Physiology Review

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Physiology Review

• A work in Progress

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National Boards Part I

• Physiology section
• Neurophysiology (23)
• Membrane potentials, action potentials, synpatic
  transmission
• Motor function
• Sensory function
• Autonomic function
• Higher cortical function
• Special senses

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National Boards Part I

• Physiology (cont)
• Muscle physiology (14)
• Cardiac muscle
• Skeletal muscle
• Smooth muscle
• Cardiovascular physiology (17)
• Cardiac mechanisms
• Eletrophysiology of the heart
• Hemodynamics
• Regulation of circulation
• Circulation in organs
• Lymphatics
• Hematology and immunity

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National Boards Part I

• Physiology (cont)
• Respiratory physiology (10)
• Mechanics of breathing
• Ventilation, lung volumes and capacities
• Regulation of respiration
• O2 and CO2 transportation
• Gaseous Exchange
• Body Fluids and Renal physiology (11)
• Regulation of body fluids
• Glomerular filtration
• Tubular exchange
• Acid-base balance

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National Boards Part I

• Physiology (cont)
• Gastrointestinal physiology (10)
• Ingestion
• Digestion
• Absorption
• Regulation of GI function
• Reproductive physiology (4)
• Endocrinology (8)
• Secretion of hormones
• Action of hormones
• Regulation
• Exercise and Stress Physiology (3)

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Weapons in neurophysiologists armory

• Recording
• Individual neurons
• Gross potentials
• Brain scans
• Stimulation
• Lesions
• Natural lesions
• Experimental lesions

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Neurophysiology

• Membrane potential
• Electrical potential across the membrane
• Inside more negative than outside
• High concentration of Na outside cell
• High concentration of K inside cell
• PO4 SO4 Protein Anions trapped in the cell
  create negative internal enviiornment

8
Membrane physiology

• Passive ion movement across the cell membrane
• Concentration gradient
• High to low
• Electrical gradient
• Opposite charges attract, like repel
• Membrane permeability
• Action potential
• Pulselike change in membrane permeability to Na,
  K, (Ca)

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Membrane physiology

• In excitable tissue an action potential is a
  pulse like ? in membrane permeability
• In muscle permeability changes for
• Na
• ? at onset of depolarization, ? during
  repolarization
• Ca
• ? at onset of depolarization, ? during
  repolarization
• K
• ? at onset of depolarization, ? during
  repolarization

10
Passive ion movement across cell

• If ion channels are open, an ion will seek its
  Nerst equilibrium potential
• concentration gradient favoring ion movement in
  one direction is offset by electrical gradient

11
Resting membrane potential (Er)

• During the Er in cardiac muscle, fast Na and
  slow Ca/Na are closed, K channels are open.
• Therefore K ions are free to move, and when they
  reach their Nerst equilibrium potential, a stable
  Er is maintained

12
Na/K ATPase (pump)

• The Na/K pump which is energy dependent
  operates to pump Na out K into the cardiac
  cell at a ratio of 32
• therefore as pumping occurs, there is net loss of
  one charge from the interior each cycle,
  helping the interior of the cell remain negative
• the protein pump utilizes energy from ATP

13
Ca exchange protein

• In the cardiac cell membrane is a protein that
  exchanges Ca from the interior in return for
  Na that is allowed to enter the cell.
• The function of this exchange protein is tied to
  the Na/K pump
• if the Na/K pump is inhibited, function of this
  exchange protein is reduced more Ca is
  allowed to accumulate in the cardiac cell ?
  contractile strength.

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Action potential

• Pulselike change in membrane permeability to Na,
  K, (Ca)
• Controlled by gates
• Voltage dependent
• Ligand dependent
• Depolarization
• Increased membrane permeability to Na (Ca)
• Na influx
• Repolarization
• Increased membrane permeability to K
• K efflux

15
Refractory Period

• Absolute
• During the Action Potential (AP), cell is
  refractory to further stimulation (cannot be
  restimulated)
• Relative
• Toward the end of the AP or just after
  repolarization a stronger than normal stimulus
  (supranormal) is required to excite cell

16
All-or-None Principle

• Action potentials are an all or none phenomenon
• Stimulation above threshold may cause an
  increased number of action potentials but will
  not cause a greater action potential

17
Propagation

• Action potentials propagate (move along) as a
  result of local currents produced at the point of
  depolarization along the membrane compared to the
  adjacent area that is still polarized
• Current flow in biologic tissue is in the
  direction of positive ion movement or opposite
  the direction of negative ion movement

18
Conduction velocity

• Proportional to the diameter of the fiber
• Without myelin
• 1 micron diameter 1 meter/sec
• With myelin
• Accelerates rate of axonal transmission 6X and
  conserves energy by limiting depolarization to
  Nodes of Ranvier
• Saltatory conduction-AP jumps internode to
  internode
• 1micron diameter 6 meter/sec

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Synapes

• Specialized junctions for transmission of
  impulses from one nerve to another
• Electrical signal causes release of chemical
  substances (neurotransmitters) that diffuse
  across the synapse
• Slows neural transmission
• Amount of neurotransmitter (NT) release
  proportional to Ca influx

20
Neurotransmitters

• Acetylcholine
• Catacholamines
• Norepinephrine
• Epinephrine
• Serotonin
• Dopamine
• Glutamate
• Gamma-amino butyric acid (GABA)
• Certain amino acids
• Variety of peptides

21
Neurons

• May release more than one substance upon
  stimulation
• Neurotransmitter like norepinephrine
• Neuromodulator like neuropeptide Y (NPY)

