Physiology

A Message from the Author
Dear Emerging Biologist,

Welcome to the word of Human Physiology. I remember the
rst time my passion for biology was awakened. There I was,
sitting in my Physiology class in college and the rst section
was on the Nervous System. Wow, I was immediately
amazed at the complexity of it all. Little tiny neurons, smaller
than the human eye could see, with so much going on that
we still cannot fully explain everything thats going on in there.
However, there is one thing that I know. Many people struggle
to understand some of the concepts because of how complex
they are. That is the exact reason why you are reading this
today. These notes are the result of some crazy typing during
my physiology class, and many hours of work since then.
When I took the class, I was determined to type as much of
what my professor said, so that when it was time to study, I
had EVERYTHING I needed in my notes. That was not my
only motivating factor. I also wanted to be able to provide it as
a resource for the other students in my class.
What happened next amazed me. Everyone in that class was
using my notes. Not only that, but people who took the class years after are still using my notes today
and letting me know how much it helped them to pass a class that they thought they would fail. To
make it even better, I started getting people from different parts of the globe letting me know that my
notes helping them in their classes. This really does my heart well. To think that something that I did so
long ago (10+ years) can help so many people is just amazing.
So, I decided to spruce them up a little. I went through, made some structural changes, added some
more content and images to help to make it even MORE helpful and the result is the ebook that you
have before you. Ill also be adding lots of content and resources on Interactive Biology to help you do
even better, so be sure to visit often. In fact, I will be linking to videos that enhance the content all
throughout this study guide. Whenever, you see the following icon (except this rst one), you can click
on it and go to the relevant video.
I really hope all of these resources help you not only pass your Physiology class, but pass with a HIGH
A. My goal is to make it as easy for you as possible.
Happy Learning!
Leslie Samuel
www.Interactive-Biology.com
Human Physiology - By Leslie Samuel
Copyright 2014, www.Interactive-Biology.com. Join The Academy. - Back to Table of Contents
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Table of Contents
You may click any title to go directly to the section
The Types of Neurons p. 5 Visual Processing p.29
The Functions of Neurons p. 6 On Center, Off Surround
Ganglion cells
p.30
Ion Channels p. 7 Phonoreception p.32
Donnan Equilibrium p. 8 The Muscular System p.35
The Na-K Pump p. 9 The Sliding Filament Theory p.37
V-gated ion channels p.10 Sarcomere Structure and
Function
p.38
Conductance p.10 The Circulatory System p.40
The Nerve Impulse/Action Potential p.12 Control of the Heart Beat p.42
Refractory Periods p.12 Contraction of the Heart p.44
Conduction Velocity p.13 Regulating Stroke Volume p.44
The Synapse p.14 Regulating Cardiac Output p.45
Summation and facilitation p.16 Regulating Blood Pressure p.46
Neurotransmitters, agonists and
antagonists
p.18 Regulating Peripheral
Resistance
p.47
Organization of the Central
Nervous System
p.19 The Cardiac Cycle p.50
Organization of the Brain p.21 Human Circulatory Difculties p.52
Intellectual Functions and Sleep p.23 The Respiratory System p.54
The Sensory Nervous System p.25 The Oxygen Dissociation Curve p.56
Receptors p.25 The Human Respiratory System p.58
Photoreception p.26 Pressure changes during
Respiration
p.59
Retinal Structure p.28
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The Nervous System
The Nervous System
The Types of Neurons
There are many different types of neurons (morphologies). In this section, we will deal with the general
categories, starting with the one that is typically shown in textbooks. However, keep in mind that this is
a simplied version that is illustrated to simply show the parts of a neuron. In real life, neurons deviate
from this Classical Neuron signicantly, but have the same general structures and characteristics.
The Multipolar Neuron (Classical Neuron): This neuron has one axon (which is typical of nerve
cells, more axons are rare cases), and numerous dendrites. In this picture, the dendrites are the
treelike arborization that comes from the soma. The axon
terminals of the input are where the EPSPs and IPSPs
originate.
Dendrites are the points of synaptic connections. Some
synaptic connections are made with the soma and are
"the same" as dendrite connections. Connections on the
soma are usually the "stronger" connections. This axon
is branching (typical).
The Soma is the part of the neuron that is most like
other cells. It has the nucleus, genetic machinery, and is
where many of the metabolic processes happen.
However, mRNA molecules are sometimes targeted for a specic site for the release
of neurotransmitter.
Neurons are among the most complex of cells. The Axon has a base where it is continuous with the
soma. This swollen section is called the axon hillock, or the "spike" initiating zone (where the nerve
impulse originates). This is the rst region of the neuron with Voltage-gated (V-gated) ion
channels. This is a requirement for a nerve impulse. When the nerve impulse begins, it travels
down the axon. It then reaches the axon terminals, who's function is to release neurotransmitter,
which then cause EPSPs and IPSPs in the following neuron (to be discussed later).
Other Morphologies
Unipolar: Has no dendrites. The synaptic connections are with the soma, whos membrane
functions as dendrites.
Pseudounipolar: There is only one process coming off the soma but there are dendrites and
axons (most common in the animal world - insects and invertebrates). There is a spike initiating
zone but it isn't anatomically distinguishable.
Bipolar: Has only 2 processes coming of the soma, but the dendritic process can be complex.
One base connection.
As you can see, there are a variety of morphologies. However, they all have the same functional
regions:
The dendrites and soma: This is where the neuron receives its input
The Axon hillock and Axon: These allow the neuron to conduct nerve impulses
The Axon Terminals: These are the sites of neurotransmitter release
Axon
Axon
Terminals
Soma
Dendrites
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Detailed Diagram of a neuron
Functions of Neurons - In order for us to understand the functions of neurons, we need to rst look at
the proteins that are found in the membrane, because these proteins determine the function of neurons.
Passive or leakage ion channels: These are the routes for ions to move across the membrane.
They are always open and are distributed throughout the whole neuron. The channel is made up of
5 alpha helices. There are nonpolar parts (exterior) and the and polar parts (interior), causing a
polar route through the nonpolar lipid bilayer that is water-lled. These leakage channels are
EVERYWHERE in the neuron, but their densities are not the same everywhere.
Sodium-potassium pump (Na-K pump): This pump pumps 3 Na
+
ions out for every 2 K
+
ions that
it lets in.
V-gated ion channels: These channels can be open or closed. The factor that determines whether
it is open or closed is the membrane voltage. If it is more positive interiorly, this can cause the
channels to open. There are 2 classes that we will be talking about mainly: Na
+
and K
+
channels.
These occur in the axon and dene the axon. Because of these channels, the axon can create and
transmit nerve impulses.
Ligand-gated channel: A ligand is a typically small molecule that is bound by a larger molecule - in
this case, the channel protein. A ligand-gated channel is one that opens when it binds a specic
ligand. Neurotransmitters are the class of ligands that we will be dealing with. These channels
Watch Video
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dene, and are distributed in, the input region of the neuron (dendrites and soma).
These various proteins are targeted as they are synthesized for the various regions of the neurons.
Lets take another look at the functional regions of neurons in
references to the proteins:
The dendrites and soma: This is where the neuron receives its
input and is the integration area of the neuron. Proteins: Ligand-
gated ion channels, passive ion channels, Na-K pump.
The Axon hillock and Axon: These allow the neuron to
produce and conduct nerve impulses. Proteins: V-gated ion
channels, passive ion channels and Na-K pump.
The Axon Terminals: These are the sites of neurotransmitter (NT) release. Proteins: V-gated
channels (Ca
2+
), passive ion channels and Na-K pump.
Ion Channels
The cell membrane is made up of a phospholipid bilayer and is an impenetrable barrier for ions.
Cells exhibit selective permeability.
Ions can only cross cell membranes through watery pores called ion channels.
If a cell has channels for a particular ion, the cell is permeable to that particular ion.
Excitable cells are very permeable to K+ and slightly permeable to NA+. There are more K+
leakage channels than Na+ leakage channels
Leakage Channels are ion selective.
Ion selectivity - tetrodotoxin (TTX). This is a protein that is toxic and is found in a species of
japanese sh. It plugs the opening of leakage and V-gated Na+ channels, showing that they are
selective for NA+.
There is another toxic substance called tetraethyl ammonium (TEA), which plugs up K+ channels.
More evidence that these channels are ion selective.
The inside of the membrane is negatively charged. This is due to:
Negatively charged proteins that are found inside the cell.
The Na-K pump, which pumps 3 Na+ out of and 2 K+ into the cell.
When you add more channels, conductance will increase and resistance
decreases. If you add K+ channels the conductance of K+ will increase. If you
add Na+ channels, conductance for Na+ increases. Adding K+ channels will not
change conductance for Na. Conductance for K+ is 100 times greater than Na+
(passively).
There are 2 factors that control the passive movement of ions across the membrane:
Diffusion
Charge
Because inside the cell is negatively charged, that will pull K+ into the cell. However, Diffusion pulls it
outside of the cell. This causes an equilibrium to be established when the rate of movement by diffusion
equals the rate of movement by charge. This is called the Donnan Equilibrium.
Watch Video
Passive ion channels and
Na-K pumps are found all
throughout the membranes
of neurons.
Electric current
is the movement
of charge.
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Donnan Equilibrium
The Isoelectric point of a protein is the pH at which it has a net charge of zero. If there are a lot of
carboxyl groups, the isoelectric point will be more acidic. Intracellular proteins in most cells have an
average isoelectric point of 4.5 - 4.7. Cellular pH is 7.2. This gives the proteins in a cell a negative
charge.
Membrane potential (Em) = charge across the membrane.
Resting potential (Erest) = membrane potential of a resting nerve cell.
In resting neurons the membrane potential ranges between -50-80mV
Lets look at how the Donnan equilibrium is established. Lets say that we are starting off with + charged
ions outside the cell. There is an electrical charge inward (due to the negative charge inside the cell),
and a movement by concentration inward. The internal concentration increases. There will come a point
where the concentration inside and outside will be equal. However, there will still be an inward
movement due to charge.
Eventually, the concentration of that ion will be greater on the inside than outside. At this point, diffusion
will then send the ion out. The charge inside is becoming less negative. There will come a point where
the outward movement by concentration gradient equals the inward movement by concentration. This
point is the Donnan equilibrium for that particular ion.
How to calculate Equilibrium Potential
There are two types of work in this situation: Work done by diffusion and work done by charge
attraction. At Donnan equilibrium Work by diffusion (osmotic work - OW) = work by charge attraction
(Electrical work - EW). So the net work = 0
OW = RT* ln(C1/C2) EW= nFE
n = charge of Ion
F = Farraday constant
E = Voltage difference
(V): E= (RT/nF)ln(C1/C2)
(mV): E = 58 log(C1/C2) <--- Take home message
For a + charged ion: C1 = Outside concentration, and C2 = inside concentration
For a - charged ion: C1= Inside concentration, and C2 = outside concentration
E = equilibrium pot.
Eion = equilibrium potential for a particular ion (ENa/EK etc.)
Em (membrane potential) = -60mV
Concentration ratio (10 out/1 in)
Ena = 58 log (C1/C2) = 58mV
Watch Video
Watch Video
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The Na-K pump
The Na-K pump traverses the membrane and has binding sites for both Na and K. It starts off with the
pump protein in it's low energy conguration. It has an ATP bound to it but the ATP hasn't given away its
phosphate as yet. The pump is open to the inside of the cell. There are 3 binding sites for Na+. When 3
Na+ bind, there is a signal that causes an inorganic phosphate (Pi) from the ATP to be transferred to
the Protein. This then causes a conformational change to it's high energy state. In this high energy
conguration, the pump is open to the outside of the cell. The Na no longer ts it's binding sites so Na is
released.
The binding sites for K now t K ions. When 2 K+s binds to the binding site, then the Phosphate is
removed (the ester link is hydrolyzed). ATP then attaches to the protein and the pump opens to the
inside. Binding sites for K no longer t so the 2 K+ are released to the inside.
If you get rid of all the K outside, Na will not be pumped and vice versa. Both are needed for the
function of the Na-K pump.
Membrane potential of a "resting" neuron
Resting potential (Erest) = Membrane potential of a "resting" neuron.
Nerve impulse
Force for changing Em--> nerve impulse
DF = Em - Eion
DFna = Em - Ena
= -65mV - 58mV
DFna = -123mV
DFk = -65mV - (-93mV) = 25mV
During a nerve impulse:
Eion doesn't (really) change
Em does change
What has to happen before the DF can move ions?
