Cardiovascular Physiology

***Make sure you know the equations from the cardiovascular lectures. Important equations to know
are list right below. These equations will help you answer questions on the exam! You will not need a
calculator for the exams.

Eg. CO = HR x SV. You may be asked what happens to CO if you increase HR? If HR increases (and SV
remains the same), CO will increase.

Important equations to know:

F= ∆P/R --> blood flow = change in pressure over resistance

 R = 8 L η/ π r4  The relationship between viscosity, vessel radius, and vessel length is
defined by Poiseuille’s equation:

EF (ejection fraction) = SV/EDV

SV = EDV - ESV
CO = HR x SV
MAP = CO x TPR
PP = SP – DP (pulse pressure = systolic pressure – diastolic pressure)

Lecture 1 recording 1: Hemodynamics

 Why Do We Have a Cardiovascular System?:

 To provide oxygen and nutrients and remove wastes like carbon dioxide from cells
 Rapid system
 Provides a steep concentration gradient within the vicinity of every cell…very important
in multicellular organisms as diffusion is too slow a process
 Hemodynamics:  this is the study of blood flow
 The study of blood flow and relates Ohm’s law to fluid flow, looking at the relationship
between blood flow, blood pressure, and resistance to blood flow
 F = ∆P/R
o F = flow
o ∆P = pressure difference between two fixed points (P1 and P2)
o R = resistance to flow
o Blood flow is related to the pressure difference between the two fixed points
and inversely proportional to the resistance
o Resistance is defined as the friction that impedes flow, or how difficult it is for
blood to move between 2 points at any given pressure
 Blood always flows from a region of higher pressure to a region of lower pressure
o The pressure difference between 2 points provides the driving force for blood
flow
o To have flow, the pressure difference must overcome resistance to flow (∆P > R)
 Our bodies can change factors that affect blood flow: by changing resistance blood flow
can be altered
 o The major mechanism for changing blood flow is to alter the resistance of blood
vessels, in particular arterioles
 The figures in this slide show: it is not the absolute pressures in the cardiovascular
system that determine flow, but the pressure difference between two points
o The pressures in the two tubes are very different, but the pressure differences
are the same
 Hydrostatic pressure → blood hydrostatic pressure is the pressure that the volume of
blood within our circulatory system exerts on the walls of the blood vessels that contain
it  think hydraulic systems (and its pressure on the pipes)
o Often called ‘pressure’ and it varies throughout the cardiovascular system
o This is the pressure that the blood exerts on the veins and what not
 Hemodynamics:
 It is not the absolute pressure at any point in the cardiovascular system that determines
flow rate but the difference in pressure between two relevant points  and the only
way we can calculate the abs pressure is to calculate the difference in pressure between
the two points  because there needs to be a difference in pressure in order to create
flow
o There must be a pressure difference to create flow; if there is no pressure
difference, the flow will be 0 mL/min
 The pressure difference must be greater than the sum of all resistances
to create flow
 What Determines the Resistance to Blood Flow?
 Resistance can be calculated numerically from the formula F=delta P/R, but it cannot be
measured as it is determined by several factors  so we can calculate the pressure but
we cannot measure it  this is because the resistance of blood is controlled by many
factors
o Factors that determine resistance to blood flow: viscosity of the blood, length of
the blood vessel, and diameter of the blood vessel
o
 Viscosity → the friction between molecules of a flowing fluid
o Blood contains many molecules and the formed elements in blood (red blood
cells, white blood cells, and platelets). Interaction between different
components in blood produces friction which contributes to resistance to blood
flow.
 Hematocrit, or the number of red blood cells in the blood, affects
viscosity
 Blood vessel length and diameter affect the amount of vessel wall that the blood is in
contact with
o Friction develops between the moving blood and the stationary vessel walls
o The greater the contact between the vessel walls and the blood, the greater the
friction produced and the greater the resistance to flow
o A vessel with a longer length will produce more friction than a shorter vessel
o Vessel diameter can change by constriction or dilation of the vessel
  Constriction of the vessel will reduce the diameter of the vessel while
dilation of the vessel will increase the vessel diameter
 Blood flows through vessels in concentric (circle) layers
 In smaller diameter vessels, more blood is in contact with the vessel
wall, as there are less concentric layers of blood flowing through the
smaller vessel; this generates more friction as the blood moves through
the vessel
 In larger diameter vessels, some blood will be in contact with the vessel
walls, but many of the layers will move through the vessel without
contacting the vessel wall; friction in the larger diameter vessel will be
less than that produced in the smaller diameter vessel
 The relationship between viscosity, vessel radius, and vessel length is defined by
Poiseuille’s equation:
o Resistance (R) is equal to 8 times eta times L divided by pi times r raised to the
fourth power
 R = 8 L η/ π r4
 R = the resistance to blood flow, η =the blood viscosity, L = the vessel
length and r= the inside radius of the vessel
 Resistance to flow is directly proportional to the length of the vessel and
the blood viscosity and inversely proportional to the radius of the vessel
 The factor with the greatest effect on resistance is the diameter or the
radius of the vessel as r is raised to the 4th power
 Very small changes in vessel diameter therefore lead to large changes in
resistance; our bodies are able to alter vessel diameter by constricting
and relaxing vascular smooth muscle in the wall of the blood vessels and
change the resistance to blood flow in our bodies

Lecture 1 recording 2: Cardiovascular System Functions and Components

 Functions of the Cardiovascular System:

 To deliver oxygen and nutrients and remove waste products of metabolism
 Fast chemical signaling to cells by circulating hormones or neurotransmitters
 Thermoregulation
 Mediation of inflammatory and host defense responses against invading
microorganisms
 Components of the Cardiovascular System:
 Heart, blood vessels and blood
 Components of the Cardiovascular System:
 Vessels: arteries, arterioles, capillaries, venules and veins
 Arterioles → small branching vessels with high resistance
 Capillaries → transport of blood between small arteries and veins; exchange of
materials between blood and cells in the body (think capillaries in alveoili)
 All arteries carry blood away from the heart
 All veins carry blood back to the heart
  It’s a Closed circulatory system cuz it allows for greater pressures to be generated when
the heart contracts
 Anatomy of the Heart:

 Heart has 4 chambers: 2 atria and 2 ventricles

 Atria:
o Thin-walled chambers
o Low pressure chambers
o Receive blood returning back to the heart (think of the atria as chill)
 Ventricles:
o Thick-walled chambers (thicker than atria)
o Responsible for the forward propulsion of blood when they contract

 Apex of heart is the lowest superficial surface of the heart

 Base of heart is the upper surface of the heart where the blood vessels attach
 Think of these as the oppsite: the apex is the lowest area dn the heart is the toppest
part!
 Septa:  these are the muscular parts of the heart and they have walls that separate the left
and right side of the body
 Left and right sides of the heart are divided by septa, or muscular walls
o Interatrial septum → separates left and right atria
o Interventricular septum → separates left and right ventricles (lit in the name)
o Allows heart to function as a dual pump
 Left side pumps highly oxygenated blood to systemic circuit (body)
 Right side pumps poorly oxygenated blood to pulmonary circuit (lungs)
(think that the process starts from the left just like when we write 
and it pumps out blood to the body and then goes throughout the
whole body and grabs the poorly oxygenated blood and sends it back to
the right side  the lungs)

Lecture 1 recording 3: Blood Flow

 Blood Flow:
  The circulatory system can be divided into two serial circuits: the pulmonary circulation
and the systemic circulation
o Pulmonary circuit → carries blood to and from the gas exchange surfaces of the
lungs; blood entering the lungs is poorly oxygenated; once blood enters the
lungs, oxygen diffuses from the lung tissues to the blood; blood leaving the
lungs is highly oxygenated
o Systemic circuit → transports blood to and from the rest of the body; blood
entering the body tissues is highly oxygenated; oxygen diffuses from the blood
to the interstitial fluid surrounding the tissue cells; blood leaving the tissues is
poorly oxygenated
 Serial means in sequence
 Path of Blood Flow:
 Systemic circuit → moves blood to and from the tissues in the body
 The left side of the heart receives blood from the pulmonary circulation and pumps it to
the systemic circulation
 The right side of the heart receives blood from the systemic circulation and pumps it to
the pulmonary circulation

Pulmonary
valve
Poorly Highly
Right oxygenated Pulmonary oxygenated Pulmonary
Lungs
ventricle blood trunk/artery blood vein

Left
Right AV Pulmonary Circulation atrium Left AV
valve valve
Systemic Circulation Left
ventricle
Highly
Right Vena Body oxygenated Aortic
Aorta blood
atrium cava cells/tissues valve

Here are the steps:

1. Lets start at the pulmonary valve, and this is the valve

that poorly oxygenated blood enters thru and it goes into the
 pulmonary trunk and this leads way to the lungs

2. In the lungs, gas exchange of the blood and oxygen and co2 occurs and
now we have oxygenated blood
3. Then the oxygenated blood goes thru the pulmonary veins:

4. And into the LEFT AV VALVE, (which is the valve between the top and

bottom of the left section and it specifically

enters the left atrium and then into the left ventricle

5. And then it goes thru the Aortic Valve

6. And then this highly oxygenated blood goes thru AORTA and into the
rest of the body
7. And then from the right atrium it goes to the right ventricle
8. And then back to the pulmonary trunk and to the left atrium
 9. And then the blood is making its way back into the lungs cuz they’re de-
oxygenated and then it goes thru the vena cava

10. And the first site of the blood is that it always enters into the right
atrium cuz its job is to send it to the left side of the body so the blood
can be oxygenated
11. And note that the atrium is at the top so blood will always enter there
first

 Blood moves from the pulmonary circuit to the heart and then to the systemic circuit
before returning back to the heart: it moves in series
 Arteries → carry blood away from heart; most carry highly oxygenated blood except
pulmonary trunk and pulmonary arteries which carry poorly oxygenated blood to lungs
 Veins → carry blood to the heart; most carry poorly oxygenated blood back to the heart
except pulmonary venules and pulmonary veins which carry highly oxygenated blood
back to the left atrium from the lungs
 Series vs Parallel Flow:
 Series blood flow found in cardiovascular system  which is blood to the lungs!!!
o Pulmonary and systemic circuits  which are pulmonary and systemic cirucuits
 Parallel flow to most organs
o This means that each organ is supplied by a different artery and therefore its
blood flow can be independently regulated so they’re all independent but
the liver is not independent.
 An exception is the liver – it receives blood flow in parallel and in series
(will talk about in GIT section)
 Distribution of Blood Flow at Rest and During Exercise
 Cardiovascular system can not only increase the rate of blood flow, but it can also alter
the distribution of our blood flow, depending on the needs of your body, increasing
blood flow to areas that need more blood and decreasing blood flow to areas that do
not need as much blood at that time

Lecture 1 recording 4: The Pericardium

 Functions of the Pericardium:

  Pericardium → a fibrous sac surrounding the heart and the roots of the great blood
vessels leading into and out of the heart
o Functions:
 Stabilizes the heart in the thoracic cavity (which is the area where the
heart and lungs are etc.)
 Provides protection to the heart by physically surrounding it
 Reduces friction as the heart beats by secreting the pericardial fluid
 Limits overfilling of the heart chambers
 The Pericardial Structure:
 3 layered sac: fibrous pericardium, parietal pericardium and visceral pericardium
o Fibrous pericardium → outer layer of the pericardial sac; provides protection for
the heart and stabilizes the heart in the thoracic cavity by attaching to
structures in the chest; holds the heart in place; limited distensibility (inability of
structure to streatch) which prevents the sudden, rapid overfilling of the heart
o Parietal pericardium → part of the serous pericardium; lies underneath the
fibrous pericardium and is attached to it
o Visceral pericardium → part of the serous pericardium; innermost layer of the
pericardial sac, and is also called the epicardium when it comes into contact
with the heart muscle;
o Pericardial cavity → separates the parietal pericardium from the visceral
pericardium; both parietal and visceral pericardium secrete fluid which
decreases friction between pericardial membranes as heart beats
o Serous layer → a layer composed of cells that secrete a fluid
 The Pericardial Structure:

(Another view of the pericardium)

