6-5-14 p.

1
Human cells need ATP which we have very little of
We need constant oxygen in cells so it can be used in the mitochondria
If we dont have oxygen we arent going to be able to generate ATP and the cells will die
Unicellular organisms dont have cardiovascular systems reasons are: 1. Oxygen could
diffuse into the cell 2. Aerobic co2 and water can diffuse out 3. Glycolytic cycle product
is lactic acid so it could diffuse out
Animals become multicellular so they had to develop a cardiovascular system
Mammals and humans have 4 chamber hearts
http://skaggs.us/heart/heart.jpg
http://drugline.org/img/term/left-atrium-8590_2.jpg
Human heart drawing
Piece of tissue right down the middle is called the septum. It separates the heart into the
left heart and right heart
We have piece of tissue called fibrous ring
septum and fibrous ring separates the heart to bottom half and top half which generates
four chambers
the top chambers are called atria
we have left and right atrium and below them we have the right and left ventricle
The heart is hollow (have space or cavity inside)
Each of the left and right ventricles have free walls individually, and the left and right
atrium also have free walls
The free walls are made up of cardiac cells , have -80 mv, high sodium outside, high K
inside, has actin, has myosin, has SR which means that they can make AP

So the free wall can contract and can apply pressure to each of the 4 chambers
Septum runs down the middle, fibrous ring runs across
We have right and left atrium and right and left ventricles
The heart is not symmetrical top to bottom and left to right
Ex. Not like a pizza
The free wall of left ventricle is 3x thicker, 3x more actin, 3x myosin and troponin, so it
produces 3x the pressure in left ventricle

http://www.vhlab.umn.edu/atlas/left-ventricle/free-wall/index.shtml

Chamber diameter= size of chamber
Left ventricle chamber and right ventricle chamber are not different in size
Primary difference between the two chambers is the thickness of the free wall
The atrium diameter is smaller than the ventricular chambers
Fibrous ring not split in the middle so it makes two small chambers and two bigger
chambers
Septum has two parts 1. There is an atrial septum which goes down to the fibrous ring 2.
We also have ventricular septum
Genetic disorders/congenital (means existing at birth) disorders
There are Atrial septal defects and ventricular septal defects
Artery called aorta comes out of LV exits out and goes to cells of our body, then it goes
to capillaries, and blood returns back
Our circulatory system is crossed
LV out to cell of our body, returning to RA
Conversely we have an artery coming out of RV called pulmonary artery or PA which
leads to tiny blood vessels and to the lungs
Circulation goes RV out to PA to our lungs
Circulations are crossed kind of like the contralateral concept last test
We have systemic circulation which starts at the LV, to aorta, to capillaries out to cells,
and blood vessels that bring blood flow back is called vena cava (vena cava is a vein)
Systemic circulation: LV, aorta, capillaries, vena cava, RA
Pulmonic system: RV, PA, capillaries at our lungs, blood vessel bring blood flow to LA
are called pulmonary veins
A capillary is an extremely small blood vessel located within the tissues of the body, that
transports blood from arteries to veins.
These two circulation systems are crossed
= Pulmonary circulation starts on the right and ends on left and vice versa
There is a disease called transposition of the great arteries
In healthy person blood leaving RV is very low in oxygen content= deoxygenated
hemoglobin or deoxygenated blood
Starting from Pulmonary artery: low oxygen > oxygen diffuse out of lungs into blood
stream > high oxygen in blood stream > oxygenated blood in aorta > oxygen diffuse out
of capillary into mitochondria for aerobic energy reproduction > resynthesize ATP
In vena cava high oxygen or low oxygen?
= low oxygen because oxygen has already diffused from in the blood stream into the cells
Vena cava > RA
When Pulmonary and systemic are not crossed is called transposition
Transposition means trans means across
Two major arteries on heart 1 aorta 2. PA which are called great arteries
Normally aorta exits out of LV
Normally PA comes out RV
Transposing arteries: aorta come out of RV, PA come out of LV
LV> pulmonary artery> LA
RV> AORTA > CELLS >RA
During development = transposition of great arteries= happened to child they would die
70 years ago= die because the circulations are not crossed and you dont get oxygen
down to your cells and baby comes out blue > dead
Solution is to go to surgery, and snip off two vessels and make them crossed again
3 congenital heart disorders
1. transposition of great arteries
2. atrial septal defects (hole)
3. ventricular septal defect
Transposition of great arteries= aorta is supposed to come out of LV and PA supposed to
come out RV = but they got transposed so the downside is that you cant get oxygen
down to cells and cell death occurs
Could not get surgeon in, kid born and is blue = vessels transposed. Solution is to stick
catheter and create atrial septal defect which is septostomy
In transposition of great arteries there is great amount of oxygen on one side
Atrial Septostomy= hole in septum= oxygenated blood can mix with low oxygenated
blood which is enough to keep cells alive long enough to surgically cross the two systems
In uterus the baby is in fluid so there is no use in it breathing and it gets oxygen from the
mother
We have atrial septal defect called foramen ovale in utero: blood goes to babys cells,
fetus taking oxygen, returning to RA, dont want to go to RV and go to lungs because
lungs are not working, so uterus pumps oxygen to LA and back around again, skipping
the pulmonary circulation
http://nationwidechildrens.congenital.org/pics/pfo3.gif