The conductance of that membrane for the ion has to increase. Something has to make that ion more
able to move across the membrane. That something has to do with the V-gated ion channels. During a
nerve impulse ions move across the membrane so readily that the pump is not really a factor. The
conductance is really big and the ions can move quite freely across the membrane. Lets look at how
that happens.
This means that the Em is far away from Ena. This will result in a
force trying to move Na+ into the cell because Na+ wants to be at its
equilibrium. Its where the ion is most comfortable. Force to move
ions across membranes = Em - Eion = Driving force (DF). So DF
for Na+ will be -118mV. If the channels are opened, Na+ will rush
into the cell until DF = 0 at 58 mV (all or nothing).
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V-gated ion channels
Na-channel: This protein is an integral protein in the membrane. Its presence makes the membrane
axonal (in other words, it gives it the ability to produce an action potential). It traverses the membrane
via 24 helices. There are 4 groups of 6 helices (alpha component). There are two features of each of
these groups that we are crucial:
Helix four in each group (M4) has a bunch of amino acid residues that bear + charges (a lot of
amine bearing R groups). This is the trigger that opens the v-gated Na Channels. It is a positively
charge voltage sensor. There are at least 40 different genes that encode for V-gated Na channels
and there are variants on a theme. When we talk about the v-gated Na channel we are
generalizing.
Between M5 and M6, there is a loop of amino acids that is not in helix formation. These loops lines
the pore providing the environment that the Na ions move through. These are also what makes the
channel selective.
Subcomponents of the V-Gated Na Channel
Selectivity lter - involves critically located negative charges (CO-OH R groups) and residues that
remove the hydration shell from Na ions.
Activation gate - It is a piece of the protein that can close and open the pore. It is a sequence of
amino acids that face the inside of the membrane.
Voltage sensor: positively charged helix pore. Helix 4- repelled outward by a positive change in Em.
The positive helices are repelled towards the outside of the cell when there is a positive change on
the inside of the cell (positive repels positive). It is linked to the activation gate and causes it to
open. Na ions can then move in. The opening of this channel can only be described in terms of
probability. There isn't a particular value that all of them will open at. Some channels require a
bigger positive change.
There is also an inactivation gate that closes automatically about .5 -1ms. This channel cannot be
opened again until the Em inside gets back negative when the nerve impulse is nearly over.
The Voltage gated K channel has no inactivation gate and stays open longer than the V-gated Na
channel. The amount of positive change that makes K gate open is much greater than that for Na
channels. That means that Na channels open rst.
Conductance
Gna is the conductance of the axonal membrane for Na. Erest = -70. Ek=-93. Ena=58. If conductance of
the membrane goes up for Na it's going to move in. Ethres: ring threshold for the neuron.
Denition of threshold: The threshold is the membrane potential that when reached will result in a
nerve impulse.
It is crucial that the v-gated Na channels open at a lower membrane
potential than K channels, because the membrane potential wouldn't
change much. As Na comes in, K would go out.
- 10 -
Because Em reaches a value where increase in Gna that is signicantly greater than the increase of Gk,
this results in more Na entering than K leaving, thus the Em becomes more positive. If Em becomes
more positive, Gna will increase. More v-gated Na channels will open, and Em becomes more positive
(positive feedback).
Denition of Threshold revisited: Threshold is the membrane potential that results in a greater
increase in Gna than in Gk. The threshold varies depending on the architecture of the axon, especially
in the spike initiating zone.
In the situation when the resting potential reaches the threshold we get the positive feedback, which
results in a nerve impulse (action potential).
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The Nerve Impulse/Action Potential
Here are the Sequence of events that will lead to the production of a nerve impulse/action potential:
A stimulus causes Em to reach the threshold. This means that more v-gated Na channels open than
v-gated K channels, which also means that more Na
enters than K leaves (large DFna). Therefore, Em
becomes more "+".
As Em becomes more positive, more v-gated Na
channels open, which means that Gna increases, which
means more Na enters. This is called depolarization.
Essentially all v-gated Na channels open and Gna
becomes maximal. Therefore Em approaches Ena. The
driving force for Na decreases and inactivation gates
start closing.
At this point, V-gated K channels start to open. Nerve
impulses reaches a peak near Ena.
During repolarization. V-gated Na channels inactivate,
V-gated K channels open, membrane potential moves
towards Ek (negative).
After hyperpolarization. Em->Ek. V-gated K channels
are closing. V-gated Na channels reset to close.
Repolarization is necessary to reset the v-gated Na channels from inactivated to their closed
conformation.
Refractory Periods
Whenever an action potential happens in a neuron, there is a period that follows wherein it is difcult to
cause another action potential. This is called the refractory period. There are two types:
Absolute refractory period: During this period, the axon cannot be stimulated strongly enough to
create another action potential. The ring threshold is innitely high. No matter how strongly you
stimulate the axon during this period, no impulse will happen. This is because it is a period during
which V-gated Na channels are either open or inactive. In these states, they cannot be reopened.
V-gated Na channels start resetting at the end of the absolute refractory period.
Relative refractory period: It takes a higher than normal (resting) stimulus to create an action
potential.
Early in the relative refractory period, the threshold is very high, which means that it takes a very
large stimulus to create an action potential because only a few v-gated Na channels are reset to
closed.
In the middle of the relative refractory period, the threshold is higher than during rest but lower
than at the beginning. This requires a stimulus that is larger than rest but smaller than at the
beginning. This is because more v-gated Na channels are reset to closed.
Watch Video
Watch Video Watch Video Watch Video
- 12 -
At the end of the relative refractory period, threshold reaches its lowest value, which is typical of
rest. The stimulus required for threshold equals what is required at rest. All v-gated channels are
closed.
Conduction Velocity
When an action potential begins, Na enters into the cell and positive charges are repelled in both
direction. This is electrical conduction along the axon and is called electrotonic conduction. This
current is made up of positive charges. It is fast and progressively lost (due to resistance). The
movement of the Na across the membrane is not nearly as fast as current ow along the membrane,
but is not lost, because it is determined by Ena. So Electrotonic conduction is faster than movement
across the membrane. Eventually, the current that ows along the axon will die out, or will be too small
to reach ring threshold, and have to wait for the slower process of moving Na across the membrane to
catch up.
The larger ! is, the faster the conduction velocity will be. Large diameter axons conduct nerve impulses
faster because they conserve that longitudinal electrical current due to the lower Longitudinal
resistance.The axons in most nerves are myelenated. This means that in the peripheral nervous
system (PNS), Schwann cells envelop the axon and grow around the axon so that we end up with a
number of layers. The Schwann cells are full of myelin, which is a non conducting lipid material. The
Schwann cell envelops the axon with an impenetrable barrier for ions. This makes Rm much much
greater, and the nerve impulse will travel much faster.
There are no v-gated channels under the Schwann cell. They are only found at the nodes. This also
allows the action potential to travel faster because it doesnt have to wait for v-gated Na channels to
open all along the axon, which is a slower process. It jumps from node to node in a process called
saltatory conduction.
Watch Video
! = !(rm/rl)
rm: Resistance across the membrane of the axon
rl: Resistance along the length of the axon
Watch Video
In a nerve, there are many axons. Theres a fast conducting group (alphas), a bit slower
group (betas) and a slow group (gammas), so when you look at the electrical activity of the
nerve in a graph, you will often see 3 peaks.
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THE SYNAPSE
Electrical conduction
When the signal is going to ow from one neuron to the next, it
encounters resistance. The resistance of the presynaptic
membrane is approximately 10
11
ohm. The resistance is the
synaptic cleft is 10
8
ohm. The post synaptic resistance is 10
11

ohm. The current will go to the environment with least resistance,
so most of the current will be lost via the smaller resistance in the
synaptic cleft.
One way of decreasing the resistance is by having a large
presynaptic membrane (lower resistance of 10
5
ohm), a small
synaptic cleft (higher resistance of 10
11
ohm) and and having a
large postsynaptic membrane. With this setup, the current will go
to the postsynaptic membrane with the smaller resistance instead
of leaving the synaptic cleft with a big resistance.
There are gap junctions in the pre and post synaptic membrane.
A gap junction is an array of 2 sets of connexons with direct
electrical access from 1 cell to the next. Some connexons can be
either open or closed.
Axon terminals (telodendrites) - Release neurotransmitters
The synaptic bouton is characterized by being lled with synaptic vesicles. They contain
neurotransmitter. There is a special postsynaptic membrane that responds to the neurotransmitter
molecules from the presynaptic membrane.
In the synaptic bouton, we nd Ca pumps taking Ca out, and v-gated Ca channels that brings Ca in.
When a nerve impulse comes along, V-gated Ca channels open and Ca moves into the bouton, and
that starts the process to release neurotransmitter into the synaptic cleft.
Starting conditions
We have synaptic vesicles in the terminal. They are inactive.
Synaptic vesicles are anchored to actin laments by the protein
synapsin I. As nerve impulse comes along, V- gated Ca channels
open and Ca goes inside the terminals. First, 4 Ca ions are picked
up by an internal protein called calmodulin, which then makes it
active. Calmodulin then activates a calmodulin-dependant protein
kinase (protein kinase II). Protein Kinase II causes synapsin to
release the synaptic vesicle from the actin ber. Now we go into
the docking stage.
There are two other proteins on the synaptic vesicle called
synaptophysin and synaptobrevin that are involved in the docking process. Ca binds to these 2
proteins and activates them, causing them to separate.
Synaptobrevin acts as a V-SNARE. There are 2 proteins in the presynaptic membrane that determines
where docking will take place, SNAP-25 and syntaxin (makes a T-SNARE). The combination of V-
SNARE and T-SNARE allows for the docking of the synaptic vesicle to the presynaptic membrane.
Kinases are enzymes that
catalyses phophorylation of
proteins. The most likely parts
of a protein to be
phosphorylated is an R group
with an OH
- 14 -
There is another protein called synaptotagmin (located on the vesicle), that leads to the fusion with the
presynaptic membrane. This causes exocytosis of neurotransmitter into the synaptic cleft.
The fusion of the membranes causes to bouton to increase in size. And because of this, you get a
recycling process in which you get new synaptic vesicles breaking off at the neck. The NT goes across
the synaptic cleft and binds to receptors in the dendritic membrane and open ion channels.
The Chemical synapse - post synaptic
Two types of Receptors (for neurotransmitters):
Ionotropic receptor - These are fast acting
receptors. The neurotransmitter binds to the
receptor site on the protein and the protein
includes a ion selective channel which opens as
a result of binding (ligand-gated ion channels)
Metabotropic receptor - Neurotransmitter
binds to a protein receptor in the membrane
which goes to the activation of a G-protein
which usually activates a second messenger
system.
Examples of post synaptic receptors:
The Nicotinic receptor
This receptor binds the neurotransmitter acetylcholine (ACh). When ACh binds to the receptor, it opens
the channel and the predominant effect is that Na+ moves into the cell. K+ also leaves, but the
overwhelming effect is Na+ coming in due to its strong driving force.
The nicotinic receptor is made up of 5 subunits. There are 2 alpha subunits. It takes 2 ACh's to bind the
2 alpha subunits to open the channel. When the ACh binds to the 2 separate alpha units, the channel
Watch Video
Nicotine also activates the nicotinic
receptor, and thats why we call nicotine
an agonist (a molecule that mimics the
effect of NT). Chemicals that have
effects on the Nervous system
(psychotropic) affect the behavior of NT.
- 15 -
opens and the net effect is Na entering. When Na enters we get an excitatory post synaptic potential
(EPSP).
The ACh is then quickly released so the channels can close. There is also an enzyme called
acetylcholinesterase that brakes down acetylcholine and inactivates it.
When a neurotransmitter binds to a ionotropic receptor, the result is either a depolarizing or
hyperpolarizing change in dendritic Em. If it depolarizes we call it an EPSP. If it hyperpolarizes (inhibits)
we call it an IPSP.
Synaptic transfer: What happens between the dendrite and axon. When Na+ enters, this will change
the membrane potential and makes the inside more positive EPSP. This positive charge ows by
electrotonic conduction down to the Spike initiating zone. If it is large enough to make it to threshold, it
causes the production of a nerve impulse.
When a nerve impulse is created, you cannot make another one. There will be a period of time when
the threshold is innitely high. This is the absolute refractory period (ARP). Big EPSP make nerve
impulses faster than small EPSP because the ring threshold during RRP drops below the membrane
potential of the EPSP sooner. This means that more NT can make even bigger EPSP's that makes
more nerve impulses even quicker.