 Cardiac Tamponade:
 Pericarditis → an inflammation of the pericardium caused by viruses, bacteria, fungi,
trauma or malignancy; leads to fluid accumulation in the pericardial cavity
 Cardiac tamponade → compression of heart chambers due to excessive accumulation of
pericardial fluid; heart's movement is limited and heart chambers cannot fill with
adequate amount of blood (ie. a decrease in ventricular filling)

Lecture 1 recording 5: The Heart Wall and Cardiac Muscle Cells

 Ventricular Walls:
 The muscular wall of the left ventricle is thicker than the right ventricle
o The increased thickness allows the left ventricle to generate higher pressures as
it contracts compared to the right ventricle, allowing it to pump blood around
the entire systemic circulatory system
o Right ventricle only needs to pump blood to the lungs and does not need to
develop pressures as great as those developed by the left ventricle
 The Heart Wall  which is the muscular stuff that the heart is made out of
 Heart wall has 3 layers: epicardium, myocardium and endocardium
o Epicardium → also called visceral pericardium
  Layer immediately outside the heart muscle and covers the outer
surface of the heart; connective tissue attaches it to the myocardium;
functions as a protective layer for the heart
o Myocardium → the muscular wall of the heart and lies underneath the
epicardium
 Contains muscle cells or myocytes which contract and relax as the heart
beats
 Contains nerves and blood vessels
o Endocardium → innermost layer of the heart wall
 Lines heart cavities and the heart valves; a thin layer of endothelium
which is continuous with the endothelium of the attached blood vessels
 The entire circulatory system (heart chambers, heart valves and blood vessels) is lined
by endothelium which forms an interface between the blood and the heart chamber or
blood vessel wall, providing a smooth surface for blood to flow over
 3 layers (endocardium, myocardium, and epicardium) are found in both atria and both
ventricles
o The layers do show variation between the different chambers of the heart
 The ventricles have a thicker myocardium than the atria; the left
ventricle has a thicker myocardium than the right ventricle
 Cardiac Muscle Cells:
 Myocytes = cardiac muscle cells
o Branched or Y shaped cells
o Joined longitudinally or end to end to adjacent myocytes
 Allows for greater connectivity in the heart,
o Striated or stripped appearance (Actin and myosin)
o A single centrally located nucleus
o Rich in mitochondria (Provide ATP for the muscle cells to contract)
o Adjacent cells are held together by intercalated disk
 The membranes of 2 different myocytes are closely opposed and very
intertwined at their region of attachment
 2 types of specialized intercellular junctions at intercalated
disks: desmosomes and gap junctions
 Desmosomes:  CAN WITHSTAND stretching and twisting and actually couples one cell to
another
 Adhering junctions that hold cells together in tissues subject to considerable mechanical
stress or stretching.
 Mechanically couple one heart cell to another
 Proteins involved: cadherins, plaques, intermediate filaments
o Cadherins from one cell attach to cadherins from another cell
 Gap Junctions:
 Communicating junctions
 Electrically couple heart cells, allowing ions to move between cells
o Important for spread of action potential
 Proteins involved: connexons
  Arrangement of the Heart Muscles:
 Muscle fibers are arranged spirally around the heart chambers
 Important for emptying blood into arteries when ventricles contract

Lecture 2 recording 6: The Heart Valves

 The Four Valves of the Heart:

 There are 4 heart valves:
o Atrioventricular (AV) valves (up and down) → found between the atria and the
ventricles on both the left and right sides of the heart.
 AV valve located between the left atrium and left ventricle is the
bicuspid (think left side = liberals = bi) or mitral valve
 AV valve located between the right atrium and the right ventricle is the
tricuspid valve.

o Semilunar (arterial) valves

for the aortic valve and the pulmonary valve → found between the ventricles
and the arteries into which the ventricles pump their blood
 Valve between the left ventricle and the aorta is the aortic valve
 Valve between the right ventricle and the pulmonary trunk is the
pulmonary valve
 Valves:
o Made of fibrous tissue (collagen) covered by endothelium (which is the thin
layer of cells that covers blood vessles and what not
o The valve flaps are also called leaflets or cusps
 Valve rings:
o Made of cartilage
o These are what the valves attach to
 The Valves and the Path of Blood Flow:

(This slide shows the position of the heart valves in the circulatory circuit)

 How do the Valves Function?:

 Function of the heart valves?
o Ensure unidirectional flow of blood through the heart
 Important so that blood flowing out of heart does not mix with new
blood coming into the heart
 The valves open and close passively due to differences in pressure or pressure gradients
o Energy is not expended to open or close a valve
 o Valves do not require muscles to open or close them
o A forward pressure gradient opens a one way valve; a backwards pressure
gradient closes a one-way valve
o Valves normally do not open in the opposite direction
 Atrioventricular (AV) Valves:
 Found between the atrium and the ventricle
 Prevent the backflow of blood into the atrium when the ventricle contracts
 When the pressure in the atrium exceeds the pressure in the ventricle, the
atrioventricular valve will open, allowing blood to flow from the atrium into the
ventricle so that the ventricle will fill with blood
 When the ventricle contracts and achieves a pressure greater than the pressure in the
atrium, the valve will shut, preventing the backflow of blood from the ventricle into the
atrium
 Tricuspid valve → Av valve located between the right atrium and the right ventricle;
consists of three cusps or leaflets attached at the circumference to the valve rings
 Bicuspid or mitral valve → AV valve located between the left atrium and the left
ventricle; consists of two cusps or leaflets attached at the circumference to the valve
rings
 Each AV valve is part of an AV valve apparatus, which consists of the cusps or leaflets of
the valve, chordae tendineae and papillary muscles
 Anatomy of the AV Valve Apparatus:
 Atrioventricular valve apparatus:
o The edges of the AV valve leaflets are attached to tough, thin fibrous cords of
tendinous-type tissue called chordae tendineae
o The chordae tendineae extend from the edges of the leaflets and attach to
papillary muscles
o Papillary muscles → cone shaped muscles that protrude from the inner surface
of the ventricular walls
 Papillary muscles do contract, and when they contract they pull on the
chordae tendineae to become tight (taut)
 This holds the valve in its closed position

 Function of the AV Valve Apparatus:

 Heart valves open and close passively due to pressure gradients; there are no muscles
involved in opening and closing the valve
 When the left ventricle is relaxed:
o AV or bicuspid valve is open and the semilunar or aortic valve is closed
o Papillary muscles are also relaxed and chordae tendineae are slack or have low
tension
o When the bicuspid valve is open, blood can flow from the left atrium into the
left ventricle; the ventricle fills with blood as the aortic valve is closed; blood
enters the ventricle but cannot leave
 o Note that whenever blood form the body enters the heart, it first enters the
atrium and then the ventricle and it goes from the atrium to the ventricle and
etc in order to ensure proper circulation of blood throughout the body
 When enough blood enters the left ventricle and it begins to contract,
o The ventricle will squeeze its volume of blood as it contracts, increasing
pressure inside the ventricle
o As the pressure in the ventricle rises above the pressure in the atrium, blood is
pushed back towards the bicuspid valve; but the increased pressure causes the
bicuspid valve to close as there is a greater pressure in front of this valve (just
o Closing of the bicuspid valve prevents the backflow of blood into the atrium as
the ventricle is continuing to contract
o The papillary muscles also contract when the ventricle contracts
 This pulls the chordae tendineae downward or taut; chordae tendineae
have tension
 Pulling of the chordae tendineae by the papillary muscles keeps the AV
valve in a closed position in the face of a strong backward pressure
gradient from the ventricle contracting  and that’s the only reason we
have the muscle and the chordae tendineae Is IT KEEPS the av valve
closed when the valve is closed during a strong backward pressure
gradient from the ventricle contracting
 The AV valve apparatus keeps the AV valves from everting, or opening
backwards, into the atrium
 If the AV valves did evert, blood would flow the wrong way from
the ventricle to the atrium
 Important: contraction of the papillary muscles does not open or close the valves; the
valves open and close passively due to pressure differences across the valves  the
only thing opening the valves are the pressure differences the papillary muscles
 As the pressure in the ventricle continues to increase as the ventricle continues to
contract, the pressure in the ventricle will eventually exceed the pressure in the aorta,
opening the aortic valve, allowing blood to flow out of the ventricle; this is a forward
pressure gradient
 Arterial (Semilunar) Valves:  these ones don’t have chordae tendineae or papillary muscles like
the atrioventricular valves do
 Semilunar or arterial valves:
o Found between the ventricle and the artery into which the ventricle ejects its
blood
o 3 leaflets or cusps (left and right semilunar valves)
 Pulmonary valve → valve found between the right ventricle and the
pulmonary trunk
 Aortic valve → valve found between the left ventricle and the aorta
o Do not have chordae tendineae or papillary muscles (no valve apparatus
associated with these valves)
  The pressure pushing back against the valve from the artery is not high
enough to force the valve to evert or open backwards into the ventricle,
as the artery does not contract
o Open when the pressure in the ventricle is greater than that in the artery into
which the ventricle ejects its blood
o When the ventricle begins to relax, the pressure in the ventricle will decrease;
when the pressure in the ventricle falls below the pressure in the artery, the
semilunar valve will close, preventing the backflow of blood from the artery into
the ventricle; same thing except this time w the artery
 Semilunar valves open/close due to pressure differences across the valve; there are no
muscles or energy expended to open/close these valves
 Pulmonary Valve:

(This is an image of a valve)

Lecture 2 recording 7: The Heart’s Skeleton and Coronary Circulation

 Cardiac Skeleton:  includes heart valve rings and connective tissue between the hear valves
 The fibrous skeleton of the heart:
o Made of dense connective tissue
o Includes the heart valve rings and the dense connective tissue between the
heart valves
o Functions:
 Physically separates the atria from the ventricles
 Electrically inactive and blocks the direct spread of electrical impulses
from the atria to the ventricles
 Provides support for the heart, providing a point of attachment for the
valves leaflets and cardiac muscle
 Coronary Circulation:
 The heart, like other organs, receives its blood supply through arteries that branch from
the aorta
o Coronary circulation is part of the systemic circulatory system and supplies
blood to and provides drainage from the tissues of the heart
 Coronary arteries → arteries supplying the heart
 Aortic sinus is a dilation or out-pocketing of the ascending aorta;
site where the left and right coronary arteries
 Cardiac veins → collect poorly oxygenated blood and empty into the
coronary sinus, which returns blood to the right atrium
 Coronary Circulation:
 Coronary sinus → a collection of veins joined together to form a large vessel that
collects blood from the myocardium (muscular middle layer of heart) of the heart and
empties into the right atrium, returning the poorly oxygenated blood back to the right
side of the heart
 The blood is coming from the coronary veins, which
collect blood from the myocardium (muscular middle
 layer of the heart) and converge into the coronary
sinus. The coronary sinus then empties into the right
atrium, returning poorly oxygenated blood back to the
heart.  and this transports
 Systole → represents the time during which the left and right ventricles contract and
eject blood into their respective artery
 Diastole → represents the period of time when the ventricles are not contracting;
relaxed
 Myocardial blood flow is not steady:
o Blood flow almost ceases while the heart is contracted (systole) and peaks while
the heart is relaxed (diastole)
 Coronary Artery Disease:
 Coronary artery disease:
o Caused by atherosclerosis (buildup of fat) of the coronary arteries supplying
blood to the heart tissues
o Atherosclerosis is a condition in which the arteries become hardened and
narrowed because of an excessive accumulation of plaque in the vessel wall
 Atherosclerotic plaque → made of fat, cholesterol, calcium and other
substances in the blood
 When plaque builds up, the diameter of that artery is narrowed,
providing resistance to blood flow, reducing flow through the arteries
supplying the heart tissue
 Coronary Artery Disease:
 Angina → chest pain; when a plaque is present in a coronary artery, restricted blood
flow to the heart muscle may result in or chest pain.
 Myocardial infarction → heart attack; atherosclerotic plaques can grow so large that
they completely block arterial blood flow, causing a heart attack; heart muscle dies due
to loss of blood supply

Lecture 2 recording 8: Cardiac Muscle and Membrane Potential

 The Cardiac Syncytium:

 Cardiac muscle cells = myocytes
o Joined by intercalated discs which contain gap junctions and desmosomes
 Mechanically, chemically, and electrically connect myocytes to one
another
 The entire heart tissue resembles a single, enormous muscle cell
and the cardiac muscle is called a syncytium (a set of cells that
act together)
 Gap junctions allow excitation, or action potentials, to spread quickly from one myocyte
to another by cell-to-cell contact
o Cardiac muscle cells are so tightly connected that when one of the myocytes
becomes excited, the action potential spreads to all of them through gap
junctions
  The heart is a functional syncytium: multinucleated cell sheet
 Cardiac muscle has 2 syncytia: the left and right atria act as one
functional syncytia and the left and right ventricles also act as
another functional syncytia
 This gives the heart an all or none property- either all of the
myocytes respond and are excited or none of the myocytes
respond
 Cardiac Muscle:
 The heart contracts in series: first the left and right atria contract together and then the
left and right ventricles contract together
 Action potentials lead to contraction of heart muscle cells and ejection of blood
 Autorhythmicity (automaticity) → the heart contracts or beats rhythmically as a result
of action potentials that it generates itself
o Action potentials in the heart are generated without nervous or hormonal
stimulation
o The rhythmicity of the heart is myogenic in origin, which means muscular in
origin
 2 types of specialized cardiac muscle cells or myocytes: contractile cells and conducting
cells
o Contractile cells:
 Perform the mechanical work of pumping or contracting to propel blood
forward; generate pressure to move blood
 ~ 99 % of myocytes are contractile cells
 Do not normally initiate their own action potentials, but contract when
stimulated by an action potential passed to them through gap junctions
from an adjacent contractile cell that has been stimulated by an action
potential or an adjacent conducting cell.
o Conducting cells:  THESE CELLS CONDUCT AND INTIATE ELECTRICAL IMPULSES
IN THE HEART
 Autorhythmic cells which initiate and conduct action potentials which
are responsible for contraction of the contractile cells
 Conducting cells are myocytes (muscle cells) which initiate and conduct
action potentials without nervous or hormonal stimuli
 Have very few myofibrils (protein filaments needed for contraction) and
do not contribute to the heart’s contraction and the movement of
blood.
 ~ 1 % of myocytes are conducting cells
 Part of the conducting system of the heart
 Are in electrical contact with each other and the cardiac
contractile cells through the gap junctions
 =

(This is just a review of the nerve/muscle action potential)

Lecture 2 recording 9: The Heart’s Conducting System

 Components of the Conducting System:
 The spread of action potentials through the myocardium leads to the contraction of the
heart muscle cells
 The heart contracts in series: first both atria depolarize and contract as a unit before
both ventricles depolarize and contract as a unit
 The conducting system contains myocytes, or cardiac muscle cells, that are capable of
initiating and propagating action potentials
o Autorhythmic myocytes
o The conducting myocytes are found in: sinoatrial node (SAN), internodal
pathways, atrioventricular node (AVN), the bundle of His (AV bundle), the left
and right bundle branches, Purkinje fibers
o SAN located in the wall of the right atrium; AVN located at the base of the right
atrium; internodal pathways extend from the SAN to the AVN and also cross the
interatrial septum to the left atrium; bundle of His passes through the cardiac
skeleton; left and right bundle branches travel along the interventricular
septum; left and right bundle branches make contact with Purkinje fibers, which
extend into the myocardium of the ventricles
 Cardiac Skeleton:
 Non-conducting or it will not allow action potentials to travel across it
 Physically separates the atria from the ventricles: stimuli cannot cross from the atria to
the ventricles through the cardiac skeleton
o The only electrical connection between the atria and ventricles in a normal
heart is the AVN and the Bundle of His
 Sinoatrial (SA) Node:
 All the cells in the conducting system are capable of initiating action potentials
o The rate at which each region action potentials differs
 Conducting myocytes in the SAN generate action potentials at the fastest rate; 60 to
100 action potentials per minute
 This stimulus is then passed on to the other regions of the conducting system through
gap junctions, generating action potentials in these other regions before they have time
to initiate their own action potentials
 SAN generates action potentials that drive the rest the conducting system.
o Cardiac pacemaker → initiates action potentials that set the heart rate
 SAN generates action potentials → internodal pathways → contractile cells of both the
left and the right atria → left and right atria contract at same time → stimulus is also
passed by the internodal pathways to AVN → the wave of depolarization must pass
through the AVN and the Bundle of His to excite the ventricles due to presence of
cardiac skeleton
 Cells of conducting system are muscle cells
 Atrioventricular (AV) Node:
 Stimulus passes to the AVN through the internodal pathways from the SAN
 AV nodal delay: the propagation of action potentials through the AVN is relatively slow:
takes ~ 100 milliseconds for the stimulus to pass through the AVN to the Bundle of His
 o This delay ensures that the atria depolarize and contract before the ventricles
depolarize and contract
 The ventricular myocardium must be relaxed to fill with blood from the
atria
 Ensures ventricles are relaxed and have time to fill with blood before
they contract
 Excitation of the Ventricles:
 AVN and Bundle of His are the only electrical connection between the atria and
ventricles in a normal heart
 Left and right bundle branches travel along intraventricular septum and make contact
with Purkinje fibers
 Purkinje fibers
o Large number, diffuse distribution (ie. all over the ventricles), fast conduction
velocity
o Stimulus depolarized left and right ventricular myocytes and causes contraction
nearly simultaneously due to Purkinje fibers
 Sequence of Excitation:
 This slide shows the spread of excitation from the sinoatrial node to the atrioventricular
node and the left and right atria
 Cells are connected by gap junctions, which offer a low resistance pathway for excitation
to spread from cell to cell
o Ions move from cell to cell through gap junctions
 Summary: Conducting System of the Heart:
 This figure demonstrates how the wave of depolarization spreads across the heart
 Myocytes in the SAN initiate the action potential; action potential passes through the
conducting myocytes in the internodal pathways to the contractile myocytes of both the
left and right atria causing depolarization and contraction of the atrial myocardial cells;
action potential also passes through the conducting myocytes in the internodal
pathways to the AVN; it takes 100 msec for the stimulus to pass through the AVN;
stimulus passes to the conducting cells of the Bundle of His which divides into the left
and right bundle branches; wave of depolarization spreads down the interventricular
septum; the bundle branches separate at the apex of the heart and enter the ventricles
and make contact with the Purkinje fibers; Purkinje fibers spread the depolarizing
stimulus to the ventricles
 The chambers of the heart contract in series: first both atria depolarize and contract,
and then both ventricles depolarize and contract, leading to the movement of blood
through the heart
 Wolff-Parkinson-White Syndrome:
 There is an extra connection in the heart called an accessory pathway
o An accessory pathway is an abnormal piece of muscle that connects directly
between the atria and the ventricles
 Allows electrical signals to bypass the AVN and move from the
atria to the ventricles faster than usual
  Electrical impulses may also be transmitted abnormally from the
ventricles back to the atria
 Disrupts the coordinated movement of electrical signals through
the heart, leading to an abnormally fast heartbeat, called
tachycardia, and other arrhythmias

Lecture 3 recording 10: Action Potentials in the Heart

*Know the action potentials, the phases of the action potentials and the ion channels/ions involved
for the slow/fast action potentials in the heart

 Two Types of Action Potentials:

 Fast and slow action potentials
o Fast: found in contractile myocytes in the atrial myocardium, ventricular
myocardium, bundle of His, Bundle branches (left and right) and Purkinje fibers
o Slow: found in conducting myocytes in the sinoatrial node and atrioventricular
node
 The terms fast and slow describe how quickly the membrane potential changes during
the depolarization phase of the action potential
o Fast action potential:
 Rapid rate of depolarization in which the membrane potential rises very
quickly from the threshold potential to the new transiently positive
potential
o Slow action potential:
 Slower rate of depolarization, in which the membrane potential takes
more time to reach the new potential
o Why do action potentials have different rates of depolarization? Depends on the
ions and ion channels involved in the depolarization phase
 The Cardiac Action Potential:
 Phases of the cardiac action potential are associated with changes in permeability of the
cell membrane mainly to Na+, K+, Ca2+ ions
 Opening and closing of ion channels alters permeability
 [K+]IN > [K+]OUT
 [Ca2+]OUT > [Ca2+]IN
 [Na+]OUT > [Na+]IN
 SA Node Action Potential:
 Phases of the slow action potential: pacemaker potential, depolarization and
repolarization

 SAN cells:
o Pacemaker potential → it is not a steady or true resting potential but a slow
depolarization to threshold; gradual depolarization of the membrane potential
to threshold
o When threshold is reached, the depolarization phase of the action potential
occurs
  Pacemaker potential allows the SAN cells (these are muscle cells) to generate regular
spontaneous action potentials without any external influence from nerves or hormones
 Stages of slow action potential and ion channels involved:
o Pacemaker potential → 3 ionic conductances involved: 1) progressive reduction
in K+ permeability (K+ channels that opened during the repolarization phase of
the previous action potential gradually close due to the return of the membrane
to negative potential), 2) F-type channels (depolarizing Na+ current; Na+ moves
into cell), 3) T-type channels (Ca2+ channel; T= transient; opens only transiently
(briefly), contributes an inward Ca2+ current, provides a final depolarization to
bring the membrane to threshold)
o Depolarizing phase → L-type channels (Ca2+ channel; L= long-lasting; channels
open more slowly and remain open for a prolonged or long period)
 The Ca2+ currents depolarize the membrane more slowly than voltage-
gated Na+ channels so the rising phase of the action potential occurs
much more slowly than if Na+ was responsible for the rising phase;
action potentials are therefore called ‘slow’ action potentials
(remember voltage-gated Na+ channels are responsible for the
depolarization phase of the nerve/muscle action potential)
 The long opening of the L-type channels prolongs the nodal action
potential- it is approximately 150 milliseconds in duration
(nerve/muscle action potentials ~ 2 milliseconds)
o Repolarization phase → opening of voltage-gated K+ channels; K+ leaves the cell
 SAN cells undergo repeated cycles of drifting pacemaker potential and firing of the
action potential, allowing these cells to generate action potentials in the absence of any
hormonal or nervous stimuli
o Gradual depolarization of the pacemaker potential allows SAN to generate
action potentials
 The slow-type action potential is also seen in the AVN
 Summary of Slow Action Potential:
 Slow type action potential: Ca2+ currents are responsible for the depolarization phase of
the action potential and not Na+; Ca2+ moves much more slowly through its channels
than Na+ does moving through voltage-gated Na+ channels, giving a slower
depolarization phase
 Pacemaker potential → provides the SAN with automaticity (ability of the cells to
generate action potentials independent of external nervous or hormonal stimuli)
o The movement of ions through ion channels is responsible for the pacemaker
potential, bringing the cell membrane to threshold where an action potential
will fire; ion channels will open/close as cell moves through the pacemaker
potential based only on the cell’s membrane potential, and not as the result of
any external hormonal or nervous stimuli
 Repolarization phase: Opening of K+
channels and closing of L-type Ca2+
Depolarization phase: L-type channels. K+ exits through K+ channels.
channels open at threshold and Ca2+
slowly enters cell.
0
Pacemaker potential: Closing of Threshold

Membrane potential (mV)

K+ channels, Na+ entering
through F-type channels and Ca2+
–50
entering through T-type channels
Ca2+ enters through
Na+ enters through T-type channels
Begin: -60 mV. F-type channels
K+ channels begin to –100
close 0 0.15 0.30
Time (sec)

 AVN → ‘slow type action potential’; slow pacemaker potential than SAN pacemaker
potential
o As the SAN pacemaker potential reaches threshold first, it will pass its stimulus
to other cells in the heart, driving the heart rate at a rate of 60 - 100
beats/minute
o If SAN becomes damaged, the AVN may generate action potentials to drive the
ventricles, but at a lower rate of ~ 40 - 60 beats/minute

 Ventricular Muscle Cell Action Potential:

Depolarization: Notch: Due to transient

Opening of fast opening of K+ channels
0 voltage-gated Na+
channels at
Plateau: Ca2+ entering
tential (mV)

threshold
through L-type channels and Repolarization:
slow opening of K+ channels Opening of K+ channels
 channels

