Physiology Review

A work in Progress
 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
 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
 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
 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%)
 Weapons in neurophysiologist’s
armory
• Recording
– Individual neurons
– Gross potentials
– Brain scans
• Stimulation
• Lesions
– Natural lesions
– Experimental lesions
 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
 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++)
 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
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
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
 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
 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.
 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
 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
 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
 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
 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
 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
 Neurotransmitters
• Acetylcholine
• Catacholamines
– Norepinephrine
– Epinephrine
• Serotonin
• Dopamine
• Glutamate
• Gamma-amino butyric acid (GABA)
• Certain amino acids
• Variety of peptides
 Neurons
• May release more than one substance
upon stimulation
– Neurotransmitter like norepinephrine
– Neuromodulator like neuropeptide Y (NPY)
 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
 Response of Postsynaptic Cell
• Stimulation causing an AP
  EPSP >  IPSP > threshold
• Stimulation leading to facilitation
  EPSP >  IPSP < threshold
• Inhibition
  EPSP <  IPSP
 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
 Transduction
• Stimulus is changed into electrical signal
• Different types of stimuli
– mechanical deformation
– chemical
– change in temperature
– electromagnetic
 Sensory systems
• All sensory systems mediate 4 attributes
of a stimulus no matter what type of
sensation
– modality
– location
– intensity
– timing
 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
 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
 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
 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)
 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
 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.
 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.
 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
 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)
 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
 Mechanoreceptors in Glabrous
(non hairy) Skin
Superficial Deep
Small field Large field
Rapid Meissner’s Pacinian
adaptation
Corpuscle Corpuscle
Slow Merkel’s Ruffini
adaptation
Disc End Organ
 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
 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
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.
 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”
 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
 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
 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
 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
 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
 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
 Nociceptive pathways
• Fast • Slow
• A delta fibers • C fibers
• glutamate • substance P
• • paleospinothalamic
neospinothalamic
• polymodal/chemical
• mechanical, thermal
• poor localization
• good localization
• dull, burning, aching
• sharp, pricking • terminate; RF
• terminate in VB – tectal area of mesen.
complex of thalamus – Periaqueductal gray
 Nociceptive pathways
• Spinothalamic-major
– neo- fast (A delta)
– paleo- slow (C fibers)
• Spinoreticular
• Spinomesencephalic
• Spinocervical (mostly tactile)
• Dorsal columns- (mostly tactile)
 Pain Control Mechanisms
• Peripheral • Central
• Gating theory • Direct electrical + to
– involves inhibitory brain -> analgesia
interneruon in cord • Nociceptive control
impacting nocicep.
pathways descend to
projection neurons
• inhibited by C fibers cord
• stimulated by A alpha & • Endogenous opiods
beta fibers
• TENS
 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
 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)
 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
 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
 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)
 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
 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
 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
 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
 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
 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
 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
 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
 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.
 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
 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
 Special Senses
• Vision
• Audition
• Chemical senses
– Taste
– Smell
 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
 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
 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)
 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
 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  apart on
retina can be distinguished as two
separate points
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
 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
 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
 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
 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
 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
 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
 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 Magnocellular
LGN of LGN
Function color vision B&W movment
 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
 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
 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
 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”
 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
 Dark Adaptation
• In sustained darkness reform light sensitive
pigments (Rhodopsin & Cone Pigments)
  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
 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)
 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
 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
 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
 Visual Association Cortex
• Visual analysis proceeds along many
paths in parallel
– form
– color
– motion
– depth
 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)
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
 Raising/lowering/torsioning
Abducted Adducted
Eye Eye
Superior rectus Inferior oblique
Elevate
Inferior rectus Superior oblique
Depress

Superior oblique Superior rectus

Torsion
Inferior oblique Inferior rectus
 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
 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
 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
 Different Levels of Sound
• 20 dB- whisper
• 60 dB- normal conversation
• 100 dB- symphony
• 130 dB- threshold of discomfort
• 160 dB- threshold of pain
 Frequencies of Audible Sound
• In a young adult
• 20-20,000 Hz (decreases with age)
• Greatest acuity
• 1000-4000 Hz
 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)
 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
 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
 Cochlea
• System of 3 coiled tubes
– Scala vestibuli
– Scala media
– Scala tympani
 Scala Vestibuli
• Seperated from the scala media by
Reissner’s membrane
• Associated with the oval window
• filled with perilymph (similar to CSF)
 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
 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)
 Scala Tympani
• Associated with the round window
• Filled with perilymph
– baths lower bodies of hair cells
 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
 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)
 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
 Primary Auditory Cortex
• Located in superior gyrus of temporal lobe
• tonotopic organization
– high frequency sounds
• posterior
– low frequency sounds
• anterior
 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)
 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
 Exteroceptive chemosenses
• Taste
– Works together with smell
– Categories (Primary tastes)
• sweet
• salt
• sour
• bitter (lowest threshold-protective mechanism)
• Olfaction (Smell)
– Primary odors (100-1000)
 Taste receptors
• May have preference for stimuli
• influenced by past history
– recent past
• adaptation
– long standing
• memory
• conditioning-association
 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)
 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
 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
 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
 Adaptation of taste
• Rapid-within minutes
• taste buds account for about 1/2 of
adaptation
• the rest of adaptation occurs higher in
CNS
 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)
 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
 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
 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
 Characteristics of Odorants
• Volatile
• slightly water soluble-
– for mucus
• slightly lipid soluble
– for membrane of cilia
• Threshold for smells
– Very low
 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
 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
 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)
 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
 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
 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
 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
 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
 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
 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
 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)
 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
 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
 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
 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
 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
 Enteric Nervous System
• Located in wall of GI tract (100 million
neurons)
• Activity modulated by ANS
 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
 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
 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
 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
 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
 Neuropeptides (visceral
afferent)
– Angiotension II
– Arginine-vasopressin
– bombesin
– calcitonin gene-related peptide
– cholecystokinin
– galamin
– substance P
– enkephalin
– somatostatin
– vasoactive intestinal peptide
 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
 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
 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
 Effects of Stimulation
• Airway smooth muscle: S dilation P
constriction
• Ducts: S dilation P constriction
• Immune System: S inhibits, P ??
 Fate of released NT
• Acetylcholine (P) rapidly hydrolysed by
aetylcholinesterase
• Norepinephrine
– uptake by the nerve terminals
– degraded by MAO, COMT
– carried away by blood
 Precursors for NT
• Tyrosine is the precursor for Dopamine,
Norepinephrine & Epinephrine
• Choline is the precursor for Acetylcholine
 Receptors
• Adrenergic
– Alpha
– Beta
• Acetylcholine receptors
– Nicotinic
• found at synapes between pre & post ganglionic
fibers (both S & P)
– Muscarinic
• found at effector organs
 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
 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)
 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
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 ’s
in preganglionic SNS or Para tone
and/or ’s in neuroendocrine (NE)
effectors
 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
 Important Central Autonomic
Areas
• Nucleus Tractus Solitarius
• Parabrachial Nucleus
• Locus Coeruleus
• Amygdala
• Cerebral Cortex
• Hypothalamus
• Circumventricular Organs (fenestrated
caps)
Control of Complex Movements
• Involve
– Cerebral Cortex
– Basal Ganglia
– Cerebellum
– Thalamus
– Brain Stem
– Spinal Cord
 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
 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
 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
 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
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
 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
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
 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)
 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
 Postural Reflexes
• Three types of postural reflexes
– vestibular reflexes
– tonic neck reflexes
– righting reflexes
 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
 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
 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
 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
 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
 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
 Semicircular Canals
• Thought to have a predictive function to
prevent malequilibrium
• Anticipitory corrections
• works in close concert with cerebellum
especially the flocculonodular lobe
 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
 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
 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
 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
 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)
 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)
 Postural Mechanisms (cont)
• In sway, contraction of muscles to maintain
balance occur in distal to proximal sequence
– forward sway
• Gastro>ham>para
– backward sway
• Tib>quad>abd
• responses that stabilize posture are
facilitated
• responses that destabilize posture inhibited
 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
 Basal Ganglia
• Input nuclei
– Caudate
– Putamen
• caudate + putamen = striatum
– Nucleus accumbens
• Output nuclei
– Globus Pallidus-external segment
– Subthalamic nucleus
– Substantia nigra
– Ventral tegmental area
 Basal Ganglia
• Consist of 4 principal nuclei
– the striatum (caudate & putamen)
– the globus pallidus (internal & external)
– the substantia nigra
– subthalamic nucleus
 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
 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
 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
 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
 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
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
 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
 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
 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
 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
 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
 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
 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)
 Lingustic Dominance &
Handedness
• Dominant Hemisphere
– Left or mixed handed
• Left- 70% Right- 15% Both- 15%
– Right handed
• Left- 96% Right- 4% Both- 0%
 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
 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
 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
 Hippocampal formation
• Plays an important role in declarative
memory
– Declarative- making declarative statements of
memory
• Episodic-daily episodes of life
• Semantic-factual information
 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)
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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 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
 Cardiac Cycle
• Systole
– isovolumic contraction
– ejection
• Diastole
– isovolumic relaxation
– rapid inflow- 70-75%
– diastasis
– atrial systole- 25-30%
Cardiac cycle:

Pressure changes
Over time

Left ventricular
Volume changes

EKG
 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%
 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
 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
 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
 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
 Law of Laplace
• Wall tension = (pressure)(radius)/2
• At a given operating pressure as ventricular
radius  , developed wall tension .
  tension   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
 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
 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
 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
 Homeometric autoregulation
• Ability to increase strength of
contraction independent of a length
change
– Flow induced
– Pressure induced
– Rate induced
 Extrinsic Influences on heart
• Autonomic nervous system
• Hormonal influences
• Ionic influences
• Temperature influences
 Control of Heart by ANS
• Sympathetic innervation-
– + heart rate
– + strength of contraction
– + conduction velocity
• Parasympathetic innervation
– - heart rate
– - strength of contraction
– - conduction velocity
 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
 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
 Major Hormonal Influences
• Thyroid hormones
– + inotropic
– + chronotropic
– also causes an increase in CO by  BMR
 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
 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
 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)
 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
 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
 Electrocardiography
• P wave-atrial depolarization
• QRS complex-ventricular depolarization
• T wave-ventricular repolarization
 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)
 Type of Deflection
Wave of Wave of
Depolarization Repolarization
Moving deflection deflection
toward + elect.
Moving  deflection  deflection
toward - elect.
 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
 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  demand must be met by  coronary flow
 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
 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
 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
 Hemodynamics
• Flow
• Pressure gradient
• Resistance
• Ohm’s Law
– V = IR (Analogous to  P = QR)
 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=P/R
– Flow is directly proportional to  P and
inversely proportional to resistance (R)
 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.
 Resistance
• R= 8l/ r4
  = 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
– R T = R 1 + R2 + R 3 + … R N
– RT = sum of individual R’s
• The systemic circulation is predominantly a
parallel circuit
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
 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/ velocity
 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)
 Hematocrit
• % of packed cell volume (10 RBC’s)
• Normal range 38%-45%
 Laminar vs. Turbulent Flow
• Streamline • Cross mixing
• silent • vibrational noise
• most efficient • least efficient
• normal • frequently associated
with vessel disease
(bruit)
 Reynold’s number
• Probability statement for turbulent flow
• The greater the R#, the greater the
probability for turbulence
• R# = v D /
– v = velocity, D = tube diameter,  = density,
 = viscosity
– If R# < 2000 flow is usually laminar
– If R# > 3000 flow is usually turbulent
 Doppler Ultrasonic Flow-meter
• Ultrasound to determine velocity of flow
• Doppler frequency shift  function of the
velocity of flow
– RBC’s moving toward transmitter, compress
sound waves,  frequency of returning waves
• Broad vs. narrow frequency bands
– Broad band is associated with turbulent flow
– narrow band is associated laminar flow
 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
 Distensibility Vs. Compliance
• Distensibility =  Vol/ Pressure X Ini. Vol
• Compliance =  Vol/ Pressure
• Compliance = Distensibility X Initial Vol.
Volume-Pressure relationships

