1.

Introduction to Physiology

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Physiology Study of function in living organisms Mechanisms controlling internal environments regardless of what happens in external environment mechanisms of homeostasis Physical and chemical factors responsible for normal function and disease (pathology) Homeostasis Maintenance of relatively stable conditions within the internal environment to ensure normal function despite a variable external environment o Internal environment: fluid cells are bathed in (interstitial fluid & blood plasma) DOES NOT INCLUDE CELLS! Just the SPACE the cells are in o External environment: region outside the body AND the inside of digestive, respiratory, and urogenital tracts e.g. kidneys and bladder (these tracts connect to the outside, but only some are continuously so e.g. lungs) Almost all organs within the body are involved in maintaining homeostasis, controlled by 2 systems:

o 1. Endocrine system (hormones, slow) o 2. Nervous system (instant) Negative feedback control system Both systems use negative (and positive: amplify effect) feedback control system Set point is a desired value(e.g. 37C), controlled variable (body temperature) detected by sensor (nervous system) and reported to the control center (hypothalamus), which notices the difference between current and set point value, activate effector (organs and systems to generate heat) thus changing the controlled variable back to the set point (37C) which SHUTS OFF the effectors (thus negative feedback

 positive feedback = controlled variable keeps control center going Levels or organization in human body Atoms molecules macromolecules (DNA) cellular organelles (many similar/common in all cells, though some are highly specialized - e.g. muscle cells has more contracting protein)

tissue (groups of cells with same specialized function - e.g. muscle tissue) organs (two or more types of tissue form a functional unit - e.g. heart) organ systems (several organs cooperate for a common function - e.g. cardiovascular system = heart and blood vessels) organism All these organ systems 1 common function: maintain homeostasis

2. Body Fluids

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Introduction Homeostasis means volume of fluid & concentration of chemical ions of internal environment (which is bathed in fluids) need to be strictly controlled. Body Fluid Compartments Total body water (TBW) = 42L in average 70kg standard man 60% 1. Intracellular fluid (inside the cells) 67% (by volume) Extracellular fluid (=internal environment of the body =everything outside the cells) o 2. Interstitial fluid (fluid directly outside the cells) 26% o 3. Plasma (liquid portion of the blood) 7% 92% water and 8% other substances (proteins, ions, nutrients, gases, waste products) colloidal solution (containing suspended substance, such as plasma proteins, that wont settle out) Plasma volume is relatively constant despite water intake (due to water loss through kidneys, lungs, digestive tract, and skin)

Chemical Composition Big difference in concentration between the inside and outside of the cell (intracellular and extracellular), but small between interstitial fluid and plasma (extracellular) o Much higher concentrations of Na+, Ca2+, Cl- outside the cell o Most K+ and protein ions are inside the cell o SALTY (Na+ outside) BANANA (K+) Difference in ion concentration caused by the selectively permeable nature of cell membrane (the barrier between intra/extra cellular fluid)

o Only some substances can cross easily o Doe this through channels, pores, special transport systems

3. Human Cell

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Basic Cell Organelles Nucleolus: dense body within the cell nucleus containing specific DNA that produces the RNA found in ribosomes Centriole: bundles of microtubules that move DNA strands during cell division Endoplasmic Reticulum: continuation of cells nuclear membrane, responsible for synthesis, storage and transport of proteins and lipid molecules o Rough ER: covered with rows of ribosomes (protein synthesis, packaged into vesicles and transported to Golgi apparatus) o Smooth ER: no ribosomes (lipids/fatty acids synthesis) Mitochondrion: Produces ATP (energy storage and transfer) powerhouse of the cell o # of mitochondria depends on cells energy needs o can replicate themselves even without cellular division Golgi Apparatus: package proteins from rough ER into membranebound vesicles o Produces both secretory vesicles (transport proteins to cell membrane and releast into extra-cell environment) and

storage vesicles (e.g. lysosome; store contents to use within cell) o Lysosome: act as digestive system of cell have enzymes that destroy damaged organelles, bacteria, and molecules to be broken down The Cell Membrane Separates intracellular environment from extracellular environment Selectively permeable important for intake of nutrients and emission of waste Made up of mainly phospholipid molecules + proteins (channels and pores), carbohydrates (cell recognition), cholesterol (stability) o Phospholipid molecule: phosphate polar head with lipid nonpolar tail o Phospholipid bilayer: two layers, tail to tail to form non-polar centre (barrier to water/water-soluable substances, e.g. glucose, urea, ions), heads facing outside and insides of cell

Cholesterol molecule: inserted into the non-polar centre, helps to make membrane impermeable to some water soluble molecules and keep membrane flexibility despite temperature change Associated proteins: o Enzymes: found inside/outside membrane: catalyze reactions o structural proteins: usually inside surface, strengthen membrane, anchor organelles to the inside surface Membrane spanning protein: span entire width of the membrane, act as gates/channels controlling movement of substances Carbohydrate molecule: can be on membrane proteins/lipids

forms protective layer of glycocalyx -> role in immune response and cell-cell recognition Membrane Proteins Receptors: attachment of chemical hormones/neurotransmitters Enzymes: help chemical reactions/breakdown of molecules Ion channels/pores: allow water-soluble substances to travel Membrane-transport carriers: transport larger molecules and molecules against conc. grad. across the membrane Cell-identity markers: antigens (foreign particles that stimulate the immune system)/glycoproteins Membrane-transport mechanisms Endocytosis(coming into cell)/exocytosis (leaving the cell): of small molecules through transport of a vesicle (which just fuses with membrane; contents dont actually cross it through an opening) Diffusion: movement of molecules from high to low concentration (moving down the chemical concentration gradient), stops when gradient is 0 and thus equilibrium (still travel, no macro change) o Ions have both chemical gradient and electrical gradient (opposite charges attract). The two gradients may be in different directions, and when they balance and ions stop moving, that is an electrochemical equilibrium o Lipid-soluble substances can diffuse right through the cell membrane, only controlled by concentration (O2, CO2, fatty acids, some steroid hormones)

o Water-soluble substances (e.g. ions) cant diffuse directly, need specific protein channels/pores o Diffusion factors (things that limit rate of movement through protein channels) Size of channels, charge on molecule and channel, electrochemical gradient, number of channels o Facilitated diffusion: larger substances cant pass through protein channels, they attach to specific protein carriers which causes the protein to change shape and let them through Requires no energy, powered by concentration gradient Rate of transport limited by # protein carriers Once all carriers working, saturated, no faster rate Protein carriers = specific, and may be inhibited Active Transport o Moves against concentration gradient (e.g. Na-K pump) o Requires protein carriers, can be saturated, and shows chemical specificity and competitive inhibition just like facilitated diffusion, BUT USES ENERGY! (ATP) Osmosis Water moving down its concentration gradient across a membrane (diffusion of water) Happens when solute molecules cant diffuse themselves; water move to area of lower concentration (higher solute concentration) Affected by o Permeability of membrane to solutes o Concentration of solutes (inside/outside) o Pressure gradient across the cell membrane Units of Osmosis: osmole (Osm) Osmotically active particle = one that causes osmosis (e.g. Na+, Cl, K+, glucose) 1 osmole = 1 mole of osmotically active ion/substance osmolality/osmolarity = sum of osmole / kg or L (sum of molarity of ALL osmotically active ions/substances) e.g. 1.5 M CaCl2 = 1.5 M Ca++, 3 M Cl-, total 4.5 Osm Glucose dont dissociate, only dissolve, so 1M glucose = 1 osm/kg Typical human cell /body fuids = 300mOsm/kg

