Bio 3302 Lec 2

Mechanisms of oxygen delivery and co2 removal is based upon 2

systems circulatory system and respiratory system
Oxygen moves around in cells by the use of diffusion
o The time for diffusion depends on how far the oxygen has to
travel
o Time required= distance2
As distance gets larger time required to increases fairly
quickly
o Larger animals need a system to enhance the rate of delivery of
oxygen
Metabolic rate also come into play in terms of oxygen delivery
o The higher the metabolic rate the more oxygen needed
Ex large animals with very low metabolic rates may not
really need a circulatory system
Ex 2 small animals with very high met rates may need a
circ system in order for faster O2 delivery
o Once animal that is an exception to this rule of having a high
met rate= having a circ system
These are insects. They have the highest known met rates
but dont use their circ system for oxygen delivery
This is b/c they have a tracheal system which circulates
gas until it is very close to the tissues and then oxygen
diffuses from the end of the tracheal system into the
mitochondria
Circ system can also be used for
o Waste excretion
o Nutrient delivery
o Cell to cell communication
o Hormone transport
o Thermoregulation
Circ syst will transport anything that can move in a fluid
but it can also transport heat
o Generates force
Animals with hydrostatic skeletons rely on fluid force
generated by the circ system
o Animals that need to enlarge or extend an organ also uses the
circ system to do so.
Ex monarch butterfly
Monarch caterpillars and they use the circ system to
move
Once they are done feeding off milkweed they will
form into a crystal

And they emerge from the crystals with their wings

folded up the force that unfurls their wings is
hydrostatic force provided by a circ system
Circ system has 3 key elements
o A pump
Usually a heart but not always
The pumps work by generating force and pushing the fluid
a head of them(+pressure)
3 basic types of pumps
Peristaltic pump
o Ex type of heart found in insects and
crustaceans
o Its a tube with muscular walls and a wave of
contractions passes along the tube pushing the
blood in front of it
o This heart has force generation and direction
built into one
Direction in which contraction moves
determines the direction in which the
blood moves
Chamber pump with contractile walls
Ex Human heart
o muscle chamber and when muscle contracts it
squeezes the blood pushing it out
o in order for blood to move in the right
direction a series of valves are needed to
direct the flow
chambered pump with non-muscular walls; but is
surrounded by external factor(muscle) that
compresses
o this also needs valves to direct flow
o the external muscle will contract squeezing
the chamber and then the valves determines
where the fluid flows
o ex of this type of pump in humans
The large veins in the leg act as
chambers to collect blood and when one
moves their legs muscle contraction
squeeze those veins to return blood to
the heart.
o Network of vessels(vascular system)
3 types of tubes
Arteries

o Take blood from heart to the periphery of the

animal
Capillaries
o Specialized for exchange of material
Veins
o Collect blood from periphery and take it back
to the heart
Not all 3 are present in all animals
Collectively known as vascular system or peripheral
system
o Circulating fluid
This can be blood or haemolymph
Open vs closed system shows where you see the presence or absence
of the diff types of blood vessels(bvs)
Open Circulatory System
o Animals with open circ system do not have capillaries
o Blood will be pump by the heart into a set of arteries form there
it goes to the tissues directly
The blood bathes the tissues directly; there is only
exchange between the circulating fluid and the tissues
themselves
o Circulating fluid is then collected up and returned back to the
heart and this may/may not involve some type of venous system
o It is quite difficult to direct flow with an open system
Tend to be low flow, low pressure, low resistance systems
o If the system of vessels is open one cannot distinguish between
the circulating fluid and the fluid that is bathing the tissues
directly
o Animals with open circ systems have haemolymph instead of
blood
Makes up 30% of animals body mass
Closed Circulatory system
o The blood is in vessels the entire way; from leaving the heart to
returning to the heart
Animals with higher met rates tend to have closed circ
systems
This is a evolutionary trend
o Reason for this trend is the ability to better
control the rate of blood flow and hence the
rate of O2 delivery with a closed separated
system
As met rate increases you tend to see the trend of
closed circ system
Within these animals a second trend can be seen

As met rate goes up there tends to be more

separating of blood flow to the gas exchange
organs(resp circ) and blood flow to the rest of the
tissues(systemic circ)
o As met rate goes up there is an increased
separation between the respiratory and
systemic circulatory systems
o The animals with higher metabolic rates are
air breathers and along with this there is a
shift to separating out the respiratory and
systemic circulation
Basic fish plan;
Closed implies that there is a complete set of vessels
Blood leaves the heart and arteries exchange between the
tissue and blood occurs in the capillaries and blood
returns to the heart in veins
It is a continuous circuit of vessels with an exchange
between the circulating fluid and the tissues happening at
the capillaries
These circulatory systems are found in all vertebrates(fish,
amphibians, reptiles, mammals, birds) and in a number of
invertebrates particularly ones that have a high metabolic
rate(cephalopods-squid and octopus; or in animals that use the
circ system for a hydrostatic skeleton-earth worm)
b/c blood is circulating in vessels all the time the circ system
provides quite a bit of resistance to flow and so higher pressures
must be generated in order to move the blood through the
closed systems of vessels
these are often considered to be high pressure/high
resistance systems
more force must be generated to move the fluid around
but they are able to direct and control the speed of the
flow
In this case one can distinguished between the circulating
fluid(blood) and the fluid that bathes the tissues (interstitial
fluid ISF)
Blood contains red blood cells and proteins in the palms
ISF lacks both rbcs and proteins
Keeping blood and ISF separate is quite important
Plasma proteins that escape from the blood and into
the ISF have to be collected up and returned to the
blood
o The is a function of the lymphatic system
Together the blood and ISF make up the ECF(in both closed and
open systems)

ECF accounts for about 30% of body mass

But in this case blood is only about 5% of that total with
the remaining amount being the ISF

