1. Physiology Review
A work in Progress

2. 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

3. 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

4. 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

5. 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%)

6. Weapons in neurophysiologist’s
armory
• Recording
– Individual neurons
– Gross potentials
– Brain scans
• Stimulation
• Lesions
– Natural lesions
– Experimental lesions

7. 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++)

9. Membrane physiology
• In excitable tissue an action potential is a
pulse like D in membrane permeability
• In muscle permeability changes for:
– Na+
"Ý at onset of depolarization, ß during repolarization
– Ca++
"Ý at onset of depolarization, ß during repolarization
– K+
"ß at onset of depolarization, Ý 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 3:2
– 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 Ý contractile strength.

14. 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

19. 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

23. Response of Postsynaptic Cell
• Stimulation causing an AP
S EPSP S IPSP threshold
• Stimulation leading to facilitation
S EPSP S IPSP threshold
• Inhibition
S EPSP S IPSP

24. 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 ( Meissner’s)
• Pressure
– III
• Nociception, temperature, some touch (crude)
– IV- nociception and temperature (unmyelinated) crude
touch and pressure

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

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

27. 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

28. 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

29. Adaptation
• Slow-provide continuous information
(tonic)-relatively non adapting-respond to
sustained stimulus
– joint capsul
– muscle spindle
– Merkel’s discs
• punctate receptive fields
– Ruffini end organ’s (corpusles)
• activated by stretching the skin

30. 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
– Meissner’s corpuscles- 30-40 Hz
– (Hz represents optimum stimulus rate)

31. 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

32. 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.

33. 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.

34. 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

35. Mechanoreceptors in the Skin
• Rapidly adapting cutaneous
– Meissner’s corpuscles in glabrous (non hairy)
skin- (more superficial)
• signals edges
– Hair follicle receptors in hairy skin
– Pacinian corpuscles in subcutaneous tissue
(deeper)

36. Mechanoreceptors in the Skin
• Slowly adapting cutaneous
– Merkel’s discs have punctate receptive fields
(superficial)
• senses curvature of an object’s surface
– Ruffini end organs activated by stretching the
skin (deep)
• even at some distance away from receptor

37. Mechanoreceptors in Glabrous
(non hairy) Skin
Rapid
adaptation
Superficial Deep
Small field Large field
Slow
adaptation
Meissner’s
Corpuscle
Pacinian
Corpuscle
Merkel’s
Disc
Ruffini
End Organ

38. 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

39. 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

40. 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
Messiner’s, others by slowly adapting Merkel’s,
still others by Paccinian corp.

41. 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

43. 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

44. 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

45. 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

46. 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

47. 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

48. 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

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

50. 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 - analgesia
• Nociceptive control
pathways descend to
cord
• Endogenous opiods

51. 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

55. 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 afferent’s 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 GTO’s
• 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

59. Summary
• Spindles in conjunction with GTO’s
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 Ý frequency of
IPS

61. 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

62. 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 vacuum=300,000 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 ( 2 deg of
visual field)
– outside fovea visual acuity decreases to
more than 10 fold near periphery
• point sources of light two m 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 Þ ¯ 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)
Ý of retinal sensitivity 10,000 fold
• cone adaptation-100 fold
– Adapt first within 10 minutes
• rod adaptation-100 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 l
• 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 ß size of pupil (miosis)
• Symp + causes Ý 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 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
Reissner’s 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 (4500Hz)
• hair cells near helicotrema (apex)
– long and slender
• respond best to lower frequencies (200 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 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
1000’s 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 Bowman’s 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 doesn’t 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 D 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 (Auerbach’s)
– 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
• Eye:S dilates pupils
P- constricts pupil, contracts ciliary
muscle increases lens
strength
• Glands:in general stimulated by P but S + will
concentrate secretion by decreasing blood
flow. Sweat glands are exclusively
innervated by cholinergic S
• GI tract:S -, P + (mediated by enteric)
• Heart: S +, P -
• Bld vessels:S 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

157. Higher control of ANS
• Many neuronal areas in the brain stem
reticular substance and along the
course of the tractus solitarius of the
medulla, pons, mesencephalon as
well as in many special nuclei
(hypothalamus) control different
autonomic functions.
• ANS activated, regulated by centers in:
– spinal cord, brain stem, hypothalamus,
higher centers (e.g. limbic system
cerebral cortex)

158. Neural immunoregulation
• Nerve fibers project into every organ
– involved in monitoring both internal
external environment
– controls output of endocrine exocrine
glands
– essential components of homeostatic
mechanisms to maintain viability of organism
– local monitoring modulation of host
defense CNS coordinates host defense
activity

159. Central Autonomic Regulation
• Major relay cell groups in brain regulate
afferent efferent information
• convergence of autonomic information
onto discrete brain nuclei
• autonomic function is modulated by D’s
in preganglionic SNS or Para tone
and/or D’s in neuroendocrine (NE)
effectors

160. Central Autonomic Regulation
• different components of central autonomic
regulation are reciprocally innervated
• parallel pathways carry autonomic info to
other structures
• multiple chemical substances mediate
transduction of neuronal infomation

161. Important Central Autonomic
Areas • Nucleus Tractus Solitarius
• Parabrachial Nucleus
• Locus Coeruleus
• Amygdala
• Cerebral Cortex
• Hypothalamus
• Circumventricular Organs (fenestrated
caps)

162. Control of Complex Movements
• Involve
– Cerebral Cortex
– Basal Ganglia
– Cerebellum
– Thalamus
– Brain Stem
– Spinal Cord