Membra
Stable resting phase:
Leak of K+ through K+
channels
Threshold
250 - 300 msec
-100
0 0.15 0.30
 K+ conductances involved in theTimeresting
(sec)phase, the notch and the repolarization phase
have varying properties and involve different subsets of K+ channels; simply know that
various K+ channels are involved
 Duration of the action potential is ~ 250 to 300 milliseconds, due to the long plateau
phase
o This affects the duration of the refractory period
 This fast-type action potential is also found in the atrial contractile cells (atrial
myocardium)
 Comparison of Cardiac Action Potentials:
(This is for interest only- it shows the action potentials in different regions of the heart.
While the SAN and AVN have the same slow type action potential, which varies from
each other; the atrial myocardium and ventricular myocardium have the fast type action
potential, which also varies from each other)

Lecture 3 recording 11: The Electrocardiogram (ECG, EKG)

 The Electrocardiogram (ECG, EKG):

 A recording of the electrical activity of the heart
 A measure of the currents generated in the extracellular fluid by the changes occurring
simultaneously in many cardiac cells
o Can be measured by an array of electrodes placed on the body surface.
o Electrical activity can be seen from different angles
 The electrical signal becomes weaker as it travels through the body tissues to the
surface of the skin
o Voltage changes in the heart’s ventricular muscle are ~ 100 millivolts in
magnitude, but only 1 millivolt at the surface of the skin
 Used to diagnose problems with the heart’s conducting system
 Placement of Electrodes in the 12 Lead ECG:
 ECG allows different angles for viewing heart’s electrical activity
 An established electrode pattern results in specific tracing pattern
o Look for differences in the established tracing patter if there are electrical
problems in the heart
 ECG Recording:
 ECG represents changes occurring simultaneously in many cardiac cells
o ECG is not recording changes from individual cardiac cells,
 P wave:
o First wave on ECG
o Represents depolarization of the atria
o Upward deflection in the trace
o Approximately 25 milliseconds after the P-wave, the atria will contract
 QRS complex:
o Wave consisting of 3 peaks, labelled Q, R and S
 o Represents depolarization of the ventricles
o When the ventricles are depolarizing, the atria repolarize
 Atrial repolarization is too small an electrical event to be recorded at
the surface of the skin
 T wave:
o Upward deflection
o Represents repolarization of the ventricles
 The ECG and the Heart’s Actions Potentials:
 ECG → shows a 1 millivolt difference in the membrane potential recorded,
 Action potential → shows changes of approximately 110 millivolts
 Some ECGs:
 Many myocardial defects alter normal action potential propagation, and as a result the
shapes and timing of the waves on the ECG vary
 AV node block → a type of heart block in which conduction between the atria and
ventricles is impaired; partial or complete interruption of the impulse from the atria to
the ventricles
 Normal ECG: P-wave always followed by the QRS complex and the T-wave; synchrony
between the atria and ventricles: first the atria depolarize and then the ventricles
depolarize
 Partial AV node block: the damaged AV node permits only every other atrial impulse to
be transmitted to the ventricles; every second P-wave is not followed by a QRS complex
or a T-wave
 Complete AV node block: electrical depolarizations of the atria are not transmitted to
the ventricles; no synchrony between atrial and ventricular electrical activities
 Any component of the heart’s conduction system is capable of initiating action
potentials to drive the heart
o Different regions generate action potentials at different rates
 SAN generates action potentials at fastest rate; in a normal healthy
heart, the SAN generates action potentials which drive the rest of the
hearts conducting system; heart’s pacemaker

Lecture 3 recording 12: Excitation-contraction Coupling in the Heart

 Cardiac Myocytes:
 Cardiac myocyte → muscle cell of the heart
 Intercalated disk → where the membranes of two adjacent myocytes are extensively
intertwined; both desmosomes and gap junctions
 Sarcolemma → plasma or cell membrane of a cardiac
 Sarcoplasmic reticulum → a special type of smooth endoplasmic reticulum which stores
and pumps Ca2+
o Ca2+ is important for excitation-contraction coupling
 Cardiac Myocytes:
 Cardiac myocytes:
o Contain myofibrils
 Myofibrils are made up of sarcomeres
  Sarcomeres → contractile unit of muscle; contain the protein
filaments actin and myosin
Actin → thin filament
Myosin → thick filament
Orderly arrangement of actin and myosin in the
myofibrils gives cardiac muscle its striated or striped
appearance
o T-tubules → invaginations of the sarcolemma; surround myofibrils; transmit
action potentials propagating along the surface membrane to the interior of the
muscle fiber; lie in close proximity to the sarcoplasmic reticulum and contain
many L-type Ca2+ channels
 Excitation-contraction Coupling (ECC) in Cardiac Muscle:
o Excitation-contraction coupling → the process by which the arrival of an action
potential at the cell membrane leads to contraction of the muscle cell
o Steps involved in ECC:
 Ca2+ levels control contraction of the cardiac muscle
 Ca2+ is normally found in low concentrations in the cytoplasm of
the cell, and high concentrations in the extracellular fluid
 During the plateau phase of the action potential, extracellular Ca2+
enter the cytoplasm of the cardiac muscle cell through the L-type Ca2+
channels
 This Ca2+ is not sufficient to cause contraction of the myocytes
2+
 Ca that enters through the L-type calcium channels binds to ryanodine
receptors on the sarcoplasmic reticulum (SR)
 Ryanodine receptors bind Ca2+ and have an intrinsic Ca2+
channel; when Ca2+ binds to the ryanodine receptor, the
channel in the ryanodine receptor opens, allowing the release
of Ca2+ from the SR into the cytoplasm
 SR has a high concentration of Ca2+
 Ca2+ causes its own release from the SR following binding to the
ryanodine receptor = calcium-dependent calcium release or calcium-
induced calcium release
 SR is the source of ~ 95% of the Ca2+ in the cytoplasm
 Ca2+ is important for contraction of the cardiac muscle cells
 Activation of Cross-bridge Cycling by Calcium:

(Review of cross-bridge cycling)

 Troponin → contains binding sites for Ca2+ and tropomyosin, and regulates access to
myosin-binding sites on actin
 Tropomyosin → partially cover the myosin-binding sites on actin at rest, preventing
cross-bridges from making contact with actin
 EEC in Cardiac Muscle: Contraction:
 Steps involved in contraction:
 o Excitation spreads along the sarcolemma, or plasma membrane, from
ventricular myocyte to ventricular myocyte by gap junctions
o Excitation spreads down to the interior of the myocyte by T-tubules
o T-tubules also contain many L-type calcium channels
o During the plateau phase of the fast action potential, the permeability of the
myocyte to Ca2+ increases as L-type Ca2+ channels in the sarcolemma and T-
tubules open following a change in membrane potential
 This Ca2+ entering the myocyte binds to ryanodine receptors on the SR
o Ryanodine receptors (Ca2+ -release channels)
 Following binding of Ca2+, the ryanodine receptors contain an intrinsic
channel that opens to allow Ca2+ to exit the SR into the cytoplasm of the
cell (calcium-induced calcium release)
o Cytosolic Ca2+ binds to troponin, inducing a conformational change in the
regulatory complex; binding sites on actin are now able to bind to the energized
cross-bridge on the myosin head
 Cross-bridge cycling and shortening of the sarcomere and contraction of
the muscle
 Release of Calcium During EEC:

(Review of the steps involved in ECC in the heart)

 L-type calcium channels → voltage-gated Ca2+ channels and are a type of modified DHP
receptor, or dihydropyridine receptor
o We talked about these DHP receptors in our section on nerve, muscle and
synapse. *
 Calcium-dependent calcium release or calcium-induced calcium release → calcium
causes its own release from the sarcoplasmic reticulum
 In cardiac muscle there is no physical coupling or physical connection between the L-
type calcium channel (which is a modified dihydropyridine receptor) and the ryanodine
receptor
o It is Ca2+ that enters the cell through the L-type Ca2+ channels that then moves to
and binds to the ryanodine receptors on the sarcoplasmic reticulum membrane;
this causes the release of Ca2+ from the sarcoplasmic reticulum (calcium-
dependent calcium release)
 Excitation-contraction Coupling: A Comparison:
 Comparison of skeletal muscle and cardiac muscle
 Skeletal muscle → no calcium-dependent calcium release; instead there is a physical
coupling of the dihydropyridine receptor, or the DHP receptor, and the ryanodine
receptor that results in the opening of an intrinsic Ca2+ channel in the ryanodine
receptor (We discussed this in the nerve/muscle/synapse section)
 Cardiac muscle → no physical coupling or physical connection between the L-type Ca2+
channel, which is a modified dihydropyridine receptor, and the ryanodine receptor; L-
type Ca2+ channels in the membrane open following the arrival of an action potential;
the Ca2+ that enters the cell through the L-type Ca2+ channels moves to and binds to the
 ryanodine receptors in the SR causing the release of Ca2+ from the SR (calcium-
dependent calcium release or calcium-induced calcium release)

Lecture 3 recording 13: Excitation-contraction Coupling in the Heart: Relaxation

 ECC in Cardiac Muscle: Relaxation:

 Relaxation of the ventricular myocardium is important as the ventricles only fill with
blood when they are relaxed (diastole)
 The interaction of myosin with actin causes cross-bridge cycling and muscle contraction;
Ca2+ plays a role in cross bridge cycling by binding to troponin, allowing interaction
between actin and myosin
 To end a contraction Ca2+ must be removed from troponin
o Ca2+ levels in the cytoplasm must be reduced to pre-release levels. How?:
 L-type Ca2+ channels close to reduce influx of Ca2+ into the cell
 SR will no longer be stimulated to release Ca2+ into the cytoplasm as Ca2+
is no longer entering the cell and binding to ryanodine receptors on the
SR
 SR contains Ca2+-ATPases to pump Ca2+ in the cytosol back into the SR
 Ca2+ is also removed from the myocyte by a Na+/Ca2+ exchanger found in
the sarcolemma
 The reduced binding of Ca2+ to troponin will block the sites of
interaction between myosin and actin, allowing for relaxation of the
myofibrils
 Uptake of Calcium During ECC:
 Removal of Ca2+ from the cytosol:
o Ca2+-ATPase on the SR – removes the majority of Ca from2+ the cytosol
o Na+/Ca2+ exchanger found in the sarcolemma
o (also closing of L-type Ca2+ channels as we saw in previous slide)
 Refractory Period:
 Refractory period → a period of time during and after an action potential in which an
excitable membrane cannot be re-excited
 Due to the long plateau phase of the ventricular action potential, the refractory period
lasts almost as long as the contraction
o Absolute refractory period ~ 250 milliseconds
 The membrane will not respond to another stimulus, regardless of how
strong it is
 Membrane of the muscle cell is refractory due to the inactivation of the
fast voltage-gated sodium channels that open during the depolarization
phase of the action potential
 After the voltage-dependent Na+ channels close, they enter a state of
inactivation and cannot be opened again until the membrane of the
muscle cell has returned back to negative potentials, where the
channels will begin to recover and are ready to be opened again
o The long refractory period prevents tetanus
Lecture 4 recording 14: Phases of the Cardiac Cycle

 The Cardiac Cycle:

