Plasma Membrane Transport and Cell Physiology Notes

Lecture: Plasma Membrane and Transport
I. Structure of the Plasma Membrane
A. plasma membrane - the surface encapsulating a cell
B. Fluid Mosaic Model
1. bilayer of phospholipids
a. hydrophilic heads - P04 end "water"
"loving" attracted to water on inner/outer
parts of cell
b. hydrophobic tails - fatty acids "water"
"fearing" attracted to each other on inside
of bilayer
c. glycolipids - some carbohydrates attached
to outer lipids (involved in cell to cell
recognition)
d. cholesterol - regulates fluidity of
membrane
2. proteins interspersed throughout the membrane
a. functions of membrane proteins
i. receptors - hormones, neurotransmitters
ii. enzymes - reactions in & out of cell
iii.transport - ions and molecules
b. integral proteins - inserted into the bilayer
i. transmembrane - across entire bilayer

c. peripheral proteins - on inner & outer surface
d. glycoproteins - carbohydrates on outer surface
i. glycocalyx - outer carbohydrate coat (cell recognition and identification)
3. plasma membrane is fluid: it can easily shift
& flow
a. two layers can slide over one another
b. some proteins float freely throughout
membrane
c. many proteins attached to cytoskeleton
i. allows for regional specialization
4. Features of Plasma Membrane
a. microvilli - fingerlike extensions of cell
i.found in kidney and intestine
ii. increases surface area for absorption
iii. actin filaments for support
b. tight junctions - cell-cell adhesion proteins
i.generally at surface of epithelium
ii. prevent passage between cells
iii. "seal" layer of cells into a sheet
c. desmosomes - anchor cells to cells &
basement
i. carbohydrates of glycoprotein
intermingle
ii. keratin filaments anchor to cytoplasm
iii. hemidesmosome - anchor to basement
membrane
II. Plasma Membrane Transport
A. General Features
1. interstitial fluid - bathes all cells and tissues
a. released by capillaries into organs/tissues
b. recaptured by lymph vessels back to heart
c. contains salts, nutrients, hormones, etc.

2. selectively permeable - only certain things pass
a. passive transport - nature does the work
b. active transport - cell must use energy
(ATP)
B. Passive Transport Processes (no cellular energy required)
1. diffusion - movement of particles from area
of HIGH concentration to area of LOW
concentration until equal
a. concentration gradient - difference in
concentration between HIGH and LOW
areas
i. larger gradient - larger driving force
ii. faster = higher temperature or smaller
particle
2. simple diffusion across the cell membrane
a. nonpolar molecules (oxygen, carbon
dioxide, urea)
i. oxygen blood (high)  cells (low)
ii. CO2 cells (high)  blood (low)
iii. urea cells (high)  blood (low)
b. fat soluble molecules (small fats and
steroids)
3. osmosis - the movement of a solvent (such as WATER) from an area of LOW solute
concentration (such as NaCl) to an area of HIGH solute concentration
solution = solvent + solute
(dissolving liquid) (dissolved particles)
a. molarity - moles of solute / liters of solvent (moles/liter = Molar)
i. mole - grams of substance = mol. wt. substance
l mole H = 1 gram H
1 mole C = 12 grams C
1 mole NaCl = 58 grams NaCl
1 mole C6H12O6 = 180 grams C6H12O6

58 grams NaCl/l liter water = 1 mole NaCl/liter = 1 Molar NaCl (lM NaCl)
180 g Glucose/1 liter water = 1 mole glucose/liter = 1 Molar glucose (1M Glucose)
b. osmolarity - measure of concentration of
particles in a solution
i. 1 molar Glucose = 1 osmol Glucose
ii.1 molar NaCl = 2 osmol NaCl
WHY? in water NaCl dissociates  Na+
+ Cl-
(for each salt molecule their are 2 parts)
Movement Across Membrane Permeable to Water Only (not solutes)
Conditions Water Movement Terminology
osmo(in) = osmo(out) no net movement isotonic
osmo(in) > osmo(out) water moves IN inside is hypertonic
osmo(in) < osmo(out) water moves OUT inside is hypotonic
c. osmotic pressure - driving force generated by
the concentration gradient
*the larger the difference in concentrations between the INSIDE and OUTSIDE, the larger the
osmotic pressure (driving force is greater)
d. hydrostatic pressure - pressure of cell wall in plant cells that balances the osmotic
pressure, preventing more water from entering the cell
e. observable implications of osmosis
i. crenate - water moves out and cell shrinks
ii. lyse - water moves in and cell bursts
f. clinical implications of osmosis
i. isotonic I.V. - Ringers (0.9% NaCl; 5% glucose)
ii. hypertonic I.V. - to treat edema (water excess)
iii. hypotonic I.V. - to treat dehydration

4. filtration - hydrostatic pressure > osmotic
pressure (Squeezing a leaky water balloon)
a. WATER moves from HIGHER osmo  LOWER osmo
5. facilitated diffusion - see-saw protein carries across or channels allow through (goes
with the concentration gradient so it is still a form of passive transport)
a. carrier protein - "open outside" <-> "open inside"
i. very specific for the molecule transported
ii. uses energy of natural diffusion (water-
wheel)
iii. glucose carrier is typical
b. protein channels - passage of charged & polar
i. Na+
, K+
, Cl-
channels are very specific
can be opened or closed on command
C. Active Transport Processes (energy of the cell required)
1. active transport - transport solutes against a concentration gradient (goes against
diffusion)
a. solute pumps - Na+
, K+
, Ca++
, amino acids
(relies on ATP energy source)
i. rely on energy of ATP to overcome forces of nature
ii. uniport - one specific particle only
iii. coupled system - two particles together
symport - same direction
antiport - opposite directions
b. Na+
-K+
ATPase Pump - creates ion concentration gradient for cell [Na+
]OUT HIGH;
[K+
]IN HIGH
i. ATP is used by this pump to move 3 Na+
out of the cell and bring 2 K+
into the
cell
ii. Na+
will want to move INTO cell; K+
will want to move OUT of cell
2. bulk transport - cell membrane pouching process
a. exocytosis - cell vesicle moves to

membrane with contents, merges, then
releases material
i. hormone/neurotransmitter release; mucus secretion; expulsion of
extracellular proteins (collagen, elastin, matrix)
b. endocytosis - engulfment by cell membrane pouch which then buds off into the
cytoplasm
i. phagocytosis ("eat" "cell"" process") - plasma membrane raps around large
mass
(bacteria, dead cell, cell debris)
phagosome  lysosome (digestive enzymes)
macrophages - immune cells that engulf
ii. pinocytosis - "drink" "cell"" process"
iii. receptor-mediated endocytosis -
receptors on the cell surface bind to
desired molecule before the
engulfment
insulin, low density lipoproteins (LDL), and Fe++
can be ligands for such receptors
III.The Resting Membrane Potential (voltage across the membrane)
A. voltage - energy that results from separation of charges (also called potential difference
- potential)
1. The Na+
-K+
ATPase Pump creates concentration gradients for both Na+
and K+
a. [Na+
]OUT > [Na+
]IN
b. [K+
]IN > [K+
]OUT
2. Results in NET flow of positive charge out of the cell
1 cycle = 3Na+
out & 2K+
in
3. Na+
Channels normally closed so that Na+
cannot easily move back into the cell.

4. K+
Channels normally slightly open so that K+
can slowly leak out
5. The net movement of Na+
and leaking of K+
to the outside of the cell causes a
POTENTIAL DIFFERENCE (voltage) across the membrane.
6. resting membrane potentials for cells generally range: -20 mV to -200mV
7. electrochemical gradient - charge & concentration
i. Na+
: {electro-IN; chemical-IN}
ii. K+: {chemical-OUT = electro-IN}
IV.Functions of Glycoproteins on Cell Membrane (Glycocalyx)
A. Determination of ABO Blood Types
1. Sugar moiety on glycoprotein of red blood
cell (RBC)
a. signature for immune response of foreign blood
B. Binding of Dangerous Toxins
1. proteins of cholera and tetanus bind to cell by identifying specific carbohydrates
on proteins
C. Identification of Specific Cell Types
1. Sperm knows egg by specific glycoproteins
2. Cell-cell interaction during embryogenesis and tissue differentiation
3. Immune cells identifying foreign cells and material such as bacteria, viruses, and
cancer cells

Lecture: Physiology of Hearing and Equilibrium
I. Physical Characteristics of Sound
A. Sound as Vibration of Air Molecules Traveling in Waves
1. vibration of medium - sound travels in compression waves through a particular
medium
a. solid-------------> liquid ----------------> gas
fastest slowest
2. sound as a wave - the series of high pressure and low pressure areas are called
“compressions” and “rarefactions”, respectively
a. sine wave - graphic representation of areas of compression and
rarefaction of a sound wave
b. wavelength - the distance between 2 areas of compression for a
given sound wave
c. frequency - the number of waves that pass a given point in one
second (1/s = 1 Hertz)
i. short wavelength/high frequency - high pitched tones
ii. long wavelength/low frequency - low pitched tones
iii. human frequency range - 20Hz - 20,000 Hz (2-3 Hz
distinction)
d. amplitude - intensity of energy in a given wave of sound; signified by
height of sine wave
i. loudness - subjective interpretation of the intensity of a sound
ii. decibel - logarithmic scale to measure the intensity of sound waves
Energy in the Sound Wave Perceived Loudness
0 dB threshold for audibility barely audible
10 dB l0 X 0 dB 2 X 0 dB
20 dB 100 X 0 dB 4 X 0 dB
30 dB 1000 X 0 dB 8 X 0 dB
40 dB 10,000 X 0 dB 16 X 0 dB
iii. human amplitude range - 0 dB - 120 dB (130 dB = pain level)

II. Transmission of Sound to the Inner Ear
air -->
external auditory canal -->
tympanic membrane (ear drum) -->
ossicles (malleus, incus, stapes.) -->
oval window of cochlea -->
vibration of cochlear fluid -->
basilar membrane of cochlea
III. Resonance of Basilar Membrane & Excitation of Hair Cells
A. Resonance of Basilar Membrane
1. vibration of oval window -> perilymph vibration
2. for 20 - 20,000 Hz only, vibration of vestibular membrane
3. vestibular membrane vibration -> endolymph vibration
4. endolymph vibration -> vibration of basilar membrane
5. basilar membrane “fibers” of different length, thickness, and tension like strings of a
piano
a. resonance - different fibers of basilar membrane have different “natural
frequencies”
b. SPECIFIC parts of basilar membrane vibrate only at SPECIFIC frequency (pitch)
B. Excitation of Hairs Cells of Organ of Corti
1. cochlear hair cells - rest on the basilar membrane, contain "stereocilia" which project into
the "tectorial membrane" just above
a. basilar m. vibration -> hair cell vibration
b. hair cell vibration -> opening/closing channels
c. depolarization/hyperpolar -> cochlear nerve
d. cochlear nerve impulses -> to brain
IV. Anatomical Pathway to the Brain
cochlear nerve (vestibulocochlear VIII)->
spiral ganglion -->
cochlear nuclei (medulla) -->
superior olivary nucleus -->
lateral lemniscal tract -->
inferior colliculus -->
medial geniculate body of thalamus -->
auditory cortex (superior temporal lobe)

V. Processing of Auditory Information
A. Perceiving Pitch (Frequency) - location of vibration on the basilar membrane
B. Perceiving Differences in Loudness (Intensity) - amplitude increases, more hair cells of the
basilar membrane (with same pitch) are activated
C. localizing Source of Sound
1. superior olivary nucleus - first point where sound from both ears come together
a. relative intensity - the amplitude of sound waves hitting the different ears
b. relative timing - the difference in timing in which a sound reaches both ears
VI. Typical Hearing Disorders
A. conduction deafness - disruption in sound vibrations to basilar membrane (ext & mid ear)
1. blocked auditory canal (wax, fluid)
2. perforated tympanic membrane (eardrum)
3. otitis media - middle ear infection/inflammation
4. otosclerosis - hardening of the earbone joints
B. sensorineural deafness - disruption anywhere in pathway from hair cells to the auditory cortex
1. loss of hair cells (explosion, chronic loud noise)
2. damage to vestibulocochlear nerve (VIII)
3. damage to nuclei/tracts to the cortex
C. tinnitus - chronic perception of clicking or ringing
1. sudden blow to the tympanic membrane
2. gradual deterioration of afferents in cochlear nerve
D. Menierre's Syndrome - effects both hearing and balance; results in tinnitus, vertigo, and
interspersed nausea and vomiting
1. may be too much endolymph beneath basilar membrane
2. symptoms can be treated somewhat with drugs
3. endolymph may be drained periodically
4. hearing loss is progressive
VII. Equilibrium and Balance: The Vestibular Apparatus