22
Postsynaptic Cell Response

• Varies with the NT
• Excitatory NT causes a excitatory postsynaptic
  potential (EPSP)
• Increased membrane permeability to Na and/or
  Ca influx
• Inhibitory NT causes an inhibitory postsynaptic
  potential (IPSP)
• Increased membrane permeability to Cl- influx or
  K efflux
• Response of Postsynpatic Cell reflects
  integration of all input

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Response of Postsynaptic Cell

• Stimulation causing an AP
• ? EPSP gt ? IPSP gt threshold
• Stimulation leading to facilitation
• ? EPSP gt ? IPSP lt threshold
• Inhibition
• ? EPSP lt ? IPSP

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Somatic Sensory System

• Nerve fiber types (Type I, II, III, IV) based on
  fiber diameter (Type I largest, Type IV smallest)
• Ia - Annulospiral (1o) endings of muscle spindles
• Ib - From golgi tendon organs
• II
• Flower spray (2o) endings of muscle spindles
• High disrimination touch ( Meissners)
• Pressure
• III
• Nociception, temperature, some touch (crude)
• IV- nociception and temperature (unmyelinated)
  crude touch and pressure

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Transduction

• Stimulus is changed into electrical signal
• Different types of stimuli
• mechanical deformation
• chemical
• change in temperature
• electromagnetic

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Sensory systems

• All sensory systems mediate 4 attributes of a
  stimulus no matter what type of sensation
• modality
• location
• intensity
• timing

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Receptor Potential

• Membrane potential of the receptor
• A change in the receptor potential is associated
  with opening of ion (Na) channels
• Above threshold as the receptor potential becomes
  less negative the frequency of AP into the CNS
  increases

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Labeled Line Principle

• Different modalities of sensation depend on the
  termination point in the CNS
• type of sensation felt when a nerve fiber is
  stimulated (e.g. pain, touch, sight, sound) is
  determined by termination point in CNS
• labeled line principle refers to the specificity
  of nerve fibers transmitting only one modality of
  sensation
• Capable of change, e.g. visual cortex in blind
  people active when they are reading Braille

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Adaptation

• Slow-provide continuous information
  (tonic)-relatively non adapting-respond to
  sustained stimulus
• joint capsul
• muscle spindle
• Merkels discs
• punctate receptive fields
• Ruffini end organs (corpusles)
• activated by stretching the skin

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Adaptation

• Rapid (Fast) or phasic
• react strongly when a change is taking place
• respond to vibration
• hair receptors 30-40 Hz
• Pacinian corpuscles 250 Hz
• Meissners corpuscles- 30-40 Hz
• (Hz represents optimum stimulus rate)

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Sensory innervation of Spinal joints

• Tremendous amount of innervation with cervical
  joints the most heavily innervated
• Four types of sensory receptors
• Type I, II, III, IV

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Types of joint mechanoreceptors

• Type I- outer layer of capsule- low threshold,
  slowly adapts, dynamic, tonic effects on LMN
• Type II- deeper layer of capsule- low threshold,
  monitors joint movement, rapidly adapts, phasic
  effects on LMN
• Type III- high threshold, slowly adapts, joint
  version of GTO
• Type IV- nociceptors, very high threshold,
  inactive in normal joint, active with swelling,
  narrowing of joint.

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Stereognosis

• The ability to perceive form through touch
• tests the ability of dorsal column-medial
  lemniscal system to transmit sensations from the
  hand
• also tests ability of cognitive processes in the
  brain where integration occurs
• The ability to recognize objects placed in the
  hand on the basis of touch alone is one of the
  most important complex functions of the
  somatosensory system.

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Receptors in skin

• Most objects that we handle are larger than the
  receptive field of any receptor in the hand
• These objects stimulate a large population of
  sensory nerve fibers
• each of which scans a small portion of the object
• Deconstruction occurs at the periphery
• By analyzing which fibers have been stimulated
  the brain reconstructs the pattern

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Mechanoreceptors in the Skin

• Rapidly adapting cutaneous
• Meissners corpuscles in glabrous (non hairy)
  skin- (more superficial)
• signals edges
• Hair follicle receptors in hairy skin
• Pacinian corpuscles in subcutaneous tissue
  (deeper)

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Mechanoreceptors in the Skin

• Slowly adapting cutaneous
• Merkels discs have punctate receptive fields
  (superficial)
• senses curvature of an objects surface
• Ruffini end organs activated by stretching the
  skin (deep)
• even at some distance away from receptor

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Mechanoreceptors in Glabrous (non hairy) Skin
Superficial Deep
Small field Large field
Rapid adaptation
Meissners Corpuscle Pacinian Corpuscle
Merkels Disc Ruffini End Organ
Slow adaptation
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Somatic Sensory Cortex

• Receives projections from the thalamus
• Somatotopic organization (homunculus)
• Each central neuron has a receptive field
• size of cortical representation varies in
  different areas of skin
• based on density of receptors
• lateral inhibition improves two point
  discrimination

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Somatosensory Cortex

• Two major pathways
• Dorsal column-medial lemniscal system
• Most aspects of touch, proprioception
• Anterolateral system
• Sensations of pain (nociception) and temperature
• Sexual sensations, tickle and itch
• Crude touch and pressure
• Conduction velocity 1/3 ½ that of dorsal columns

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Somatosensory Cortex (SSC)

• Inputs to SSC are organized into columns by
  submodality
• cortical neurons defined by receptive field
  modality
• most nerve cells are responsive to only one
  modality e.g. superficial tactile, deep
  pressure, temperature, nociception
• some columns activated by rapidly adapting
  Messiners, others by slowly adapting Merkels,
  still others by Paccinian corp.

