Physiology Exam 2 Lecture Objectives

Cardiovascular System and Cardiac Action Potential:

1. Major components of cardiovascular system and describe major functions
a. Heart
b. Blood Vessels
c. Closed-2-circuit system
d. Right Heart:
i. Receives deoxygenated blood from veins
ii. Goes to pulmonary circuit
e. Left heart:
i. Receives oxygenated blood from pulmonary circuit
ii. Goes to systemic circuit
2. Hearts function as dual pump and 4 chambers of heart:
a. Dual Pump:
i. Pulmonary
ii. Systemic
b. 4 Chambers:
i. Right Atria: receives deoxygenated blood from veins
ii. Right Ventricle: sends deoxygenated blood to pulmonary circuit
iii. Left Atria: receives oxygenated blood from pulmonary circuit
iv. Left Ventricle: pumps oxygenated blood to systemic circuit
3. Difference between left and right heart function, understand physiological reasons and
consequences of these differences

a. Cardiac output remains 100% from right to left heart

b. Once output leaves left heart, it allocates various amounts to organs
i. Changes with physical activity
ii. More blood to skeletal muscles during exercise
c. Normal Output: 5L/min (5 L * 60min/hr * 24 hr/day = 7200 L/day)
d. Exercise Output: 25L/min
4. Differences in blood vessel composition and how these differences affect function of
vessels in cardiovascular system
a. Aorta: (classified as an artery)
i. Large vessel diameter
ii. Diameter: 25 mm
iii. Thickness: 2 mm
iv. Composition is mostly Elastic Fibers:
1. Need withstand large amounts of blood from Left Ventricle
b. Artery (elastic vessels)
i. Composition mainly Elastic Fibers + Smooth Muscle
ii. Vessel Diameter: 4mm (medium artery)
iii. Thickness: 1mm (medium artery)
c. Arterioles (resistance vessels)
i. Composition mostly Smooth Muscle
1. Responsible for changes in wall thickness
2. Relaxed lumen increases more blood flow
ii. 60% resistance of CVS is at arterial level
iii. Diameter: 30 micrometers
iv. Thickness: 20 micrometers
d. Capillary (exchange vessel)
i. Gas exchange with O2 and CO2
ii. Made of Endothelium
iii. Smallest Vessels
e. Venules:
i. Collage Fibers > Endothelium
ii. Carry blood into veins
f. Veins (reservoir vessels)
i. Very large diameter
ii. Less elastic than arteries, mostly smooth muscle, then collagen
iii. Similar in size to large artery like aorta
iv. During metabolic stress, body uses this reservoir of blood
v. Diameter: 20 mm
vi. Thickness: 1 mm

g. Relationship between BP, Cross-Sectional Area, Velocity of Blood Flow:

i. BP:
1. High: arterial circulation
2. Low: venous circulation
3. Pulsatile flow in arterial circulation due to contraction/relaxation of
heart, but dies down in venous circulation
ii. Velocity & CSA:
1. Inverse relationship between CSA and velocity
2. Capillaries have most CSA, but lowest velocity
3. Aorta has more blood flow velocity than Vena Cava

5. Compare/contract pacemaker and non-pacemaker cardiac action potentials: area in

heart they are present, ionic mechanism responsible for resting potential, ionic currents
underlying 5 phases of action potential, difference between pacemaker and nonpacemaker AP.
a. Pacemaker: spontaneously fires action potentials (automaticity)
i. SA and AV Nodes

Phase 4: Pacemaker potential

NOT resting potential
Slow diastolic depolarization because
of slow influx of Na+
Phase 0: Ca2+ channels open
Slow b/c Ca2+ channels slow
Phase 3: delayed rectifying K+ channels open

b. Cardiac (Contractile) Cells: respond to electrical activity (refractory period)

i. Conductivity: ability of heart of conduct action potential from site of origin to
cardiac cells illustrates functional syncytium
ii. Atria and Ventricular Muscles

Phase 0: fast because Na channel opens

Phase 2: L-type DHPR Ca2+ channels open
allows longer repolarization
K+ ions still moving out
Phase 3: Ca2+ channels close
Phase 4: inward rectify K+ channels open

c. Purkinje Fibers: mix of slow and fast response action potential

i. Type of Pacemaker Cell

d.