Fish
o The circulatory plan in the fish is fairly simple
Blood is pumped by the heart, goes to the gills and is
oxygenated, the oxygenated blood is carried to the
systemic tissues where it gives up its oxygen and the
blood returns to the heart
o The problem with this circ sys is that the heart has to pump
blood to the gills and the systemic circulation both of which are
sites of resistance
Heart must generate relatively high pressures
The gills as the first point of the system are going to see
relatively high points of pressure
They are able to withstand this because there is
water on the other side of the gill to counter balance
this pressure
Pressure of the system as a whole is limited to the
pressure that the gills can withstand
o Fish heart has 4 chambers in a series
Blood enters the sinus venoses the atrium
ventriclebulbous or conus arteriosis
The ventricle is where the main force generation
occurs
Bulbous and conus arteriosis are structurally
different but share the same purpose functionally
which is to maintain blood flow when the heart
relaxes
o Same function as the aorta in a mammal
o Sinus venosus is only found in fish; it disappears it land living
organisms
Mammals and birth
o Essential there are 2 two chambered hearts
They are physically together in the same organ however
when broken down you have 2, 2 chambered hearts
o The left side of the heart and a right side.
Left side Always on the right when looking at a diagram
and right side is the left in the diagram
o The left side of the hear takes blood returning from the lungs
and pumps it out to the systemic circulation
o The right side of the heart takes blood returning from systemic
circulation(deoxygenated) and it pumps it to the lungs to be
oxygenated

o Each side of the heart both have an atrium and a ventricle

Left for systemic; right for pulmonary
o Low pressure is needed in the pulmonary circuit and high
pressure in the systemic circulation
This is possible because in effect they have 2 hearts
The left/right sides are operating independently
So the left ventricle can generate high pressure to send
blood to the systemic circulation
The right ventricle generates lower pressure to send blood
to the pulmonary circuit
o The only problem with this circulatory design is that blood flow
always has to go to both parts
As it comes back from the systemic circulation it has to go
back to the pulmonary circuit
There is no way to stop blood flow to the lungs (like when
you hold your breath...doesnt happen bud)
Intermittent air breathers- amphibians; reptiles+ air breathing fish
o Typically have lower metabolic rate
o Heart has 2 atria; one for blood collection from the lungs and
one that is collecting blood from the systemic circulation
o Typically has one ventricle- that directs the flow of blood to the
tissues
In reptiles its partially separated into a left and right
ventricle
In amphibians there is only one ventricle
So deoxygenated blood from the tissues and oxygenated
blood from the lungs come into the same ventricle and are
pumped out to the lungs and tissue
o Even though there is a single ventricle the oxygenated and
deoxygenated blood is relatively separated
The mechs for this are not well understood
o Blood pressure in this animal as a whole is fairly low
Having a high bp will destroy its lung
Bp is limited by what the lungs can withstand
Low bp and low met rate animals
o The advantage of this is that when the animal is under water/
holding its breath the lungs become useless
So the system reduces blood flow to the lungs and
redistributes it to the skin where it can still take up
oxygen
o When it resurfaces it redistributes the blood back to the blood
It has the capacity to shunt blood to diff organs depending
on its require
The presence of a single ventricle makes this possible

o Same idea is seen in reptiles though there is as light separation

in ventricles
o Same plan in air breathing fish
lung fish
o These fish can drown
o Obligate air breathing fish without any access to air they will
drown
o They have a set out gills, a lung and a heart
o They have low met rates
o Tend to breath once every five minutes
During the rime spent underwater the animal is depleting
the oxygen in its lung
o There is a single 4 chambered heart (like a standard fish heart)
As the blood leaves the heart it is directed to the gills
The gills are separated into anterior gills which are not
used for O2 uptake and posterior gills which are used for
O2 uptake
From the posterior gills the blood moves up either to the
lung-if there is usable oxygen here- or if there is no
useable O2 in the lung the ductus opens up and directs
the blood from the gills to the systemic tissues
Oxygenated blood is directed by anterior gills to the
tissues
Deoxygenate blood is directed to posterior gills which
direct to lungs if there is air there or it its directed to the
tissues
The state of the ductus determines whether the blood goes
to the tissues or to the lungs
o The ventricle generates pressure for the lungs, gills, systemic
tissues. Systemic circuit as a whole
Must be a low pressure pump so the lungs are blown
These are low met rate animals
Lecture 3
Mammalian heart
Systemic half on the left has much thicker walls which allows for
higher levels of pressure
Blood returning from lung enters the left atrium and from there goes
into the left ventricle and is pumped out to the systemic tissue where
it is deoxygenated
o The deoxygenated blood is pumped into the right atrium and
then into the right ventricle and is pumped out to the lung
This heart is a chambered heart with contractile walls and based on
this there are valves that direct blood flow

In the mammalian heart there are vales between the atria and the
ventricles to control blood flow
Heart is made of cardiac muscle
o It is similar to skeletal muscle
o These are considered to be striated because they contain
sarcomeres
o They are quite short and are connected end to end by
intercalated discs
In these discs one will find gap junctions
Which are communicating junctions that allow
electrical communication between the different cells
of the heart so they can contract as a unit
o The heart is innervated by the ANS
Within the ANS; there are 2 divisions
Sympathetic
o Responsible for fight/flight alarm type
situations
o Neurotransmitter of choice is noradrenaline
Interact with receptor in the tissues that
are adrenergic receptors
o B-1 receptors are more important for the heart
Parasympathetic
o Responsible for housekeeping or vegetative
functions
o the rest and digest system
o Responsible for functions outside of alarm
situations
o Neurotransmitter of choice is acetylcholine
Interacts with muscular genic receptors
in the effector organ
Main one for the heart is the m2
receptor
Both sympathetic and parasympathetic divisions are active
and in most tissues you can find innervation from both
Heart is innervated by both but they have opposite
affects
o Sympathetic will increase heart rate to allow
for response in emergency situation
o Parasympathetic will slow it down
They have antagonistic effects
ANS allows good control of internal functions without any
conscious control
Most of the heart is made of cardiac muscle cells and these come in
two types