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Somatosensory cortex

• Brodman area 3, 1, 2 (dominate input)
• 3a-from muscle stretch receptors (spindles)
• 3b-from cutaneous receptors
• 2-from deep pressure receptors
• 1-rapidly adapting cutaneous receptors
• These 4 areas are extensively interconnected
  (serial parallel processing)
• Each of the 4 regions contains a complete map of
  the body surface homonculus

42
Somatosensory Cortex

• 3 different types of neurons in BM area 1,2 have
  complex feature detection capabilities
• Motion sensitive neurons
• respond well to movement in all directions but
  not selectively to movement in any one direction
• Direction-sensitive neurons
• respond much better to movement in one direction
  than in another
• Orientation-sensitive neurons
• respond best to movement along a specific axis

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Other Somatosensory Cortical Areas

• Posterior parietal cortex (BM 5 7)
• BM 5 integrates tactile information from
  mechanoreceptors in skin with proprioceptive
  inputs from underlying muscles joints
• BM 7 receives visual, tactile, proprioceptive
  inputs
• intergrates stereognostic and visual information
• Projects to motor areas of frontal lobe
• sensory initiation guidance of movement

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Secondary SSC (S-II)

• Secondary somatic sensory cortex (S-II)
• located in superior bank of the lateral fissure
• projections from S-1 are required for function of
  S-II
• projects to the insular cortex, which innervates
  regions of temporal lobe believed to be important
  in tactile memory

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Pain vs. Nociception

• Nociception-reception of signals in CNS evoked by
  stimulation of specialized sensory receptors
  (nociceptors) that provide information about
  tissue damage from external or internal sources
• Activated by mechanical, thermal, chemical
• Pain-perception of adversive or unpleasant
  sensation that originates from a specific region
  of the body
• Sensations of pain
• Pricking, burning, aching stinging soreness

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Nociceptors

• Least differentiated of all sensory receptors
• Can be sensitized by tissue damage
• hyperalgesia
• repeated heating
• axon reflex may cause spread of hyperalgesia in
  periphery
• sensitization of central nociceptor neurons as a
  result of sustained activation

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Sensitization of Nociceptors

• Potassium from damaged cells-activation
• Serotonin from platelets- activation
• Bradykinin from plasma kininogen-activate
• Histamine from mast cells-activation
• Prostaglandins leukotriens from arachidonic
  acid-damaged cells-sensitize
• Substance P from the 1o afferent-sensitize

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Nociceptive pathways

• Fast
• A delta fibers
• glutamate
• neospinothalamic
• mechanical, thermal
• good localization
• sharp, pricking
• terminate in VB complex of thalamus

• Slow
• C fibers
• substance P
• paleospinothalamic
• polymodal/chemical
• poor localization
• dull, burning, aching
• terminate RF
• tectal area of mesen.
• Periaqueductal gray

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Nociceptive pathways

• Spinothalamic-major
• neo- fast (A delta)
• paleo- slow (C fibers)
• Spinoreticular
• Spinomesencephalic
• Spinocervical (mostly tactile)
• Dorsal columns- (mostly tactile)

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Pain Control Mechanisms

• Peripheral
• Gating theory
• involves inhibitory interneruon in cord impacting
  nocicep. projection neurons
• inhibited by C fibers
• stimulated by A alpha beta fibers
• TENS

• Central
• Direct electrical to brain -gt analgesia
• Nociceptive control pathways descend to cord
• Endogenous opiods

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Muscle Receptors

• Muscle contain 2 types of sensory receptors
• muscle spindles respond to stretch
• located within belly of muscle in parallel with
  extrafusal fibers (spindles are intrafusal
  fibers)
• innervated by 2 types of myelinated afferent
  fibers
• group Ia (large diameter)
• group II (small diameter)
• innervated by gamma motor neurons that regulate
  the sensitivity of the spindle
• golgi tendon organs respond to tension
• located at junction of muscle tendon
• innervated by group Ib afferent fibers

52
Muscle Spindles

• Nuclear chain
• Most responsive to muscle shortening
• Nuclear bag-
• most responsive to muscle lengthening
• Dynamic vs static bag
• A typical mammalian muscle spindle contains one
  of each type of bag fiber a variable number of
  chain fibers (? 5)

53
Muscle Spindles

• sensory endings
• primary-usually 1/spindle include all branches
  of Ia afferent axon
• innervate all three types
• much more sensitive to rate of change of length
  than secondary endings
• secondary-usually 1/spindle from group II
  afferent
• innervate only on chain and static bag
• information about static length of muscle

54
Gamma Motor System

• Innervates intrafusal fibers
• Controlled by
• Reticular formation
• Mesencephalic area appears to regulate rhythmic
  gate
• Vestibular system
• Lateral vestibulospinal tract facilitates gamma
  motor neuron antigravity control
• Cutaneous sensory receptors
• Over skeletal muscle, sensory afferent
  activating gamma motor neurons

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Golgi tendon organ (GTO)

• Sensitive to changes in tension
• each tendon organ is innervated by single group
  Ib axon that branches intertwines among braided
  collagen fascicles.
• Stretching tendon organ straightens collagen
  bundles which compresses elongates nerve
  endings causing them to fire
• firing rate very sensitive to changes in tension
• greater response associated with contraction vs.
  stretch (collagen stiffer than muscle fiber)

56
CNS control of spindle sensitivity

• Gamma motor innervation to the spindle causes
  contraction of the ends of the spindle
• This allows the spindle to shorten function
  while the muscle is contracting
• Spindle operate over wide range of muscle length
• This is due to simultaneously activating both
  alpha gamma motor neurons during muscle
  contraction. (alpha-gamma coactivation)
• In slow voluntary movements Ia afferents often
  increase rate of discharge as muscle is shortening

