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 neurophysiologists
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 ( Meissners)
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
Merkels discs
punctate receptive fields

Ruffini end organs (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
Meissners 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
Meissners 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
Merkels discs have punctate receptive fields
(superficial)
senses curvature of an objects surface

Ruffini end organs activated by stretching the

skin (deep)
even at some distance away from receptor

Mechanoreceptors in Glabrous
(non hairy) Skin

Rapid
adaptation

Slow
adaptation

Superficial
Small field

Deep
Large field

Meissners
Corpuscle

Pacinian
Corpuscle

Merkels
Disc

Ruffini
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 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
Messiners, others by slowly adapting Merkels,
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
A delta fibers
glutamate
neospinothalamic
mechanical, thermal
good localization
sharp, pricking
terminate in VB
complex of thalamus

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

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

Central
Direct electrical + to
brain -> analgesia
Nociceptive control
pathways descend to
cord
Endogenous opiods

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

Spindles and GTOs

As a muscle contracts against a load:
Spindle activity tends to decrease
GTO activity tends to increase

As a muscle is stretched
Spindle activity increases
GTO activity will initially decrease

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

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 EdingerWestphal 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
Eye
Elevate
Depress
Torsion

Adducted
Eye

Superior rectus

Inferior oblique

Inferior rectus

Superior oblique

Superior oblique
Inferior oblique

Superior rectus
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
Reissners 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
1000s of taste buds on side
circumvallate-stout central stalks in serous filled
moats with taste buds on sides in fluid

40-50 modified epithelial cells grouped in

barrel shaped aggregate beneath a small
pore which opens onto epithelial surface

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 postcentral 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 Bowmans 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 doesnt relay via
thalamus (from lateral pathway)
learned control/adversion

Newer- passes through the thalamus to

orbitofrontal cortex (from lateral pathway)
- conscious analysis of odor

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 (Auerbachs)
between longitudenal & circular muscle layer
controls gut motility
can coordinate peristalsis in intestinal tract that has
been removed from the body

excitatory motor neurons release Ach & sub P

inhibitory motor neurons release Dynorphin &
vasoactive intestinal peptide

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 bodys 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
Wernickes & 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
toward + elect.

deflection

Moving
deflection
toward - elect.

deflection

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
Ohms 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= 8l/ 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
RT = R1 + R2 + R3 + RN
RT = sum of individual Rs

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 RBCs

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 RBCs

in small vessels cells line up which

decreases viscosity and offsets the above to
some degree (Fahaeus-Lindquist)

Hematocrit
% of packed cell volume (10 RBCs)
Normal range 38%-45%

Laminar vs. Turbulent Flow

Streamline
silent
most efficient
normal

Cross mixing
vibrational noise
least efficient
frequently associated
with vessel disease
(bruit)

Reynolds 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
RBCs 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 arterialvenous 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

Coronary-250 ml/min
Brain-750 ml/min
Organs-3100 ml/min
Inactive muscle-650
ml/min
Active muscle-650
ml/min
Skin- 500 ml/min

Exercise = 24 L/min

Coronary-1000 ml/min
Brain-750 ml/min
Organs-600 ml/min
Inactive muscle-300
ml/min
Active muscle-20,850
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 ,
d is p la c e m e n t

N e r v e I m p u ls e s
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 e r fu s io n - - - - - > B lo o d

P co2, P o2, pH

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 mls

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 anaphylaxsisconstriction-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

Boyles Law
At a constant T the V of a given quantity of gas is
1/ to the P it exerts

Avogadros 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

Grahams Law
the rate of diffusion of a gas is 1/ to the
square root of its molecular weight

Henrys Law
the quantity of gas that can dissolve in a fluid
is = to the partial P of the gas X the solubility
coefficient

Daltons 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

Oxygen 159 mmHg
Nitrogen 597 mmHg
CO2 .3 mmHg

H2O vapor 47 mmHg

Oxygen 104 mmHg
Nitrogen 569 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 cant 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 of ECF- 10.5 L

Plasma 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++, HCO3and Mg++.
20% of H2O absorbed exclusively by descending thin limb

Distal tubule & collecting duct

Reabsorbs 12% of filtered Na+ and Cl-, variable amounts of H 2O
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 RBCS

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