Physiology

• Lipid bilayer


  • Phospholipids have a glycerol backbone (hydrophilic head) and two fatty acid tails (hydrophobic)
  • Hydrophobic tails face each other and form a bilayer
  • Lipid-soluble substances can cross cell membranes by dissolving in the hydrophobic lipid bilayer
  • Water-soluble substances cannot dissolve in the lipid of the membrane, but may cross through water-filled channels or be transported by carriers
• Integral proteins


  • Anchored to and imbedded in the cell membrane through hydrophobic interactions
  • May span the cell membrane
  • Include ion channels, transport proteins, receptors, and G proteins
• Peripheral proteins


  • Not imbedded in the cell membrane
  • Not covalently bound to membrane components
  • Loosely attached to the cell membrane by electrostatic interactions
• Tight junctions


  • Attachments between cells, often epithelial cells
  • May be an intercellular pathway for solutes, depending on size, charge, and characteristics
  • May be "tight" (impermeable) or "leaky" (permeable)
• Gap junctions


  • Attachments between cells that permit intercellular communication
  • Permit current flow and electrical coupling between myocardial cells
• Simple diffusion


  • The only form of transport that is not carrier mediated
  • Occurs down an electrochemical gradient ("downhill")
  • Does not require metabolic energy and is therefore passive
• Measuring diffusion


  1. J = PA(C1 - C2)

  2. J = flux (flow) (mmol/sec)

  3. P = permeability (cm/sec)

  4. A = area (cm2)

  5. C1 = concentration1 (mmol/L)

  6. C2 = concentration2 (mmol/L)
• Sample calculation for diffusion

  • Urea concentration of blood is 10 mg/100 mL
  • Urea concentration of proximal tubular fluid is 20 mg/100 mL
  • Permeability to urea is 1 x 10^-5 cm/sec
  • Surface area is 100 cm2
  • Flux = 1 x 10^-5 cm/sec * 100 cm2 * (20/100 - 10/100) mg/mL = 0.1 mg/sec from lumen to blood (high to low concentration)
• Characteristics of different types of transport

  • Simple diffusion: Downhill, No carrier, No metabolic energy, No Na+ gradient, No inhibition of Na+-K+ pump
  • Facilitated diffusion: Downhill, Yes carrier, No metabolic energy, No Na+ gradient, No inhibition
  • Primary active transport: Uphill, Yes carrier, Yes metabolic energy, No Na+ gradient, Inhibits Na+-K+ pump if it
  • Cotransport: Uphill*, Yes carrier, Indirect metabolic energy, Yes Na+ gradient in same direction, Inhibits
  • Countertransport: Uphill*, Yes carrier, Indirect metabolic energy, Yes Na+ gradient in opposite direction, Inhibits
• Flux


  The rate of flow of a substance across a surface or through a membrane
• The minus sign preceding the diffusion equation indicates that the direction of flux, or flow, is from high to low concentration
• 1 mL = 1 cm3
• Characteristics of Different Types of Transport

  • Simple diffusion
  • Facilitated diffusion
  • Primary active transport
  • Cotransport
  • Countertransport
• Simple diffusion


  • Occurs down an electrochemical gradient
  • Does not require metabolic energy
  • Is passive
• Facilitated diffusion


  • Occurs down an electrochemical gradient
  • Does not require metabolic energy
  • Is carrier-mediated
  • Exhibits stereospecificity, saturation, and competition
• Primary active transport


  • Occurs against an electrochemical gradient
  • Requires direct input of metabolic energy in the form of ATP
  • Is carrier-mediated
  • Exhibits stereospecificity, saturation, and competition
• Cotransport (Symport)


  • Two or more solutes are transported in the same direction
  • One solute (usually Na+) is transported downhill and provides energy for the uphill transport of the other solute(s)
  • Metabolic energy is not provided directly but indirectly from the Na+ gradient
• Countertransport (Antiport)


  • The solutes move in opposite directions across the cell membrane
  • One solute is transported uphill while the other is transported downhill
  • Metabolic energy is not provided directly but indirectly from the Na+ gradient
• Permeability


  The ease with which a solute diffuses through a membrane
• Factors that increase permeability: Increased oil/water partition coefficient of the solute, decreased radius (size) of the solute, decreased membrane thickness
• Small hydrophobic solutes (e.g., O2, CO2) have the highest permeabilities in lipid membranes
• Hydrophilic solutes (e.g., Na+, K+) must cross cell membranes through water-filled channels, or pores, or via transporters
• Carrier-mediated transport


  • Includes facilitated diffusion, primary active transport, and secondary active transport
  • Exhibits stereospecificity, saturation, and competition
• Osmolarity


  The concentration of osmotically active particles in a solution
• Two solutions that have the same calculated osmolarity are isosmotic
• If two solutions have different calculated osmolarities, the solution with the higher osmolarity is hyperosmotic and the solution with the lower osmolarity is hyposmotic
• Osmosis


  The flow of water across a semipermeable membrane from a solution with low solute concentration to a solution with high solute concentration
• The osmotic pressure increases when the solute concentration increases
• Two solutions having the same effective osmotic pressure are isotonic
• If two solutions separated by a semipermeable membrane have different effective osmotic pressures, the solution with the higher effective osmotic pressure is hypertonic and the solution with the lower effective osmotic pressure is hypotonic
• Reflection coefficient (σ)


  A number between zero and one that describes the ease with which a solute permeates a membrane
• If the reflection coefficient is one, the solute is impermeable and will exert maximal effective osmotic pressure
• If the reflection coefficient is zero, the solute is completely permeable and will not exert any osmotic effect
• Effective osmotic pressure


  The osmotic pressure (calculated by van't Hoff's law) multiplied by the reflection coefficient
• Ion channels


  Integral proteins that span the membrane and, when open, permit the passage of certain ions
• Ion channels


  • Are selective, permitting the passage of some ions but not others
  • May be open or closed, controlling the flow of ions
  • Their conductance depends on the probability that the channel is open
• Voltage-gated channels


  • Opened or closed by changes in membrane potential
• Ligand-gated channels


  • Opened or closed by hormones, second messengers, or neurotransmitters
• Selective


  Can flow through (when channel is open), cannot flow through (when channel is closed)
• Conductance of a channel

  Depends on the probability that the channel is open. Higher probability = higher conductance/permeability