 The cardiac cycle can be divided into systole and diastole
 Systole → ventricular contraction and ejection of the blood
 Diastole → ventricular relaxation and filling of the ventricles with blood
 The cardiac cycle length is the period of time from the beginning of one heartbeat to the
beginning of the next
o Each heart beat involves one ventricular systole and one ventricular diastole
o The heart spends most of the time in diastole
 The longer time spent in diastole is important for ventricular filling as
the ventricles only fill with blood when they are relaxed
 Systole:
 Ventricular systole can be divided into two phases: isovolumetric ventricular contraction
and ventricular ejection
o When the ventricles contract, they squeeze the volume of blood in their
chambers, generating pressure; pressure creates blood flow
o Isovolumetric = ‘iso’ + ‘volumetric’; same volume (constant/unchanging volume)
 Iso = same
 Volumetric = volume
 Isovolumetric ventricular contraction → ventricles contract, all heart
valves closed (AV and semilunar valves), blood volume in ventricles
remains constant, pressures rise; muscle develops tension but cannot
shorten
 Blood cannot enter or exit the ventricles because the valves are
closed
 During isovolumetric ventricular contraction, the ventricular
walls do develop tension as they contract and squeeze the
blood in the chamber, raising the ventricular blood pressure.
The blood is incompressible and cannot flow anywhere as the
valves are closed
 Ventricular myocardium is squeezing against the incompressible
blood and the volume is not changing; the ventricular muscle
fibers cannot shorten
 Ventricular ejection phase → pressure generated by the ventricles
during contraction now exceeds the pressure in the artery into which
the ventricle ejects its blood
 This forward pressure gradient opens the semilunar valves,
allowing the ventricular muscle fibers to shorten as the
ventricles continue contracting and eject their volume of blood
into the arteries
 AV valve is closed during ventricular ejection, being held in the
closed position by the chordae tendineae and the papillary
muscles
  Ventricular muscle fibers are shorten as the blood is ejected
from the ventricles
o Stroke volume → the volume of blood ejected from each ventricle during
systole, or during contraction
 The left and right ventricles eject the same volume of blood when they
contract, but the left ventricle does this with more pressure than the
right ventricle
 When contracting, the ventricles do not eject their entire volume of
blood
 Diastole:
 Ventricular diastole can be divided into two phases: isovolumetric ventricular relaxation
and ventricular filling
o The ventricles can only fill with blood while the ventricular myocardium, or the
muscle layer of the ventricles, is relaxed
o Isovolumetric ventricular relaxation → all heart valves closed, blood volume
remains constant, pressures drop
 AV valve and semilunar valve are closed
 During isovolumetric ventricular relaxation, ventricular volume is not
changing and the pressure inside the ventricles is dropping as the
myocardium is relaxing
o Ventricular filling → AV valves open, blood flows into ventricles from atria;
ventricles receive blood passively (atria are relaxed)
 When the atria are in diastole they receive blood returning back to the
heart in the veins; once that the atria are full of blood (and the
ventricles are relaxed), pressure in the atria rises above the pressure in
the ventricles (the pressure in the atria is simply due to the volume of
blood in the atria); this is a forward pressure gradient
 The forward pressure gradient will open the AV valves, allowing blood
to flow from the relaxed atria to the relaxed ventricles
 2 phases of ventricular filling: passive ventricular filling and atrial
contraction
 Passive ventricular filling → the ventricles receive
approximately 70 per cent of their blood volume
In passive ventricular filling both the atria and the
ventricles are relaxed; atria have a greater pressure
than the ventricles because they are full of blood
 Atrial contraction or atrial kick → completes ventricular filling;
remember ventricles are still relaxed
 Phases of the Cardiac Cycle:

(This slide goes over the phases of the cardiac cycle, looking at what is happening in the
ventricles and the atria. Make sure you understand the phases of systole (isovolumetric
ventricular contraction, ventricular ejection) and diastole (isovolumetric ventricular diastole,
ventricular filling (passive ventricular filling and atrial contraction))
  Cardiac cycle → the rhythmical contraction and relaxation of the heart’s chambers
coordinated by the electrical activity in the heart; represents the events that occur in
the chambers of the heart during one single heart beat
 The same series of events occurs in both the left and right sides of the heart at the same
time; the difference being that when the left ventricle contracts, it contracts with more
force/pressure than the right ventricle, due to the thicker myocardium, or the thicker
muscle layer

Lecture 4 recording 15: The Pressure-volume Curve

 Pressure-volume Curve:
 Also called Wiggers diagram
 Pressure is the key to understanding blood flow patterns and the opening and closing of
valves:
o Pressure is generated when the muscles of the heart chamber contract as well
as when a chamber fills with blood
o Blood always flows from a region of higher pressure to a region of lower
pressure
o Valves open and close in response to a pressure gradient; a forward pressure
gradient opens a one-way valve while a backward pressure gradient shuts a
one-way valve

 Pressure-volume Curve:
 End-diastolic volume (EDV) → the amount or volume of blood in each ventricle at the
end of ventricular diastole; measured in millilitres (mL)
 End-systolic volume (ESV) → the amount or volume of blood in each ventricle at the end
of ventricular systole, or at the end of ventricular contraction and ejection; in mL
 When the ventricles contract they do not eject their entire volume of blood
o Stroke volume (SV) → the volume of blood pumped out of each ventricle during
systole
 Calculated as: SV = EDV - ESV
 Typical SV values for an adult at rest are ~ 70 - 75 mL

Lecture 4 recording 16: More on the Pressure-volume Curve

 Pressure-volume Curve:

(Make sure you understand the Wigger’s diagram and the events that occur. Listed below
are some examples of questions that can be asked based on this diagram)

 Wigger’s diagram; shows the pressure and volume changes for the heart
 The same events occur simultaneously on both sides of the heart

Pressure in
 as ventricle 110
opens
contracts

Pressure (mmHg)
Aortic valve
Isovolumetric closes
Isovolumetric
ventricular 50 ventricular
contraction relaxation
Left atrium and Left AV
 Below are 2 questions from the practice questions which show the type of question you
ventricle are valve opens
mayrelaxed.
be asked based on knowledge of the pressure-volume curve:
Aortic 0
valve closed.
130

Left ventricular volume (mL)

 During ventricular filling:
Left AV Ventricular
valve closes EDV ejection
o The ventricles contract
65 are
o The semilunar valves QRSclosed
Ventricle Passive filling
almostofull
The atrioventricular (AV) valves are ESV
closed
from passive P T
filling ECG
o Blood flows from the ventricles to the atria through the AV valve
1st 2nd
o The pressure in the ventricles decreases
Diastole Systole Diastole
2 3 4 1
Phase of cardiac cycle
 During ventricular ejection:

o The AV valves are open; the semilunar valves are closed

o The AV valves are open; the semilunar valves are open
o The AV valves are closed; the semilunar valves are open
o Blood flows from the atria to the ventricles
o The ventricle empties its entire volume of blood

 The Right Heart:

 The right ventricle develops lower pressures than the left ventricle during systole
 Right ventricle undergoes the same series of events as the left ventricle

 Heart Sounds:
 First heart sound → lub; caused by closure of the AV valves at the beginning of
isovolumetric ventricular contraction and signifies the onset of ventricular systole
 Second heart sound → dub; caused by closure of the semilunar valves and signifies the
onset of ventricular diastole
 The heart sounds reflect turbulence when the valves passively snap shut as the
pressures across the valves change
 The valves on the left and right sides of the heart are also closing at the same time
o Lub and dub signify closing of the valves on both sides of the heart; both the left
and right AV valves close together and make the sound lub and both semilunar
valves close together and make the sound dub
 Heart Sounds and Murmurs:
 Normally blood flow through valves and vessels is laminar flow and makes no sound
o Laminar flow is characterized by smooth concentric layers of blood moving in
parallel down the length of a blood vessel
o The highest velocity (Vmax) is found at the central axis, or the center, of the
vessel and the lowest velocity (V=0) is found along the vessel wall
 o The flow profile is parabolic once laminar flow is fully developed
o This occurs in long, straight blood vessels, under steady flow conditions
o Under conditions of high flow, particularly in the ascending aorta, laminar flow
can be disrupted and become turbulent
 Abnormal flow may be turbulent
o Turbulent flow makes a sound and is called a murmur
o Stenotic valve → a valve in which the leaflets do not open completely; this can
occur when the valve leaflets become stiffer due to calcium deposits or scaring
of the valve; when blood flows through a stenotic valve, it becomes turbulent
and this is heard as a murmur
o Insufficient valve → does not close completely due to widening of the aorta or
scaring of the valve; blood flows backwards through the leaky valve and
produces turbulence which is heard as a murmur

Lecture 4 recording 17: The ANS and Cardiac Output

 Autonomic Innervation of the Heart:

 The heart is innervated by sympathetic and parasympathetic fibers
o Sympathetic innervation through the thoracic spinal nerves
 Sympathetic postganglionic fibers innervate the entire heart, including
the atria, ventricles, SA node and AV node
 Neurotransmitter released: norepinephrine
o Parasympathetic innervation through the vagus nerve
 Parasympathetic postganglionic fibers innervate the atria, SA node and
AV node
 Neurotransmitter released: acetylcholine
 Important: ventricles do not receive significant parasympathetic
innervation and the ventricular myocardium is not affected by
parasympathetic activity
 (Do not need to know the type of receptors on this slide)
 Effect of the ANS on the Heart:
 Parasympathetic stimulation:
o Decrease heart rate by decreasing the rate of depolarization, or the rate of rise
to threshold, of the pacemaker potential;
o Decrease the conduction of the electrical impulses through the AVN, increasing
AV nodal delay; this means that it will take longer for the stimulus to pass
through the AVN into the ventricles
o Decrease contractility of the atrial myocardium, decreasing the force of
contraction; remember the ventricular myocardium receives little or no
parasympathetic innervation, and as a result parasympathetic stimulation has
no effect on contractility of the ventricle
  Sympathetic stimulation:
o Increase heart rate by increasing the rate of depolarization, or the rate of rise,
of the pacemaker potential to threshold
o Increase conduction of the electrical impulses through the AVN, decreasing AV
nodal delay; this means it takes less time for the stimulus to pass through the
AVN to the ventricle
o Increase the contractility of the atrial and ventricular myocardium, increasing
the force of contraction
 Remember: the parasympathetic system will only decrease the force of contraction in
the atria, as the ventricles receive little or no parasympathetic innervation
 Cardiac Output:
 Cardiac output (CO) → the amount of blood pumped by each ventricle in one minute;
CO = HR x SV
 Stroke volume (SV) → the amount of blood pumped out of each ventricle during systole;
typical stroke volumes are 70 - 75 mL
 Cardiac output differs from stroke volume in that it is measured per unit time
 Factors Affecting Cardiac Output:
 As CO = HR x SV by altering the either the heart rate (HR) or the stroke volume (SV), we
can alter cardiac output (CO)
 How do we alter heart rate (HR)?
o Heart rate may be altered by modifying the activity of the SAN (heart’s
pacemaker)
 How do we alter stroke volume (SV)?
o Stroke volume can be altered by varying the strength of the contraction of the
ventricular myocardium
 When the ventricles contract, they do not empty their entire volume of
blood; altering the strength of contraction of the ventricular
myocardium will alter the SV, or the volume of blood pumped out
 An increased strength of contraction will increase SV; a decreased
strength of contraction will decrease SV

Lecture 4 recording 18: Factors Affecting Cardiac Output: Heart Rate

 Factors Affecting Heart Rate:

 The heart has resting autonomic tone; both the sympathetic and parasympathetic
systems are active at a steady background level (called tone)
 One division of the ANS will dominate when its rate of firing raises above a tonic level
while the other’s falls below
 Parasympathetic and sympathetic effects are antagonistic for heart rate
o To increase HR, sympathetic stimulation will increase while parasympathetic
stimulation will decrease; to decrease HR, the parasympathetic stimulation will
increase while sympathetic stimulation will decrease
  Under resting conditions, parasympathetic effects dominate for heart rate
 To increase HR: must increase the activity of the sympathetic division
o Increased sympathetic activity and increased release of epinephrine from the
adrenal medulla will stimulate/increase the activity of the SAN, increasing HR
and CO
o As the sympathetic and parasympathetic systems are antagonistic, activity in
the parasympathetic system must be decreased when sympathetic activity is
increased
 To decrease HR: must increase the activity of the parasympathetic division
o Increased parasympathetic activity will inhibit or decrease the activity of the
SAN, thereby decreasing HR and CO
o As the sympathetic and parasympathetic systems are antagonistic, activity in
the sympathetic system must be decreased when parasympathetic activity is
increased
 Sympathetic and parasympathetic effects on the heart are extrinsic factors or they
originate outside the heart
 Important: the conducting myocytes in the heart are responsible for initiating the heart
rate; cells of the SA node are the heart’s pacemaker generating the action potentials
that are responsible for the HR
 Sympathetic and parasympathetic systems can then modify the activity of the SAN
 Effect of the ANS on Heart Rate:
 Sympathetic stimulation of the SAN → increases the slope of the pacemaker potential
causing a faster depolarization to threshold; faster rise to threshold increases heart rate
o Sympathetic stimulation increases the slope of the pacemaker potential by
increasing the permeability of the F-type and T-type channels
 F-type channels allow Na+ to enter the cell
 T-type channels allow Ca2+ to enter the cell
 Increasing permeability of these channels causes more positive
charge to enter into the cell, bringing the cells to threshold
more rapidly
 Parasympathetic stimulation of the SAN → decreases the slope of the pacemaker
potential causing a slower depolarization to threshold; slower rise to threshold
decreases heart rate
o Parasympathetic stimulation decreases the slope of the pacemaker potential by:
 Decreasing F-type channel permeability, reducing the movement of Na +
into the cells
 Increasing K+ channel permeability, causing more K+ to leave the cell,
making the cell more negative inside
 The pacemaker potential starts from a more negative value,
closer to the equilibrium potential for K+, taking more time to
reach threshold
 Effect of the ANS on the Pacemaker Potential:
 Sympathetic stimulation: pacemaker potential rises more quickly to threshold, or takes
less time to reach threshold, increasing the heart rate
  Parasympathetic stimulation: pacemaker potential rises more slowly to threshold, or
takes more time, decreasing heart rate
 Summary of the Factors Affecting Heart Rate:
 Epinephrine, a hormone secreted by the adrenal medulla into the blood, acts similarly to
norepinephrine released by sympathetic nerves
 To increase HR → increased plasma epinephrine, increased release of norepinephrine
from sympathetic nerves and decreased release of acetylcholine from parasympathetic
nerves acts on the SAN to increase HR
 Sympathetic and parasympathetic systems are antagonistic for heart rate
 To decrease HR → (reverse the direction of the arrows); increase parasympathetic
activity and decrease sympathetic activity to the SAN, as well as reducing epinephrine
release

