Summary Fysiologie Spier/Zenuw

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Summary - Fysiologie Spier/Zenuw

  • 1 Fysiologie Spier/Zenuw

  • Intracellular Fluid (ICF)
    inside cells/intracellular compartment
  • Extracellular Fluid (ECF)
    outside/extracellular compartment
  • Total Body Water
    = ICF + ECF
    60% of male, 50% of female, 65-75% infant
    fat cells less H20 than muscle
    Ratio ICF:ECF = 60%:40%
  • ECF Consists of:
    plasma, interstitial, transcellular fluid
  • Hematocrit:
    fraction of blood volume contained in cells of blood
  • Plasma:
    20% ECF, within cardiac chambers & blood vessels within intravascular compartment
  • Blood Volume definition + type cells
    total volume of intravascular compartment
    cells: erythrocytes, leukocytes, platelets
  • Plasma volume definition
    extracellular or blood volume
  • Interstitial Fluid
    = 75% of ECF, outside of intravascular compartment, bathes the non-blood cells of the body (separated by capillaries)
  • Two ICF compartments
    1. Dense connective tissue (cartilage, bones)
    2. Bone matrix
  • Transcellular Fluid
    = ~5% of ECF, trapped within spaces completely surrounded by epithelial cells 
    1. synovial fluid (joints
    2. CSF
  • Concentrations in ICF
    High K
    Low Na, Cl
  • Concentrations in ECF
    High Na
    High Cl
    Low K
    Cell uses Na-K pup to export Na into ECF and K into cell.
  • Difference between Plasma Fluid & Interstitial due to..
    IF has no plasma proteins (can't cross capillary walls), affecting solute distribution due to volume occupation and charge
  • Effect Protein Charge
    plasma proteins = net negative charge -> retain cations in plasma
    [cation] in interstitium is <5% 
    [anion] in interstitium is >5%
  • Osmolality
    = the total concetration of all particles that are free in a solution
    expressed as: # of osmotically active particles per kg of H20.
    (All body fluid compartments =~290 mOsm)
  • Electroneutrality
    = the number of positive charges in the overall solution must equal the number of negative charges
  • Anion Gap
    = difference between major ignored cations/anions in blood plasma
  • Ignored Anions
    anionic proteins, anionic metabolites
    e.g. acetoacetate, B-hydroxybutyrate
  • Solute Transport
    = passive, non-coupled transport across permeable membrane
    solute moves down its electrochemical gradient = electrochemical potential energy difference
  • Electrochemical Potential (deltaE)
    1. chemical potential
    2. voltage difference of charged solutes
  • Non-coupled transport
    = movement of X across membrane is not directly coupled to the movement of any other solute or chemical reaction
  • Osmolarity
    = the # of osmotically active particles per liter of total solution
    Osmolality: is per kg of H2)
  • Steady state
    = when both driving forces acting and the rate of transport are constant with time
  • Equilibrium
    = the particular steady state in which there is no net driving force and thus no net transport
    @ Egm: chemical & electrical potential energy difference across the membrane are equal but opposite.
  • Integral Membrane Proteins (Function)
    passive moment through intrinsic membrane proteins as most ions & hydrophilic solutes partition poorly in lipid bilayer
  • Types of Integral Membrane Proteins
    1. Pore e.g porins
    2. Channel
    3. Carrier
  • Membrane Protein Pore
    = always open
    e.g. aquaporin H20 channels, perforin released by lymphocytes
  • Membrane Protein Channel
    = alternately open/closed with barrier/gate
    e.g. virtually all ion channels
    opening/closing = "gating"
  • Membrane Protein Carrier
    = at least 2 gates, no continuous path as gates never open at the same time
    e.g. includes carriers that do facilitated diffusion
  • Process Carrier Protein
    1. Carrier open to outside
    2. X enters from the outside & binds @binding site
    3. Outer gate closes and X becomes occluded (still bound)
    4. Inner gate opens (still bound)
    5. X exits and enters the inside of the cell
    6. Inner gate closes
    Cycle can go in reverse order
  • Porins
    = large pres, aqueous transmembrane
    mitochondrial porin: solutes diffuse passively cytosol -> intermembrane space