Ionic Mechanism for Resting Potential:

i. Na+, Ca2+, Cl- are higher extracellularly
ii. K+ is higher intracellularly

6. Cardiac refractory period and phases. Importance to normal electrical activation and
contraction of heart
a. 2 Phases of Cardiac Refractory Period:
i. Effective Refractory Period
1. Absolute Refractory Period
a. Almost full duration of contractile cell action potential
b. Cannot generate a new action potential
2. Relative Refractory Period:
a. Can generate a new action potential, but needs greater stimulus
ii. Supranormal Refractory Phase (vulnerable phase)
1. Ions almost completely recovered from initial activation
2. Normal action potential can occur
3. Allows action potential to fire at earlier rate
b. Length of AP: 150-250 ms:
i. Able to prevent tetanus
ii. Allows blood to fill heart
c. Allows time for recovery for ion channels to be activated when next stimulus is
applied

7. List cardiac pacemakers. Why sinus node is normal pacemaker of heart

a. SA (sinus node):
i. Normal pacemaker of heart
1. Drives heart rate
2. Creates Overdrive Suppression: fastest pacemaker suppresses the other
two slower pacemakers
3. Fastest pacemaker (70-80 AP/min)
4. If SA injured or dies, AV node is now fastest, thus it will control
normal heart rate
ii. Fires initial AP, which travels to ventricles through muscle structure
(functional syncytium)
1. Intercalated disks allow cardiac myocytes to act as functional
syncytium
2. Intercalated Disks: desmosomes + gap junctions
3. Gap Junction allows flow of current
b. Pacemakers:
i. Sinoatrial (SA) Node (located: atria)
ii. Atrioventricular (AV) Node (atria)
iii. Purkinje Fibers (ventricles)

8. Effects of sympathetic and parasympathetic innervation on Heart Rate, Conduction

Velocity, and Contractility.
a. Sympathetic:
i. Heart Rate:
ii. Conduction Velocity:
iii. Contractility:
b. Parasympathetic:
i. Heart Rate:
ii. Conduction Velocity:
iii. Contractility: ?
c. Autonomic Control (ANS) is done through G protein
d. Parasympathetic Postganglionic synapses on Heart
i. Ach released bind to muscarinic receptors (M2)
ii. G-protein activated, specifically Gi (for heart)
iii. Decreases action potential firing rate
iv. Pacemaker potential becomes hyperpolarized
1. K+ efflux, Ca2+ influx
2. Longer to reach threshold
v. Typically, Vagus Nerve (CN X)
e. Sympathetic Postsynaptic synapse on Heart
i. NE released binds to 1 receptors
ii. Activates Gs cascade
iii. Increases action potential firing rate
iv. Pacemaker potential becomes more polarized:
1. Na+ and Ca2+ influx
2. Faster to threshold

Electrical Activity of the Heart:

1. Specialization conduction pathways and cardiac muscle depolarization in heart
a. Initial start: pacemaker (SA node)
b. Functional Syncytium due to intercalated discs
c. SA Node AV Node (right atrium) Bundle of HIS Left/Right Bundle
Branches Purkinje Fibers (responsible for ventricles)
i. From right atrium, impulse go to left atrium also
ii. Malfunction from SA to AV node could cause ventricles to not contract

2. Compare conduction velocities in different areas of heart

a. AV Node:
i. Slowest:
1. gives atria time to depolarize and contract
2. Parasympathetic control at AV and SA node
b. Purkinje:
i. Fastest
c. Fast Response due to voltage gated Na+ channels
d. Slow response due to Ca2+ channels
e. Speed of electrical conduction due to speed of tissue
depolarization

3. Relationship between action potential and electrocardiogram (ECG).

a. ECG: represents multiple actions potentials taking place in heart within period of time
b. Action potential: intracellular recording of electrical activity in one cell
c. ECG:
i. X axis: heart rate
ii. Y axis: voltage
4. Describe, label, and explain waves, complexes, segments, and intervals on normal ECG
a. Waves: upward or downward deflection in isoelectric line
i. P Wave: atrial depolarization
ii. QRS Complex: ventricular depolarization (includes atria repolarization)
iii. T Wave: ventricular repolarization
b. Segment: isoelectric line only
i. PR Segment: from end of P wave to beginning of QRS complex
ii. ST Segment: from end of QRS complex to beginning T wave
c. Intervals: both waves and segments together
i. PR Interval:
1. 0.12-0.2 sec.
2. Beginning of P wave to beginning of QRS complex
3. Time for action potential from SA to AV Node
ii. QRS Interval:
1. 0.06-0.1 sec
2. Beginning to end of QRS complex
3. Ventricular depolarization
4. Used to diagnose Heart Block
iii. QT Interval:
1. <0.42 secs
2. Beginning QRS complex to end of T wave
3. Represents complete activation of ventricles

