Download Human Physiology Lecture Reading Notes

Human Physiology Lecture Reading Notes
Lecture 2: Homeostasis
Membranes
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General function of cell membrane:
o Physical isolation: separates intra- and extra-cellular fluid
o Regulation of exchange: controls entry of ions and nutrients into cell, and release of
waste + products
o Communication: contains proteins that recognise and respond to molecules/changes
in external environment
o Structural support: proteins hold cytoskeleton to maintain cell shape, also specialised
junctions
All membranes consist of lipid, protein and SMALL amount of carbohydrate
o More metabolically active = more protein
o Lipids mostly phospholipids (as a bilayer, tails inwards)
o Proteins studded within bilayer
o Extracellular surface of glycoproteins + glycolipids
3 types of lipids in membrane:
o Phospholipids
o Sphingolipids: fatty acid tail, head either phospholipid or glycolipid, longer than
phospholipid
o Cholesterol: hydrophobic, make membrane impermeable to water-soluble molecules,
increase flexibility in range of temps
Membrane proteins:
o Integral proteins: tightly bound to the membrane, removed by disrupting the membrane
structure with detergents to destroy membrane’s integrity. Eg. transmembrane proteins
o Peripheral proteins: attached to other membrane proteins by non-covalent interactions
and can be separated from the membrane by chemical methods that do not disrupt the
integrity of the membrane. Eg. enzymes
o Transmembrane proteins: called membrane-spanning proteins b/c the protein’s chains
extend all the way across the cell membrane. When a protein crosses the membrane
more than once, loops of the amino acid chain protrude into the cytoplasm +
extracellular loops + phosphate groups may attach to the intracellular loops
Membrane carbohydrates – mostly sugars attached either to membrane proteins or lipids.
o Found on external surface of cell where they form a protective layer known as the
glycocalyx
o Glycoproteins on cell surface play a key role in the body’s immune response
Homeostasis
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2 distinct fluid compartments: cells + fluid surrounding cells
Extracellular fluid = buffer b/n cells and environments outside the body
Water moves freely b/n cells and extracellular fluid
Osmotic equilibrium: because of free movement of water, extra- and intracellular
compartments reach this
Chemical disequilibrium: some solutes are more concentrated in one body compartment
than the other
o Extracellular fluid: sodium, chloride, calcium more concentrated outside than inside
o Intracellular: potassium more concentrated inside
Proteins concentrated in plasma but cannot cross blood vessels
Smaller molecules and ions pass freely b/n endothelial cells thus have same concentration in
plasma and interstitial fluid
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If solutes leak across cell membranes, energy is required to return them to the compartment
they left
o K+ leaks out of cell, Na+ leaks into cell… returned by Na+K+ATPase
Distribution of electrical charge between intra- and extra-cellular comparments…
o Body electrically neutral
o Few extra negative ions found in intracellular fluid, positive ions in extracellular
o Inside of cells slightly –ive related to outside
o Electrical disequilibrium – ionic imbalance
o Changes in disequilibrium create electrical signals
Homeostasis is not the same as equilibrium
Diffusion
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Movement of molecules from an area of higher concentration to lower concentration
Passive process – does not require input of energy from some outside source
Uses only kinetic energy possessed by all molecules
Diffuse down the chemical gradient
Rate of diffusion depends on magnitude of concentration gradient
Net movement of molecules occurs until the concentration is equal everywhere
Diffusion is rapid over short distances but much slower over long distances
Diffusion is directly related to temperature
Diffusion rate is inversely related to molecular weight and size – smaller molecules require less
energy thus diffuse faster
Diffusion can take place in an open system or across a partition that separates two
compartments
Ions do not move by diffusion – influenced by electrical gradients because of the attraction of
opposite charges and repulsion of like charges
Diffusion = passive movement of uncharged molecules down concentration gradient due to
random molecular movement
Diffusion across membranes…
o Lipid-soluble molecules can pass thru phospholipid bilayer
o Lipophilic substances that can pass thru lipid centre of a membrane move by diffusion
Diffusion directly across phospholipid bilayer = simple diffusion
