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Human physiology part 4 Human physiology part 4 Presentation Transcript

  • Neural Control Mechanisms Section A
    John Paul L. Oliveros, MD
  • Neural Tissue
    Neuron:
    basic unit of the nervous system
    Serves as integrators
    Neurotransmitters:
    chemical messengers released by nerve cells
    Parts:
    Cell body
    Dendrites
    Axon
    Axon terminals
  • Neural Tissue
    Parts of a neuron
    Cell Body
    Contains nucleus and ribosomes
    Genetic information and machinery for protein synthesis
    Dendrites
    Receive inputs from other neurons
    Branching increases the cell’s receptive surface area
    Axon
    AKA nerve fiber
    Single long process that extends from the cell body to its target cells
    INITIAL SEGMENT
    AKA axon hillock
    Portion of axon closest to the cell body plus parts of the cell body
    “Trigger zone”
    Collaterals
    Main branches of the axon
    Axon Terminal
    Ending of each branch of axon
    Releases neurotransmitters
    Varicosities
    Bulging areas along the axon
    Also releases neurotransmitters
  • Neural Tissue
    Myelin Sheath
    Layers of plasma membrane wrapped around the axon by a nearby supporting cell
    Speeds up conduction of electrical signals along the axons and conserves energy
    Oligodendroglia: CNS
    Schwann cells: PNS
    Nodes of Ranvier
    Spaces between adjacent sections of myelin
    Axons plasma is exposed to ECF
  • Neural Tissue
    Axon Transport
    Movement of various organelles and materials from cell body to axon and its terminal
    To maintain structure and function of the axon
    Microtubules
    Rails along which transport occurs
    Linking proteins
    Link organelles and materials to microtubules
    Function as motors of axon transport and ATPase enzymes
    Provide energy from split ATP to the motors
    Axon Terminalcell body
    Opposite route of transport
    Route for growth factors and other chemical signals picked up at the terminals
    Route of tetanus toxins and polio and herpes virus
  • Neural Tissue
  • Neural Tissue
    synapse
    Specialized junction between two neurons where one alters the activity of the other
    Presynaptic neuron
    Conducting signals toward a synapse
    Postsynaptic neuron
    Conducts signals away from a synapse
  • Neural tissue
    Glial Cells/Neuroglia
    90% of cells in the CNS
    Occupy only 50% of CNS
    Physically and metabolically support neurons
    Types:
    Oligodendroglia
    Form myelin covering of CNS axons
    Astroglia
    Regulate composition of ECF in the CNS
    Remove K+ ions and neurotransmitters around syapses
    Sustain neurons metabolically (provide glucose and remove ammonia)
    Embryo: guide neuron migration and stimulate neuron growth
    Many neuron like characteristics
    Microglia
    Perform immune functions in te CNS
    Schwann cells
    Glial cells of the PNS
    Produce myelin sheath of the peripheral nerve fibers
  • Neural Growth and degeneration
    Embryo:
    Precursor cells: develop into neurons or glial cells
    Neuron cell migrates to its final location and sends out processes
    Growth cone: specialized tip of axons that finds the correct route and final target of the processes
    Neurotropic factors: growth factors for neural tissue in the ECF surrounding the growth cone or distant target
    Synapses are then formed once target tissues are reached
    Neural development occurs in all trimesters of pregnancy and upto infancy permanent damage by alcohol, drugs, radiation, malnutrition, and viruses
    Fine tuning:
    Degeneration of neurons and synapses after growth and projection of axons
    50-70% of neurons die by apoptosis
    Refining of connectivity in the nervous system
  • Neural growth and regeneration
    Neuron damage
    Outside CNS
    Does not affect cell body
    Severed axon can repair itself and regain significant function
    Distal axons degenerates
    Proximal axon develops growth cone and grows back to target organ
    Within CNS
    No significant regeneration of the axon occurs at the damage site
    No significant return of function
  • Section B
    Membrane Potentials
  • Basic principles of electricity
    Electric potential
    Potential of work obtained when separated electric charges of opposite signs are allowed to come together
    Potential differences/potential
    Difference in the amount of charge between two points
    Volts: unit of electric potential
    Millivolts: measurement in biological systems
    Current
    Movement of electric charge
    Depends on the potential differences between charges and the material on which they are moving
    Resistance
    Hindrance to electric charge movement
    Ohms law:
    I= E/R
    Insulator
    Materials with high electrical resistance
    Conductor
    Materials with low electrical resistance
    e.g. water
  • Resting Membrane Potential
