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# Human physiology part 2

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• 1. Human Physiology<br />Chapter 6: Movement of molecules across cell membranes<br />John Paul L. Oliveros, MD<br />
• 2. Diffusion<br />Molecules of any substance are in a continuous state of movement or vibration<br />The warmer the substance is, the faster its molecules move<br />The average speed of the “thermal motion” depends on the mass of the molecule<br />Water= 2500km/h<br />Glucose= 850km/h<br />In solutions, molecules cannot travel very far before colliding with other molecules<br />The movement of molecules are random<br />The random thermal movement of molecules will redistribute solutes in a solution from regions of higher concentration to regions of lower concentration<br />Diffusion: movement of molecules from one location to another due to random thermal motion<br />
• 3. Diffusion<br />
• 4. Diffusion<br />
• 5. Diffusion<br />Flux<br />amount of material crossing a surface in a unit of time<br />Net Flux<br />The difference between the 2 one-way fluxes<br />Determines the net gain/loss of molecules from compartments separated by a membrane<br />Always occur in the direction from higher to lower concentration<br />Distribution Equilibrium<br />The two one-way fluxes are equal in magnitude but opposite in direction<br />Net flux is equal to zero<br />No further changes in the concentration of a substance in the 2 compartments will occur<br />
• 6. Diffusion<br />Properties of diffusion:<br />Three fluxes can be determined at any surface (2 opposite one-way fluxes; one net flux)<br />The net flux is the most important component in diffusion since it is the net amount of material transfered from one location to the other<br />The direction and the magnitude of the net flux are determined by the concentration difference<br />The net flux always proceeds from regions of higher concentration to regions of lower concentration<br />The greater the difference of concentration between any two regons the greater the magnitudeof the net flux<br />
• 7. Diffusion<br />Factors determining the magnitude of the net flux at any given concentration difference<br />Temperature<br />Inc. Temp inc. Speed of molecular movement inc. Net flux<br />Mass of the molecule<br />Inc. mass dec. Speed of mol. Mov.  dec net flux<br />Surface area<br />Inc S.A.  inc space for diffusion  inc net flux<br />Medium of which the molecules are moving<br />Air > Water<br />
• 8. Diffusion<br />Diffusion rate vs Distance<br />Diffusion times increase in proportion to the square of the distance over which the molecules diffuse<br />265 days<br />15ms<br />
• 9. Diffusion<br />Diffusion through membranes<br />Magnittude of the net flux is directly proportional to the difference in concentration across the membrane, the surface area of the membrane, and the membrane permeability constant<br />
• 10. Diffusion<br />Diffusion through the lipid bilayer<br />Major limiting factor of diffusion across membrane<br />Polar molecules disolve into cells slowly or not at all<br />Organic molecules<br />Nonpolar molecules dissolve rapidly <br />Can dissolve in the nonpolar regions of the lipid membrane<br />Oxygen, carbon dioxide, fatty acids, steroid hormones<br />
• 11. Diffusion <br />Diffusion of Ions through Protein Channels<br />Ions (Na+, K+, Cl -, Ca++) diffuse faster in cells with more integral membrane proteins<br />Integral proteins form channels<br />Selectivity on passage of ions<br />Diameter<br />Polarity of surface<br />
• 12. Diffusion<br />Role of Electric Forces on Ion Movement<br />Membrane potential<br />Separation of charges across the cell membrane<br />electric force that influences movemnt of ions across membranes<br />Same sign elcetric charges repel each other<br />Different sign charges attract each other<br />Most cellss are electrically negative  atract + charged ion<br />Electrochemical gradient<br />Electrochemical difference across a membrane<br />Concentration difference + electrical difference (membrane potential<br />
• 13. Diffusion<br />Regulation of Diffusion through ion channels<br />Channel gating<br />Process of opening and closing ion channels<br />Patch clamping<br />Technique that helped study ion channels<br />Ligand sensitive channels<br />Binding of specific molecules to channel proteins produces allosteric or covalent changes of the protein<br />Voltage-gated channels<br />Changes in the membrane potential causes movement of charged regions of the channel proteins<br />Mechanosensitive channels<br />Stretching the membrane affect the conformation of some channel proteins<br />