There is an opposite kind of response in ionotropic receptors of different types.
Inhibition - for inhibition we need a different neurotransmitter and we need a different ionotropic
receptor. There are two important NT's - GABA and glycine. These both affect two different receptors,
but both open and close Cl- channel. There has to be a Cl pump that pumps Cl-. GABA is the most
common.
The DF for Cl moves it in and we get an IPSP. This will travel electrotonically down on to the axon as
well. This will only be meaningful in that it can stop a nerve impulse from being created.
There are 2 common poisons that affect inhibitory ionotropic receptors: strychnine and arsenic.
Strychnine is an inhibitor/antagonist for the ionotropic receptor that responds to glycine. It will eliminate
IPSP's and Nerve impulses will travel like CRAZY.
Summation and facilitation
Summation is the addition of PSPs. There are two types of summation:
Spatial Summation - summating PSPs originate from 2 different synaptic inputs.
Temporal Summation - summating PSPs originate from the same synaptic input.
There is a very crucial factor --> Summation requires a time overlap, whether we are talking about
temporal or spatial summation.
Watch Video
The control by the central nervous system is like having a whole series of trafc stops at each
synapse. It is the pathway control by the CNS that controls your behavior.
- 16 -
Facilitation is a process that results in increased NT release as a result of a presynaptic synapse,
activating a second messenger system. Sensory neuron responds to stimulus, releases NT and creates
a response in Motor neuron that we are recording. An axon terminal releases NT to the Presynaptic
membrane. The NT is seratonin.
A seratonin receptor binds seratonin (metabotropic) from the facilitory neuron. This activates a G-
protein, which activates an adenylate cyclase, which produces cAMP (2nd messenger). This cAMP
activates a cAMP-dependent protein kinase (pk). This phosphorylates a K channel in the bouton. This K
channel closes. Repolarization slows down so nerve impulse lasts longer, and more v-gated Ca
channels stay open longer. More Ca gets in, more vesicles fuse with the membrane, thus more NT
released.
The degree of facilitation changes depending on how much time is elapsed between the initial and
subsequent response.
The Muscarinic receptor - A metabotropic receptor for acetylcholine is the muscarinic receptor, so
called because muscarine is the agonist (articial anologue). It has 7 transmembrane helices and
between helix 3 and 4, there is a binding site for ACh. There is also a signal loop that contacts the G
protein, breaking it down in such a way that the G protein attaches to the channel and closes it.
**There are a variety of different ways that acetylcholine can affect different muscarinic receptors.**
All of the small NT that are involved with ionotropic receptors also have metabotropic receptors that
respond to them. The role of a metabotropic receptor is to regulate some process, not to directly
produce PSPs like ionotropic receptors.
Watch Video
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Neurotransmitters, agonists and antagonists
Fast - ionotropic: NT is always a "small" molecule. Examples are ACh and Glutamate (both
excitatory), GABA and Glycine (inhibitory), Dopamine and seratonin (some cases). In the fast
neurotransmitter system, ACh and glutamate will be consistently excitatory, and GABA and glycine
are consistently inhibitory. In the slow system they can be either fast or slow.
Slow - metabotropic.
Cholinergic - ACh-like
ACh
Succinyl choline (agonist)
Carbabhol
Nicotine (it's presence multiplies the effect of ACh). This causes the nervous system to slow
down the release of ACh. Then you become dependent of that substance to return back to
normal --> General mechanism of addiction.
Curare: Antagonist for ACH. It blocks the channel in nicotinic receptors by attaching to the
binding site, paralyzing the muscle.
Monoamines
Adrenergic (has affects similar to adrenaline/epinephrine)
Catacholamine. Dopamine is the "feel good" molecule in the nervous system. It is produced by
dopaminergic neurons. When these neurons die, it results in Parkinson's disease. Injecting
dope was one of the rst ways of treating Parkinsons.
Cocaine has it's major effect by increasing dopamine levels by slowing down the inactivation of
dopamine. Then you get the same addictive effect. Which NT is released is a function of how far
the pathway goes. Mescaline has an effect that mimics dopamine (sort of an agonist). Speed
increases the production of Epinephrine and norepinephrine tremendously. Seratonin is another
"feel-good" molecule. It is very intimately related to your sense of well-being. This is related to
depression. An individual with low levels is more likely to become depressed. Prozac raises
seratonin levels by slowing down the inactivation of seratonin.
Amino Acid Neurotransmitters
Glutamic acid - most important excitatory NT. It is a CNS NT in vertebrates. It is secreted within
neurons, put into synaptic vesicles and is secreted at synapses.
Glycine and GABA - inhibitory. The only difference between GABA and Glutamate is 1 COOH
group. The GABA receptor includes a ligand gated Cl- channel. The GABA channel has some
modulatory sites. The substances that modulates this channel are called modulators (not
agonists). On the GABA receptor there is a benzodiazapine site.
Valium is a common benzodiazapine. Valium is a tranquilizers/anxiolitic substance. Xanax is
also a benzodiazapine. When a bazodiazapine attaches to the site and then GABA attaches, the
channel opens and stays open longer. Without a benzodiazapine, the channel does not open as
long. So benzodiazapines increase inhibition and are used to help you sleep. Barbituates
operate in the same way but are more addictive.
Neuropeptides - released in large vesicles.
Opioids - creates a sense of euphoria and blocks pain - endorphins/enkepalins. They are
normally produced. Endorphins seems to be produced as a result of physical excercise. They
block pain pathways.
Substance P - one of it's effects is to increase the input of pain inducing stimuli.
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Organization of the Nervous System
It is estimated that there are over 100 billion neurons in the human body. Needless to say, there is need
for a signicant amount of organization within the nervous system.The Nervous system is divided into 2
Parts:
The Central Nervous System (CNS): this is made up of the brain and spinal
cord. This is where the control happens.
The Peripheral Nervous System (PNS): this is everything outside of the CNS
(i.e. nerves). The main purpose of the PNS is to connect the CNS to the limbs
and organs.
Groups of Neurons
There are clusters of neurons found throughout the nervous system. If these
structures are found within the CNS, they are refered to as nuclei (singular:
nucleus). If they are found outside the CNS, they are refered to as ganglia
(singular: ganglion).
Organization of the spinal cord
In the spinal cord we have
Gray matter, which is on the inside - This is where we nd all the synaptic
connections and somata. It is where control happens
White matter, which is on the outside - It contains myelenated axons and is the
wiring of the system.
The white matter is divided into tracts/pathways. These tracts contains axons that are going to similar
parts of the nervous system. If there is damage in the reex, that suggest that there is damage with the
corresponding tract. That is why doctors take reex tests.
Reexes
Some of the most elemental processes happens at the spinal cord in a predictable way. The Knee jerk
reex is extremely simple because the sensory neuron connects directly to a motor neuron and the
response is uncontrollable. Because there is no place for further processing to occur, if there is a
stimulus, there WILL BE a response. As interneurons are placed in the center, it becomes more
sophisticated.
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There is a single interneuron in the eye jerk reex so it is controllable (if you try really hard). This type of
setup is refered to as a simple reex arc, where there is a sensory neuron that transfers the signal to an
interneuron (relay neuron) in the spinal cord, which then transfers a signal to a motor neuron, which
goes to the muscle. Where the axons come together in a bundle we call a nerve. The nerve splits into a
dorsal root (sensory) and a ventral root (motor) when it is entering the spinal cord. The morphology of
sensory neurons is typically pseudounipolar running from body receptors running to the spinal cord.
There are pain receptors in the nger. Lets say that you touch a hot stove. Sensory neurons are
stimulated and send a signal to the spinal cord. This causes a reex that is mediated by the spinal cord.
This causes the jerk reex. However, there is also synaptic transfer that goes all the way up via the
spinal cord and to the somasetic cortex and that is where feeling comes into play.
Different touch receptors in the body make different connections but they all end in the somasetic
cortex. This part in the brain does not send anything back to the region of pain. The pain is actually in
your mind.
The connection of the body to the brain also happens on the motor side, so movement or the motor
response is done by the motor cortex in the brain.
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Organization of the brain
The brain starts where the spinal cord enters the
occipital bone through the foramen magnum (opening
of the skull). There is no sudden change in the
organization once the spinal cord enters the foramen
magnum. No anatomical difference exists between just
inside the brain and just outside the brain.
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The Brain Stem: This is the Lower part of the brain
and includes the following
The medulla. It is relatively simple in
organization, not very big but crucially
important. It is involved in the regulation of
many of the bodily processes that are
controlled automatically like blood pressure,
heart rate, respiration etc (autonomic
functions).
The Pons. This is located directly above the
medulla and regulates relaxation
The Midbrain.
Cerebellum - dorsal outgrowth of the medulla. It is involved in the control of movement. Resent
research indicates that it is also involved in spatially organized senses and movement, and even
spatial memory. To move an object from one place to the next, you always base movement on the
knowledge of movement just accomplished.
The cerebellum is checking the command to move with the movement accomplished. If the two
dont match it corrects it. There is feedback to the cerebellum of movement and error correction is
dependent on the cerebellum. One of the most obvious results of damage in this region is spastic.
This is a loss of coordination.
Thalamus + hypothalamus: These are outgrowths of a region of the developing brain called the
diencephalons (developmental term). They are not huge but extremely important.
The hypothalamus has a number of important functions. The posterior pituitary is a direct
outgrowth of the hypothalamus. The posterior pituitary combined with the anterior pituitary make
up the pituitary gland. The anterior pituitary does not develop from the brain, but is controlled by
the brain in a very heavy way. It controls much of the rest of the endocrine system and it is in
turn controlled by hypothalamic neurons. In the hypothalamus, there are a number of regions
involved in control of behavior and other physiological processes. e.g. we can identify specic
groups of neurons in the hypothalamus, destroy them and the experimental animal will eat itself
to death in about a week. There are neurons, which produce neurochemicals that says "That is
enough already", which turns down the sense of hunger.
There are other nerve cells that do the opposite. They produce neurochemicals that stimulate
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hunger. If they are missing, the experimental organisms will starve to death. There are other
neurons that if you inject concentrated salt solution, the animal starts drinking. These nerve cells
detect the osmolarity of the cerebral uid and tell the animal to drink. This shows only a few of
the physiological and behavioral processes controlled by the hypothalamus. The hypothalamus
controls the cerebral hemisphere.
The Thalamus: These are the walls of the tube. It is just above the hypothalamus and
regulates, in very important ways, the functioning of the cerebral cortex. Nerve trafc in and out
of the cerebral cortex to the rest of the body all goes through the thalamus. If you are going to
move, that's a result of what happens in your cortex, but the command neurons for your moving
makes synaptic connections in the thalamus before going to the rest of the body. It is a
regulatory gateway to the rest of the body.
There are two Cerebral Hemispheres. In the spinal cord, gray matter is central, and white matter
surrounds it. In the cerebral hemispheres most of the gray matter is on the surface. We use the term
cerebral cortex to refer to the outer surface of the cerebral hemispheres. It is typically only 8-10 layers
deep. The blood supply comes from the surface. This is clearly the most metabolically active part of the
brain.
The central white matter (myelenated axons) gives you the bulk of the cerebral hemispheres. The
corpus callosum, along with some other connections, connects the 2 hemispheres and coordinates
what happens between the left and right hemispheres.
The Cerebral cortex
The visual association area is a region that is very active when you are building complex visual images.
The general interpretive area is active in putting together different types of stimuli (e.g. smell and vision.
The visual cortex is primary. The general interpretive area is more complex. The motor cortex is just
anterior to the central sulcus.
The most anterior part of the motor cortex controls the most posterior part of the body. The right motor
cortex controls the left side of the body and vice versa. Your body is represented upside down and
backwards in the brain. Right=Left and Up=down.
The degree of control puts a requirement on the nervous system puts a demand for more neurons. The
more nely we control movement, the more of the motor cortex we take up. A big part of the motor
cortex is for speech.
You can't teach a monkey to speak because they have a smaller portion of the motor cortex attributed
to speech. However, these animals are more highly coordinated muscularly than we are, so they can be
taught to speak sign language.
The way station in vision is the lateral geniculate. This is a region of the thalamus. The thalamus is
also a gateway for regulating consciousness.
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The motor association area is next to the motor cortex and is crucial to developing nely tuned
movements. The primary motor cortex will send the signals out, but it will go through the motor
association area.
The broca's area is associated to speech. Damage to this area will result in organisms that cannot
form words.