    Resting membrane potential
    The potential difference across the plasma membrane under resting conditions
    Inside cell: negative charge (-70mV)
  • Resting membrane potential
    Magnitude of membrane potential is determined by:
    Differences of specific ion concentrations in the intracellular and extracellular fluids
    Differences in membrane permeabilities to the different ions
  • Resting membrane potential
    Equilibrium potential:
    the membrane potential at which flux due to concentration gradient is equal to the flux due to electrical potential but at opposite directions
    No net movement of ion because opposing fluxes are equal
    Membrane potential will not undergo further change
    Its value depends on the concentration gradient of an ion across the membrane
  • Resting membrane potential
  • Resting Membrane Potential
    In a resting cell, Na+ and K+ ion concentrations don’t change because the ions moved in and out by the Na+,K+-atpase pump equals that moved by the membrane channels electrical potential across membranes remain constant
    Electrogenic pump
    Pump that moves net charge across the membrane and contributes to the membrane potential
    Na+,K+-ATPase pump:
    Sends out 3 Na+ ions for moving in 2K+ ions
    Makes the inside of the cell more negative
  • Graded Potentials and Action Potentials
    Nerve cells transmit and process information through transient changes in the membrane potential from it s resting level
    Two forms of signals
    Graded potential
    Over short distances
    Action potential
    Long distance signals
    Depolarized
    Potential is less negative than the resting level
    Overshoot
    A reversal of the membrane potential polarity
    Cell inside becomes positive relative to the outside
    Repolarize
    When the depolarized membranepotential returns toward the resting value
    hyperpolarize
    The potential is more negative than the resting lavel
  • Graded potential
    Changes in the membrane potential confined to a relatively small region of the plasma membrane
    Die out within 1-2 mm of site
    Produced by a specific change in the cell’s environment acting on a specialized region of the membrane
    Magnitude of the potential change can vary
    Local current is decremental
    Amplitude decreases with increasing distance from the origin
  • Graded Potential
  • Graded Potential
  • Action Potentials
    Rapid and large alterations in the membrane potential
    100mV from -70mV then reporalize to its resting membrane
    Excitable membranes:
    Plasma membranes capable of producing action potentials
    e.g. Neurons, muscle cells, endocrine cells, immune cells, reproductive cells
    Only cells in the body that can conduct action potentials
    Excitability:
    Ability to generate action potentials
  • Ionic basis of action potentials
    Resting state:
    K+ and Cl- ion membranes open
    Close to K+ equilibrium
    Depolarizing phase
    Opening of voltage-gated Na+ channels 100x
    More + Na ions enter the cell
    May overshoot: inside on the cell becomes positvely charged
    Short duration of action potentials
    Resting membrane returns rapidly to resting potential because
    Na+ channels undergo inactivation near the peak of the action potential to then close
    Voltage gated K+ channels begin to open
  • Ionic basis of action Potentials
    Afterhyperpolarization
    Small hyperpolarization of the membrane potential beyond the resting level
    Some of voltage gated K+ ions are still open after all Na+ have closed
    Chloride permeability does’t change during action potential
    The amount of ions involve is extremely small and produces infinitesimal changes in the intracellular ion concentration
    Na+,K+-ATPase pump makes sure that concentration gradient of each ions are restored to generate future action potentials
  • Mechanism of ion-channel changes
    1st part of depolarization:
    Due to local current opens up voltage gated channels sodium influx  increase in cell’s positive charge  increase depolarization (positive feedback)
    Delayed opening of K+ channels
    Inactivation of Na+ channels:
    Due to change in the conformation channel proteins
    Local anesthetics
    e.g. Procaine, lidocaine
    Block voltage gated Na+ channels
    Prevent sensation of pain
    Animal toxins:
    Puffer fish: tetrodotoxin
    Prevent na+ component of action potential
    In some cells: Ca++ gates open prolonged action potential
  • Threshold and the all-or-none response
    The event that initiates the membrane depolarization provides an ionic current that adds positive charge to the inside of the cell
    Events:
    K+ efflux increases
    Due to weaker inside negativity
    Na+ influx increases
    Opening of voltage gated channels by initial depolarization
    As depolarization increaes mor voltage gated channels open
    Na+influx eventually exceeds K+ efflux positive feedback starts action potential