Baby gets delivered 1
st
minute or 2
nd
min of birth the foramen ovale closes up and now
we have two separate circulations that are crossed
In some people foramen ovale doesnt close all the way which is called the patent
foramen ovale = atrial septal defect
Patent foramen ovale = bad thing
Patent foramen ovale= good if you were born with transposition of great arteries
Surgeons purposely Create the hole so that the baby can survive long enough so it can
have surgery
Patent foramen ovale is bad in 2 day child= intermixing= RA (low), LA (high)= oxygen
going out to cells, lowers oxygen going to cells. You get a mixing of deoxygenated and
oxygenated blood and so not as much oxygen can go out to cells.
Patent foramen ovale good in fetal life in transposition of great arteries
In fetal circulation, mother puts oxygen in through placenta.
Foramen means hole
Ovale= oval hole
Foramen ovale allows bypass of fetal lungs which are useless (skip RV)
Patent means remains open
A patent foramen ovale = low amount of blood /deoxygenated going to cells to the aorta
because of inter mixing of high oxygenated blood and low oxygenated blood in the
atrium (RA and LA) >cells > death
In kids some of blood goes through patent foramen ovale, some goes out to lungs two
ways to stop the blood flow from going to the lungs
There are 4 valves located in the heart
Mitral valve from LA to LV
RA TO RV is tricuspid valves
These two valves are embedded in fibrous rings which are collectively called the AV
valves"
Two more valves 1. between LV and aorta called aortic valve and 2. one that seperates
RV from PA is called pulmonic valve Collectively there are called semi-lunar valves
The semilunar valves (SV) are two valve structures that sit between the right ventricle and the
pulmonary artery and between the left ventricle and the aorta.
The valves are made of cusps or leaflets
The mitral valve is the only one in healthy human being made of two cusps
50% of cusp is overlapped with other cusp
Advantage of having overlap is that it makes blood hard to go backwards
Blood goes backwards through valve called regurgitation
If the Valves were flat the blood would go backwards
Valves thick means 1. More surface area 2. Blood squeezes laterally onto the two cusps
together and creates a better seal to prevent regurgitation
When the mitral valve breaks and allows blood to go backwards mitral regurgitation
There can also be Tricuspid regurgitation
Symptom of mitral regurgitation valve is that cusps are not working perfectly and blood
goes backwards. Some of blood goes backwards and the size of the LA gets hypertrophy
or dilates or gets larger which is not usually what brings people in. Person would have
trouble with breathing with their lungs and trouble breathing can be a lot of other things
as well.
Differential diagnosis
Ex. Being able to not breath could be asthma, could be lung cancer. So physician figures
out symptoms and what they could be and eliminate possibilities.
Mitral regurgitation makes an extra sound and when you put stethoscope you would hear
the blood regurgitation. Hear heart murmur = mitral regurgitation because you can hear
blood going backwards which is differential diagnosis
Mitral valve = pope hat has two pieces of material called miter cap= dissecting
animals it looked like miter cap
Tricuspid valve= three cusps
Aortic has three cusps and the pulmonic valve has three cusps
Weakest part of valves of the three cusps is not the cusps the weakest part is the seams
(where they meet) where the valve meets because blood can regurgitate through there
Amount of Seams in two cusp valve is one
Three cusps = 3 seams which greatly increase chance of blood regurgitating
Mitral valve has two cusps because there is a congenital heart condition called tricuspid
mitral valve
Tricuspid mitral valve = mitral valve now has three cusps= more seams = blood has
greater chance of regurgitating = end up with mitral regurgitation
Pressure in physio we use mmHg (millimeters of mercury).
Pressure of 10 mmHg= pressure to raise 10mmHg off of gravity= get tired of saying
mmHg= 1 mmHg is same as saying 1 torr= alberto torrichelli
Ex. Squeeze on toothpaste tube and toothpaste come out
= squeeze on chamber can develop pressure
LV or RV generates higher pressure
= LV because of the free wall it has which is 3x thicker in LV. So it has 3x of cardiac
cells and so actin a myosin cross bridges more = pressure when it is contracting can go up
to 120 torr in healthy and not contracting can drop to 4 torr.
Ex. Tube increases, decrease, increase pressure (fluctuates)
Heart contracting= systole
Diastole= heart is relaxing
LV systolic pressure = free wall contracting = squeeze toothpaste (analogy) = pressure
goes up and stop squeezing pressure goes down = LV systolic pressure is120 torr
LV diastolic pressure (not contracting) = 4 torr
Congenital condition tricuspid mitral valve = mitral regurgitation
Tricuspid valve doesnt regurgitate in healthy person because the systolic pressure in RV
is much lower than it is in the LV.
RV systolic pressure = is 25 mmHg (free wall not as thick as LV)
RV diastolic pressure = 2 mmHg
Dont get regurgitation in tricuspid valve because systolic pressure in RV is lower
compared to LV
Other congenital valve disease people are born with bicuspid aortic valve = aortic valve
is supposed to have three cusps but if it only has two cusps it cant open all the way so
you cant have as much blood flow. Symptomology 1. Cant get oxygen 2. Become
fatigued/ cyanotic (blue skin)
6-5-14 p.2
Atrium have pressures
Atrium are smaller and have free walls which contract and put pressure
Atrium contract and relax so they have to have a high pressure and a low pressure
High pressure = systolic pressure which is when heart is contracting
Low pressure = diastole
Atrial pressures are lower than ventricular pressures because of the size of the free
wall
The walls in atrium are very thin so not a lot of cells are going to contract and cause
pressure
We can replace the valves
Replace mitral valve for a person with mitral regurgitation
2 choices
1. Mechanical man made valve made of titanium and the half-life is forever, however
they cause blood clots to form on them.
2. Or you could put in a pig valve aka biological replacement which has a life-span
of 15 years. Good thing about pig valve is that it is naturally occurring tissue so it
doesnt form blood clots.
Ex. Rose vs. thorn analogy
Younger than 65. Valve put in for younger people is mechanical valve. Older than 65
give biologic cause something else kill you before valve fails.
Blood clots starts to form on mechanical valve > brain > get stuck in capillaries in
brain. So they got to put you on anticoagulants to stop clotting.
What would happen if you get cut as a martial artist with anticoagulants and
mechanical valve? (question)
Ross procedure: With Aortic regurgitation could put in pig valve. Take out pulmonic
valve and transfer over to where the aortic valve is supposed to be and put pig valve
over to the RV where the pulmonic is supposed to be.
Pig valve lasts 15 years on left side of the heart where there is high pressure. Pig
valve lasts much longer applied to the right side because the pressures are much
lower.
Downside of this procedure is you have to cut two valves, anesthesia, it takes 2x
longer for surgeons
Can take the biologic valve and not have to worry about taking antithrombotic
medicine
Move native valve to left hand side and put biologic on right hand side = ross
procedure
Pig valve (biologic valve) on right side lasts 45 years which is 3x greater, than putting
it on the left side of 15 years
Ross procedure = dont have to take anticoagulants or antithrombotic

6-9-14 p.1
All 4 of the chambers have a free wall and chamber diameter
Free walls have actin, myosin, SR, t-tube which causes them to contract
PA takes blood to our lungs where it gets oxygenated
Pulmonary circulation cross with systemic circulation
Systemic circulation goes out aorta to our body
Jam blood in lungs (like plastic bags) they become very stiff (by way of mitral
regurgitation ( blood going back to the lungs)
Systolic (contracting) in LV= 120 mmHg, free wall is bigger, need to get blood to brain
against gravity
systolic in RV= 25 mmHg
RV (dont need high pressure because not going against gravity) >lungs> LA (gravity not
affecting),

NOT GOING AGAINST GRAVITY Look at pic
http://3.bp.blogspot.com/-0k259Eyg8gE/TjK-
16ds5hI/AAAAAAAADxk/s9bMA1DAjxw/s400/HeartLungs.jpg