• A  volume   pressure
• In systemic arteries a small  volume is
associated with a large  pressure
• In systemic veins a large  volume is
associated with a small  pressure
• Veins are about 8 X more distensible and 24
X more compliant than systemic arteries
• Wall tone 1/ compliance & distensibility
 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
 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
 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
 Local Vasodilators
• Adenosine
• carbon dioxide
• adenosine phosphate compounds
• histamine
• potassium ions
• hydrogen ions
• PGE & PGI series prostaglandins
 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  metabolic demand
• In the kidney both renal Q and glomerular
filtration rate (GFR) are autoregulated
 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)
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
 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
 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
 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
 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
 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
 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
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
 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%
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
 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
 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
 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
 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  filtration and/or 
reabsorption will  lymph formation
 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
 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)
 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
 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
 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)
 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 
with age, hydralic filtering is reduced, and
work load on the heart is increased
 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)
 Effects of SNS +
• Most post-ganglionic SNS terminals release
norepinephrine.
• The predominant receptor type is alpha ()
  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
 SNS (cont)
• SNS + causes widespread vasoconstrictor
causing  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)
 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  CCP
 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
Vascular & Cardiac Function
• Vascular function
– At a given MCFP as Central Venous
Pressure , venous return 
• If MCPF = CVP; venous return goes to 0
• Cardiac function
– As central venous pressure increases,
cardiac output increases due to both
intrinsic & extrinsic effects
 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
 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
 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
 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
 Baroreceptors
• Spray type nerve endings in vessel walls
– Especially abundant in Carotid Sinus & Arch of Aorta
• Stimulated when stretched
– Inhibits “Pressor Center” via IX X CN & NTS
• Net Effects
– Vasodiation & decreased cardiac output
• Carotid sinus reflex
• more sensitive to changing P than static P
• buffer function
– buffer changes in BP to changing blood volume
• lack of long term control due to adaptation
– resetting within 1-2 days
 Low Pressure Baroreceptors
• Located in atrial walls & pulmonary
arteries
• augment arterial baroreceptors
• minimize arterial pressure changes in
response to blood volume changes
 Stretch on Atrial Wall
• Baroreceptor reflex- “low pressure”
– decreased heart rate
– increased urine production
• decreased SNS in renal nerves
• decreased secretion of ADH
• Bainbridge reflex- increase heart rate
• Release of Atrial Natriuretic Peptide
– dirurectic, natriuretic, vasodilator
 Renal-Body Fluid System
• Arterial Pressure (AP) Control
• Increased ECF will cause AP to rise
• In response the kidneys excrete excess
ECF
 Determinants of long term AP
• The degree of shift of the renal output
curve for water and salt
• The level of the water and salt intake line
• Increased total peripheral resistance will
not create a long term elevation of BP if
fluid intake and renal function do not
change
 Control of blood pressure
• Most autoregulation of both renal blood
flow and glomerular filtration takes place at
the afferent arteriole
• Normal glomerular filtration rate is about
100 ml/min
• Normal renal blood flow is about 1.25
L/min (25% of Cardiac Output)
 The Kidney
• Afferent arterioles supply the glomerular
capillaries where filtration takes place
• Efferent arterioles drain the glomerular
capillaries and give rise to the peritubular
capillaries where reabsorption takes place
• vasa recti
– specialized peritubular capillaries associated
with juxtamedullary nephrons
Renal control of blood pressure
• When the extracellular fluid levels rises, the
arterial pressure rises
• The kidney excretes more fluid, thus bringing the
pressure back to normal
– SNS + causes renin secretion which causes the
formation of angiotensin, which in turn stimulates
release of Aldosterone from the adrenal cortex and
ADH from the posterior pituitary
• All of the above promote increased blood pressure by either
causing H2O reabsorption and/or vasoconstriction
 Role of afferent & efferent
arterioles in autoregulation
• In kidney
– constriction of afferent arterioles will decrease
both renal Q and GFR
– constriction of efferent arterioles will decrease
renal Q but increases GFR by creating back
pressure
– therefore in the face of a rising arterial BP
constriction of the afferent arterioles alone can
autoregulate both Q and GFR (within limits)
 Hormones regulating RBF
• Decrease renal blood flow (RBF)
– norepinephrine
– epinephrine
– angiotensin II
• Increase renal blood flow (RBF)
– prostaglandins (E & I)
 Tubuloglomerular feedback
• Moniters NaCl in the Macula densa of the
distal tubule
  NaCl in Macula densa + renin release
from the Juxtaglomerular (JG) cells
  renin  angiotensin II levels   efferent
arteriole resistance
  NaCl in Macula densa also causes
dilatation of afferent arteriole
 Generation of hypertension
• Tie off one renal artery
– development of systemic hypertension
• elevation of renin and angiotensin II
– no development of uremia
• Tie off one renal artery and remove kidney
– no development of hypertension or uremia
• Tie off and remove both kidneys
– development of both hypertension and uremia
 Circulatory Readjustments at
Birth
• Increased blood flow through lungs & liver
– pulmonary vascular resistance decreases
• decreased RVP, pulmonary arterial BP
• Loss of blood flow through the placenta
– doubles the systemic vascular resistance
• increased LAP, LVP, aortic BP
• Closure of Foramen Ovale, Ductus
Arteriosis, & Ductus Venosus
 Circulatory Readjustments
(cont)
• Closure of Foramen Ovale
– due to reversal of pressure gradient between RA and
LA, flap closes
• Closure of Ductus Arteriosis
– Reversal of flow from aorta to pulmonary artery, and
increased oxygen levels cause constriction of smooth
muscle
• Closure of Ductus Venosus
– cause unknown
– allows portal blood to perfuse liver sinuses
 Circulation in Fetus
• Right and Left Ventricle pump in parallel
into the aorta
• Very little pulmonary blood flow
• Low pressure in aorta due to low TPR
because of placenta-umbilical arteries
• Blood returning from the placenta via the
umbilical veins bypass liver and flow
directly into inferior VC via dutus venosus
 Circulation in Fetus
• In the fetus there exsits two right to left
shunts for blood to bypass the lungs
• Foramen Ovale shunts most blood
returning to the the heart from the inferior
vena cava to the left atrium
• Ductus Arteriosus shunts most blood
returning to the heart from the superior
vena cava to the aorta
 Exercise
• Greatest stress on the CV system
• Sympathetic nervous system orchestrates
many of the changes associated with
exercise
• Cardiac output is increased 5-6 fold
• Blood flow is shifted primarily from organs
to active skeletal muscle
 The role of the SNS
• SNS stimulation due to:
– Cerebral cortex stimulation (central command)
– Reflex signals from active joint proprioceptors
and muscle spindles
– Local chemoreceptor signals originating in the
active muscle
• SNS effects
– Increased HR and SV (CO)
• Induces local metabolic vasodilatation at the heart
 SNS effects (cont)
• SNS stimulation of pre-capillary resistance
vessels (organs and inactive skeletal
muscle) decreases blood flow
• SNS stimulation of veins causes
constriction which mobilizes blood out of
veins increasing venous return
– Redistribution of blood volume
• SNS stimulation of vascular smooth
muscle in walls of arteries help maintain
slightly increased blood pressure during
exercise
 Tissues that escape SNS
vasoconstriction
• Heart
• Brain
• Lungs
Increased flow to active muscle
• Increased blood flow to the active muscle is
NOT mediated by the SNS but by the local
release of tissue metabolites in response to the
increase in metabolism “Local vasodilators”
(partial list)
– Adenosine
– CO2
– K+
– Histamine
– Lactic acid
 Blood Flow
• Rest CO = 5.9 L/min • Exercise = 24 L/min
– Coronary-250 ml/min – Coronary-1000 ml/min
– Brain-750 ml/min – Brain-750 ml/min
– Organs-3100 ml/min – Organs-600 ml/min
– Inactive muscle-650 – Inactive muscle-300
ml/min ml/min
– Active muscle-650 – Active muscle-20,850
ml/min ml/min
– Skin- 500 ml/min – Skin- initially↓, then
↑as body temp ↑
 CV changes during exercise
• Cerebral cortical activation of the SNS
– SNS effects
• vasoconstriction of arterioles to  flow to non active
tissues (viscera)
• vasoconstriction of veins to  MCFP which  venous
return
• stimulation of heart ( HR, SV)   CO
• TPR  due to vasodilatation in active muscle
• Increased O2 uptake which decreases VO2
  AVO2 difference (AO2 stays relatively
constant
 Effect of exercise on CV endpoints
• HR ↑ (60-180 b/min)
• SV ↑ to a point and then may ↓
• CO ↑ (5-25 L/min)
• Systolic BP ↑
• Diastolic BP ↑ (slightly)
• Mean arterial BP ↑ (slightly)
• Total peripheral resistance ↓
• Oxygen consumption ↑ (.25-5.0 L/min)
• Arteriovenous oxygen difference ↑ (25-50%)
 AP changes during exercise
  SBP due to the  CO >  TPR (also 
SNS contributes to )
  DBP only slightly (and may  )
  Pulse Pressure (SBP-DBP)
 venous return during exercise