163. Motor Cortex
• Primary motor cortex
– somatotopic arrangement
– greater than 1/2 controls hands speech
– + of neuron stimulate movements instead
of contracting a single muscle
• Premotor area
– anterior to lateral portions of primary motor
cortex below supplemental area
– projects to 10 motor cortex and basal
ganglia

164. Motor Cortex (cont.)
• Supplemental motor area
– superior to premotor area lying mainly in the
longitudnal fissure
– functions in concert with premotor area to
provide:
• attitudinal movements
• fixation movements
• positional movements of head eyes
• background for finer motor control of arms/hands

165. The reticular nuclei
• Pontine reticular nuclei
– transmit excitatory signals via the pontine
(medial) reticulospinal tract
– stimulate the axial trunk extensor muscles
that support the body against gravity
– receive stimulation from vestibular nuclei
deep nuclei of the cerebellum
– high degree of natural excitability

166. The Reticular Nuclei (cont.)
• Medullary reticular nuclei
– transmit inhibitory signals to the same
antigravity muscles via the medullary
(lateral) reticulospinal tract
– receive strong input from the cortex, red
nucleus, and other motor pathways
– counterbalance excitatory signals from the
pontine reticular nuclei
– allows tone to be increased or decreased
depending on function needing to be
performed

167. Role of brain stem in controlling
motor function
• Control of respiration
• Control of cardiovascular system
• Control of GI function
• Control of many stereotyped movements
• Control of equilibrium
• Control of eye movement

168. Primary Motor Cortex
• Vertical Columnar Arrangement
– functions as an integrative processing system
• + 50-100 pyramidal cells to achieve muscle
contraction
– Pyramidal cells (two types of output signals)
• dynamic signal
– excessively excited at the onset of contraction to initiate
muscle contraction
• static signal
– fire at slower rate to maintain contraction

169. Initiation of voluntary movement
• Plan and Program
– Begins in somatosensory association areas
• Execution
– Motor cortex outputs
• To the cord - skeletal muscle
• To the spinocerebellum
– Feedback from the periphery
• To the spinocerebellum

170. Postural Reflexes
• Impossible to separate postural adjustments
from voluntary movement
• maintain body in up-right balanced position
• provide constant adjustments necessary to
maintain stable postural background for
voluntary movement
• adjustments include static reflexes
(sustained contraction) dynamic short term
phasic reflexes (transient movements)

171. Postural Control (cont)
• A major factor is variation of in threshold
of spinal stretch reflexes
• caused by changes in excitability of motor
neurons changes in rate of discharge in
the gamma efferent neurons to muscle
spindles

172. Postural Reflexes
• Three types of postural reflexes
– vestibular reflexes
– tonic neck reflexes
– righting reflexes

173. Vestibular function
• Vestibular apparatus-organ that detects
sensations of equilibrium
• Consists of semicircular canals utricle
saccule
• embedded in the petrous portion of
temporal bone
• provides information about position and
movement of head in space
• helps maintain body balance and helps
coordinate movements

174. Vestibular apparatus
• Utricle and Saccule
– Macula is the sensory area
• covered with a gelatinous layer in which many
small calcium carbonate crystals are imbedded
• hair cells in macula project cilia into gelatinous
layer
• directional sensitivity of hair cells to cause
depolarization or hyperpolarization
• detect orientation of head w/ respect to gravity
• detect linear acceleration

175. Vestibular apparatus (cont)
• Semicircular canals
– Crista ampularis in swelling (ampulla)
• Cupula
– loose gelatinous tissue mass on top of crista
• stimulated as head begins to rotate
• 3 pairs of canals bilaterally at 90o to one
another. (anterior, horizontal, posterior)
– Each set lie in the same plane
• right anterior - left posterior
• right and left horizontal
• left anterior - right posterior

176. Semicircular Canals
• Filled with endolymph
• As head begins to rotate, fluid lags behind
and bend cupula
• generates a receptor potential which alters
the firing rate in VIII CN which projects to
the vestibular nuclei
• detects rotational acceleration
deceleration

177. Semicircular Canals
• Stimulation of semicircular canals on side
rotation is into. (e.g. Right or clockwise
rotation will stimulate right canal)
• Stimulation of semicircular canals is
associated with increased extensor tone
• Stimulation of semicircular canals is
associated with nystagmus

178. Semicircular Canals
• Connections with vestibular nucleus via
CN VIII
• Vestibular nuclei makes connections
with CN associated with occular
movements (III,IV, VI) and cerebellum
• Can stimulate nystagmus
– slow component-(tracking)can be initiated
by semicircular canals
– fast component- (jump ahead to new focal
spot) initiated by brain stem nuclei

179. Semicircular Canals
• Thought to have a predictive function to
prevent malequilibrium
• Anticipitory corrections
• works in close concert with cerebellum
especially the flocculonodular lobe

180. Other Factors - Equilibrium
• Neck proprioceptors-provides
information about the orientation of the
head with the rest of the body
– projects to vestibular apparatus
cerebellum
– cervical joints proprioceptors can override
signals from the vestibular apparatus
prevent a feeling of malequilibrium
• Proprioceptive and Exteroceptive
information from other parts of the body
• Visual signals

181. Posture
• Represents overall position of the body
limbs relative to one another their
orientation in space
• Postural adjustments are necessary for all
motor tasks need to be integrated with
voluntary movement

182. Vestibular Neck Reflexes
• Have opposing actions on limb muscles
• Most pronounced when the spinal circuits
are released from cortical inhibition
• Vestibular reflexes evoked by changes in
position of the head
• Neck reflexes are triggered by tilting or
turning the neck