Show heart circulation to brain going against gravity

http://heartzine.com/diagrams/circulatory-system.jpg

LV need high pressure
Low LV systolic pressure = dizziness= syncope = light headed = pass out
Ex. Giraffe is an animal has heart one place and brain 5 feet above heart. LV blood
pressure in giraffe of 120 mmHg would not be enough (pump half way up the neck),
blood pressure of a giraffe is 250 mmHg. Giraffe generate 250 mmHg because it has a
big LV freewall to generate high systolic pressure to pump blood against gravity (in other
words pump blood to the brain from the heart).
Systolic pressure in LA = 12 mmHg
Systolic pressure in RA = 6 mmHg
Located high in RA = cells that are called SA node (outside layer of heart diagram in
real)
SA node pic
http://webanatomy.net/histology/cardiac/sa_node.jpg
SA node = -80mv (RMP) = proteins in SA node called funny Na+ channels
Funny Na+ channels = integral membrane proteins = located in phospholipid bilayer of
SA node cells = funny because they are odd compared to other proteins in our body=
open by themselves about once per sec= generate AP
Funny Na+ channels = opens once per sec on its own= high Na outside the cell because
of Na/K atpase
Funny Na+ channels opens, Na comes in (high to low conc) = cell reach threshold and we
have AP in SA node cells> -80 mv in atrial cells
Embedded in free wall over the chamber in RA are sa node cells
The sinoatrial node is a group of cells positioned on the wall of the right atrium, near the
entrance of the superior vena cava.
There are gaps between cell membrane of SA node cells and all of the atrial cells which
are called gap junctions
AP in healthy person starts at SA node because of the funny Na channels. Funny Na
channels located at SA node cells which are what other cells dont have. SA node cell is
called the pacemaker
Na+ diffuse into next cell coming from the SA node originally because positive ions are
attracted to the negative charge in the atrial cells which gives us threshold and we have
the neighboring atrial cells being able to generate AP (Analogy of this is domino effect)
Put funny channels in bicep than we would spasm
AP spreads to next groups of cells sequentially
AP does not go back to SA node because there is hyperpolarization in the cells that had
AP and also where the AP originated from (SA node) which causes it to move one
direction
Funny channels are only expressed in certain cells which is the SA node
AP spread across two atrium the two atrium are contracting
AP in atrium is sequential which spread across two atrium causing them to contract and
so the atrial cells must have gap junctions
Atrium contract the blood is ejected from atrium to ventricles
Cardiac cycle = each beat of the heart has 5 individual phases that the heart has to beat,
relax, and refill
When SA node funny channels open and allow SA node to reach AP, AP spread
sequentially across two atrium, this causes two atrium to contract and cause pressure to
go to LA (12mmHg) RA (6mmHg), blood is then ejected from atrium to ventricles. This
whole phase is called active filling of the ventricles which is phase 2.
He is going to ask what ends and starts next phase
Events that occurs that starts active filling is AP of SA node which is caused by the
opening of the funny Na channels
Only one SA node in a healthy person
You can develop multiple areas that are generating AP in atrium.
Atrium then quivers which is called atrial fibrillation or a-fib, the two atrium have lost
coordinated sequential fashion because there are multiple APs in the atrium
Person in a-fib. The ventricles would fill less because you have less active filling.
Not ejecting a lot of blood and blood pressure falls = syncope
Warfarin
Lining inside all of the blood vessels of humans is called the endothelium which is in
contact with the blood
Endothelium is cells in contact with flowing blood. These cells secrete a substance out
into the bloodstream called NO (nitric oxide) and TPA.
Blood will coagulate outside of the body.
Ex. you get cut and blood goes on table the blood will coagulate.
Endotheliums two secretions NO and TPA are anticoagulants. And so when you drop
blood onto the table there is no NO and TPA so it coagulates.
Why would you have a-fib? Multiple AP in atrium. Atrium quivering. Blood hasnt
circulated, so it clots because it doesnt rub up against endothelium. People in a-fib die
from stroking. Clot forms > out aorta >carotid artery > brain. All tissue downstream dies
because of no blood going to cells which means no oxygen going to cells and so Na/ K
pumps are not working because there is no ATP.

http://upload.wikimedia.org/wikipedia/commons/thumb/e/e6/Gray506.svg/220px-
Gray506.svg.png

http://cdn.c.photoshelter.com/img-
get/I0000Ez8vFoblhZk/s/600/600/prn43100DS.jpg

http://weill.cornell.edu/cms/health_library/images/ei_2397.gif
Clot forms and jams in small blood vessel all the tissue downstream dies = ischemic
stroke. Ischemia means lack of blood flow which means lack of oxygen.
Another type of stroke is high blood pressure and the blood vessel ruptures. This is bad
because you would have lack of blood flow going past that. This is called hemorrhagic
stroke.
Kill tissue in most medial aspects of left motor cortex which is where upper motor
neurons are before they decussate in the medulla. Paralysis = right leg
Ischemic stroke right face paralysis = lateral aspect of left motor cortex
Have a stroke and enter emergency room within first 3 hours= TPA will be given to the
patient to stop clots and clot will dissolve
Can only give TPA within first 3 hours when symptomology starts
Stroke occur 12 hours ago breaking up clot is more dangerous than leaving it because the
tissue downstream is dead
Embolus is something that moves downstream
An ischemic stroke can occur in two ways: embolic and thrombotic strokes.
Give TPA to person who has hemorrhagic stroke = cause more blood to be ejected
Bleed out in brain means you have a hemorrhage stroke. Give TPA to person with
hemorrhage then you screw it up because it is just going to hemorrhage more.
Only give TPA to people with ischemic stroke
Atrial fib= increase chance of stroking = because correct amount of TPA and NO is not
added to blood so clot forms goes to brain and they stroke. Person in A-fib would be
given warfarin which is a cheaper anticoagulant than NO and TPA.
Mechanical valves cause formation of clots which means you have to be given warfarin
for the rest of your life
What brings on a-fib
A-fib occurs when atrium gets enlarged and when they havent contracted. Mitral
regurgitation would cause blood to go backwards to go into atrium. The LA gets
enlarged. People with mitral regurgitation would have higher chance of stroke because it
could cause a-fib which can in turn cause thrombus formation or blood clot.
Mitral regurgitation >atrial enlarge > atrial fibrosis > a-fib
What causes a fib. As atrium enlarges there is a production of collagen fibers which gets
interspersed between the gap junctions of the atrial cells. This is known as fibrosis.
Fibrosis means collagen fibers inserted into the tissue. The coordinated AP has a hard
time to get from cell to cell.
Blood moves for one reason which is to go from high pressure to low pressure
Funny channel >SA node AP > ap spreading across two atrium via gap junctions
sequentially > cause atrium to contract > increase pressure in atrium causing pressure in
atrium to be greater than in ventricles. Ventricles are not contracting at this point.
Pressure in right ventricle when it contract is 25 when it relax it is 4.
Pressure in RV when it relaxes is 4 mmHg and pressure in RA is 6 when it contracts. So
blood goes from high to low pressure from RA to RV.
This whole process is called active filling
Active filling = atrium actually have to contract
AP gets to AV node which is located in the atrial septum just above the fibrous ring
AP spread across atrium> Atrium contract > AP goes to AV node> AV node slows AP
down 1/10
th
of a sec which is called AV node delay
AV node delay = you dont want AP get down into because you dont want ventricles
contracting until all of active filling has occurred or until they are full
Sequential= in atrium=
Ex. boom boom boom of toothpaste
Close the cap of the toothpaste and you squeeze = max pressure
Humans can have all cell contract simultaneous
Ex. Child balloon is 60 mmHg. 120 mmHg is big
Mammals two ways to generated high pressures 1. Sequential contraction (atrium) into
simultaneous contraction which occurs in ventricles. 2. Simultaneous contraction to occur
on closed ventricle because it generates high pressure
Tissue that pierces in fibrous ring called Bundle of His
Gap junctions found between atrial cells
There are no gap junctions in the fibrous ring which means that the AP that occurred in
atrium has no way to get into ventricles which means ventricles cant have AP and cant
contract and you be dead
Bundle of His pierces through fibrous ring and it then splits running on either side of the
ventricular septum which are called the Left bundle branch and right bundle branch.
Bundle branches come down and little fibers come off of these left and right branches
and go out into the free walls of left and right ventricles. Little fibers called purkinje
fibers which are located pierced into the free walls.
Big cells means AP can move very fast which is why Bundle of His, left and right bundle
branches, and purkinje fibers are big.
AP gets to bundle of his then gets to all cells of free wall rapidly >all cells in free walls of
two ventricles and they contract simultaneously so pressure increases in LV/RV and the
mitral and tricuspid valves closes which is S1. S1 means the end of active filling.
Ventricle squeezes
Isometric volumetric contraction= iso means the same= simultaneous contraction on a
closed system= all 4 valves closed= drives pressure of ventricles to increase
What starts isometric volume contraction and ends active filling = s1
6-9-14 p.2
AP starts in sa node> spread gap junction around whole atrium> atrium contract cause
blood flow into ventricle> Filling of ventricles = active filling of ventricles> AP goes to
AV node and allows =ventricles to get full > bundle of his > left and right bundle
branches >purkinje fibers> then AP spreads to all the ventricle cells of the free wall > and
the ventricles pressure rises because they are contracting
http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/en/stomat/ptn/1/12
%20Cardiovascular%20system.files/image079.jpg