    Threshold potential
    Membrane potential when the net movement of positive charge through ion channels is inward
    Action potential only occurs after this is reached
    About 15mV less negative than resting membrane potential
    Threshold Stimuli
    strong enough to depolarize the membrane to threshold potential
    Subthreshold potentials
    Weak depolarizations
    Membrane returnsto resting level as soon as stimuli is removed
    No action potential generated
    Subthreshold stimulus
    Stimuli that causes subthreshold potentials
  • Threshold and the all-or-none response
    Stimuli with magnitude more than the threshold magnitude elicit action potentials with exactly the same amplitude with that of a threshold stimulus
    Threshold:
    membrane events not dependent on stimulus strength
    Depolarization generates action potential because the positive feedback is operating
    All-or-none response
    Action potentials occur maximally or they do not occur at all
    Firing of the gun analogy
  • Refractory periods
    Absolute refractory period
    During action potential, a 2nd stimulus, no matter how strong, will not produce a 2nd action potential
    Na+ channels undergo a closes and inactive state at the peak of the action potential
    Membrane must be repolarized to return Na+ channels to a state which they can be opened again
    Relative refractory period
    Interval followng the absolute refractory period during which a 2nd action potential can be produced
    Stimulus must be greater than usual
    10-15ms longer in neurons
    Coincides with the period of hyperpolarization
    Lingering inactivation of Na+ channels and increased number of K+ channels open
    Additional action potentials fired
    Depolarization exceeds the increased threshold
    Depolarization outlasr the refractory period
  • Action Potential Propagation
    The difference in potentials betwen active and resting regions causes ions to flow
    Local current depolarizes the membrane adjacent to the action potential site to its threshold potential producing another action potential action potential propagation
    Gunpowder trail analogy
    Action potentials are not conducted decrementally
    Direction of the propagation is away from a region of the membrane that has been recently active
    Due to refractory period
  • Action potential propagation
    Muscle cells
    Action potentials are initiated near the middle of these cylindrical cells and propagate towards the 2 ends
    Nerve cells
    Initiation at one end and propagate towards the other end
    Velocity of action potential propagation depends on
    Fiber diameter
    The larger, the faster
    Myelination
    Myelin is an insulator
    Action potential only in the nodes of ranvier
    Concentration of Na+ channels is high
    Saltatory conduction/ jumping of action potentials from one node to the other as they propagate
    Faster conduction
  • Initiation of action potential
    Afferent neurons
    Initial depolarization threshold achieved by a graded potential (receptor potential) generated by sensory receptors at the peripheral ends
    Efferent neurons/ interneurons
    Depolarization threshold due to either:
    1. Graded potential generated by synaptic input
    2. Spontaneous change in the neurons membrane potential (pacemaker potential)
    Occurs in absence of external stimuli
    e.g. Smooth muscle, cardiac muscles
    Contnuous change in membrane permeability no stable resting membrane potential
    Implicated in breathing, heart beat, GIT movements
  • Section C
    Synapses
  • Synapses
    Anatomically specialized junction between 2 neurons
    Electrical activity of a presynaptic neuron influences the elcetrical/metabolic activity of a postsynaptic neuron
    100 quadrillion synapses in the CNS
    Excitatory synapse
    Membrane potential of postsynaptic neurons is brought closer to the threshold
    Inhibitory synapse
    Postsynaptic neuron membrane potential is brought further away from the threshold or stabilized
    Convergence
    Neural input from many neurons affect one neuron
    Divergence
    Neural input from one neuron affects many other neurons
  • Functional anatomy of synapses
    2 types of synapses:
    Electrical synapses
    Pre and postsynaptic cells joined by gap junctions
    Numerous in cardiac and smooth muscle cells
    Rare in mammalian nervous system
    Chemical synapses
    Synaptic cleft
    Separates pre and post synaptic neurons
    Prevents direct propagation of electric current
    Signals transmitted by means of neurotransmitter
    Co-transmitters
    Additional neurotransmitter simultaneously released with another neurotransmitter
    Synaptic vesicles
    Store neurotransmitter in the terminals
  • Functional anatomy of synapses
    Presynaptic cell:
    Action potential axon terminal depolarization  voltage-gated Ca++ channels open Ca++ enters  fusion of synaptic vesicles to PM  release of transmitters by exocytosis