• 14. Mediated Transport Systems<br />Transporters/carriers<br />Integral membrane proteins that mediate the passage of large or polar molecules and non-diffusional movement of ions<br />Factors determining magnitude of solute flux<br />Extent to which transporter binding sites are saturated<br />The number of transporters in a membrane<br />Rate of conformational change in the transport protein<br />
• 15. Mediated Transport Systems<br />When transporters are reportedly almost saturated, the maximal transport flux depends on the rate of conformational change of the transporter to transfer its protein from one surface to the other<br />
• 16. Mediated Transport System<br />Facilitated Diffusion<br />Uses a transporter to move solutes downhill, from a higher to lower concentration until concentration between the 2 sides are the same<br />Really doesn’t involve diffusion but end results are the same<br />No energy is involved<br />E.g. Glucose transport<br />
• 17. Mediated Transport Systems<br />Active Transport<br />Uses energy to move a substance against its electrochemical gradient (uphill)<br />Requires binding of the substance to the transporter in the membrane<br />AKA pumps<br />Also exhibits specificity and saturation<br />Active transport<br />Needs continuous input of energy<br />Alter the affinity of the binding site on the transporter; higher affinity when facing one side of the membrane than the other<br />Alter the rates at which the binding site on the transporter is shifted from one surface to the other<br />Two types:<br />Primary active transport<br />Secondary active transport<br />
• 18. Mediated Transport System<br />Primary active transport<br />Transporter: ATPase<br />ATP breakdown and phosphorylation of ATPaseenergy<br />Events during active transport<br />Exposure of binding site to ECF<br />Binding of solute to the binding site<br />Removal of the PO4 group of the transporter<br />Release of solute to ICF<br />Rephosphorylation of binding site as it agian exposed to ECF<br />
• 19. Mediated Transport Systems<br />Primary Active Transport<br />Na, K-ATPase<br />Present in all plasma membranes<br />High intracellular K+ and low intracelluilar Na+<br />1 ATP 3 Na+, out<br />, 2K+ in<br />Ca-ATPase<br />In plasma membrane and endoplastic reticulum<br />H-ATPase<br />In PM, mitochondria and lysosomes<br />H, K-ATPase<br />In acid secreting cells of stomach and kidneys<br />
• 20. Mediated Transport System<br />Secondary Active Transport<br />Use ion concentration gradient as energy source<br />Events during secondary active transport<br />Altering the affinity of the binding site for the solute<br />Altering the rate of at which the binding site is shifted from one surface to the other<br />Protein allosteric modulation due to ion binding<br />
• 21. Mediated Transport System<br />Secondary Active Transport<br />Cotransport<br />Solute moves with same direction as ion<br />Countertransport<br />Solute move opposite direction of ion<br />
• 22. Mediated Transport System<br />Secondary active transport<br />Na+, Ca++ countertransport<br />Digitalis<br />Inhibits Na+,K+-atpase in heart muscle cells<br />Increase in IC Na+<br />Increase in IC Ca++<br />Increase in force of contraction of heart muscles<br />
• 23. Mediated Transport System<br />
• 24. Mediated Transport system<br />
• 25. Mediated Transport System<br />
• 26. Osmosis<br />Water<br />Small polar molecule<br />0.3 nm in diameter<br />Plasma membranes 10x more permeable to water than artificial membranes<br />Aquaporins: <br />Membrane proteins that form channels where water can diffuse<br />Number differs in different membranesa<br />Can be alterted in response to various signals<br />Osmosis<br />Net diffusion of water across membranes<br />Additon of solute decreases concentration  concentration difference  flux<br />Mol Wt of H20 = 18<br />1L H20 =1kg<br />Conc. Of H20 in pure H20 = 1000/18 = 55.5M<br />1 molecule of solute will displace1 molecule of H20<br />Dec in H20 conc= conc of solute<br />1M of glucose = 54.5 M H20<br />
• 27. Osmosis<br />The degree to which H20 conc is decreased by addition of a solute depends upon the number of particles (molecules/ions) of solute in a solution and not upon the chemical nature of the solute<br />e. g. Concentration of 1 mol glucose solution = 1mol AA soultion= 1 mol urea solution<br />A molecule that ionizes in a solution decreases the water concentration in proportion to the number of ions formed<br />e.g. 1 M of MgCl++ lowers water conc 3x than 1 M glucose<br />
• 28. Osmosis<br />Osmolarity<br />Total solute concentration of a solution<br />1 osm = 1 molecule of particle in a solution<br />1M of glucose = 1osm<br />I M of NaCl = 2 osm<br />The higher the osmolarity, the lower the water concentration<br />