o 99% is made up of strongly contractile muscle cells

Packed full of sarcomeres; responsible for generating
force
o Other 1% are the cells of the conducting system
Pacemaker cells
They do not have a lot of contractile apparatus
They are specialized for controlling and coordinating
heart beat
Include the cells of the sinoatrial node, the atrial
ventricular node and the other cells forming the
conducting system that direct electrical activity over the
heart as a whole
The pacemaker cells have a resting potential that is quite unstable
o They have arresting potential that changes over time-pacemaker
potential and the presence of this changing resting potential is
the key characteristic of a pacemaker cell
o The pacemaker cells slowly depolarize because of the changing
membrane potential and when they reach a certain threshold
they trigger an action potential which the trigger a heartbeat/
contraction of heart
Initiate heart beat+ control it
o The pacemaker potential reflects the presence of the funny
channel
It is considered to be funny because it is open and then
slowly closes and it functions as a Na+ leak channel
Allows Na+ to leak into the cell causing a gradual
depolarization
o Also present in the cell are voltage gated Ca2+ channels(ttypes)
when the membrane potential depolarizes to the
threshold these channels open and it creates an action
potential
o this is what initiates the heart beat in a vertebrate heart and
because it is a muscle cell for the initiation of this heart beat;
vertebrates hearts are considered to be myogenic
neurogenic: nervous activity activate heart beat
gap junctions allow electrical communication between cells
o once an action potential is fired within a cell that is then spread
to the other cells in their heart
o spreads from one heart cell to another by the gap junctions
o the heart rate is then set by the cells that depolarize most
quickly and these happen to be the cell of the sinuses venoses in
fish or sinoatrial node in mammals
pacemaker cells set the heart rate

the pacemaker cells in human sinoatrial node fire at rate of 100 time
per minute
o 100 depolarizations a minute
o This means the heart rate should be 100beats/min
o Heart beat is controlled by other mechanisms
There is input from the parasympathetic nervous system
that regulates heart rate
Sinoatrial node is in the atrium of the mammalian heart and it fires its
action potential first and this spreads across the atria real quick
o It slows down when it gets to the atrial ventricular node
o There is a layer of connective tissue between the two atria and
the two ventricle
o The cells of the atria re connected by gap junctions and the cells
of the ventricle are connected by gap junctions
But the atria and the ventricles do not communicate
This layer of connective tissue means there is no electrical
communication between the atria and ventricles except
through the atrial ventricular node
Conduction though this part of the system is quite slow
Once it gets through this system it speeds up
tremendously and shoots up through the ventricles at a
rate of 4or 5 m/s
ECG
o Measures the consequence of all the action potentials in the bod
fluid as a whole
It is the sum effect of all the action potentials happening
together
o Measured by placing electrodes upon the bodys surface not by
trying to impale a single heart cell to measure membrane
potential of that cell
o In the standard mammalian EKG there is a small wave called the
p wave
This shows the atria depolarizing
o There is a larger wave(QRS): this is the ventricles depolarizing
o Small t wave- this is the ventricular repolarization
o The repolarizing of the atrium is not seen because it occurs at
the same time that the ventricles depolarize and so it is masked
by this
o Value of the EKG tries to figure out what is going on in the heart
The heart as a pump
o Electrical activity in the conducting system has to be converted
into muscle contractions in 99% contractile part of the heart
To get these cells to contract the heart first has to be
depolarized

A strong action potential is needed in the muscle

contractile cells (an ex can be found in slide 22/23)
There is stable resting potential; there is a strong
depolarization, then there is a plateau phase

Slide 22
Action potential f contractile cells
o Stable resting potential and when it is triggered it undergoes
depolarization and a voltage gated Na+ channel opens allowing
Na+ to pour into the cell and this gives you a strong
depolarization
There is also a voltage gated Ca2+ channel that opens a
little bit later and this calcium channel stays open for a
while and that is how one gets the plateau region
This is an L-type gates calcium channel; in
pacemaker there is a t-type calcium channel
The flow of calcium into the cell triggers calcium
release from stores within the cell
o Not only have calcium moving into the cell
through the voltage gated channels you also
have calcium being released from stores inside
the cell
o The release of these stored calcium the
triggers the contraction of the cell
Calcium inflow + calcium
released=occurrence of muscle
contraction
o The cell then repolarizes and this represents a K+ channel that
is opened which allows K+ ions to flow out.
o Note in the diagram there is a prolonged plateau phase and a
refractory period
This is long refractory period is important because the
heart has to relax and refill with blood before it can
contract again
So the refractory period allows for the cells to rest
and reset as well as gives time for the heart to relax
and be refilled with blood
The long plateau in the action potential is necessary
because it allows all the muscle cells to contract at the
same time
This also makes sure that the heart cannot go into a
tetanic contraction-no muscle cramp in the heart
Refractory period: period where the cell is resting before
another AP can occur
Slide 23

Systolic
o When heart is contracting
Diastolic
o When the heart is relaxing
Stroke volume
o Volume of blood pumped b the heart
o When heart contracts it ejects a volume of blood called the SV
and this is the difference in volume of the heart when it is
full(end diastolic volume) and after it contracts(end systolic
volume)
Most of the filling of the ventricles is due to venous pressure
o The valves between the atria and ventricle sis open and so the
blood flow through the valves to the ventricle from the atria
o This is driven by venous pressure; the atrial contraction helps
but it is only responsible for 1/3 of the volume in the ventricle
Venous pressure does all the work
For the heart to function properly output from the heart must match
the need for oxygen delivery
o This can be achieved by increasing heart rate or stroke volume
o Regulation of stroke volume is referred to as inotropic control
and its caused by both a mechanical relationship and neural and
hormonal control
The mechanical relationship is the frank-starling
relationship
See in slide 23
It shows that as end diastolic volume increases(as
heart if filled) SV also increases
o The fuller the heart the more forceful the
contraction and this ejects more blood
It is ;mechanical b/c as you fill the heart fuller it
stretches out muscle and this result in a more
forceful contraction
Very important because you always want to empty
the heart to the same point so by filling the heart
fuller you need more blood out of it to get back to
the same empty point
As heart rate goes higher there is less time needed
to fill it with blood and so the SV gets smaller there
hormonal and neural; mechanisms to accompany the
mechanical relationship and these mechs work to
stoop stroke volume from falling
o Neural/hormonal control of the heart
The sympathetic nerves innervate the ventricles and
strongly contractile muscle cells they release