Lecture 5 recording 19: Factors Affecting Cardiac Output: Stroke Volume

 Factors Affecting Cardiac Output:

 CO = SV x HR; by altering SV, CO can be altered
 Stroke volume (SV) → the volume of blood the ventricle ejects during each contraction,
or during systole
o 3 factors that affect the stroke volume: 1) the end diastolic volume (EDV), also
called the preload, 2) the contractility of the ventricular myocardium, and 3) the
afterload
 Factors Affecting Stroke Volume: EDV:
o Remember: 3 factors that affect the stroke volume: 1) the end diastolic volume
(EDV), also called the preload, 2) the contractility of the ventricular myocardium,
and 3) the afterload
 Factor affecting stroke volume: end-diastolic volume (EDV), also called the preload
o EDV → the volume of blood in the ventricles at the end of ventricular diastole,
or the volume of blood in the ventricles after the ventricles have completed
filling
o The heart has an intrinsic mechanism to alter stroke volume
 Intrinsic means that it that originates or occurs inside, in this case, the
heart
 This intrinsic mechanism because the ventricles will contract more
forcefully when they have been stretched prior to contraction
 How are the ventricles stretched? Increased stretch is
accomplished by filling the ventricles more fully with blood
 The relationship between the end-diastolic volume and stroke volume is
defined by the Frank-Starling mechanism
 How do we fill the ventricles more fully with blood? Increase the venous
return, or the amount of blood returning to the heart through the veins;
this will more fully fill the ventricles with blood, increasing the EDV,
increasing SV, which ultimately increases CO
  Preload → the tension or load on the ventricular myocardium before it begins to
contract, or the amount of filling of the ventricles at the end of diastole, which is the
EDV
 Sympathetic stimulation of venous smooth muscle will act to increase the return of
blood to the heart through venoconstriction, increasing filling of the ventricles
o Sympathetic effect on venous smooth muscle is an extrinsic mechanism, which
originates outside the heart.
o Why does the parasympathetic system in the diagram not affect the venous
volume? Most of the blood vessels in our body receive only sympathetic
innervation to their smooth muscle and not parasympathetic innervation
 The Frank-Starling Mechanism:
 Frank-Starling mechanism
o Intrinsic mechanism
o Occurs independent of neural or hormonal stimulation
o The relationship between EDV and SV is defined by the Frank-Starling
mechanism
o As you increase EDV, you increase SV
 Why does an increased EDV lead to an increased SV?
o The main determinant for sarcomere length is the degree or amount of
diastolic filling
o The initial length of the sarcomere will affect the tension generated during
contraction
o As the ventricles become more filled with blood, the cardiac fibers or the
sarcomeres stretch out, putting more load on the sarcomeres; the ventricles will
contract more forcefully when they have been stretched, and SV will increase
o The Frank-Starling mechanism is a length-tension curve
 The Frank-Starling mechanism matches the outputs of the two ventricles
o Ensures the two ventricles pump the same amount/volume of blood and blood
does not accumulate in one circuit compared to the other
 Mechanism of the Length-tension Relationship:
 This slide explains why as the ventricle is filled more fully with blood that there is an
increased force of contraction and a greater stroke volume
 (This slide is to help you visually understand the underlined statements)

Lecture 5 recording 20: Factors Affecting Cardiac Output: More on Stroke Volume

 Factors Affecting Stroke Volume: Contractility:

o Remember: 3 factors that affect the stroke volume: 1) the end diastolic volume
(EDV), also called the preload, 2) the contractility of the ventricular myocardium,
and 3) the afterload
 Remember: the ventricles do not completely empty when they contract
o Under normal resting conditions, the ejection fraction of the ventricles is
between 50 - 75%
 o A change in the contractility of the ventricles (contractility = the strength of
contraction at any given EDV) will alter the volume of blood pumped by the
ventricles during systole, or the SV
o Increased sympathetic stimulation will increase the strength of contraction of
the ventricular myocardium, increasing SV and CO
o Altering parasympathetic activity will not affect contractility of the ventricles
and SV, as the ventricular myocardium receives little or no parasympathetic
innervation
 Sympathetic Stimulation Increases Contractility:
 The Frank-Starling mechanism still applies under sympathetic stimulation, but during
sympathetic stimulation, the stroke volume is greater at any given EDV
o At the same EDV, there is an increase in SV under sympathetic stimulation
 Increased contractility will lead to a more complete ejection of the blood, increasing the
ejection fraction
o Ejection fraction = SV/EDV
 Under sympathetic stimulation, increased contractility results in a more
complete ejection of the end-diastolic ventricular volume
 Increased sympathetic activity also acts to increase the rate of contraction and
relaxation
o Under sympathetic stimulation, the heart contracts and relaxes faster, giving
more time for the ventricles to fill, despite the increase in heart rate
 Mechanisms of Sympathetic Effects on Contractility:
 Sympathetic regulation of myocardial contractility acts through a G protein coupled
mechanism:
o A number of proteins involved in the excitation-contraction coupling process are
phosphorylated by intracellular kinases, which enhances contractility
o These proteins include: L-type Ca2+ channels in the sarcolemma, the ryanodine
receptor in the sarcoplasmic reticulum membrane, thin filament proteins- in
particular, troponin, thick filament proteins associated with the cross-bridges,
and proteins involved in pumping Ca2+ back into the sarcoplasmic reticulum

(You do not need to know the mechanisms by which this happens)

 Factors Affecting Stroke Volume: Afterload:

 When the ventricles contract they must generate sufficient pressure to exceed the
pressure in the arteries and open the semilunar valves to eject their blood into the
arteries
o Afterload → the tension against which the ventricle must eject its blood; it is
closely related to the arterial pressure; often called the ‘load’
 The greater the afterload, the longer the period of isovolumetric
contraction during which time the heart generates sufficient pressure to
open the valves and eject blood, and a smaller stroke volume
 As afterload increases, SV decreases
 Afterload is increased by any factor that restricts blood flow through the
arterial system
  Arterial blood pressure, vascular resistance, stenotic valve

Lecture 5 recording 21: The Vascular System

 The Vascular System:

(Intro slide – do not need to know any information from this slide)

 Endothelium:
 Our entire circulatory system, including our heart chambers, heart valves, and blood
vessels, is lined by a smooth, single-celled layer of endothelial cells
 The endothelium of the vessels is continuous with the endocardium of the heart
 Endothelial cells form a physical lining that blood cells do not normally adhere to in the
heart and in the blood vessels
 Pressures in the Systemic and Pulmonary Circuits:
 Blood pressure generated by contraction of the ventricles decreases by the time the
blood has completed its journey back to the atrium in both the systemic circulation and
the pulmonary circulations
 Pressures in the systemic circulation are much higher than in the pulmonary circulation
 Pulmonary vascular resistance is much lower than the systemic total resistance
o The pulmonary bed has a low resistance because it has relatively large vessels
throughout and the arterioles have much less smooth muscle than the arterioles
in the systemic circulation
 Arteries:
 Walls of arteries contain: smooth muscle, elastic fibers and connective tissue
 Muscular walls allow arteries to contract and change diameter
 Elasticity permits passive changes in vessel diameter in response to changes in blood
pressure
 Vasoconstriction → contraction of arterial smooth muscle decreases the diameter of the
artery
 Vasodilation → relaxation of arterial smooth muscle increases the diameter of the
artery
 Lined with endothelial cells
 Elastic arteries → contain many elastic fibers and few smooth muscle cells; pulmonary
trunk and aorta; can tolerate pressure changes during the cardiac cycle
 Muscular arteries → contain many smooth muscle cells and few elastic fibers; most of
the vessels in the arterial system are muscular arteries; function to distribute blood
throughout the body
 Arterioles → smallest of the arteries; composed of 1 to 2 layers of smooth muscle cells;
resistance vessels in the body; play a very important role in determining our mean
arterial pressure, or our blood pressure

Lecture 5 recording 22: Arterioles and Extrinsic Factors Altering Arteriolar Resistance

 Arterioles:
 Walls of arterioles have an abundance of circular smooth muscle that forms rings
around the arterioles
 o This allows the state of constriction of the arteriolar smooth muscle to be
regulated
 Functions: regulate blood flow to organs by regulating the amount of blood flow to
capillary beds supplying that organ and play a role in determining our mean arterial
pressure (MAP), or our average blood pressure during the cardiac cycle (also called
blood pressure)
 Arterioles have a small enough radius to offer considerable resistance to blood flow and
are called resistance vessels
 Arterioles and Resistance to Blood Flow:
 Altering the diameter of a blood vessel will alter resistance to flow:
o When diameter is decreased this increases resistance to flow and reduces the
flow to organs; when diameter is increased this decreases resistance to flow and
increases the flow to organs
 Arterioles:
o Small diameter vessels and their small diameter offers significant resistance to
flow, which is why there is a large decrease in mean arterial pressure as the
blood flows through arterioles
o Arterioles in individual organs can alter their diameter
o The pattern of blood-flow distribution depends upon the degree of arteriolar
smooth muscle contraction within each organ and tissue
o Arterioles play an important role in determining our MAP, or our blood
pressure, and by altering their diameter, the arterioles can alter blood flow to
different organs and tissues
 Arterioles and Resistance to Blood Flow:
o Arteriolar smooth muscle has intrinsic or basal tone:
 Tone - partial contraction in the absence of external factors such as
neural or hormonal stimuli
 Other factors can then increase or decrease the intrinsic/basal tone
 These factors may be extrinsic or intrinsic
Extrinsic factors: external to the organ or tissue and
alter whole body needs, such as MAP, and include
nerves and hormones
Intrinsic factors: local controls which include
mechanisms independent of nerves or hormones by
which organs and tissues alter their own arteriolar
resistances, thereby self-regulating their blood flow
 Extrinsic Controls: Nerves and Hormones:
o Extrinsic factors: are external to the organ or tissue and include nerves or
hormones to exert their effects on arteriolar smooth muscle
 Sympathetic innervation to arteriolar smooth muscle but little, or no,
parasympathetic innervation
 The sympathetic nerve fibers release norepinephrine to cause
vasoconstriction (do not need to know receptors)
  The sympathetic neurons are seldom completely inactive, but
discharge at some basal level called sympathetic tone
(Sympathetic neurons cause some degree of tonic constriction
in addition to the vessels' intrinsic tone)
 Sympathetic tone can be increased, causing further
vasoconstriction, or decreased, causing vasodilation
 Sympathetic innervation to the arteriolar smooth muscle is
important for regulating MAP
Sympathetic system regulates MAP by influencing
arteriolar resistance throughout the body
 Noncholinergic, nonadrenergic neurons affect arteriolar smooth muscle
 Release nitric oxide, a vasodilator
 Hormone: epinephrine
 Released from the adrenal medulla into the blood
 Acts on arteriolar smooth muscle to cause vasoconstriction or
vasodilation, depending on receptor to which it binds (do not
need to know which receptor causes vasoconstriction or
vasodilation)

Lecture 5 recording 23: Arterioles and Local Controls Altering Arteriolar Resistance