183. Postural Adjustments
• Functions
– support head body against gravity
– maintain center of the body’s mass aligned
balanced over base of support on the ground
– stabilize supporting parts of the body while
others are being moved
• Major mechanisms
– anticipatory (feed forward)-predict disturbances
• modified by experience; improves with practice
– compensatory (feedback)
• evoked by sensory events following loss of balance

184. Postural adjustments
• Induced by body sway
• Extremely rapid (like simple stretch reflex)
• Relatively stereotyped spatiotemporal
organization (like ssr)
• appropriately scaled to achieve goal of
stable posture (unlike ssr)
• refined continuously by practice (like
skilled voluntary movements)

185. Postural mechanisms
• Sensory input from:
– cutaneous receptors from the skin (esp
feet)
– proprioceptors from joints muscles
• short latency (70-100 ms)
– vestibular signals (head motion)
• longer latency (2x proprioceptor latency)
– visual signals
• longer latency (2x proprioceptor latency)

186. Postural Mechanisms (cont)
• In sway, contraction of muscles to maintain
balance occur in distal to proximal
sequence
– forward sway
• Gastrohampara
– backward sway
• Tibquadabd
• responses that stabilize posture are
facilitated
• responses that destabilize posture inhibited

187. Effect of tonic neck reflexes on
limb muscles
• Extension of neck + extensors of
arms/legs
• Flexion of neck + flexors of arms/legs
• Rotation or lateral bending
– + extensors ipsilateral
– + flexors contralateral

188. Basal Ganglia
• Input nuclei
– Caudate
– Putamen
• caudate + putamen = striatum
– Nucleus accumbens
• Output nuclei
– Globus Pallidus-external segment
– Subthalamic nucleus
– Substantia nigra
– Ventral tegmental area

189. Basal Ganglia
• Consist of 4 principal nuclei
– the striatum (caudate putamen)
– the globus pallidus (internal external)
– the substantia nigra
– subthalamic nucleus

190. Basal Ganglia
• Do not have direct input or output
connections with the spinal cord
• Motor functions of the basal ganglia are
mediated by the motor areas of the
cortex
• Disorders have three characteristic
types of motor disturbances
– tremor other involuntary movements
– changes in posture muscle tone
– poverty slowness of movement

191. Two major circuits of BG
• Caudate circuit
– large input into caudate from the
association areas of the brain
– caudate nucleus plays a major role in
cognitive control of motor activity
– cognitive control of motor activity
• Putamen circuit
– subconcious execution of learned patterns
of movement

192. Cerebellum-”little brain”
• By weight 10% of total brain
• Contains 1/2 of all neurons in brain
• Highly regular structure
• motor systems are mapped here
• Complete destruction produces no
sensory impairment no loss in muscle
strength
• Plays a crucial indirect role in movement
posture by adjusting the output of the
major descending motor systems

193. Functional Divisions
• Vestibulocerebellum (floculonodular lobe)
– input-vestibular N: output-vestibular N.
• fxn-governs eye movement body equilibrium
• Spinocerebellum (vermis intermediate)
– input-periphery spinal cord: output-cortex
• fxn-major role in movement, influencing medial lateral
descending motor systems
• Cerebrocerebellum (lateral zone)
– input-pontine N. output-pre motor cortex
• fxn-planning initiation of movement extramotor
prediction
• mental rehersal of complex motor actions
• conscious assessment of movement errors
• Higher cognitive function-executive functions

194. Cerebellum
• Cerebellar cortex
• three pairs of deep nuclei from which most
of output originates from.
– fastigial
– Interposed (globose emboliform)
– dentate
• connected to brain stem by 3 sets of
peduncles
– superior which contains most efferent project.
– Middle
– Inferior- most afferent from spinal cord

195. Major features of cerebellum fxn
• receives info about plans for movement
from brain structures concerned with
programming execution of movement
• cerebellum receives information about
motor performance from peripheral
feedback during course of movement
– compares central info w/ actual motor response
• projects to descending motor systems via
cortex

196. Higher Cortical function
• Cerebral Cortex
– About 100 billion neurons contained in a thin layer
2-5 mm thick covering all convolutions of the
cerebrum
– Three major cell types
• Granular, pyramidal, fusiform
– Typically 6 layers (superficial to deep)
• molecular, external granular, external pyramidal, internal
granular, internal pyramidal, mutiform
– All areas of cerebral cortex make extensive afferent
efferent connections with the thalamus

197. The Cerebral Cortex
• Layer I -Molecular Layer
– mostly axons
• Layer II-External Granule Layer
– granule (stellate) cells
• Layer III-External Pyramidal layer
– primary pyramidal cells

198. Cerebral Cortex
• Layer IV-Internal Granule Layer
– main granular cell layer
• Layer V- internal pyramidal layer
– dominated by giant pyramidal cells
• Layer VI- multiform layer
– all types of cells-pyramidal, stellate, fusiform

199. Cerebral Cortex
• Three major cell types
– Pyramidal cells
• souce of corticospinal projections
• major efferent cell
– Granule cells
• short axons-
– function as interneurons (intra cortical processing)
– excitatory neurons release 1o glutamate
– inhibitory neurons release 1o GABA
– Fusiform cells
• least numerous of the three
• gives rise to output fibers from cortex

200. Cerebral Cortex
• Most output leave cortex via V VI
– spinal cord tracts originate from layer V
– thalamic connections from layer V
• Most incoming sensory signals terminate
in layer IV
• Most intracortical association functions -
layers I, II, III
– large # of neurons in II, III- short horozontal
connections with adjacent cortical areas

