Physiology

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Physiology

• Cardiovascular System

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Cardiac Muscle Heart

• Review heart and circulatory system anatomy
• Heart muscle cells
• 99 contractile
• 1 autorrhythmic

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Cardiac Muscle and the Heart

• Myocardium
• Heart muscle
• Sits in the media stinum of the thoracic cavity
• Left Axis Deviation
• May have a right axis deviation with obesity
  and/or pregnancy
• May hang in the middle of the thoracic cavity if
  the individual is very tall

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The Heart

• The heart has four chambers
• Right and left atrium
• Atria is plural
• Right and left ventricle

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Blood Flow Through the Heart

• Deoxygenated blood enters the right atrium of the
  heart through the superior and inferior vena cava
• Deoxygenated blood
• Has less than 50 oxygen saturation on hemoglobin

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The systemic circulation

• Receives more blood than the pulmonary
  circulation does
• Receives blood from the left ventricle
• Is a high pressure system compared to the
  pulmonary circulation
• Both (b) and (c) above are correct
• All of the above are correct

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The chordae tendinae

• Keep the AV valves from opening in the opposite
  direction during ventricular contraction
• Hold the AV valves during diastole
• Hold the right and left ventricles together
• Transmit the electrical impulse form the atria to
  the ventricles
• Contract when the ventricles contract

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The aortic valve prevents backflow of blood from
the aorta into the left ventricle during
ventricular diastole

• True
• False

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A mammalian heart has __________ chamber(s)

• One
• Two
• Three
• Four

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Hemoglobin

• Quaternary Structure
• Four Globin proteins
• Globin carries CO2, H, PO4
• Four Heme attach to each Globin
• Heme binds O2 and CO
• Heme contains an Iron ion
• About 1 million hemoglobin molecules per red
  blood cell
• Oxygen carrying capacity of approximately 5
  minutes

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Heart Valves Ensure One-Way Flow of Blood in the
Heart

• Atrioventricular Valves
• Located between the atria and the ventricle
• Labeled Right and Left
• Right Valve is also called Tricuspid
• Left Valve is also called Bicuspid or Mitral

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Heart Valves

• Papillary muscles are attached to the chordae
  tendinae
• Chordae tendinae are also connected to the AV
  valves
• Just prior to ventricular contraction the
  papillary muscles contract and pull downward on
  the chordae tendinae
• The chordae tendinae pull downward on the AV
  valves
• This prevents the valves from prolapsing and
  blood regurgitating back into the atria.

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Follow Path of Blood through Heart
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Blood Flow

• Due to gravity deoxygenated blood enters the
  right/left atrium (by way of the pulmonary veins)
  and flows through the open AV valve directly into
  the ventricles
• The filling of the ventricles with blood pushes
  the AV valve upward
• They are held in place by the chordae tendinae
• Right before the valves shuts completely the
  atria contract from the base towards the apex of
  the heart in order to squeeze more blood into the
  ventricle
• The AV valves snapping shut creates the Lub
  sound of the heart beat

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Blood Flow

• When the AV valves are shut the Pulmonary and
  Aortic semi-lunar valves are also shut
• Diastole
• Quiescence of the heart

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Myocardial Contraction (Systole)

• After Diastole occurs the ventricles begin to
  contract from the apex towards the base of the
  heart
• The deoxygenated blood on the right side of the
  heart is pushed through the pulmonary trunk after
  opening the semi-lunar valve to the pulmonary
  arteries into the lungs to become oxygenated.
• The oxygenated blood on the left side of the
  heart is pushed through the aorta after opening
  the semi-lunar valve into the systemic circulation

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Blood Flow

• The Ventricles do not have enough pressure to
  push all of the blood out of the pulmonary trunk
  and aorta
• The blood falls back down due to gravity
• The semi-lunar valves snap shut
• The Dup sound of the heart beat

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Blood Flow

• Blood is always flowing from a region of higher
  pressure to a region of lower pressure

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Atrial and Ventricular Diastole