    Postsynaptic cell:
    Binding of neurotransmitters to receptors  opening or closing of specific ligand sensitive -ion channels
    One way conduction across synapses in general
    Brief synaptic delay (0.2 sec) from action potential at presynaptic neuron to membrane potential changes in post synaptic cell
  • Functional anatomy of synapses
    Fate of unbound neurotransmitters
    Are actively transported back to the axon terminal/glial cells
    Diffuse away from the receptor site
    Enzymatically transformed into ineffective substances
    2 kinds of chemical synapse
    Excitatory
    Response is depolarization
    Open postsynaptic-membrane ion channels permeable to positvely charged ions
    Excitatatory postsynaptic potential (EPSP)
    Potential change wherien there is net movemnt of positively charge ions into the cell to slightly depolarize it
    Graded potential to bring the postsynaptic neuron closer to threshold
    Inhibitory
    Lessens likelihood for depolarization and action poterntial
    Opening of Cl- or sometimes K+ channels
    Inhibitory postsynaptic potential (IPSP)
    Hyperpolarizing graded potential
  • Activation of a postsynaptic cell
    In most neurons, one excitatory synaptic event by itself is not enough to cause threshold to be reached in the postsynaptic neuron
    Temporal summation:
    Axon stimulated before the 1st EPSP has died away
    The 2nd EPSP adds to the previous one and creates a greater input than from 1 input alone
    Input signals arrive at the same cell at different times
    The potentials summate because there is a greater number of open ion channels
    Spatial summation:
    2 inputs occured at different locations on the same cell
  • Activation of a postsynaptic cell
  • Synaptic effectiveness
    A presynaptic terminal does not release a constant amount of neurotransmitters everytime it is activated
    Presynaptic synapse (axon-axon synapse)
    Axon terminal of one ends on an axon terminal of another
    Effects:
    Presynaptic inhibition
    Decrease the amount of neurotransmitter secreted
    Presynaptic facilitation
    Increase the amount of neurotransmitter secreted
  • Modification of Synaptic transmission by Drugs and Disease
    All synaptic mechanisms are vulnerable to drugs
    Agonist:
    Drugs that bind to a receptor and produces a response similar to normal activation of a receptor
    Antagonis:
    Drugs that bind to the receptor but aren’t able to activate it
    Diseases:
    Tetanus toxin
    Protease that destroys certain proteins in the synaptic-vesicle docking mechanism of inhibitory neurons to neurons supplying the skeletal muscle
    Botulinum toxin and spider venom
    Affect neurotransmitter release from synaptic vesicles
    Interfere with docking proteins
    Act on axons different from those acted upon by tetanus toxin
  • Synaptic effectiveness
  • Neurotransmitters and Neuromodulators
    Neuromodulators
    Messengers that cause complex responses/modulation
    Alter effectiveness of synapse
    Modify postsynaptic cell’s response to neurotransmitters
    Change the presynaptic cell’s release, release, re-uptake, or metabolism of a transmitter
    Receptors for neuromodulators bring about changes in the metabolic processes in neurons via G-proteins
    Changes occur within minutes, hours, or days
    enzyme activity
    Protein synthesis
    Associated with slower events
    Learning
    Development
    Motivational states
    Sensory/motor activities
  • Neurotransmitters and neuromodulators
    Acetylcholine (ACh)
    Synthesized from choline and acetyl coenzyme A
    Reducing enzyme: acetylcholinesterase
    Mostly in the PNS, also in CNS
    Nerve fibers: cholinergic
    Receptors: nicotinic, muscarinic
    Function: attention, learning, memory
    Pathology: Alzheimers
    Biogenic amines
    Synthesized from AA and contain an amino group
    MC: dopamine, norepinphrine, serotonin, histamine
    Epinephrine: biogenic amine hormone secreted by adrenal medulla
    Norepinephrine: important neurotransmitter in CNS and PNS
  • Neurotransmitters and neuromodulators
    Catecholamines
    Dopamine, norepinephrine, epinephrine
    Contain a catechol ring and an amine group
    Synthesized from tyrosine
    Reducing enzyme: Monoamine oxidase
    Catecholamine releasing neurons mostly in brainstem and hypothalamus but axons go to all parts of the CNS
    Function: state of consciousness, mood, motivation, directed attention, movement, blood-pressure regulation, and hormone release
    Catecholamines
    Fibers: adrenergic, noradrenergic
    Receptors: Alpha, Beta
    Further divide in Alpha1, alpha2, Beta1 and Beta2 receptors
  • Neurotransmitters and neuromodulators
  • Neurotransmitters and neuromodulators
    Serotonin
    Biogenic amine synthesized from trytophan
    Effects have slow onset and innervate virtually every structure of the brain and spinal cord.
