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Physiology 2130
Paul Gillespie

Module 1 Introduction to Physiology - physiology: study of function in living organisms; how organisms control their internal environments regardless of the external environment - also explains the physical and chemical factors that maintain normal function and disease Homeostasis - internal environment: cells are in this fluid; interstitial fluid, blood plasma - external environment: region outside body - also space/contents of digestive, respiratory, urogenital tracts! - homeostasis: maintenance of stable conditions in internal regardless of external Negative Feedback Control Systems - found throughout body, perform diff funcs (body temp, fluid volumes) - ex: heating system of house - set point: 20 C - sensor/control centre (not usually combined in body): thermostat - effector: furnace - controlled variable: heat - controlled variable, detected by sensor, shuts off by effector (- control centre also called integrator?) - how negative feedback controls body temp: - set point is 37 C - control centre: hypothalamus - hypothalamus activates organs (effector) by conserving heat/cool down body by sweating Positive Feedback Control Systems - also called feedforward systems - controlled variable stimulates own production - sensor detects controlled variable, which signals control centre for the effector to produce more of the controlled variable - large amounts of controlled variable produced 1 - ex. action pot'l of nerve cells, ovulation Negative and Positive Feedback - both neg and pos feedback maintain homeostasis in the body - rely on nervous and endocrine system - nervous system: brain, spinal cord, nerves - adapted for rapid communication of nerves - endocrine system responds more slowly - communicates with hormones The Body's Structural Hierarchy - atoms make molecules, molecules make macromolecules, macromolecules form cellular organelles - some cells have taken these organelles into highly specialized structures, giving a specific purpose - groups of cells with same specialization: tissue - ex. muscle cells have special proteins that cause muscle to contract; muscle tissue contains these cells - two or more tissues: organ - ex. heart has connective tissue, muscle tissue, conducting tissue - several organs do common function: organ system -ex. cardiovascular system: blood vessels, heart - all organ systems make an organism - internal environment must be maintained for organ systems to run properly Module 2 Body Fluids - the volume of fluid and concentration of ions is controlled so organ systems can work with homeostasis Body Fluid Compartments - body is divided into 2 fluid compartments: - intracellular fluid compartment (IFC): inside all cells - extracellular fluid compartment (EFC): outside all cells - makes up the internal environment of the body - divided into interstitial fluid compartment: fluid right outside the cells, and plasma: watery part of blood - for average body, total body water is 42 L with ICF with 28 L, interstitial 11 L, plasma 3 L - most of the water (67%) is found inside the cell, interstitial has 26%, plasma has 7% Plasma - pale yellow fluid; 92% water, 8% proteins (albumins, globulins, fibrinogen)/ions/nutrients/gases/waste - colloidal solution with suspended substances that do not settle out of solution Chemical Composition of Body Fluids - difference between ion concentrations in plasma and interstitial fluid is very small - di+ference between intracellular and outside cell is very big - Na : 15 mOsm/L H O 2ntra, 150 inter, 148 plasma - K : 150 intra, 5.0 inter, 4.8 plasma - Ca : 0 intra, 2.4, 2.5 - - Cl: 9, 125, 102 - protein ions: 4, 0.2, 1.2 2 + - thus only K has higher intra - the cell membrane, barrier between intra and extra fluid, is selectively permeable - some substances cross easily, some not, some too large - because of channels, pores, transport systems Module 3 The Human Cell Basic Cell Organelles - Golgi apparatus: packaging proteins from rough ER into vesicles (secretory and storage vesicles) - secretory vesicle: transport proteins out of the cell for use in the body in a process called secretion - free ribosomes: granules of RNA and protein; manufactures proteins from amino acids - lysosome: type of storage vesicle produced by Golgi; act as digestive system of cell, where enzymes destroy damaged organelles and bacteria, and break down biomolecules - mitochondrion: where ATP is generated - endoplasmic