201. Cerebral Cortex
• All areas of the cerebral cortex have
extensive afferent and efferent
connections with deeper structures of
brain. (eg. Basal ganglia, thalamus
etc.)
• Thalamic connections (afferent and
efferent) are extremely important and
extensive
• Cortical neurons (esp. in association
areas) can change their function as
functional demand changes

202. Concept of a Dominant
Hemisphere
• General interpretative functions of
Wernicke’s angular gyrus as well as
speech motor control are more well
developed in one cerebral hemisphere
@ 95% of population- left hemisphere
– If dominate hemisphere sustains damage
early in life, non dominate hemisphere can
develop those capabilities of speech
language comprehension (Plasticity)

203. Lingustic Dominance
Handedness
• Dominant Hemisphere
– Left or mixed handed
• Left- 70% Right- 15% Both- 15%
– Right handed
• Left- 96% Right- 4% Both- 0%

204. Right brain, left brain
• The two hemispheres are specialized
for different functions
– dominant (usually left)
• language based intellectual functions
• interpretative functions of symbolism,
understanding spoken, written words
• analytical functions- math
• speech
– non dominant (usually right)
• music
• non verbal visual experiences (e.g. body
language)
• spatial relations

205. Allocortex
• Made up of archicortex paleocortex
• 10% of human cerebral cortex
• Includes the hippocampal formation which
is folded into temporal lobe only viewed
after dissection
– hippocampus
– dentate gyrus
– subiculum

206. Hippocampal formation
• Three parts
– Hippocampus- 3 layers (I, V, VI)
– Dentate gyrus- 3 layers (I, IV, VI)
– Subiculum
• Receives 10 input from the entorhinal
cortex of the parahippocampal gyrus
through:
– perforant alveolar pathway

207. Hippocampal formation
• Plays an important role in declarative
memory
– Declarative- making declarative statements of
memory
• Episodic-daily episodes of life
• Semantic-factual information

208. Memory
• Memories are caused by groups of
neurons that fire together in the same
pattern each time they are activated.
• The links between individual neurons,
which bind them into a single memory,
are formed through a process called
long-term potentiation. (LTP)

209. Classification of Memory (cont)
• Memory can also be classified as:
• Declarative-memory of details of an
integrated thought
– memory of: surroundings, time
relationships cause meaning of the
experience
• Reflexive (Skill)- associated with motor
activities
– e.g. hitting a tennis ball which include
complicated motor performance

210. Role of Hippocampus in
Memory
• The hippocampus may store long term
memory for weeks gradually transfer it
to specific regions of cerebral cortex
• The hippocampus has 3 major synaptic
pathways each capable of long-term
potentiation which is thought to play a role
in the storage process

211. Storage of Memory
• Long term memory is represented in
mutiple regions throughout the nervous
system
• Is associated with structural changes in
synapes
– increase in # of both transmitter vesicles
release sites for neurotransmitter
– increase in # of presynaptic terminals
– changes in structures of dendritic spines
– increased number of synaptic connections

212. Memory (cont)
• The memory capability that is spared
following bilateral lesions of temporal lobe
typically involves learned tasks that have
two things in common
– tasks tend to be reflexive, not reflective
involve habits, motor, or perceptual skills
– do not require conscious awareness or
complex cognitive processes. (e.g.
comparison evaluation

213. Memory
• Environment alters human behavior by
learning memory
• Learning
– process by which we acquire knowledge
about the world
• Memory
– process by which knowledge is encoded,
stored retrieved

214. Neural Basis of Memory
• Memory has stages continually
changing
• long term memory- plastic changes
• physical changes coding memory are
localized in multiple regions of the brain
• reflexive declarative memory may
involve different neuronal circuits

215. Higher Cortical Function
• Primary areas
– Visual- occipital pole (BM 17)
– Auditory-superior gyrus of temporal lobe (BM
41)
– Primary motor cortex-pre central gyrus (BM 4)
– Primary somatosensory cortex- post central
gyrus (BM 3,1,2)
• Secondary and Association areas
– Large percentage of human brain

216. Association Areas
• Integrate or associate info. from diverse
sources
• Large % of human cortex
• High level in the hierarchy
• Lesions here have subtle and unpredictable
quality

217. Association Areas
• Prefrontal
– Executive functions Judgment
• Planning for the future
• holding organizing events from memory for prospective
action
• Processing emotion-learning to control emotion (acting
unselfishly)
• Parieto-occipito-temporal
– Spatial relationships
– Recognizing complex form
• prosopagnosia
• Limbic
– Motivation, behavioral drives, emotion

218. Heart muscle
• Atrial Ventricular
– striated enlongated grouped in irregular
anatamosing columns
– 1-2 centrally located nuclei
• Specialized excitatory conductive
muscle fibers (SA node, AV node, Purkinje
fibers)
– contract weakly
– few fibrils

219. Syncytial nature of cardiac
muscle • Syncytium = many acting as one
• Due to presence of intercalated discs
– low resistance pathways connecting cardiac
cells end to end
– presence of gap junctions

220. SA node
• Normal pacemaker of the heart
• Self excitatory nature
– less negative Er
– leaky membrane to Na+/CA++
– only slow Ca++/Na+ channels operational
– spontaneously depolarizes at fastest rate
• overdrive suppression-inhibits other cells automaticity
– contracts feebly
• Stretch on the SA node will increase Ca++
and/or Na+ permeability which will increase
heart rate

221. AV node
• Delays the wave of depolarization from
entering the ventricle
– allows the atria to contract slightly ahead of
the ventricles (.1 sec delay)
• Slow conduction velocity due to smaller
diameter fibers
• In absence of SA node, AV node may act
as pacemaker but at a slower rate