    Has 16 different receptor types
    Function:
    Motor: excitatory
    Sensation: inhibitory
    Lowest activity during sleep and highest during alert wakefulness
    Motor activity, sleep, food intake, reproductive behavior, mood and anxiety
    Present in non-neural cells (e.g. Platelets, GI tract, immune system)
    Amino Acid Neurotransmitters
    Amino acids that function as neurotransmitters
    Most prevalent neurotransmitter in the CNS and affect virtually all neurons there
    Excitatory Amino Acids
    Glutamate
    Aspartate
    Function: learning, memory, neural development
    Pathology: epilepsy, alzheimers, parkinsons disease,
    Neural damage after stroke, brain trauma
    Drugs: phencylidine (angel dust)
    Inhibitory Amino Acids
    GABA (gamma-aminobutyric acid)
    Glycine
    Drugs: valium
  • Neurotransmitters and neuromodulators
    Neuropeptides
    Composed of 2 or more AA linked together by peptide bonds
    Function as hormones or paracrine agents
    Synthesis: from large proteins produced by ribosomes
    Fibers: peptidergic
    Endogenous opioids
    B-endorphin, dynorphins, enkephalins
    Receptors are site of action of opiate drugs (morphine, codeine)
    Function: analgesia, “jogger’s high”, eating and drinking behavior, CVS regulation, mood and behavior
    Substance P
    Released by afferent neurons
    Relay sensory information into the CNS
    Nitric Oxide
    Diffuse into the intracellular fluid of nearby cells from cells of origin
    Messenger between neurons and effector cells
    Activate cGMP
    Function: learning, development, drug tolerance, penile erection, sensory and motor modulation
    ATP
    Very fast acting excitatory transmitter
    Adenine
  • Section D
    Structure of the nervous system
  • Structure of the nervous system
    Definition of terms
    Axon/nerve
    Long extension from a single neuron
    Nerve
    Group of many nerve fibers that are travelling together to the same general location in the PNS
    Pathway/tract
    A group of nerve fibers travelling together in the CNS
    Commisure
    Pathway/tract that links the right and left halves the CNS
    2 types of pathways in the CNS
    Long neural pathways
    Neurons with long axons carry information directly between the brain and the spinal cord or between large regions of the brain
    Little opportunity for alteration in the information transmitted
    Multineural/multisynaptic pathways
    Made up of many neurons and many synaptic connections
    Many opportunities for neural processing along the pathway
    Ganglia
    Group of neuron cell bodies in the PNS
    Nuclei
    Group of neuron cell bodies in the CNS
  • Structure of the nervous system
  • Spinal Cord
    Gray matter
    Composed of:
    interneurons
    cell bodies and dendrites of efferent neurons
    entering fibers of afferent neurons
    ganglia
    More cells than myelinated fibers
    Butterfly shaped and gray
    White matter
    Groups of myelinated axons of interneurons (fiber tracts / pathways)
    Dorsal root
    Where groups of afferent fibers from the PNS enter the SC
    Dorsal root ganglia
    Small bumps on the dorsal root
    Contain cell bodies of afferent neurons
    Ventral roots
    Where axons of the efferent nerves leave the SC
    Spinal nerves
    Where the dorsal and ventral root combine a short distance from the SC
    31 pairs, divided into 4 levels (cervical, thoracic, lumbar, sacral)
  • Spinal Cord
  • Brain
    4 subdivisions
    Cerebrum
    Diencephalon
    Brainstem
    Cerebellum
    Forebrain:
    Cerebrum
    Diencephalon
    Brainstem:
    Midbrain
    Pons
    Medulla oblongata
  • Brain
    Cerebral ventricles