57
CNS control of spindle sensitivity

• In movement the Ia afferents discharge rate is
  very sensitive to variartions in the rate of
  change of muscle length
• This information can be used by the nervous
  system to compensate for irregularities in the
  trajectory of a movement to detect fatigue of
  local groups of muscle fibers

58
Spindles and GTOs

• As a muscle contracts against a load
• Spindle activity tends to decrease
• GTO activity tends to increase
• As a muscle is stretched
• Spindle activity increases
• GTO activity will initially decrease

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Summary

• Spindles in conjunction with GTOs provide the
  CNS with continuous information about the
  mechanical state of a muscle
• For virtually all higher order perceptual
  processes, the brain must correlate sensory input
  with motor output to accurately assess the bodies
  interaction with its environment

60
Transmission of signals

• Spatial summation
• increasing signal strength transmitted by
  progressively greater of fibers
• receptor field
• of endings diminish as you move from center to
  periphery
• overlap between fibers
• Temporal summation
• increasing signal strength by ? frequency of IPS

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Neuronal Pools

• Input fibers
• divide hundreds to thousands of times to synapse
  with arborized dendrites
• stimulatory field
• Decreases as you move out from center
• Output fibers
• impacted by input fibers but not equally
• Excitation-supra-threshold stimulus
• Facilitation-sub-threshold stimulus
• Inhibition-release of inhibitory NT

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Neuronal Pools

• Divergence
• in the same tract
• into multiple tracts
• Convergence
• from a single source
• from multiple sources
• Neuronal circuit causing both excitation and
  inhibition (e.g. reciprocal inhibition)
• insertion of inhibitory neuron

63
Neuronal Pools

• Prolongation of Signals
• Synaptic Afterdischarge
• postsynaptic potential lasts for msec
• can continue to excite neuron
• Reverberatory circuit
• positive feedback within circuit due to
  collateral fibers which restimulate itself or
  neighboring neuron in the same circuit
• subject to facilitation or inhibition

64
Neuronal Pools

• Continuous signal output-self excitatory
• continuous intrinsic neuronal discharge
• less negative membrane potential
• leakly membrane to Na/Ca
• continuous reverberatory signals
• IPS increased with excitation
• IPS decreased with inhibition
• carrier wave type of information transmission
  excitation and inhibition are not the cause of
  the output, they modify output up or down
• ANS works in this fashion to control HR, vascular
  tone, gut motility, etc.

65
Rhythmical Signal Output

• Almost all result from reverberating circuits
• excitatory signals can increases amplitude
  frequency of rhythmic output
• inhibitory signals can decrease amplitude
  frequency of rhythmic output
• examples include the dorsal respiratory center in
  medulla and its effect on phrenic nerve activity
  to the diaphragm

66
Stability of Neuronal Circuits

• Almost every part of the brain connects with
  every other part directly or indirectly
• Problem of over-excitation (epileptic seizure)
• Problem controlled by
• inhibitory circuits
• fatigue of synapses
• decreasing resting membrane potential
• long-term changes by down regulation of receptors

67
Special Senses

• Vision
• Audition
• Chemical senses
• Taste
• Smell

68
Refraction

• Light rays are bent
• refractive index ratio of light in a vacuum to
  the velocity in that substance
• velocity of light in vacuum300,000 km/sec
• Light year 9.46 X 1012 km
• Refractive indices of various media
• air 1
• cornea 1.38
• aqueous humor 1.33
• lens 1.4
• vitrous humor 1.34

69
Refraction of light by the eye

• Refractive power of 59 D (cornea lens)
• Diopter 1 meter/ focal length
• central point 17 mm in front of retina
• inverted image- brain makes the flip
• lens strength can vary from 20- 34 D
• Parasympathetic increases lens strength
• Greater refractive power needed to read text

70
Errors of Refraction

• Emmetropia- normal vision ciliary muscle relaxed
  in distant vision
• Hyperopia-farsighted- focal pt behind retina
• globe short or lens weak convex lens to correct
• Myopia-nearsighted- focal pt in front of retina
• globe long or lens strong concave lens to
  correct
• Astigmatism- irregularly shaped
• cornea (more common)
• lens (less common)

71
Visual Acuity

• Snellen eye chart
• ratio of what that person can see compared to a
  person with normal vision
• 20/20 is normal
• 20/40 less visual acuity
• What the subject sees at 20 feet, the normal
  person could see at 40 feet.
• 20/10 better than normal visual acuity
• What the subject sees at 20 feet, the normal
  person could see at 10 feet

72
Visual acuity

• The fovea centralis is the area of greatest
  visual acuity
• it is less than .5 mm in diameter (lt 2 deg of
  visual field)
• outside fovea visual acuity decreases to more
  than 10 fold near periphery
• point sources of light two ? apart on retina can
  be distinguished as two separate points

73
Fovea and acute visual acuity

• Central fovea-area of greatest acuity
• composed almost entirely of long slender cones
• aids in detection of detail
• blood vessels, ganglionic cells, inner nuclear
  plexiform layers are displaced laterally
• allows light to pass relatively unimpeded to
  receptors

74
Depth Perception

• Relative size
• the closer the object, the larger it appears
• learned from previous experience
• Moving parallax
• As the head moves, objects closer move across the
  visual field at a greater rate
• Stereopsis- binocular vision
• eyes separated by 2 inches- slight difference in
  position of visual image on both retinas, closer
  objects are more laterally placed