222. Cardiac Cycle
• Systole
– isovolumic contraction
– ejection
• Diastole
– isovolumic relaxation
– rapid inflow- 70-75%
– diastasis
– atrial systole- 25-30%

223. Cardiac cycle:
Pressure changes
Over time
Left ventricular
Volume changes
EKG

224. Ventricular Volumes
• End Diastolic Volume-(EDV)
– volume in ventricles at the end of filling
• End Systolic Volume- (ESV)
– volume in ventricles at the end of ejection
• Stroke volume (EDV-ESV)
– volume ejected by ventricles
• Ejection fraction
– % of EDV ejected (SV/EDV X 100%)
– normal 50-60%

225. Terms
• Preload-stretch on the wall prior to
contraction (proportional to the EDV)
• Afterload-the changing resistance
(impedance) that the heart has to pump
against as blood is ejected. i.e. Changing
aortic BP during ejection of blood from the
left ventricle

226. Atrial Pressure Waves
• A wave
– associated with atrial contraction
• C wave
– associated with ventricular contraction
• bulging of AV valves and tugging on atrial muscle
• V wave
– associated with atrial filling

227. Function of Valves
• Open with a forward pressure gradient
– e.g. when LV pressure the aortic pressure
the aortic valve is open
• Close with a backward pressure gradient
– e.g. when aortic pressure LV pressure the
aortic valve is closed

228. Heart Valves
• AV valves
– Mitral Tricupid
• Thin filmy
• Chorda tendineae act as check lines to prevent
prolapse
• papillary muscles-increase tension on chorda t.
• Semilunar valves
– Aortic Pulmonic
• stronger construction

229. Law of Laplace
• Wall tension = (pressure)(radius)/2
• At a given operating pressure as ventricular
radius Ý , developed wall tension Ý.
Ý tension Þ Ý force of ventricular contraction
– two ventricles operating at the same pressure but
with different chamber radii
• the larger chamber will have to generate more wall
tension, consuming more energy oxygen
• This law explains how capillaries can
withstand high intravascular pressure
because of a small radius, minimizes
developed wall tension

230. Control of Heart Pumping
• Intrinsic properties of cardiac muscle cells
• Frank-Starling Law of the Heart
– Within physiologic limits the heart will pump
all the blood that returns to it without allowing
excessive damming of blood in veins
• heterometric homeometric autoregulation
• direct stretch on the SA node

231. Mechanism of Frank-Starling
• Increased venous return causes increased
stretch of cardiac muscle fibers. (Intrinsic
effects)
– increased cross-bridge formation
– increased calcium influx
• both increases force of contraction
– increased stretch on SA node
• increases heart rate

232. Heterometric autoregulation
• Within limits as cardiac fibers are
stretched the force of contraction is
increased
– more cross bridge formation as actin overlap
is removed
– more Ca++ influx into cell associated with the
increased stretch

233. Homeometric autoregulation
• Ability to increase strength of
contraction independent of a length
change
– Flow induced
– Pressure induced
– Rate induced

234. Extrinsic Influences on heart
• Autonomic nervous system
• Hormonal influences
• Ionic influences
• Temperature influences

235. Control of Heart by ANS
• Sympathetic innervation-
– + heart rate
– + strength of contraction
– + conduction velocity
• Parasympathetic innervation
– - heart rate
– - strength of contraction
– - conduction velocity

236. Interaction of ANS
• SNS effects and Parasympathetic effects
blocked using propranolol (beta blocker)
atropine (muscarinic blocker) respectively.
– HR will increase
– Strength of contraction decreases
• From the previous results it can be concluded
that under resting conditions:
– Parasympathetic NS exerts a dominate inhibitory
influence on heart rate
– Sympathetic NS exerts a dominate stimulatory
influence on strength of contraction

237. Cardioacclerator reflex
• Stretch on right atrial wall + stretch
receptors which in turn send signals to
medulla oblongata + SNS outflow to heart
– AKA Bainbridge reflex
– Helps prevents damning of blood in the heart
central veins

238. Major Hormonal Influences
• Thyroid hormones
– + inotropic
– + chronotropic
– also causes an increase in CO by Ý BMR

239. Ionic influences
• Effect of elevated [K+]ECF
– dilation and flaccidity of cardiac muscle at
concentrations 2-3 X normal (8-12 meq/l)
– decreases resting membrane potential
• Effect of elevated [Ca++] ECF
– spastic contraction

240. Effect of body temperature
• Elevated body temperature
– HR increases about 10 beats for every degree
F elevation in body temperature
– Contractile strength will increase temporarily
but prolonged fever can decrease contractile
strength due to exhaustion of metabolic
systems
• Decreased body temperature
– decreased HR and strength

241. Terminology
• Chronotropic (+ increases) (- decreases)
– Anything that affects heart rate
• Dromotropic
– Anything that affects conduction velocity
• Inotropic
– Anything that affects strength of contraction
• eg. Caffeine would be a + chronotropic agent
(increases heart rate)

242. EKG
• Measures potential difference across the
surface of the myocardium with respect to
time
• lead-pair of electrodes
• axis of lead-line connecting leads
• transition line-line perpendicular to axis of
lead

243. Rate
• Paper speed- 25 mm/sec 1 mm = .04 sec.
• Normal rate ranges usually between 60-80
bps
• Greater than 100 = tachycardia
• Less than 50 = bradycardia

244. Electrocardiography
• P wave-atrial depolarization
• QRS complex-ventricular depolarization
• T wave-ventricular repolarization

