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 witho 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 muscleo 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 capillarieso 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 systemo When blood is flowing in single vessels it flows at a high velocityo 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 lengtho 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

Poiseuille’s 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 poiseuille’s equationo Laminar flowo 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 diametero In these bv, the blood cells line up in the

middle of the vessel- so not scatteredo 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 effecto 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 don’t 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 rigido This assumption has consequences for the productions that are

made based on P’s equationo In slide 32 the two tubes have the same ΔP 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 P’s 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 oscillationso 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 one’s 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 arterioleso Their small size provide a high amount of resistance

Small radius=high resistanceo Pressure drops abruptly as it goes through the precapillary

vesselso 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 vesselso 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 conditiono 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 sphincterso These are just little bands of smooth muscle leading into the

capillary bedo They set blood flow at a local levelo They are not innervated and respond to local conditiono Help to determine where blood goes within the capillary bedo This takes blood to the capillaries

Capillarieso Thin walled vesselso Very numerouso Form an extensive network so that any cell is predicted to be 3

or 4 cellso 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 exchangeo More is coming later

Post-capillary resistance vesselso Blood exists the capillaries and flow into the post-cap resistance

vesselso These are the venoules and the smallest veinso 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

Capacitanceo These are the large veinso Highly distensible the walls are relatively thino Their walls contain smooth muscles and so the radius can be

adjusted to the amount of blood that is presento Allows them to function as capacitance vessels

Large changes in volume but little change in pressureo 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 it’s 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 diffusiono 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 capillarieso 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

cleft’s 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 cleftso 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 compositiono Blood contains blood cells and plasma proteins; interstitial fluid

does noto Interstitial fluid is 3x more in volume than bloodo 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 pressureo 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 hypothesiso There is a circulation within the capillaries with no net loss of

fluido However this is not trueo 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 6Lymphatic 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 blockedo 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

Kwashiorkor’s 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 definitionso Ischemia

Lack of blood flowo 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

ischemiao Reynaud’s 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 patternso 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 sphincterso is within a tissue; regulating blood flow

within a capillary bed Neural and hormonal mechanism

o Under control of the sympathetic nervous systemo Sympathetic neurons release noradrenaline which then acts on

α1 adrenergic receptors that are present in the smooth muscle of the arteriole walls

o When the α1 adrenorecepotrs are activated they increase cytosolic calcium levels in the muscles cells;;the muscles contract and vasoconstriction occurs

Blood vessels become smallero 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 α1 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 ß2 receptoro the ß2 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 α1 and ß2 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 α-1 receptorso skeletal muscles contain α1 receptors(how cold induces

lessened blood flow to the hands work however they also contain a lot of ß2 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 ß 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 α1 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 flowo ex nitric oxide

inflammatory mediatorso promotes vasodilation and increases blood flowo ex histamine

metabolic controlo 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 sphincterso 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 oxygeno 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 there’s 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 α1 receptorso lack of heat results in vasoconstrictiono In the case of Reynaud’s 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 increaseo This is the basis of vasodilation in reactive hyperemiao 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 ΔP=QR

See slide 50 Regulation of blood pressure= regulation of ΔP

In order to regulate ΔP; Q and R must be regulated as well

Q= SV x HRo In mammals heart rate is adjusted more than

stroke volume R(Total periphery resistance)

o Focus is mostly on arterioleso 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 systemo 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 arcso One of the most important reflex arcs involved in regulation bp

is the baroreceptor reflex arco 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 AP’s 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