Somasthetic cortex
Sensory area (cortex)
Somatic association area - where more highly developed body based sensory experiences are
located. This is where your body position sense is put together.
Intellectual functions
Your intellectual function is an outcome of everything your brain is doing. The frontal and prefrontal
lobes are very important in intellectual functions. The thalamus is also very much involved. The
thalamus is the interconnecter, and in intellectual function the activity of different parts of the cortex are
interconnected through the thalamus. Another important part are the association areas. They integrate
input from different senses to make complex integrations of what's going on.
One of the most important functions of intellectual functions is MEMORY - By memory we mean the
ability to be aware of something that has happened and is no longer happening. Memory happens in
stages:
The rst stage is sensory memory: The ability to remember the information from where your eyes
just was and connect it to where you eyes are now - e.g. reading - (seconds)
Short term memory: (1 - 2 hours). Based in part on an "active circuit". There are pathways in your
brain that get connected and reverberate. In addition there are also some molecular components.
Long term memory: clearly dependent on molecular changes at different places in the cortex.
There is one region of the cortex called the hippocampus. Damage to or deterioration of the
hippocampus retards memory.
CONSCIOUSNESS
The hypothalamus and thalamus are involved in regulating the change from conscious to unconscious
and vice versa. In the hypothalamus there are groups of neurons that seem to induce sleep/
unconsciousness and other groups that seem to induce consciousness, but it does it through the
thalamus.
The reticular activating system (RAS) - based on a network of interconnected neurons, located
primarily in the brain stem - reticular formation. It interconnects with the hypothalamic and thalamic
stems. Sensory input goes to the RAS as well as to the parts of the brain where you get sensory
experience. The sensory input activates the RAS. When someone pokes you in your sleep and you
wake up, it is not because of the touch but it is because it goes to the RAS.
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Consolidation: Transformation of short term into long term. It happens when you sleep.
Especially happens in REM (rapid eye movement) sleep. MMDA receptors are important in
this process.
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If you are awake and you are put into an area where there is hardly
any sensory stimulus (sensory depravation), you begin to hallucinate
and after a while you can get emotional problems.
Sleep is unconsciousness. Deep sleep is marked by a delta wave in
the EEG. There is hardly any brain activity. In the sleep cycle you
tend to have varying levels of consciousness. It cycles. The time-
period between 2 points in a cycle is typically 1.5 - 2 hrs.
The High point in the cycle is called REM sleep. Here is when you
dream. Everyone should dream every 1.5-2 hours. This is also where
consolidation happens. It is called Rapid eye movement sleep because if you put electrodes in the
corner of the eye you will see muscle contractions in the eye.
Sleep rhythm is very
important, and if you dont
have enough alpha and
delta waves, you can go
crazy.
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THE SENSORY NERVOUS SYSTEM
Receptors
There are two types of receptor cells from a developmental perspective:
Primary - neuron or derived from neuron. Developmentally, they are derived from the neuroblast -
embryonic cells that produce a number of different kind of cells, one of which are neurons.
Secondary - Epidermal derivative but not from Neuroblast. (comes from the part of epiderm that
makes the body covering). The receptors respond to stimuli and usually cause in the increase of
neurotransmitter release.
Common mechanism - production of a change in membrane potential, which is excitatory - Receptor
potential (generator potential). Receptor cells are specialized to respond to a particular class of
stimulation.
Pacinian corpuscle - has a special series of membranes surrounding the ending of a neuron (where a
dendrite would be). It responds to applied pressure by depolarizing (receptor potential). As stimulus
strength increases, we see that Em change increases. If it reaches threshold, you get an action
potential. receptor potentials either produce AP's directly or cause the release of neurotransmitter, and
the NT produces AP's in another cell. Receptor potential acts as an EPSP.
Mechanoreceptors - based on the stimulus stretching it open. The more of these channels open,
the bigger the Receptor potential. Strong stimuli produce a bigger receptor potentials. Bigger
receptor potentials makes faster nerve impulses (more frequently).
Stretch receptors (e.g. craysh) - located along the muscle. Stretching moves these dendrites,
located in these dendrites are the same kind of channels as in the mechanoreceptors. If the stretch
is small we see a small receptor potential --> slow nerve impulses. If the stretch is large we see a
large receptor potential and that will lead to quicker nerve impulses.
Tonic stretch receptor - Continually "res" in response to an unchanging stimulus.
Phasic receptor - completely adapts to an unchanging stimulus. They respond specically to
change in stimulus.
Receptors without axons (no APs produced by receptor). The stimulus strikes the receptor, and the
receptor responds with a receptor potential and there is an increase in the release of NT, which then
goes to an EPSP postsynaptically and then action potentials in a sensory neuron.
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Photoreception
Different color light have different wavelengths. When light moves, it is moving in a linear direction while
oscillating. Wavelength is the length of one full oscillation. Photons are a kind of electromagnetic
radiation.
Can photons that have the same wavelength transfer different amounts of energy? Not usually. Bright
and dim is a function of the amount of photons.
The energy associated with a photon is called the quantum. Shorter wavelengths have more energy.
E.g. UV light is damaging because of the large amount of energy.
The camera eye
Accommodation (focusing).
Control of the amount of light which
goes to the retina (pupil).
Image formation on the retina.
Receptors - Rods and cones
General overview of vision
Light enters the eyes through the pupil.
The pupil determines how much light
enters. The lens then focuses the light onto
the retina, where the rods and cones are.
The rods and cones transfer signals to the
bipolar cells, which then transfers the
signal to ganglion cells - the cells that
make up the optic nerve.
The ganglion cells project (sends a connection to) to the lateral geniculate (structure in the thalamus).
All of the optic bers end in the lateral geniculate.
Interneuron - a neuron that is wholly contained within the CNS. The lateral geniculate bers that
project to the visual cortex are interneurons. The vision occurs in a region of the midbrain called the
optic tectum in amphibians.
The Nitty Gritty of vision
Lets take a look at what happens inside the rods when light hits the retina. The process that happens in
the cones are relatively similar to what happens in the rods.
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Rhodopsin is the visual pigment that is found in the outer segment of rods. Rhodopsin has two
subunits, a small molecule called retinal (slightly processed vitamin A), and a big protein called Opsin.
Retinol has 2 states, a cis state and a trans state. The cis state is a higher energy conguration.
Retinol in rhodopsin is called cis retinol. The numbers is the maximum wavelength of absorption.
When a photon strikes a rhodopsin molecule, the energy is used to change retinol to its low energy
conguration (trans). Thats all the photon contributes to the process. The retinol then begins to break
away from the opsin. This breakdown continues spontaneously until they are separated.
Opsin is an enzyme. It is inactive in its rhodopsin form. When retinol breaks away from opsin, it opens
up a catalytic site (active site). In the rod there is a G protein called transducin. Opsin catalyzes the
addition of a GTP to the Talpha subunit of the G protein (substitution). This removes the inactivating
subunits. The Talpha GTP activates another enzyme (phosphodiesterase) which breaks down cAMP
or cGMP. This phosphodiesterase is inactive because of the two inactivating alpha proteins. The two
alpha units are removed by the phosphodiesterase so that we free up an active cGMP
phosphodiesterase. The transducin takes on the alpha subunits.
The crucial event that leads to vision is next. The phosphodiesterase breaks down cGMP, and it is
this single step that leads to vision.
Talpha from transducin then activates cGMP phosphodiesterase by taking off the 2 alpha subunits
(phosphodiesterases always inactivate cAMP of cGMP). This suggests that cGMP is in high
concentration and that light lowers this concentration.
There are two enzymes in this pathway: Opsin and Phosphodiesterase. Thus, 2 sites of amplication
In the outer segment of the rod there are Na channels that are open when cGMP is present. When
cGMP is broken down, this closes these cGMP dependent Na channels, which decreases Na
conductance in the outer segment. In the rod, this happens in the outer segment, meaning that in the
dark a rod has a high Na conductance. Gna = (approx) Gk. This means that the resting potential will be
positive. Em = (approx) (Ena+Ek)/2
In the light, Gna<Ek. Em approaches Ek. This will lead to a hyperpolarization.
Rods do not have the proteins in the membrane, nor the structure to produce nerve impulses. It does
have a lot of synaptic vesicles. In the dark, Em is more positive than Erest. There is a increase of
neurotransmitter release of NT. In the light, Em goes towards Ek, the result is a decrease in the release
of NT.
Summary of Vision (up to this point):
Photon of light enters the eye via the pupil
Lens focuses light onto retina
In the Rods
Photon strikes rhodopsin
Retinal changes from cis to trans form
Retinal breaks away from Opsin exposing the active site
Opsin catalyzes the substitution of GTP on Talpha subunit of Transducin
THE RECEPTOR POTENTIAL CHANGE IN RESPONSE TO LIGHT IS HYPERPOLARIZED
CAUSING A REDUCTION IN NT RELEASE
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Talpha GTP activates phosphodiesterase (PDE)
PDE breaks down cGMP
This closes cGMP-dependent Na Channels
The rod HYPERPOLARIZES
Amplication is really important because a single photon is enough to see light.
Retinal structure
There are a few layers in the retinal structure:
The receptors - rods and cones
Bipolar cells
Ganglion cells - somata of optic nerve bers.
Amacrine cells
Horizontal cells ---> modifying cells.
The breakdown of rhodopsin leads to hyperpolarization, which reduces NT release between the rod
and bipolar cells.These cells depolarize as a result of the reduction of neurotransmitter release by the
rod or cones. The hyperpolarization of the rod leads to the depolarization of the bipolar cells. Bipolar
cells have no axon, so the EPSP travels electrotonically.
The ganglion cells produces nerve impulses in response to the release of NT from the bipolar cells.
This is the rst place we see nerve impulses. These processes lead to vision.
Organization of photoreceptors
Rods - 125,000,000/retina
Rhodopsin is the pigment in Rods.
Rods are more sensitive to light than cones are. 100x more sensitive than cones.
Leads to black and white vision
Vision is not very high in detail.
Rods are uncommon in the center of the retina (visual center/fovea).
Cones
3 other visual pigments in the cones - red, blue and green absorbing pigments. Each of these
pigments are built like rhodopsin, but the protein is somewhat different. They are activated by
light in the same way. The effect on Na conductance is the same, except they don't absorb light
quite as readily. These leads to color vision.
There are "only" 6,000,000 cones/retina
Concentrated in the center of the retina (fovea).
We use cones for detail vision
Ganglion cells
Only 1,000,000/retina

Receptive eld of a ganglion cell
Light has to go through
all these cell layers to
reach the pigment layer
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Each ganglion cell has a receptive eld, which is dened by the location of the receptors that it is
connected to in the retina. Receptor density also determines the ability to discriminate 2 points.
There are 150,000 cones/mm
2
in the fovea. That means that they are very tightly packed. A ganglion
cell in this region can be connected to a single cone. That means that it's receptive eld is very detailed.
As you go out to the lateral edges of the retina, density of receptors goes down and the number of
receptors attached to ganglion cells goes up to sometimes thousands of receptors, mostly rods.
There are cones throughout the retina, but they are relatively very low in number.
Cones come in three types. In order for the brain to interpret what is happening on the retina it would
have to know what type of receptors a particular ganglion cell are where the receptive eld for the
ganglion cell is. This label is anatomical and the general picture is called "the principle of connectivity".
It is how the sensory neurons are attached to the visual center that denes what the brain gets out of
that stimulation. This principle is a general principle, not just visual. Any nerve impulse coming over a
particular sensory connection will be interpreted by the brain based on the connectivity of the neurons.
Cortical maps
In an experiment the target shaped stimulus with radial lines was centered on the visual elds of a
monkey. They sacriced the animal, cut up the visual cortex and used the technique which would stain
darkly the cortical neurons that were active before the cut was made. What was noticed was that the
same spatial pattern was represented on the cortex of the brain.
The spatial relationship between the receptors that were stimulated is retained in the organization of
response in the cortex. A cortical map is a term we apply to the fact that the spatial location of receptors
that are stimulated is represented in a map-like fashion in the appropriate area in the cortex.
VISUAL PROCESSING
Visual edges are sharpened and make more contrast. When you have a lighter gray and a darker grey,
the processing in the retina emphasizes the edge. If you look at Rectangles A, B and C, you will notice
that Rectangle B is slightly lighter to the left. However, Rectangles B and C are identical. The edges are
emphasized because its next to the darker rectangle. This is due to processing that happens in the
retina.
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In processing, the central nervous system does route control. It controls the pathway of Nerve impulses
going the CNS. It is the role of the synapses to regulate this. This process illustrated above is called
lateral inhibition. The more stimulated area on the retina inhibits the response of the less stimulated.
