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Human physiology part 2

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