• SNS constriction of veins

• Intermittent skeletal muscle activity
coupled with one way valves in veins
“venous pump”
  frequency & depth of respiration
increased negative thoracic pressure
 VO2 Maximum
• The maximum volume of oxygen that one
can take up from the lungs and deliver to
the tissues/minute
• Can range from 1.5 L/min in a cardiac
patient to 3.0 L/min in a sedentary man to
6.0 L/min or greater in an endurance
athlete
• Function of CO and AV O2 difference
– Proportional to increases in SV as training
occurs
 Pulmonary Physiology
• Respiratory neurons in brain stem
– sets basic drive of ventilation
– descending neural traffic to spinal cord
– activation of muscles of respiration
• Ventilation of alveoli coupled with
perfusion of pulmonary capillaries
• Exchange of oxygen and carbon dioxide
 R e s p ir a t o r y C o n t r o l S y s t e m

C e re b ra l C o rte x

M e c h a n o re c e p to rs R e s p ir a t o r y c e n t e r - M e d u lla C h e m o re c e p to rs
N e r v e I m p u ls e s
S p in a l C o r d
F o rc e , N e r v e I m p u ls e s
d is p la c e m e n t R e s p ir a t o r y M u s c le s

L u n g & C h e s t W a ll
V e n t ila t io n
R e s p ir a t o r y m e m b r a n c e
D iffu s io n
P co2, P o2, pH
P e r fu s io n - - - - - > B lo o d
 Respiratory Centers
• Located in brain stem
– Dorsal & Ventral Medullary group
– Pneumotaxic & Apneustic centers
• Affect rate and depth of ventilation
• Influenced by:
– higher brain centers
– peripheral mechanoreceptors
– peripheral & central chemoreceptors
 Muscles of Ventilation
• Inspiratory muscles-
– increase thoracic cage volume
• Diaphragm, External Intercostals, SCM,
• Ant & Post. Sup. Serratus, Scaleni, Levator Costarum
• Expiratory muscles-
– decrease thoracic cage volume
• Abdominals, Internal Intercostals, Post Inf. Serratus,
Transverse Thoracis, Pyramidal
– Under resting conditions expiration is passive and is
associated with recoil of the lungs
 Movement of air in/out of
lungs
• Considerations
– Pleural pressure
• negative pressure between parietal and visceral pleura
that keeps lung inflated against chest wall
• varies between -5 and -7.5 cmH2O (inspiration to
expiration
– Alveolar pressure
• subatmospheric during inspiration
• supra-atmospheric during expiration
– Transpulmonary pressure
• difference between alveolar P & pleural P
• measure of the recoil tendency of the lung
• peaks at the end of inspiration
 Compliance of the lung
 V/P
• At the onset of inspiration the pleural
pressure changes at faster rate than lung
volume-”hysteresis”
• Air filled lung vs. saline filled lung
– Easier to inflate a saline filled lung than an air
filled lung because surface tension forces
have been eliminated in the saline filled lung
 Collapse of the lungs
• If the pleural space communicates with
the atmosphere, i.e. pleural P =
atmospheric P, the lung will collapse
• Causes
– puncture of parietal pleura
• sucking chest wound
– erosion of visceral pleura
– also if a major airway is blocked the air
trapped distal to the block will be absorbed
by the blood and a segment would collapse
Effect of Thoracic Cage on Lung
• Reduces compliance by about 1/2 around
functional residual capacity (at the end of
a normal expiration)
• Compliance greatly reduced at high or low
lung volumes
 Pleural Pressure
• Lungs have a natural tendency to collapse
– surface tension forces 2/3
– elastic fibers 1/3
• What keeps lungs against the chest wall?
– Held against the chest wall by negative
pleural pressure “suction”
 Pleural Fluid
• Thin layer of mucoid fluid
– provides lubrication
– transudate (interstitial fluid + protein)
– total amount is only a few ml’s
• Excess is removed by lymphatics
– mediastinum
– superior surface of diaphragm
– lateral surfaces of parietal pleural
– helps create negative pleural pressure
 Surfactant
• Reduces surface tension forces by forming
a monomolecular layer between aqueous
fluid lining alveoli and air, preventing a
water-air interface
• Produced by type II alveolar epithelial cells
• complex mix-phospholipids, proteins, ions
– dipalmitoyl lecithin, surfactant apoproteins,
Ca++ ions
 Static Lung Volumes
• Tidal Volume
– amount of air moved in or out each breath
• Inspiratory Reserve Volume
– maximum vol one can inspire above normal
inspiration
• Expiratory Reserve Volume
– maximum vol one can expire below normal
expiration
• Residual Volume
– volume of air left in the lungs after maximum
expiratory effort
 Static Lung Capacities
• Functional residual capacity (RV+ERV)
– vol. of air left in the lungs after a normal expir.,
balance point of lung recoil & chest wall forces
• Inspiratory capacity (TV+IRV)
– max. vol. one can inspire during an insp effort
• Vital capacity (IRV+TV+ERV)
– max. vol. one can exchange in a resp. cycle
• Total lung capacity (IRV+TV+ERV+RV)
– the air in the lungs at full inflation
Determination of RV, FRC, TLC
• Of the static lung volumes & capacities,
the RV, FRC, & TLC cannot be
determined with basic spirometry.
• Helium dilution method for RV, FRC, TLC
• FRC= ([He]i/[He]f-1)Vi
• [He]i=initial concentration of helium in jar
• [He]f=final concentration of helium in jar
• Vi=initial volume of air in bell jar
Determination of RV, FRC, TLC
• After FRC is determined with the previous
formula, determination of RV & TLC is as
follows:
• RV = FRC- ERV
• TLC= RV + VC
• ERV & VC values are determined from
basic spirometry
– VC, IRV, IC  with restrictive lung conditions
 Pulmonary Flow Rates
• Compromised with obstructive conditions
– decreased air flow
• minute respiratory volume
– RR X TV
• Forced Expiratory Volumes (timed)
– FEV/VC
• Peak expiratory Flow
• Maximum Ventilatory Volume
 Dead Space
• Area where gas exchange cannot occur
• Includes most of airway volume
• Anatomical dead space (= 150 ml)
– airways
• Physiological dead space
– = anatomical + non functional alveoli
• FRC (2300 ml) - dead space (150 ml) =
2150 ml (alveolar vol.)
 Control of Airway Smooth
Muscle
• Neural control
– SNS-beta receptors causing dilatation
• direct effect weak
• indirect effect predominates
• function unclear
– Parasympathetic-muscarinic receptors causing
constriction
– NANC nerves (non adrenergic, non cholenergic)
• inhibitory release VIP & NO  bronchodilitation