75
Accomodation

• Increasing lens strength from 20 -34 D
• Parasympathetic causes contraction of ciliary
  muscle allowing relaxation of suspensory
  ligaments attached radially around lens, which
  becomes more convex, increasing refractive power
• Associated with close vision (e.g. reading)
• Presbyopia- loss of elasticity of lens w/ age
• decreases accomodation

76
Formation of Aqueous Humor

• Secreted by ciliary body (epithelium)
• 2-3 ul/min
• flows into anterior chamber and drained by Canal
  of Schlemm (vein)
• intraocular pressure- 12-20 mmHg.
• Glaucoma- increased intraocular P.
• compression of optic N.-can lead to blindness
• treatment drugs surgery

77
Photoreceptors

• Rods Cones
• Light breaks down rhodopsin (rods) and cone
  pigments (cones)
• ? rhodopsin ? ? Na conductance
• photoreceptors hyperpolarize
• release less NT (glutamate) when stimulated by
  light

78
Bipolar Cells

• Connect photoreceptors to either ganglionic cells
  or amacrine cells
• passive spread of summated postsynaptic
  potentials (No AP)
• Two types
• ON- hyperpolarized by NT glutamate
• OFF- depolarized by NT glutamate

79
Ganglionic Cells

• Can be of the ON or OFF variety
• ON bipolar ON ganglionic
• OFF bipolar OFF ganglionic
• Generate AP carried by optic nerve
• Three subtypes
• X (P) cells
• Y (M) cells
• W cells

80
X vs Y Ganglionic cells
Cell type X(P) Y(M)
Input Bipolar Amacrine
Receptive field Small Large
Conduction vel. Slow Fast
Response Slow adaptation Fast adaptation
Projects to Parvocellular of LGN Magnocellular of LGN
Function color vision BW movment
81
W Ganglionic Cells

• smallest, slowest CV
• many lack center-surround antagonistic fields
• they act as light intensity detectors
• some respond to large field motion
• they can be direction sensitive
• Broad receptive fields

82
Horozontal Cells

• Non spiking inhibitory interneurons
• Make complex synaptic connections with
  photorecetors bipolar cells
• Hyperpolarized when light stimulates input
  photoreceptors
• When they depolarize they inhibit photoreceptors
• Center-surround antagonism

83
Amacrine Cells

• Receive input from bipolar cells
• Project to ganglionic cells
• Several types releasing different NT
• GABA, dopamine
• Transform sustained ON or OFF to transient
  depolarization AP in ganglionic cells

84
Center-Surround Fields

• Receptive fields of bipolar gang. C.
• two concentric regions
• Center field
• mediated by all photoreceptors synapsing directly
  onto the bipolar cell
• Surround field
• mediated by photoreceptors which gain access to
  bipolar cells via horozontal c.
• If center is on, surround is off

85
Receptive field size

• In fovea- ratio can be as low as 1 cone to 1
  bipolar cell to 1 ganglionic cell
• In peripheral retina- hundreds of rods can supply
  a single bipolar cell many bipolar cells
  connected to 1 ganglionic cell

86
Dark Adaptation

• In sustained darkness reform light sensitive
  pigments (Rhodopsin Cone Pigments)
• ? of retinal sensitivity 10,000 fold
• cone adaptation-lt100 fold
• Adapt first within 10 minutes
• rod adaptation-gt100 fold
• Adapts slower but longer than cones (50 minutes)
• dilation of pupil
• neural adaptation

87
Cones

• 3 populations of cones with different
  pigments-each having a different peak absorption
  ?
• Blue sensitive (445 nm)
• Green sensitive (535 nm)
• Red sensitive (570 nm)

88
Visual Pathway

• Optic N to Optic Chiasm
• Optic Chiasm to Optic Tract
• Optic Tract to Lateral Geniculate
• Lateral Geniculate to 10 Visual Cortex
• geniculocalcarine radiation

89
Additional Visual Pathways

• From Optic Tracts to
• Suprachiasmatic Nucleus
• biologic clock function
• Pretectal Nuclei
• reflex movement of eyes-
• focus on objects of importance
• Superior Colliculus
• rapid directional movement of both eyes

90
Primary Visual Cortex

• Brodman area 17 (V1)-2x neuronal density
• Simple Cells-responds to bar of light/dark
• above below layer IV
• Complex Cells-motion dependent but same
  orientation sensitivity as simple cells
• Color blobs-rich in cytochrome oxidase in center
  of each occular dominace band
• starting point of cortical color processing
• Vertical Columns-input into layer IV
• Hypercolumn-functional unit, block through all
  cortical layers about 1mm2

91
Visual Association Cortex

• Visual analysis proceeds along many paths in
  parallel
• form
• color
• motion
• depth

92
Control of Pupillary Diameter

• Para causes ? size of pupil (miosis)
• Symp causes ? size of pupil (mydriasis)
• Pupillary light reflex
• optic nerve to pretectal nuclei to
  Edinger-Westphal to ciliary ganglion to pupillary
  sphincter to cause constriction (Para)

93
Function of extraoccular muscles

• Medial rectus of one eye works with the lateral
  rectus of the other eye as a yoked pair to
  produce lateral eye movements
• Medial rectus adducts the eye
• Lateral rectus abducts the eye

94
Raising/lowering/torsioning
Elevate Depress Torsion
Abducted Adducted Eye Eye
Superior rectus Inferior oblique
Inferior rectus Superior oblique
Superior oblique Inferior oblique Superior rectus Inferior rectus
95
Innervation of extraoccular muscles

• Extraoccular muscles controlled by CN III, IV,
  and VI
• CN VI controls the lateral rectus only
• CN IV controls the superior oblique only
• CN III controls the rest