noradrenaline which acts on 1 androgenic receptors and

this increases the force of contraction
As you increase sympathetic activity at any given
volume more blood is released from the heart; vice
versa for decreased sympathetic activity
Frank Starling relationship describes the change in
SV for a change in filling
o For any given level of sympathetic stimulation
there is a spec frank starling curve
o (only sympathetic control over SV)
o Circulating catecholamines
Sympathetic cells release noradrenaline
The cell that you find in the centre of the adrenal
gland are sympathetic neurons but instead of
releasing neurotransmitter onto the nerve it
releases the NTM into the blood and it circulates as
a hormone
Which is responsible for the fight or flight response
This too can regulate strong volume by acting on the
1 adrenergic receptors
heart rate
o controlling heart rate is the chonotropic effect
o the pacemaker is innervated by both the sympathetic and
parasympathetic systems
contains 1andrenrgic receptors activated by sympathetic
system or by circulating catecholamines
also contains m2 muscarinic receptors activate by ACh
which are activated by the parasympathetic system
sympathetic leads to an increase; parasympathetic causes
it to decrease
o Sympathetic nervous system
When the 1 receptor is activated by adrenaline or
noradrenaline it acts to open the sodium channels more to
get a faster depolarization(faster pacemaker potential)
o parasympathetic
When ACh acts on the m2 receptors it has the effect of
opening up potassium channels which allows positively
charged ions escape from the cell and there for it
depolarizes more slowly
The consequence of this is as low heart rate
o At rest both the sympathetic and parasympathetic systems are
active
o Sympathetic tone which helps set the resting heart rate
o Parasympathetic tone

Parasympathetic nerve that goes to heart is the vagus

nerve(can also be called vagal tone)
This also helps set the resting heart rate.
o Chonotropic effects only affects the pacemaker potential

BIO3302
Lec 4

Blood vessels
3 types (arteries capillaries and veins)
All of them are lined by endothelial cells
o The cells the blood is in contact with
o A type of epithelial cell lining on a basement membrane
In capillaries the endothelial cells are the only cells present
In arteries and veins on top of the endothelial layer there are layers of
connective tissue and smooth muscle
o Connective tissue has elastic elements for flexibility and
collagen so there is too much flexibility
Blood leaves the hear through the aorta which then splits into arteries
and then arteriole and the arteriole leading to the capillaries
o The capillaries are the smallest vessels but they are the most
numerous and a result the surface area is highest in this place
Capillaries coalesce into venoules and veins and eventually lead back
to a single vessel that returns blood to the heart7
Capillaries are the site of exchange between the blood and the tissues
o A large surface area facilities effective exchange
This also means that the velocity of blood flow in the
capillaries is very low
Flow from human heart= 5L/min
This means that there is 5 L/min throughout the whole
circ system
o When blood is flowing in single vessels it flows at a high velocity
o When blood flows through capillaries which count as a broad
channel when all capillaries are taken into account, the velocity
of flow is very slow
Think in terms of a river
Water passing down the grand canyon is channeled
through a narrow river and so the speed of the
water is very high;
As it approaches the ocean it opens up into a delta
which is a very large area with very low flow
As area gets larger in the capillaries the velocity of
movement falls
This is important because it is a point of exchange

Low speed of blood through the capillaries allows

time for exchange to occur
Pressure generated by the heart is what drives the blood through the
circ system and this pressure drives blood flow through resistance
o The smaller vessels(arterioles, capillaries and venoules) provide
the most resistance
As blood passes the aorta and blood comes back through
the veins Bp falls.
The relationship between pressure, resistance and flow are important
in figuring out the circ system works
Resistance is proportional to the length
o It is inversely proportional to radius4
As the radius gets smaller the resistance increases to the
fourth power
Meaning small changes in radii results in large impacts in
resistance
o Viscosity also affects resistance
Thicker it is, higher the resistance
Poiseuilles equation describes flow as a function of the driving force
and the resistance(length, viscosity and radius4)
There are a number of assumptions linked with poiseuilles equation
o Laminar flow
o Straight rigid tubes
Assumes laminar flow
Laminar flow is one that shows the parabolic profile found
in slide 31
All the layers are sliding past each other in an organized
fashion giving parabolic velocity profile where blood in
the center is moving the fastest
Most places in the circ system flow is laminar and so this
assumption is needed
o Viscosity
The internal friction to try and get these layers of blood
sliding past each other
Resistance to sliding
The circ system gives high resistance in that plasma has
2x the viscosity of water and when the blood cells are
added resistance become 3-4x more than water
We tend to assume that viscosity is constant in the entire
circ system
One exception to this is present in vessels that are
quite small
Vessels that are around 0.3mm in diameter

o In these bv, the blood cells line up in the

middle of the vessel- so not scattered
o So what is left on the edges is plasma and the
viscosity of plasma is less than blood.
o This is a good thing because it lowers the
amount the work the heart has to do since
resistance has been lowered
o Making It easier to get blood through the
small blood vessels
o This is known as the Fahraeus Lindgvist effect

o Turbulent flow
In a clinical setting turbulent flow is used to measure Bp
Bp pump is used based on turbulent flow
o Also assume that the lengths of the blood vessels dont change
and so the main determinant of resistance in the circulatory
system is the radius of the vessels
o Another
Straight rigid tubes
o BV are rarely straight and they are not rigid
o This assumption has consequences for the productions that are
made based on Ps equation
o In slide 32 the two tubes have the same P however the low
pressure vessel will have lower flow than the high pressure
vessel
In a vessel that can change sizes high pressure will
expand the vessel and so a higher starting pressure, this
tends to stretch the vessel and increases the radius and
lowers resistance.
This fact can screw up the assumptions one makes when
using Ps equation
This fact is taken into consideration by calculating
compliance
o Compliance is the change in volume for a given change in
pressure
In highly compliant vessels one can see high changes in
volume for only small changes in pressure.
This is the bases of giving blood
The venous system is compliant
Large changes in blood volume with very little
pressure
Meaning you can take a litre of blood out of the
venous system with affecting overall blood pressure.
Because of this high compliance the venous system
tends to act like a reservoir