Tonicity: ability of solution to cause osmosis across layer o Isotonic solution: same concentration as cell o Hypotonic solution: lower conc. than in cell (swell) o Hypertonic solution: higher conc. than in cell (shrink) Concentration Gradients & Membrane Permeabilities Not very permeable to Na+, Cl- and Ca++ ions, few channels for them on the memraben More permeable to K+, some will leak out down its conc. grad. There are more specific ion channels we have yet to learn Membrane Potentials Charge difference between the inside of the cell (-) and the outside (+) Resting Membrane Potential Immediately inside the cell membrane = anions (-) and immediately outside the membrane = cations (+) This potential difference present even every resting cell = ~ -70mV (comparing inside to outside)

Equilibrium Potentials o Electrochemical equilibrium: when the force of chemical conc. grad. (drives ion from high to low conc) and electrical grad. (drives ion toward area of opposite charge) equalize in magnitude but opposite in direction, and no net mov. of ion. o Equilibrium potential of an ion = electrical potential the inside of cell (-70mV) need to be to stop movement of ion down its concentration gradient. E(K+)=-90mV (wants to get out, so make inside very electrically attractive) E(Na+)=+60mV (want to get in, so make inside positive to keep it out)

E(Cl-)=-70mV o Since actual resting potential is -70mV, some K+ will get out and some Na+ will leak in, but we have pumps to balance that Sodium/Potassium Pump o Integral membrane protein that pumps 3 Na+ out and 2 K+ in, making the inside more negative to reach the resting potential of 70mV electrogenic pump o Requires ATP since pumps both against concentration gradients active transport o Without it, most cells would just burst; net pumping out means reducing particles in side so less water come in Significance of Resting Membrane Potential o Excitable cells can use the membrane potential to do work Then spontaneously regenerate electrical potentials at their membranes Two types: nerves & muscles

4. Nerve Cells

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Review: all cells have membrane potentials, inside-, outside+; maintained by electrochemical gradients of intracellular and extracellular ions (K+ inside, Na, Cl-, Ca++ outside) Action Potential Nerve cells and muscle cells are considered excitable: use resting membrane potential to generate an electrochemical impulse called action potential How nerve cells communicate with one another Important for muscle contractions Nerve Cell Structure Dendrites: thin branching processes of cell body receive incoming signals, increase overall SA to communicate. # varies depending on where the neuron is located Cell body: control centre of the cell, containing nucleus/organelles Axon: carries the action potential, may or may not be myelinated Myelin Sheath: insulator for axon, phospholipid layer, forcing ion exchange to take place only at nodes of Ranvier Collaterals: branchings of axon near its terminal end, serve to increase number of possible target cell for neuron to interact

 Action Potential

Voltage-Gated Sodium Channel: activation gate normally closed while inactivation is opened (both gates on intracellular side). Depolarization: activation gate opens quickly, Na+ pour into the cell until inactivation gate closes and flow stops absolute refractory period, wont open to fire another action potential regardless of stimulation, then go back to normal configuration which is inactivation gate open and activation gate closed. Voltage-Gated Potassium Channel: only one gate, opens as Na+ gate enters inactivated period after depolarization, K+ flow out of the cell repolarization until gate closes and returns to resting configuration Depolarization begins on axon hillock, has highest concentration of voltage gated channels. When membrane of nerve cell depolarizes, Na gate open and Na rushes in down its concentration gradient, inside becomes more positive/depolarized rapidly to +35mV, sodium quickly becomes inactivated (miliseconds), meanwhile potassium open, and K+ rushes out, causing

repolarization back to normal, except K gate closes but more slowly, K+ continues to rush out causing slight hyperpolarization (-90mV relative refractory period (possible to fire another action potential if very strong stimulus to reach threshold). Resting potential will restore through passive movement of ions through leak channels to -70mV. Threshold for Starting an Action Potential Action potential only occur if almost all of the Na+ voltage-gated channels open to form a large enough +charge = -55mV (threshold for generating an action potential). If below, the K+ and Cl- leak channels (always open) will make K+ go out and Cl- come in to repolarize back to normal (no AP then) called natural repolarizing forces. If above, AP will always occur. All-ornothing

Round peak of action potential = N-gate beginning to close while K-gate beginning to open (as K+ leaves and voltage go down, some Na+ still coming in to slow down this decline initially) Important Facts No appreciable change in conc. grad. of ions after one action potential (very small fraction participate in the first place). However, since only Na+ goes in and K+ goes out, can occur thousands of times before insufficient con.gra. between intra/extra cell. Also, the pumps arent required for repolarization? Action Potential Propagation Propagation/conduction: action potential will travel down the axon of the nerve from hillock to the axon terminal where it will communicate with another cell Unmyelinated axon: initial action potential makes inside positive +35mV (Na+ entered); positive charge moves toward adjacent, charged membrane and creates a local current (+ -); adjacent now depolarizes, triggering Na+ channels to open, depolarizing the region to threshold and new action potential fired! So on. o The travelling is unidirectional due to inactivate voltage-gated channels which will be in the state of absolute refractory o Each depolarization acts as the stimulant for the next one adjacent to it down the axon; the first is triggered by depolarizing stimulus Myelinated axon: insulated with fatty material myelin produced by Schwann cells so few ions can leak through membrane. Voltagegated Na+ and K+ channels can only exist at gaps between the myelin nodes of Ranvier, so each action potential moves towards

the adjacent node of Ranvier (negative) directly. o Jumpts from one node to next saltatory conduction o Much faster than unmyelinated fibers Action potentials will almost always have fixed height/amplitude, since its all-or-nothing (either have above threshold to reach 35 for a full potential and pass it on or none at all) and potentials cant overlap (abs. refractory) Multiple Sclerosis (MS)

Myelination speeds up conduction of action potentials, but for people with MS, immune system attacks and damages myelin surrounding axon of nerves, can interrupt flow of action potential such that no transmission occurs. If damaged nerve connected to a muscle, paralysis. Synaptic Transmission Connection between the axon terminal and another cells (nerve/muscle/organ) chemical synapse Neuromuscular junction (between neuron and muscle cell) Motor nerve fiber: neuron contacting a muscle cell Presynaptic axon terminal: axon terminal contacting muscle cell o Contains Ca++ voltage-gated channels, also open when cell membrane depolarizes o Also contains synaptic vesicles containing neurotransmitter acetylcholine (ACh), activated by inflowing Ca++ Basement membrane of axon terminal (the muscle cell-contacting membrane) contains enzyme acetylcholinesterase (AChE) Sarcolemma: muscle cell membrane directly under the axon terminal End plate: the region interfacing motor fiber/muscle cell below synaptic cleft (gap between the two): contains receptors for acetylcholine associated with ligand-gated ion channels

 1. action potential arrives at presynaptic nerve fibre terminal causing voltage-gated Ca2+ channels to open and Ca++ flow into nerve cell 2. Ca++ triggers fusing of synaptic vesicles to membrane and release Ach into synaptic cleft (exocytosis) 3. Ach diffuses across synaptic cleft, attach to ACh receptors on muscle cell postsynaptic membrane 4. ligand-gated (ACh is the ligand here) ion channels on muscle cell open (Na and K gates) and Na+ flow in while some K+ leaves, local depolarization end plate potential (EPP) not action potential, happens before it. 5. depolarization of EPP spreads to adjacent cell membrane, threshold reached and large amounts of Na+ flows into muscle cell, triggers action potential. Muscle cell contracts. 6. Ach broken down to acetic acid and choline by enzyme AChE, only choline reabsorbed by presynaptic terminal to be recycled and combine with acetic acid

note: if you have an action potential on motor nerve, always have enough to generate an action potential on the muscle (threshold overcame)