The neuron class that starts this processing are horizontal cells. These cells run laterally. Horizontal
cells that are involved in the synapses where light is intense send out inhibition to cells that are involved
in the synapses where light is not as intense.
On center, off surround ganglion cells
The ganglion cell in this example (G) makes synaptic connections with 2 bipolar cells (B). These bipolar
cells make synaptic connections with 4 rods (R). That denes the center of that ganglion cells
receptive eld. It is the connection that goes from receptor to bipolar cell to ganglion cell.
If a spot of light stimulated in the center, it strikes the receptors
which hyperpolarizes and causes the on bipolar cell to be
depolarized, which then releases NT to the Ganglion cells and
we get a burst of Nerve impulses in the axons of the Ganglion
cells.
If a spot of light stimulates Rods in the surround of the ganglion
cells receptive eld (not directly connected to that ganglion cell),
it causes hyperpolarization of those rod cells. The surround
receptive eld's connections are not directly with the ganglion
cells, but via horzontal cells (H).
In the surround response, the light stimulus strikes a rod, and
the rod sends NT to bipolar cells which hyperpolarizes and
reduces it's NT release. This results in the horizontal cells
inhibiting the ganglion cells and this is called lateral inhibition.
The ganglion cells have a response called a post inhibitory
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rebound, which means that after they are inhibited the actually depolarize many times above ring
threshold and you get a burst of Nerve impulses. This ganglion cell is described as having an on center
response, but having an off surround response (it produces a burst of nerve impulses when the light
goes off from the surround).
The surround receptive eld includes all the receptors that are not connected directly to the bipolar cell
but via horizontal cells.
On bipolar cells get stimulated when it gets NT from receptor cells. Off bipolar cells get inhibited
when it gets NT.
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PHONORECEPTION
Sound travels at about 800ft/sec. It dies out because it's a point source. The amount of energy goes
down as the distance from the sound source increases, because the same amount of sound is spread
over a greater area. Another reason for the decrease in energy is because some energy is lost as heat.
The wavelength determines the pitch of a sound. It is the distance between two points with the same
density in a cycle. Shorter wavelengths give higher pitch sound and longer wavelength give a lower
pitch sound.
The unit for frequency is Hz (cycles/sec). Ideally, human hearing responds at a range between
20-20,000 Hz. Speech denition happens at high frequencies. Sounds travels through elastic
(compressible) mediums, e.g. Air.
The structure of the mammalian ear
External ear (Pinna) - focusses sound down into the ear.
Middle ear - Begins with the tympanic membrane and
includes the ossicles (maleus, incus and stapes). There
is an opening to the Eustachian tube which goes down
to the mouth cavity (usually closed). Tympanic cavity.
Inner ear (encased in bone) - Stapes connects to the
inner ear via the oval window.
Cochlea (where the receptors are located, where
hearing really starts)
Round window.
The inner ear is uid lled.
TRANSFER OF SOUND WAVES TO THE INTERNAL EAR
When sound waves hit the tympanic membrane, it vibrates. This causes the bony ossicles to vibrate,
which causes vibrations in the uid of the internal ear. This bony cavity is lled with uid. When the oval
window moves in, it creates a pressure in the internal uid and this pushes the round window out. The
whole purpose of this whole apparatus (minus the semicircular canals for balance) is to get the
vibrations into the uid of the internal ear and it is these vibrations that lead to our perception of sound.
The middle ear is a closed cavity. When the pressure on the outside of the tympanic membrane is
larger than the pressure in the middle ear, the tympanic membrane moves in. This makes it necessary
for the Eustachian tube to open to equalize the pressure so that the tympanic membrane doesn't "pop".
Fluid is much less compressible than ear. It takes more energy to create pressure waves in uid.
Because of this, it is necessary for impedance matching to happen in the internal ear.
Impedance matching
There are two ways that impedance matching is accomplished in the ear:
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The tympanic membrane is 18.6 times larger than the oval window. This takes all of the pressure
creates over the whole tympanic membrane and focus it down on a smaller surface. This will create
a much bigger force on the oval window.
The ossicles are a system of levers. There is a ratio of the maleus to the stapes of 1.3 to 1. The
maleus moves 1.3 times as much as the stapes. This also gives you an increase in force
These two processes together impedance match the air outside to the water inside
The function of Cochlea
The basilar membrane extends throughout the cochlea. It is narrow nearest to the oval window, and
gets progressively wider and has natural frequencies along the basilar membrane. The narrow end
bounces up and down in response to high frequencies, and the wider end response to lower
frequencies.
When the oval window moves in as a result of a sound wave, the vibrations coming from the oval
window go through the upper half of the cochlea. This causes a vibration in the basilar membrane.
When the basilar membrane vibrates, the vibration goes through the membrane to the lower half, which
is attached to the round window. When the oval window goes in, the round window goes out. The rst
stage of discriminating the pitch of sound is where we make the basilar membrane vibrate.
The basilar membrane is supported by bony ridges running down the cochlea. The basilar membrane is
not wide enough to respond too the lowest pitch of sound that we hear at about 200 cycles per second.
These low frequencies cause the entire basilar membrane to vibrate. This is interpreted as a low pitch
sound in the brain.
Cochlea and Organ of Corti
Scala vesibuli/vestibular canal gets its vibrations from the oval window. The scala tympani is the
lower half. At the end there is direct communication between the scala vestibuli and the scala tympani.
This opening is called the halocotrema. The uid in the scala tympani and the scala vestibui is the
same. It is continuous.
The reissner's membrane separates the vestibular canal and the cochlea duct. It is transparent to
sound. The scala vestibuli and the cochlear duct respond to the oval window in the same way. The uid
in the cochlear duct is different. It is endolymph, not perilymph. (This difference is crucial. This
endolymph is higher in K.) So, sound waves makes the basilar membrane vibrate up and down,
transferring the vibrations to the scala tympani.
ORGAN OF CORTI
Watch Video
Watch Video
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The organ of corti is located on the basilar membrane. This organ has some very important
structures.
Tectorial membrane is a very important structure. It is located on the organ of corti and extends all
the way along the cochlea.
Hair cells are the "most important" cells in the ear. They are cells which sit in the organ of corti. We
have an inner row of hair cells, and 3 outer rows. They have steriocilia.
All other cells have a supportive function.
Branches of the acoustic nerve actually make synaptic connections with the hair cells. There are 4
rows of hair cells:
The inner row are the receptors for hearing. There are about 15,000 hair cells in the inner row.
3 outer rows. There are about 32,000 hair cells in the outer row. These are involved in modulating
the response of the organ of corti to sound. They are not the actual receptors even though they look
like the inner row.
Mechanics of vibration (movement of the basilar membrane).
The basilar membrane vibrates up and down. This makes the organ of corti do the same kind of
vibration, but as the organ of corti goes up, it makes the tectorial membrane vibrate "like a windshield
wiper". It moves up and down but also laterally.
The steriocilia (hair) of the hair cells are in contact with the tectorial membrane, which means that the
steriocilia of the hair cells are being tweaked back and forth by the tectorial membrane. It is the
tweaking of the hair cells that leads to hearing. As the organ of corti moves, the steriocilia are
deformed.
The scala vestibuli and the scala tympani contains perilymph. The cochlear duct has endolymph.
Endolymph has a very high K
+
concentration and the organ of corti and hair cells are in endolymph.
The steriocilia are connected together in pairs. There is a long cilium and a shorter cilium and a bridge
between the two cilia. The short cilium has mechanically gated K channels. As these hair cells get
Watch Video
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tweaked, that causes the channels to open. This will lead to an inux of K
+
into the hair cell, which
produces a receptor potential. The receptor potential is transferred electrically down to a place with
synaptic vesicles and creates an EPSP in neurons that make up the Auditory nerve.
The receptor potential opens K
+
gated Ca
2+
channels. This does 2 things:
Increases receptor potential.
Increases neurotransmitter release directly.
Recruitment is a result of individual receptors having different thresholds. A very low intensity of sound
only causes a response in some hair cells. As you increase the intensity of stimulation, this will result in
a response in more receptors. In other words, more receptors are recruited.
There are 2 ways of sensing intensity of the stimulation:
Individual receptors responding more vigorously
More receptors responding
There is a maplike relationship between the auditory cortex and the receptors. The organ of corti
projects on to the auditory cortex in a maplike fashion. High frequencies that are caught in the region
closes to the oval window excite the area in the auditory cortex more anteriorly.
The Muscular System
Vertebrate skeletal muscle
Motor neurons leave spinal cord through ventral root and connect to muscle cells via synaptic
connections. Motor neurons make connections to more than one muscle cell. When a motor neuron
release ACh, all muscle cells that receive input from that motor neuron will respond. This is called the
motor unit - a unit of muscle contraction.
When one neuron res, only the cell(s) that are connected respond. If you want to have very ne
contractions like in the eye, you want to minimize the amount of muscle cells that are connected to a
motor neuron. In really ne contractions we have 1 motor neuron to 1 muscle cell.
On the cortical map, you can see which part of the cortex is connected to which part of the body. We
nd that the part that controls the hand has a large portion of the cortex, and the part for the feet is
small. This is because there is a very ne degree of control when it comes to the hands because there
is much more controlled motion with the hands and ngers.
The membrane around the muscle cell is called the sarcolemma. There are a number of nuclei in each
muscle cell (polynucleated). Muscle cells are so long that you need more than 1 nuclei to furnish it with
the DNA and other machinery that are necessary to keep muscle cells running.
The boutons of the motor neuron sits in a depression of the muscle. This depression is called a gutter.
The muscle membrane here has folds, and wed nd the Acetyl choline (ACh)receptors in the folds of
the muscle membrane.
Watch Video
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The units in the muscle cell are bundles of myobril. Myobrils are
made up of actin (thin laments) and myosin (thick laments). These
2 proteins form the bulk of the myobril.
There are 3 types of arrangements in the bundles:
Only thin laments
Only thick laments
both laments - One thick lament is surrounded by 6 thin laments.
A myobril is made up of sacromeres. Thick laments overlap thin laments. The distance between 2 Z
lines is 1 sacromere.
There is a sarcoplasmic reticulum run around the muscle. At every place you have a Z line, the
sarcoplasmic retiticuli go deep into the muscle. There are also T tubules running around the Z line. The
terminal cisternae is a part of the sarcoplasmic reticulum that stores Calcium. It runs very close to the T
tubules. This proximity is very important.
Within the sarcoplasmic reticulum there is a protein which binds calcium when it comes in. On the T
tubule there is a protein (Dihydropyridine receptor) that binds to another protein called the Ryanodine
receptor (on sarc membrane) that both act as calcium channels. This allows Calcium to go into the T
tubule from the sarcoplasmic reticulum.
There are also pumps in the sarcoplasmic ret that pumps ca from the cytoplasm into the sarcoplasmic
reticulum and is bound by a protein called calsequesterin.
Myober = muscle cell.
Myobril = units inside the
muscle cell.
Watch Video
- 36 -
The Sliding lament theory
Actin is made up of thin laments and myosin is made up of thick laments. Actin laments is
associated with 2 other proteins: Troponin and tropomyosin. Myosin have "heads" radiating in different
directions as shown below.
Because myosin and actin are interdigitated, the heads have binding sites on the actin laments. When
the muscle is at rest that area is not available. The tropomyosin protein covers the area where the
heads bind. When the muscle gets stimulated and the Ca
2+
is released, Ca
2+
is taken up by troponin.
When troponin binds ca, tropomyosin changes its conformation and move out of the way, exposing the
binding site. Myosin heads attach to actin. When ATP gets broken down, actin and myosin slides
across each other and we get muscle contraction.
When an impulse comes through the motor neuron, the impulse causes Ca
2+
to get into the presynaptic
vesicle, neurotransmitters get released, and bind to receptors on postsynaptic membrane. The post
synaptic potential spreads.
The muscle membrane(sarcolemma) contains V-gated channels. This causes an impulse in the muscle,
which is then propagated along the sarcolemma, and goes via the T tubule system deep into the
muscle cell. The dihydropyridine receptor gets stimulated, which then activates the ryanodine receptor.
Watch Video
- 37 -
This channel opens, Ca
2+
is released. Ca
2+
binds to troponin, causing a conformational change in the
tropomyosin. Actin binds to myosin, ATP is hydrolyzed and the muscle contracts.
Molecular structure and function of sarcomere
Thick myosin lament
Made up of individual subunits that are the myosin units.