And the arterial end acts as a pressure reservoir

o Important in maintaining function of the circ
system
Blood vessels by function
Windkessesl vessels
o These dampen pressure oscillations
o These are the aorta and the largest arteries
They function to dampen pressure oscillation therefore
maintaining blood flow
o Ventricle pushes blood into the aorta
The aorta though elastic has low compliance
This mean that when the heart ejects blood into the aorta
the aorta stretches a little bit to accommodate that volume
When the heart relaxes and starts to fill again, the stretch
rebounds
There is elastic recoil, and this maintains blood
pressure and blood flow while the heart is relaxed
and not contraction
It is this recoil that maintains blood in ones body while
the heart is in diastolic.
o If blood flow relied solely on the ventricles it would flow when
the heart is contracting and stop flowing when the heart
relaxes.
The elastic recoil from the aorta prevent pressure from
dropping and therefore maintains blood flow
o The ability to dampen pressure oscillations are due to the elastic
element in the wall of the aorta and large arteries(the
Windkessesl vessels)
If these vessels disappear or harden heart functions is
affected
These vessels also have very thick walls b/c they are high
pressure vessels and they have a large radius
o The large radius is another important function on its own
These vessels distribute blood to the heart out to the
periphery
The most effective way to do that is to be low resistance
vessels
The large radius=low radius
o Large radius+ low pressure= thick walls
As blood leaves the aorta and large arteries it passes into
progressively smaller arteries and then the arterioles
Pre-capillary resistance vessels
o These are the smallest arteries and arterioles
o Their small size provide a high amount of resistance

Small radius=high resistance

o Pressure drops abruptly as it goes through the precapillary
vessels
o These vessels set and regulate blood pressure and in turn
regulate blood flow
o In a fight or flight system blood is redirected away from your
intestines and towards the exercising muscles and this
redirection of blood is accomplished by the pre-cap resistance
vessels
Alternatively when one has just had lunch and the gut is
busy digesting, blood is being directed to the blood and
away from skeletal muscles
This too is done by the pre-cap resistance vessels
o Structural feature involving their ability to set blood pressure
and blood flow is the smooth muscle that lines the walls of these
vessels allows the radius to be adjusted
The smooth muscles in walls regulated by both the
nervous system and the endocrine system (sympathetic
system or hormones)
They are also regulated by environmental condition
o When one is working out and the muscles are
metabolically active and produce more CO2
and waste products local metabolic conditions
will regulate blood flow so increased blood
flow will get to the exercising muscles
Pre-capillary sphincters
o These are just little bands of smooth muscle leading into the
capillary bed
o They set blood flow at a local level
o They are not innervated and respond to local condition
o Help to determine where blood goes within the capillary bed
o This takes blood to the capillaries
Capillaries
o Thin walled vessels
o Very numerous
o Form an extensive network so that any cell is predicted to be 3
or 4 cells
o Site of exchange
Thin walls and high surface area help with the exchange
High surface area results in low velocity of flow are also
important for exchange
o More is coming later
Post-capillary resistance vessels

o Blood exists the capillaries and flow into the post-cap resistance
vessels
o These are the venoules and the smallest veins
o The walls of these vessels contain smooth muscle and so the
radius can be adjusted to help control pressure within the
capillary bed
If constricted there is higher pressure in the capillaries
Capacitance
o These are the large veins
o Highly distensible the walls are relatively thin
o Their walls contain smooth muscles and so the radius can be
adjusted to the amount of blood that is present
o Allows them to function as capacitance vessels
Large changes in volume but little change in pressure
o This is important they act as a volume reservoir
When giving blood, blood is taken from the venous
reservoir
When one exercises and an increase in blood flow is
needed, volume is immobilized from the venous reservoir
to increase blood flow to exercising muscles
If volume of the system is not adjusted to the volume of blood that is
there
o Standing still/perfectly for two long and the skeletal muscle
pumps cannot return blood to the heart
o Blood will pool in the lower extremities and the consequence of
that is fainting
o This happens because
Blood pools in the venous system which is very complaint
and due to gravity blood will be pulled down
Typically the muscles pump the blood pooled into the
venous system back to the heart
But in the case of standing perfectly still the muscles
are not moving and so cannot do this
This results in a decrease of venous flow to the heart and
when this falls it results in a decrease in cardiac output
This decrease in cardiac output reduces blood flow to the
brain and the consequence of this is fainting.
If there is no constant flow to the brain the circ system
rearranges the position in order to redistribute the blood
back to the brain
The brain is very sensitive to lack of oxygen and
requires constant flow
Loss of blood also results ^^
Capillary function

These are the key to the circ system b/c its in the capillaries that
exchange between tissues and blood occur
Capillaries are important in the exchange of nutrients, gasses, waste
products
o This occurs by diffusion
o The Fick equation basically tells you how much is diffusing and
this is dependent on:
The amount that is being transferred
the amount that is transferred by diffusion depends
on the gradient and the gradient is set by partial
pressure or concentration
if the cells are using oxygen you are given a partial
pressure gradient for oxygen movement from the
blood to the tissues
using up glucose will give a concentration gradient
Permeability
Lipid soluble (O2 +CO2) vs lipid insoluble
substances(or water soluble like glucose or urea/
ions/amino acids)
Lipid soluble molecules can simple move through
the walls of the capillaries through the cell
membrane
Water soluble compounds can only move through the
walls of the capillaries either by being transported
or by moving though water channels
Capillaries vary in permeability and water channels
that are present
Depends on surface area
Larger surface area the more diffusion
Inversely proportional to the thickness of the walls
Diffusion is harder to accomplish in a thick wall vs a
thin wall