5. Muscles

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Introduction (dont need to know) Muscles: utilize chemical energy from metabolism of food to perform useful work Skeletal muscle: voluntary motion Smooth muscle: walls of blood vessel, airways, various ducts, urinary bladder, uterus, and digestive tract Cardiac muscle: found in the heart Over 600 different muscles with three principle functions Movement, heat production, and body support/poster Structure of Skeletal Muscle Muscles made up of bundles of fasciculi (singular: fascicle) surrounded by connective tissue perimysium, each made up of groups of muscle cells (= muscle filbres), each cell contains many bundles of myofibril containing 2 types of myofilmanets: thin myofilaments (made up of protein: actin and troponin & tropomyosin) and thick myofilaments (protein myosin) Muscle contraction: interaction of thin and thick myofilaments

Structure of a Muscle Cell >1 nucleus cell membrane = sarcolemma , transmit action potential o has small tube-like projections extending into the cell called transverse (T) tubules: conduct action potential deep into the cell where contractile proteins are located

Myofibrils are surrounded by sarcoplasmic reticulum (SR): network of tubes containing Ca2+ ions (essential for contraction) o Terminal cisternae: membranous enlargement of the SR surrounding the T-tubles and where the Ca2+ are stored

Thin Myofilament Mainly globular protein actin strung together like beads on 2 long protein strands tropomyosin (twisted necklace), each actin molecule contains a special binding site for the other contractile protein myosin (on thick myofilament) Troponin: regulatory proteins o Troponin A: binds to actin o Troponin T: binds to tropomyosin o Troponin C: binds with Ca2+

At rest, tropomyosin is held by troponin complex to cover up actins binding sites for myosin

Thick Myofilament Made up of protein myosin: long bendable tail and two heads (both can bind to actin, and also can bind and split ATP)

Actin/Myosin Relationship Z disk = where thin myofilaments are anchored and extended from o Region from one Z disk to another is called a sarcomere: the smallest functional contractile unit of the muscle cell M line (vertical to length of muscle cell) = where groups of thick myofilaments extend from Under microscope: A band = thick filaments, I band = thin

Muscle Contraction: Sliding Filament Theory Muscle contraction: interaction between actin/myosin Head of myosin molecule attaches to binding site on actin forming a crossbridge, myosin changes shape, causing its head to swing and produce the power stroke: much like dragon boat! Slides actin past myosin, but neither thin/thick filaments shorten during contraction, only the sarcomere shortens; this is why entire muscle shortens when contracted Excitation-Contraction Coupling (what turns action potential into a muscle contraction)

Process by which action potential coming from neuromuscular junction spread out over sarcolemma, down to T-tubules (which are like a continuation of the sarcolemma), into core of muscle cell to produce a contraction. The AP travels very close to sarcoplasmic reticulum, opening Ca2+ channels and release Ca2+ from terminal cisternae of the SR. The Ca2+ ions will bind to troponin C on thin myofilmanets and cause tropomyosin to uncover myosin binding site of actin. Power stroke occur! Actin-Myosin and ATP Cycle (need both AP and ATP for contraction!) 1. ATP ADP + Pi occur in ATP binding site of myosin, releasing energy to it 2. Ca2+ released from sarcoplasmic reticulum by an action potential binds to Troponin C, tropomyosin roll off myosin-binding sites on actin 3. Powerstroke occurs, but myosin remain binded until ADP and Pi released from myosin head and a new ATP comes in; then the cycle repeats Relaxation of Muscle Action potential stops, Ca2+ no longer diffuse out of sarcoplasmic reticulum, special calcium pumps pump Ca2+ back into SR up its concentration gradient with ATP (but only so fast since pumps can be saturated, thats why when we tire our muscles they dont just relax quickly), tropomyosin will cover myosin binding sites again. But remember: as long as there are still Ca2+ around, the muscle will remain contracted. http://www.youtube.com/watch?v=0kFmbrRJq4w Altering Force of Contraction (how we can lift different weights) 2 ways to increase tension (force of contraction): increasing voltage by recruiting more motor units and putting them to work, or increasing frequency of action potential and summing twitch contractions 1) Recruit motor units Motor unit: motor neuron and all the muscle cells it causes to contract (each cell innervated by only one motor neuron); number of cells a neuron controls varies, from a few to 200+ 2) Summation Twitch Contractions Muscle twitch: from one action potential in motor neuron, simplest and smallest muscle contraction

Twitch Duration=10-100ms, where as duration AP is 2ms; this means you can have multiple AP during one twich, between 5-50! And all of them can add up. Latent period: time delay from when AP occur on motor and to muscle contracts; caused by events at neuromuscular junction, generation of AP on muscle cell, thin and thick myofilaments interactions Increasing the frequency of action potentials = stimulus (until the max of 1 every 2ms) can increase force of contraction: summation of twitch contraction, caused by the fact a twitch has longer duration than AP. Cant be summed up in neuron due to absolute refractory period caused by inactivation of Na+ v-gated channels. Maximal tetanic contraction: reached at high frequencies shown by plateau in muscle tension; no relaxation at all

6. Nervous System

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Introduction Nervous System 1. central nervous system (CNS) brain and spinal cord 2. peripheral nervous (PNS) others nerves - outside the CNS (go to muscles/organs like heart) o somatomotor nervous systems (going to skeletal muscles) somatic motor system o autonomic nervous systems (other organs like heart ) Basic Structure of the Brain Two cerebral hemispheres (left and right) o left hemisphere sends signals to right side, and vice versa o each hemisphere = divided up into 4 lobes with specific functions: frontal lobe, parietal love, temporal lobe, occipital lobe

brain stem: controls some of the most basic functions (heart rate/respiration) o contains midbrain, pons, and medulla oblongata o medulla = continuous with the spinal cord Cerebellum: responsible for coordinated movement Diencephalon: thalamus & hypothalamus Bumps = gyri, dips = sulci increase surface area Neurons and Glial Cells (makes the brain)

Glial = 90% of the brain provides environment for the neurons Maintain delicate internal environment of the CNS Gluing things together, regulate the nutrients & environment Regulate passage of substances between blood / brains interstitial space Astrocytes, microglia, and oligodendrocytes (produce myelin) Neurons = information transmitting/processing cells Bipolar neurons: 2 processes extending from cell body (e.g. retina) Unipolar: one process extending from the cells body (peripheral nerves outside the CNS) generally sensory/transmit signals to/from spinal cord (body lies off to one side of axon, but middle) Multipolar: many branching dendrites (most common in CNS)

Languages of Nervous System / Neural Coding Information travels down axons in the form of an action potential Neural coding: the stronger the stimuli (heavier it is) the more action potential per second (higher frequency) Synaptic Transmission: the chemical synapse

The way nerve cells communicate with one another (similar to neuromuscular junction) neurons meet with each other via axon terminal of one neuron (presynaptic neuron before synapse) releasing neurotransmitter chemical to and meeting with dendrites of another neuron (postsynaptic neuron after synapse) 1. presynaptic neurons makes neurotransmitters stored in synaptic vesicles and 2. action potential travel to presynaptic neuron depolarizes membrane, opens voltage-gated Ca++ channels Ca++ flow into axon terminal along the concentration gradient release of the neurotransmitter from the synaptic vesicles into the synaptic clef (exocytosis) release of neurotransmitter is triggered by Ca++ ion influx 3. neurotransmitter cross the synaptic cleft, bind to chemical receptors on postsynaptic cell membrane that are associated with opening of chemicallygated ion channels positive ions flux in (Na+)