• The heart at rest
• The atria are filling with blood from the veins
• The ventricles have just completed contraction
• AV valves are open
• Blood flow due to gravity

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Atrial Systole Completion of Ventricular Filling

• The last 20 of the blood fills the ventricles
  due to atrial contraction

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Early Ventricular Contraction

• As the atria are contracting
• Depolarization wave moves through the conducting
  cells of the AV node down to the Purkinje fibers
  to the apex of the heart
• Ventricular systole begins
• AV Valves close due to Ventricular pressure
• First Heart Sound
• S1 Lub of Lub-Dup

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Isovolumic Ventricular Contraction

• AV and Semilunar Valves closed
• Ventricles continue to contract
• Atrial muscles are repolarizing and relaxing
• Blood flows into the atria again

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Ventricular Ejection

• The pressure in the ventricles pushes the blood
  through the pulmonary trunk and aorta
• Semi-lunar valves open
• Blood is ejected from the heart

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Ventricular Relaxation and Second Heart Sound

• At the end of ventricular ejection
• Ventricles begin to repolarize and relax
• Ventricular pressure decreases
• Blood falls backward into the heart
• Blood is caught in cusps of the semi-lunar valve
• Valves snap shut
• S2 Dup of lub-dup

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Isovolumetric Ventricular Relaxation

• Semilunar valves close
• AV valves closed
• The volume of blood in the ventricles is not
  changing
• When ventricular pressure is less than atrial
  pressure the AV valves open again
• The Cardiac Cycle begins again

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Cardiac Circulation

• Blood flowing through the heart has a high fat
  content
• Curvature as well as diameter of the arteries is
  important to blood flow through the heart
• Vasoconstriction due to sympathetic nervous
  system input
• Norepinephrine/Epinephrine
• Alpha Receptors not Beta

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Myocardial Infarction

• Heart Attack
• Due to plaque build up in the arteries
• Decrease in blood flow to myocardium
• Depolarization of muscle cannot occur due to
  myocardial death
• Myocardium doesnt work as a syncytium any longer
• Destruction of gap junction or connexons

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Atherosclerosis

• Plaque in the arteries
• Elevated Cholesterol in the blood
• Cholesterol is cleared by the liver
• HDL High Density Lipoprotein
• H for healthy
• LDL Low Density Lipoprotein
• L for Lethal
• Omega 3 fatty acids
• Rotorooter for the arteries

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If a Patient Has a Left Atrial Infarction Then

• What happens to heart contraction and blood flow
  through the heart?
• What type of outward problems might your patient
  have?
• What recommendations might you give the patient
  to live a better life?
• There are some things they better not do or they
  will die. What are these things (in general)?

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Angioplasty/Open Heart Surgery
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Unique Microanatomy of Cardiac Muscle Cells

• 1 of cardiac cells are autorhythmic
• Signal to contract is myogenic
• Intercalated discs with gap junctions and
  desmosomes
• Electrical link and strength
• SR smaller than in skeletal muscle
• Extracelllar Ca2 initiates contraction (like
  smooth muscle)
• Abundant mitochondria extract about 80 of O2

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Cardiac Muscle Cells Contract Without Nervous
Stimulation

• Autorhythmic Cells
• Pacemaker Cells set the rate of the heartbeat
• Sinoatrial Node
• Atriventricular Node
• Distinct from contractile myocardial cells
• Smaller
• Contain few contractile proteins

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Excitation-Contraction (EC) Coupling in Cardiac
Muscle

• Contraction occurs by same sliding filament
  activity as in skeletal muscle
• some differences
• AP is from pacemaker (SA node)
• AP opens voltage-gated Ca2 channels in cell
  membrane
• Ca2 induces Ca2 release from SR stores
• Relaxation similar to skeletal muscle
• Ca2 removal requires Ca2 -ATPase (into SR)
  Na/Ca2 antiport (into ECF)
• Na restored via?