The heavy meromyosin is made up of a head and a tailpiece.
The light meromyosin has only a tailpiece.
There are 2 places where movement takes place in this unit. The head can ex along with the tail of the
heavy meromyosin, which gives you the power for muscle contraction. However, the contraction
depends on connection. It is pulling the actin. To do that the myosin head has to connect to the actin.
Thin actin lament
Made up of g actin monomers.
A cross bridge from the myosin will connect to a special site on the actin monomer.
The whole actin lament is called f actin.
It is the availability of the binding sites that starts the contraction. There is a protein called tropomyosin
that lays right over the binding site, making the binding site unavailable. There is a third protein
complex called troponin (has 3 subunits), which is a calcium receptor. Troponin binds 4 calcium ions in
order to do its thing.
The terminal cisternae releases Ca
2+
when we have a action potential. The Ca
2+
binds troponin,
causing a change in conformation of the tropomyosin, which causes it to move. Then binding sites on
actin are available, and as soon as this happens, contraction begins. The myosin can't cross bridge
with the actin until the binding site is available. The head of the myosin lament is phosphorylated,
putting it in the high-energy state (resting).
As soon as the binding sites become available, the myosin forms a cross bridge with the actin. The next
step is the power stroke (exing of the head). The phosphate is removed and the myosin goes to its
lower energy state and we get the power stroke.
These cross bridges stay until we have energy. When we add ATP, the cross bridge breaks. Binding a
new ATP breaks the cross bridge. In order to put it back to it's resting state (energized), the head has to
be phosphorylated by the ATP.
When Ca
2+
gets pumped back into the terminal cisternae, it stops the effect of Ca
2+
on the muscle and
muscle contraction ceases.
Energy Source for Muscle Contraction
The energy source for contraction is ATP. Muscle is very richly supplied with mitochondria. Glycogen is
a storage source of energy. It is a polymer of glucose units. The largest energy storage in the muscle is
in glycogen. Another place of glycogen storage is in the liver. Glycogen has to be broken down into
glucose in the liver taken to the muscle via the bloodstream.
In anaerobic glycolysis, you are re-oxidizing NADH by reducing pruvate into lactic acid.
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Then the lactic acid is being reoxidized to pyruvate, which then goes through the Krebs cycle to yield
ATP. The excess goes through neogenesis to regain glucose.
You cannot do anaerobic glycolysis with fatty acids. Our major ATP source is electron transport and is
oxygen dependent. We don't store ATP. We store molecules that can make ATP. However, in the
muscle this is different. Creatine can take up a phosphate and get a higher energy bond than ATP.
At rest ATP can phosphorylate creatine to creatine phosphate. When contraction is happening, Creatine
phosphate can phosphorylate ADP to get ATP. If things get really tough, 2 ADP can be converted into
ATP and AMP. The most important thing for contraction here is being able to make ATP available.
Types of muscles cells
Monoterminal - Each muscle cell has a single motor end plate. All monoterminal muscle cells have
a membrane that generates an all or nothing Muscle impulse.
Slow phasic: A phasic muscle cell is one that is designed to contract with strength but not for a long
time. Has a relatively slow onset of contraction. It also has many mitochondria and is thus a heavily
aerobic muscle. So in this muscle we have lots of fat. Tetanus occurs at a very low frequencies of
stimulation.
Fast phasic: This varies between having few mitochondria and no mitochondria. It is primarily
anaerobic, so it's energy comes from carbohydrates through anaerobic metabolism. It is the white
meat and fatigues easily.
Fast phasic oxidative: Have many mitochondria and they don't fatigue as easily. They contract very
rapidly (fast twitch). Takes a very high frequency of stimulation to achieve tetanus.
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The Circulatory System
- 40 -
The Heart and Major Vessels
The blood goes through the heart twice and the valves are crucial. The heart is the pump and it has
two halves. 1 half (right) sends the blood to the lungs and the other (left) to the rest of the body. There
is an alternating rhythm of contraction with the atrial and the ventricular contractions.
Blood comes in from the body via the vena cava and empties into the right atrium (see gure above).
Blood moves from the right atrium through the tricuspid valve (One of a pair that we call the
atrioventricular valves [A.V. Valves]).
The blood moves through the tricuspid valve to the right ventricle. Then it moves through the pulmonary
valve (semilunar valve) to the pulmonary artery (without much oxygen). Then the blood goes through
the lungs to the pulmonary veins and then to the left atrium, through the mitral valve (a.v. valve) to the
left ventricle (most important - creates pressure for circulation). Then it goes through the aortic valve to
the major artery, which is the aorta, and then to the rest of the body.
Watch Video
- 41 -
Control of the Heart Beat
The Pacemaker
The pacemaker is a group of specialized muscle cells that do not contract. It is found in the right atrium
right where it joins with the superior vena cava and is called the sino atrial (S.A.) node. The sino atrial
node cells set the rythm for the beating of the heart.
There is no resting potential in the pacemaker cells because the Membrane Potential never remains
stable. There is rst a higher Na
+
conductance than K
+
conductance, and Na
+
moves through special
channels into the pacemaker. So the potential continuously moves towards ring threshold. Late in the
cycle Ca
2+
channels open and potential continues to move towards threshold, and we get an action
potential much longer than we've seen in the past. Then K
+
conductance decreases. It is an all or
nothing impulse, but it just lasts longer, and we have no resting potential.
How is the heart rate regulated in terms of speed?
Regulation happens through 2 substances that are produced by the autonomic nervous system.
ACh (parasympathetic) - decreases heart rate. When ACh increases, that causes an increase in K
+

conductance. K
+
hyperpolarizes the cell, making it harder for depolarization to happen. The effect of
this is a decrease in heart rate.
Epinephrine (sympathetic) - increases heart rate. With normal epinephrine levels, we have a
relatively high Na
+
and Ca
2+
conductance and a low K
+
conductance. If epinephrine levels increase
we get a higher Na
+
and Ca
2+
conductance, thus depolarization happens faster, which results in a
higher heart rate.
The Sa node is a group of specialized muscle cells that dont contract. All they do is generate the
electrical rythm for the rest of the heart - the pacemaker potential. The SA node cells do not have a
stable resting Em. It is always uctuating.
Watch Video
Pacemaker Cell Pacemaker Cell Pacemaker Cell
Na
+
K
+
Na
+
Ca
2+
K
+
K
+
Na
+
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- 42 -
At the lowest potential, the SA node cells are leaky and allows Na to leak in. This depolarizes the
membrane. When it gets to ring channels, V-gated Ca channels open and you get a very fast
depolarization to the peak of the action potential. At the peak, K
+
channels open. When K channels
open, K
+
leaks out and you get hyperpolarization. Then the process happens again.
The SA node does not depend on the nervous system for the
rythm, but they do receive innovation from the nervous system
(autonomic). The parasympathetic bers released ACh and the
sympathetic bers release Epinephrine.
Epinephrine makes Na
+
and Ca
2+
channels very leaky. This
results in faster depolarization. Thus, if we increase
Epinephrine levels, we get an increase in heart rate. This is
called positive chronotropy because the speed is increased. Positive inotropy means that each
heartbeat is stronger.
ACh makes K
+
channels sensitive, and slows down heart rate. This effect is negative chronotropy
and negative inotropy.
The signal travels from the SA node at a speed of 1m/s to the AV node at a speed of 0.05m/s (slows
down).Then it travels down the AV bundle at a speed of 4m/s to the purkinje bers at and is then carried
to the rest of the heart muscle. This delay in speed between the SA node and AV node allows for the
ventricle to get full with blood before it contracts.
The cells from the AV node can become a pacemaker if the Signal does not get from the SA node to the
AV node. The SA node dictates because it has the fastest spontaneous activity, so it serves as the
pacemaker. But if it doesnt work, the AV node, which has the next fastest spontaneous activity, will act
as the pacemaker.
Some organisms have a
neurogenic heart. We have
a myogenic heart.
1. Sinoatrial node
2. Atrioventricular node
3. Bundle of His
4. Left bundle branch
5. left posterior fascicle
6. Left-anterior fascicle
7. Left ventricle
8. Ventricular septum
9. Right ventricle
10. Right bundle branch
Electrical conduction system by J. Heuser
Heart by Patrick J. Lynch; illustrator; C. Carl Jaffe; MD; cardiologist Yale University Center for Advanced Instructional Media
- 43 -
Isovolumetric contraction of the ventricle
After the atria contract, the QRS wave appears. QRS is the stage of ventricular depolarization. At this
stage, the ventricle don't immediately change in size. Since the Valves are all closed, this builds up
pressure in the ventricles. This is when the force that goes to pump blood is generated.
The systolic pressure comes from 0 to about 110 mm HG. This is a lot of tension/pressure. It becomes
so much that it gets higher than the aortic pressure. When the pressure gets above the aortic pressure,
it opens the pulmonary valve and the aortic valve. This marks the end of the isovolumetric contraction
of the ventricle.
Ventricular contraction
The stroke volume is the amount of blood that is ejected from the heart. The stroke volume is about 70
ml. End diastolic volume (EDV) is approximately 130 mL. The residual amount of blood that remains is
approximately 60ml (End systolic volume: ESV). Ejection fraction = SV/EDV and is approximately 53%
at rest and 90% during exercise.
When Ventricles expand, the pressure becomes less, then AV valves open.
RegRegulating Stroke Volume
If the heart is to regulate how much blood it's going to pump, it has to be able to regulate EDV and ESV.
There are 3 ways to increase the EDV:
Increase ventricular contraction (epinephrine from sympathetic neurons- positive inotropy). This in
essence decreases ESV
Increase the amount of time for lling
Increase the amount of blood returning from the rest of body (venous return).
Increasing Venous Return with The skeletal muscle pump
There are skeletal muscle pumps that surround our veins. If you are exercising your muscle they
contract in a way that forces more blood through the veins faster. So the activity of the skeletal muscle
increases venous return
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Improving stroke volume by decreasing ESV
Increasing the pressure generated during systole. (Inuenced by Catecholamines)
Improving pulmonary and aortic pressure by lowering the pressure. This is accomplished by
exercise also.
The Frank-Starling mechanism
When the heart is stretched due to being more lled with blood, that enhances the actin myosin overlap
in a way that causes the heart to contract stronger. If there is less blood in the heart, the tension will be
less and the contraction will be less. The Frank-Starling mechanism states that the heart will adjust
itself for whatever volum you give it.
Regulation of Cardiac Output
C.O. = Cardiac Output
H.R. = Heart Rate
S.V. = Stroke Volume
Stroke volume is the amount of blood ejected per stroke. End diastolic volume is the amount of blood in
the left ventricle before it contracts (isovolumetric stage). It is the maximum amount of blood. End
Systolic Volume is the amount of blood remaining in the heart after contraction.
Stroke volume = E.D.V. - E.S.V. - These 2 values are regulated independently

Regulation of E.D.V.
Skeletal muscle pump - This increases venous return, which in essence is increasing E.D.V.
Increased sympathetic activity, which means that there is an increase in the availability of
epinephrine and norepinephrine. Epinephrine is delivered to body tissue. It comes from the adrenal
Watch Video
C.O = H.R. * S.V.
Watch Video
What happens to the way Cardiac output takes place as you do exercise?
If you start off in a state of poor tness, but then you start doing a good Cardiovascular exercise
regularly, you nd that reaching a certain level gets easier an easier. This does not mean that your
muscles needs less blood and oxygen. It means that one of the major things that happens during
training is that the heart ejects more blood with each contraction. This refers to the stroke volume.
Resting heart rate also drop. Fit athletes may have very low resting heart rates.
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medulla, which is sort of a reservoir and is full of capillaries. The source of norepinephrine is the
same as epinephrine. It is delivered directly to the tissue it affects. So epinephrine and
norepinephrine can be delivered to the same tissue, but by different means. Most of the time they
have the same effects.
Increased Epinephrine and norepinephrine release also increases venous tone. There is a smooth
muscle layer that contracts and is inuenced by epinephrin and norepinephrine. With increased
venous tone the walls of the veins shape up a little and make it easier for blood to ow.
These 2 things inuence the amount of blood returning to the heart. You get increased venous return,
which in essence increases end diastolic volume.
Regulation of E.S.V.
There is only one general way to change E.S.V and that is to change how much the ventricle contracts.
The more it contracts, the smaller the E.S.V. is. There are two major sources for changes in E.S.V.