96
Sound

• Units of Sound is the decibel (dB)
• I (measured sound)
• Decibel 1/10 log --------------------------
  
• I (standard
  sound)
• Reference Pressure for standard sound
• .02 X 10-2 dynes/cm2

97
Sound

• Energy is proportional to the square of pressure
• A 10 fold increase in sound energy 1 bel
• One dB represents an actual increase in sound E
  of about 1.26 X
• Ears can barely detect a change of 1 dB

98
Different Levels of Sound

• 20 dB- whisper
• 60 dB- normal conversation
• 100 dB- symphony
• 130 dB- threshold of discomfort
• 160 dB- threshold of pain

99
Frequencies of Audible Sound

• In a young adult
• 20-20,000 Hz (decreases with age)
• Greatest acuity
• 1000-4000 Hz

100
Tympanic Membrane Ossicles

• Impedance matching-between sound waves in air
  sound vibrations generated in the cochlear fluid
• 50-75 perfect for sound freq.300-3000 Hz
• Ossicular system
• reduces amplitude by 1/4
• increases pressure against oval window 22X
• increased force (1.3)
• decreased area from TM to oval window (17)

101
Ossicular system (cont.)

• Non functional ossicles or ossicles absent
• decrease in loudness about 15-20 dB
• medium voice now sounds like a whisper
• attenuation of sound by contraction of
• Stapedius muscle-pulls stapes outward
• Tensor tympani-pull malleous inward

102
Attenuation of sound

• CNS reflex causes contraction of stapedius and
  tensor tympani muscles
• activated by loud sound and also by speech
• latency of about 40-80 msec
• creation of rigid ossicular system which reduces
  ossicular conduction
• most effective at frequencies of lt 1000 Hz.
• Protects cochlea from very loud noises, masks low
  freq sounds in loud environment

103
Cochlea

• System of 3 coiled tubes
• Scala vestibuli
• Scala media
• Scala tympani

104
Scala Vestibuli

• Seperated from the scala media by Reissners
  membrane
• Associated with the oval window
• filled with perilymph (similar to CSF)

105
Scala Media

• Separated from scala tympani by basilar membrane
• Filled with endolymph secreted by stria
  vascularis which actively transports K
• Top of hair cells bathed by endolymph

106
Endocochlear potential

• Scala media filled with endolymph (K)
• baths the tops of hair cells
• Scala tympani filled with perilymph (CSF)
• baths the bottoms of hair cells
• electrical potential of 80 mv exists between
  endolymph and perilymph due to active transport
  of K into endolymph
• sensitizes hair cells
• inside of hair cells (-70 mv vs -150 mv)

107
Scala Tympani

• Associated with the round window
• Filled with perilymph
• baths lower bodies of hair cells

108
Function of Cochlea

• Change mechanical vibrations in fluid into action
  potentials in the VIII CN
• Sound vibrations created in the fluid cause
  movement of the basilar membrane
• Increased displacement
• increased neuronal firing resulting an increase
  in sound intensity
• some hair cells only activated at high intensity

109
Place Principle

• Different sound frequencies displace different
  areas of the basilar membrane
• natural resonant frequency
• hair cells near oval window (base)
• short and thick
• respond best to higher frequencies (gt4500Hz)
• hair cells near helicotrema (apex)
• long and slender
• respond best to lower frequencies (lt200 Hz)

110
Central Auditory Pathway

• Organ of Corti to ventral dorsal cochlear
  nuclei in upper medulla
• Cochlear N to superior olivary N (most fibers
  pass contralateral, some stay ipsilateral)
• Superior olivary N to N of lateral lemniscus to
  inferior colliculus via lateral lemniscus
• Inferior colliculus to medial geniculate N
• Medial geniculate to primary auditory cortex

111
Primary Auditory Cortex

• Located in superior gyrus of temporal lobe
• tonotopic organization
• high frequency sounds
• posterior
• low frequency sounds
• anterior

112
Air vs. Bone conduction

• Air conduction pathway involves external ear
  canal, middle ear, and inner ear
• Bone conduction pathway involves direct
  stimulation of cochlea via vibration of the skull
  (cochlea is imbedded in temporal bone)
• reduced hearing may involve
• ossicles (air conduction loss)
• cochlea or associated neural pathway (sensory
  neural loss)

113
Sound Localization

• Horizontal direction from which sound originates
  from determined by two principal mechanisms
• Time lag between ears
• functions best at frequencies lt 3000 Hz.
• Involves medial superior olivary nucleus
• neurons that are time lag specific
• Difference in intensities of sounds in both ears
• involves lateral superior olivary nucleus

114
Exteroceptive chemosenses

• Taste
• Works together with smell
• Categories (Primary tastes)
• sweet
• salt
• sour
• bitter (lowest threshold-protective mechanism)
• Olfaction (Smell)
• Primary odors (100-1000)

115
Taste receptors

• May have preference for stimuli
• influenced by past history
• recent past
• adaptation
• long standing
• memory
• conditioning-association

116
Primary sensations of taste

• Sour taste-
• caused by acids (hydrogen ion concentration)
• Salty taste-
• caused by ionized salts (primarily the Na)
• Sweet taste-
• most are organic chemicals (e.g. sugars, esters
  glycols, alcohols, aldehydes, ketones, amides,
  amino acids) inorganic salts of Pb Be
• Bitter- no one class of compounds but
• long chain organic compounds with N
• alkaloids (quinine,strychnine,caffeine, nicotine)

117
Taste

• Taste sensations are generated by
• complex transactions among chemical and receptors
  in taste buds
• subsequent activities occuring along the taste
  pathways
• There is much sensory processing, centrifugal
  control, convergence, global integration among
  related systems contributing to gustatory
  experiences