When they all contract the pressure starts to rise
Contract LV pressure goes up and exceeds pressure in LA and mitral valve closes
Contract RV pressure goes up and exceed pressure in RA and tricuspid valve closes
Closure of mitral and tricuspid valves = S1
Ventricles then contract isovolumetrically
120 mmHg LV and 25 mmHg in RV
When pressure in RV and LV exceeds pressure in aorta the aortic valve and pulmonic
valve open
Started isometric volume contraction = s1, ends isovolumetric contraction = opening of
aortic and pulmonic valves
Opening valves does not makes a sound and blood ejected out of LV into aorta and RV in
PA is called the stroke volume which 70 mL of blood ejected per beat at rest
Closing of a valve makes a sound because the leaflets overlap
LV into aortic, RV to PA= 70 mL of blood ejected called stroke volume at rest
Contraction doesnt go backwards and is sequential because the cell is hyperpolarized
Sequential in atrium rather than simultaneous= because you dont have to pump blood far
to get to the ventricles
To get blood from ventricles you need simultaneous
Ends isovolumetric contractions and starts ejection phase = opening of aortic and
pulmonic valves
Mitral regurgitation stroke volume LV= less than 70 ml because some of blood going
back up
Difference between all 4 valves and blood ejected is that pulmonic and aortic valves are
now open
Blood ejected and ventricles contract and eject blood= 70 ml/beat called stroke volume
Someone has mitral regurgitation anticipate that stroke volume from LV is greater,
less, or equal? Less than 70
Syncope in morning
Mitral regurgitation may lead to a-fib
Blood ejected and ventricles contracted then go to relax. So LV and RV pressures go
down. Now there is pressure out here in the blood. And pressure in LV and RV are now
less than 120. So Aortic and pulmonic closes which is called S2
What ends ejection phase and starts ventricles relaxing? S2
Blood ejects out of LV as long as aortic valve is open
Physician should hear two sounds if they put stethoscope
Ventricle is relaxing and so pressure goes down. Blood has been filling this whole time
the atrium and this is called venous return.
Venous return. As blood is returning back to atrium and they are starting to fill the
pressure in the atrium goes up. Pressure in ventricles going down. Mitral and tricuspid
valves now open.
Contraction of atrium isnt what opens mitral and tricuspid vales. What opens the valves
is blood returning back, the ventricles relaxing which cause the valves to open. Blood
starts to fill the two ventricles and the atrium are not contracting. Called Passive filling
of the ventricles. Ventricles 80% of its filling occurs during Venous return, passive
filling of the ventricles
How would you fill a big ventricle by squeezing on little tiny atrium
Venous return fills the atrium which opens mitral and tricuspid valve, and blood flows
and ventricles fill 80% of the way which is called passive filling of the ventricles
Someone in a-fib doesnt die because the ventricle still gets passive filling.
What now happens SA node > funny channels> ap> spread across atrium sequentially>
atrium contract and fill rest of the ventricles by active filling
80% of ventricles filling occurs from venous return
6-10-14 p.1
Thrombus is a blood clot in bloodstream
Thrombus isnt trouble until it breaks loose and travels through blood stream
Thrombus can go to brain and cause ischemic stroke= on move is called embolus
Increase risk for thrombus emboli= a-fib = not rubbing up against blood vessels
Blood vessel= cross sectional= lumen where blood is flowing through
= three layers 1. Outside layer= tunica externa 2. Middle layer = tunica media which is
made up of vascular smooth muscle, relax= vasodilation, contract=vasoconstriction, help
change. Change size of blood vessel which can change resistance of blood vessel which
controls blood pressure 3. Inner most layer is called tunica intima and absolute inner most
portion of tunica intima is called endothelium
Endothelium secret 1. NO 2. TPA
TPA stands for tissue plasminogen activator which will breaks clots down
Plasminogen breaks clots that are formed.
Ischemic stroke you can inject TPA
Anti =against, thrombotic = break down small clots which is what TPA is
TPA activates plasminogen
When do thrombus emboli form = form when blood stasis which is when it is pooling=
stasis means it is pooling some place and not rubbing against endothelium and not getting
TPA and NO
A-fib cause blood stasis? What is happening is that atrium is fibrillating. This would
cause blood stasis, does not get NO and TPA and so you have greater chance of thrombus
emboli formation
Ex. David bloom was put in a tank and left him there for 36 hours. He is squished and did
not drink anything. What happened was thrombus emboli in his leg which went back to
RA.>RV> PA> lungs. Clots sticking in lungs is called pulmonary embolism.
Thrombus emboli on right side. Venous side going vena cava > RA> RV> pulmonary
artery> lungs. This is a pulmonary embolism
Thrombo embili on left side. LA>LV> AORTA> brain. Get ischemic stroke
An ischemic stroke develops when a blood vessel (artery) supplying blood to an area of the brain
becomes blocked by a blood clot. The clot may form in the blood vessel (thrombus) or travel from
somewhere else in the blood system (embolus).