5. Normal calibration and units of measurement on ECG

a. ECG Paper Calibration
i. Small box = 0.04 secs. / 0.1 mV
ii. Large box = 0.2 secs / 0.5 mV
iii. 5 Large Boxes = 1 sec / 1mV

6. List abnormalities an EG is capable of detecting and how such abnormalities alter

appearance of ECG
a. Arrhythmia: abnormality in origin (initiation) and/or conduction (propagation) of
cardiac impulse
i. 5 Types:
1. Normotopic: electrical impulse originates at SA Node but is too fast,
slow or irregular
a. Sinus Bradycardia: too slow
b. Sinus Tachycardia: too fast
c. Sinus Arrhythmia: irregular
2. Ectopic: originates from another area (focus) than SA Node
a. Result from:
i. Failure of normal pacemaker
ii. Ectopic focus fires at rate higher than SA node
b. Premature Beats: ectopic foci generate action potentials at rate
higher than SA node
i. Premature Atrial Depolarization Abnormal P wave
ii. Premature Ventricular Depolarization
c. Supraventricular Tachycardia:
i. Sustained ectopic arrhythmia rapid heart rate
ii. Caused by electrical impulses from above ventricles
3. Re-entrant: electrical impulse moves in continuous pattern determined
by changes in anatomical arrangement
4. Conduction Block: electrical impulse originates at SA, follows usual
conduction path, but has unexpected blocks and delays
5. Pre-excitation Syndromes: electrical activity moves in accessory
pathways, providing shortcut
a. Ex: Wolf-Parkinson White Syndrome
b. Normal Heart Rate: 60-100 beats/min 3-5 large boxes
i. Measure from R to R wave intervals
ii. Tachycardia: < 3 boxes
iii. Bradychardia: > 5 boxes
iv. Irregular: various boxes between R to R intervals during each cycle
c. AV Junctional Heart Blocks
i. Blocks in impulse propagation at level of AV Node
ii. First Degree (AV) Block:
1. Action potentials conducted through AV junction
2. Velocity of conduction is depressed longer PR interval (>0.22 sec.)
iii. Second Degree (AV) Block:
1. Action potential not conducted through AV junction
2. Some action potentials do not reach ventricles partial block
3. Some P waves followed by QRS, some not
4. Abnormal ratio of P:QRS (3:2, 3:1, etc)
iv. Third Degree (AV) Block:
1. All action potentials completely blocked at AV junction
2. Leads to cardiac arrest unless latent ventricular pacemaker fires

3. Atria activated by supraventricular pacemaker and veticles activated

by ventricular pacemakers at a slow rate
4. No PR interval and lower number of QRS complex
5. QRS and T waves larger than P since ventricles are larger
7. Using ECG recordings, identify:
a. Atrial and ventricular fibrillation

b. AV junctional (heart) blocks

c. Effects of Myocardial Infarction on ECG

i. Myocardial Infarction: reduced blood flow (ischemia) to cardiac muscle
1. Damages muscles
2. Relates to time tissue has been oxygen deprived
3. Infarction Zones:
a. Ischemia: insufficient blood supply to heart muscle
b. Injury: prolonged ischemia
c. Necrosis (infarction): death of myocardial cells
d. Fibrosis: collagen deposition at site of necrotic cell
i. Attempt to repair damage cells
ii. Changes in ECG:
1. After several hours: no cell death (infarction) yet
a. R Wave: normal
b. ST Segment: elevated
c. T Wave: peaked
2. After 1 day: injury extent to epicardial surface
a. R Wave: amplitude diminishing
b. ST elevation more marked
st
3. 1 and 2nd Day:
a. R Wave gone
b. Q Wave: significant
c. T Wave: inversion begins
d. ST: elevation may decrease
4. After 2 3 Days: infarction complete
a. More emphasized response as in 1st and 2nd Days
5. Several weeks months
a. Infarcted tissue replaced by scar
b. R Wave: may return
c. Q Wave: persists as before
d. ST: may be around baseline
e. T Wave: less inverted, near baseline