118
Taste Buds

• Taste neuroepithelium - taste buds in tongue,
  pharynx, larynx.
• Aggregated in relation to 3 kinds of papillae
• fungiform-blunt pegs 1-5 buds /top
• foliate-submerged pegs in serous fluid with
  1000s of taste buds on side
• circumvallate-stout central stalks in serous
  filled moats with taste buds on sides in fluid
• 40-50 modified epithelial cells grouped in barrel
  shaped aggregate beneath a small pore which opens
  onto epithelial surface

119
Innervation of Taste Buds

• each taste nerve arborizes innervates several
  buds (convergence in 1st order)
• receptor cells activate nerve endings which
  synapse to base of receptor cell
• Individual cells in each bud differentiate,
  function degenerate on a weekly basis
• taste nerves
• continually remodel synapses on newly generated
  receptor cells
• provides trophic influences essential for
  regeneration of receptors buds

120
Adaptation of taste

• Rapid-within minutes
• taste buds account for about 1/2 of adaptation
• the rest of adaptation occurs higher in CNS

121
CNS pathway-taste

• Anterior 2/3 of tongue
• lingual N. to chorda tympani to facial (VII CN)
• Posterior 1/3 of tongue
• IX CN (Petrosal ganglion)
• base of tongue and palate
• X CN
• All of the above terminate in nucleus tractus
  solitarius (NTS)

122
CNS pathway (taste cont)

• From the NTS to VPM of thalamus via central
  tegmental tract (ipsilateral) which is just
  behind the medial lemniscus.
• From the thalmus to lower tip of the post-central
  gyrus in parietal cortex adajacent opercular
  insular area in sylvian fissure

123
Olfactory Membrane

• Superior part of nostril
• Olfactory cells
• bipolar nerve cells
• 100 million in olfactory epithelium
• 6-12 olfactory hairs/cell project in mucus
• react to odors and stimulate cells

124
Cells in Olfactory Membrane

• Olfactory cells-
• bipolar nerve cells which project hairs in mucus
  in nasal cavity
• stimulated by odorants
• connect to olfactory bulb via cribiform plate
• Cells which make up Bowmans glands
• secrete mucus
• Sustentacular cells
• supporting cells

125
Characteristics of Odorants

• Volatile
• slightly water soluble-
• for mucus
• slightly lipid soluble
• for membrane of cilia
• Threshold for smells
• Very low

126
Primary sensations of smell

• Anywhere from 100 to 1000 based on different
  receptor proteins
• odor blindness has been described for at least 50
  different substances
• may involve lack of a specific receptor protein

127
Receptor

• Resting membrane potential when not activated
  -55 mv
• 1 impulse/ 20 sec to 2-3 impulses/ sec
• When activated membrane pot. -30 mv
• 20 impulses/ sec

128
Glomerulus in Olfactory Bulb

• several thousand/bulb
• Connections between olfactory cells and cells of
  the olfactory tract
• receive axons from olfactory cells (25,000)
• receive dendrites from
• large mitral cells (25)
• smaller tufted cells (60)

129
Cells in Olfactory bulb

• Mitral Cells- (continually active)
• send axons into CNS via olfactory tract
• Tufted Cells- (continually active)
• send axons into CNS via olfactory tract
• Granule Cells
• inhibitory cell which can decrease neural traffic
  in olfactory tracts
• receive input from centrifugal nerve fibers

130
CNS pathways

• Very old- medial olfactory area
• feeds into hypothalamus primitive areas of
  limbic system (from medial pathway)
• basic olfactory reflexes
• Less old- lateral olfactory area
• prepyriform pyriform cortex -only sensory
  pathway to cortex that doesnt relay via thalamus
  (from lateral pathway)
• learned control/adversion
• Newer- passes through the thalamus to
  orbitofrontal cortex (from lateral pathway)
• - conscious analysis of odor

131
Medial and Lateral pathways

• 2nd order neurons form the olfactory tract
  project to the following 1o olfactory
  paleocortical areas
• Anterior olfactory nucleus
• Modulates information processing in olfactory
  bulbs
• Amygdala and olfactory tubercle
• Important in emotional, endocrine, and visceral
  responses of odors
• Pyriform and periamygdaloid cortex
• Olfactory perception
• Rostral entorhinal cortex
• Olfactory memories

132
Homeostasis

• Concept whereby body states are regulated toward
  a steady state
• Proposed by Walter Cannon in 1932
• At the same time Cannon introduced negative
  feedback regulation
• an important part of this feedback regulation is
  mediated by the ANS through the hypothalamus

133
Autonomic Nervous System

• Controls visceral functions
• functions to maintain a dynamic internal
  environment, necessary for proper function of
  cells, tissues, organs, under a wide variety of
  conditions demands

134
Autonomic Nervous System

• Visceral largely involuntary motor system
• Three major divisions
• Sympathetic
• Fight flight fright
• emergency situations where there is a sudden ? in
  internal or external environment
• Parasympathetic
• Rest and Digest
• Enteric
• neuronal network in the walls of GI tract

135
ANS

• Primarily an effector system
• Controls
• smooth muscle
• heart muscle
• exocrine glands
• Two neuron system
• Preganglionic fiber
• cell body in CNS
• Postganglionic fiber
• cell body outside CNS

136
Sympathetic Nervous System

• Pre-ganglionic cells
• intermediolateral horn cells
• C8 to L2 or L3
• release primarily acetylcholine
• also releases some neuropeptides (eg. LHRH)
• Post-ganglionic cells
• Paravertebral or Prevertebral ganglia
• most fibers release norepinephrine
• also can release neuropeptides (eg. NPY)