Blood returning back from lungs to LA and from body to RA= venous return= atrium are
filling and atrium has no contraction and pressure in atrium exceeds pressure in ventricles
because of blood flow= AV valves open and blood flows into ventricles which fills 80%
of the ways and no contraction is going on which is called passive filling
Systolic pressure are when ventricles are going to contract
Ventricles not contracting in passive filling so there are low pressures in the ventricles
Opening of valves do not make sound
Passive filling account for 80% of filling of ventricles
Funny channels in SA node now depolarize > AP> ap spreads sequentially via gap junc>
spread across atrium > atrium contract
LA contract = 12 mmHg RA contract = 6 mmHg which jams more blood down into
ventricles called active filling which accounts for 20% of ventricle filling
You dont want the ventricles to contract until all of the active filling so AP goes to AV
node and AV node delay happens > AP gets to bundle of his (ap starts in sa node and can
get into ventricles this way)
Dead if there were gap junc in fibrous rings because AP would spread into ventricles
sequentially. Sequential does not generate high enough pressure
Bundle of his> l+r bundle branches > purkinje fibers out to free wall. AP spreads around
with aortic and pulmonic valves closed and ventricle starts to contract. Pressure in LV is
13mmHg compared to LA pressure of 12 mmHg the mitral valve will close. So AV
valves close and we hear it called S1. And aortic valves are still closed
Pressure of 40 in LV of relaxation. The aortic valve has not opened yet because its
pressure is 80 mmHg
Period of time ventricles are contracting will all 4 valves closed called isometric
volumetric contraction. This generates high pressure. The aortic valve and pulmonic
valve now open and blood is ejected about 70 ml/beat which is called stroke volume.
Ends isometric volumetric contraction and starts ejection phase = opening of the aortic
and pulmonic valves which you do not hear. The ventricles now start to relax and the
pressure in the bloodstream now causes the aortic and pulmonic valves to snap shut.
What starts ejection phase is opening of valves and ends ejection phase is closing of the
valves which is S2. End of ejection phase This is called ventricular relaxtion
Ventricles contracting >ejecting blood> relaxing> atrium have been experiencing venus
return> mitral and tricuspid valves are open and we start cardiac cycle again
Each beat is made up of 5 phases of cardiac cycle
To decide which side of pressure opens and close valves =
Ex. analogy of Bully on the other side of the door. If you are stronger then him you will
open the door if he is stronger than you he will keep the door closed.
Same idea with the 4 valves of our heart. Higher pressure on one side will cause opening
or closing if going against lower pressure.
Blood pressure never goes lower than 80 mmHg
Valves open for one reason put greater pressure than other side
Mitral valve open = Pressure in atrium exceed pressure in ventricle. Mitral valve closes
pressure in LV is greater than the pressure in the LA.
Valves only open because of changes in pressure
Aortic valve opens when LV pressure exceeds pressure in aorta
LV pressure exceed pressure in aorta with ventricular systole
Venous return increases atrial pressure to make its pressure greater than ventricular
pressure to make the valves open
Two major problems that can happen to the valve
Ex. With a window, could get window stuck and cant close and you cant open it
1. the valve could develop so it doesnt open all the way. Blood would be forced through
narrow valve and it becomes turbulent. Stenosis means narrowing. This is called mitral
stenosis could have stenosis with any of the 4 valves.
2. Valve opens fine but when it closes it cant seal all the way. The valve is called
insufficient. Insufficient valve results in blood regurgitation. Could have insufficiency
with any of the 4 valves.
Healthy person you should hear S1 close of mitral and tricuspid and s2 closure of
pulmonic and aortic valves. More than two sounds it is called a murmur.
Between s1 and s2 ventricles are ventricular systole
Between s2 back to s1 are ventricular diastole
Any sound occurs between s1 and s2 is called a systolic murmur. Which is phase 3 and
4 of the cardiac cycle.
Any murmur between s2 and next s1 is called diastolic murmur.
Mitral stenosis = problem is mitral valve not open all the way. Stenotic valves make a
sound when the valve is open. When mitral valve opens normally blood flows smooth.
Atrium trying to force blood flow through a narrow opening which makes the blood
turbulent.
Ex. Whistle. Lips are stenotic which cause turbulence of air and sound is produced. Valve
is stenotic its going to make a sound when fluid is flowing through the valve and so it
becomes turbulent and makes a murmur.
Regurgitating or insufficient valve make noise. The valve closes and blood goes back and
it makes a murmur
Stenotic valve makes sounds when it is open and blood is flowing through it.
Regurgitating valve makes sound after it closes and blood goes backwards through it.
Mitral stenosis = Making sound when mitral valve is open, cant tell where it opened but
you can tell where it closed. Mitral valve closes at S1. Mitral valve open before S1
Mitral regurgitation= mitral valve= regurgitating so blood going backwards so mitral
valve is closed before regurgitation. Sound would be
MS= occur between S2 and next S1 = diastolic murmur
MR= systolic murmur= between s1 and next s2= ventricles are contracting some blood
regurgitates back
AS = aortic valve is affected and it is a narrow valve so it will make a sound when blood
flows through the narrow valve. Makes sound between s1 and s2= systolic murmur
We have early systole and late systole
MR= pan systolic murmur= pan means the whole time it is making a sound
AS= systolic murmur= During isometric volume contraction dont hear sound because
valve has not opened. Aortic Stenosis is a late systolic murmur.
A.S.= occurs during ejection phase because stenosis sounds occur only when blood is
flowing = Late systolic
Ventricle contracting during phase 3 and 4
Only phase blood flow flowing through aortic valve= ejection phase 4
A.R. make sound after aortic valve closes. Aortic valve closes at s2. Aortic valve make
sound after s2. Diastolic murmur occurring early.
MS = late diastolic murmur.
6-10-14 p.2
Amount of blood ejected 70 ml/Bt= stroke volume
SA node in most human being spontaneously depolarizes because of Na funny channels
which open once per second or 60 times per minute
AP> gap junctions across the atrium > 5 phases occur
Cardiac cycle
1. Passive Filling (80%)
2. Active Filling (20%)
S1
3. IVC (contraction of ventricles)
4. Ejection phase
S2
5. Ventricular Relaxation
Rate at which you have cardiac cycle is 60-100 BPM or heart rate does not have a name
Anything less than 60 bpm is called bradycardia
Any heart rate greater than 100 bpm called tachycardia
SA node by itself will depolarize
-80 mv > funny channels open > SA node depolarize to threshold > AP >back to RMP
>repeat process
Areas between RMP and threshold and opening is the funny channels in SA node which
is called pre potential skeletal muscles and other cells dont have pre potentials
Skeletal muscles have stable RMP
SA node cells have pre potential which is do to occur once per second same as 60 beats
per minute
Made funny channels open faster what would happen is that Na go in faster and it reach
threshold sooner. So slope of pre potential is steeper incline so you become tachycardia.
Made funny channels open slower = bradycardia. Slope of pre potential will take longer
for it to reach threshold.
So we can control heart rate. Heart rate not always 60 bpm.
Ex. Go for run you become tachycardia. Sleep at night become bradycardia.
Can control rate of opening of funny channels. What controls the rate of opening funny
channels are two nerves coming down and can release chemicals or neurotransmitters
onto SA node. One is called sympathetic nervous system
Ex. Called fight or flight. Sympathetic activate under exercise and fear.
Sympathetic nervous system releases norepinephrine and it makes the funny channels
tachycardia.
Fight or flight = releases norepinephrine to SA node and funny channels open faster and
heart rate increases
Parasympathetic nervous system releases Ach. Ach on SA node.
Ex rest and digest.
ACh it slows the rate that cell reaches threshold.
Heart rate X stroke volume = cardiac output = 4900 ml/min
Normal resting stroke volume = 70 ml/beat
Normal heart rate = 70 beats per min