A. Linear Movement: The Maculae of the Vestibule
1. vestibule - bony cavity of the inner ear between the cochlea and the semicircular canals
a. saccule and utricle - smaller sacs housed within the vestibule
b. maculae - patch of "supporting cells" and "hair cells" along the utricles and
saccules
i. hair cells - like hair cells of basilar membrane, respond when bent
c. otolithic membrane - jelly-like sheet that abuts the "stereocilia" of the hair cells
i. otoliths - "ear stones" that rest on top of the otolithic membrane
2. horizontal acceleration - maculae of UTRICLE is in the horizontal plane; hairs bend
when motion is FORWARD/BACKWARD
3. vertical acceleration - maculae of SACCULE is in the vertical plane; hairs bend when
motion is UP/DOWN
B. Angular Movement: The Crista of Semicircular Canals
1. semicircular canals - three bony "hula-hoop" extensions of vestibule in three different
planes
2. crista ampullaris - like maculae, contain hair cells that respond to flow of endolymph in
canals
a. cupula - like otolith membrane, gelatinous "cap" into which hair cells project
3. change in angular (rotational) acceleration - movement of the head in non-linear (circular
or angular) direction is monitored by three canals
4. vestibular nystagmus - movement of eyes to remain fixed on object when on "merry-go-
round"
5. vertigo - false feeling of gravity or motion
C. Equilibrium Pathway: Coordinating Inputs in Brain
activated hair cells of crista ampularis ->
afferent axon fibers (vestibulocochlear nerve) -> vestibular nuclear complex OR cerebellum
1. vestibular nuclei - also receive input from eyes and somatic proprioceptors; coordinates
information to help control motion of eyes, neck, limbs
2. cerebellum - also receives input from eyes and somatic proprioceptors; coordinates
information to help regulate head position, posture, and balance
D. Problems with Equilibrium

1. dizziness, nausea, imbalance, vomiting
2. motion sickness - conflict between visual/somatic inputs and action of the vestibular
apparatus
a. Bonine, Dramamine, Scopolamine - block inputs from vestibular apparatus to the brain

Lecture: Physiology of Vision
I. Overview of Light and Optics
A. Wavelength and Colors of Visible Radiation
1. electromagnetic radiation
gamma rays X-rays UV light VISIBLE LIGHT Infrared Radio Wave
short medium long
(10-5
nm) (380-750 nm) (102
nm)
2. wave-photon duality - light travels in wave-like fashion with "single packets"
of energy called photons
3. visible spectrum - different colors of light have different wavelengths
Violet Blue Green Yellow Orange Red
380nm 480nm 550nm 630nm 680nm 730nm
4. color of an object - the color of an object is determined by which
wavelengths are REFLECTED back to the retina (not absorbed by the object)
a. white - all wavelengths reflected by object
b. black - all wavelengths absorbed by object
B. Refraction of Light and Convex Lenses
1. light refraction - light will bend when it passes from one medium (air)
into another (lens) e.g. pencil in glass of water
2. convex lens - (thicker at center, tapered at edge) causes light to bend so
that it comes together at a focal point
a. real image - image at focal point of convex lens ---> inverted &
reversed
3. focusing light on the retina
a. cornea - constant (unchanging) refraction
b. lens - can change refraction and focal length; ciliary muscles

change convexity of the lens
4. Focusing for Distance Vision
a. far point of vision - distance beyond which lens will not change its
shape (about 20 feet) (flattest point of the lens)
b. emmetropic eye - normal, healthy eye
5. Focusing for Close Vision
Less than 6 feet, several adjustments are made:
a. accommodation of lens - lens shape becomes more convex, light
rays bend more sharply, shorter focal length for the closer object (ciliary
muscles for lens)
i. near point of vision - shortest distance for focusing
(maximum convexity of lens); about 8-10 inches; gets worse with
age
ii. presbyopia - poor close vision in elderly; inelasticity of the
lens
b. accommodation of pupils - constriction of pupils; better focus, less
divergent rays (constrictor muscles of iris)
c. convergence of eyes - eyes rotate medially to keep image on center
of the retina (medial rectus muscles of eyeballs)
C. Vision Problems Related to Refraction
1. myopia ("nearsighted") - distant objects are blurred; distant objects are
focused in front of the retina, rather than directly on it
a. eyeball too long; lens too strong
b. concave lens can correct light before eye
2. hyperopia ("farsightedness") - close objects are blurred; close objects are
focused beyond the retina, rather than directly on it
a. eyeball too short; poor refraction of a lens
b. convex lens can correct light before eye
3. astigmatism - blurry images at all distances; unequal curves on lens and/or
cornea, creating discontinuous image on the retina

II. Anatomy, Biochemistry, & Physiology of Photoreceptors
A. Functional Anatomy of Photoreceptors
1. General Structure of Rods and Cones
"pigmented base" of retina outer segment (pigmented discs)
connecting stalk
inner segment (mitochondria)
outer fiber
cell body (nucleus)
inner fiber
synaptic ending
"neural layer" bipolar cell
ganglion cell (axons carried to brain by optic nerve)
a. outer segment - contain membrane-bound discs with pigments that absorb and
react to light
i. rods - pigment discs stacked like pennies all the way to the base,
membranes are DISTINCT from the plasma membrane
1. sensitive to dim light (night vision)
2. respond to ALL wavelengths (colors)
3. only "grey" information to the brain
4. 100 rods per ganglion cell to brain
5. widely spread throughout the retina
6. not good for visual acuity
ii. cones - pigment discs taper off toward the base, membranes are
CONTINUOUS with the plasma membrane
1. require bright light for stimulation
2. different cones have different pigments specific for certain
wavelengths (colors)
3. can convey color information to brain
4. 1-3 cones per ganglion cell to brain
5. primarily concentrated in fovea (center)
6. essential for visual acuity
B. Biochemistry of Visual Pigments

1. opsin - transmembrane protein in the membrane of pigmented discs of
rods and cones
2. retinal - light absorbing molecule that changes shape when struck by a
photon of light
a. vitamin A - precursor to retinal (eat your carrots!!!!!!)
b. 11-cis isomer of retinal - non-activated form of retinal, prior to
absorption of photon energy; has a "kinked" double bond
c. all trans isomer of retinal - activated form of retinal, after struck by
photon of light; double bond straightens out
C. Excitation of Rods
1. rhodopsin - visual pigment in rods; in membranes of pigmented discs of
outer segment
2. bleaching of pigment - breakdown of rhodopsin after the absorption of
light
11-cis retinal  rhodopsin  all-trans retinal
+ scotopsin light + scotopsin
3. all-trans retinal - causes HYPERPOLARIZATION of rod
a. Na+
channels (open in dark) are closed
b. rod is hyperpolarized (increased negativity)
c. Ca++
channels in synapse close
d. less neurotransmitter released by the rod
D. Excitation of Cones
1. photopsins - 3 distinct pigments in cones are sensitive to 3 different parts of
visible spectrum
a. blue cones - maximum sensitivity at 455 nm
b. green cones - maximum sensitivity at 530 nm
c. red cones - maximum sensitivity at 625 nm
2. different colors - differential activation of each of the three different cones
3. color blindness inherit gene for one of the photon proteins that is deficient
(mainly male), most common are red and green mutations
E. Light and Dark Adaptation of Rhodopsin

1. light adaptation - very dark  very bright
a. rhodopsin in rods is quickly bleached out
b. sensitivity to shallow light disappears
c. rods are inhibited by other retinal cells
d. cones are activated to take over (5 mins.)
e. consensual pupil reflex - constriction
2. dark adaptation - very bright  very dark
a. cones are gradually cease to be stimulated
b. "bleached out" rods can produce rhodopsin
c. rods eventually take over in the dim light
d. pupillary dilation - pupils increase size
3. nyctalopia (night blindness) - deficiency in function of rods during dim-light
situations
a. vitamin A deficiency is general cause
III. The Visual Pathway: Photoreceptors to Occipital Cortex
RETINA photoreceptors (rods & cones) ->
bipolar cells ->
ganglion cells (axons = optic nerve) ->
AXON PATH optic nerves (from each eye retina)
optic chiasma (medial fibers cross over)
optic tracts (opposite visual field)
THALAMUS lateral geniculate body of thalamus ->
AXON PATH optic radiation (fibers to cortex)
CEREBRAL CORTEX occipital lobe - primary visual cortex
other brain areas that receive visual information:
1. superior colliculi - for control of extrinsic eye muscles
2. pretectal nuclei - mediate pupillary light reflexes
3. suprachiasmatic nucleus of hypothalamus - circadian rhythm
IV. Binocular Vision and Depth Perception

A. binocular vision - two eyes have overlapping regions of the visual field, so that
the same point is seen from slightly different angles
1. depth perception - a result of binocular vision in which person can perceive
relative distances based on information gathered in both eyes

Lecture: Circulatory Physiology
I. Factors Involved in Blood Circulation
A. Blood Flow - the actual VOLUME of blood moving through a particular site (vessel or organ)
over a certain TIME period (liter/hour, ml/min)
B. Blood Pressure - the FORCE exerted on the wall of a blood vessel by the blood contained within
(millimeters of Mercury; mm Hg)
blood pressure = the systemic arterial pressure of large vessels of the body (mm Hg)
C. Resistance to Flow (Peripheral Resistance) - the FORCE resisting the flow of blood through a
vessel (usually from friction)
1. viscosity - a measure of the "thickness" or "stickiness" of a fluid flowing through a pipe
a. V water < V blood < V toothpaste
b. water flows easier than blood
2. tube length - the longer the vessel, the greater the drop in pressure due to friction
3. tube diameter - smaller diameter = greater friction
D. Relation Between Blood Flow, Pressure, Resistance
difference in blood pressure ( P)
Blood Flow (F) =
peripheral resistance (R)
a. increased P -> increased flow
b. decreased P -> decreased flow
c. increased R (vasoconstriction) -> DECREASED flow
d. decreased R (vasodilation) -> INCREASED flow
II. Systemic Blood Pressure
A. Blood Pressure Near the Heart
1. HEART produces blood pressure by pumping the blood
2. Blood pressure decreases with distance from Heart
3. systolic arterial blood pressure - pressure in aorta (& major arteries) in middle of
ventricular contraction (120 mm Hg in healthy adult)
4. diastolic arterial blood pressure - pressure in aorta (& major arteries) during ventricular
diastole, when semilunar valves are closed (80 mm Hg in healthy adult)

5. mean arterial pressure (MAP) - the "average" blood pressure produced by the heart (93
mm Hg in healthy adult)
mean arterial pressure = diastolic pressure + 1/3 pulse pressure
** pulse pressure = systolic pressure - diastolic pressure
6. blood pressure decreases throughout system
L ventricle -->120 mm Hg
arteries -->120 - 60 mm Hg
arterioles -->60 - 40 mm Hg
capillaries -->40 - 20 mm Hg
venous -->20 - 10 mm Hg
R atrium -->10 - 0 mm Hg
7. venous return - venous blood pressure is so low, other factors contribute to venous blood
flow
a. respiratory pump - breathing action of thorax "squeezes" blood back toward the heart
b. muscular pump - contraction/relaxation of skeletal muscles "milk" blood up veins to
heart
III. Factors Affecting Blood Pressure
A. Cardiac Output ( = stroke volume X heart rate)
CO = SV (ml/beat) x HR (beats/min)
= 70 ml/beat x 60 beats/min = 4200 ml/min
1. increased cardiac output -> increased blood pressure
2. increased stroke volume -> increased blood pressure
3. increased heart rate -> increased blood pressure
B. Peripheral Resistance
1. arteriole constriction ---> increased blood pressure
2. resistance inversely proportional to the "fourth power" of the radius change
C. Blood Volume
1. hemorrhage - decrease in blood pressure
2. salt/fluid - increase in blood pressure
3. polycythemia - increase in blood viscosity
4. RBC anemia - decrease in blood viscosity