• stimulatory  bronchoconstriction, mucus secretion,

vascular hyperpermeability, cough, vasodilation
“neurogenic inflammation”
 Control of Airway Smooth
Muscle (cont.)
• Local factors
– histamine binds to H1 receptors-constriction
– histamine binds to H2 receptors-dilation
– slow reactive substance of anaphylaxsis-
constriction-allergic response to pollen
– Prostaglandins E series- dilation
– Prostaglandins F series- constriction
 Control of Airway Smooth
Muscle (cont)
• Enviornmental pollution
– smoke, dust, sulfur dioxide, some acidic
elements in smog
• elicit constriction of airways
– mediated by:
• parasympathetic reflex
• local constrictor responses
 Effect of pH on ventilation
• Normal level of HCO3- = 25 mEq/L
• Metabolic acidosis (low HCO3-) will
stimulate ventilation (regardless of CO2
levels)
• Metabolic alkalosis (high HCO3-) will
depress ventilation (regardless of CO2
levels)
 Pulmonary circulation
• Pulmonary artery wall 1/3 as thick as aorta
• RV 1/3 as thick as LV
• All pulmonary arteries have larger lumen
– more compliant
– operate under a lower pressure
– can accommodate 2/3 of SV from RV
• Pulmonary veins shorter but similar
compliance compared to systemic veins
 Total Pulmonic Blood Volume
• 450 ml (9% of total blood volume)
– reservoir function 1/2 to 2X TPBV
– shifts in volume can occur from pulmonic to
systemic or visa versa
• e.g. mitral stenosis can  pulmonary volume
100%
• shifts have a greater effect on pulmonary
circulation
 Systemic Bronchial Arteries
• Branches off the thoracic aorta which supplies
oxygenated blood to the supporting tissue and
airways of the lung. (1-2% CO)
• Venous drainage is into azygous (1/2) or
pulmonary veins (1/2) (short circuit)
– drainage into pulmonary veins causes LV output to be
slightly higher (1%) than RV output & also dumps
some deoxygenated blood into oxygenated
pulmonary venous blood
 Pulmonary lymphatics
• Extensive & extends from all the
supportive tissue of lungs & courses to the
hilum & mainly into the right lymphatic duct
– remove plasma filtrate, particulate matter
absorbed from alveoli, and escaped protein
from the vascular system
– helps to maintain negative interstitial pressure
which pulls alveolar epithelium against
capillary endothelium. “respiratory membrane”
 Pulmonary Pressures
• Pulmonary artery pressure = 25/8
– mean = 15 mmHg
• Mean pulmonary capillary P = 7 mmHg.
• Major pulmonary veins and left atrium
– mean pressure = 2 mmHg.
Control of pulmonary blood flow
• Since pulmonary blood flow = CO, any
factors that affect CO (e.g. peripheral
demand) affect pulmonary blood flow in a
like way.
• However within the lung blood flow is
distributed to well ventilated areas
– low alveolar O2 causes release of a local
vasoconstrictor which automatically
redistributes blood to better ventilated areas
 ANS influence on pulmonary
vascular smooth muscle
• SNS + will cause a mild vasoconstriction
• Parasympathetic + will cause a mild
vasodilitation
 Oxygenation of blood in
Pulmonary capillary
• Under resting conditions blood is fully
oxygenated by the time it has passed the
first 1/3 of pulmonary capillary
– even if velocity  3X full oxygenation occurs
• Normal transit time is about .8 sec
• Under high CO transit time is .3 sec
which still allows for full oxygenation
• Limiting factor in exercise is SV
 Effect of hydrostatic P on
regional pulmonary blood flow
• From apex to base capillary P  (gravity)
– Zone 1- no flow
• alveolar P > capillary P
• normally does not exsist
– Zone 2- intermittant flow (toward the apex)
• during systole; capillary P > alveolar P
• during diastole; alveolar P > capillary P
– Zone 3- continuous flow (toward the base)
• capillary P > alveolar P
– During exercise entire lung  zone 3
Pulmonary Capillary dynamics
• Starling forces (ultrafiltration)
– Capillary hydrostatic P = 7 mmHg.
– Interstitial hydrostatic P = -8 mmHg.
– Plasma colloid osmotic P = 28 mmHg.
– Interstitial colloid osmotic P = 14 mm
• Filtration forces = 15 mmHg.
• Reabsorption forces = 14 mmHg.
• Net forces favoring filtration = 1 mmHg.
• Excess fluid removed by lymphatics
 The lung as an organ of
metabolism
• As an organ of body metabolism the lung
ranks second behind the liver.
• One advantage the lung has over the liver is
the fact that all blood passes through the
lungs with every complete cycle
• Some examples
– Angiotensin I converted to Angiotensin II
– Prostaglandins inactivated in one pass through
pulmonary circulation
 Basic Gas Laws
• Boyle’s Law
– At a constant T the V of a given quantity of gas is
1/ to the P it exerts
• Avogadro’s Law
– = V of gas at the same T & P contain the same #
of molecules
• Charles’ Law
– At a constant P the V of a gas is  to its absolute
T
• The sum of the above gas laws:
– PV=nRT
 PV = nRT
• P=gas pressure
• V=volume a gas occupies
• n= number of moles of a gas
• R= gas constant
• T= absolute temperature in Kelvin(C - 273)
 Additional Gas Laws
• Graham’s Law
– the rate of diffusion of a gas is 1/ to the
square root of its molecular weight
• Henry’s Law
– the quantity of gas that can dissolve in a
fluid is = to the partial P of the gas X the
solubility coefficient
• Dalton’s Law of Partial Pressures
– the P exerted by a mixture of gases is =  of
the individual (partial) P exerted by each gas
Atmospheric Air vs. Alveolar Air
• H2O vapor 3.7 mmHg • H2O vapor 47 mmHg
• Oxygen 159 mmHg • Oxygen 104 mmHg
• Nitrogen 597 mmHg • Nitrogen 569 mmHg
• CO2 .3 mmHg • CO2 40 mmHg
Diffusion across the respiratory
membrane
• Temperature 
• Solubility 
• Cross-sectional area 
• sq root of molecular weight 1/ 
• concentration gradient 
• distance 1/ 
• Which of the above are properties of the gas?
Relative Diffusion Coefficients
• These coefficients represent how
readily a particular gas will diffuse
across the respiratory membrane & is 
to its solubility and 1/ to sq. rt of MW.
– O2 1.0
– CO2 20.3
– CO 0.81
– N2 0.53
– He 0.95
 Alveolar gas concentrations
• [O2] in the alveoli averages 104 mmHg
• [CO2] in the alveoli averages 40 mmHg
 The respiratory unit
• Consists of about 300 million alveoli
• Respiratory membrane
– 2 cell layers
• alveolar epithelium
• capillary endothelium
– averages about .6 microns in thickness
– total surface area 50-100 sq. meters
– 60-140 ml of pulmonary capillary blood
Diffusing capacity of Respiratory
Membrane
• Oxygen under resting conditions
– 21 ml.min/mmHg
– mean pressure gradient of 11 mmHg.
– 230 ml/min
– increases during exercise
• Carbon dioxide diffuses at least 20X more
readily than oxygen
 O2 & CO2 in expired air
• As one expires a normal tidal volume of
500 ml the concentrations of O2 & CO2 
– [O2] start high & fall toward the end of
expiration (159-104 mmHg)
– [CO2] start low & rise toward the end of
expiration (0-40 mmHg)
– the first air expired is from the dead space
– the last 1/2 of expired air is from alveoli
 Alveolar air turnover
• Each normal breath (=tidal volume) turns
over only a small percentage of the total
alveolar air volume.
– 350/2150
• Approximately 6-7 breaths for complete
turnover of alveolar air.
– Slow turnover prevents large changes in gas
concentration in alveoli from breath to breath
 Ventilation-Perfusion ratios
• Normally alveolar ventilation is matched to
pulmonary capillary perfusion at a rate of
4L/min of air to 5L/min of blood
• 4/5 = .8 is the normal V/P ratio
• If the ratio decreases, it is usually due to a
problem with decreased ventilation
• If the ration increases, it is usually due to a
problem with decreased perfusion of lungs
 Ventilation-Perfusion ratios
• A decreased V/P ratio as ventilation goes
to zero
– Alveolar PO2 will decrease to 40 mmHg
– Alveolar PCO2 will increase to 45 mmHg
– Results in an increase in “physiologic shunt
blood”- blood that is not oxygenated as it
passes the lung
 Ventilation-Perfusion ratios
• An increased V/P ratio due to a decreased
perfusion of the lungs from the RV
– Alveolar PO2 will increase to 149 mmHg
– Alveolar PCO2 will decrease to O mmHg
– Results in an increase of physiologic dead
space- area in the lungs where oxygenation is
not taking place “includes non functional
alveoli”
 Transport of O2 & CO2
• Oxygen- 5 ml/dl carried from lungs-tissue
– Dissolved-3%
– Bound to hemoglobin-97%
• increases carrying capacity 30-100 fold
• Carbon Dioxide- 4 ml/dl from tissue-lungs
– Dissolved-7%
– Bound to hemoglobin (and other proteins)-23%
– Bicarbinate ion-70%
 Blood pH
• Arterial blood (Oxygenated)
– 7.41
• Venous blood (Deoxygenated)
– 7.37 (slightly more acidic but buffered by
blood buffers)
– In exercise venous blood can drop to 6.9
 Respiratory exchange ratio
• Ratio of CO2 output to O2 uptake
– R= 4/5=.8
• What happens to Oxygen in the cells
– converted to carbon dioxide (80%)
– converted to water (20%)
• As fatty acid utilization for E increases the percentage
of metabolic water generated from O2 increases to a
maximum of 30%.
• If only CHO are used for energy no metabolic water is
generated from O2, all O2 is converted to CO2
Oxy-Hemoglobin Dissociation
• As Po2 , hemoglobin releases more oxygen
– Po2 = 95 mmHg  97% saturation (arterial)
– Po2 = 40 mmHg  70% saturation (venous)
• Sigmoid shaped curve with steep portion below
a Po2 of 40 mmHg
– slight  in Po2  large release in O2 from Hgb
• Shift to the right (promote dissociation)
– increase temperature
– increase CO2 (Bohr effect) decrease pH
– increase 2,3 diphosphoglycerate (2,3 DPG)
 Carbon Dioxide
• carried in form of bicarbinate ion (70%)
– CO2 + H2O  H2CO3  H+ + HCO3-
– carbonic anhydrase in RBC catalyses reaction
of water and carbon dioxide
– carbonic acid dissociates into H+ & HCO3 -
– Chloride shift
• As HCO3- leaves RBC it is replaced by Cl -