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Cardiac Contraction

• Action Potentials originate in Autorhythmic Cells
• AP spreads through gap junction
• Protein tunnels that connect myocardial cells
• AP moves across the sarcolemma and into the
  t-tubules
• Voltage-gated Ca 2 channels in the cell membrane
  open
• Ca 2 enters the cell which then opens ryanodine
  receptor-channels
• Ryanodine receptor channels are located on the
  sarcoplasmic reticulum and Ca 2 diffuses into
  the cells to spark muscle contraction
• Cross bridge formation and contraction occurs

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Myocardial Contractile Cells

• In the myocardial cells there is a lengthening of
  the action potential due to Ca 2 entry

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APs in Contractile Myocardial Cells

• Phase 4 Resting Membrane Potential is -90mV
• Phase 0 Depolarization moves through gap
  junctions
• Membrane potential reaches 20mV
• Phase 1 Initial Repolarization
• Na channels close K channels open
• Phase 2 Plateau
• Repolarization flattens into a plateau due to
• A decrease in K permeability and an increase in
  Ca 2 permeability
• Voltage regulated Ca 2 channels activated by
  depolarization have been slowly opening during
  phases 0 and 1
• When they finally open, Ca 2 enter the cell
• At the same time K channels close
• This lengthens contraction of the cells
• AP 200mSec or more
• Phase 3 Rapid Repolarization
• Plateau ends when Ca 2 gates close and K
  permeability increases again

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Myocardial Autorhythmic Cells

• Anatomically distinct from contractile cells
  Also called pacemaker cells
• Membrane Potential 60 mV
• Spontaneous AP generation as gradual
  depolarization reaches threshold
• Unstable resting membrane potential ( pacemaker
  potential)
• The cell membranes are leaky
• Unique membrane channels that are permeable to
  both Na and K

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Myocardial Autorhythmic Cells, contd.
If-channel Causes Mem. Pot. Instability

• Autorhythmic cells have different membrane
  channel If - channel
• If channels let K Na through at -60mV
• Na influx gt K efflux
• slow depolarization to threshold

allow current ( I ) to flow
f funny researchers didnt understand
initially
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Myocardial Autorhythmic Cells, contd. Pacemaker
potential starts at -60mV, slowly drifts to
threshold
AP
Heart Rate Myogenic Skeletal Muscle contraction
?
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Myocardial Autorhythmic Cells, contd.
Channels involved in APs of Cardiac Autorhythmic
Cells

• Slow depolarization due to If channels
• As cell slowly depolarizes If -channels close
  Ca2 channels start opening
• At threshold lots of Ca2 channels open ? AP to
  20mV
• Repolarization due to efflux of K

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Autorhythmic Cells

• No nervous system input needed
• Unstable membrane potential
• -60mV
• Pacemaker potential not called resting membrane
  potential
• At -60mV If (funny) channels permeable to K
  and Na open
• Na influx exceed K efflux
• The net influx of positive charge slowly
  depolarizes the autorhythmic cells
• As the membrane becomes more positive the If
  channels gradually close and some Ca 2 channels
  open
• The influx of Ca 2 continues the depolarization
  until the membrane reaches threshold
• At threshold additional Ca 2 channels open
• Calcium influx creates the steep depolarization
  phase of the action potential
• At the peak of the action potential Ca 2
  channels close and slow K channels open
• Repolarization of the autorhythmic action
  potential is due to the efflux of K

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Cardiac Muscle Cell Contraction is Graded

• Skeletal muscle cell all-or-none contraction in
  any single fiber for a given fiber length. Graded
  contraction in skeletal muscle occurs through?
• Cardiac muscle
• force ?? to sarcomere length (up to a maximum)
• force ? to of Ca2 activated crossbridges
  (Function of intracellular Ca2 if Ca2in low
  ? not all crossbridges activated)

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Length Tension Relationship
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Autonomic Neurotransmitters Modulate Heart Rate

• The speed at which pacemaker cells depolarize
  determines the rate at which the heart contracts
• The interval between action potentials can be
  altered by changing the permeability of the
  autorhythmic cells to different ions
• Increase Na and Ca 2 permeability speeds up
  depolarization and heart rate
• Decrease Ca 2 permeability of increase K
  permeability slow depolarization and slows heart
  rate