    perforin: T-cell release monomers -> create pore
  • Complement Cascade
    monomers of C9
  • NPC
    = nuclear pore complex = regulate traffic in/out nucleus, transports huge molecules with process using ATP hydrolysis
  • Aquaporins
    gated channel, AQP1: in lipid bilayer, exists as tetramers
  • Gated Channels
    = alternately open/close
    polypeptide subuntis with a-helical membrane spanning segments
  • Functional Components of Gated Channels
    1. Gate
    2. Sensor(s)
    3. Selectivity Filter
    4. Open channel pore
  • Gate of Gated channels function
    = determines open/closed by reflecting a different conformation of membrane protein
  • Sensor(s) of Gated channels
    responds to 1 of several signals:
    1. changes in membrane voltage
    2. 2nd messenger proteins acting on cytoplasmic face of membrane protein
    3. ligands (neurohumeral agonists) binding to extracellular face of membrane protein
  • Selectivity filter of Gated Channels
    determines classes of ions (cations, anions) or the particular ions (Na, K, Ca) that have acces
  • Sodium Channels
    - electrochemical driving force is NEGative
    --> inward directed driving force favours passive Na flow into every cell of body 
    - responsible for action potential
  • Potassium Channels
    - electrochemical driving force close to 0, somewhat positive
    --> either at equilibrium or tends to efflux
    - responsible for resting potential, terminates AP's
  • Calcium Channels
    - electrochemical driving force is NEGative
    --> tends to move out of cell
    - transmembrane signalling in excitable & non-excitable cells  
    - generates AP's
  • Proton Channels
    Hv1 H+ Channels
    open: H+ moves into cells
    closed: in normal conditions, activate during depol. or cytoplasm acidifies (moves out)
    - Hv1 mediate H+ extrusion during AP's
  • Anion Channels
    passive, non-coupled transport of Cl- or HCO3-
    electrochemical driving force is moderately +ve, moves out of cell
  • Na-K pump
    primary active transport, uses ATP, extrudes Na and takes up K
    - located in plasma membrane, a&B subunits
    1 cycle: 3 Na efflux --> 2K influx -> intracellular hydrolysis of 1 ATP
    - maintains low Na and high K
  • Active transport definition
    = process transferring a solute against its electrochemical potential energy difference
  • Primary Active Transport
    driving force needed to cause net transfer of a solute is associated with an exergonic chemical reaction (ATP hydrolysis)
  • Secondary Active Transport
    driving force provided by coupling uphill movement of solute to downhill movement of 1 or more other solutes for which a favourable electrochemical potential exists.
  • ATPases
    pumps energized by ATP hydrolysis (primary active transport!)
    e.g Na-K pump
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Cross-Bridge Cycle Step 6
ADP release
- dissociation of ADP from myosin
- leaves actomyosin complex in rigid attached state
Cross-Bridge Cycle Step 5
Power Stroke:
- conformational change causes neck to rotate around head
- bending causes actin/myosin filament to pass each other
- pulls Z-lines closer together shortening sarcomere and generates force
Cross-Bridge Cycle Step 4
Release of Pi from myosin
- triggers increased affinity of myosin-ADP complex for actin
- strong cross-bridge state
- = RATE LIMITING STEP
Cross-Bridge Cycle Step 3
Weak cross-bridge formation
- cocked myosin loosely bound to new position actin filament
- 6 actin filaments surround 1 thick
Cross-Bridge Cycle Step 2
Breakdown ATP-> ADP +inorganic phosphate (Pi) at myosin head
- products retained within myosin active site
- myosin head in cocked position
Cross-Bridge Cycle Step 1
ATP Binds to head of MHC
- reduces affinity of myosin for actin
- myosin head releases from actin
Cross-Bridge Cycle Start
Start:
-Absence ATP/ADP
- Myosin attached to actin
Nebulin
runs from Z-disk along the actin thin filaments
- interacts with actin and controls the length of thin filament
- contributes to structural integrity of myofibrils
Titin
= elastic filament of sarcomeres
runs alongside thick filaments, spans 1/2sarcomere
(N-terminus at Z disk, C-terminus at M line)
MLCKs vs. Phosphatases
MLCKs: enhance cross bridge interactions
Phosphatase's: force potentiation in skeletal muscle