Neurotransmitters Chemicals released by neurons at their axon terminals stored in synaptic vesicles released in response to action potential and causes response in postsynaptic neuron o Excitatory depolarization may fire an action potential (glutamate) o Inhibitory hyperpolarization decreases chance of firing action potential (gamma-amino-butryic acid GABA) Unlike in neuromuscular junction (NMJ), neurotransmitter doesnt have to be acetylcholine o Norepinephrine (amine), GABA (aa), glycine (aa), neuropeptides Major different from NMJ: rather than a single AP in motor neuron ALWAYS producing a single AP in muscle cell, at chemical synapse, single action potential on presynaptic neuron will NOT produce an action potential on a postsynaptic neuron. o Note: 1 neuron only releases one specific neurotransmitter Excitatory postsynaptic potential - EPSP Excitatory Neurotransmitters are released from presynaptic neuron and bind to their receptors causing chemically gated channels to open + ions (Na+ mostly) flux into dendrites local depolarization of membrane = EPSP (excitatory postsynaptic potential) very local event like End-Plate Potential; but EPSP diminishes (with time & distance) still no AP (action potential) yet though need voltage-gated channels to open = essential for AP production o most V-gated channels = found at axon hillock, so EPSP must be strong enough to depolarize all the way to there o theres no v-gated channels on dendrites/cell body Increasing strength of an EPSP (both = additive effect) o Spatial summation of EPSPs: many EPSPs generated at many different synapses on the same postsynaptic neuron at the same time o Temporal summation of EPSPs: many EPSPs generated at the same synapse by a series of high-frequency Aps on the presynaptic neuron

o Both can help the EPSP travel to axon hillock and open a sufficient number of v-gated channels to reach threshold (from -70mV to -55mV) and fire the action potential

Inhibitory Postsynaptic Potentials IPSP Stimulus causes a hyperpolarization by opening different chemically gated channels that let Cl- in or K+ out (either way making the inside/membrane potential more negative) hence hyperpolarization o Makes membrane potential even further away from threshold shut off the nerve cell Summation (spatial and temporal) can also occur in IPSP (since the only difference is which chemically gated channels they open on postsynaptic dendrite) produce larger hyperpolarization

Important*: one neuron will ONLY RELASE ONE SPECIFIC NEUROTRANSMITTER. Its not like they can choose. But brain can choose which neuron to activate to achieve desired effect Properties of EPSP and IPSP (they =/= action potential!) Occur in dendrite region of neuron (localized!) must spread to axon hillock, by the time of which if depolarization still large enough to make mem.potent.> (-55mV), FIRE! (ap = only on axon) Can have varying sizes, big or small (change by 1mV or 10mV, sure!) (ap = all or nothing) Spread but decay over distance & time fades away like ripples Can be summed: temporal (throwing rocks one after another to the same spot) or spatial (throw whole bunch of rocks at the same time) (ap cannot be added due to refractor period) Can be integrated/combined (>1 presynaptic neuron on one postsynaptic neuron, some firing EPSP some firing IPSP = signals battle / stronger wins / cancel out in postsynaptic neuron) o THIS BATTLE = SYNAPTIC INTEGRATION

 The Somatic Motor System How the brain controls muscles to perform voluntary movements (brain part responsible for activating muscles, spinal tract which sends the info down, and muscles send sensory info back to brain) Structure & Organization of Motor System Premotor cortex, Supplementary Cortex, primary motor cortex = in the frontal lobe

1. The Premotor Cortex e.g. picking up a coffee cup decision comes from prefrontal cortex passes signal to premotor cortex (frontal lobe): determines the way an action will be carried out / develops strategy for movements necessary for action (how to move which muscle group in what order) after sequence of muscle contractions developed, pass this to supplementary 2. The Supplementary Motor Cortex programs the motor sequences the more complex/repetitious the movement, the more important to have the supplementary motor cortexs role program written, sent to primary 3. Primary motor cortex activate the neurons that will eventually activate the appropriate muscles arranged in a specific manner as if entire body was projected onto the surface of the brain like a map topographical representation = motor homunculus (specific area of motor cortex activates a particular muscle) 4. Cortico-spinal Tract major motor pathway from primary motor cortex to motor neurons (which communicates with muscle cells) tract begins in primary motor cortex, down to brain stem, and enter the spinal cord and down until they synapse with motor neurons (directly contacting the muscle at corresponding places in body)

In medulla (inside brain stem): 80% nerve fibers cross over to contralateral side (the other side of the body), the other 20% originally ipsilateral nerves will cross over to contralateral side as they reach their destination in spinal cord 5. Muscle Receptors send signals back to the brain proprioception: awareness of the positions of the limbs and extent of muscle contract at any given time muscle sense (e.g. touch 2 index fingers close-eyed) allows us to make movements without looking constantly only possible due to muscle receptors: 1. muscle spindles: detect length and stretch of muscle & rate of change in muscle length 2. Golgi tendon organs: detect muscle tension

1. Muscle spindles: series of intrafusual fibers (inside the extrafusal fibers: real contractile muscle cells), (central) sensory region, 2 sets of gamma motor neurons, and sensory neuron that originates in sensory region When muscle stretches, so does sensory region of spindle, depolarizes & triggers action potential in the sensory nerve,

sending signals to brain (more stretch = more depolarization = more AP); brain can decipher how stretched the muscle is AND relative position of limb in space attached to the muscle (proprioception) alpha-gamma coactivation during contraction: signals from CNS travel through alpha motor neurons in extrafusal fibers to cause muscle contraction during which gamma motor neurons also send signals to contract intrafusal fibers so it can continue to send info to brain (or else it goes into slack and stops working) The reflect arc: a most basic example of integrated neural activity NO BRAIN INVOLVED. Receptor (skin) receptor potential action potential in afferent neuron spinal cord, causes AP there and on interneurons AP in efferent neuron activate effector (like muscle) Does not require output by brain, goes to brain but only because thats already the shortest path connecting receptor & muscle

Stretch Reflex An example of reflex arc found in all muscles (here = quadriceps muscle) Tapping tendon small stretch in muscle stretch in muscle spindles which triggers AP in afferent neuron entering spinal cord efferent = quadriceps contract while hamstring relax lower legs kicks out

Cerebellum little brain Contains more neurons than the rest of the brain combined!

Contribute to generation of accurate limb movements, correcting ongoing movements, modifying strength of some reflexes o Receive and compares info from 2 sources: signal from primary motor cortex travelling out to muscles & proprioception (position of limbs in space) back to brain should match, and if not, cerebellum modify signals from primary motor cortex

Involved with learning of new muscle movements Vestibular ocular reflex (staring at one spot while moving your head LOL) Limbic System & Hypothalamus (emotional centre & hemeostasis ctrl) Both of these regions together coordinate variety of autonomic, hormonal, and motor effects associated with hemeostasis and emotional behaviours (eating, drinking, sex, attack memory) Limbic System

Composed of hypothalamus, amygdala, hippocampus, and cingulate cortex (and septum) forms ring around brain stem Link higher thought processes of brain with more primitive emotional response of fear/rage/sexual pleasure Linked to feeding, drinking, pain, motivation, learning Respond correctly to changes in our environment

Hypothalamus Based of brain anterior to brain stem small portion, yet important functions A major regulator! Regulates temperature control, body water, food intake, cardiovascular, circadian clock, and coordinates emotional behaviours, controlling hormones released from pituitary gland (mostly negative feedback control)

The Pituitary Gland Also small and important (only s small pea-sized thing below hypothalamus Control and release hormones closely regulated by hypothalamus

The Autonomic Nervous System (ANS) Unlike somatomotor system, not under voluntary control Controls heart rate, pupils in eyes, smooth muscle in walls of arteries/veins, glands and other organs 2 divisions: sympathetic and parasympathetic nervous system; each system sends neurons to each of the organs (adrenal = only SYN) the two always work in opposite in an organ of one excite the other inhibit Sympathetic (SYN) Activate body functions of fight or flight situations Increase heart rate/BP, dilate airways and blood vessels to muscles, shut down digestive system Parasympathetic (PSYN) Storage & conservation of energy rest and relaxation

Neurotransmitters of ANS

Both use acetylcholine (Ach) between preganglionic/postganglionic neuron, but SYN uses norepinephrine (NE) onto target organ as well as Ach while PSYN only uses Ach.