Autonomic nervous system affect - This means that there will be an increase in the availability of
epinephrine and norepinephrine. These are delivered in the same way as in regulating E.D.V. In
this case they also have the effect of increasing contractility. This is a function of the increased
availability of Ca
2+
.
The stretched ventricular muscle will enhance contractility, which
means more cross bridges. -> Stronger contraction. This is
called the Frank-Starling mechanism. So this is a direct result of
E.D.V. because this stretches the ventricle. So we have looked
at the regulation of stroke volume.
Blood pressure regulation
The pressure in the aorta uctuates. The pressure in the aorta is the lowest the instant before the aortic
valve opens. This is the diastolic pressure. As the ventricle contract, the pressure in the aorta is
increased to a peak and this is called systolic pressure.
When we talk about regulation of pressure we have to remember that the pressure in the large artery
(aorta) is increasing.
Pulse pressure = systolic pressure - diastolic pressure
So the numbers that we typically hear are 80mm Hg and 120mm Hg, so the typical pulse pressure is
approximately 40mm Hg.
Mean arterial pressure (MAP)
What MAP does is to nd the area under the curve, dene a rectangle with the same total area and
dene the value of the top of the rectangle as MAP. This turn out to be easier to calculate than trying to
dene the area under the curve. We can do so with the following formula:
MAP = DP + 1/3P.P
ACh is involved in regulating
heart rate, but not Stroke
Volume
Watch Video
- 46 -
This, once again is the average pressure in the large artery
A second formula for calculating MAP
MAP = CO * PR
Peripheral Resistance (PR) is the total resistance to blood ow in the body. The major arteries and
smaller arteries have very thick walls, and are made to be exible. However, these arteries tend not to
constrict or dilate actively. They dont get bigger or smaller on average. If there was something that
changed the diameter, resistance to ow would change. This means that the arteries aren't the place to
change the cross sectional diameters.
Capillaries are histologically made up of single epithelial cells. They are only one cell layer thick. So
there isn't any muscle or connective tissue. Capillaries aren't the place either.
So this only leaves one place - Arterioles. Arterioles contain an inner circular layer of smooth muscle.
This layer can contract or relax leading to constriction or dilation. This affects peripheral resistance,
which increases with constriction and decreases with dilation.
Surprisingly, we have twice as much circulatory volume in our body than blood. Most of that circulatory
volume is in the capillary beds. So this means that some capillary beds have to be shut out completely.
There are two types of medical situations in which our blood "gets lost".
Fainting - not enough blood going to the brain. When this happens, you lay them down on the
grown and elevate the legs so the blood can go to your heart and especially to the brain. Fainting is
a result of a system-wide vasodilation. So the blood pools in your lower extremities.
In a really serious vasodilation, the result is shock. Blood pressure drops dramatically for a long
period of time. The heart will quit contracting if it doesnt have enough blood to pump. This can
sometimes be irreversible.
Regulating Peripheral Resistance
Alpha receptors (found on the arterioles) have a 7 transmembrane sequence (2nd messenger). It is
mainly responsive to norepinephrine. This comes from sympathetic neurons released at the site. these
contact the receptor. There is a G protein that activates phosphatidyl inositol, which releases IP3, which
causes release of Ca
2+
from the cisternae and the sarcoplasmic reticulum. This causes
vasoconstriction.
The smooth muscle cells are also supplied with beta2 receptors. They are some distance from
sympathetic nerve endings. Thus it will be much more responsive to epinephrine. So here is the
sequence of events. The epinephrine contacts the beta2 receptor (7 transm). This activates a g protein,
which activates adenylate cyclase, which produces cAMP, which activates Ca
2+
pumps (into cisternae).
This causes a decrease in Ca
2+
levels, leading to vasodilation.
There is another kind of receptor called a beta1 receptor. They are located in the cardiac muscle. In this
case, the causative agent is mainly norepinephrine, because these are near nerve endings. It is also
receptive to epinephrine, but not as much. This causes an increase in cAMP, which then causes the
Watch Video
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increased availability of Ca. This gives stronger contraction of cardiac muscle cells. ESV decreased
because heart muscle cells contract stronger.
High levels of norepinephrine will activate alpha receptors leading to vasoconstriction. So vasodilation
happens best at moderate levels. This does not mean that when the level of norepinephrine is high that
the beta2 receptors are not activated. It just means that both are activated, but the alpha effect
predominates. When you are exercising a lot, you want blood ow to muscles to increase. So what you
want to do is to activate the beta2 effect in your muscles. During heavy exercise, moderate levels of
epinephrine are pumped out. High levels are saved for emergencies. This keeps blood pressure high
enough, so that high levels of blood will go through your heart and supply the brain with the necessary
nutrients.
There is another inuence that we need to emphasize because of its importance and that is the control
by local metabolites. These things will typically result in vasodilation. Lets say youre out jogging. The
greatest energy use is in the legs. This uses ATP by using oxygen and producing CO2. This increases
H
+
levels. This muscle can continue being active because as a result, local metabolites causes
vasodilation in local areas.
Blood viscosity
If the blood gets thicker, it gets harder to pump, but we are not going into that.
Angiotensin and MAP
There is a protein circulating in the blood normally called angiotensinogen. This protein is inactive in
this form. If there is a decrease in MAP, the kidney senses this and will (via the juxtaglomerular
apparatus) release another protein called renin. This is an enzyme that acts on angiotensinogen. It
breaks off part of the inactivating polypeptides.
When this happens, It then becomes angiotensin I, which is slightly active. This then goes out to the
body. At various places in the circulatory system especially in the lungs there is this converting enzyme
called angiotensin converting enzyme (ACE). This converting enzyme changes angiotensin I to
angiotensin II, which is the most potent vasoconstrictor in the body by causing the smooth muscle in
the arteriole to contract. This was rst thought to be an emergency regulator, but now it is seen to be
normal.
There is a group of drugs called ACE inhibitors that block ACE. Having high blood pressure is a major
health problem. About 85% is not yet understood, but we do know that the most common problem is
that there is too much vasoconstriction.
Pressure reexes
Watch Video
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For you to regulated body processes, your body has to be able to know how the body is currently
functioning. This can result in short term/immediate regulation via the nervous system.
How does the nervous system know what the blood pressure is?
Baroreceptors
These receptors are located in the arteriole system and they sense blood pressure. They are found
primarily in 2 locations: The aortic body and the carotid body.
The aortic body is a thickening in the aorta. Its ring rate increases in direct proportion with the amount
of pressure in the aorta. These pressure receptors send nerve impulses to the medulla, which is the
primary blood pressure regulating center. There are also connections up to the thalamus, hypothalamus
an the cortex, but we are not going to go there.
With an increase MAP, we get increase in the rate of ring of the baroreceptors, which goes into the
medulla. This is where we talk about pressure reexes. This has 2 effects:
It increases parasympathetic activity
It decreases sympathetic activity.
This combination will cause a reduction in cardiac output. The decrease in sympathetic activity will
cause a decrease in Peripheral resistance. With these 2 reduced, we get a decrease in MAP.
We started with an increase in MAP, and this response causes a reduction in MAP. This is why we call it
a pressure reex.
If we started with a decrease in MAP, this would lead to a decrease in parasympathetic activity, and an
increase sympathetic activity. As a result, MAP would increase.
When we have high or low blood pressure the brain tries to adjust via the activity of the Medulla.
Sometimes, we take drugs. Some drugs that are used affect CO, but this also affects how active you
can be. Others inuence PR by blocking Ca
2+
channels. This causes vasodilation. Others blocks ACE.
Then we don't get angiotensin II, and then we get an increase in vasodilation.
Long term regulation of MAP
Long term regulation of MAP is accomplished by regulating blood or uid volume. An increase in the
uid volume raises the resistance to ow. The most important long term regulation is accomplished by
the kidneys. Another general approach is using a diuretic, which interferes with the absorption of water,
and you decrease uid volume.
The baroreceptors are not the only route into the medullary regulation. There are series of other
mechanisms that we are going to mention very briey:
Chemoreceptors - the are located in the same places as baroreceptors - both the carotid and
aortic bodies and elsewhere. These chemoreceptors will detect an increase in CO2 levels,
increased H
+
concentration (as a result of increased CO2 because of Carbonic acid) or a decrease
in O2. If one of these things happen, the result is an increased sympathetic activity. Clearly, each
of these would indicate there is not enough blood in the area where the chemoreceptors are
located.
A receptors - There is an A receptor which responds to changes in heart rate. They then send
signals to the medullary center, which will either cause an increase in parasympathetic or
sympathetic activity depending on which is appropriate - whether it is necessary to increase or
decrease heart rate.
- 49 -
B receptors - These receptors are excited by lling. These too send signals to the medullary
center, which will then increase sympathetic activity. If you are running, blood is getting back to your
heart faster because of the skeletal muscle pump. The B receptors send signals to the medulla,
which will caus an increase in sympathetic activity, which increases heart rate. This also reduces
ADH production and this will cause an increased urine output.
C receptors - these innervate the junction between the right atrium and the vena cava. This can
cause a medullary reex, which can be either sympathetic or parasympathetic depending on what's
appropriate.
When secretory cells stretch, they released naturetic peptide, which results in a decrease in ADH,
Renin, and aldosterone release, which increases urine production. The overall result is a decrease
in MAP
Distribution of blood in the body
When you are sitting, you are not ooding your muscles with blood. C.O. is not very high. While we are
using our brain, it does require some blood, but not as much as during physical activity. As you become
more active, blood goes to different places.
Resting C.O. is approximately 5L/min. This keeps you warm. When you start exercising, your cardiac
output increases about 5 times and the distribution changes. This is caused by vasodilation in the
muscles via beta II receptors/epinephrine, and also the local metabolites. So if you are jogging, your
quadriceps and gastrocnemius muscles will get the most of the blood.
It is not smart to go swimming after you eat. If you swim, you are going to ood blood to your muscles.
If you are digesting, there is a lot of blood trying to go there. The muscles that are being pushed hard
dont get enough blood and will cramp. Cramping is simply a runaway contraction, which probably
means that there is too much Ca
2+
. If there is not enough ATP to run the Ca
2+
pumps to pump the Ca
2+

back out, we will get too much calcium. This results in cramping.
Pressure changes throughout the circulatory system
- 50 -
This graph shows a lot. Lets start with the left ventricle (top blue line). The pressure changes from
almost 0 to over 120mm Hg. The very low pressure is necessary to allow blood to ow into the
ventricles and the high pressure creates the pressure for circulation. When the blood gets into the aorta
and large arteries, the pressure only drops so far.
You're arteries have 2 important components. a lot of elastic connective tissue and smooth muscle,
which can both be stretched. When the ventricles contract, arteries stretch because it is full of blood.
This stretched artery is storing the pressure from the ventricles. When the arteries relax, the aortic
valve closes to prevent backow into the ventricle. So the pressure in the arteries remain high because
they are full of blood. The Arteries then constrict to drive blood to the vasculature of the body. As the
blood moves out into the small vessels, the pressure drops. The blood is being forces out into smaller
vessels.
The pressure in your large arteries hardly show any difference from place to place. So we can check
blood pressure many places. As the blood moves into the smaller arteries, the blood cells bump against
the edges and we get friction. We then see a rapid drop off in pressure to the arterioles. When the
blood gets into the capillaries, there is no longer a uctuation.
The smallest capillaries are where the greatest exchange takes place and blood cells move through
them in a line. The blood is in these exchange areas for less than a second. Then the blood continues
into the venules and into the large veins but the pressure is continuously dropping. The total cross
sectional area is huge in the capillaries. The rate of ow decreases.
Watch Video
Watch Video
The whole purpose of circulation is the movement of materials from one place to another. How
does this movement of substances into and out of the capillaries happen?
- 51 -
Movement of material into and out of blood
Blood pressure = hydrostatic pressure.
If there is a high pressure inside the capillaries and the walls have fairly large pours, uids and small
molecules will ow out of the capillary walls. This process is called ltration. These substances go into
the tissue uid. The concentration of small molecules going to the tissue uid is the same as he
concentration in the blood. This will lower the water concentration in the plasma, which means that we
will have a setup for osmosis to occur. Water will them move into the capillaries.
Net hydrostatic pressure = Blood pressure - tissue pressure. (This is the pressure moving uids in).
The ltration pressure = net hydrostatic pressure - net osmotic pressure.
We have blood in an arteriole going into a capillary. As the blood goes into the capillary the H.P. goes
down due to the large amount of friction. In other words the pressure that moves stuff out is decreasing.