245. Leads
• A pair of recording electrodes
– + electrode is active
– - electrode is reference
• The direction of the deflection (+ or -) is
based on what the active electrode
sees relative to the reference electrode
• Routine EKG consists of 12 leads
– 6 frontal plane leads
– 6 chest leads (horizontal)

246. Type of Deflection
Wave of
Depolarization
Wave of
Repolarization
Moving
toward + elect.
Ýdeflection ßdeflection
Moving
toward - elect.
ß deflection Ý deflection

247. Hypertrophy
• Hypertrophy of one ventricle relative to the
other can be associated with anything that
creates an abnormally high work load on
that chamber.
– e.g. Systemic hypertension increasing work
load on the left ventricle
– prolonged QRS complex ( .12 sec)
– axis deviation to the side of problem
– increased voltage of QRS in V leads

248. Blood flow to myocardium
• The myocardium is supplied by the
coronary arteries their branches.
• Cells near the endocardium may be able
to receive some O2 from chamber blood
• The heart muscle at a resting heart rate
takes the maximum oxygen out of the
perfusing coronary flow (70% extraction)
– Any Ý demand must be met by Ý coronary
flow

249. Circulation
• The main function of the systemic
circulation is to deliver adequate
oxygen, nutrients to the systemic
tissues and remove carbon dioxide
other waste products from the systemic
tissues
• The systemic circulation is also serves
as a conduit for transport of hormones,
and other substances and allows these
substances to potentially act at a
distant site from their production

250. Functional Parts
• systemic arteries
– designed to carry blood under high
pressure out to the tissue beds
• arterioles pre capillary sphincters
– act as control valves to regulate local flow
• capillaries- one cell layer thick
– exchange between tissue (cells) blood
• venules
– collect blood from capillaries
• systemic veins
– return blood to heart

251. Basic theory of circulatory
function
• Blood flow is proportional to metabolic
demand
• Cardiac output controlled by local tissue
flow
• Arterial pressure control is independent of
local flow or cardiac output

252. Hemodynamics
• Flow
• Pressure gradient
• Resistance
• Ohm’s Law
– V = IR (Analogous to D P = QR)

253. Flow (Q)
• The volume of blood that passes a certain
point per unit time (eg. ml/min)
• Q = velocity X cross sectional area
– At a given flow, the velocity is inversely
proportional to the total cross sectional area
• Q = D P / R
– Flow is directly proportional to D P and
inversely proportional to resistance (R)

254. Pressure gradient
• Driving force of blood
• difference in pressure between two points
• proportional to flow (Q)
• At a given Q the greater the drop in P in a
segment or compartment the greater the
resistance to flow.

255. Resistance
• R= 8hl/p r4
h = viscosity, l = length of vessel, r = radius
• Parallel circuit
– 1/RT= 1/R1+ 1/R2 + 1/R3 + … 1/RN
– RT smallest individual R
• Series circuit
– RT = R1 + R2 + R3 + … RN
– RT = sum of individual R’s
• The systemic circulation is
predominantly a parallel circuit

256. Advantages of Parallel Circuitry
• Independence of local flow control
– increase/decrease flow to tissues
independently
• Minimizes total peripheral resistance
(TPR)
• Oxygen rich blood supply to every tissue

257. Viscosity
• Internal friction of a fluid associated with
the intermolecular attraction
• Blood is a suspension with a viscosity of 3
– most of viscosity due to RBC’s
• Plasma has a viscosity of 1.5
• Water is the standard with a viscosity of 1
• With blood, viscosity 1/µ velocity

258. Viscosity considerations at
microcirculation
• velocity decreases which increases
viscosity
– due to elements in blood sticking together
• cells can get stuck at constriction points
momentarily which increases apparent
viscosity
– fibrinogen increases flexibility of RBC’s
• in small vessels cells line up which
decreases viscosity and offsets the above
to some degree (Fahaeus-Lindquist)

259. Hematocrit
• % of packed cell volume (10 RBC’s)
• Normal range 38%-45%

260. Laminar vs. Turbulent Flow
• Streamline
• silent
• most efficient
• normal
• Cross mixing
• vibrational noise
• least efficient
• frequently associated
with vessel disease
(bruit)

261. Reynold’s number
• Probability statement for turbulent flow
• The greater the R#, the greater the
probability for turbulence
• R# = v D r/h
– v = velocity, D = tube diameter, r = density,
h = viscosity
– If R# 2000 flow is usually laminar
– If R# 3000 flow is usually turbulent

262. Doppler Ultrasonic Flow-meter
• Ultrasound to determine velocity of flow
• Doppler frequency shift Þ function of the
velocity of flow
– RBC’s moving toward transmitter, compress
sound waves, Ý frequency of returning waves
• Broad vs. narrow frequency bands
– Broad band is associated with turbulent flow
– narrow band is associated laminar flow

263. Distensibility Vs. Compliance
• Distensibility is the ability of a vessel to
stretch (distend)
• Compliance is the ability of a vessel to
stretch and hold volume

264. Distensibility Vs. Compliance
• Distensibility = D Vol/D Pressure X Ini. Vol
• Compliance = D Vol/D Pressure
• Compliance = Distensibility X Initial Vol.