    4 interconnected cavities
    Filled with cerebrospinal fluid
  • Brain
  • Brain
  • Brain
  • Peripheral nervous system
    Consists of 43 pairs of nerves
    Each nerve fiber is surrounded by a schwann cell that wrap some of the fibers with its membrane (myelin sheath)
  • Autonomic nervous system
    Efferent innervation of all tissues other than skeletal muscle
    Parallel chains, each with 2 neurons, connect the CNS and the effector cells
  • Autonomic nervous system
    Anatomy of sympathetic nervous system
    Preganglionic sympathetic fibers leave the spinal cord only between T1-L3
    Sympathetic trunks extend throughout the entire length of the spinal cord (cervical to sacral)
    Ganglia outside T1-L3 receive preganglionic fibers from the thoracolumbar region
    Preganglionic fibers travel up or down for several segments before forming synapses with postganglionic neurons
  • Autonomic nervous system
    Neurotransmitters
    Acetylcholine
    Major neurotransmitter released between pre- and postganglionic fibers in the autonomic ganglia
    Parasympathetic
    Acetylcholine: major neurotransmitter between postganglionic fibers and effector cells
    Sympathetic
    Norepinephrine: major neurotransmitter between postganglionic fibers and effector cells
  • Autonomic nervous system
  • Autonomic nervous system
    The heart, many glands, and smooth muscle cells have dual innervation (both sympathetic and parasympathetic)
    Usually the effect of sympathetic is the opposite of parasympathetic innervation in these tissues
    The activity of parasympathatetic and symphatetic is reciprocal with each other
    Fight-or-Flight response
    Full response of the sympatheitic nervous system
    Increase response during physical or psychological stress
    Animal is forced to challenge an attacker or run away from it
    Heart rate and BP increases
    Blood flow to skeletal muscles, heart, and brain increases
    Liver releases glucose
    Pupils dilate
    Blood flow to GIT and skin decreased
  • Autonomic nervous system
  • Blood supply, blood brain barrier phenomenon, cerebrospinal fluid
    meninges
    Protect and support the CNS
    Produce, circulate and absorb CSF
    3 layers
    Dura mater: next to the bone
    Arachnoid: in between
    Pia mater: next to nervous tissue
    Cerebrospinal fluid
    Fills the space between the arachnoid and the pia mater (subarachnoid)
    Hydrocephalus:
    flow of CSF is obstructed
    CSF accumulates
    Increase ventricular pressure compression of BV in brain  inadequate blood flow to neurons  neuronal damage and mental retardation
  • Blood supply, blood brain barrier phenomenon, cerebrospinal fluid
    Glucose
    In normal conditions, it is the only substrate metabolized by the brain to supply its energy requirements
    Stroke
    Neuronal death due to stoppage of blood supply to a region of a brain
    Blood supply
    2% of body weight
    Receives 12-15% of total blood supply
    High oxygen utilization
    Blood-brain barrier
    Complex group of mechanisms that closely control both the kinds of substances that enter the extracellular fluid of the brain and the rates in which they enter
    Minimizes harmful substance that enter but reduces access of immune system to the brain
    Made up of cells that line up the smallest blood vessels of the brain
    Lipid soluble substances enter the brain easily
    Non-lipid soluble substances uses membrane transport proteins
    Choroid plexus
    Cells in the area secrete CSF
    Responsible for decreased K+ and Ca++ and increased Na+ and Cl- in CSF compared to plasma
    Trap toxic heavy metals (e.g. lead)
  • The end