 Local Controls: Active Hyperemia:

 Local controls: mechanisms independent of nerves or hormones; mechanisms by which
the organ or tissue alters its own arteriolar resistance, thereby regulating its own blood
flow
o Active hyperemia → local control which acts to increase blood flow when the
metabolic activity of an organ or tissue increases
 Hyperemia → an excess of blood in the vessels supplying an organ or
tissue
 Arteriolar smooth muscle is sensitive to local chemical changes in the
extracellular fluid surrounding the arterioles, such as oxygen or carbon
dioxide levels or pH
 Local chemical changes are the result of changes in metabolic activity
 These altered chemical changes act on smooth muscle in the arterioles
to cause vasodilation and increase blood flow
 Does not involve any nerves or hormones
 Local Controls: Flow Autoregulation:
o Flow autoregulation:
 Locally mediated changes in arteriolar resistance also occur when a
tissue or organ experiences a change in its blood supply resulting from a
change in blood pressure
 An increase in arteriolar pressure will increase blood flow to an organ; a
decrease in arteriolar pressure will decrease blood flow to an organ
 Altered blood flow will change the concentration of local chemicals
(oxygen, carbon dioxide and hydrogen ions)
  The change in the level of local chemicals will alter the state of
constriction of the arteriolar smooth muscle, altering blood flow to
bring the concentration of local chemical substances back to normal
 Occurs at a constant metabolic activity and is the result of a change in
pressure in an organ and, as a result, blood flow
 Can occur when the blood pressure to an organ increases or
decreases
 No nerves or hormones are involved in the mechanism of flow
autoregulation
 Local Controls: Flow Autoregulation:
 Flow autoregulation is not only mediated by changes in local chemical factors, but also
by the myogenic response
o Myogenic response → the direct response of arteriolar smooth muscle to
stretch
 An increase in arterial pressure and blood flow causes arterial walls to
stretch, in addition to changing levels of local chemical factors.
Arteriolar smooth muscle responds to this stretch by contracting. This
will reduce blood flow to the organ toward normal levels.
 At the same time there is an increased stretch in the arteriolar walls due
to the increased blood flow, there is an increase in oxygen levels and a
decrease in metabolites. These changes in these local chemicals will also
act to constrict the arteriolar smooth muscle, to bring levels back to
normal.
o Flow autoregulation → occurs in response to both changes in local chemical
factors and the degree of stretching of the arteriolar smooth muscle (myogenic
response)
 More Local Controls:
 Reactive Hyperemia:
o Form of flow autoregulation
o Occurs at constant metabolic rate
o Occurs due to changes in the concentrations of local chemicals
o Occlusion of blood flow → greatly decreases oxygen levels and increases
metabolites → arterioles dilate → blood flow greatly increases once occlusion
removed

Lecture 6 recording 24: Capillaries

 Capillaries:
 Thin walled vessels one endothelial cell thick
 Supported by a basement membrane
 Contain no smooth muscle or elastic fibers
 Function in the rapid exchange of material between the blood and the interstitial fluid
 Adjacent endothelial cells are joined laterally by tight junctions but leave gaps of
unjoined membrane called intercellular clefts
 o Intercellular clefts act as channels or water-filled spaces between endothelial
cells through which small water-soluble substances can pass through
 May have fused-vesicle channels
o Endothelial cells contain large numbers of endocytic and exocytic vesicles which
fuse together to form continuous vesicular channels across the cell
 Types of Capillaries:
 3 types of capillaries: continuous capillary, fenestrated capillary, sinusoidal capillary
 Continuous Capillary:
 Continuous capillaries:
o Uninterrupted/complete endothelium and continuous basement membrane
(basal lamina)
o Tight junctions between adjacent endothelial cells
 Often incomplete in capillaries, leaving intercellular clefts that allow for
the exchange of water and other very small molecules between the
blood plasma and the interstitial fluid
o Have the lowest permeability of all capillary types allowing the exchange of
water, small solutes, and lipid-soluble material only
o Plasma proteins, other large molecules, platelets and blood cells cannot pass
through continuous capillaries
o Found in most tissues
o Pericytes → lie external to the endothelium; may help stabilize the walls of
blood vessels and help regulate blood flow through capillaries
 Continuous Capillaries:

(Slide showing another view of a continuous capillary)

 Fenestrated Capillaries:
 Fenestrated capillaries:
o Endothelial cells have numerous fenestra or pores
 Fenestra → membrane-lined cylindrical conduits that run completely
through the endothelial cell, from the capillary lumen to the interstitial
space
o Surrounded by an intact or complete basement membrane
o Fenestra or pores allow for the rapid exchange of water and solutes, including
larger solutes such as small peptides
o Found in tissues where capillaries are highly permeable, such as endocrine
organs, the choroid plexus, the GI tract and the kidneys
o Lipid-insoluble molecules may move through intercellular clefts as well as
through the fenestrae
o Fenestrae make this type of capillary much more permeable than continuous
capillaries
 Sinusoids:
 Sinusoids (sinusoidal capillaries):
o Large diameter, flattened and irregularly shaped
o Called discontinuous capillaries
 o Have very large fenestrae and large gaps between adjacent endothelial cells
o Basement membrane very thin or absent
o Allow the free exchange of water and solutes, including large substances such as
red blood cells, cell debris, and plasma proteins
o Found only in liver, bone marrow and spleen
 Microcirculation:
 Capillaries are part of the microcirculation, or the circulation of blood through the
smallest vessels in the body
o These vessels includes arterioles, metarterioles, capillaries, venules and veins
o A capillary bed can be supplied by more than one arteriole
 If one arteriole becomes blocked, blood can enter the capillary bed by
another arteriole
 Blood flow to capillary beds is variable
 Precapillary sphincters → ring of smooth muscle which guards the
entrance to the capillary
 Contract and relax in response to local conditions to alter the
flow of blood in the capillary beds
 Receive no innervation
o In the microcirculation, capillaries branch from arterioles or metarterioles
 Metarterioles → also called precapillary arterioles; small blood vessels
arising from an arteriole, pass through a capillary network and empty
into a venule; contain smooth muscle cells enabling them to regulate
blood flow by changing diameter; are not ‘true’ capillaries as they have
smooth muscle cells
 Distribution of Blood Flow at Rest and During Exercise:
 Our body redirects our blood flow depending on our body’s needs by increasing and
decreasing blood flow to different capillary beds

Lecture 6 recording 25: Capillary Exchange

 Capillary Exchange:
 Materials are exchanged across the walls of capillaries by diffusion, vesicle transport or
bulk flow
 Blood flows very slowly through capillaries to maximize the time for the exchange of
substances between the plasma and the interstitial fluid
 Diffusion → net movement of substances from a region of high concentration to a
region of low concentration
o Diffusion looks at the movement of one substance only down its own
concentration gradient
o Diffusing substances have only a short distance to travel across capillaries, as
capillaries have a small diameter and have a thin capillary wall due to the fact
that they are only one endothelial cell thick
o Mechanism by which nutrients, oxygen and metabolic end products cross
capillary walls
 o Substances that are lipid-soluble can diffuse across the plasma membrane of
endothelial cells
o Substances that are lipid-insoluble must move through a water-filled channel
(intercellular cleft, fenestrae found in fenestrated capillaries and sinusoids, or
fused vesicle channels)
 Transcytosis → a process involving vesicles in which endothelial cells pick up material on
one side of the plasma membrane by pinocytosis or receptor-mediated endocytosis,
transport the vesicles across the cell, and discharge the material on the other side by
exocytosis
o Vesicles may fuse together to form a water-filled channel, called a fused vesicle
channel, from one side of the endothelial cell to the other through which
substances may move
 Substances move through the fused vesicle channel by diffusion
 Capillary Exchange:
 Bulk flow → the movement of protein-free plasma across the capillary wall
o Various constituents of the fluid cross the capillary wall in bulk, or as a unit
o During bulk flow, the quantity of solutes moving across capillary walls in the
plasma is extremely small compared to the much larger transfer of solutes that
occurs by diffusion
 The function of bulk flow is not the exchange of nutrients and metabolic
end products across capillary walls but rather the distribution of the
extracellular fluid volume (ie. Bulk flow is important for distribution of
extracellular fluid volume and less important for exchange of nutrients
and metabolic end products)
 Extracellular fluid includes the plasma and the interstitial fluid
 Normally, there is more interstitial fluid than plasma
o Filtration → movement of protein-free plasma by bulk flow from the capillary
plasma to the interstitial fluid through water-filled channels
o Reabsorption → movement of protein-free plasma by bulk flow from the
interstitial fluid to the capillary plasma
o The concentration of solutes in the filtered fluid, with the exception of plasma
proteins, is the same as in the plasma
 Bulk Flow: Hydrostatic Pressure:
 Bulk flow looks at the movement of protein-free plasma across the capillary wall
 Bulk flow is driven by different pressures; it occurs because of differences in the
hydrostatic and colloid osmotic pressures between the capillary plasma and the
interstitial fluid
 Hydrostatic pressure → the force of a fluid against a membrane
o Capillary hydrostatic pressure → the pressure exerted by the blood on the
inside of the capillary walls and forces protein-free plasma out of the capillaries
into the interstitial fluid
o Interstitial fluid hydrostatic pressure → is the pressure exerted on the outside of
the capillary wall by the interstitial fluid and forces fluid into the capillaries; this
pressure is very negligible and does not contribute significantly to bulk flow
 Bulk Flow: Colloid Osmotic Pressure:
 Colloid osmotic pressure → the osmotic pressure due to the presence of impermeable
proteins
o The proteins are impermeable (they cannot cross capillary walls)
 As a result the concentration of proteins will not be equal in the plasma
and in the interstitial fluid
 The difference in protein concentration between the plasma and the
interstitial fluid creates an osmotic force; the proteins draw fluid
towards them, into the compartment that they occupy, as water moves
from a region of high water concentration to a region of low water
concentration
 Solutes such as sodium or potassium do not have this effect as they can
move across capillary walls through pores or water-filled channels
 Solutes such as sodium and potassium have equal
concentrations in the plasma and in the interstitial fluid
o Blood colloid osmotic pressure → the osmotic pressure due to the presence of a
large number of non-permeating plasma proteins, such as albumin, within the
blood; proteins pull water into the capillaries
o Interstitial fluid colloid osmotic pressure → is the result of the small amount of
proteins which do escape the capillaries into the interstitial fluid; favors fluid
movement out of the capillary, but it is very small and does not contribute
significantly to bulk flow
 Bulk Flow: Net Exchange Pressures:
 Net exchange pressure = PC + πIF – PIF – πC (you do not need to memorize this formula,
but understand how net filtration pressure is calculated)
o P = hydrostatic pressure; pi = colloid osmotic pressure; C – capillary; IF -
interstitial fluid
o The net pressure is the sum of the outward pressures and the inward pressures
 Outward pressures = capillary hydrostatic pressure and the interstitial
fluid osmotic pressure
 Inward pressures = the osmotic force due to the plasma protein
concentration and the interstitial fluid hydrostatic pressure

(Below: for the net pressures at the arterial and venous ends of the capillary you do not
need to know the numbers (ie 35 vs 15 mmHg hydrostatic pressure, but understand that
this pressure decreases along the length of the capillary and why this is more filtration at
arterial end and more absorption at venous end), understand what hydrostatic pressure
and colloid osmotic pressure are)