reticulum: site for synthesis, storage, transport of proteins and lipid molecules - cell membrane: regulate passage of substances into and out of cell - centriole: direct movement of DNA strands during cell division - nucleolus: has specific DNA producing the RNA found in ribosomes The Cell Membrane - separates intracellular environment from extracellular environment - selectively permeable: proteins, nucleotides, large molecules cannot penetrate membrane whereas other molecules and ions can - membrane made up of proteins that form channels and pores, carbohydrate molecules for cell recognition, cholesterol for stability - hydrophilic head, hydrophobic tail, cholesterol molecule (in the lipid layer), enzyme, carbohydrate, membrane spanning protein (acts as gates to control movement of substances in and out of cell), structural proteins (attached to inside surface of membrane, to strengthen it) Phospholipids - made up of a hydrophilic phosphate head and hydrophobic fatty acid (lipid) tails - many phospholipids form a lipid bilayer - fatty acid tails are major barrier to water and water-soluble substances (ions, glucose, urea) - fat-soluble substances penetrate this part, lik2 O ,2CO , and steroids 3 Membrane Proteins - receptors for attachment of hormones and neurotransmitters - enzymes that break down molecules - ion channels to allow water-soluble substances into the cell - membrane-transport carriers transport molecules across membrane - cell-identity markers (antigens or glycoproteins) stimulate the immune system - membrane-transport mechanisms: - endocytosis/exocytosis - cell that secretes large molecules that can't go past lipid bilayer, so they go through exocytosis - after ER, the molecules are packaged in a vesicle, which moves to the Golgi apparatus and their membranes merge; vesicle releases content for modification - as molecules leave Golgi, packaged in vesicle, moves in the plasma membrane - the contents don't actually cross plasma membrane - this process can go in reverse (endocytosis) - diffusion through lipid bilayer - diffusion through protein channels - facilitated diffusion - active transport Diffusion - movement of molecules from an area of high conc to low conc b/c of the molecules' random thermal motion - electrically charged molecules tend to move to areas of opposite charge (down electrical gradient) - if chemical and electrical gradient are opposite directions, movement of ion will stop moving when it reaches electrochemical equilibrium (elec force = chem force) Diffusion of Lipid-Soluble Substances - lipid soluble substances (O , CO , fatty acids, steroid hormones) pass through the cell membrane; water soluble 2 2 substances have a tough time - water soluble can't diffuse directly thru fatty acid region of the cell membrane but may still cross it - Na , K cross cell membranes through special channels Diffusion Factors - rate of movement of molecules through protein channels depends on: - size of protein channels - limit size of molecule - charge of the molecule - proteins will have charges too (+ charge can't go through + charge channel) - how great the electrochemical gradient is - greater gradient, greater rate of movement - # of channels in the membrane - more channels, more ions diffused Facilitated Diffusion - water-soluble substances that can't diffuse through the lipid bilayer/too large for protein channels still cross quickly - they attach to specific protein carriers on the membrane and change the shape of the protein - does not req energy, powered by concentration gradient of the molecule - different from simple diffusion as rate of transport limited by # of protein carriers - once all carriers full, cannot go faster; they are saturated - chemical specificity and competitively inhibited by molecules with similar shape Active Transport 4 - requires protein carriers - saturated, chemical specificity, competitive inhibition all exist - involves use of energy - moves molecules up concentration gradients, low to high - energy comes from ATP and ADP and inorganic phosphate (PE) Osmosis - most abundant substance to diffuse: water - needs special pores; cannot diffuse through hydrophobic portion of lipid membrane - usually, amt of water diffusing in is same as water diffusing out - so volume of cell stays constant - but when there is a conc difference, the net movement of water goes down its conc gradient - called osmosis - a solution with high conc of a solute will have a low water conc - whereas pure water has high water conc - water molecules move to high conc of solute - osmosis affected by permeability of membrane to solutes, conc gradients of the solutes, and pressure gradient across cell membrane Units of Osmosis + - + - osmotically active particle: particle that causes osmosis; Na , Cl, K , glucose - osmole: unit to describe # of o.a.p. in a solution - osmolality: # of osmoles/kg of water - osmolarity: # of osmoles/L of solution - ex: What is the osmolality of a 1 molar solution of NaCl? - NaCl dissociates into Na and Cl --> 2 o.a.p., thus 2 osmoles/kg of water - ex: What is the conc of a 1.5 molar sol'n of CaCl ? 