Types of capillaries
o Continuous capillaries
Capillaries where there are no major gaps
Just narrow intercellular clefts between the cells about
4nm in width
Will allow water and ions to pass through
But no proteins can enter through these clefts b/c the
clefts are small

In some areas there are no intracellular cleft ex the blood

brain barrier
This occurs b/c the capillaries in the brain have tight
junctions instead of intracellular clefts
o Fenestrated capillaries
These have holes/pores 80nm in diameter
Increases the ease in which water soluble molecules can
cross the walls
These holes are still too small for proteins to go through
o Sinusoidal capillaries
Has gaping holes between the cells
And these holes are large enough for a blood cell to get
through s well as an incomplete basement membrane

Lec 5
Capillaries manage fluid balance
In a closed system animal has blood an interstitial fluid and these two
fluids differ in composition
o Blood contains blood cells and plasma proteins; interstitial fluid
does not
o Interstitial fluid is 3x more in volume than blood

o Losing blood causes the interstitial fluid to become a source of

fluid that brings the blood volume back to normal
Capillaries allow fluid to move into the interstitial fluid or out of the
interstitial fluid to maintain volume
Fluid balance in capillaries is driven by two sets of pressures
o There is a filtration pressure that tends to move fluid out of the
capillaries
This is created by the hydrostatic pressure for blood that
blood pressure
o There is also fluid pressure in the interstitial tissues which is the
interstitial fluid hydrostatic pressure
Normally blood pressure is greater than hydrostatic fluid
pressure
This difference tends to drive fluid out of the
capillaries
o Filtration pressure: blood pressure- interstitial pressure
o There is a difference in osmotic pressure between he interstitial
fluid and the blood his is because the blood has proteins and the
interstitial fluid does not
Osmotic pressure of blood is greater than that of the
intestinal fluid and that tend to draw fluid into the
capillaries
Absorption pressure= osmotic pressure of blood- osmotic
c pressure of IF
If filtration pressure is greater than absorptive pressure water moves
out of the capillaries and if the absorptive pressure is greater than
filtration pressure water will move into the capillaries.
Under normal donations at the arterial end of the capillary there is a
tendency to lose water b/c blood pressure is high and the osmotic
pressure stays constant throughout the length of the capillary
o At the venous end bp is lower therefore there is a tendency for
water to move back into the capillaries.
o So essentially there is a circulation water exited at the arterial
end and taken up at the venous end
o If these two things do not match fluid loss or fluid gain into the
circ system will occur
Starling Landis hypothesis
o There is a circulation within the capillaries with no net loss of
fluid
o However this is not true
o The lost fluid is collected by the lymphatic system
Carries the fluid and proteins that leak out and puts it
back into the circ system

Lecture 6
Lymphatic system
There is overall a net loss of fluid from the capillaries this lost fluid or
proteins needs to go back to the circulatory system
This return is the function of the lymphatic system
The lymphatic system parallels the venous system;
o It has leaky lymph capillaries collect fluid and protein that are
lost from the circulatory system and they return it to the circ
system
The lymph vessels are very thin walled and non-muscular but they
are compressed by surrounding muscles
o They have valves that direct fluid flow
o Fluid that accumulates in the lymph capillaries are gradually
moved into the circulatory system
o The lymph vessels empty into the large veins in the neck
This is where the lowest pressures of the circulatory
system are found
Although lymph flow is not a large as cardiac output
Cardiac output=5l/min
Lymphatic flow= 2ml/min
Without the lymph flow to collect the fluid and proteins you end up
with oedema
o Oedema occurs when the tissue swells
The importance of the lymphatic system becomes more prominent
when its function is blocked
o Filariasis
A diseases in which larval nematodes invade the lymphatic
system by blocking the lymph vessels resulting in
extremely severe oedema
Under normal conditions sometimes the lymphatic system cannot
keep up with fluid loss
Kwashiorkors syndrome
In K syndrome the individual is getting enough calories to maintain
life but is protein deficient
The consequence of this causes tissue oedema in the lower legs, feet
and esp. in the abdomen
In K syndrome the lymphatic system is working normally
The physiological basis of K syndrome
o Loss of fluid into surrounding tissues is caused by insufficient
protein in the blood to balance the absorptive force and
filtration force

o The filtration becomes greater than absorption and so there is

net loss of fluid
o As the fluid leaves the circ system and accumulates in the
tissues the hydrostatic pressure of the ISF increases
As a result the filtration rate becomes smaller and
balance is re-established where filtration=absorption
except for the fact that tissue oedema persists
o If the lymphatic did clear away all the fluid; the cycle would just
repeat itself
o Low osmotic pressure in the blood lowers the absorptive force
and so there is net loss of fluid.
This net loss of fluid into the tissues increases the
hydrostatic pressure of the fluid making the filtration
force smaller and bringing things back into balance
But with significant tissue oedema
Control of regional circulation
Circulatory system works on a priority system so the tissues that are
least resistance to oxygen lack have the highest priority for blood
flow
o Ex the brain-very susceptible to lack of O2 top of priority
system; next in line are the Heart+ gas exchange organ.
Everything else happens to be expendable
o If there is a problem with lack of blood the blood will be cut off
from non-essential tissues like the viscera in order to maintain
blood flow to the essential tissues
Important definitions
o Ischemia
Lack of blood flow
o Hyperemia
Higher blood flow than normal
Active hyperemia
Occurs when tissues are metabolically active
During exercise
Reactive hyperemia
The higher than usually blood flow that follows
ischemia
o Reynauds syndrome
People that suffer from this have an unusually strong
response to cold
Hands become white because blood flow is
completely shut off
It can be so strong that the tissues can become ischemic