Cardiac output (Q or or CO ) is the volume of blood being pumped by the heart, in particular
by a left or right ventricle in the time interval of one minute.
We have 5L of blood circulated around when you have heart rate 70 bpm and 70 ml/beat
Training depresses sympathetic nervous system so parasympathetic takes over
Lance Armstrong resting heart rate is 29 bpm. With us we are probably 50 or 60 bpm
Lance Armstrong can increase heart rate faster and at rest sympathetic is depressed.
Heart rate sympathetic and parasympathetic system controls heart rate
Stroke volume = ejected per beat is 70 ml
During passive filling ventricle is filling up and now atrium contract and squeeze last
pieces of blood. LV and RV have 140 ml of blood in them. This is called end diastolic
volume. Done relaxing = 140 ml
Called end diastolic volume because it hasnt contracted yet
LV/RV eject 70 ml so there are 70 mls left. You dont empty each ventricle with each
beat. End of contraction 70 ml is left which is called end systolic volume.
70 ml is ejected
Formula for stroke volume= end diastolic volume (EDV) - end systolic volume (ESV)=
140-70= 70
Ejection fraction= SV/EDV = 70/ 140 = = 50% of resting human being
Tiger chase sam
Sam wants to become tachycardia so you can have more beats and pump more blood
around. Fill something to 140 ml and pump only 50% and do it again.
Ex. This is like filling garbage truck with 140 lbs and dumping 50% which is stupid.
Advantage of filling 140 ml and eject 50% of it at rest.
Ex. Tiger chases sam she fills to 140 and contract more forcefully when tiger chases. 20
left in ventricles SV is 120.
Under fight or flight conditions you want cardiac output to go up more so tiger cant get
sam. Sam become tachycardia
End diastolic volume of 70 and eject all of it out stroke volume would be 70 ml
Under fight or flight if you eject all blood out first time fill to 70 eject it all tiger chases
Sam she cant increase stroke volume.
Fill to 140 eject 50%. Tiger comes fill to 140 and eject 120. By only ejecting 50% at rest
this allows sam at fight or flight to increase SV because she can contract more forcefully
and use the reserved blood.
Downside of fill to 70 take out 70 you cant increase SV
You need to increase SV and heart rate for more oxygen and more ATP
Chronotropic means HR
Chrono means time.
Drugs make heart rate go up are positive Chronotropic drugs. Negative Chronotropic
drugs make heart rate go down
Inotropic refers to how forceful the heart is beating
Normal ejection fraction is 50%. Tiger chasing sam you want to be more forceful heart
beat so EF goes up and therefore when EF goes up. EF AT 50% HEART IS PRETTY
NORMAL.
Heart diseases and heart not being able to pump very forcefully means the EF is low. If
you have EF of 20% you dead. Positive inotropic response make EF go up. Negative
inotropic response make EF go down
Ex. Cardiac failure EF of 20%. Give drug positive inotropic drug to increase the EF up.
6-11-14 p.1
Sympathetic nervous system come down and releases called norepinephrine out to SA
node, causes funny channels to open faster and makes pre potential slope steeper =
tachycardia = + heart rate
Parasympathetic= release ACh out to SA node cause funny channels to open slower so
this causes Bradycardia which is slowing the heart rate
Receptor that binds is called the beta-1 adrenergic receptor
There is also an alpha adrenergic
Adrenergic refers to it binds to norepinephrine
Beta-1 adrenergic receptor agonists
Agonist= something binds to receptor and produces effect
Mimicking nor epi= agonist of the beta 1 adrenergic receptor which would cause heart
rate to increase = beta 1 adrenergic receptor is a positive chronotropic which is making
heart rate go faster
Amine = means it is a beta 1 adrenergic receptor agonist = make heart rate go up
Someone went into shock= anaphylactic shock = low blood pressure = give B1AR
agonist to make heart rate go up and increase blood pressure
B
1
AR antagonist = blocking so norepi cant have effect on SA node so Ach takes over.
These slow the heart rate down. They are chronotrops. Classic drug for this is
Propranolol. Olol= beta 1 AR antagonists which will antagonize or block and are
beta blockers.
Blocking beta receptor going to cause heart rate to go down and therefore it is a negative
Chronotropic
Positive chronotrops= speeds up HR. Nega= slow down HR
Cardiac output= HR x SV (stroke volume)
HR normal = 60-100 bpm
Less than 60 is bradycardia
More than 100 is tachycardia
Lower HR lower flow and so less CO
Inotropes are referring how forceful the heart beats. In your heart right now
70 ml ejected = SV better term is ejection fraction
Ejection = how much blood is ejected expressed as fraction
140 with 70 ml ejected = 70 left
Ejection fraction increases because you want more blood to circulate so you can get more
oxygen down to mitochondria and be able to generate ATP
50% = EF at rest but during exercise or fight or flight EF might increase to 75%
Ventricles have sarcomeres. Heart started failing and you could no longer contract
forcefully and blood not pumped out = blood remain in the ventricles and they heart gets
enlarged. Sarcomeres only work if you could get myosin heads to reach up and cross
bridge with actin. With sarcomere enlarged the force would be less because the heart gets
congestive or dilated. The ventricles get stretched out more and more and actin and
myosin lose ability to overlap congestive heart failure. Actin and myosin are not
optimally overlapping. So you would have small EF. Tiger would love to see you have
small EF with less oxygen and less ATP for you.
Give someone a drug that is a positive inotrope so you can bring EF back up to 50%.
Amine= positive Chronotropic and positive inotropes. Amines= funny channels open
faster and make the cardiac cells beat more forceful.
Gave dobutamine (positive inotrope) to a person in class right now expect EF to be 25%,
50, 75, 225. It would be 75% because we already at 50%. Person with 25% EF = give
positive inotrope to get it back to 50%
Each cardiac cycle produces a systolic and diastolic
Blood pressure in capillaries is 40 mmHg
Pressure in vein or venous system is 5 mmHg
Point is BP 120/80 is the blood pressure in the aorta or big arteries
Pressure in Capillaries is 40 mmHg because you have lost pressure due to circulation of
blood
Blood pressure gradient = high in arteries, middle in capillaries, and low in veins
What controls blood pressure is Ohms law
Ohm law is V (voltage) = I(flowing electrons) x R(resistance)
V= current times resistance for electricity
Water act just like electricity
So they obey ohms law
BP = cardiac output (flowing blood) x TPR (resistance) which is analogous to Ohms law
TPR = 1/r^4. Small tubes have high resistance. Big tubes have low resistance
Ex. You can look at this mathematically. When the # on the denominator of a fraction
gets smaller what happens to the number? The number gets bigger. And vice versa for #
getting bigger on denominator.
Resistance is inversely related to size of tube
Ex. Thin straw used to drink has very high resistance
TPR= fourth power function which means changing size of tube from 1 in radius to a 2in
radius. Resistance will get smaller.
Very small changes in size of blood vessels will effect resistance a lot
Change size of blood vessels = tunica media = middle layer of blood vessels which has
vascular smooth muscle which can make blood vessels get bigger (vasodilation) or
contract (vasoconstriction)
Inner most layer is made of endothelium in tunica intima
With Vasodilation is resistance getting smaller or greater? Resistance gets smaller
You only need to change size of blood vessels a little cause resistance is inversely
proportional to a fourth power function which means very small changes make big
differences in resistance
BP = cardiac output (flow coming out heart or blood pumped) x TPR (set by radius of
size of all blood vessels)
Ex.Thumb over hose water squirts farther. More flow and put hand over get you to squirt
more. Put thumb on hose = decrease radius so you increase resistance and you are going
to have more pressure. And this squirts further
1/3 of Americans have condition called hypertension
Hypertension is when (normal = 120 systolic /80 diastolic). Go to 160 mmHg or 100
mmHg = hypertension = high blood pressure
High pressure in blood vessels = tunica intima with endothelium will be damaged so NO
and TPA will not be produced or put out in bloodstream normally. People who are
hypertensive have great risk of stroke and blood clots.
Two ways to treat hypertension either decrease cardiac output or TPR because BP =
cardiac output (flowing blood) x TPR (resistance) which is analogous to Ohms law

