake of large solutes & requires membrane receptors. 2. Pinocytosis: non - specific uptake of large solutes. 3. Phagocytosis: uptake of particles, e.g. bacteria, by phagocytic cells of the immune system. - Exocytosis: secretion of large molecules from the cell via secretory vesicles. Receptor-Mediated Endocytosis • Although Cholesterol is hydrophobic it enters cells from the IF by Receptor-Mediated Endocytosis. • This ensures that cells can take in cholesterol even if the ECF concentration is lower than the ICF. Lipoprotein with cholesterol Receptor protein Martini & Bartholomew, fig 3-10 Definition of OSMOSIS OSMOSIS is the simple diffusion of solvent (water) molecules through a SEMIPERMEABLE MEMBRANE. Martini & Bartholomew, fig 3-6 2 glucose solutions separated by a semipermeable (= selectively permeable) membrane solvent (H2O) can cross membrane A SEMIPERMEABLE MEMBRANE is selectively permeable to the solvent (e.g. H2O) but does not allow passage of the solute, (e.g. sugar). solute (glucose) cannot cross membrane Concentrations of Solute & Solvent in a Solution • A more concentrated solution (e.g. 5% glucose) has • a greater solute concentration but • a lower solvent concentration than a less concentrated (i.e. more dilute) solution (e.g. 1% glucose). Solution A • 1% glucose • Lower concentration of solute (glucose) • Greater concentration of solvent (water) A Water molecules B Glucose molecules Martini & Bartholomew, fig 3-6 Solution B 5% glucose • Greater concentration of solute (glucose) • Lower concentration of solvent (water) Semipermeable membrane Solute Particles Lower the Concentration of Water • Solute particles attract water molecules forming hydration shells. • This effectively reduces the concentration of freely diffusible water. H2O molecules form hydration shell around solute particle Freely diffusible solvent (H2O) can cross membrane Solute particle Water molecule Hydration shell lowers freely diffusible [H2O ] H2O in hydration shells cannot cross membrane NET OSMOSIS NET OSMOSIS is the NET DIFFUSION of WATER (or solvent) through a semi-permeable membrane • from a region of HIGH H2O concentration to LOW H2O concentration or • from LOW SOLUTE concentration to a HIGH SOLUTE concentration, until an OSMOTIC EQUILIBRIUM occurs. Solution A (1%) • Low [solute] • High [solvent] Solution B (5%) • High [solute] • Low [solvent] A B Volume increased Volume decreased net osmosis 3% glucose Martini & Bartholomew, fig 3-6 • At equilibrium, the solvent & solute concentrations on each side of the membrane are equal. • Net Osmosis has caused the volume of solution B to increase and volume of solution A to decrease. 3% glucose OSMOTIC PRESSURE • OSMOTIC PRESSURE (=osmotic potential) is a measure of the ability of a given solution to attract H2O molecules by net osmosis. • Therefore NET OSMOSIS will occur from a solution of lower osmotic pressure into a solution of higher osmotic pressure until an OSMOTIC EQUILIBRIUM is reached. 1% glucose 3% glucose 5% glucose Net osmosis 1% glucose solution • HIGH H2O concentration • LOW SOLUTE concentration • LOW OSMOTIC PRESSURE time net osmosis 3% glucose Osmotic equilibrium 5% glucose solution • LOW H2O concentration • HIGH SOLUTE concentration • HIGH OSMOTIC PRESSURE OSMOLAR CONCENTRATION The most important variable influencing the osmotic pressure of a solution is the total concentration of solute particles, called the osmolar concentration. Osmolar concentration = molar concentration x particles per molecule. For electrolytes Osmolar concentration = molar concentration x # ions per molecule. 1 molar glucose → 1 osmolar (1 osmol/L) 1 molar NaCl → 2 osmolar (2 osmol/L) i.e. Na+ + Cl1 molar CaCl2 → 3 osmolar (3 osmol/L) i.e. Ca++ + 2Cl- OSMOSIS Summary Osmosis simple diffusion of solvent (water) molecules through a SEMIPERMEABLE MEMBRANE. Osmotic Equilibrium Solution 1 ↑[H2O ] ↓[solute] Solution 2 ↓ [H2O ] ↑[solute] hydration shell lowers freely diffusible [H2O ] ↓ Volume in solution 1 Net osmosis into solution 2 ↑ Volume in solution 2 ------ Semipermeable Membrane Allows diffusion of solvent H2O but NOT solute Solute Particles attract H2O molecules forming hydration shells OSMOSIS Summary -2 1 1% glucose solutions 2 1 Net osmosis Osmotic pressure [solute] [H2O] ≪ 5% glucose solutions 3% glucose 1 2 3% glucose Osmotic equilibrium Osmotic pressure Osmotic pressure [solute] [solute] = [solute] [H2O] [H2O] ≫ [H2O] In net osmosis H2O molecules obey the law of diffusion. = = Osmotic pressure ↓volume ↑volume 1 2 • OSMOTIC PRESSURE (osmotic potential) is a measure of the ability of a given solution to attract H2O molecules. • Osmotic pressure is determined by the total osmolar [solute]. Diffusion & Osmosis in the Body • Simple Diffusion and Osmosis occur in the body to transport molecules over short distances within cells and across membranes. • Simple Diffusion and Osmosis therefore occur across the Cell membrane and the Capillary wall. OSMOSIS across the Cell Membrane • The cell membrane is a semipermeable (=selectively permeable) membrane since • although Na+ and K+ can freely diffuse through the cell membrane, active transport pumps them in the opposite direction i.e. up their concentration gradients. • The cell membrane thus acts as if it were impermeable to these ions, to Cl- which follows Na+ and to large organic molecules (e.g. proteins) which cannot diffuse across the membrane due to their size and charge. Cl+ Na Net Diffusion + Cl K K+ K+ ICF K+ Protein anions H2 O Na+ H2 O K+ Na+ Na+ Cell membrane IF Cl- ClClNa+ Cl- Active Transport Osmotic Equilibrium Osmosis Across The Cell Membrane • Na+, K+, and proteins are “non-penetrating” solutes for the cell membrane. • Any change in the concentrations of any of these non-penetrating solutes results in net osmosis across the cell membrane and a change in cell volume. Effect of Hypertonic Solutions on the Cell & ECF • Raising the extracellular [Na+] (sodium retention by the body) raises the extracellular osmotic pressure and causes net osmosis out of cells (cellular dehydration) & cellular shrinking (CRENATION). • The ECF in this case is HYPERTONIC to cells and since it has a higher osmotic pressure than the ICF is HYPEROSMOTIC to the ICF. Hypernatremia ↓ ICF vol ↑ ECF vol crenation (= 0.2 M) Cell shrinks ↓ ICF vol Osmolarity of ICF = 0.3 osmoles/L net osmosis out of cells Solution is hypertonic edema ↑ ABP Hypertonic ECF ↓ [H2O ] ↑ [solute] ↑ OP Effect OSMOSIS of Hypotonic across Solutions the Cell onMembrane the Cell & -ECF 2 • Lowering the extracellular [Na+] lowers the extracellular osmotic pressure which causes net osmosis into the cells (cellular overhydration) and the cell membrane may burst (HEMOLYSIS). • The ECF in this case is HYPOTONIC and HYPOOSMOTIC to the ICF. Hyponatremia ↑ ICF vol ↓ ECF vol hemolysis ↓ ABP Cell expands (= 0.1 M) Hypotonic ECF ↑ [H2O ] net osmosis into cells Solution is hypotonic ↓[solute] ↓ OP Effect OSMOSIS of Isotonic across Solutions the Cell on Membrane the Cell & -ECF 3 • A solution in which the extracellular osmolar [Na+] is equal to the intracellular osmolar [non -diffusible solutes] will be in OSMOTIC EQUILIBRIUM, cause no change in cell volume and is said to be ISOTONIC. • The ECF in this case has the same osmotic pressure as the ICF so is ISOSMOTIC to the ICF. 0.15M NaCl 8.7g/L 0.87 g% Isotonic saline (= 0.15 M) Normal RBC osmotic equilibrium iso Summary of OSMOSIS & RED BLOOD CELLS CELLS are normally in OSMOTIC EQUILIBRIUM with the ECF, i.e. the ICF & ECF are ISOTONIC. If blood cells are exposed to non - isotonic fluids net osmosis will occur and they will expand and burst or else shrink. RED BLOOD CELL Hypotonic solution Hypertonic solution Isotonic solution H2 O Hemolysed cell H2 O H2 O Normal cell H2 O Crenated cell OSMOSIS across the Capillary Wall • The body normally maintains an ISOTONIC ECF and removes excess water and electrolytes by excretion (via kidneys). • Plasma proteins are non – penetrating solutes for the capillary membrane & determine the osmotic pressure of the blood. • Plasma proteins attract water into blood at capillaries so helping to prevent edema. • Any drop in plasma protein level (e.g. from hepatic disease) will lower the osmotic pressure of the blood causing net osmosis out of the blood and edema. Hepatic Disease (cirrhosis) Decreased plasma proteins Decreased Blood Osmotic Pressure Net osmosis Edema DIALYSIS • Dialysis is the process of separating SMALL MOLECULES (crystalloids, e.g. NaCl, glucose, amino acids) from LARGE MOLECULES (colloids, mainly proteins) across a SEMIPERMEABLE (DIALYSING) MEMBRANE. • HEMODIALYSIS is the process of purifying the blood by allowing dialysis to occur between the blood and a dialysing fluid. • HEMODIALYSIS RESTORES HOMEOSTASIS in cases of kidney failure. Arterial blood enters HEMODIALYSIS Net diffusion Dialysing Fluid leaves Net osmosis Net diffusion Blood cells & colloids do not cross membrane Purified blood returned to vein Dialysing membrane Allows small molecules across Dialysing Fluid enters HEMODIALYSIS Semipermeable Dialysing membrane separates blood from dialysate fluid. Source MedBroadcast.com Comparison of Methods for Crossing the Cell membrane NEEDS NEEDS PROCESS MEMBRANE ATP SIMPLE DIFFUSION FACILITATED DIFFUSION OSMOSIS ACTIVE TRANSPORT DIALYSIS UP or ONLY in ACTIVE DOWN LIVING or PASSIVE CONC GRAD CELLS NEEDS a CARRIER EXAMPLES