7. Sensory Systems

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Intro To maintain homeostasis (stable internal environment despite external conditions) body needs to detect changes in external environment to react appropriately sensory systems! Somatosensory system (touch) Visual system (vision) Auditory & vestibular system (hearing) Olfactory system (smell Gustatory system (taste) Transduction of environmental information Translating the information about external environment into language brain understands: action potentials Environmental stimuli (light/heat/touch/sound) detected by sensory receptors, convert into action potentials Environmental Stimuli: converts stimuli to AP Mechanical stimulus: touching/vibrating the skin stretch sensory receptors in skin and open ion channels depolarization of sensory neuron to produce AP Chemical stimulus: sour taste / odor in nose binds with receptors to cause depolarization and AP Light energy: absorbed by photoreceptors of eye (retinas rod and cone cells) AP Gravity and motion: detected by hair cells in vestibular system AP Adequate Stimulus: the stimulus a receptors particularly good at detecting specialized to be the most sensitive to it E.g. adequate stimulus for rod and cone cells of retina is light However, receptors can sense more than 1 type of stimuli; rod and cone can also sense pressure Receptor Potentials only occur in receptors, after they are stimuluated Similar to the way excitatory neurotransmitter produces EPSP at chemical synapse which then generates AP at axon hillock if strong enough Sensory receptor stimulated by environmental stimulus change in ion permeability causes local depolarization called receptor potential in the receptor cell

Receptor has no voltage-gated ion channels, no AP, so receptor potential need to spread to a sensory neuron which has v-gated channels; usually first node of Ranvier on the axon AP generated and propagated along axon into spinal cord Many similarities with EPSP & IPSP, shared characteristics include Generally depolarizing but can be hyperpolarizing as well Caused by an increase in permeability to Na+ ions (or K+ for hyperpolarizing stimulus) Local and dont propagate down the neuron like AP; spread and decrease in strength with time/distance from stimulus Potential strength is proportional to strength of stimulus thus likelihood of firing an AP Receptor Potential & Neural Coding Heavier weight trigger receptor to produce larger receptor potential trigger more AP on sensory neurons axon high-frequency AP reaches brain (process of conveying weight to brain using AP frequency = neural coding) Somatosensory System Detects and processes sensations of touch, vibration, temperature and pain (mostly from skin) each sensation requires a few different sensory receptors, but skin receptors collective called cutaneous receptors: Hair follicle: receptors sensitive to fine touch and vibration Free nerve ending: respond to pain and temperature (hot/cold) Ruffinis corpuscles: detect touch Meissners corpuscles: detect low-frequency vibrations (30-40 cycles/sec) and touch Pacinian corpuscle: detect high frequency vibrations (250-300 cycles/sec) and touch

 Receptive Field (of a receptor): area on surface of the skin where an adequate stimulus will activate a particular receptor to fire an AP in neuron If cells outside of the receptive field is stimulated no AP produced Somatosensory Pathways from Periphery to Brain How receptors deliver information/AP up to the brain (2 pathways) 1. Spinothalamic Tract Transmits information of basic sensations (pain, temperature, crude touch) Information in Sensory neuron (= lower spinal cord, 1st order neuron) upper spinal cord (1st synapse with 2nd order neuron), crosses to contralateral side ascends to thalamus: relay station for all senses except smell 2nd synapse with 3rd order neuron somatosensory cortex 2. Dorsal Column, Medial Lemniscal System Transmits information associated with more advanced sensations (fine detailed touch and vibration, proprioception, and muscle sense) Same as spinothalamic tract EXCEPT dont cross in lower spinal cord, travels up spinal cord and cross in upper spinal cord after the synapse with 2nd order neuron thalamus & synapse into 3rd order neuron somatosensory cortext

*somatosensory = for sensory information, motor = for voluntary movement info Primary Somatosensory Cortex the purple thing in parietal lobe behind central sulcus where sensory information 1st reach the brain

The primary somatosensory cortex, just like primary motor cortex, has a topographical representation of the entire body on its surface like a map somatosensory homunculus (vs. motor homunculus) Not to scale, some places require processing of more sensory information (hands, tongue, lips the sensitive parts, also have more receptors) and has a larger proportion in homunculus The Visual System Consists of the eye (photoreceptors: light AP), visual pathway (transmits AP to brain), primary visual area (in occipital lobe of the brain which processes the incoming signals) The Eye

A camera: light cornea (amount of light passing through regulated by iris) flips the light upside down focus onto retina at back of the eye, whose photoreceptors called rods and cones center of vision = focused onto a part of retina = fovea (highest concentration of cone cells)

Rods cells & cone cells the photoreceptors of the Eye

Rods Cones Extremely sensitive to light so functions best under low light Only 1 type of photopigment, do not detect colour Found mostly in the region on retina outside/around fovea

Functions best under bright light, ideal for detecting detail 3 types of cone cells each with different photopigment sensitive to their own primary colour located in fovea (large concentrations) both dont have axons, so dont generate AP, only receptor potentials that causes release of inhibitory neurotransmitter from their synaptic ending IN THE DARK Other cells of the Retina Pigment layer on retina at very back of eye of other cells to absorb excess light (bipolar cells, ganglion cells, horizontal cells, amacrine cells) and combines with rods/cones to produce action potential Transduction of Light to Action Potentials weird

Dark: cone & rod cells naturally depolarized because Na+ is flowing into them release inhibitory neurotransmitter when no light, bipolar cells inhibited and no AP no image Light: strikes rod&cone cells = close their Na+ channels only, but K+ can still leak out as usual, cell hyperpolarizes, no inhibitory neurotransmitters, means bipolar cells can depolarize spontaneously without inhibition and AP fired in ganglion cells image! Types of Eye Movements We need to move our eyes in a number of ways to focus light from particular object onto fovea Saccades: rapid jerky movements (reading words on your computer) Smooth pursuit: smooth movement of eye following a moving object (watching a plane in the sky while keeping head still) Vestibular ocular reflex: focus on an stationary object while shaking your head Vergences: object moving away (eyes diverge) /approaching you ( converging) The Auditory System Converts sound waves into AP and travel to the auditory system of the brain our most acute hearing occurs in range 1000 3000 Hz Structure 1. External (outer) ear: the physical ear and the external auditory canal 2. Middle ear: eardrum (tympanic membrane) and 3. ear ossicles (3 bones connected like a lever system: malleus, incus, stapes), and 6. Eustachian tube 4. Inner ear: vestibular apparatus (sense of balance) and 5. cochlea (processing sound)

 Structure of the Cochlea shell/garden snail, with the inside hollow area divided into 3 compartments/duct: upper=scala vestibule (vestibular duct), middle = cochlear duct (insert basilar membrane here in between middle & lower - contains organ of Corti) lower = scala tympani Sound waves vibrate basilar membrane, bend hair cells on it