High pressures damage endothelium and so they dont produce as much NO and TPA.
Pressure goes to 160 the pressure damages endothelium and you get clots and ischemic
strokes and also great increase in hemorrhagic stroke.
Before blood vessel rupture = there is a bulge called an aneurysm = catch early enough
they will treat with stent
Hypertension 1. Damage endothelium 2. Increase chance for ischemic stroke and also
hemorrhagic stroke
Cardiac output = heart rate x stroke volume
Patient with hypertension (high BP) = dont give dobutamine (increase heart rate) which
increase cardiac output which increase BP
Dobutamine used for low BP like when you are in shock
Hypertension= give negative Chronotropic = propranolol. Anything with olol = beta
blockers= beta 1 AR antagonists = lower heart rate >lower cardiac output > lower
pressure
B1AR = in the heart
Beta 2 means they are outside the heart like in lungs and other
Could give a beta blocker or try to vasodilation blood vessels for hypertension
Vasodilation > lower resistance > means lower pressure. Drug that does this is B1AR
antagonist work in heart to lower flow. You want vasodilation you dont want drug
working in heart. Need to relax vascular smooth muscle because it is located in tunica
media of blood vessels. If you prevent Ca+ getting into vascular smooth muscle so the
cell wont contract. So drug given to vasodilate are called Ca channel antagonists or
blockers. Amine= beta 1 ar agonists cause it is + chrontropic and +inotropic. Olol drugs
are B1 ar antagonists or block = inotropic and chonotropic = bradycardia. Pine drugs
= work only in vascular smooth muscle by blocking Ca+ from being able to enter
vascular smooth muscle = no contraction = vasodilation = decrease TPR = decrease BP
Grandma took 10 pine drugs. Symptom = syncope. Lower BP too much cant pump
blood against gravity and you cant get blood to brain.
Beta blockers and ca blockers = propranolol and nifedipine = multipharmicate giving
small dosages of each and reduce side effects and still get the BP where you want
Could use one drug but there would be more side effects
Exercise lower blood pressure cause vasodilate
Scripps internal medicine got tired of medicine. Opened up clinic with nutritionist.
Hypertensive drugs and exercise.
6-11-14 p.2
Humans have 4-6 L of total blood. Adults averagely have 5L of blood. 5l/ min was the
cardiac output
Three major places take blood out. 1. Brachial artery splits to Radial and ulnar arteries
Try not taking out of brachial artery.
Damage a radial artery you still have ulnar or vice versa
Stick needle in artery you dont need a vacuum there is so much pressure and so you stick
needle and it automatically fills
Centrifuge blood all of red blood cells called erythrocytes they will be forced to bottom
of tube and straw colored fluid on top called plasma
More plasma than red cells which means it is not a 50-50 split. You measure it with
hematocrit (HCT) or crit.
Hematocrit = % of blood made of red blood cells
Males 40-45% is normal range for hematocrit in healthy males
Females is 35-40%
Hematocrit goes over 50% = polycythemia = great increase for stroke= great thrombus
emboli= die from ischemic stroke= because so many red cells that TPA and NO cant
stop them from forming clots. Poly means multiple. Polycythemia = multiple blood cells
Anything less than 32% hematocrit = anemia
Structure of human red blood cell is a bi concave disk
Diameter of human capillary is 7.5 um. And diameter of blood cell is 8 um. As red blood
cells get into capillaries have to deform to get through the vessel. Bi concave disk shape=
gives cells flexibility with flex point in the middle and so they lose biconcave disk shape
when they go into human capillary.
Sickle cell anemia= low hematocrit = Red cells are not bi concave but rather they are
sickle shaped and they lose flexibility and deformity. These sickle cells get stuck in the
capillaries.
No nucleus in red blood cells. That means they live for 100 days and then they are
destroyed
No mitochondria in red blood cells
Role of red blood cells is to carry oxygen to other cells. If you put mitochondria in red
blood cells the blood cell would use the oxygen that is supposed to be destined for other
cells.
There is a protein hemoglobin (Hb), 210-240 million hemoglobin molecules in side each
red blood cell.
Hemoglobin is a tetramer. It has 4 proteins associated. It has 2 alpha proteins that are
identical and 2 beta proteins. 2 alpha chains and 2 beta chains. Alpha 2 beta 2 tetramer.
On each chain has a structure hooked to it called the Heme. 1 molecule of iron hooked to
each Heme. Each molecule of Fe can bind 1 molecule of oxygen. Proteins bind Heme
which have 1 Fe and which can bind oxygen
Most common form of anemia is iron deficiency anemia. It is when you Dont eat right
amount of Fe. Leads to Lack of oxygen, fatigue, cyanosis (mucous membrane turns blue)
Hb > lungs oxygen going to diffuse from lungs into bloodstream> oxygen hook onto Fe
Hb >after pass lungs >
Oxygen passed to cells that means hemoglobin would look like it has no oxygen on Fe
because oxygen went out to cells
Plasma = 90% water, 7% are proteins
7% protein = albumin which are plasma proteins
3% of plasma is made of Na, Ca, K
You can Give plasma 2x a week
Take 1 unit of blood = 480 ml = 1/10 of blood. Can only take blood every 2 month
because you got to build all the hemoglobin back which means you have to build back the
alpha, beta, and Heme units.
6-12-14 p.1
BP arterial system= high pressure of 120 mmHg
BP not 120 mmHg around whole system
BP = has blood pressure gradient
BP = 40 mmHg in capillaries
5 mmHg in the venous system
Vein = blood does not come out easily cause of pressure
Cut artery= arterial walls are thick and have endothelium inside and thick layer of smooth
muscle in tunica media = blood flowing through tube and pressure in artery is 120 mmHg
which is high pressure (two childs balloons)
Force fluid out of artery laterally but it cant
Capillary is thin walled and made of endothelial cells and thickness is not very high
Blood pressure in capillary is 40 mmHg
There is water in the capillary and also red cells (donate only every 2 months) which look
like bi concave disks, plasma made up of 90% H20 (can donate plasma 2-3 x a week), &5
of plasma is made of plasma proteins and 3% is Na, K, Ca
At capillary 40 mmHg, what could happen is fluid can be forced through capillary and
that fluid that is forced out of bloodstream plasma would get smaller and you would
become increase hematocrit and become polycythemia which leads to thrombus emboli.
Capillaries are thin walled so oxygen can diffuse out to cells of our body. Price we pay is
that fluid could be forced out of capillaries which would accumulate outside of capillaries
and our plasma volume would go down
Way to bring fluid back in concept is called starling forces of capillary fluid exchange
No fluid exchange on arteries because they are thick
How fluid forced out of capillaries and how they are brought back in
Arteries lead into small capillaries which lead to venous system (veins bring blood flow
back to heart)
Cells that capillary are in contact with could be brain, lungs, skeletal muscle
Fluid inside cells called ICF , fluid outside called ECF
Between cells and capillary is a space of fluid called interstitial fluid and
Water is located either inside cells which is ICF or fluid outside called ECF
ECF broken down into two areas 1. Interstitial fluid 2. Plasma volume (PV)
Capillaries thin walled = small holes in capillaries because endothelial cells dont fit
perfectly = where water molecules can be forced out when it is put under pressure
Ex. Garden hose water goes through garden hose and water comes out the end. Took ice
pick and put holes in hose what would happen is water goes out of hose and majority
goes out of end. Water goes from high pressure to low pressure.
Water is going to be forced out of capillary, out into interstitial fluid. The plasma volume
would go down because fluid is being forced out into the interstitial fluid. This is related
to edema.
Edema is fluid accumulating in interstitial space
Pulmonary edema = fluid in interstitial space in lungs
Cerebral edema = fluid accumulate in interstitial space in brain
Capillaries are permeable and water is going to be forced out into interstitial space due to
pressure. Plasma has water and 7g or 7% plasma proteins.
7g of plasma protein are too big to get through holes of capillaries. Therefore it is called
capillary membrane is semi-permeable which means it is permeable to something like
water and it is not permeable to plasma proteins. Therefore,
Ex. Lab experiment. Take u-tube which has a semi-permeable membrane. Frog bladders
are semi-permeable. Mimics capillary. Pour water into and it evens out on both sides of
u-tube. Now put a little bit of blue dye on one side and it is tiny. What is going to happen
is that blue dye is going to go from high conc to low conc and diffuse. Diffusion can only
occur if membrane is permeable to a substance. Now if you put proteins on one side the
protein wants to diffuse from high conc to low conc but it cant and therefore water will
move towards the plasma protein and you come back later the u-tube would look like side
with plasma protein (water elevated) and other side with (water lowered). This is called
osmosis
Two things to make osmosis 1. Have to have semi-permeable membrane permeable to
water 2. Substance not permeable
Permeable= substance diffuse. Substance not permeable then water will move towards
the thing that is not permeable. This is called osmosis
One side has 100% water. The amount of water on other side is 7% of PP and 93% is
H2O. Osmosis is diffusion of water going from its high conc to its low conc. Get low
conc. Get 93% Because you took up space by putting non diffusible particle.
Two forces acting on water
No osmosis on arteries because the walls are not semi permeable
Capillaries are semi permeable therefore. Side of capillary closest to arteries is called
arterial side of capillary and another half called venous half of capillary.
Two forces that are acting on water molecules as they enter arterial side of capillary. BP
is trying to force blood out of capillary from high pressure to low pressure. BP out in
interstitial fluid is 0 because ti isnt hooked up to the heart. Pressure in is 40 mmHg. So
water will go from high to low pressure. What else is happening is that you have semi
permeable membrane and you have h2o on both sides (you have plasma and interstitial
water on other). In plasma you have 7g of pp. Osmosis will occur
7 g/ 100 ml of plasma = 7% in plasma. 7g/ 100ml = exert an osmotic pressure of 25
mmHg (difference in pressure between 93% water and 100% water)
Starling forces = BP forcing water out and osmosis brining water back in
BP force more fluid out of capillary than is being brought back in by osmosis.
BP 40 mmHg on arterial side of capillaries
BP 10 mmHg on venous side of capillary
To force blood through a capillary there is frictional loss of energy
10 mmHg is like taking the hose and turning down the flow of water
To have fluid flow through a tube there is less pressure blood pressure gradient
10 mmHg pressure force it out of the capillary and there is still 7g of plasma protein.
Water is going to be attracted.
Ex. Bank account 100 bucks spend 40 find 25 spend 10 more dollars and then friend
gives 25. Still 100 bucks
Fluid flows into capillaries, BP tries to force fluid out, osmosis brings fluid back in.
Hematocrit would be the same in artery 40% as it would be in capillary because of
analogy of bank account being similar to BP forcing fluid out and osmosis bringing fluid
back in. This is called starling forces
At our capillaries the BP is greater than the osmotic forces causing the net amount of
fluid going out to interstitial fluid but on venous side of capillary BP falls to less than
osmotic pressure. Plasma proteins are bringing more fluid in than is forced out and the
net result at the capillary fluid exchange is that the fluid is lost on arterial side but exactly
same amount of fluid is gained on venous side of the capillary.
5 potential ways edema could be caused
1. high/increase arterial blood pressure so more water forced out then could be brought
back in. Excess fluid in interstitial fluid which is called edema)
Ex. Exposed to low oxygen levels
= high altitude pulmonary edema 1. Excess fluid in interstitial 2. Lungs get stiff and
difficult time breathing exchanging oxygen is difficult
or high altitude cerebral edema 1. Fluid in interstitial space of brain 2. Going to push
brainstem down through cranium. Hole above brainstem called foramen magnum. Brain
swells and it pushes brainstem down through foramen magnum. Die from respiratory fail
2. low plasma protein conc. (dont eat protein)
3 grams of pressure = half of pressure that 7g would which is 12.5 mmHg. Less fluid
being brought in= edema.
Ex. Kwashiorkor = protein malnutrition= dont eat enough amount of protein you can
develop protein so you lose plasma protein.
Ex. Ascites = abdominal edema = abs enlarge abnormally
3. Increase in capillary permeability. .bigger holes in in capillary membrane then proteins
can get out and membrane no longer semi-permeable. So you cant have osmosis
bringing fluid back in
4. Venous obstruction = Increase pressure on venous side
Caused by Venous obstruction. Anything obstruct venous return which is blood flowing
back to our heart which causes the blood to go back to capillary and increase pressure and
force more fluid out.
Ex. Inferior vena cava brings blood back to RA. 7 lb. fetus the baby now starts to
compress onto inferior vena cava and you get decreased venous return and the blood is
pooling on lower extremities. Or could be tumor and block the vein.
5. Lymphatic ducts failed called lymph edema = take a long time to occur because its
only going to be excess fluid not brought back.
Fluid forced out by BP 90% of fluid is brought back in by osmosis. 3 L a day not brought
back in and fluid would start to accumulate = cause edema. We had to have a system to
get the little bit of fluid back in. There are small capillary ducts located between cells in
interstitial space called lymphatic ducts.
Lymphatic ducts get bigger and there are two major vessels that come up through chest
wall called left and right lymphatic ducts and they empty back into the heart. The extra
3L per day is brought back to the heart through lymphatic ducts.
Ex. Women have breast lesion they try to surgically remove it and they remove lymph
ducts and they have edema
Ex. Radiation on lymphatic duct and damaging it = edema formation
Ex. Elephantiasis = parasitic worm called thalarasis = hide lymphatic duct and block it
Ohms law = BP = cardiac output x TPR
Go to high altitude low levels of o2 causes blood vessels in brain and lungs to
vasoconstriction = increase resistance. So BP goes up and more fluid is brought out than
could be brought back in by osmosis because you only have 7g of pp.
15 mmHg going out and 15 Hg going in = no edema
Ex. W.C. fields = alcoholic = edema = plasma proteins are made in liver= cirrhosis to
liver or liver cancer, or hepatitis = decrease pp
Decrease pp = cause edema formation
1. Dont eat protein pp goes down
2. Liver disease so you cant make consumed protein to pp
3. Ate protein > made plasma protein > and then you urinate the protein out
Ex. Of capillary permeability. Throw basketball at you, smash finger, has edema
formation. Tissue damage in cells. The cells will cause increase in a substance called
histamine which bind to capillary membrane and it increases capillary permeability.
Increase in capillary permeability