2 - dissociates into 1.5 Ca and 3.0 Cl, thus 4.5 osmoles/kg - tonicity: ability of a solution to cause osmosis across a cell membrane - fluid inside a human cell has a conc of 300 mOsm/kg water - isotonic solution: same conc as body fluids; ex. a red blood cell in such a solution would not induce osmosis - hypotonic solution: lower conc compared to cells; would cause osmosis; cell would swell - hypertonic solution: higher conc compared to cells; cause osmosis out of the cell; cell would shrink Concentration Gradients and Membrane Permeabilities - Na, Ca, Cl ions have high conc outside cell whereas K ion has conc higher inside cell - Na, Ca, Cl have large conc gradients but have few channels through which they can diffuse - membrane is more permeable to K , so some will leak out - channels open due to a variety of stimuli: chemical, voltage Membrane Potentials - electrical potential: charge difference between 2 points - membrane potential: cells in the body have a charge diff between inside of cell and outside (separated by membrane) Resting Membrane Pot'l - anions accumulate immediately inside the cell membrane; same amount of cations accumulate outside - creates an electrical potential difference across membrane - present in resting cells, so it is called the resting membrane pot'l - all cells have this - -70 mV 5 Eq'm Pot'ls - any ion has two forces acting on it: chemical conc gradient (drives ion from high-->low conc), electrical gradient (drives ion to area that has opposite charge) - when these forces are equal in magnitude but in opposite directions, there is no net mvmt: electrochemical equilibrium - equilibrium potential: elec pot'l that must be applied to inside of cell to stop mvmt of it down its conc gradient - larger conc grad, larger eq'm pot'l needed - above are voltages that need to be applied to the inside of the cell to stop ion from moving down its conc grad Sodium/Potassium Pump - membrane protein that maintains conc grads for Na and K ions - pumps 3 Na ions out and 2 K ions in - makes inside of cell more negative, so it is electrogenic pump - pumps the ions against their conc grads; requires ATP - thus it is active transport - excitable cells can use the membr pot'l to do work and regenerate elec pot'ls at their membranes - two types of exc. cells: nerves, muscles Module 4 Nerves Introduction - excitable cells: nerve and muscle cells; they use resting membrane pot'l to generate an electrochemical impulse (action pot'l) - action pot'l considered to be the "language" of nervous system - how nerve cells communicate - action pot'l also needed for muscle contractions Structure of a Nerve Cell (Neuron) - dendrites: receive incoming signals; increase SA of a neuron - cell body (soma): centre of cell/directs activity of the cell - axon: projection of cell body which carries signal through action pot'l - myelin sheath: layered phospholipid sheath (insulator for the axon) - node of ranvier: action pot'ls jump from node to node - collaterals: branchings of axon near its terminal end; increase # of target cells in which neuron can interact - terminal bouton / axon terminal: swelling at end of axon collateral; contains mitochondria and membrane-bound vesicles; facilitate transmission of signal across synapse to target cell 6 Action Potential - rapid reversal of the resting membrane - changes from resting (-70 mV) to +35 mV (depolarization) - then returns (repolarization) to -70 mV - then briefly becomes more negative at -90 mV (hyperpolarization) - returns to resting level - movement of ions causes these changes Voltage-Gated Channels - these channels in the neuron are found on the axon; essential for action pot'l - voltage-gated sodium and voltage-gated potassium channels Voltage-Gated Sodium Channels - channel specific for sodium, no other molecules go through - only open when there is depolarization