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Autonomic Neurotransmitters Modulate Heart Rate

• The Catecholamines norepi and epi increases ion
  flow through If and Ca2 channels
• More rapid cation entry speeds up the rate of the
  pacemaker depolarization
• ?1-adrenergic receptors are on autorhythmic cells
• cAMP second messenger system causes If channels
  to remain open longer

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Autonomic Neurotransmitters Modulate Heart Rate

• Parasympathetic neurotransmitter (Acetylcholine)
  slows heart rate
• Ach activates muscarinic cholinergic receptors
  that
• Increase K permeability and
• Decrease Ca2 permeability

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Electrical Conduction in the Heart Coordinates
Contraction

• Action potential in an autorhythmic cell
• Depolarization spread rapidly to adjacent cells
  through gap junctions
• Depolarization wave is followed by a wave of
  contraction across the atria from the sinoatrial
  node on the right side of the heart across to the
  left side of the heart and then from the base to
  the apex
• From AV nodes to the atrioventricular bundle in
  the septum (Bundle of His)
• Left and right bundle branches to the apex
• Purkinje Fibers through the ventricles branches
  from apex to base and stopping at the
  atrioventricular septum

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Pacemakers Set the Heart Rate

• SA Node is the fastest pacemaker
• Approximately 72 bpm
• AV node approximately 50 bpm
• Bundle Branch Block
• Complete Heart Block

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In order to increase heart rate at the SA node

• Potassium permeability across the membrane must
  increase
• Sodium permeability across the membrane must
  increase
• Potassium impermeability across the membrane must
  increase
• Sodium impermeability across the membrane must
  increase

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The neurotransmitter responsible for increasing
potassium permeability at the SA node is

• Norepinephrine
• Epinephrine
• Acetylcholine
• Serotonin

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The initiation of the heartbeat normally
originates from the

• Atrio-ventricular (A-V) node of the heart
• Sino-atrial (SA) node of the heart
• Central nervous system
• Thyroid

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Electrocardiogram

• Einthovens triangle
• Electrodes are attached to both arms and left leg
  to form a triangle
• Lead I- negative electrode attached to right arm
• Lead II positive electrode attached to left arm
• Lead III Ground attached to the left leg

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Electrocardiogram ECG (EKG)

• Surface electrodes record electrical activity
  deep within body - How possible?
• Reflects electrical activity of whole heart not
  of single cell!
• EC fluid salt solution (NaCl) ? good
  conductor of electricity to skin surface
• Signal very weak by time it gets to skin
• ventricular AP ? mV
• ECG signal amplitude 1mV
• EKG tracing ? of all electrical potentials
  generated by all cells of heart at any given
  moment

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ECG

• P wave
• Depolarization of the atria
• Atrial contraction begins almost at the end of
  the P wave
• QRS complex
• Ventricular depolarization
• Ventricular contraction begins just after the Q
  wave and continues through the T wave
• T wave
• Ventricular repolarization

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ECG

• PQ or PR segment
• Conduction through AV node and AV bundle
• Q wave
• Conduction through bundle branches
• R wave
• Conduction beginning up the Purkinje Fibers
• S wave Conduction continue up half way
• ST segment
• Conduction up the second half of Ventricles

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ECG

• When an electrical wave moving through the heart
  is directed toward the positive electrode, the
  ECG waves goes up from the baseline
• If net charge movement through the heart is
  toward the negative electrode, the wave points
  downward

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Einthovens Triangle and the 3 Limb Leads
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Why neg. tracing for depolarization ??
Net electrical current in heart moves towards
electrode EKG tracing goes up from baseline
Net electrical current in heart moves towards
- electrode EKG tracing goes Down from
baseline
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Info provided by EKG

• HR
• Rhythm
• Relationships of EKG components
• each P wave followed by QRS complex?
• PR segment constant in length? etc. etc.

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For the Expert

• Find subtle changes in shape or duration of
  various waves or segments.
• Indicates for example
• Change in conduction velocity
• Enlargement of heart
• Tissue damage due to ischemia (infarct!)