265. Volume-Pressure relationships
• A D volume µ D pressure
• In systemic arteries a small D volume is
associated with a large D pressure
• In systemic veins a large D volume is
associated with a small D pressure
• Veins are about 8 X more distensible and 24
X more compliant than systemic arteries
• Wall tone 1/µ compliance distensibility

266. Control of Blood Flow (Q)
• Local blood flow is regulated in proportion to
the metabolic demand in most tissues
• Short term control involves vasodilatation
vasoconstriction of precapillary resist. vessels
– arterioles, metarterioles, pre-capillary sphincters
• Long term control involves changes in tissue
vascularity
– formation or dissolution of vessels
– vascular endothelial growth factor angiogenin

267. Role of arterioles
• Arterioles act as an intergrator of multiple
inputs
• Arterioles are richly innervated by SNS
vasoconstrictor fibers and have alpha
receptors
• Arterioles are also effected by local factors
(e.g.)vasodilators, circulating substances

268. Local Control of Flow (short
term) • Involves vasoconstriction/vasodilatation of
precapillary resistance vessels
• Local vasodilator theory
– Active tissue release local vasodilator
(metabolites) which relax vascular smooth
muscle
• Oxygen demand theory (older theory)
– As tissue uses up oxygen, vascular smooth
muscle cannot maintain constriction

269. Local Vasodilators
• Adenosine
• carbon dioxide
• adenosine phosphate compounds
• histamine
• potassium ions
• hydrogen ions
• PGE PGI series prostaglandins

270. Autoregulation
• The ability to keep blood flow (Q) constant
in the face of a changing arterial BP
• Most tissues show some degree of
autoregulation
• Q µ metabolic demand
• In the kidney both renal Q and glomerular
filtration rate (GFR) are autoregulated

271. Control of Flow (long term)
• Changes in tissue vascularity
– On going day to day reconstruction of the vascular
system
• Angiogenesis-production of new microvessels
– arteriogenesis
• shear stress caused by enhanced blood flow velocity
associated with partial occlusion
– Angiogenic factors
• small peptides-stimulate growth of new vessels
– VEGF (vascular endothelial growth factor)

272. Changes in tissue vascularity
• Stress activated endothelium up-regulates
expression of monocyte chemoattractant
protein-1 (MCP-1)
– attraction of monocytes that invade arterioles
– other adhesion molecules growth factors
participate with MCP-1 in an inflammatory
reaction and cell death in potential collateral
vessels followed by remodeling
development of new enlarged collateral
arteries arterioles

273. Changes in tissue vacularity
(cont.)
• Hypoxia causes release of VEGF
– enhanced production of VEGF partly mediated
by adenosine in response to hypoxia
– VEGF stimulates capillary proliferation and may
also be involved in development of collateral
arterial vessels
– NPY from SNS is angiogenic
– hyperactive SNS may compromise collateral
blood flow by vasoconstriction

274. Vasoactive Role of Endothelium
• Release prostacyclin (PGI2)
– inhibits platelet aggregation
– relaxes vascular smooth muscle
• Releases nitric oxide (NO) which
relaxes vascular smooth muscle
– NO release stimulated by:
• shear stress associated with increased flow
• acetylcholine binding to endothelium
• Releases endothelin endothelial
derived contracting factor
– constricts vascular smooth muscle

275. Microcirculation
• Capillary is the functional unit of the
circulation
– bulk of exchange takes place here
– Vasomotion-intermittent contraction of
metarterioles and precapillary sphincters
– functional Vs. non functional flow
• Mechanisms of exchange
– diffusion
– ultrafiltration
– vesicular transport

276. Oxygen uptake/utilization
• = the product of flow (Q) times the arterial-venous
oxygen difference
• O uptake = (Q) (A-V O2 difference)
– Q=300 ml/min
– AO2= .2 ml O2/ml
– VO2= .15 ml O2/min
• 15 ml O2 = (300 ml/min) (.05 mlO2/ml)
• Functional or Nutritive flow (Q) is associated with
increased oxygen uptake/utilization

277. Capillary Exchange
• Passive Diffusion
– permeability
– concentration gradient
• Ultrafiltration
– Bulk flow through a filter (capillary wall)
– Starling Forces
• Hydrostatic P
• Colloid Osmotic P
• Vesicular Transport
– larger MW non lipid soluble substances

278. Ultrafiltration
• Hydrostatic P gradient (high to low)
– Capillary HP averages 17 mmHg
– Interstitial HP averages -3 mmHg
• Colloid Osmotic P (low to high)
– Capillary COP averages 28 mmHg
– Interstitial COP averages 9 mmHg
• Net Filtration P = (CHP-IHP)-(CCOP-ICOP)
• 1 = 20 - 19

279. Colloid Osmotic Considerations
• The colloid osmotic pressure is a function
of the protein concentration
– Plasma Proteins
• Albumin (75%)
• Globulins (25%)
• Fibrinogen (1%)
• Calculated Colloid Effect is 19 mmHg
• Actual Colloid Effect is 28 mmHg
– Discrepancy is due to the Donnan Effect

280. Donnan Effect
• Increases the colloid osmotic effect
• Large MW plasma proteins (1o albumen)
carries negative charges which attract +
ions (1o Na+) increasing the osmotic effect
by about 50%

281. Effect of Ultrastructure of Capillary
Wall on Colloid Osmotic Pressure
• Capillary wall can range from tight
junctions (e.g. blood brain barrier) to
discontinuous (e.g. liver capillaries)
• Glomerular Capillaries in kidney have
filtration slits (fenestrations)
• Only that protein that cannot cross
capillary wall can exert osmotic pressure

282. Reflection Coefficient
• Reflection Coefficient expresses how
readily protein can cross capillary wall
– ranges between 0 and 1
– If RC = 0
• All colloid proteins freely cross wall, none are
reflected, no colloid effect
– If RC = 1
• All colloid proteins are reflected, none cross
capillary wall, full colloid effect