IV. Regulation of Blood Pressure
A. Nervous System Control
1. control of arteriole diameter
2. directs blood flow to proper organs and tissues that need it
3. REFLEX PATHWAY:
baroreceptors/chemoreceptors/brain -->
afferent nerve fibers -->
medulla (vasomotor center) -->
vasomotor (efferent) nerve fibers -->
smooth muscle of arterioles
B. Vasomotor Fibers to Smooth Muscle of Arterioles
1. sympathetic fibers that release norepinephrine (NE); cause vasoconstriction of arterioles
C. Vasomotor Center of the Medulla
1. sympathetic neuron cell bodies in the medulla
2. receive input from baroreceptors, chemoreceptors, and brain
3. vasomotor tone - general constricted state of arterioles set by vasomotor center
D. Baroreceptors
1. blood pressure receptors large arteries (carotid sinuses, aortic arch, neck/thorax arteries)
2. send blood pressure information to vasomotor center of medulla
increased pressure --> decreased pressure -->
inhibits vasomotor center --> stimulates vasomotor center ->
vasodilation vasoconstriction
E. Chemoreceptors
1. located in aortic arch and carotid arteries
a. carotid and aortic bodies
2. monitor OXYGEN and pH levels of the blood
low OXYGEN or low pH -------> increase blood pressure, return blood to lungs quickly
F. Higher Brain Centers Control on BP
1. hypothalamus & cortex also effect vasomotor area
G. Chemical Controls of Blood Pressure

1. hormones of adrenal medulla - "fight-or-flight" response to fear; release of
norepinephrine and epinephrine from adrenal medulla; causes vasoconstriction and
increased BP
2. atrial natriuretic factor (ANF) - secreted by the atria of the heart, promotes general
decline in blood pressure kidney releasing more Na+
and water, reducing fluid volume
3. antidiuretic hormone (ADH) - released by the hypothalamus, causes increase in blood
pressure by getting the kidneys to conserve water in the body; e.g. during hypotensive
situations
4. endothelium derived factors
a. endothelin - strong vasoconstrictor
b. endothelium derived relaxing factor - vasodilation
5. alcohol - causes vasodilation
H. Renal (Kidney) Regulation
1. direct regulation - fluid loss through urine
a. low pressure/volume --> conserve water
b. high pressure/volume --> release more water
2. renin-angiotensin mechanism
low blood pressure -->
release of renin -->
formation of angiotensin II--> vasoconstriction
release of aldosterone --> Na+
/water reabsorption (by kidney)
V. Variations in Blood Pressure
A. Measuring Blood Pressure
1. vital signs - blood pressure, pulse, respiratory rate, and body temperature
2. auscultory method of blood pressure measurement
a. “sphygmomanometer” wrapped around upper arm
b. inflate above systolic pressure of brachial a.
c. pressure released, first sounds - systolic pr.
d. disappearance of sounds - diastolic pr.
B. Hypotension (below normal blood pressure, < 100/60)

1. factors - age, physical conditioning, illness
2. orthostatic hypotension - generally in elderly, drop in blood pressure during postural
changes
3. chronic hypotension - ongoing low blood pressure
a. low blood protein levels (nutrition)
b. Addison’s disease (adrenal cortex malfunction)
c. hypothyroidism
d. also sign of various types of cancer
C. Hypertension (above normal blood pressure at rest, > 140/90)
1. factors - weight, exercise, emotions, stress
2. chronic hypertension - ongoing high blood pressure
a. prevalent in obese and elderly
b. leads to heart disease, renal failure, stroke
c. also leads to more arteriosclerosis
d. primary hypertension - unidentified source
i. high Na+
, cholesterol, fat levels
ii. clear genetic component (in families)
iii. diuretics - promote water removal
iv. NE blockers - slow vasoconstriction
e. secondary hypertension - identifiable disorder
i. kidney disorders
ii. endocrine (hormone) disorders
iii. arteriosclerosis
VI. Blood Flow in the Body
A. General Features
1. delivery of oxygen and removal of carbon dioxide
2. gas exchange in the lungs
3. absorption and delivery of nutrients from GI tract
4. processing/waste removal in the kidneys
5. normal blood flow at rest
abdominal organs 24%
skeletal muscle 20%
kidneys 20%
brain 13%

heart 4%
other 15%
B. Velocity of Blood Flow
1. velocity directly related to the TOTAL cross-sectional area of the vessel(s)
FASTEST aorta 40-50 cm/s
arteries 20-40 cm/s
arterioles 1-20 cm/s
SLOWEST capillaries 0.1-1 cm/s
C. Local Regulation of Blood Flow
1. autoregulation - regulation of blood flow by altering arteriole diameter
a. oxygen and carbon dioxide levels
b. prostaglandins, histamines, kinins
c. needy areas --> more blood flow
2. myogenic response - change in flow through arteriole in response to stretch of smooth
muscle
3. reactive hyperemia - increase in blood flow to area where an occlusion has occurred
4. increased vasculature - results from prolonged lack of oxygen/nutrients to an area (eg.
heart)
D. Blood Flow to Skeletal Muscles
1. active (exercise) hyperemia - increased blood flow to muscles during heavy activity
a. decreased oxygen and increased lactic acid
b. visceral organ blood flow is decreased
E. Blood Flow to The Brain
1. MUST maintain constant blood flow (750 ml/min)
2. sensitive to low pH and high carbon dioxide
3. blood pressure tightly regulated in the brain
a. fainting -> below 60 mm Hg
b. edema (brain swelling) -> above 180 mm Hg
F. Blood Flow to The Skin
1. intimately involved in temperature regulation

increased body temperature ->
hypothalamic inhibition of vasomotor area ->
vasodilation of vessels in skin ->
increased blood flow ->
sweating -> (bradykinin -> more vasodilation)
G. Blood Flow to the Lungs
1. short pathway from heart, less pressure required
2. low oxygen level --> vasoconstriction
H. Blood Flow to the Heart
1. blood to coronary arteries during diastole
2. vasodilation from ADP and carbon dioxide
VII. Blood Flow in the Capillaries
A. Exchange of Gases and Nutrients
1. diffusion - all molecules move DOWN the concentration gradient (from HIGH to LOW)
into or out of the blood
2. oxygen/nutrients (blood ------> body cells)
carbon dioxide/ wastes (body cells ------> blood)
B. Fluid Movements
1. hydrostatic pressure - force from the capillary wall on the blood itself
a. filtration pressure - the pressure forcing fluid and solutes through capillary clefts
2. osmotic pressure - force driving fluid in the direction of HIGHER solute concentration
3. movement out: Hydrostatic pressure > Osmotic difference
movement in : Hydrostatic pressure < Osmotic difference
4. normal fluid movement 1.5 ml/min in the entire body
C. Circulatory Shock
1. circulatory shock - blood pressure gets so low that blood will not flow adequately
2. hypovolemic shock - circulatory shock resulting from loss of fluid (bleeding, diarrhea,
burn)
a. heart rate increases rapidly
b. general vasoconstriction of vessels
3. vascular shock - extreme vasodilation causes sudden drop in blood pressure

a. snake and spider bites with NE blockers
b. septicemia - bacterial infection
4. cardiogenic shock - heart is unable to provide sufficient blood pressure

Lecture: Muscle Physiology
I. Anatomy of Skeletal Muscle CELL (Muscle Fiber)
A.General Features
1. multinucleated cells (syncytium: from fusion)
2. sarcolemma - special name for plasma membrane
3. very long compared to other cells (1 - 300 mm)
4. not unusually wide diameter (10 - 100 microns)
5. sarcoplasm - rich in glycogen and myoglobin
6. myoglobin - stores oxygen; similar to hemoglobin
7. special structures: myofibrils and sarcoplasmic reticulum
B. Ultrastructure of Myofibrils
¼
1. muscle cell contains many parallel myofibrils
2. myofibrils have DARK bands (A bands) and LIGHT bands (I bands) that cause
"striated" appearance of muscle
3. A band and I band result from the arrangement of overlapping and non-
overlapping regions of two types of myofilaments
a. thick filaments (myosin)
b. thin filaments (actin)
4. sarcomere - smallest contractile unit of muscle cell
a. Z-line - connection of actin filaments; dividing line between two adjacent
sarcomeres
b. M-line - connection of myosin filaments
c. H-zone - non-overlapping region of the myosin filaments around the M-line
d. A-band - length of myosin filaments
e. I-band - length of non-overlapping actin filaments
Each muscle cell (fiber) is composed of many myofibrils. Each myofibril contains hundred
of accordion-like sarcomeres laid end-to-end. Muscle contraction occurs when the
sarcomeres contract by the sliding motion of actin and myosin filaments.
C. Molecular Structure of Actin & Myosin Filaments
1. thick filaments (myosin filaments) 12-16 nm
a. composed of about 200 myosin proteins
i. myosin has a golf club like shape
ii.2 heads (cross bridges) - can bind to the actin filaments and use
ATP

iii.tail - shaft of the thick filament
2. thin filaments (actin filaments) 5-7 nm
a. 2 helical chains of F actin (G actin subunits)
I. G actin can bind with myosin heads
ii.tropomyosin - rod-like protein that helps to stiffen F actin
structure
iii.troponin - globular protein that can bind Ca++
to regulate
actin/myosin binding
D. Sarcoplasmic Reticulum and T Tubules
1. sarcoplasmic reticulum - smooth ER that houses Ca++
a. surrounds each myofibril
b. fused to each other at H zones and A/I bands
c. terminal cisternae - around A/I bands
2. T (transverse) Tubules - passageways from extracellular space to the terminal
cisternae of SR
a. passage of nerve message directly to SR
b. passage of glucose, oxygen, salts to fiber
II. Contraction of Skeletal Muscle Cell
A. Sliding Filament Model (Actin/Myosin Sliding Mechanism)
1. Ca++
released from sarcoplasmic reticulum
2. Ca++
binds to TnC region of Troponin
3. Troponin changes shape, moving Tropomyosin, exposing binding site on actin
filament
4. Attachment - myosin head with ADP + Pi binds actin
5. Power Stroke - myosin head bends, pulling along the actin filament, ADP + Pi are
released
6. Detachment - ATP binds to the myosin head, causing detachment from Actin
7. Re-cocking the Head - hydrolysis of ATP  ADP + P releases energy to re-cock
the myosin
8. some myosin heads are in contact with actin at all times, allowing "walking
motion" to occur
9. 1 cycle = 1 % muscle contraction
10. motion continues until no more ATP is present or Ca++
levels drop by re-uptake
into SR
11. rigor mortis - muscles stiffen because Myosin heads remain attached to the Actin
filaments

III. Regulation of Contraction of a Single Skeletal Muscle Cell
A.Neuromuscular Junction (nmj)
1. neuromuscular junction - nerve/muscle intersection
a. 1 motor neuron/axon supplies several fibers
b. 1 centrally located junction per fiber
c. synaptic vesicles - sacs that contain acetylcholine (ACh- neurotransmitter)
d. synaptic cleft - space between the axon terminal and the sarcolemma of the
muscle cell
e. motor end plate - highly folded part of sarcolemma beneath the synaptic
cleft; rich in ACh receptors
B.Signal Transmission and Electrical Excitation of Muscle
1. Nerve Signal Causes Release of ACh from Axon End
a. action potential along axon causes depolarization of axon terminal
b. decreased membrane potential causes Voltage-Dependent Ca++
Channels on axon
terminal to open
c. Ca++
influx into axon terminal causes exocytosis of ACh containing synaptic
vesicles
d. ACh diffuses across the synaptic cleft to bind to ACh receptors of the motor end
plate
2. Electrical Excitation of the Sarcolemma
I. Like most cell membranes, the sarcolemma of muscle cells is polarized: it has
more negative charge inside than outside.
II.ACh triggers an Electrical Excitation of the sarcolemma by opening chemically
gated Na+
Channels, allowing positive charge to rush into the cell. The muscle
cell becomes less negative or becomes depolarized.
a. ACh binds to ACh Receptors which open ACh-Dependent Na+ Channels
b. these Na+
Channels allow Na+
to flow into the muscle cell, causing
depolarization
c. depolarization at the neuromuscular junctions spreads to adjacent sites
d. Vo1tage-Dependent Na+
Channels at the adjacent sites open, allowing more Na+
in
e. A wave of depolarization therefore spreads across the entire cell
f. this cannot be stopped and is called an all-or-none response

g. entire process occurs in about 1 millisecond (1/1000 second)
h. A refractory period occurs in which the muscle cell must repolarize to its
resting state.
This happens when the Voltage-Dependent Na+
Channels close, Voltage-
Dependent
K+
Channels open, and the Na+
-K+
ATPase pump rebalances the ion
concentrations.
Repolarization generally takes very little time (3 milliseconds), while
contraction can last
up to 100 milliseconds (1/10 sec). Limits how fast the cell can "re-fire" and
contract!
3. Importance of Acetylcholine and Neuromuscular Junction
a. After binding to ACh Receptors on sarcolemma, ACh is quickly broken down by
an enzyme known as Acetylcholinesterase (AChE)
b. myasthenia gravis - autoimmune disease where immune system attacks ACh
Receptors
c. ACh Antagonists - chemicals that block an ACh receptor
i. snake venoms - curare and other venoms
4. Coupling of Excitation and Contraction
a. latent period - time between excitation & contraction
i. action potential passes down the T Tubules from the sarcolemma surface
ii.T Tubule depolarization causes the release of Ca++
from the sarcoplasmic
reticulum
iii. Ca++
increase causes uncoupling of Troponin and sliding of filaments described
above
iv. ATP-Dependent Ca++
Pumps pump the Ca++
back into the sarcoplasmic
reticulum
v. Low Ca++
levels allows Troponin/Tropomyosin blockade of actin and muscle
relaxes
b. Calcium Sequesters - bind Ca++
in the cell so it will not form Calcium Phosphate
crystals
i. calmodulin and calsequestrin
REMEMBER: A Skeletal Muscle CELL (Fiber) will contract in an All-or-None fashion when