In order to re-establish blood flow one must apply an

external heating source(running hands under warm
water)
Control mechanisms of different blood flow patterns
o Local mechanism
Act at the level of the tissue;
and neural and hormonal mechanisms; higher level of
control going down to the tissues
these mechs operate at the arteriole and pre-capillary
sphincters
control at arterioles allows blood to be directed to
some tissues but not others
o in a flight-fight response control of the
arterioles seeds blood to the exercising
muscles but not to the digestive muscles or
kidney
control at precapillary sphincters
o is within a tissue; regulating blood flow
within a capillary bed
Neural and hormonal mechanism
o Under control of the sympathetic nervous system
o Sympathetic neurons release noradrenaline which then acts on
1 adrenergic receptors that are present in the smooth muscle
of the arteriole walls
o When the 1 adrenorecepotrs are activated they increase
cytosolic calcium levels in the muscles cells;;the muscles
contract and vasoconstriction occurs
Blood vessels become smaller
o Vasomotor tone
The background level of activity in the sympathetic nerve
going to the smooth muscles of blood vessels
An increase in sympathetic activity cause the vessels to
constrict further but it can also decrease sympathetic
activity to decrease level of constriction/dilate
No parasympathetic component. It is all being run by the
sympathetic system
o The 1 adrenorecepotrs provides the mechanism to cause
vasoconstriction
These receptors are found in most arterioles but not in
arterioles found in the brain, heart, or lungs/gills
The activation of the sympathetic nervous system will
result in the shutdown of blood flow to the
viscera(abdominal organs) by causes vasoconstriction

but this will not affect blood flow to the brain, heart
or gas exchange organ
helps maintain priority
second level on control at the level or arterioles
o based on the sympathetic nervous system but this time the
adrenal medulla releases a circulating catecholamine
o this acts on the 2 receptor
o the 2 receptor are scattered throughout blood vessels and are
found in the arteriole smooth muscle
these cause the muscle to relax
when they are activated the blood vessels dilate
both the 1 and 2 receptors can be found in the same tissues
however you will typically find slightly different distributions between
tissues
o the viscera is well endowed with -1 receptors
o skeletal muscles contain 1 receptors(how cold induces
lessened blood flow to the hands work
however they also contain a lot of 2 receptors which
allow you to override the vasoconstrictor response in
emergency situations
when it is a true fight or flight situation one gets a kick of
adrenaline
adrenal gland suddenly releases adrenaline into
circulation; when this happens adrenergic
receptors are activated and you get vasodilation
in a true full out sympathetic panic blood flow is shut
down to the viscera through the 1 receptors while at the
sometimes causing vasodilation in the skeletal muscles
allowing to escape from the predator
all this is at the level of the smooth muscle of the arteriole
wall
Local Control Mechanism of blood flow
this controls arterioles and pre-capillary sphincters
heat
o promotes vasodilation
compounds produced and released from endothelial cells
o promotes vasodilation and increases blood flow
o ex nitric oxide
inflammatory mediators
o promotes vasodilation and increases blood flow
o ex histamine
metabolic control

o when tissues are metabolically active they automatically

experience vasodilation and this does not require nerves or
hormones
o this is because metabolic activity decreases O2 levels and
increases CO2, proton, adenosine, K+ (collectively known as
metabolites)
o this combination of low O2 and high metabolites causes
vasodilation
o this acts on the arterioles and the pre-capillary sphincters
o it is also very highly developed in skeletal muscles
skeletal muscles that are metabolic active experiences
increase in blood flow and this is the basis of reactive
hyperemia
pulmonary capillaries respond in the opposite fashion to oxygen
o low oxygen levels causes pulmonary capillaries to constrict
rather than dilate
o low O2 in the lung means that, that part of the lung is not
getting good air flow
the purpose of the lung is to take up oxygen theres no
point sending blood to where there is no oxygen
so this mechanism redirects blood to where there is more
oxygen
on the other hand in skeletal muscles, low O2 results in increased
blood flow to deliver O2 to exercising tissue
Physiological basis of:
cold induced ischemia
o when exposed to cold the sympathetic system is activated
shutting down blood flow to the hands
this is caused by the response of 1 receptors
o lack of heat results in vasoconstriction
o In the case of Reynauds syndrome blood would be
completely shut off from the hands.
Individual runs hands under warm water using heat to
get the vessels to dilate
reactive hyperemia
o when there is no blood flow to the tissues during ischemia,
metabolism still contains but oxygen is just not being
supplied and those levels fall
o the metabolites are not being removed and so their levels
increase
CO2, adenosine, proton, K+ etc. levels increase
o This is the basis of vasodilation in reactive hyperemia

o There is accumulation of metabolite and loss of oxygen and

so when blood flow is re-established there is a higher than
normal blood flow to bring conditions back normal.
Control of blood pressure
The maintenance of blood flow is blood pressure
Maintaining blood pressure maintains blood flow to the brain, heart
and lungs/gills
The other value lies in the maintenance of fluid balance between the
blood and the tissue
Regulation of blood flow is accomplished by two mechanism
o Chronic mechanism
Requires hours to days to come into effect and are based
on the kidneys
If bp is too high then one urinates more in order to reduce
blood volume and this brings b back to normal
Urine flow rate is being matched to either the
increase or decrease in volume to bring it back to
normal
This is mechanism is great for long term control of blood
volume and blood pressure
But does not help with moment to moment
processes
o Acute mechanism
Based on neural reflex arc
They specifically regulate heart rate and the radius of the
arterioles in order to control blood pressure
They are based on P=QR
See slide 50
Regulation of blood pressure= regulation of P
In order to regulate P; Q and R must be regulated
as well
Q= SV x HR
o In mammals heart rate is adjusted more than
stroke volume
R(Total periphery resistance)
o Focus is mostly on arterioles
o Construction of arterioles resistance increase;
if the arterioles are dilated resistance will go
down
Vasoconstriction or vasodilation of arterioles tend to
set pressure
But do not forget the venous system
o Constriction of the venous system is important
because it moves blood back to the heart