Prescribe for edema due to damage of cells Ex. Basketball. Give anti- histamine which is
histamine antagonist. This gets rid of some of the edema.

Why would we evolve to create edema from histamine? Have cell damage you need to
get white blood cells out of blood stream out to where damage is from bacteria. The
white blood cells are in plasma. Increase permeability so you can get white blood cells
out to destroy the bacteria. Price we pay capillary is permeable for white blood cells to go
out is that some of plasma proteins escape and we get edema formation. Diapedesis is
movement of white blood cells from blood stream to where damage is.

Ex. Burns = capillary permeability. Heat will damage endothelial membrane and no
longer make it semi-permeable.
Anaphylactic shock = low blood pressure = ohms law = allergic reaction causing BP to
drop really low = bad things like syncope = allergic to peanuts or bee venom instead of
histamine produced locally it is produced all over the place = losing fluid. Symptoms 1.
Edema 2. Hands swollen. Plasma volume is dropping rapidly because losing fluid out to
interstitial space and BP goes really low.
Carry epi-pen
BP = cardiac output x TPR
Cardiac output = HR x SV
BP falling (what will kill them) from allergy to bee venom and you are swelling from
edema. BP is dropping really low and you want it to go back up. Epinephrine is a beta 1
adrenergic receptor agonist. Beta 1 is in the heart. Epinephrine has + Chronotropic
response and + inotropic response. Increase cardiac output by increasing HR to bring BP
up.
Epipen dont not get rid of histamine and edema