 Arterial end of the capillary:

o Capillary hydrostatic pressure (arterial end) ~ 35 mmHg
 Hydrostatic pressure will decrease as blood moves along the length of
the capillary towards the venous end
 Pushes fluid out of the capillary
o Blood colloid osmotic pressure (due to proteins in the blood) ~ 28 mmHg
  Draws fluid into the capillary
 Blood colloid osmotic pressure remains the same along the length of the
capillary
o Interstitial fluid hydrostatic pressure is ~ 0mmHg
 Does not cause movement of fluid
o Interstitial fluid colloid osmotic pressure ~ 3mmHg
 Causes fluid to move out of the capillary
o At the arterial end of the capillary: net pressure is 35 + 3 – 0 – 28 = 10 mmHg
 This is a positive number and favors filtration of fluid from the capillary
into the interstitial fluid
 Venous end of the capillary:
o Capillary hydrostatic pressure (venule end) ~ 15mmHg
 Pushes fluid out of the capillary
o Blood colloid osmotic pressure (due to protein in the blood) ~ 28mmHg
 Draws fluid into the capillary (as it did at the arterial end)
o The interstitial fluid hydrostatic pressure and the interstitial fluid colloid
osmotic pressure also have the same values at the venous end as at the arterial
end of the capillary
 Interstitial hydrostatic pressure ~ 0 mmHg
 Does not cause the movement of fluid
 Interstitial fluid colloid osmotic pressure ~ 3 mmHg
 Causes fluid to move out of the capillary
o At the venous end of the capillary: net pressure is 15 + 3 – 0 – 28 = -10 mmHg
 This is a negative number and favors the absorption of fluid from the
interstitial fluid into the capillary
 The four factors that determine the net filtration pressure are termed the Starling forces
 Net Filtration and Net Reabsorption Along the Capillary:
 The capillary hydrostatic pressure changes significantly along the length of the capillary
o 35 mmHg at the arterial end and 15 mmHg at the venous end due to friction
between the flowing blood and the capillary wall
 The transition between filtration and reabsorption occurs where the sum of the outward
pressures is equal to the sum of the inward pressures
o As the hydrostatic pressure at the arterial end is greater than at the venous end
of the capillary, this transition does not occur in the exact middle between the
arterial and venous ends of the capillary, but occurs closer to the venous end of
the capillary
 More filtration than absorption occurs along the length of the capillary
 The difference excess filtered fluid moves back into the lymphatic system to eventually
return to the venous system (you do not need to know the numbers (litres of fluid) just
that more fluid is filtered than absorbed; excess is returned to the lymphatic system)

Lecture 6 recording 26: Venous System

 Distribution of Blood Volume:

 At rest, ~ 60% of the blood volume is found in the venous system
 o Liver, bone marrow, and skin have a large volume of blood
 Veins:
o Expand and recoil passively with changes in pressure
o High capacitance vessels as can store large amounts of blood
o Highly distensible, expanding easily at low pressures and have little elastic recoil
o Reservoir for blood
 Venous Valves:
 Venous system is a low pressure system
 Venous valves → composed of two leaflets or folds; prevent the backflow of blood into
the capillaries
o Aid in returning blood to the heart and ensuring blood flows in one direction
only
o Compartmentalize the blood within the veins, so the weight of the blood is
distributed between the compartments
 Varicose veins occur when the walls of the veins near the valves become weakened or
stretched and the valves do not work properly; blood pools in the veins and vessels
become distended
 Mechanisms for Venous Return:
 Smooth muscle in veins
o Innervated by sympathetic neurons which cause contraction smooth muscle to
increase pressure
 Skeletal muscle pump
o Compresses veins
o Venous pressure increases, forcing more blood back to heart
 Respiratory pump (will talk about more in respiration)
o Inspiration causes an increase in venous return
 Venous Return and the Frank-Starling Law:
 Relationship between venous return and the Frank-Starling law:
o Skeletal muscle pump, respiratory pump and increased sympathetic activity to
venous smooth muscle will increase venous return by increasing venous
pressure
o Increased venous return to the heart will increase the end-diastolic volume
o ……now we have the Frank Starling mechanism: increase EDV → increase
cardiac fiber length → increase force during contraction → increase SV

Lecture 7 recording 27: The Lymphatic System

 The Lymphatic System:

 There is more filtration than absorption along the length of a capillary; the excess fluid is
returned to the circulatory system by the lymphatic system
 Components of the Lymphatic System:
 Lymphatic system → consists of a system of small organs, called lymph nodes, and
tubes, called, lymphatic vessels, through which lymph flows
 Lymphatic capillaries:
o Distinct from blood capillaries
 o Also made of only a single layer of endothelial cells resting on a basement
membrane
o Have large water-filled channels that are permeable to all interstitial fluid
components, including proteins
o No tubes flow into them (ie they have a round ‘end’)
o Interstitial fluid enters the lymphatic capillaries through bulk flow
 Lymphatic capillaries empty into lymph vessels
 Lymph vessels contain one-way valves to ensure that lymph flows in one direction only:
into the right atrium
 Lymph passes through lymph nodes which play a role in defense and are part of the
immune response
 Components of the Lymphatic System:
 Lymphatic capillaries:
o Closed ended (no vessels flow into them)
o Extend into the interstitial space surrounding tissue cells
o Thin walls to allow tissue fluid, or interstitial fluid, to enter the lymphatic
capillaries
 The fluid is called lymph once it enters the lymphatic system
 Mechanism of Blood Flow:
 The lymph system returns interstitial fluid to the circulatory system, along with small
amounts of plasma proteins that have escaped the blood vessel capillaries
 Mechanisms that contribute to the flow of lymph within the lymphatic system:
o Lymph vessels beyond the lymphatic capillaries have smooth muscle
 Generates rhythmic contractions, responds to stretch, innervated by the
sympathetic nervous system
o One-way valves
o Skeletal muscle contractions
o Respiratory pump

Lecture 7 recording 28: Blood Pressure

 Arterial Blood Pressure:

 Blood pressure is determined by the volume of blood in the vessels and the compliance
of a vessel
o Compliance → ability of a vessel to distend and increase volume with increasing
transmural pressure, which is the pressure inside the vessel minus the pressure
outside the vessel
 Compliance = ΔVolume/ ΔPressure (Δ = change) (do not memorize this
formula)
 The greater the compliance of a vessel, the more easily it can be
stretched
 During systole, the ventricle pumps blood into the adjacent artery
o Approximately 1/3rd of the volume of blood ejected by the ventricle leaves the
artery; the remainder of the stroke volume remains in the arteries during
systole, distending the arterial walls and increasing the arterial pressure
 o When ventricular contraction ends, the stretched arterial walls recoil passively,
and blood continues to be driven into the arterioles during diastole, even
though no new blood is entering the artery from the ventricle
o This passive recoil maintains perfusion through the capillaries while the
ventricles are in diastole
o As blood leaves the arteries, the arterial volume and pressure slowly decrease
o The next ventricular contraction occurs while the artery walls are still stretched
by the remaining blood and this means that the arterial pressure does not
decrease to zero
 Large arteries (aorta) act as pressure reservoirs due to their elastic recoil and maintain
blood flow while the ventricles relax
 Arteries are compliant (but not as compliant as veins)
 Arterial Blood Pressure:
 Systolic pressure → the maximum arterial pressure reached during peak ventricular
ejection
 Diastolic pressure → the minimum arterial pressure reached just before ventricular
ejection begins
 Arterial pressure is generally recorded as systolic pressure divided by diastolic pressure
 Pulse pressure → systolic pressure minus the diastolic pressure (PP = SP – DP)
 Blood Pressure:

(You do not need to memorize this table or the symptoms of high or low blood pressure
talked about in this slide)

 120/80 mmHg is normal blood pressure

 Hypertension → is defined as chronically increased arterial blood pressure, or high
blood pressure
 Hypotension → abnormally low arterial blood pressure
 Mean Arterial Pressure (MAP):
 Blood pressure changes during the cardiac cycle
o Maximal during systole and minimal during diastole, that is it is pulsatile
 MAP = diastolic pressure + (pulse pressure/3) (do not memorize this formula)
 MAP is the pressure driving blood into the tissues averaged over the cardiac cycle
(Remember: you need pressure to create flow)
o At pressures below 60 mmHg the tissue cells in the body will not get sufficient
blood and the oxygen and nutrients they need
 The blood pressure is pulsatile as the blood leaves the heart, that is, it increases and
decreases during systole and diastole
o The aorta is very compliant and dampens (or reduces) the pulsatile output of
the left ventricle, thereby reducing the pulse pressure
o As the distance from the heart increases, the pulse pressure decreases due to
the cumulative effects of elastic rebound along the arterial system
 At the level of the aorta we see very large waves, but at the level of the
arterioles the waves become smaller and smaller until they disappear
  The pressure surge from the ventricles is absorbed as it moves along the
arterial system and eventually disappears at the level of the arterioles
 No pressure oscillations are seen in the capillaries
 Mean Arterial Pressure (MAP):
 MAP decreases as the distance from the heart increases
 The largest drop in pressure occurs at the level of the arterioles
o The large pressure drop is due to the high resistance of the arterioles
o Arterioles are small diameter arteries and provide resistance to blood flow, can
alter state of constriction of smooth muscle

Lecture 7 recording 29: Factors Controlling Mean Arterial Pressure

 Mean Arterial Pressure:

 Maintaining sufficient mean arterial pressure is a prerequisite for ensuring adequate
perfusion or blood flow to all our organs and tissues
 MAP is maintained within a specific range
o Too low a blood pressure would mean that tissues of the body would not
receive sufficient oxygen and nutrients, and waste products would accumulate
o Chronically high blood pressure can cause damage to the arteries, the heart and
kidneys, along with other organs in the body
 Mean systemic arterial pressure (MAP) is the arithmetic product of two factors:
o MAP = CO x TPR
 CO = cardiac output
 TPR = total peripheral resistance
 CO and TPR are the main factors used to calculate the mean arterial
pressure
 TPR is the combined resistance to flow of all the systemic blood vessels
o Note: Systemic blood vessels and not pulmonary vessels as the pulmonary
circulation provides little resistance to flow
o Friction between the blood and the walls of the blood vessels produces
resistance, which impedes blood flow
 Factors that alter total peripheral resistance alter blood flow
o Major site of resistance in the systemic circuit → arterioles
 Changes in TPR are due primarily to changes in the resistance of the
arterioles
 TPR is determined primarily by total arteriolar resistance
 Blood flowing through arterioles experiences resistance as it
contacts the arteriolar wall, as they have a small diameter, and
the pressure drop through the arterioles will be great
 Summary of Factors Controlling MAP:

(This slide is a summary of all the concepts we have looked at so far. As you go through this
slide, think about each of those concepts)
Lecture 7 recording 30: Cardiovascular Regulatory Mechanisms

 Regulation of Mean Arterial Pressure:

 Short-term regulation:
o Seconds to hours
o Baroreceptors reflexes modify the activity of autonomic nerves supplying the
heart and blood vessels as well as changes in the secretion of hormones
o Adjusts cardiac output (CO) and total peripheral (TPR) resistance by ANS
 Long-term regulation:
o Adjust blood volume
o Restore normal salt and water balance through mechanisms that regulate urine
output and thirst
 Arterial Baroreceptors:
 Arterial baroreceptors are mechanoreceptors that detect changes in your blood
pressure
o Carotid sinus and the aortic arch baroreceptors
o Respond to changes in MAP as well as changes in pulse pressure
 Respond to changes in pressure when the walls of the vessel stretch and
relax
 Pulse pressure is the difference between the systolic and the diastolic
pressures
 Afferent neurons travel from the baroreceptors to the brainstem and provide input to
the neurons of the cardiovascular control center
 Baroreceptor Action Potential Frequency:
 The rate of discharge of the carotid sinus baroreceptor is directly proportional to the
MAP
 Baroreceptor Action Potential Frequency:
 The baroreceptors continuously generate action potentials in response to ongoing
pressure in the arteries
 An increase in will increase the frequency of action potentials generated by the
baroreceptors
 A decrease in MAP will decrease the frequency of firing of the baroreceptors
 An increase in pulse pressure can occur with the calculated MAP still being normal
o An increase in pulse pressure will cause an increase in the overall action
potential frequency
 The Medullary Cardiovascular Center:
 Medullary cardiovascular center:
o Located in the medulla oblongata in the brainstem
o The neurons in this center receive input from the baroreceptors which
determines the frequency of action potentials sent from the medullary
cardiovascular center to alter vagal stimulation (parasympathetic) to heart and
sympathetic innervation to heart, arterioles and veins
o Increase in arterial pressure → increase the rate of firing of the arterial
baroreceptors → signals medullary cardiovascular center to decrease
 sympathetic activity to the heart, arterioles and veins, and increase
parasympathetic neuron activity to the heart → decrease the arterial pressure
 Baroreceptors adapt to sustained changes in arterial pressure
o Only used for short term regulation of blood pressure
 Other Reflexes:
o Chemoreceptors primarily function to regulate respiratory activity
 Aortic and carotid bodies (We will look at in respiration; do not need to
know for cardiovascular section)