On the other hand, as water moves from the blood into the tissue uid, the net osmotic pressure goes
up. The part of the capillary bed nearest to the arteriole is where the net ltration pressure is the
highest, and the part closest to the venule is where the net osmotic pressure will be the highest. The
point in the middle where the 2 pressures are equal is called the dynamic center.
In high blood pressure situations, the H.P. is high and it drops across the capillary bed but you end up
with more of the cap bed involved in giving off uid to the tissue and a small region taking uids in. This
will result in a net dropoff of water into the tissue. This leads to an abnormal amount of uid
accumulation in tissue, which is called edema.
HUMAN CIRCULATORY DIFFICULTIES
Hypertension/high blood pressure
The most common form is called essential (primary) hypertension. Causes:
Increased uid volume in the body, which means increased blood volume. The cause of urine
production is blood pressure. If you lower blood pressure signicantly, urine production can drop to
nothing. If you increase blood pressure, this will raise urine production very much. We tend to keep
uid volume normal at a normal MAP. A person with higher MAP regulates urine output around that
MAP (graph).
Another major cause is increased peripheral resistance. That would largely be because there is
too much average vasoconstriction.
Neurogenic - One of the major causes is that there is an overproduction of an anterior pituitary
hormone called ACTH, which results in an overproduction of the hormone cortisol, which can lead
to hypertension.
Common ways of treating hypertension is by either increasing vasodilation (Ca channel blockers an
ACE inhibitors), or to reduce cardiac output (beta blockers - reduce heart rate). The third approach is to
reduce uid volume (diuretics).
Atherosclerosis
Plaque can be deposited in large arteries. This is called atherosclerotic plaque. High cholesterol levels
in the blood, especially in low density lipoprotein or LDL cholesterol. There is another form called HDL,
which is good for you.
- 52 -
When this stuff accumulates in the large arteries, one of its favorite locations is the coronary arteries,
which are the arteries that feed your heart. There are 5 or 6 of these. This is usually the case with
bypass surgery. They also tend to deposit in the carotid arteries (feed the brain). Both of these
situations lead to a high probability of thromboses. An embolus is a oating blood clot or some other
particles. When that comes to lodge in a particular place, it becomes a thrombus.
The most common place is in the coronary artery, which can lead to a heart attack because the heart is
deprived of blood. It is more likely to lodge in a coronary artery that's stuffed with a plack deposit. If the
thrombus lodges in one of the major arteries going to the brain this can result in a stroke.
Atheriosclerosis can lead to an even more serious stage, especially with high bp. This stage is called
arteriosclerosis. Sclerosis is hardening. This results from calcication of the plack. It becomes hard
and rigid. When coroners squeeze the arteries of older corpses it can sound like twigs breaking.
- 53 -
The Respiratory System
Transport Of Gases
Cellular Respiration Equation:
C6H12O6 + 6O2 -> 6CO2 + H2O
One of the main functions of blood is taking Oxygen to and removing CO2 from the tissues.
Oxygen transport. The solubility of oxygen in water is .3 mL to 100mL plasma. On the other hand,
whole blood carries 20mL per 100mL. This difference is due to the presence of hemoglobin.
Watch Video
- 54 -
Oxygen transport occurs primarily via red blood cells, which have hemoglobin. Hemoglobin is made up
of 2 different types of protein chains. 2 alpha and 2 beta chains, which are very similar. These 4 chains
together make up a hemoglobin molecule. Within hemoglobin there is a crucial subunit called a heme
group. This heme group with a central ion associates with an Oxygen molecule. It is not a covalent
bond. There is a physical attraction (charge). The ion can take on and give off an oxygen molecule very
easily.
One oxygen can associates with each heme group. So a hemoglobin molecule can associate with up to
4 Oxygen molecules. In associating with oxygen, the individual units change in position with respect to
each other. As O2 comes in, the actual hemoglobin molecule changes shape, increasing afnity for
oxygen.
Deoxyhemoglobin has a relatively low afnity for O2. As it begins to load up with Oxygen, the afnity for
oxygen increases. Hemoglobin, in its oxygenated state has a higher afnity for O2. When the
hemoglobin leaves the lungs and goes to the body, we see the reverse effect. The hemoglobin gives up
its oxygen. The shape changes in a lower oxygen environment reducing afnity for oxygen and causing
oxygen to be delivered (blue line).
Watch Video
- 55 -
The relationship between the transfer of O2 and the amount of O2 in the environment is shown in the
oxygen disassociation/association curve (above .
The partial pressure of O2 (PO2): this is a measure of how much O2 is available in that particular
environment. The air that you breath is 20% O2. If the pressure of the air is at 760 mm Hg, then the PO2
will be around 152 mm Hg. Since the air in the lungs is saturated with water and water takes up some
of that, the actual value is around 110 mm Hg. The curve expresses the level of saturation of
hemoglobin based on the amount of O2 in the environment. It is S shaped. When hemoglobin is in the
lungs, it will saturate, but when it goes to a tissue, it drops, and will deliver O2.
The Oxygen Dissociation Curve
The crucial factor is AFFINITY. The greater the afnity the less oxygen it takes to load hemoglobin up.
As the tissues and the blood plasma pH becomes more acid, hemoglobin afnity is reduced. Since that
acidity is going to happen in the tissues, this means that the tissue that's more acidic will get more
oxygen.
Blood goes from the heart, to the lungs, back to the heart, and then out to the tissues. When it goes
through tissues, it only goes through one set of capillaries. It comes to the tissues loaded with oxygen.
The more acidic the tissue environment, the more the hemoglobin unloads oxygen.
The tissue becomes acid due to the production of CO2, which leads to Carbonic acid formation.
Hemoglobin loads up at a PO2 of about 100. In the muscles there is a molecule called myoglobin, which
is very similar to hemoglobin. However, it only has one heme group instead of 4. When we look at the
oxygen dissociation curve of myoglobin we see that it loads up at a lower PO2 than Hemoglobin. So
when hemoglobin unloads O2, myoglobin readily takes it up.
Hemocyanin (found in Horshoe crabs) has an oxygen dissociation curve like myoglobin. It has a
High afnity for oxygen. So this pigment has an easy time picking up oxygen, but a hard time
delivering it. The tissue PO2 has to be very low.
- 56 -
Mice have high metabolic rates. They burn oxygen much more rapidly than we do. Animals that live at
high altitudes have an oxygen dissociation curve shifted to the left. This means it loads up with oxygen
more easily, but can't be as active because they have to create low PO2 in there tissues.
A mouse living at high altitudes will have an Oxygen dissociation curve shifted to the left. It needs to
load up easily, but it can't be as active. If you nd an organism of the same species living at sea level,
the curve will be shifted to the right. This means that there is an important adaptation that occurs that
depends on Oxygen availability.
Lets now look at how CO2 is transported.
CO2 + H2O <--> H2CO3 <--> H
+
+ HCO
3-
We have CO2 going into the blood and Oxygen going into the tissue. The rst reaction that happens is
that 7% of the CO2 that we produced goes to the reaction above leading to the production of Carbonic
acid. The blood buffers are good enough to handle that much carbonic acid. This stays in the plasma.
Now, 70% of the CO2 goes through the following reaction inside the red blood cell forming H+ and
HCO3- by the enzyme Carbonic anhydrase. This is where hemoglobin takes on another function. When
oxyhemoglobin (HbO8) releases O2, it also picks up protons. In this case, hemoglobin is the buffer. This
causes a problem.
The bicarbonate will go through the RBC membrane out to the plasma. This will increase the charge
across the membrane and will stop bicarbonate from leaving if there isn't another mechanism for
getting rid of it.
When bicarbonate leaves, Cl
-
comes in and takes care of the charge. This is called the chloride shift
and depends on specic permeases for Cl
-
and bicarbonate ion. The process of transport can then
continue.
The other 23% produces Carbamino Hemoglobin (HbCO2): CO2 + Hb (deoxyhemoglobin) <--> HbCO2.
It never forms carbonic acid.
WHEN YOU GET TO THE LUNGS WE GET THE REVERSE OF ALL OF THIS: Oxygen is picked up
and CO2 is delivered.
Respiratory Exchange: The exchange of gases between organism and environment.
A planaria is a atworm. It does not have a respiratory system. Because it's at and thin, all or the cells
are close enough to the environment.
Here are the requirements for a Respiratory Surface:
Large surface area.
It has to be moist - Gas exchange happens in solution
Has to happen near active cells or have easy acces to them - cells that are using oxygen and
producing CO2
Watch Video
- 57 -
How do we fulll those requirements?
The respiratory surface of both lungs is about the size of a tennis court, which is pretty huge. Why
not just put it on our back? Because moisture loss would be too big.
The air that we breathe out is typically saturated with water.
Our lungs are inside our bodies. Since they arent close to all of our active cells, we have to add a
circulatory system. This respiratory area has to be highly vascular so that the blood is not very far
away from the air.
The Human respiratory system
Lungs
Our lungs are elastic/stretchy. This is because of elastic connective tissue and a little bit of smooth
muscle, but they can't be a muscular organ like the heart that themselves contract and expand. We
have to have an elastic lung that is very thin and facilitates gas exchange.
The 3 Cavities:
Intrapulmonary: inside the lungs. It is open to the atmosphere all the time.
Thoracic cavity: The whole cavity that contains the lungs and heart. It is sealed.
Pleural cavity: Bounded by the pleural sac. This sac has 2 layers: A parietal layer that lines the
thoracic cavity and a visceral layer that covers the lungs. It is uid lled, which acts as a lubricant.
Breathing involved an active change in the volume of the thoracic cavity, reducing and increasing its
pressure. We are going to see how that happens. But before that, lets look at the actual structure in the
lungs that supports gas exchange.
Trachea - main airway between the mouth and the lungs.
2 major bronchi - large tubes, one going to each lungs.
Bronchioles - small tubes
Alveolar duct
Alveolar sac - terminating the duct
Alveoli - where the major gas exchange happens
- 58 -
The alveolar duct and sac are covered with a capillary network. The blood gets oxygenated and goes
back via the pulmonary vein to the heart.
Pressure Changes During Respiration
If there is going to be pressure changes in the thoracic cavity there has to be volume changes.
Thoracic cavity pressure changes
Diaphragm: The boundary between the thoracic cavity and the abdominal cavity. The diaphragm is
kind of oval shaped. It is a band of muscle, and there is central connective tissue, which is strong but
non-contractile. Its shape at rest is domelike.
Thoracic cavity wall:
The external intercostal muscles - These are involved in inspiration.
The internal intercostal muscles - These are involved in expiration.
Eupnea - normal/quiet breathing.
Inspiration has to result in a reduced thoracic cavity pressure. So making the cavity larger does this.
The cavity is made larger by 2 sets of muscle contractions:
The diaphragm contracts
Watch Video
- 59 -
The external intercostals contract.
Both of these will enlarge the volume of the thoracic cavity, which reduces the pressure in the pleural
cavity, which means then that the pressure in the pulmonary cavity is greater than the pressure in the
pleural cavity, forcing the lungs to expand.
Expiration - passive. The diaphragm relaxes, the external intercostals relax.
When diaphragm contracts, this reduces abdominal cavity space, increasing the pressure in the
abdominal cavity. When it relaxes, the abdominal organs push the diaphragm back into place. When
thoracic cavity pressure goes up, pleural cavity pressure goes up above pulmonary pressure, and that
forces air out.
Why don't the lungs collapse at the end of an expiration?
The lungs are very elastic. This means that after we have expiratory movements, the lungs
continue to become smaller. This reduces thoracic cavity pressure below atmospheric pressure. If
the pressure in the thorax, and thus the pleural cavity, increases, this keeps the lungs from getting
too small.
Surfactant - released by special cells in the lungs that reduces surface tension of water. Part of the
constriction of the lungs is the combined effect of surface tension and elasticity.
Dyspnea - forced breathing.
The inspiratory phase is the same as Eupnea with two additional muscles connected to the clavicle
(neck muscles).
The expiratory phase is different. It involves the internal intercostals and the abdominal
musculature. The internal intercostals pull the rib cage down. The abdominal muscle contract and
force the diaphragm up by increasing abdominal pressure.
What happens if and of the walls of the thoracic cavity are penetrated?
This is called a Pneumothorax, and that happens as a result of trauma. This means that the individual
cannot breathe. When the diaphragm contracts, it simply sucks air though the hole in the wall.
Fortunately, the 2 lungs are separate, so if only 1 lung collapse, you can use the other one. When you
have a bilateral pneumothorax, breathing is no longer possible.
- 60 -
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