Increases venous ceiling pressure and

fills the heart fuller to help increase
cardiac output
Regulating blood pressure is mostly dependent on the
regulation of heart rate and the radius of the arteriole
In an acute sense
Acute mechanism of blood pressure control is depends on neural
reflex arcs
o One of the most important reflex arcs involved in regulation bp
is the baroreceptor reflex arc
o Baroreceptors
Sensory receptors that detect pressure as stretch in a
blood vessel wall
Found in the walls of blood vessels
They are the sensory component of the neural reflex arc
Under normal conditions he baroreceptors fire at an
intermediate rate (produce APs at a background
rate)
If pressure goes up the vessels expand a little bit
and this cause the baroreceptors to become more
active telling the brain that bp has gone up.
If bp falls blood vessels reduce in stretch and the
baroreceptor firing decreases and it tells the brain
that blood pressure has fallen
To allow for the maintenance of blood flow to the brain
baroreceptors are found in the aortic arch b/c that
monitors bp in the systemic circ as a whole
The baroreceptors are also found in the carotid sinus
The arteries taking blood from the heat to the veins
are carotid arteries in the neck these arteries spilt
and just at the end where they split there is a little
widening g called the carotid sinus
The baroreceptors found here are perfectly placed
to monitor blood pressure to the brain.
o In this neural arc the information of blood pressure entering the
brain goes to the cardiovascular centre of the brain in the
brainstem
Takes int information coming from the baroreceptors
Processes the information and then ends out appropriate
response
These responses regulate heart rate and the smooth
vessels of the blood vessel walls- the arterioles in
particular
BIO3302 Lec 7

Lec 6 recap
Baroreceptor reflex is one of the really important neural pathways for
the acute regulation of blood pressure
o But its not the only neural pathway
o There are chemoreceptors that detect blood and CO2 levels
that help regulate blood pressure
Baroreceptors are still the key mechanism for the adjustment of blood
pressure on a moment to moment basis
o Going from lying down to standing up
They are sensory receptors in the all of the aorta and carotid sinuses
and are activated by stretch
o Have a resting firing rate and as pressure goes up they fire
more, as pressure falls they fires less
o This degree of firing is integrated by the cardiovascular center
in the medulla and appropriate output is sent to the effector
organs(heart and smooth muscle in blood vessel walls) and they
adjust pressure
To adjust pressure heart rate and vasoconstriction of the
arterioles are adjusted and this occurs in a negative
feedback fashion
Slide 52
o Arterial blood pressure has increased
Could happen if one quickly drink a large volume of water
Or going from standing up to lying down
o Increase in bp and want to bring down to the normal value
This increase is detected by the baroreceptors
Causes the firing to increase
Firing is detected and integrated by the cardiovascular
center in the brain stem
o It adjust the sympathetic and parasympathetic activity in the
heart and blood vessels
o Heart
If blood pressure increased, decrease cardiac output must
occur to bring heart rate down
Parasympathetic control
So heart rate has to slow down by increasing the
parasympathetic activity through the vagus nerve
and m2 receptors
o Need to increase vagal tone
The increase in parasympathetic activity will in turn
decrease heart rate and decrease cardiac output
Sympathetic control

Decrease in sympathetic activity will lower heart

rate and stroke volume
1 receptor activation allows for this
all of these process will lower heart rate and in turn lower
blood pressure
o the vasomotor center
in order to reduce bp vasodilation is needed in this center
vasodilation is achieved by decreasing sympathetic
activity which decreases tonic activity in the arteries and
veins and this will cause them to dilate which lowers
resistance and reduces bp
1 receptors are involved
when baroreceptors are at the normal resting value, then everything
is in the tonic/background level of activity and there is no need to
change activity
o as soon as activity changes and any minor changes in bp are
immediately corrected through this pathway
problem with baroreceptors is that they adapt to the change of
pressure over time
o if one has consistently high bp(hypertension) the baroreceptors
reset so that the high bp becomes the new norm
o same thing for hypotension
the adjustment of vasodilation/constriction arterials cause an
immediate effect on pressure b/c such activity affects resistance
o on the other hand the adjustment of vasomotor tone to the
venous system, venous return is affected which affects cardiac
output which affects blood pressure
Exercise
increases met rate an in turn increase O2 consumption by 5-10x
o this mean that increased oxygen delivery to the exercising
tissues
o in part this oxygen delivery is the responsibility of the circ
system
to meet the high O2demand caused by exercise an increased cardiac
output is needed so more o2 can get to the tissues
o there is also a redistribution of cardiac output
some tissues are not used very much where other are
heavily used
the blood is redistributed to meet the needs of the tissues
slide 54
o the blood flow priorities during rest+ exercise
Large increase in cardiac out put
Significant changes where the blood is going to

But these changes occur with only small

consequences on blood pressure
P=QR
P remains the same
Increase in Q
R would decrease
Circulatory responses to exercise
Hyperemia
o Exercising muscles need increased blood flow
o Active hyperemia is one method of achieving such
It is a local metabolic effect
o Even before you start exercising there is an increase in
sympathetic activity in anticipation of exercise
This causes dilation of some of the blood vessels in
skeletal muscles b/c some of the sympathetic neurons can
release ACh
As the sympathetic system is activated there is some
vasodilation to the skeletal muscle
o As soon as the muscle starts exercising active hyperemia takes
over and massive blood flow to exercising muscle can occur
Increases Cardiac Output
o This increase in blood flow has to be met with increasing
cardiac output
o The increased sympathetic activity increases heart rate and the
force of contraction of the heart
Peripheral Vasoconstriction
o This will be achieved through the1 receptors
o Blood flow going to abdominal organs will be reduced
o It could cause vasoconstriction in muscle fibers but active
hyperemia takes over
o Does cause constriction of the veins; this is a benefit because it
increases venous return and this helps to increase cardiac
output
As you exercise the skeletal muscle pumps in the legs also
promote venous return and this helps cardiac output
An increase in cardiac output tends to increase bp, however at the
same time there is an increase in cardiac output there is an overall
fall in peripheral resistance
o The fall in peripheral resistance is driven primarily by
vasodilation in skeletal muscles
o There is vasoconstriction to abdominal muscles but this
constriction is offset by the vasodilation in the skeletal muscle
So over all resistance falls and cardiac out increases and
pressure stays the same