 Sound: only when the wave of air pressure hits parts of the ear/microphone does it turn into electrical information (AP) and interpreted as sound, so if a tree falls and no one hears it, no sound created, only air waves Sound frequency: number of sound waves per unit time Sound intensity (loudness): amplitude of the sound wave Transfer and Amplification of Sound Vibrations airwaves travel through air, reach outer ear, funneled into external auditory canal, strike tympanic membrane, vibrates back and forth while the ear ossicles amplifying the pressure waves through its levering action Stapes causes oval window (much smaller than tympanic membrane) to vibrate, waves amplified 15-20 times now due to levering and membrane size difference

Fluid inside cochlea (perilymph) transmits waves to hair cells embedded in basilar membrane detect vibrations and turn them into AP in the auditory nerve Basilar (Basement) Membrane Wide and thin and at top of cochlea while narrow and thick at base (near oval window); tension also varies along its length (loose at top and tight at base) Low frequency stimulate hair cells the top (loose), high frequency stimulate hair cells near oval window how we can detect diff freq. (also length/stiffness of hair cells differ)

Sound: vibration AP When basilar membrane vibrates, hair cells bend, ion channels open, cells depolarize, neurotransmitter releases from hair cells, neurons of auditory nerves excited and fire AP Louder sound = stronger vibration = more bent the hair cells = more neurotransmitter = higher frequency of AP Signals flow to auditory cortex in temporal lobe of brain Vestibular System Inner ear next to cochlea maintaining balance, equilibrium, postural reflexes by detecting linear & rotational motion Detect linear and rotational motion + position of head relative to rest of body + vestibular ocular reflex Structure Semicircular canals: detect rotational and angular accelerations of head o 3 of these canals, one for each plane of motion o canals filled with fluid (endolymph)

o end of canal = ampula (a swelling) inside of which is crista ampullaris (sensory region) contains sensory hair cells fixed at base and top embedded in gelatinous cupula o example: turn your head left = horizontal rotation, endolymph inside canals will seem to move to the right, hits cupula and bends hair cells embedded in it when bending in a specific direction, hair cells depolarize and fire AP (bent to opposite direction = hyperpolarize)

o Otolith organs: detect linear accelerations o 2 of these, detect acceleration in vertical plane and horizontal plane, as well as position of head when tilted Utricle detects horizontal acceleration/deceleration (e.g. in a car) (UH university hospital LOL) Saccule detects vertical acceleration/deceleration (e.g. in an elevator) Both together detect head tilts o Each otolith organ contain many hair cells anchored at base and top embedded in gelatinuous membrane which has otolith crystals in it for added weight/inertia

o at rest: AP produced in vestibular nerve o accelerating vertical/horizontal plane: otolith crystals lag behind, move in opposite direction to acceleration bends cilia of hair in opposite direction of acclereation and cause them to increase frequency of AP in vestibular nerve (in proportion ot acclereation) o Note: travelling at constant velocity = feels nothing o Decelerate: bend in the forward acceleration direction, AP decrease further from resting state (more rapid deceleration = lower AP frequency) The incredible hair cell o They are involved with processing sound by auditory system, as well as balance/equilibrium by vestibular system o When at rest, hair cells release small resting level of neurotransmitter from base onto sensory nerve AP there

o When stereocilia (top) bend toward the larger kinocilium (below it) like during an acceleration, hair cell releases more neurotransmitter more AP o When stereocilia bend away from kinocilium (deceleration), releases less neurotransmitter less AP

Receptors dont produce AP!

8. Circulatory System I: The Heart

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The Heart Size of your fist, sits in chest cavity between lungs 4 principal functions of cardiovascular system: o transports oxygen and nutrients to all cells of body o transports CO2 and waste products from cells o helps regulate body temperature and pH o transports and distributes hormones and other substances Anatomy The Heart 2 side-by-side pumps: right atrium and ventricle: pumps blood to lungs left atrium and ventricle: pumps blood to rest of the body o left ventricles wall is much thicker than right ventricles since it needs to contract more forcefully to pump blood for body ensure one-way flow of blood through heart Right atrioventricular valve (R-AV valve) = tricuspid valve Left atrioventricular valve (L-AV valve) = bicuspid/mitral valve 2 valves in each ventricle only (left and right AV valves for blood coming in and pulmonary valve in right ventricle and aortic valve in left ventricle for blood going out)

Valves:

Circulation Through the Heart Blood enters heart at right atrium after flowing through body Pass through right atrioventricular valve right ventricle Right ventricle contracts, ejects blood out of heart through pulmonary valve into the pulmonary artery to lungs Blood in lung, CO2 out, O2 in Blood returns to heart through pulmonary vein into left atrium From left atrium left ventricle through the left atrioventricular valve Left ventricle contracts, blood ejects through aortic valve into aorta out to the body

 Myocardial Cells (myo = muscle, cardio = heart) of the Heart 1. contractile cells: similar to skeletal muscle cells, forms most of the walls of atria & ventricles features and contract almost same as muscle fibers o same contractile proteins actin and myosin, arranged in bundles of myofibrils and surrounded by sarcoplasmic reticulum difference

o have only one nucleus, but far more mitochondria (make up 1/3 of volume!) o extremely efficient at extracting oxygen (around 80% of the oxygen from passing blood, 2x of normal cells) o cells much shorter, branched, joined together by special structures called intercalated discs

Intercalated discs have o Tight junctions: bind cells together o Gap junctions: allow for movement of ions and ion current between myocardial cells heart can conduct AP from cell to cell without nerves! extremely important

o 2. nodal/conducting cells: similar to nerve cells, contract only very weakly self-excitability system: they are able to spontaneously generate AP (thus heart impulse) without nervous input (like regular neurons) o origin for AP: sinoatrial node (SA node) first area to spontaneously depolarize and make AP, called the pacemaker of the heart (in upper posterior wall of right atrium o AP then travel through atria to atrialventricular node (AV node) bundle of His purkinje Fibers ventricular muscle

o transmission system: can rapidly conduct AP to atrial and ventricular muscle too carry impulses throughout the heart

SA Node Action Potential All cells of heart can generate AP spontaneously, but SA node = fastest Review: these ions also responsible for AP in heart (except AP begin by itself) Na+, K+, Ca++ most important

The Na+ permeability in node is higher, so Na+ will move into the cell down its concentration gradient (same as Ca++) and cells are slightly more positive over time initial depolarization (not AP) K+ (trying to leave cell) permeability in SA node decrease over time, and Na+/K+ pump pumping K+ into cells together, spontaneous AP! Na+ and Ca++ flowing in, K+ build up inside, membrane potential of SA: -60 mV -40mV (threshold for these cells) o Completely spontaneous, so SA nodal cells dont have a stable resting membrane potential o Once o o

Slow depolarization always = pacemaker potential -40mV reached, voltage-gated Ca++ channels open Ca++ rapidly flow in, depolarization phase (of actual AP) Close when voltage-gated K+ channels open (K+ go out of cell to repolarize) return to lowest value of -60mV. Repeat. o (similar to neural AP, except Ca+ replace Na+ flow in and the values are different) Conducting System of Myocardial Cells AP speeds up through atrial muscle AV node (conduction is the slowest here!!! need to slow it down to ensure atria finished contracting before ventricles start, or else WHERE TO GO?!) reach base of heart through Bundle of His (faster, takes AP to bottom of heart apex) Purkinje fiber then spread AP throughout ventricular muscle (fast here; ventricular muscle contracts from apex upward so blood can be forced up and out through valves at top of ventricles) ITS LIKE SQUEEZING UP TOOTHPASTE! Electrocardiogram (ECG) Heart sits in conducting fluid, good conductors of electricity and electrical current can be spread to surface of body Can measure electrical potentials generated by heart by placing electrodes on skin around heart electrocardiogram (ECG)

P wave = depolarization of atrial muscle leading to its contraction o No wave for repolarization of atrial muscle QRS complex = depolarization of ventricular muscle prior to its contraction T wave repolarization of the ventricular muscle as it relaxes

The Cardiac Cycle All the mechanical, electrical, and valvular events taking place in heart during a single contraction 5 steps: systole = contraction, diastole = relaxation 1. Atrial systole AV valve open! Atria depolarizes (P) and contract; lime higher than red because atrial pressure > ventricular pressure, but latter increases with

atrial pressure as does ventriculars volume (increase to end diastolic volume 100% of max ventricular volume; EDV!)