• 29. Osmosis<br />Membrane impermeable to solutes but permeable to water<br />Just like plasma membrane<br />Equilibrium:<br />Equal concentrations in both compartments<br />Volume in expands in the compartment with more solutes<br />if compartments are infinitely expandle, net transfer doesn’t create a pressure gradient<br />
• 30. Osmosis<br />Membrane impermeable to solutes but permeable to water but non-expandable/limited expansion<br />H20 moves to compartment with more solutes  increase in pressure of compartment oppose net water entry<br />Osmotic pressure: the pressure that must be applied to the solution to prevent the net flow of H2O into the solution<br />
• 31. Osmosis<br />Extracellular osmolarity and cell volume<br />85% of EC solutes are Na++ and Cl-<br />Na++ moved out by Na, K-ATPase pump<br />Cl- moved out by secondary active-transport pumps<br />Both ions behave as non-penetrating solutes<br />Intracellular<br /> K+ and organic molecules<br />Organic molecules are large and polar, thus are non-penetrating<br />K+ is moved preferably moved into cells by Na, K-ATPase pump<br />Both intracellular extracellular osmolarity are kept at 300 mOsm<br />
• 32. Osmosis<br />
• 33. Endocytosis and Exocytosis<br />Endocytosis: <br />Folding of regions of PM  small pockets  IC vesicles<br />Exocytosis:<br />IC vesicles  fusion with PM  release of contents EC<br />
• 34. Endocytosis<br />Pinocytosis (cell drinking)<br />Fluid endocytosis<br />Enclosure of a small volume of ECF<br />Adsorptive endocytosis<br />Molecules bind to membrane CHONs and are carried along with ECF inside the cell when membrane invaginates<br />Phagocytosis (cell eating)<br />Large particles are engulfed by cells<br />PM folds around the surface of the particle so that little ECF is enclosed within the vesicles<br />
• 35. Exocytosis<br />Funtions:<br />To replace portions of PM removed during endocytosis<br />Route for impermeable CHONs getting outside cell<br />New CHONs  endoplasmic reticulum processing in golgi apparatus  vesicles  plasma membrane  released to ECF<br />Release triggered by stimuli that leads to an increase in cytostolic concentration in cells<br />Stimuli opens Ca++ channels in PM and/or membranes of IC organelles<br />Increase in Ca++ activates CHONs requiredfor the vesicle membrane to fuse with the PM and secrete contents EC<br />For rapid secretion of materials in response to stimulus<br />
• 36. Epithelial Transport<br />Epithelial cells<br />Line hollow organs and tubes<br />Regulate absorption and secretion of substances across membranes<br />Luminal/Apical membrane<br />Surface facing a hollow or fluid filled chamber<br />Basolateral membrane:<br />Adjacent to network of blood vessels<br />Opposite apical membrane<br />2 pathways crossing the epithelium<br />Paracellular pathway<br />Diffusion between adjacent cells<br />Limited due o tight junction membranes<br />Transcellular pathway<br />Movement across cell from apical to basal membrane<br />
• 37. Epithelial Transport<br />Transcellular Transport<br />Through diffussion and mediated transport<br />Different transport and permeability characteristics between apical and basement membranes<br />Substances undergo active transfusion across the overall epithelial layer<br />e.g. GI tract, kidneys, glands<br />
• 38. Epithelial Transport<br />
• 39. Glands<br />Glands<br />Secrete specific substances into the extracellular fluid or the lumen of ducts in response to appropriate stimuli<br />Formed during embryonic development by the infolding of the epithelial layer of an organ’s surface<br />Types of Glands<br />Exocrine gland<br />Secretions flow through the ducts and are discharged into the lumen of an organ or the surface of the skin<br />e.g. Sweat glands, salivary glands<br />Endocrine gland<br />Ductless glands<br />Secretions are released directly on the interstitial fluid surrounding the gland cells<br />Secretions then diffuses into the blood carrying it to all of the body<br />
• 40. Glands<br />Endocrine glands<br />Hormones<br />Major class of chemical messengers<br />Non-hormonal organic substances<br />e.g. Liver: glucose, A.A., fats, CHONs,<br />Types of glandular secretions<br />Organic material<br />Synthesized by cells<br />Salts and water<br />From blood supplying the tissue<br />
• 41. Glands<br />Glands<br />Undergo low basal rate of secretion<br />Signal (nerve signals, hormones)  augnmentation of secretions<br />Mechanisms in increasing secretion:<br />1. increase rate of synthesis by increasing enzyme<br />2. providing Ca ++ for exocytosis<br />3. altering pumping rates of transporter or opening ion channels<br />Glands<br />Volume of secretion increased by increasing Na+ pump activity or controlling the opening of Na+ channels in the PM<br />Increase in Na+ in the epithelium increases flow of H20 by osmosis<br />