of the membrane (inside becomes more positive) - summary of what occurs: - depolarization of membrane - activation gates open immediately - Na flows into cell, down conc grad + - inactivation gate closes; Na can't flow anymore - channel returns to rest (inactivation gate open; activation gate closed) - goes into absolute refractory period Voltage-Gated Potassium Channels - one gate that opens when membrane de+olarizes - do not open immediately like the Na channel though - open when Na channel become inactivated - summary of what occurs: - depolarization of membrane 7 - brief pause; K voltage-gated channels open (whereas Na channel open immediately) + - K flow out of cell, down elec/chem grads - gate closes, channel returns to rest - ready to open again; no inactivation period + - K voltage-gated channels begin opening as Na channel begin entering inactivated period The Action Pot'l - membrane pot'l rapidly reverses from -70 mV to +35 mV - begins at axon hillock, which contains largest # of voltage-gated channels - summary of what occurs: - strong depolarization at axon hillock triggers opening of Na voltage-gated channels + - Na rushes into neuron, down its electrochemical gradient - membrane depolarizes to +35mV + + - Na channels become inactivated; K channels begin opening - K rushes out, down its grad - membrane repolarizes (+35 mV to -70 mV) - K continues to rush out; membrane hyperpolarizes (-90mV) - K channels begin to close - membrane pot'l slowly returns to rest (-70 mV) Refractory Periods - absolute refractory period: when Na gates will not open for another action pot'l - second refractory period: relative refractory period - during action pot'l when membrane is hyperpolarized ( -) - buildup of pos charge; area of membrane next to it now depolarizes - depolarization triggers Na channels to open - Na rushes into cell and depolarizes the region to threshold --> new action pot'l - repeats; propagated along membrane Unidirectional Nature of Action Pot'l - voltage-gated channels are in absolute refractory; inactivated and won't open - cannot generate action pot'l Propagation of Action Pot'l Down a Myelinated Nerve - saltatory conduction - myelinated axons insulated with myelin, fatty material produced by Schwann cells in the peripheral nervous system and oligodendrocytes in the CNS - nodes of Ranvier: gaps between the myelin where voltage-gated channels exist - summary of what occurs: - + charge from existing action pot'l attracted to and moves toward adjacent node of Ranvier that is negative - node of Ranvier depolarizes - depolarization triggers Na channels to open - Na rushes in, depolarizes region to threshold, new action pot'l - repeated; propagated - "saltatory conduction" - jump from one node to next - much faster than conduction in unmyelinated fibres - action pot'l, like unmyelinated axons, cannot back up the axon b/c of absolute refractory period All-or-Nothing Principle - either have full action pot'l or not - either reaches threshold or not - b/c of absolute refractory period of Na channels, 2 action pot'ls cannot be fired at same time - action pot'ls have fixed height Multiple Sclerosis - disease where immune system damages the myelin surrounding the axon of the nerves - interrupts flow of action pot'ls, so no transmission occurs - thus paralysis occurs Synaptic Transmission - chemical synapse: neuron will almost contact another nerve cell, muscle cell, or organ - neuromuscular junction (NMJ): synapse between neuron and muscle cell - action pot'l from nerve cell triggers action pot'l on muscle cell that leads to contraction of that muscle cell NMJ - motor nerve fibre: neuron that contacts a muscle cell - membrane of the presynaptic axon terminal contains Ca voltage-gated channels - open when cell membrane depolarizes, like Na/K channels - axon terminal of motor cell also contains synaptic vesicles that have acetylcholine (ACh) - basement membrane of axon terminal has acetylcholinesterase (AChE) 9 - sarcolemma (muscle cell membrane) under axon terminal is thrown into folds - this region is the end plate - which contains receptors for ACh, associated with ligand-gated ion channels - gap between motor fibre and muscle cell is the synaptic cleft Events at NMJ - action pot'l on motor nerve cell, you will generate action pot'l on the muscle - one action pot'l will release enough ACh, causing muscle to contract Module 5 Muscles - muscles: biological machines that utilize chemical energy from breakdown/metabolism of food