• Bound to hemoglobin (23%)

– reacts with amine radicals of hemoglobin &
other plasma proteins
• Dissolved CO2 (7%)
 Neural control of ventilation
• Goals of regulation of ventilation is to keep
arterial levels of O2 & CO2 constant
• The nervous system adjusts the level of
ventilation (RR & TV) to match perfusion
of the lungs (pulmonary blood flow)
• By matching ventilation with pulmonary
blood flow (CO) we also match ventilation
with overall metabolic demand
 Neural control of ventilation
• Dorsal respiratory group
– located primarily in the nucleus tractus
solitarius in medulla
• termination of CN IX & X
• receives input from
– peripheral chemoreceptors
– baroreceptors
– receptors in the lungs
– rhythmically self excitatory
• ramp signal
• excites muscles of inpiration
– Sets the basic drive of ventilation
 Neural control of ventilation
• Pneumotaxic center
– dorsally in N. parabrachialis of upper pons
– inhibits the duration of inspiration by turning off
DRG ramp signal after start of inspiration
• Ventral respiratory group of neurons
– located bilaterally in ventral aspect of medulla
– can + both inspiratory & expiratory respiratory
muscles during increased ventilatory drive
• Apneustic center (lower pons)
– functions to prevent inhibition of DRG under some
circumstances
 Neural Control of Ventilation
• Herring-Breuer Inflation reflex
– stretch receptors located in wall of airways
– + when stretched at tidal volumes > 1500 ml
– inhibits the DRG
• Irritant receptors-among airway epithethium
– +  sneezing & coughing & possibly airway
constriction
• J receptors - in alveoli next to pulmonary caps
– + when pulmonary caps are engorged or pulmonary
edema
• create a feeling of dyspnea
 Chemical Control of Ventilation
• Chemosensitive area of respiratory center
– Hydrogen ions-primary stimulus but can’t cross
membranes (blood brain barrier-BBB)
– carbon dioxide-can cross BBB
• inside cell converted to H+
• rises of CO2 in CSF- effect on + ventilation faster due
to lack of buffers compared to plasma
– unresponsive to falls in oxygen-hypoxia
depresses neuronal activity
– 70-80 % of CO2 induced increase in vent.
 Chemical Control of
Ventilation
• Peripheral Chemoreceptors
– aortic and carotid bodies
– 20-30% of CO2 induced increase in vent.
– Responsive to hypoxia
• response to hypoxia is blunted if CO2 falls as the oxygen
levels fall
– responsive to slight rises in CO2 (2-3 mmHg) but
not similar falls in O2
– sensitivity altered by CNS
• SNS decreasing flow-increased sensitivity to hypoxia
Respiratory adjustments at birth
• Most important adjustment is to breath
• normally occurs within seconds
• stimulated by:
• cooling of skin
• slightly asphyxiated state (elevated CO2)
• 40-60 mmHg of negative pleural P
necessary to open alveoli on first breath
 Renal Physiology