ITS motor neuron stimulates it to fire by releasing ACh!!!!!!!!!!
IV. Contraction of a Skeletal MUSCLE
A.Motor Unit - a single motor neuron and all of the muscle cells stimulated by it
1. # muscle cells per motor neuron = 4 - 400
i. muscles of fine control (fingers, eyes and face): fewer muscle cells per neuron
ii.muscles of posture and gross movement (gluteus maximus): more muscle cells
per neuron
2. axon terminals are distributed on muscle fibers throughout the muscle (not one
region)
i. stimulation of one motor unit causes weak contraction throughout the whole muscle
B. Muscle Twitch - the response of a muscle to a single short electrical stimulus
1. strong twitch - many motor units activated; weak twitch - few motor units are
activated
2. latent period (3 ms) - time after stimulation for coupling to occur and contraction
to start
3. contraction period (10 - 100 ms) - from beginning of contraction to maximum
force (tension)
4. relaxation period (10 - 100 ms) - time from maximum force to original relaxed
state
C. Graded Muscle Responses (smooth, not All-or-None)
1. Frequency of Stimulation (Wave Summation) - a motor unit may be stimulated
over and over again so no relaxation period is possible
i. frequency of stimulation cannot be greater than 1 every 3 ms (REFRACTORY
PERIOD)
ii.motor neurons generally deliver action potentials in volleys with varying
frequency
iii.tetanus - smooth muscle contraction that occurs when summation is so great that
the relaxation period disappears

2.Summation of Multiple Motor Units - as strength of stimulus is increased, more and
more motor units are activated in the muscle itself
i. threshold stimulus - level of stimulus at which first motor units are activated
ii.maximal stimulus - level of stimulus at which all motor units of a muscle are
activated
Muscles of the hand show summation of motor units well. When weak force and
delicate motion is needed, few motor units are activated (those with the least # muscle
fibers per motor unit). However, when great force is needed, the strength of the
stimulus is increased to recruit more motor units (with many muscle fibers per motor
unit).
3. Asynchronous Motor Unit Summation - motor units activated in different cycles
"average out to produce a smooth muscle contraction
D.Treppe: The Staircase Effect - When a muscle is first used, it will show a gradual
increase in force with a maximal stimulus until it is 'warmed up".
E. Muscle Tone - slightly contracted state of muscle that is maintained by reflexes
originating in the spinal cord. Maintains posture and readiness for active contraction.
F. Isometric and Isotonic Contractions
a. muscle tension - force generated by a muscle
b. load - force resisting movement of a muscle.
Muscle tension must be greater than load to move it.
c. isometric contraction - muscle doesn’t change length (trying to lift a box that is too
heavy)
d. isotonic contraction - muscle moves the load (doing bicep curls with weights)
V Force, Velocity, and Duration of Skeletal Muscle Contraction
A.Force of Contraction - determined by several factors
1. number of motor units activated
2. size of muscle (in cross section)
a. size increased by increasing the SIZE of individual muscle cells (not increasing
cell #)
3. Series-Elastic Elements

a. sheath around the muscle and the connective tissue tendons that attach muscle to
bone
b. "stretching" of non-contractile parts allows time for muscle to produce a tetanic
contraction
4. Degree of Muscle Stretch (Actin-Myosin Overlap)
a. optimal force can be generated when muscle is between 80 - 120% of resting
length
B.Velocity and Duration of Contraction
1. Effect of the Load on a Muscle
a. smaller the load, faster the contraction
b. larger load: slower contraction/less duration
2. Type of Muscle Fiber
a. Red Slow-Twitch Fibers (small, red)
i. slow twitch; slow acting myosin ATPases
ii lots of myoglobin (red) to store oxygen
iii. many mitochondria, active enzymes
iv. use fat as primary fuel source
v. very aerobic, long duration contraction
b. White Fast-Twitch Fibers (large, pale)
i. fast twitch; fast acting myosin ATPases
ii.few mitochondria, primarily anaerobic
iii.glycogen stores used for anaerobic resp.
iv. lactic acid produced, fatigues quickly
V. rapid, intense, short duration contraction
c. Intermediate Fast-Twitch Fibers (medium, pink)
i. fast twitch; fast acting myosin ATPases
ii.aerobic with myoglobin present
iii. somewhat resistant to fatigue
3. Muscle Composition by Fiber Type
a. most muscles have combinations of all 3 types
b. people differences are genetically determined

VI. Effect of Exercise (and no exercise) on Skeletal Muscle
A.Physiological Adaptations from Exercise
1. aerobic exercise - that requiring steady oxygen
a. capillaries, myoglobin, mitochondria increase
b. better endurance and strength
2. resistance exercise - short duration, high load
a. actin, myosin, myofibers all increase
b. hypertrophy - increase in muscle size
b. glycogen stores and connective tissue increase
B Disuse Atrophy
1. lack of use can result in loss of size (atrophy) and strength of a muscle
2. denervation - lack of nervous stimulation can also cause severe atrophy
VII.Muscle Metabolism
A.Pathways for Synthesis of ATP for Contraction
1. ADP - Creatine Phosphate (Immediate Reserve)
Creatine-phosphate + ADP  Creatine + ATP
(Creatine Kinase)
a. used for first 3 - 5 seconds of activity while respiration processes are warming up
2. Anaerobic Respiration (Lactic Acid Fermentation) (Insufficent Oxygen Supply)
glycolyis glucose  pyruvic acid (INSUFFICIENT oxygen)
pyruvic acid  lactic acid
** used for short-term, intense activity (10 - 15 sec)
** used when oxygen demand CANNOT be met by resp/circ
** yields only 2 ATP per glucose
** lactic acid is reconverted to pyruvic acid when oxygen becomes available
** pyruvic acid then broken down all the way to C02 to release 34 more ATP

3. Aerobic Respiration (Sufficient Oxygen Supply)
glycolyis glucose  pyruvic acid (SUFFICIENT oxygen)
pyruvic acid  H20 + C02
** used for more prolonged, steady activity (walking)
** used when oxygen demand CAN be met by resp/circ
** yields 36-38 ATP per glucose (18-19 X anaerobic!!!)
** glycolysis occurs in the sarcoplasm
** oxidative reactions, using pyruvic acid to make more ATP, occurs in the mitochondria
B. Muscle Fatigue, Oxygen Debt, and Heat Production
1 muscle fatigue - inability of a muscle to contract on a physiological basis
a. when there is less ATP than the muscle requires
b. lactic acid decreases pH, affects enzymes
c. salt loss (Na+
, K+
, Ca++
); ionic imbalance
d. ATP required to drive Na+
-K+
ATPase Pump
2. contractures - continuous contracted state of the muscle ("heads" are not released)
3. oxygen debt - oxygen must be "paid back" in order to restore muscle to original rested
state:
a. restore reserves of ATP and Creatine Phosphate
b. lactic acid converted back to pyruvic acid
c. restore reserves of glucose and glycogen
d. restore oxygen reserves (stored in myoglobin)
e. athletic conditioning increases the efficiency of oxygen use, thereby reducing oxygen
debt
4. heat production - muscle contraction produces heat which can be dangerous (extreme body
temperature) or can be useful (generate heat by shivering)

Lecture: Neurophysiology
I. Overview of Nervous System Organization
A. Central Nervous System (CNS) - brain and spinal cord
B. Peripheral Nervous System (PNS) – spinal/cranial nerves
1. Sensory (Afferent) Division - TO the CNS
a. somatic afferents - from skin, muscle, joints
b. visceral afferents - from membranes & organs
2. Motor (Efferent) Division - FROM the CNS
a. Somatic Nervous System (Voluntary) - to skeletal muscles
b. Autonomic Nervous System (Involuntary) - to organs & glands
i. Sympathetic Division
ii. Parasympathetic Division
II. The Structure of a Neuron (Nerve Cell)
A. neuron - special cells of nervous system that carry messages in the form of electrical
Impulses
B. Supporting Cells of Neurons
1. Support Cells of the CNS (Glial Cells)
a. astrocytes - regulate environment
around neurons and selective transport
from capillaries
b. microglia -eat infectious microbes of CNS
c. ependymal cells - line cavities of brain
and spinal cord, flushing cerebrospinal
fluid (CFS)
d. oligodendrocytes - form “myelin sheaths”
around axons of CNS; increase speed of
impulses
2. Support Cells of the PNS
a. Schwann cells form "myelin sheaths" around axons; also assist in
regeneration of axon
b. satellite cells - control chemical environment
C. Special Characteristics of Neurons
1. amitotic - "not mitotic"; they cannot reproduce or regenerate after certain
point in life

2. longevity - neurons can survive entire lifetime
3. high metabolic rate - require OXYGEN and GLUCOSE at all times
D. Neuron Cell Body (soma; perikaryon)
1. major part from which the processes (axons and dendrites) project; 5-140
micron diameter
2. single large spherical nucleus with nucleolus
3. Nissl Bodies - Rough Endoplasmic Reticulum (rER); make proteins and
plasma membrane
4. nucleus - a collection of cell bodies in the CNS
5. ganglion - a collection of cell bodies in the PNS
E. Typical Neuron Processes (Dendrites & Axon)
1. dendrites - branching, rootlike extensions off the cell body
receptive/input component of the neuron; incoming signals are forwarded to the cell body
signals of dendrites are NOT all-or-none action potentials, but are graded potentials that
result from summation of inputs
2. axon - extension that carries an all-or-nothing action potential from the
cell body to the target; conducting component of the neuron connecting it
to other cells or neurons
a. tract - a bundle of axons in the CNS
b. nerve - a bundle of axons in the PNS
c. axolemma - plasma membrane of neuron
d. axon hillock - the cone-shaped region of attachment of the axon to the
cell body; site where action potential is triggered
e. axon collaterals- rare branches of an axon
f. telodendria - typical terminal branches of an axon which may number
up to 15,000
g. synaptic knobs/ boutons/ axon terminals - at the end of each
telodendria, abut the target tissue to secrete a chemical
neurotransmitter; secretory component of the neuron
h. axon depends upon the cell body for everything: organelles, proteins,
and enzymes for synthesis of neurotransmitter
i. anterograde transport - movement of material from cell body to
synaptic knobs
ii. retrograde transport - movement of material from synapse to
cell body
3. myelin sheath - wrap of Scwhann cells (PNS) and oligodendricytes (CNS)
around the axon
a. increases speed of action potential signal [myelinated (150 m/s);
unmyelinated (1 m/s)]

b. nodes of Ranvier - gaps between myelin cells at regular intervals on axon
c. white matter of brain - areas with myelinated axons
d. gray matter of brain - areas with cell bodies and unmyelinated cell
processes
F. Structural Classification of Neurons
1. multipolar neuron - has three or more cell processes; typically many dendrites and
one axon (throughout the CNS)
2. bipolar neuron - have two (bi) processes: one dendrite and one axon, each
extending from opposite sides of the cell body (retina of the eye)
3. unipolar neuron - one long process attached to the cell body by a “T” like
extension
a. peripheral process – the part that starts at the sensory receptor (eg. Skin)
b. central process – the part that terminates in the CNS (eg. Spinal cord)
G. Functional Classification of Neurons
1. sensory (afferent) neuron - transmit impulses from sensory receptors TOWARD
the CNS
a. almost all are unipolar and located just outside the spinal column
i. Dorsal Root Ganglion of the spinal cord (sensory info from body)
2. motor (efferent) neuron - transmit impulses AWAY FROM the CNS to the target
tissue
a. almost all are multipolar, with cell bodies in the CNS
3. association neuron (interneuron) – between sensory and motor neurons
III. Basic Principles of Electricity
A. voltage (potential difference/potential) - measure of the potential energy that results
from the separation of Positive and Negative charges
1. more charge separated = larger voltage
less charge separated = smaller voltage
2. volts - units of voltage
millilvolt (mV) = l/l000 volt (typical unit used for membrane voltages)
B. current - the flow of electrical charges from one area to another (eg. Na+ into a cell)
1. currents in the body are usually the flow of ions (Na+, K+, Cl-, Ca++)