o Rate of diffusion depends on the ability of the diffusing molecule to dissolve in the lipid
layer of the membrane
o Diffusion rate depends on how permeable the membrane is to the diffusion molecules
o Rate of diffusion across a membrane is directly proportional to the surface area of the
membrane
§ Larger the surface area, the more molecules can diffuse across per unit time
Flick’s law of diffusion has several factors:
o Size of diffusing molecule
§ As molecule size increases, membrane permeability decreases)
o Lipid solubility of the molecule
§ As solubility increases, membrane permeability increases
o Composition of the lipid bilayer across which it is diffusion – alterations in lipid
composition of the membrane change how easily diffusing molecules can slip between
the individual phospholipids
Flux of a molecule across a membrane depends on the concentration gradient and the
membrane’s permeability to the molecule
Protein-Mediated Transport
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Vast majority of solutes cross membranes with the help of membrane proteins
Mediated transport = passive and moves molecules down their concentration gradient
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Facilitated diffusion = net transport stops when concentrations equal on both sides of memb.
Active transport = protein-mediated transport requires energy from ATP or another outside
source and moves a substance against its concentration gradient
Carried out by proteins known as transporters
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4 broad categories of membrane proteins…
o Structural: connect membrane to cytoskeleton to maintain shape of cell, create cell
junctions that hold tissues together, attach cells to extracellular matrix by linking
cytoskeleton fibers to extracellular collagen and other protein fibers
o Enzymes: catalyse chemical reactions that take place on cell’s external surface or just
inside the cell
o Receptors: part of body’s chemical signally system, binding of receptor with its ligand
usually triggers another event
o Transporters: moves molecules across membranes – channel proteins (water-filled
passageways that directly link the intracellular and extracellular compartments) and
carrier proteins (bind to the substances that they carry but never form a direct
connection between the intracellular and extracellular fluid)
Channel proteins – have pore + gap junctions, movement through these smaller channels is
mostly restricted to water and ions
o May be specific for one ion or may allow ions of similar size and charge to pass
o Selectivity of a channel determined by diameter of its central pore + electrical charge of
amino acids that line the channel
o If channel is positively charged, positive ions repelled, negative ions pass thru
o Channel gates take several forms –
§ Open channels: gate is mostly open, allowing ions to move back and forth across
membrane without regulation – ie. leak channels
§ Gated channels: gate mostly closed, allows channels to regulate movement of
ions through them… controlled by chemicals or voltage or physical forces
Carrier proteins – bind with specific substrates and carry them across the membrane by
changing conformation, small organic molecules that are too large to pass through use carriers
o Uniport carriers – use one kind of molecule
o Contransporter – move more than one kind of molecule at one time
o Symport carriers – molecules being transported are moving in same direction
o Antiport carriers – molecules are being carrier in opposite directions
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Channel proteins move many more molecules per second than carrier proteins
Carriers never create a continuous passage between inside and outside of cell
Carries transport molecules across a membrane in both directions – can restrict a protein to 1D
One side of carrier protein creates a barrier that prevents free exchange across membrane
Molecule being transported binds to carrier on one side of membrane – changes conformation
of the carrier protein so that the opening closes
Facilitated diffusion uses carrier proteins
Primary active transport – known as ATPases – sometimes caused pumps. Eg. sodium
potassium pump
Secondary active transport – uses kinetic energy of one molecule moving down its
concentration gradient to push other molecules against their concentration gradient
Specificity – ability of a transporter to move only one molecule or only one group of closely
related molecules
Competition – transporter may move several members of a related group of substances, but
those substrates compete with one another for binding sites on the transporter.
Saturation – rate of substrate transport depends on substrate concentration and the number of
carrier molecules.