Glomerular Filtration and Renal

blood flow
 Renal Clearance
• The Amount of a substance in urine
reflects 3 processes
– Glomerular filtration
– Reabsorption of the substance from the
tubule back into blood
– Secretion of the substance from the blood into
the tubular fluid
• Excreted=filtered – reabsorbed + secreted
 Renal Clearance
• Represents the volume of plasma from
which all the substance has been removed
and excreted into the urine per unit time
– Cx = (Ux) (V)/ Px (example in parenthesis)
• Cx = clearance from the plasma (100 ml/min)
• V = Urine flow (1 ml/min)
• Pa = Plasma concentration (1mg/ml)
• Ux = urine concentration (100 mg/min)
 Measurement of GFR
• Clearance of Inulin = GFR
– Polyfructose molecule (m.w. 5000)
– Freely filtered at glomerulus
– Not reabsorbed or secreted
– Amount excreted in urine/min = amount
filtered at glomerulus/min = GFR
– Average GFR = 125 ml/min (7.5 L/hr or
180 L/day)
 Filtration Fraction
• Not all plasma coming into the kidney and
the glomerulus is filtered
• Filtration Fraction (FF) = GFR/RPF
– GFR= glomerular filtration rate
– RPF= renal plasma flow
• FF averages .15 - .20
 Filtration + Reabsorption
• Clearance of Glucose
• Glucose is freely filtered at the glomerulus
– Filtered Load (FL) of glucose = GFR X Pg
• Pg = [glucose]plasma
• Glucose is reabsorbed from the tubular
fluid by cells of the proximal tubule
– Tubular transport maximum for glucose
averages 375 mg/min
• FL < 375 mg/min; all glucose reabsorbed, 0
clearance
• FL > 375 mg/min; some glucose in urine, some
clearance
 Filtration + Secretion
• Clearance of PAH (p-Aminohippuric acid)
• PAH is an organic acid excreted into the
urine by glomerular filtration and tubular
secretion (proximal tubule)
– Total excretion = filtered load + secretion
• Transport Maximum for proximal tubule
(PT) secretion averages 80 mg/min
– Delivery to PT < 80 mg/min: all is secreted
– Delivery to PT > 80 mg/min: excess returned
to circulation
 Physiology of body fluids
• Total body water = (.6) body weight (42 L)
– ECF 1/3 (14 L)
• Interstitial fluid ¾ of ECF- 10.5 L
• Plasma ¼ of ECF- 3.5 L
• Major Cations- Na+
• Major Anions- Cl-
– ICF 2/3 (28 L)
• Major cations- Ca++, Mg++, K+
• Major Anions- Po4=, Protein, organic anions
 Osmolarity vs. Osmolality
• Osmolarity = # of solute particles/ L H2O
– Temperature dependent
• Osmolality = # of solute particles/ Kg H2O
– Temperature independent
• In dilute solutions difference is insignificant
 Tonicity
• Tonicity of a solution is related to its effect
on the volume of a cell
• Solutions can have:
– No effect- isotonic
– Increase volume “swelling” – hypotonic
– Decrease volume “shrinking” – hypertonic
• Related to osmolality and permeability of a
solute across the membrane
– To exert osmotic effects a solute must not
cross the cell membrane
 Oncotic Pressure
• Oncotic pressure is osmotic pressure
generated by large molecules (especially
proteins) in a solution
• Not a major force in considering
movement of water across cell
membranes
• Is a force for fluid movement across
capillary wall, especially the glomerulus
 Specific Gravity
• The total solute concentration in a solution
can also be measured as specific gravity
• Ratio of weight of a solution to an equal
volume of distilled water (sg of distilled
water =1gm/ml)
 Volumes of Body Fluid
Compartments
• Total body water = .6 X body weight (42L)
• ECF = .2 X body weight = 14 L (1/3)
– Interstitial Fluid 10.5 L (3/4 of ECF)
– Plasma 3.5 L (1/4 of ECF)
• ICF = .4 X body weight = 28 L (2/3)
• Volume = amount/concentration
– Total body water – tritiated water
– ECF – inulin, mannitol
– Plasma – tritiated albumin
 Capillary Fluid Exchange
• Starling forces
– Capillary hydrostatic pressure
– Capillary oncotic pressure
– Interstitial hydostatic pressure
– Interstitial oncotic pressure
• Filtration coefficient of Capillary wall
 Cellular fluid exchange
• Fluid volume = osmoles