2. voltage - greater the separation of charge, the
more "potential energy" for current to move
3. resistance - the hindrance to the flow of charge through which current must pass
(plasma membrane and ion channels)
a. insulator - HIGH resistance (low current)
(eg. rubber, wire insulation material)
b. conductor - LOW resistance (high current)
(eg. copper wire, water, most metals)
C. Ohm's Law voltage (V), current (I), resistance (R)
current (I) = voltage (V)
resistance (R)
INCREASED voltage = INCREASED current
DECREASED voltage = DECREASED current
INCREASED resistance = DECREASED current
DECREASED resistance = INCREASED current
D. Regulation of Current/Voltage - Changing Resistance (Permeability) of Cell
Membrane
1. leakage channels - channels that are always open (eg. K+ leakage channels)
2. chemical-gated (ligand-gated) channels open
or close when bound by a specific molecule
(eg. neurotransmitter: ACh, serotonin, etc.)
3. voltage-gated (dependent) channels - open or
close depending on the voltage across
membrane
E. electrochemical gradient - net result of both the "electrical gradient" and "chemical
gradient"
1. electrical gradient - positive charges move
toward negative charges and vice versa
2. chemical gradient - diffusion from area of
high concentration to low concentration
IV. Resting Membrane Potential of a Neuron: A Polarized State
A. Review of Polarized State
1. Na+-K+= ATPase Pump

[Na+]out > [Na+]in
[K+]out < [K+]in
K+ leaks out of the cell
2. K+ Leak Channels
3. Na+ channels are closed at rest
4. Cl levels [Cl-]out > [Cl-]in
Chloride ions can also leak into the cell, but the electrical gradient (due to
negative charge inside of the cell) balances the chemical gradient for Cl- to rush
in.
V. Membrane Potential and Signaling
A. Definition of Terms - (relative to resting membrane potential -70 mV)
1. depolarization - inside of cell becomes less negative; the resting potential
approaches ZERO or becomes positive (e.g. Na+ moves into the cell)
-70 mV-50 mV-30 mV0 mV+20 mV +60 mV
2. hyperpolarization - inside of the cell becomes even more negative; the resting
membrane potential gets larger (more K+ and/or Cl- channels open; K+ moves
out, and Cl- moves in)
-120 mV  -100 mV  -80 mV  -70 mV
B. graded potentials - short-term, localized depolarization or hyperpolarization that
depends on the intensity of the stimulus; the larger the stimulus, the greater the
change in voltage and the farther the current spreads in cell
Graded potentials are localized - their intensity gradually dies out at further distances
from the point of stimulation - like ripples in a pond when a rock is dropped.
decremental - it decreases over distance.
1. postsynaptic potential - potential generated by neurotransmitter on the
“postsynaptic” cell
2. receptor potential - potential generated by a stimulus (heat, light, stretch) in a
sensory neuron
C. action potential - an all-or-none, uni-directional wave of depolarization along the
length of a cell (such as the axon of a neuron; called a nerve impulse)
Steps in Action Potential generation:
1. depolarization due to opening of Na+ channels

When the membrane at the axon hillock is depolarized to a threshold level (-50 mV),
voltage-gated Na+ channels are triggered to open, allowing Na+ to rush in, causing
further depolarization, and even more Na+ channels to open. This positive feedback
loop is called Hodgkin Cycle, after the discoverer. This phenomenon spreads down
the axon like a series of falling dominos, in an "all-or-none" fashion.
2. immediate closure of the voltage-gated Na+ channels
Only 3 ms after a voltage-dependent Na+ channel opens, it closes, so that Na+ can no
longer enter the cell, and the resting potential can be regenerated. However, the local
depolarizing effect of the opening has already been passed on, causing the action
potential.
3. repolarization due to opening of K+ channels
As the Na+ channels close, voltage-dependent K+ channels open, allowing even more
K+ to rush out of the cell, until the resting membrane potential is restored.
D. threshold - the level of depolarization that will trigger an action potential (the level at
which voltage-dependent Na+ channels are triggered to open)
E. Stimulus Intensity - Coded by Action Potential Frequency
The strength of a stimulus is translated by the neuron by the FREQUENCY (# per
second) of action potentials. The more pressure on the skin, the faster are the impulses in
afferent axon.
F. Absolute Refractory Period - while Na+ channels are open, it is impossible to
generate another action potential
G. Relative Refractory Period - when Na+ channels are closed, and K+ channels
regenerate the resting potential, action potentials can occur, but the stimulus must be
greater than before
H. Factors that Influence Speed of Action Potential
1. axon diameter - larger diameter = faster impulse
2. myelin sheath - increases the speed of impulse domino effect jumps between the
nodes of Ranvier (called saltatory conduction)
a. multiple sclerosis - loss of myelin
I. Classification of Nerve Fibers
1. Group A fibers - large diameter/thick myelin (sensory and motor fibers of skin,
muscle, joints)
2. Group B fibers - medium diameter/light myelin
3. Group C fibers - small diameter/ no myelin

VI. The Synapse: Axon Terminal Meets Postsynaptic Cell
A. synapse - the junction of a neuron that allows transfer of message to "postsynaptic
cell" (eg. another neuron, muscle fiber, gland, etc.)
1. axodendritic - axon terminal -> dendrite
2. axosomatic - axon terminal -> neuron cell body
3. axonaxonic - axon terminal -> another axon
4. dendrodendritic - dendrite -> dendrite
5. dendrosomatic - dendrite -> neuron cell body
6. neuromuscular junction - axon terminal -> muscle
7. neuroglandular junction - axon terminal ->gland
8. presynaptic neuron - "before" the synapse; the neuron that is sending the signal
9. postsynaptic neuron - "after" the synapse; the affected cell receiving the signal
B. Electrical Synapse - "electrically coupled" cells that have "bridged junctions",
allowing the direct passage of ions from one cell into the next.
1. allows for direct synchronization of activity
C. Chemical Synapse - a synapse which relies on the passage of a "neurotransmitter" (eg.
ACh) across the synaptic cleft, which binds to chemically-gated ion channels on the
postsynaptic cell.
VII. Transmission of Signal Across a Chemical Synapse
1. Depolarization of Presynaptic Axon Terminal - when an action potential reaches
the axon terminal, the influx of Na+ ions causes it to become depolarized
2. Depolarization Opens Voltage-Gated Ca++ Channels - In response the
depolarization of the axon terminal, voltage-dependent Ca++ channels on
presynaptic axon terminal open, allowing Ca++ to rush INTO the cell down its
concentration gradient
3. Increased Ca++ Causes Neurotransmitter Release - As Ca++ increases in the axon
terminal, synaptic vesicles containing the neurotransmitter fuse with the plasma
membrane, releasing contents into the synaptic cleft
4. Neurotransmitter Binds Receptor - Opens Ion Channels - The released
neurotransmitter crosses the synaptic cleft reversibly binds to receptors, opening
either EXCITATORY ion channels (Na+ moves in to depolarize) or
INHIBITORY ion channels (Cl-/K+ move to hyperpolarize)

Excitatory, Postsynpatic Potentials (EPSPs) - Depolarization - Leads to MORE Action
Potentials
EPSPs result when a neurotransmitter opens Na+ channels, causing depolarization of the
cell body, and increased likelihood of generating an axon potential. EPSPs are graded
potentials, meaning they are localized and dissipate over a distance. For an action
potential to be generated on the postsynaptic cell, the "threshold" voltage must be
obtained at the axon hillock. This occurs through temporal summation and/or spatial
summation of many EPSPs from up to10,000 incoming axons terminals on the
postsynaptic cell body.
Inhibitory Postsynaptic Potentials (IPSPs) - Hyperpolarization - Leads to LESS Action
Potentials
IPSPs result when a neurotransmitter opens either Cl- channels, K+ channels, or both,
causing hyperpolarization of the cell body (-l00 mv), and decreased likelihood of
generating an action potential. Like EPSPs, IPSPs are graded potentials that are
localized and dissipate over a distance. The "integration" of EPSPs and IPSPs through
both temporal summation and spatial summation is how the postsynaptic cell makes
the "decision" whether or not to fire an action potential. If, after all EXCITATORY
and INHIBITORY input, the axon hillock reaches the "threshold" voltage, the
postsynaptic cell will fire an action potential.
5. Termination of Neurotransmitter Effects
The EPSPs and IPSPs are terminated when the neurotransmitter is released from the
receptor 3 ms), ending the flow of ions. The neurotransmitter may be degraded by
enzymes (eg. acetylcholinesterase), may be reabsorbed by the presynaptic cell (eg.
norepinephrine), or may diffuse away from the synapse.
VIII. Structure and Function Classifications of Neurotransmitters
A. General Characteristics of Neurotransmitters
1. Most neurons release only one neurotransmitter, but some may release two or
more
2. more than 100 neurotransmitters are known
3. Neurotransmitters may be synthesized in the axon terminal, or in the cell body
and then transported. In either case, the synthesizing enzymes are made in the cell
body.
B. Classification by Chemical Structure
1. Acetylcholine (ACh)
a. skeletal muscle, some autonomic neurons, and various parts of the CNS

b. choline acetyltransferase - synthesis enzyme
c. acetylcholinesterase - breakdown enzyme
d. breakdown product (choline) is recaptured by presynaptic axon for resynthesis
of ACh
e. reuptake inhibitors - drugs that block the reuptake (Prozac - serotonin for
depression)
f. nerve gas, malathion - block the activity of aceytlcholinesterase
g. some snake/spider venoms - block ACh receptor
2. Biogenic Amines
catecholamines - dopamine, norepinephrine (NE), and epinephrine
a. common biosynthetic pathway
b. enzymes determine final product in neuron
c. tyrosine is precursor to all of these
d. Dopamine blockers - used to treat Schizophrenia (thorazine &
haloperidol)
e. Amphetamines - activate Dopamine, Serotonin, and NE receptors (speed,
crank)
f. NE and Serotonin reuptake inhibitors - used to treat depression (Prozac)
g. L-Dopa used to treat Parkinson's Disease
Indolamines - serotonin and histamine
a. serotonin also derived from tyrosine, different enzymatic pathway
b. histamine derived from amino acid histidine
c. LSD - hallucinogen that blocks Serotonin receptors
3. Amino Acids - glycine, glutamate, GABA (gamma aminobutyric acid)
4. Neuropeptides - enkephalins, endorphins, substance P
a. most are associated with pain regulation
b. narcotics (heroin & morphine) - activate enkephalin receptors in brain
C. Classification by Function
1. Inhibitory or Excitatory? the action of a neurotransmitter can be either excitatory
(allow Na+ in) or inhibitory (allow Cl- in), depending on what type of channel it
opens
a. generally inhibitory - glycine & GABA
b. generally excitatory - glutamate
c. some can be either, dependent on location: most other neurotransmitters
i. ACh - exitatory on skeletal muscle, inhibitory on cardiac muscle

2. Ionotrophic vs. Metabotrophic Actions
a. ionotropic - opens Na+ or Cl- channels
b. metabotropic - promote longer lasting changes using "second messenger
system"
i. binding of neurotransmitter causes production of intracellular "second
messenger" called cyclic AMP (cAMP)
ii. cAMP can activate enzymes in the cell to alter activity of channels and
enzymes