to perform work - three kinds of muscles - skeletal: voluntary motion - smooth: found within walls of blood vessels, uterus, airways, various ducts, urinary bladder, digestive tract 10 - cardiac: found in heart - body contains over 600 diff muscles - 3 principal functions: movement, heat production, body support/posture Structure of Muscle - whole muscles made up of bundles of fasciculi - fascicle is made up of groups of muscle cells or fibres - each muscle cell contains many bundles of myofibrils - myofibrils contain thin and thick myofilaments - THIN myofilaments have protein actin along with troponin and tropomyosin - THICK myofilaments contain protein myosin - interaction of thin and thick myofilaments results in muscle contraction - ex. whole muscle: biceps - composed of groups of fasciculi surrounded by perimysium (white connective tissue) - each fascicle is made up of bundles of muscle cells/fibres - within each cell there are myofibrils, which have thin and thick myofilaments (contractile elements of the cell) Structure of a Skeletal Muscle - muscle cells/fibres have more than one nucleus - sarcolemma: muscle cell membrane that surrounds nuclei, where action pot'l is transmitted - has transverse (T) tubules: tube-like projections that extend down into cell - conduct action pot'l where contractile proteins are - myofibrils (contain contractile proteins of muscle) contain the thin and thick myofilaments, and are surrounded by sarcoplasmic reticulum (SR) - SR: mesh-like network of tubes containing Ca ions, essential for contraction - terminal cisternae: membranous enlargement at ends of and continuous with the SR Thin Myofilament - composed of actin (globular protein) - each actin molecule contains a special binding site for myosin - actin molecules strung like beads on a necklace - tropomyosin also found in thin myofilaments; cover the binding sites for myosin 11 - troponin: 3rd regulatory protein, has 3 subunits: troponin A (binds to actin), troponin T (binds to tropomyosin), troponin C (binds with Ca )+ - at rest, troponin complex holds tropomyosin over myosin binding sites 2+ - when Ca bind to troponin C, tropomyosin is pulled off myosin binding sites Thick Myofilament - made up of protein myosin - long, bendable tail; two heads that attach to myosin binding sites on actin - heads also have a site that can bind and split ATP - splitting of ATP releases energy to myosin, which powers contraction Actin/Myosin Relationship - groups of thin (actin) myofilaments and groups of thick (myosin) myofilaments are arranged in a repeating pattern (thick, thin, thick, thin) along length of myofibril - each group of thin myofilaments extends outwards in opposite directions from central Z disk - groups of thick myofilaments extend outward from a central M line - each myofilament is parallel to length of myofibril/muscle cell - sarcomere: region from one Z disk to the next; smallest functional contractile unit of muscle cell - regions with thick filaments appear as A bands - regions with thin filaments appear lighter as I bands Muscle Contraction - Sliding Filament Theory - muscle contraction comes from interaction btw actin and myosin - head of myosin attaches to binding site on actin and forms a crossbridge; myosin undergoes shape change - shape change causes myosin head to produce power stroke - slides actin past myosin - neither thin/thick filaments shorten during contraction - sarcomeres shorten Excitation-Contraction Coupling and Muscle Contraction 12 - process which action pot'l in cell membrane (sarcolemma) excites muscle cell to produce muscle contraction - action pot'l opens sarcoplasmic reticulum and open Ca channels, releasing Ca from terminal cisternae - Ca ions bind to troponin C on thin myofilaments, causing tropomyosin to uncover myosin binding sites on actin - myosin then attaches to actin, power stroke occurs Relaxation of Muscle 2+ - when action pot'ls stop, Ca stop diffusing out of SR - calcium pumps rapidly pump Ca back into SR, up conc grad - requires ATP - w/o calcium present in cytoplasm of muscle cell, tropomyosin covers myosin binding sites again - then myosin can't bind to actin; power strokes don't occur; muscle will relax Actin-Myosin and ATP Cycle 1. Splitting of ATP to ADP and Pi release energy to myosin and prepares myosin head for activity 2. Formation of crossbridges occur when Ca ions bind to troponin C; rolls tropomyosin off myosin binding sites on
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