Textbooks

• Physiology is closely intertwined with medicine
• Structure and function are inextricably linked because the living structures perform the functions
• Branches of physiology


  • Physiology of the whole person (e.g. exercise physiology)
  • Physiology of individual organ systems (e.g. cardiovascular, respiratory, gastrointestinal)
  • Cellular and molecular physiology
  • Comparative physiology
  • Medical physiology
• Physiology has evolved from a more qualitative to a more quantitative science
• Physiological genomics


  The link between the organ and the gene
• Cells and organs must interact with one another, and the method of communication is almost always molecular
• Milieu intérieur


  The well-controlled liquid environment that bathes all the anatomic elements of the tissues, the lymph or the plasma
• The milieu intérieur isolates the organs and tissues of the body from the vagaries of the physical conditions of the environment
• Some fluids contained within the body are not really inside the body at all, as they are continuous with the milieu extérieur (e.g. contents of gastrointestinal tract, sweat ducts, renal tubules)
• The constancy of the extracellular fluid (the milieu intérieur) is the condition of "free, independent life"
• Each organ system contributes to compensate and equilibrate against changes in the external environment, creating and maintaining a constant internal environment
• The surface of the cell is defined by a membrane
• Plasma membrane


  Impermeable to large molecules, selectively permeable to small molecules
• The chemical composition of the cell interior is very different from that of its surroundings
• The cytoplasm is an extraordinarily complex solution containing myriad proteins, nucleic acids, nucleotides, and sugars
• The cell expends tremendous energy to regulate the intracellular concentrations of numerous ions
• Plasma membrane


  Provides a barrier to prevent exchange between the intracellular and extracellular spaces
• The metabolic requirements of the cell demand a plasma membrane that is much more selectively permeable
• Intracellular environment


  Precisely regulated, extraordinarily complex solution containing myriad proteins, nucleic acids, nucleotides, and sugars
• Plasma membrane


  Impermeable to large molecules, selectively permeable to small molecules, provides a barrier to prevent exchange between intracellular and extracellular spaces
• Active transport


  Uses metabolic energy to drive the uphill movements of substances into or out of the cell
• Plasma membrane


  • Allows rapid modulation of permeability properties in response to various metabolic stimuli
• Phospholipids


  Lipid molecules that form the main component of cell membranes, have a glycerol backbone with two fatty acid chains and a phosphate-containing head group
• Phospholipids


  • Amphipathic - have both hydrophobic (fatty acid) and hydrophilic (head group) regions
• Phospholipid self-assembly in water

  Form monolayers, micelles, and bilayers to prevent hydrophobic tails from contacting water
• Phospholipid bilayer


  Fluid structure where individual phospholipids can diffuse within the leaflet, rate of diffusion depends on temperature and lipid composition
• Phospholipid bilayer


  • Can segregate into distinct lipid domains with different physical properties (gel-like and fluid regions)
• Major membrane lipid classes

  • Glycerol-based phospholipids (phosphatidylethanolamines, phosphatidylinositols, phosphatidylserines, phosphatidylcholines)
  • Sphingolipids (sphingomyelins, glycosphingolipids, gangliosides)
  • Cholesterol
• ATIDYLCHOLINE


  Molecular structure of a phospholipid
• Common membrane lipids


  • Phosphate
  • Inositol
  • Choline
  • Glycerol
  • Fatty acid
  • Choline
  • Galactose
  • Sphingosine
  • Serine
  • Sphingosine
• Short-chain, unsaturated fatty acids will be excluded from these regions and migrate to sol-like regions. Hence, "lakes" of lipids with markedly different physical properties can exist side-by-side in the plane of a phospholipid membrane.
• The segregation of lipid lakes in the plane of the membrane may be important for sorting membrane proteins to different parts of the cell.
• Phospholipids can diffuse in the plane of a lipid bilayer membrane, but they do not diffuse between adjacent leaflets.
• The rate at which phospholipids spontaneously "flip-flop" from one leaflet of a bilayer to the other is extremely low.
• Cholesterol


  Its polar head is a single hydroxyl group, so the energy cost of dragging this small polar hydroxyl group through the bilayer is relatively low, thus permitting relatively rapid cholesterol flip-flop.
• Pure phospholipid bilayer membranes are extremely impermeable to almost any charged water-soluble substance.
• Small uncharged polar molecules can cross phospholipid membranes fairly freely, such as O2, CO2, NH3, and water itself.
• The degree of water permeability (and perhaps that of CO2 and NH3 as well) varies extensively with lipid composition.
• In 1925, Gorter and Grendel measured the surface area of the lipids they extracted from erythrocyte plasma membranes, and found the area of the monolayer was exactly twice the surface area of the erythrocytes, confirming the plasma membrane is a bilayer.
• 1. ray diffraction studies on the myelin sheaths surrounding neuronal axons have also confirmed the bilayer structure of biological membranes.