1
Lecture: Heart Physiology
I. Cardiac Muscle (compare to Skeletal Muscle)
Cardiac Muscle Cells
fairly short
semi-spindle shape
branched, interconnected
connected (intercalated discs)
electrical link (gap junction)
common contraction (syncytium)
1 or 2 central nuclei
dense "endomysium"
high vasculature
MANY mitochondria (25% space)
almost all AEROBIC (oxygen)
myofibers fuse at ends
T tubules wider, fewer
Skeletal Muscle Cells
very long
cylindrical shape
side-by-side
no tight binding
no gap junctions
independent contract
multinucleated
light "endomysium"
medium vasculature
less mitochondria (2%)
aerobic & anaerobic
myofibers not fused
T tubules at A/I spot
II. Mechanism of Contraction of Contractile Cardiac Muscle Fibers
1. Na+
influx from extracellular space, causes positive feedback opening of voltage-
gated Na+
channels; membrane potential quickly depolarizes (-90 to +30 mV);
Na+
channels close within 3 ms of opening.
2. Depolarization causes release of Ca++
from sarcoplasmic reticulum (as in skeletal
muscle), allowing sliding actin and myosin to proceed.
3. Depolarization ALSO causes opening of slow Ca++
channels on the membrane
(special to cardiac muscle), further increasing Ca++
influx and activation of
filaments. This causes more prolonged depolarization than in skeletal muscle,
resulting in a plateau action potential, rather than a "spiked" action potential (as in
skeletal muscle cells).
Differences Between Skeletal & Cardiac MUSCLE Contraction
1. All-or-None Law - Gap junctions allow all cardiac muscle cells to be linked
electrochemically, so that activation of a small group of cells spreads like a wave
throughout the entire heart. This is essential for "synchronistic" contraction of the heart as
opposed to skeletal muscle.
2. Automicity (Autorhythmicity) - some cardiac muscle cells are "self-excitable" allowing
for rhythmic waves of contraction to adjacent cells throughout the heart. Skeletal muscle
cells must be stimulated by independent motor neurons as part of a motor unit.

2
3. Length of Absolute Refractory Period - The absolute refractory period of cardiac muscle
cells is much longer than skeletal muscle cells (250 ms vs. 2-3 ms), preventing wave
summation and tetanic contractions which would cause the heart to stop pumping
rhythmically.
III. Internal Conduction (Stimulation) System of the Heart
A. General Properties of Conduction
1. heart can beat rhythmically without nervous input
2. nodal system (cardiac conduction system) - special autorhythmic cells of
heart that initiate impulses for wave-like contraction of entire heart (no
nervous stimulation needed for these)
3. gap junctions - electrically couple all cardiac muscle cells so that
depolarization sweeps across heart in sequential fashion from atria to
ventricles
B. "Pacemaker" Features of Autorhythmic Cells
1. pacemaker potentials - "autorhythmic cells" of heart muscle create action
potentials in rhythmic fashion; this is due to unstable resting potentials
which slowly drift back toward threshold voltage after repolarization from
a previous cycle.
Theoretical Mechanism of Pacemaker Potential:
a. K+
leak channels allow K+
OUT of the cell more slowly than in skeletal muscle
b. Na+
slowly leaks into cell, causing membrane potential to slowly drift up to the threshold
to trigger Ca++
influx from outside (-40 mV)
c. when threshold for voltage-gated Ca++
channels is reached (-40 mV), fast calcium
channels open, permitting explosive entry of Ca++
from of the cell, causing sharp rise in
level of depolarization
d. when peak depolarization is achieved, voltage-gated K+
channels open, causing
repolarization to the "unstable resting potential"
e. cycle begins again at step a.
C. Anatomical Sequence of Excitation of the Heart
1. Autorhythmic Cell Location & Order of Impulses

3
(right atrium) sinoatrial node (SA) ->
(right AV valve) atrioventricular node (AV) ->
atrioventricular bundle (bundle of His) ->
right & left bundle of His branches ->
Purkinje fibers of ventricular walls
(from SA through complete heart contraction = 220 ms = 0.22 s)
a. sinoatrial node (SA node) "the pacemaker" - has the fastest autorhythmic rate (70-80 per
minute), and sets the pace for the entire heart; this rhythm is called the sinus rhythm;
located in right atrial wall, just inferior to the superior vena cava
b. atrioventricular node (AV node) - impulses pass from SA via gap junctions in about 40
ms.; impulses are delayed about 100 ms to allow completion of the contraction of both
atria; located just above tricuspid valve (between right atrium & ventricle)
c. atrioventricular bundle (bundle of His) - in the interATRIAL septum (connects L and R
atria)
d. L and R bundle of His branches - within the interVENTRICULAR septum (between L
and R ventricles)
e. Purkinje fibers - within the lateral walls of both the L and R ventricles; since left ventricle
much larger, Purkinjes more elaborate here; Purkinje fibers innervate “papillary muscles”
before ventricle walls so AV can valves prevent backflow
D. Special Considerations of Wave of Excitation
1. initial SA node excitation causes contraction of both the R and L atria
2. contraction of R and L ventricles begins at APEX of heart (inferior point),
ejecting blood superiorly to aorta and pulmonary artery
3. the bundle of His is the ONLY link between atrial contraction and ventricular
contraction; AV node and bundle must work for ventricular contractions
4. since cells in the SA node has the fastest autorhythmic rate (70-80 per minute), it
drives all other autorhythmic centers in a normal heart
5. arrhythmias - uncoordinated heart contractions
6. fibrillation - rapid and irregular contractions of the heart chambers; reduces
efficiency of heart
7. defibrillation - application of electric shock to heart in attempt to retain normal
SA node rate
8. ectopic focus - autorhythmic cells other than SA node take over heart rhythm
9. nodal rhythm - when AV node takes over pacemaker function (40-60 per minute)
10. extrasystole - when outside influence (such as drugs) leads to premature
contraction
11. heart block - when AV node or bundle of His is not transmitting sinus rhythm to

4
ventricles
E. External Innervation Regulating Heart Function
1. heart can beat without external innervation
2. external innervation is from AUTONOMIC SYSTEM
parasympathetic - (acetylcholine) DECREASES rate of contractions
cardioinhibitory center (medulla) ->
vagus nerve (cranial X) ->
heart
sympathetic - (norepinephrine) INCREASES rate of contractions
cardioacceleratory center (medulla) ->
lateral horn of spinal cord to preganglionics Tl-T5 ->
postganlionics cervical/thoracic ganglia ->
heart
IV. Electrocardiography: Electrical Activity of the Heart
A. Deflection Waves of ECG
1. P wave - initial wave, demonstrates the depolarization from SA Node
through both ATRIA; the ATRIA contract about 0.1 s after start of P
Wave
2. QRS complex - next series of deflections, demonstrates the depolarization
of AV node through both ventricles; the ventricles contract throughout the
period of the QRS complex, with a short delay after the end of atrial
contraction; repolarization of atria also obscured
3. T Wave - repolarization of the ventricles (0.16 s)
4. PR (PQ) Interval - time period from beginning of atrial contraction to
beginning of ventricular contraction (0.16 s)
5. QT Interval the time of ventricular contraction (about 0.36 s); from
beginning of ventricular depolarization to end of repolarization
V. The Normal Cardiac Cycle
A. General Concepts
1. systole - period of chamber contraction

5
2. diastole - period of chamber relaxation
3. cardiac cycle - all events of systole and diastole during one heart flow
cycle
B. Events of Cardiac Cycle
1. mid-to-late ventricular diastole: ventricles filled
* the AV valves are open
* pressure: LOW in chambers; HIGH in aorta/pulmonary trunk
* aortic/pulmonary semilunar valves CLOSED
* blood flows from vena cavas/pulmonary vein INTO atria
* blood flows through AV valves INTO ventricles (70%)
* atrial systole propels more blood > ventricles (30%)
* atrial diastole returns through end of cycle
2. ventricular systole: blood ejected from heart
* filled ventricles begin to contract, AV valves CLOSE
* isovolumetric contraction phase - ventricles CLOSED
* contraction of closed ventricles increases pressure
* ventricular ejection phase - blood forced out
* semilunar valves open, blood -> aorta & pulmonary trunk
3. isovolumetric relaxation: early ventricular diastole
* ventricles relax, ventricular pressure becomes LOW
* semilunar valves close, aorta & pulmonary trunk backflow
* dicrotic notch - brief increase in aortic pressure
TOTAL CARDIAC CYCLE TIME = 0.8 second
(normal 70 beats/minute)
atrial systole (contraction) = 0.1 second
ventricular systole (contraction) = 0.3 second
quiescent period (relaxation) = 0.4 second
VI. Heart Sounds: Stethoscope Listening
A. Overview of Heart Sounds
1. lub-dub, - , lub, dub, -
2. lub - closure of AV valves, onset of ventricular systole

6
3. dub - closure of semilunar valves, onset of diastole
4. pause - quiescent period of cardiac cycle
5. tricuspid valve (lub) - RT 5th intercostal, medial
6. mitral valve (lub) - LT 5th intercostal, lateral
7. aortic semilunar valve (dub) - RT 2nd intercostal
8. pulmonary semilunar valve (dub) - LT 2nd intercostal
B. Heart Murmurs
1. murmur - sounds other than the typical "lub-dub"; typically caused by disruptions
in flow
2. incompetent valve - swishing sound just AFTER the normal "lub" or "dub"; valve
does not completely close, some regurgitation of blood
3. stenotic valve - high pitched swishing sound when blood should be flowing
through valve; narrowing of outlet in the open state
VII. Cardiac Output - Blood Pumping of the Heart
A. General Variables of Cardiac Output
1. Cardiac Output (CO) - blood amount pumped per minute
2. Stroke Volume (SV) - ventricle blood pumped per beat
3. Heart Rate (HR) - cardiac cycles per minute
CO (ml/min) = HR (beats/min) X SV (ml/beat)
normal CO = 75 beats/min X 70 ml/beat = 5.25 L/min
B. Regulation of Stroke Volume (SV)
1. end diastolic volume (EDV) - total blood collected in ventricle at end of
diastole; determined by length of diastole and venous pressure (~ 120 ml)
2. end systolic volume (ESV) - blood left over in ventricle at end of
contraction (not pumped out); determined by force of ventricle contraction
and arterial blood pressure (~50 ml)
SV (ml/beat) = EDV (ml/beat) - ESV (ml/beat)
normal SV = 120 m1/beat - 50 ml/beat = 70 ml/beat
3. Frank-Starling Law of the Heart - critical factor for stroke volume is
"degree of stretch of cardiac muscle cells"; more stretch = more
contraction force
a. increased EDV = more contraction force
i. slow heart rate = more time to fill

7
ii. exercise = more venous blood return
C. Regulation of Heart Rate (Autonomic, Chemical, Other)
1. Autonomic Regulation of Heart Rate (HR)
a. sympathetic - NOREPINEPHRINE (NE) increases heart rate
(maintains stroke volume which leads to increased Cardiac Output)
b. parasympathetic - ACETYLCHOLINE (ACh) decreases heart rate
c. vagal tone - parasympathetic inhibition of inherent rate of SA node,
allowing normal HR
d. baroreceptors, pressoreceptors - monitor changes in blood pressure
and allow reflex activity with the autonomic nervous system
2. Hormonal and Chemical Regulation of Heart Rate (HR)
a. epinephrine - hormone released by adrenal medulla during stress;
increases heart rate
b. thyroxine - hormone released by thyroid; increases heart rate in
large quantities; amplifies effect of epinephrine
c. Ca++
, K+
, and Na+
levels very important;
* hyperkalemia - increased K+
level; KCl used to stop heart on lethal
injection
* hypokalemia - lower K+
levels; leads to abnormal heart rate
rhythms
* hypocalcemia - depresses heart function
* hypercalcemia - increases contraction phase
* hypernatremia - HIGH Na+
concentration; can block Na+
transport
& muscle contraction
3. Other Factors Effecting Heart Rate (HR)
a. normal heart rate - fetus 140 - 160 beats/minute
female 72 - 80 beats/minute
male 64 - 72 beats/minute
b. exercise - lowers resting heart rate (40-60)
c. heat - increases heart rate significantly
d. cold - decreases heart rate significantly
e. tachycardia - HIGHER than normal resting heart rate (over 100);
may lead to fibrillation
f. bradycardia - LOWER than normal resting heart rate (below 60);
parasympathetic drug side effects; physical conditioning; sign of
pathology in non-healthy patient