2. Isovolumetric ventricular contraction (early ventricular systole) Ventricles depolarizes (QRS complex) then contracts, ventricular pressure up up up, mitral valve is closed (so blood dont flow back to atrium) and isovolumetric meaning no change in ventricular volume (aortic valve still closed because pressure inside arota > ventricular pressure still)

3. Ventricular Systole (ejection period) ventricles keep contracting this phase starts @ the breaking point when ventricular pressure > aortic pressure = 80mmHg aortic valve opens, blood flows into aorta ventricular volume decreases as blood pours into aorta while pressure continues to go up to 120 mmHG until aortic valve close when ventricular pressure < aortic pressure again (end systolic volume, lowest pt)

4. Early Ventricular Diastole (isovolumetric relaxation period) Ventricular pressure < aortic pressure and keeps falling as ventricle relaxes; both valves closed and no change in volume (stays at the minimum end systolic volume ESV!)

5. Late ventricular diastole (ventricular filling period; longest phase) Ventricular pressure < atrial pressure now, mitral (AV) valve open and blood flows into ventricle, ventricular volume increases (important! 70% of ventricle is filled during this time! Even though atrium not even contracting, just the AV valve open and higher pressure in atrim) get ready for P wave again when atrium contracts (the other 30% goes in). repeat.

Heart Sounds Come from closing of the heart valves (and surrounding fluids vibration) 1st sound: closure of AV valve (lub) 2nd sound: closure of aortic and pulmonary semilunar valves (dub) Mechanical Performance of the Heart 1. Cardiac output (CO): amount of blood each ventricle can pump in 1 minute (around 5L at rest, if vigorous exercise: 20L 40L both SV/HR ^)

HR = bpm SV = vol. of blood pumped by one ventricle per heart beat 2. Control of Heart Rate Overview Controlled by all 3 nervous systems

1. Autonomic nervous system (ANS): we already know 2. Parasympathetic nervous system (PSYN): mainly in SA and AV nodes, less in atrial and ventricular muscles (mostly SA node though) Decrease heart rate and force of contraction If all 3 removed, intrinsic HR = 100bpms, but in individual, PSYN constantly slowing heart rate to 70 bpm: called vagal tone (vagus nerve transmits the slow-down signals from PSYN to SA node)

3. Sympathetic nervous system (SYN): distributed always same as PSYN but stronger innervation to ventricular muscle opposite effect, increase HR and force of contraction 3. Parasympathetic Nervous System when PSYNs neurons to the heart activated: acetylcholine released as the neurotransmitter onto SA and AV nodes causes K+ channels to open (let more K+ out) o 1. membrane potential hyperpolarize o 2. slope of pacemaker potential decrease (cant depolarize as fast, takes longer to depolarize HR goes down ) Slow down AV too (and not just SA) because you need to slow down the conduction of AP through the heart too to ensure atria have enough time to finish contraction before ventricules starts Notice: lowest membrane potential = -60, threshold = -40 (no resting potential)

4. Sympathetic Nervous System release neurotransmitter norepinephrine (+ epinephrine/adrenaline) onto SA and AV node (both nodes; same reason as above, speed up both atria and ventricles) cause opening of Na+ and Ca++ channels, enter cell, reach threshold faster, rapid depolarization heart rate go up

5. Stroke Volume

EDV = End Diastolic Volume: amount of blood in ventricle at end of diastole before contraction (max; 120mL at rest) During stage 1: atria systole; after receive blood from atrium, and ventricle pressure > atrium (AV valve closed) ESV = End Systolic Volume: just after a systole/contraction (min; 50mL at rest) During stage 4: early ventricular diastole period (isovolumetric) after it gave blood to aorta and both valves closed before pressure is less than atriums SV = different between the two Note: - if 1 one-way valve 2; valve only open when pressure 1 > pressure 2 - EDV (diastolic big volume); ESV (Systole small volume) Factors that change stroke volume

Changing force of contraction = changing stroke volume 1. Input from autonomic nervous system (PSYN or SYN) a. PSYN: release of acetylcholine onto cardiac muscle decrease amount of Ca++ entering cell (slows down depolarization) decrease force of contraction, stroke volume goes down b. SYN: release norepinephrine onto muscle cells (increase amount of Ca++ entering the cells) increasing stroke volume 2. EDV and preload: (more blood to be pumped; higher EDV = pump harder = less blood left; lower ESV) Frank-Starling Law of the Heart (dont need nervous system imput!) a. Preload: load on heart before it contracts (amount of blood in ventricle that stretches muscle of heart) = EDV b. Higher load = more Ca++ channels opened to let Ca++ in, more forceful contraction, more blood ejected 3. Changing EDV Squeeze veins more to increase venous return (blood return to heart by veins, which contain 70% of total blood volume) a. do it by activating SYN (innervates smooth muscle located in walls of veins) contract muscle around inside of vessel wall (veins have valves to prevent backflow) squeeze more blood back to heart EDV go up, SV go up, CO go up. b. By exercising: contraction and relaxation of skeletal muscle also squeeze veins since veins run between large muscle groups same effect, so exercising increases cardiac output! c. By breathing more deeply (will cover in respiratory system)

9. Circulatory System II: Blood Vessels

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Anatomy Arteries and arterioles: transport blood away from heart Large arteries branch into smaller arteries smaller arterioles capillaries Capillaries: gas exchange (smallest blood vessels) Veins and venules: return blood back to heart Capillaries converge small venules larger and larger veins

2 principal loops: pulmonary circulation: right side of heart arteries lungs branch into pulmonary capillaries and gas exchange takes place venules veins left side of heart systemic circulation: left side of heart oxygenated blood pumped out through aorta into arteries arterioles capillaries gas exchange (O2 nutrients hormones out, CO2 and waste in)

deoxygenated blood returns through venules and larger veins to right side of heart Blood Volume Distribution Total blood volume = 5L 70% in veins (thus veins called capacitance vessels) 10% arteries 15% heart and lung 5% capillaries Blood velocity and cross-sectional area of vessels As you go from arteries to arterioles to capillaries, TOTAL cross-sectional area become larger, blood pressure and blood velocity both drops (flow high to low pressure, and fast velocity in arteries to distribute blood throughout the body quickly) From capillaries to venules to veins: cross-sectional area decreases, but blood velocity goes up while pressure doesnt.