137
Mass SNS discharge

• Increase in arterial pressure
• decreased blood flow to inactive organs/tissues
• increase rate of cellular metabolism
• increased blood glucose metabolism
• increased glycolysis in liver muscle
• increased muscle strength
• increased mental activity
• increased rate of blood coagulation

138
Normal Sympathetic Tone

• 1/2 to 2 Impulses/Sec
• Creates enough constriction in blood vessels to
  limit flow
• Most SNS terminals release norepinephrine
• release of norepinephrine depends on functional
  terminals which depend on nerve growth factor

139
Parasympathetic Nervous System

• Preganglionic neurons
• located in several cranial nerve nuclei in
  brainstem
• Edinger-Westphal nucleus (III)
• superior salivatory nucleus (VII)
• inferior salivatory nucleus (IX)
• dorsal motor (X) (secretomotor)
• nucleus ambiguus (X) (visceromotor)
• intermediolateral regions of S2,3,4
• release acetylcholine

140
Parasympathetic Nervous System

• Postganglionic cells
• cranial ganglia
• ciliary ganglion
• pterygopalatine
• submandibular ganglia
• otic ganglia
• other ganglia located near or in the walls of
  visceral organs in thoracic, abdominal, pelvic
  cavities
• release acetylcholine

141
Parasympathetic nervous system

• The vagus nerves innervate the heart, lungs,
  bronchi, liver, pancreas, all the GI tract from
  the esophagus to the splenic flexure of the colon
• The remainder of the colon rectum, urinary
  bladder, reproductive organs are innervated by
  sacral preganglionic nerves via pelvic nerves to
  postganglionic neurons in pelvic ganglia

142
Enteric Nervous System

• Located in wall of GI tract (100 million neurons)
• Activity modulated by ANS

143
Enteric Nervous system

• Preganglionic Parasympathetic project to enteric
  ganglia of stomach, colon, rectum via vagus
  pelvic splanchnic nerves
• increase motility and tone
• relax sphincters
• stimulate secretion

144
Enteric Nervous System

• Myenteric Plexus (Auerbachs)
• between longitudenal circular muscle layer
• controls gut motility
• can coordinate peristalsis in intestinal tract
  that has been removed from the body
• excitatory motor neurons release Ach sub P
• inhibitory motor neurons release Dynorphin
  vasoactive intestinal peptide

145
Enteric Nervous System

• Submucosal Plexus
• Regulates
• ion water transport across the intestinal
  epithelium
• glandular secretion
• communicates with myenteric plexus
• releases neuropeptides
• well organized neural networks

146
Visceral afferent fibers

• Accompany visceral motor fibers in autonomic
  nerves
• supply information that originates in sensory
  receptors in viscera
• never reach level of consciousness
• responsible for afferent limb of viscerovisceral
  and viscerosomatic reflexes
• important for homeostatic control and adjustment
  to external stimuli

147
Visceral afferents

• Many of these neurons may release an excitatory
  neurotransmitter such as glutamate
• Contain many neuropeptides
• can include nociceptors visceral pain
• distension of hollow viscus

148
Neuropeptides (visceral afferent)

• Angiotension II
• Arginine-vasopressin
• bombesin
• calcitonin gene-related peptide
• cholecystokinin
• galamin
• substance P
• enkephalin
• somatostatin
• vasoactive intestinal peptide

149
Autonomic Reflexes

• Cardiovascular
• baroreceptor
• Bainbridge reflex
• GI autonomic reflexes
• smell of food elicits parasympathetic release of
  digestive juices from secretory cells of GI tract
• fecal matter in rectum elicits strong peristaltic
  contractions to empty the bowel

150
Intracellular Effects

• SNS-postganglionic fibers
• Norepinephrine binds to a alpha or beta receptor
  which effects a G protein
• Gs proteins adenyl cyclase which raises cAMP
  which in turn protein kinase activity which
  increases membrane permeability to Na Ca
• Parasympathetic-postganglionic fibers
• Acetylcholine binds to a muscarinic receptor
  which also effects a G protein
• Gi proteins - adenyl cyclase and has the opposite
  effect of Gs

151
Effects of Stimulation

• EyeS dilates pupils P- constricts
  pupil, contracts ciliary
  muscle increases lens strength
• Glandsin general stimulated by P but S will
  concentrate secretion by decreasing blood flow.
  Sweat glands are exclusively innervated by
  cholinergic S
• GI tractS -, P (mediated by enteric)
• Heart S , P -
• Bld vesselsS constriction, P largely absent

152
Effects of Stimulation

• Airway smooth muscle S dilation P constriction
• Ducts S dilation P constriction
• Immune System S inhibits, P ??

153
Fate of released NT

• Acetylcholine (P) rapidly hydrolysed by
  aetylcholinesterase
• Norepinephrine
• uptake by the nerve terminals
• degraded by MAO, COMT
• carried away by blood

154
Precursors for NT

• Tyrosine is the precursor for Dopamine,
  Norepinephrine Epinephrine
• Choline is the precursor for Acetylcholine

155
Receptors

• Adrenergic
• Alpha
• Beta
• Acetylcholine receptors
• Nicotinic
• found at synapes between pre post ganglionic
  fibers (both S P)
• Muscarinic
• found at effector organs

156
Receptors

• Receptor populations are dynamic
• Up-regulate
• increased of receptors
• Increased sensitivity to neurotransmitter
• Down-regulate
• decreased of receptors
• Decreased sensitivity to neurotransmitter
• Denervation supersensitivity
• Cut nerves and increased of receptors causing
  increased sensitivity to the same amount of NT