8
VIII. Imbalance of Cardiac Output & Heart Pathologies
A. Imbalance of Cardiac Output
1. congestive heart failure - heart cannot pump sufficiently to meet needs of
the body
a. coronary atherosclerosis - leads to gradual occlusion of heart
vessels, reducing oxygen nutrient supply to cardiac muscle cells;
(fat & salt diet, smoking, stress)
b. high blood pressure - when aortic pressure gets too large, left
ventricle cannot pump properly, increasing ESV, and lowering SV
c. myocardial infarct (MI) - "heart cell death" due to numerous
factors, including coronary artery occlusion
d. pulmonary congestion - failure of LEFT heart; leads to buildup of
blood in the lungs
e. peripheral congestion - failure of RIGHT heart; pools in body,
leading to edema (fluid buildup in areas such as feet, ankles,
fingers)
B. Heart Pathologies (Diseases of the Heart)
1. congenital heart defects - heart problems that are present at the time of
birth
a. patent ductus arteriosus - bypass hole between pulmonary trunk
and aorta does not close
2. sclerosis of AV valves - fatty deposits on valves; particularly the mitral
valve of LEFT side; leads to heart murmur
3. decline in cardiac reserve - heart efficiency decreases with age
4. fibrosis and conduction problems - nodes and conduction fibers become
scarred over time; may lead to arrhythmias

Lecture: Renal Physiology
I. Overview of Nephron Structure and Function
A. General Nephron Structure
1. glomerulus - site of filtration from arterial blood
2. proximal convolute tubule- first tube off glomer.
3. Loop of Henle - U-turn connecting tubules
4. distal convoluted tubule - to the Collecting Tubule
5. collecting tubule - urine from many nephron
6. peritubular capillaries - "around" the "tubes"
B. General Nephron Function
1. glomerular filtration
2. tubular reabsorption
3. tubular secretion
C. Fluid Processing in the Kidneys
180 liters of blood fluid processes each day
1.5 liters of urine produced each day
II. Glomerular Filtration
A. Filtration Membrane
1. hydrostatic pressure - forces 1/5 of blood fluid through capillary' walls into glomerular
capsule
2. filtration membrane - has three parts
a. fenestrated capillary endothelium (prevents passage of blood cells)
b. basal membrane (allows most solutes but larger proteins)
c. visceral membrane of glomerular capsule
3. solutes that can pass into glomerular capsule
< 3 nm easily pass (water, sugar, amino acids, nitrogenous waste molecules)
> 9 nm larger proteins cannot pass through
B. Net Filtration Pressure
NFP = force OUT of blood - force to remain IN blood
NFP = glomerular - (glomerular + capsular )
hydrostatic osmotic hydrostatic
pressure pressure pressure
NFP = 55 mm Hg - ( 30 mm Hg + l5mmHg)
NFP = 55 mm Hg - (45 mm Hg)
NFP = net filtration pressure = 10 mm Hg
[This is the NET forces pushing fluid/solutes OUT of blood]
1. glomerular filtration rate = milliliters of blood fluid filtered by glomerulus each minute

Factors effecting the GFR:
a. total filtration surface area
b. membrane permeability to fluid/solutes
c. Net Filtration Pressure
2. Normal GFR = 125 ml/min (7.5 L/hr, 180 L/day)
3. NFP - primary factor controlling GFR
a. bleeding - NFP drops, lowers the pressure
b. dehydration - NFP drops, lowers the pressure
D. Intrinsic Controls: Regulation of Glomerular Filtration
1. renal autoregulation - rate of FILTRATE production must be coordinated with
reabsorption rate
2. myogenic mechanism - circular muscle around the glomerular arterioles reacts to
pressure changes
a. increased blood pressure -> vasoconstriction
b. decreased blood pressure -> vasodilation
3. tubuloglomerular feedback mechanism - macula densa cells (of juxtaglomerular
apparatus) sense the solute concentration of the FILTRATE
a. low concentration > vasodilation
b. high concentration -> vasoconstriction
4. renin-angiotensin mechanism
renin (released by juxtoglomerular cells) -> angiotensinogen -> angiotensin I -> angiotensin II ->
global vasoconstrictor (rise in blood pressure) release of aldosterone (resorption of more Na+)
Factors causing release of Renin:
a. reduced stretch of juxtaglomerular cells
b. stimulation by macula densa cells (as above)
c. stimulation of juxtaglomerular cells by sympathetics
E. Extrinsic Controls: Sympathetic Innervation
1 sympathetics - cause increased release of renin
2 epinephrine - causes increased vasoconstriction
III. Tubular Reabsorption: Reabsorbing the Glomerular Filtrate
A. Overview of Reabsorption
1. filtrate - all fluid and its solutes pushed into the capsule
2. urine - filtrate minus reabsorbed substances + secreted substances
3. route of reabsorption (transepithelial process)
luminal surface of tubule cells >>
basolateral membrane of tubule cells >>
interstitial fluid between tubule cells and capillaries >>
endothelium of the peritubular capillary

4. most sugars and amino acids are reabsorbed
5. water and ion reabsorption depends on hormonal control
B. Active Tubular Reabsorption
1. glucose, amino acids, lactate, vitamins, ions
a. move across luminal surface by diffusion
b. actively transported across basolateral membrane
i. cotransported with Na+
c. diffuse into capillary by diffusion
2. transport maximum (Tm) when "carrier proteins" for specific solute becomes saturated
and cannot carry the substance across the membrane
a. diabetes mellitus - lower Tm (glucose lost)
C. Passive Tubular Resorption
1. Na+ driven into interstitial space actively (above)
2. HCO3
-
and Cl-
follow Na+ into the space
3. obligatory water resorption - water follows ions into the interstitial space between tubule
& capillary
4. solvent drags - solutes will begin to move into tubule from filtrate, following water
(especially some urea and lipid-soluble molecules)
D. Nonreabsorbed Substances
1. urea, creatinine, uric acid - most is not reabsorbed because of the following reasons
a. no carrier molecules for active transport
b. not lipid-soluble
c. too large (as with most proteins)
E. Absorption in Different Regions of Renal Tubule
1. proximal tubule - closest to the glomerular capsule
a. almost all glucose & amino acids
b. 75-80% of water and Na+
c. most active transport of ions
2. Loop of Henle - connects proximal & distal tubules
Regulates Total water retained or lost:
a. descending limb - water can return to blood vessels
b. ascending limb – water impermeable but releases ions to the interstitial space
increasing osmotic pressure so that water can be reabsorbed from other parts of
the renal tubule
3. distal tubule & collecting duct - final passageway
a. antidiuretic hormone (ADH) - causes increased permeability to Na+ and water,
allow resorption

b. aldosterone - stimulated by renin-angiotensin, enhances Na+ resorption (water
follows). Triggered by
i. lower blood pressure
ii. low Na+ concentration (hyponatremia)
c. atrial natriuretic factor (ANF) - reduces Na+ permeability, less water (in response to high
B.P.)
IV. Tubular Secretion
A. Movement from Capillaries to Tubular Cells
1. K+, creatinine, ammonia, organic acids, drugs
2. Primary functions of tubular secretion:
a. moving drugs into the urine
b. moving more urea & uric acid into urine
c. removing excess K+ from blood
d. regulating pH (H+ ion removal)
V. Regulation of Urine Concentration & Volume
A. Osmolarity - Number of Solute particles in 1 Liter water
1. independent of size of solute (Na +, glucose)
2. 1 osmol = 6.02 X l023
particle in I Liter
3. milliosmol (mosm) = 0.001 osmol
4. normal body fluids = 300 mosm
B. Countercurrent Multiplier Mechanism for Maintenance of Blood/Urine Osmolarity
1. Water moves out along Descending Limb of the Loop of Henle, creating 1200 mosm
urine at the base
2. Na+Cl- moves out along the Ascending Limb of the Loop of Henle, creating 100 mosm
urine at distal end. This salt helps pull more water out of the Descending Limb in positive
feedback mechanism.
3. In times of dehydration, Collecting Tubules leak urea to interstitial space, further
increasing water retention by increasing osmolarity.
4. Vasa recta (capillaries around Loop of Henle) have no Net Effect on water/salt balance
C. Formation of Dilute Urine
1. When water removal is needed, no ADH is released, so that the Distal and Collecting
Tubules will not actively transport Na+ out; no water moves out
2. Urine may be as low as 50 mosm
D. Formation of Concentrated Urine (Water Conservation)

1. antidiuretic hormone (ADH) - stimulates resorption of water in the Distal and Collecting
Tubules
E. Diuretics (Stimulate Water Loss)
1. alcohol inhibits action of ADH
2. caffeine - causes renal vasodilation; increases GFR
3. Na+ resorption blockers - block Na+
movement
VI. Renal Clearance
A. Renal Clearance (RC) - the rate at which the kidney can remove a substance from the blood
RC = U/P X V
U/P = concentration of substance in urine (mg/ml)
concentration of substance in plasma (mg/ml)
V = rate of the formation of urine (ml/minute)
(normal = 1 ml/minute)
B. Glomerular Filtration Rate = 125 ml/minute; (determined by challenge with "Inulin")
1. RC < 125 - reabsorption is occurring
2. RC > 125 - tubule cells secrete into the urine
VII. Characteristics and Composition of Urine
A. Physical Characteristics
1. color - clear to yellowish; influenced by diet, drugs, and health state
2. odor - slightly aromatic; influenced by diet, drugs, and health state
3. pH (H+ conc.) - usually about 6; changes in diet can effect the pH
4. specific gravity - compared density to distilled water; urine slightly heavier (with solute
s)
B. Chemical Composition
1. 95% water
2. 5% solutes - urea (breakdown of amino acids); uric acid; creatinine

Lecture: Physiology of Blood
I. Components, Characteristics, Functions of Blood
A. Major Components of Blood
1. formed elements - the actual cellular components of blood (special connective tissue)
a. erythrocytes - red blood cells
b. leukocytes - white blood cells
c. platelets - cell fragments for clotting
2. blood plasma - complex non-cellular fluid surrounding formed elements; protein &
electrolytes
B. Separation of Components in a Centrifuge
VOLUME LAYER
1. clear/yellowish PLASMA 55% top
2. thin/whitish buffy coat <1% middle
with LEUKOCYTES & PLATELETS
3. reddish mass - ERYTHROCYTES 45% bottom
hematocrit - percentage by VOLUME of erythrocytes when blood is centrifuged (normal = 45%)
C. Characteristics of Blood
1. bright red (oxygenated)
2. dark red/purplish (unoxygenated)
3. much more dense than pure water
4. pH range from 7.35 to 7.45 (slightly alkaline)
5. slightly warmer than body temperature 100.4 F
6. typical volume in adult male 5-6 liters
7. typical volume in adult female 4-5 liters
8. typically 8% of body weight
D. Major Functions of Blood
1. Distribution & Transport
a. oxygen from lungs to body cells
b. carbon dioxide from body cells to lungs
c. nutrients from GI tract to body cells

d. nitrogenous wastes from body cells to kidneys
e. hormones from glands to body cells
2. Regulation (maintenance of homeostasis)
a. maintenance of normal body pH
i. blood proteins (albumin) & bicarbonate
b. maintenance of circulatory/interstitial fluid
i. electrolytes aid blood proteins (albumin)
c. maintenance of temperature (blushed skin)
3. Protection
a. platelets and proteins "seal" vessel damage
b. protection from foreign material & infections
i. leukocytes, antibodies, complement proteins
II. Erythrocytes (red blood ells; RBCs)
A. Structure
1. 7.5 micron diameter; 2.0 micron thick
2. biconcave disk shape; ideal for gas exchange
i. spectrin - elastic protein; allows shape change
3. mature cells are anucleate (no nucleus)
3. very few organelles; mainly a hemoglobin carrier
i. hemoglobin – 33% of cell mass; carries oxygen
5. no mitochondria; only anaerobic respiration
6. ratio erythrocytes:leukocytes = 800:1
7. red blood cell count: # cells per cubic millimeter
i. normal male count - 5.1 to 5.8 million
ii. normal female count - 4.3 to 5.2 million
B. Functions (oxygen & carbon dioxide transport)
1. hemoglobin - large molecules with globin and hemes
a. globin - complex protein with 4 polypeptides (2 alpha and 2 beta polypeptides)
b. heme group - IRON containing pigment part of hemoglobin to which oxygen
binds
i. each polypeptide has one heme group;each heme carries one O2
c. normal hemoglobin levels (grams/l00 ml blood)
i. infants 14-20 grams/l00 ml
ii adult female 12-16 grams/100 ml
iii adult male 13-18 grams/l00 ml
2. states of hemoglobin