283. Lymphatic system
• Lymph capillaries drain excess fluid
from interstitial spaces
• No true lymphatic vessels found in
superficial portions of skin, CNS,
endomysium of muscle, bones
• Thoracic duct drains lower body left
side of head, left arm, part of chest
• Right lymph duct drains right side of
head, neck, right arm and part of chest

284. CNS-modified lymphatic
function • No true lymphatic vessels in CNS
• Perivascular spaces contain CSF
communicate with subarachnoid space
• Plasma filtrate escaped substances in
perivascular spaces returned to the
vascular system in the CSF via the
arachnoid villi which empties into dural
venous sinsus
• Acts a functional lymphatic system in CNS

285. Formation of Lymph
• Excess plasma filtrate-resembles ISF
from tissue it drains
• [Protein] » 3-5 gm/dl in thoracic duct
– liver 6 gm/dl
– intestines 3-4 gm/dl
– most tissues ISF 2 gm/dl
• 2/3 of all lymph from liver intestines
• Any factor that Ý filtration and/or ß
reabsorption will Ý lymph formation

286. Rate of Lymph Formation/Flow
• Thoracic duct- 100 ml/hr.
• Right lymph duct- 20 ml/hr.
• Total lymph flow- 120 ml/hr (2.9 L/day)
• Every day a volume of lymph roughly
equal to your entire plasma volume is
filtered

287. Function of Lymphatics
• Return lost protein to the vascular system
• Drain excess plasma filtrate from ISF
space
• Carry absorbed substances/nutrients
(e.g. fat-chlyomicrons) from GI tract
• Filter lymph (defense function) at lymph
nodes
– lymph nodes-meshwork of sinuses lined with
tissue macrophages (phagocytosis)

288. Arterial blood pressure
• Arterial blood pressure is created by the
interaction of blood with vascular wall
• Art BP = volume of blood interacting with
the wall
– inflow (CO) - outflow (TPR)
– Art BP = CO X TPR
• Greater than 1/2 of TPR is at the level of
systemic arterioles

289. Systole
• During systole the left ventricular output
(SV) is greater than peripheral runoff
• Therefore total blood volume rises which
causes arterial BP to increase to a peak
(systolic BP)
• The arteries are distended during this time

290. Diastole
• While the left ventricle is filling, the arteries
now are recoiling, which serves to
maintain perfusion to the tissue beds
• Total blood volume in the arterial tree is
decreasing which causes arterial BP to fall
to a minimum value (diastolic BP)

291. Hydralic Filtering
• Stretch (systole) recoil (diastole) of
the arterial tree that normally occurs
during the cardiac cycle
• This phenomenon converts an
intermittent output by the heart to a
steady delivery at the tissue beds
saves the heart work
• As the distensibility of the arterial tree ß
with age, hydralic filtering is reduced,
and work load on the heart is increased

292. Mean Arterial Blood Pressure
• The mean arterial pressure (MAP) is not
the arithmetical mean between systole
diastole
• determined by calculating the area under
the curve, and dividing it into equal areas
• MAP= 1/3 Pulse Pressure + DBP
(approximation)

293. Effects of SNS +
• Most post-ganglionic SNS terminals
release norepinephrine.
• The predominant receptor type is alpha
(a)
a response is constriction of smooth
muscle
– Constriction of arterioles reduce blood flow
and help raise arterial blood pressure (BP)
– Constriction of arteries raise arterial BP
– Constriction of veins increases venous return

294. SNS (cont)
• SNS + causes widespread vasoconstrictor
causing ß blood flow with 3 exceptions
– Brain
• arterioles weakly innervated
– Lungs
• arterioles weakly innervated
• Pulmonary BF = C.O.
– Heart
• direct vasoconstrictor effects over-ridden by SNS
induced increase in cardiac activity which causes
release of local vasodilators (adenosine)

295. Critical Closing Pressure
• As arterial pressure falls, there is a critical
pressure below which flow ceases due to
the closure of the arterioles.
• This critical luminal pressure is required to
keep arterioles from closing completely
• vascular tone is proportional to CCP
– e.g. SNS + of arterioles Ý CCP

296. Mean Circulatory Filling Pressure
• If cardiac output is stopped, arterial pressure will
fall and venous pressure will rise
• MCFP = equilibration pressure where arterial BP
= venous BP
• equilibration pressure may be prevented by
closure of the arterioles (critical closing
pressure)
• responsible for pressure gradient driving
peripheral venous return

297. Vascular Cardiac Function
• Vascular function
– At a given MCFP as Central Venous
Pressure Ý, venous return ß
• If MCPF = CVP; venous return goes to 0
• Cardiac function
– As central venous pressure increases,
cardiac output increases due to both
intrinsic extrinsic effects

298. Central Venous Pressure
• The pressure in the central veins (superior
inferior vena cava) at the entry into the
right atrium.
• Central venous pressure = right atrial
pressure

299. Vasomotor center
• Collection of neurons in the medulla pons
• Four major regions
– pressor center- increase blood pressure
– depressor center- decrease blood pressure
– sensory area- mediates baroreceptor reflex
– cardioinhibitory area- stimulates X CN
• Sympathetic vasoconstrictor tone
– due to pressor center input
– 1/2 to 2 IPS
– maintains normal arterial blood pressure

300. Control of Blood Pressure
• Rapid short term control involves the
nervous systems effect on vascular
smooth muscle
• Long term control is dominated by the
kidneys-
– Renal-body fluid balance

301. Control of Blood Pressure
• Concept of Contents vs. Container
– Contents
• blood volume
• Container
• blood vessels
• Control of blood pressure is accomplished
by either affecting vascular tone or blood
volume