---------------------------- fluid osmolality

• Addition of 2 L of isotonic NaCl to ECF
– Increase ECF by 2 L, ICF stays constant
• Addition of 2 L of H2O to ECF (2/3 1/3)
– Figure out new fluid osmolality, solve for vol
• Addition of 290 mmoles of NaCl to ECF
– Adds 580 mOsm to ECF, pulls fluid from ICF
 Innervation of the Kidney
• Sympathetic nerve fibers primarily from
the celiac plexus (No parasympathetic)
• Fibers release norepinephrine and
dopamine
• SNS innervated smooth muscle of afferent
and efferent arterioles release renin in
response to SNS +
• SNS + of nephron enhances sodium
reabsorption
 Innervation of the Bladder
• Important in controlling urination
• Smooth muscle of the bladder neck
innervated by SNS from hypogastric
nerves (alpha receptors- constriction)
• Bladder body innervated by Para fibers
from pelvic N cause sustained bladder
contraction
• Sensory fibers innervate the fundus
• Pudendal N innervate skeletal ms. Fibers
of external sphincter causing contraction
 Micturition
• Act of emptying the urinary bladder
• Two processes
– Filling of bladder to a critical level causes it to
contract,
– Neuronal reflex (micturition reflex)
• Autonomic spinal cord reflex that can be inhibited or
facilitated by brain stem and higher centers, eg. Cortex
– sensory signals reflexively cause para stimulation of
detrusor muscle opening bladder neck, allowing urine
to flow
• Process is completed by voluntarily relaxing the
external sphincter
 Renal transport
• Reabsorption-net transport from tubular lumen into the
blood-key element in solute reabsorption is Na+/K+ ATPase
• Secretion-net transport from the blood into the tubular lumen
• Proximal tubule
– Reabsorbs 67% of filtered H2O, Na+, Cl- and other solutes
– Nearly all filtered glucose and amino acids
– Secretes organic cations and anions (metabolic products)
• Loop of Henle
– Reabsorbs 20% of filtered Na+, Cl-, K+, as well as Ca++, HCO3-
and Mg++.
– 20% of H2O absorbed exclusively by descending thin limb
• Distal tubule & collecting duct
– Reabsorbs 12% of filtered Na+ and Cl-, variable amounts of H2O
– Secretes variable amounts of K+ & H+
Hormones from Anterior Pituitary
• Prolactin (leuteotropic) hormone
– stimulates the production of milk
– up regulator of immune function
• Adrenocorticotropic (ACTH)hormone
– development of adrenal glands
– production of cortisol
• Follicle Stimulating Hormone (FSH)
– stimulates gametogenesis (ova & testes)
 More hormones from Ant. Pit
• Luteinizing hormone (LH)
– + production of sex hormones from gonads
– stimulates ovulation & development of corpus
luteum
• Growth hormone or somatotrophin (GH)
– + growth
• Thyrotrophin (TSH)
– + development of thyroid gland and + secretion
of thyroxine
• Melanocyte stimulating hormone (Melanotrophin)
– + pigmentation
 Hypothalamic hormones
• Oxytocin
– produced in paraventricular nucleus
– stored and released from posterior pituitary
– milk let down
– stimulates uterine contraction
• Vasopressin/ADH (Antidiurectic hormone)
– produced in supraoptic nucleus
– stored & released from posterior pituitary
– renal reabsorption of water
– vasoconstriction
 Hypothalamic factors
• Releasing factors stimulate secretion of
anterior pituitary hormones via
hypothalamic-hypophyseal portal system
– anything ending in liberin eg. somatoliberin
• Inhibitory factors are just the opposite of
above
– anything ending in statin. e.g. somatostatin
inhibits secretion of growth hormone
– Dopamine inhibits release of prolactin
 Thyroid/parathyroid
• Thyroxine (T3 & T4)from the thyroid gland
– growth, metabolism
• Calcitonin (TCT) from the thyroid gland
– decreases plasma calcium
– decreases bone breakdown
• Parathormone (PTH) from dark chief cells
of parathyroid gland
– increases plasma calcium
– increase growth
 Adrenal Gland
• Cortisol - from Zona Faciculata (cortex)
– Increases blood glucose
– Increases metabolism
– Decreases immune response
• Aldosterone-Zona Glomerulosa-(cortex)
– Increases renal reabsorption of sodium
and renal excretion of potassium & H+
– Increases blood pressure
 Pancreas Hormone
• Insulin from Beta cells- Pancreas
– Decrease blood glucose
• Glucagon - from Alpha cells - Pancreas
– Increase blood glucose
 Kidney hormones
• Somatomedin - from kidney & Liver
– Stimulate growth
– Decrease blood glucose
• Vitamin D - from liver plus kidney
– Increase plasma calcium
– Increase growth
• Erythropoietin -from kidney
– Increase production of RBC’S
 Sex Hormones/Gonadal/males
• Androgens - from interstitial cells of leydig
-Testes
– Increase male phenotypic characteristics
– Stimulate growth
 More Sex
hormones/gonads/female
• Estrogens - from corpus luteum & placenta
– Stimulates female characteristics
– Stimulate birth process -contraction of uterus
– Stimulate growth
• Progesterone - from corpus luteum
– Stimulate female characteristics
– Decrease uterine contraction
– Stimulate growth
 Other important hormones
• Beta Endorphins - Ant. Pit, Hypothalmus
– Decrease pain
• Angiotensin II –Converted from Angio I in
lungs by converting enzyme
– Increase secretion of aldosterone
– Stimulate vasocontriction
• Melatonin - from Pineal gland
– Increase immune response & sleep
• Pheromones
– Reacts to external stimuli, stimulates aggression,
sexual attraction
 Gastrointestinal Physiology
• Ingestion
• Digestion
• Absorption
• Regulation of GI function
 Ingestion-Chewing
• Chewing functions to:
– Mix food with saliva
– Reduces size of food particles
• Facilitates swallowing
– Mixes CHO with salivary amylase
• Begins CHO digestion
 Ingestion-Swallowing
• Voluntary Phase – oral phase
– Initiated in the mouth when tongue forces a bolus of
food back toward the pharynx which contain a high
density of somatosensory receptors
• Involuntary Phase – pharyngeal & esophageal
– Reflex arc
• receptors located near pharynx send signal via IX & X CN
• Motor output from MO to striated muscle of pharynx & upper
esophagus
– Pharyngeal
• Soft palate pulled upward, epiglottis closes off larynx, upper
esophageal sphincter relaxes, peristalsis initiated
– Esophageal (lower 2/3 smooth muscle)
• Peristaltic waves (1-2) to clear esophagus
 Digestion physiology
• Alimentary tract provides the body with a
continual supply of water, electrolytes, nutrients
• In order to do this requires:
– ingestion of food
– Movement of food through the digestive tract
– Secretion of digestive juices
– Digestion and absorption
– Circulation of blood through the GI organs
– Control of these functions by the neuroendocrine
system
 Peristalsis
• Controlled by the enteric nervous system
– Myenteric plexus which lies between circular
and smooth muscle layers
• Increased activity results in
– Increased tone
– Increased intensity of rhythmic contractions
– Increased rate (slight)
– Increased velocity which creates more rapid peristaltic
waves
– Parasympathetic-Acetylcholine excites
– SNS-Norpinephrine/Epinephrine will inhibit
 Hormones of the gut
• Cholecystokinin
– Secreted by “I” (APUD) cells from mucosa of
duodenum/jejunum in response to breakdown
products of fats
• Increased contractility of the gallbladder to release bile which
emulsifies fats
• Inhibits stomach motility
• Secretin
– Secreted by “S” (APUD) cells from mucosa of
duodenum in response to acidic gastric juice
• Mild inbitory effect on gut motility
• Inhibits gastrin secretion
 Hormones of the Gut
• Gastrin
– Stimulates gastric acid [H+] secretion
– Stimulates pancreatic enzyme secretion
– Gall bladder contraction
– Gastrin is stimulated by PNS, proteins, gut
distension, and inhibited by acids and secretin
• Gastric inhibitory peptide (GIP)
– Stimulation of insulin secretion
– Secreted in response to all 3 types of nutrients
• Glucose, AA, FA
– Secreted by duodenal and jejunal mucosa
 Paracrines
• Synthesized in endocrine cells of GI tract
• Act locally via diffusion
• Somatostatin
– Secreted in response to low pH
– Inhibits secretion of other GI hormones
– Inhibits gastric H+ secretion
• Histamine
 H+ secretion