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Prolonged QRS complex
Injury to AV bundle can increase duration of QRS
complex (takes longer for impulse to spread
throughout ventricular walls).
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Heart Sounds (HS)

• 1st HS during early ventricular contraction ?
  AV valves close
• 2nd HS during early ventricular relaxation ?
  semilunar valves close

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Gallops, Clicks and Murmurs
Turbulent blood flow produces heart murmurs upon
auscultation
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Ectopic focus is the place where

• An abnormally excitable area of the heart
  initiates a premature action potential
• All of the electrical impulses of the heart
  normally terminate
• An ECG lead is attached on the outside of the
  chest
• A heart valve is attached
• The chordae tendineae attach to a valve

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During isovolumetric ventricular contraction

• Rapid filling of the ventricles occurs
• No blood enters or leaves the ventricles
• The maximum volume of blood is ejected
• The maximum rate of ejection occurs
• None of the above is correct

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The type of intercellular junction that connects
cardiac muscle fibers and allows for direct,
electrical synapsing is known as a

• Tight junction
• Desmosome
• Plasmodesmata
• Gap junction

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Cardiac muscle

• Has a shortening velocity that is greater than
  that of glycolytic (white) skeletal muscle fibers
• Has a more extensive sarcoplasmic reticulum than
  skeletal muscle
• Is an electrical syncytium
• Has a resting potential that depends mainly on
  sodium distribution
• All of the above are correct

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Spontaneous depolarization of the sinoatrial node
is produced by

• An inward leak of sodium and an increase in the
  outward leak of potassium
• An inward leak of sodium and a decrease in the
  outward leak of potassium
• Opening of fast sodium channels and a decrease in
  the outward leak of potassium
• Opening of fast sodium channels and an increase
  in the outward leak of potassium
• Neural impulses from the sympathetic nerves

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A heart murmur is characterized by

• Rapid heart contraction
• Irregular heart contraction
• Mitral valve prolapse
• Semilunar valve dysfunction

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The P wave of a normal electrocardiogram indicates

• Atrial depolarization
• Ventricular depolarization
• Atrial repolarization
• Ventricular repolarization

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Damage to the _______ is referred to as heart
block

• SA node
• AV node
• AV bundle
• AV valve

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Stenosis of the mitral valve may initially cause
a pressure increase in the

• Vena cava
• Pulmonary circulation
• Left ventricle
• Coronary circulation

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The tricuspid valve is closed

• While the ventricle is in diastole
• By the movement of blood from the atrium to
  ventricle
• By the movement of blood from atrium to ventricle
• While the atrium is contracting
• When the ventricle is in systole

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Plumbing 101Resistance Opposes Flow

• 3 parameters determine resistance (R)
• Tube length (L)
• Constant in body
• Tube radius (r)
• Can radius change?
• Fluid viscosity (? (eta))
• Can blood viscosity change??

Poiseuilles law
? R ? 1 / r4
Blood Flow Rate ? ?P/ R
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Velocity (v) of Flow

• Depends on Flow Rate and Cross-Sectional Area
• Flow rate (Q) volume of blood passing one
  point in the system per unit of time (e.g.,
  ml/min)
• If flow rate ? ? velocity ?
• Cross-Sectional area (A) (or tube diameter)
• If cross sectional area ? ? velocity ?

v Q / A
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Blood Flow

• Mechanistic Because the contractions of the
  heart produce a hydrostatic pressure gradient and
  the blood wants to flow to the region of lesser
  pressure. Therefore, the Pressure gradient (?P)
  is main driving force for flow through the
  vessels
• Blood Flow Rate ? ?P/ R

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Pressure

• Hydrostatic pressure is in all directions
• Measured in mmHg The pressure to raise a 1 cm
  column of Hg 1 mm
• Sphygmomanometer
• Flow is produce by Driving Pressure
• Pressure of fluid in motion decreases over
  distance because of energy loss due to friction

Blood Flow Rate ? ?P/ R