Pressure, Flow, and Resistance Pressure gradient: driving force of blood circulation; pressure drops throughout the flow so blood can keep moving

Resistance: friction between blood and walls of vessels (laminar flow = flow through a tube with non-uniform velocity - decreases @ closer to the walls) p1-p2 = pressure gradient (two points along the tube) Resistance increase with 1. thicker fluid (blood doesnt really change in viscosity though; dehydration) 2. longer vessel (blood vessel doesnt change length either; overweight = stretch them) 3. smaller inside diameter (cross-sectional area) = increased resistance! For this course: *memorize!

larger the blood vessel, more flow (volume/time) Control of Blood Flow in the Body Since blood pressure usually constant, best way to regulate blood flow is by changing radius of vessels generally of arterioles (their ability to constrict and dilate to a large degree) Total flow doesnt change though; constrict one arteriole means increase flow in other ones to maintain constant flow Changing Blood Flow for Needs of an Organ

Organs blood needs depend on its oxygen/nutrients need (e.g. after meal blood diverted from muscle to intestines to help digestion; converse when exercising) Vasodilating where blood flow need to increase and or vasoconstricting arterioles to decrease flow there Blood Pressure and Resistance throughout the Systemic Circulation Systolic pressure: when heart contracts listen to sound when blood enters squeezed area (higher pressure) Diastolic pressure: when heart relaxes listen to sound when blood flow becomes laminar again (lower pressure) The 120/80 we measure are of the aorta As distance from left ventricle increases, pressure falls. By the time blood reaches right atrium, pressure almost 0 mmHg.

Structure of the Blood Vessel

Both arteries and veins = 3 layers Outer layer = fibrous connective tissue Middle layer = smooth muscle and elastic tissue Inner layer = endothelial cells Veins has extra valves = ensure blood flows one direction back to the heart Capillary: just a single layer of endothelial cells permits diffusion Also clefs and fenestrations in capillary just holes which allow movement of dissolved solutes (NOT large proteins) into/out 1. Diffusion: O2, CO2, water, waste products all can diffuse through capillary into interstitial fluid o very good, thin wall and large total cross-sectional area 2. Filtration: fluid moves from capillary out to interstitial space 3. Reabsorption: movement of fluid from interstitial space back

 Arteries: larger proportion of elastic tissue allow volatile pressure changes during heart contraction Low resistance, little drop in BP highest BP Arterioles: smaller but mostly smooth muscle under control of ANS = vasoconstriction/vasodilation to control blood flow through organs Thick wall, largest resistance, large drop in BP Venules: no smooth muscle/elastic tissue blood pressure very low (lowest), just return blood to veins Veins: thinner & larger diameter to contain 70% total blood volume Smooth muscle innervated by ANS for increasing venous return/EDV, and elastic tissue allows them to expand Starling Forces 4 different forces that determine whether filtration or reabsorption occurs

Hydrostatic forces:

1. capillary hydrostatic pressure (Pc Pressure of capillary): normal blood pressure, forcing blood outwards on the walls of capillaries cause filtration 35 mmHg arterial end; 15 mmHg venous end 2. interstitial-fluid hydrostatic pressure (PIF Pressure of Interstitial-fluid; thus out of the capillaries): pressure exerted by interstitial fluid pushing back on capillary cause reabsorption -6 mmHg (negative interstitial-fluid pressure means its lower and will suck fluid out of capillaries filtration) to 6 mmHg (brain, liver, kidney: force fluid back into capillaries reabsorption, and prevents organ swelling) Osmotic forces: (due to large proteins in plasma/interstitial fluid which cant move across/diffuse) 3. osmotic force of plasma proteins (Pip Pi = osmotic pressure, p = plasma): proteins concentration inside capillary dissolved in plasma = water wants to move in reabsorption 28mmHg usually, enough to draw fluid back 4. osmotic force of proteins in interstitial space (Pi IF): protein outside capillaries draw fluid out filtration but force is low: 3 mmHG still cause filtration, maybe not net Net Filtration Pressure (NFP)

if positive net filtration pressure, fluid out of the capillary o we would be a big bloated mess? Nope, forunateuly there is lympathatic system to take up excess interstitial fluid! think of it: add forces for water out, substract forces for water in (pressure pushing out and pushing in; proteins inside absorbing in and proteins outside absorbing out)

The Lymphatic System Large network of capillaries & vessels that return excess fluid/other dissolved substances in the interstitial spaces back into circulation Excess fluid passes through the lymphatic capillaries through their one-ended openings return fluid to larger collecting vessels pass through lymph nodes which filter fluid send it back to venous circulation (near heart) through collecting ducts

Edema Accumulation of fluid in interstitial space causing swelling Doesnt occur usually: lymphatic system removes any excess fluid Occurs when: o Lifting weights, pinch off veins, increase pressure in capillaries, excess interstitial fluid o Malnutrition; decreased plasmid proteins, fluid want to move out & accumulate, bloated abdomen of malnourished children o Lymphatic system blockage/disruption

When I was in grade 7, my dad walked into a Staples store and found out line paper was on sale. 8 years later, I still havent bought another sheet of paper. Control and Regulation of Cardiovascular System Remember!

1. Local control mechanisms in the organs themselves Autoregulation: most organs & tissues control their own blood flow Individual capillary beds maintain relatively constant blood flow despite changes in BP through changing vessel radius (2 theories) 1. Myogenic Theory: occur in brain, heart, and kidneys (delicate organs)

contraction/relaxation of smooth muscle; its a reflex thats built into the arterioles sudden increase in BP arterioles momentarily expand smooth

muscle stretch flow too much oh no ! more Ca++ into muscle cells muscle cells contract and vessels constrict blood flow after constriction will decrease, so does BP Opposite occur when blood pressure drop (vasodilation occurs) 2. Metabolic Theory: changing metabolic activity of an organ = change blood flow to that organ

Exercise muscle uses oxygen & produces CO2, lactic acid, ADP and heat all of which = cause local vasodilation and increase blood flow to active tissue Opposite = when you hyperventilate, too much O2 and too little CO2, vasoconstriction and decreased blood flow (in brain = pass out) 2. Humoral mechanisms: regulation of blood flow by on chemicals in the blood vasoconstrictors epinephrine when binds to ALPHA receptors (on blood vessels in intestines/kidney) and cause vasoconstriction (recall it also increase HR and stroke volume) Angiotensin II (Ang II) most powerful vasoconstrictor; renal system Vasopressin (ADH) renal system Vasodilators Epinephrine when binds to BETA receptors (on blood vessels in skeletal/cardiac muscle & liver) Kinins: family of hormones Histamine: released from damaged cells (also increases capillaries permeability together = swelling after injury) ANF 3. Autonomic nervous system (ANS)

Equation comes from: Flow = pressure gradient / resistance On a whole body level: Cardiac Output = Mean Arterial Pressure / Total Peripheral Resistance

(Then just rearrange the equation: pressure gradient = flow x resistance) MAP (mean arterial pressure;BP) = CO x TPR (total peripheral resist.) So to increase blood pressure, either increase cardiac output (more blood pumped out) or the resistance of vessels (e.g. more kinks) The sympathetic nervous system: activated during fight/flight increase CO (previous module) as well as TPR release neurotransmitter norepinephrine general vasoconstriction BP goes up! o but dont want to decrease blood flow to muscles, so release acetylcholine to cause vasodilation there o effects similar to hormone epinephrine The parasympathetic nervous system: activated during rest and relaxation Decreases HR and SV to decrease CO Decrease TPR too general vasodilation in body (by inhibiting vasoconstricting effects of SYN) BP goes down! The Baroreceptor Reflex Example: stand up suddenly, blood pooled in legs and not returning to heart immediately (drop in venous return/EDV/CO) and BP/blood flow will drop in brain body needs to increase BP, by increase CO/TPR Drop in BP detected by baroreceptors in the aortic arch and carotid sinuses (sensor) receptors send fewer AP back to cardiovascular centre in brain stem (effector) frequency of AP proportional to blood pressure brain sends signals to o heart to increase HR/force of contract (hence CO and hence BP) o blood vessels (arterioles) to constrict and increase TPR together BP (controlled variable) returns to 120/80 (set point) Does the opposite when BP too high

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