a. oxyhemoglobin - when oxygen is bound to IRON
b. deoxyhemoglobin - no oxygen bound to IRON
c. carbaminohemoglobin - when carbon dioxide bound (to polypeptide chain)
C. Hematopoiesis and Erythropoiesis
1. hematopoiesis (hemopoiesis) - the maturation, development and formation of blood cells
a. red bone marrow (myeloid tissue) - location of hematopoiesis; in blood
sinusoids which connect with capillaries; mainly in axial skeleton and heads of
femur & humerus
b. hemocytoblast (stem cell) - the mitotic precursor to blood cells before
differentiation
i. differentiation - maturing cell becomes "committed" to being certain type
blood cell
2. erythropoiesis - the maturation, development, and formation of Red Blood Cells
(erythrocytes)
hemocytoblast ->
proerythroblast ->
early (basophilic) erythroblast ->
late (polychromatophilic) erythroblast ->
(hemoglobin) normoblast -> (nucleus ejected when enough hemoglobin)
reticulocyte -> (retaining some endoplasmic reticulum)
ERYTHROCYTE
hemocytoblast -> reticulocyte 3-5 DAYS
reticulocyte -> ERYTHROCYTE 2 DAYS (in blood)
ERYTHROCYTE lifespan 100-120 DAYS
(primarily destroyed by macrophages in the spleen)
3. Regulation of Erythropoiesis
a. hormonal controls - erythropoietin is the hormone that stimulates RBC
production
DECREASED oxygen level in blood causes KIDNEYS to increase release of erythropoietin
1. Less RBCs from bleeding
2. Less RBCs from excess RBC destruction
3. Low oxygen levels (high altitude, illness)
4. Increased oxygen demand (exercise)
Eythropoietin now genetically engineered and synthesized by AMGEN of Thousand Oaks.
Testosterone can also mildly stimulate production of RBCs in humans

b. Iron - essential for hemoglobin to carry oxygen
i. 65% of Fe in body is in hemoglobin
ii. liver and spleen store most excess Fe bound to ferritin and hemosiderin
iii. Fe in blood bound to transferrin
iv. daily Fe loss: 0.9 mg men/l.7 mg women
v. women also lose Fe during menstrual flow
c. B-complex Vitamins - Vitamin B12 and Folic Acid essential for DNA
synthesis in early mitotic divisions leading to erythrocytes
D. Erythrocyte Disorders (Anemias & Polycythemias)
1. Anemias - a symptom that results when blood has lower than normal ability to carry
oxygen
a. Insufficient erythrocyte count
i. hemorrhagic anemia - loss of blood from bleeding (wound, ulcer, etc.)
ii. hemolytic anemia - erythrocytes rupture (hemoglobin/transfusion
problems, infection)
iii. aplastic anemia - red marrow problems (cancer treatment, marrow
disease, etc.)
b. Decrease in Hemoglobin
i. iron-deficiency anemia - low Iron levels (diet; absorption, bleeding,
etc.)
ii. pernicious anemia - low Vitamin B12 (diet, intrinsic factor for Vit B
absorption)
c. Abnormal Hemoglobin (usually genetic)
i. thalassemia - easily ruptured RBCs (Greek & Italian genetic link)
ii. sickle-cell anemia - sickle-shaped RBCs (genetic Africa, Asia, southern
Europe link)
2. Polycythemia - excess RBC count, causes thick blood
a. polycythemia vera - bone marrow problem; hematocrit may jump to 80%
b. secondary polycythemia - high altitude (normal); or too much erythropoietin
release

c. blood doping in athletes - RBCs previously withdrawn are transfused before an
event; more RBCs, more oxygen delivery to the body
III. Leukocytes (white blood cells; WBCs)
A. General Structure and Function
1. protection from microbes, parasites, toxins, cancer
2. 1% of blood volume; 4-11,000 per cubic mm blood
3. diapedesis - can "slip between" capillary wall
4. amoeboid motion - movement through the body
5. chemotaxis - moving in direction of a chemical
6. leukocytosis - increased "white blood cell count" in response to bacterial/viral
infection
7. granulocytes - contain membrane-bound granules (neutrophils, eosinophils, basophils)
8. agranulocytes - NO membrane-bound granules (lymphocytes, monocytes)
B. Granulocytes - granules in cytoplasm can be stained with Wright's Stain; bilobar nuclei; 10-14
micron diameter; all are phagocytic cells (engulf material)
1. neutrophils - destroy and ingest bacteria & fungi (polymorphonuclear leuks.; "polys")
a. most numerous WBC
b. basophilic (blue) & acidophilic (red)
c. defensins - antibiotic-like proteins (granules)
d. polymorphonuclear - many-lobed nuclei
e. causes lysis of infecting bacteria/fungi
f. HIGH poly count --> likely infection
2. eosinophils - lead attack against parasitic worms
a. only 1-4% of all leukocytes
b. two-lobed, purplish nucleus
c. acidophilic (red) granules with digest enzymes
d. phagocytose antigens & antigen/antibody complex
e. inactivate chemicals released during allergies
3. basophils - releases Histamine which causes inflammation, vasodilation, attraction of
WBCs
a. RAREST of all leukocytes (0.5%)
b. deep purple U or S shaped nucleus
c. basophilic (blue) granules with HISTAMINE
d. related to "mast cells" of connective tissue
e. BOTH release Histamine with "IgE" signal

f. antihistamine - blocks the action of Histamine in response to infection or
allergic antigen
C. Agranulocytes - WBCs without granules in cytoplasm
1. lymphocytes - two types of lymphocytes
a. T lymphocytes - (thymus) respond against virus infected cells and tumor cells
b. B lymphocytes - (bone) differentiate into different "plasma cells" which each
produce antibodies against different antigens
c. lymphocytes primarily in lymphoid tissues
d. very large basophilic (purple) nucleus
e. small lymphocytes in blood (5-8 microns)
f. larger lymphocytes in lymph organs (10-17 mic)
2. monocytes - differentiate to become macrophages; serious appetites for infectious
microbes
a. largest of all leukocytes (18 microns)
b. dark purple, kidney shaped nucleus
D. Leukopoiesis and Colony Stimulating Factors (CSFs)
1. leukopoiesis - the production, differentiation, and development of white blood cells
2. colony stimulating factors (CSF) - hematopoietic hormones that promote leukopoiesis
a. produced by Macrophages and T lymphocytes
i. macrophage-monocyte CSF (M-CSF)
ii. granulocyte CSF (G-CSF)
iii. granulocyte-macrophage CSF (GM-CSF)
iv. multi CSF (multiple lymphocyte action)
v. interleukin 3 (IL-3) (general lymphocytes)
3. leukopoiesis - all cells derived from hemocytoblast
1. myeloid stem cell-> 2. lymphocyte stem cell->
myeloblast-> monoblast-> lymphoblast->
promyelocyte-> promonocyte-> prolymphocyte->
a. myelocyte-> MONOCYTE-> LYMPHOCYTE->
b. metamyelocyte-> (macrophages) (B cell  plasma cell, memory cells, T-cells)
c. band cell-> (3 month lifespan) (days-decades lifespan)
EOSINOPHIL }
NEUTROPHIL } (0.5 to 9 day lifespan)
BASOPHIL }

E. Disorders of Leukocytes
1. leukopenia - abnormally low WBC count
a. HIV infection, glucocorticoids, chemotherapy
2. leukemia - cancerous condition of "line" of WBCs
a. myelocytic leukemia (myelocytes)
b. lymphocytic leukemia (lymphocytes)
c. acute leukemia - cancer spreads rapidly
d. chronic leukemia - cancer progresses slowly
e. anemia, fever, weight loss, bone pain
f. death from internal hemorrhage or infection
g. chemotherapy & radiation therapy used to treat
3. infectious mononucleosis - caused by Epstein-Barr virus, excessive monocytes and
lymphocytes; fatigue, sore throat, fever; 3 week course
IV. Platelets (thrombocytes - "clotting")
A. General Characteristics
1. very small, 2-4 microns in diameter
2. approximately 250-500,000 per cubic millimeter
3. essential for clotting of damaged vasculature
4. thrombopoietin - regulates platelet production
B. Formation of Platelets
hemocytoblast->
myeloid stem cell->
megakaryoblast->
promegakaryocyte->
megakaryocyte-> (large multilobed nucleus)
platelets (anucleated parts of megakaryocyte cytoplasm)
V. Plasma (the liquid part of blood)
1. plasma makes up 55% of normal blood by volume
2. water is 90% of the plasma by volume

3. many different SOLUTES in the plasma
a. albumin - pH buffer & osmotic pressure
b. globulins - binding proteins & antibodies
c. clotting proteins - prothrombin & fibrinogen
d. other proteins - enzymes, hormones, others
e. nutrients - glucose, fatty acids, amino acids, cholesterol, vitamins
f. electrolytes - Na+
, K+
, Ca++
, Mg++
, Cl-
, phosphate, sulfate, bicarbonate, others
VI. Hemostasis (stoppage of blood flow after damage)
1. vascular spasms (vasoconstriction at injured site)
2. platelet plug formation (plugging the hole)
3. coagulation (blood clotting - complex mechanism)
B. Vascular Spasms
1. first response to vascular injury - VASOCONSTRICTION is stimulated by:
a. compression of vessel by escaping blood
b. injury "chemicals" released by injured cells
c. reflexes from adjacent pain receptors
C. Formation of a Platelet Plug
1. damage to endothelium of vessel
2. platelets become spiky and sticky in response
3. platelets attach to damaged vessel wall to plug it
4. platelets produce thromboxane A2 - granule release
5. serotonin release enhances vascular spasm
6. ADP - attracts and stimulates platelets at site
7. prostacylin - inhibits aggregation at other sites
VII. Coagulation (blood clotting)
A. General Events in Clotting
platelet cells activated by damage->
PF3 and/or Tissue Factor produced by platelet cells->
Factor X activated->
prothrombin activator (enzyme) produced->
prothrombin conversion -> thrombin (another enzyme)
thrombin stimulates: fibrinogen----> fibrin mesh

1. anticoagulant - chemical that inhibits clotting
2. procoagulant - chemical that promotes clotting
3. intrinsic pathway - within the damaged vessel
a. more procoagulants needed (I-XIII) toward PF3 and Factor X
b. allows more "scrutiny" before clotting occurs
4. extrinsic pathway - in outer tissues around vessel
a. tissue thromboplastin (Tissue Factor) - skips intrinsic steps straight to PF3 and Fac
X
b. allows rapid response to bleeding out of vessel (clot can form in 10 to 15 seconds)
5. After activation of Factor X, common pathway:
Factor X, PF3 (thromboplastin), Factor V, Ca++
-->
prothrombin activator ->
prothrombin converted -> thrombin (active enzyme)
thrombin stimulates: fibrinogen -> fibrin (meshwork)
Ca++
& thrombin -> Factor XIII (fibrin stabilizer)
B. Clot Retraction (shrinking of clot)
1. actomyosin - causes contraction of platelets
2. blood serum - plasma WITHOUT clotting Factors
3. platelet-derived growth factor (PDGF) - stimulates fibroblast migration and
endothelial growth
C. Clot Eradication (Fibrinolysis)
1. healing occurs over 2 - 10 days
2. tissue plasminogen activator (TPA) - causes the activation of plasminogen
3. plasminogen--> plasmin
4. plasmin degrades proteins within the clot
D. Factors Limiting Growth and Formation of Clots
1. Limiting Normal Clot Growth
a. blood moves too fast to allow procoagulants
b. factors interfere with normal clotting
i. prothrombin III - deactivates thrombin
ii. protein C - inhibits clotting Factors
iii. heparin - inhibits thrombin; prevents adherence of platelets to injured
site

Plasma Membrane Transport and Cell Physiology Notes

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