Cardiac Cycle:
1. Define Cardiac Cycle
a. Cardiac Cycle: coordination of electrical and mechanical events in 1 heartbeat
i. P to P or R to R
ii. Systolic: muscles contract
iii. Diastole: muscles relax
iv. About 75 beats per minute 0.8 sec per cycle
b. Cardiac valves maintain unidirectional blood flow
i. Semilunar Valves: Aortic/Pulmonary valves
ii. AV Valves: Mitral/Tricuspid valves (prevent backflow into atria)
2. Mechanical events during cycle:
a. Ventricular Systole
i. Isovolumetric Ventricular Contraction
ii. Rapid Ventricular Ejection
iii. Reduced Ventricular Ejection
b. Ventricular Diastole: (includes atrial systole)
i. Isovolumetric Ventricular Relaxation
ii. Rapid Ventricular Filling
iii. Reduced Ventricular Filling
3. Identify divisions of cardiac cycle, and parameters measured as displayed by Wiggers
diagram

4. Relationship between mechanical event of cardiac cycle and EKG:

a. Right Heart:
i. Less pressure since only pumping blood to pulmonary circuit
ii. 25 mm Hg
b. Left Heart:
i. More pressure due to pumping to systemic circuit
ii. 120 mm Hg
c. Volume of blood in both sides is the same

5. Describe physiological events that occur during subdivisions of cardiac cycle

a. Atrial Contraction: (a wave)
i. Pressure within atria increases, drives blood into ventricles through AV valve
ii. Contributes to ventricular filling (15-20%) vital during cardiac stress or
disease
b. Isovolumic/isovolumetric contraction: (c wave)
i. Rapid closing of valves cause rise in pressure in atria
ii. Pressure transmitted to atria, nearby veins bulging of mitral valve
c. Rapid ejection:
i. Occurs once ventricular pressure exceeds aortic pressure
ii. Semilunar valves open resulting in ejection of blood
iii. Blood is pumped into aorta
iv. Phase 3 and 4
v. Pressure of left ventricle and aorta are equal during systole
vi. 2/3 of ventricular volume emptied into aorta

d. Reduced/slower ejection
i. Blood is pumped into aorta
e. Isovolumic/isovolumetric relaxation
i. Arterial pressure begins to exceed ventricular pressure semilunar valves
close
ii. Large drop in ventricular pressure
iii. At end of Phase 4
f. Rapid filling
i. Once ventricular pressure falls below atrial pressure
ii. AV valves open and filling begins
iii. Throughout filling, ventricular pressure remains low (< 10 mmHg)
g. Reduced filing
i. Once ventricular pressure begins to exceed atrial pressure, filling ends
6. Changes in each parameter measured during subdivision of cardiac cycle
a. Aortic Pressure Curve
i. Change in aortic/arterial pressure during 1 cycle
ii. As filling occurs, aortic pressure declines
iii. Lowest point on curve = diastolic blood pressure (Phase 2)
1. Prior to aortic valve opening
iv. Highest point on curve = systolic blood pressure (Phase 4)
1. When blood is ejected into aorta, aortic pressure peaks
2. Dicrotic Notch: end of systole, aortic pressure goes down
v. Phase 7 = diastasis (ventricular filling has slowed, before atria contracts to
complete filling)
b. Left Atrial/Ventricular Pressure Curve:

c. Left Ventricular Volume:

i. Filling of heart ends with atrial contraction
ii. Phase 1: atrial systole small rise in ventricle volume
iii. Phase 2: isovolumetric, AV and Semilunar valves close
iv. Phase 3: Semilunar valves open and left ventricle volume decreases (rapid
ejection, 2/3 blood leaves)
v. Phase 4: reduced ejection, 1/3 blood leaves
vi. Phase 5: aortic valves close
vii. Phase 6: mitral valve opens and ventricles fill again
viii. Phase 7: diastasis, slow filling
ix. LVEDV LVESV = stroke volume

d. Normal and Abnormal Heart Sounds:

i. 4 sounds produced (2 normal, 2 not)
ii. 2 Audible (normal) Sounds: S1, S2:
1. First Heart Sounds (S1): vibrations with closure of AV valve, loudest
and longest sound (Lub) (Phase 2)
2. Second Heart Sound (S2): closure of semilunar valves during
isometric ventricular relaxation, high pitched, low intensity, short
frequency (Dub) (Phase 5)
iii. 2 Abnormal Sounds: S3, S4:
1. S3: rapid flow of blood from atria to ventricles in small hearts, often in
children (Phase 6)
2. S4: during atrial systole, caused by vibrations of ventricular wall with
ventricular filling, in still hearts, often in elderly. Associated with
cardiac hypertrophy. (Phase 1)

7. Define:
a. End Diastolic Volume: volume of blood in ventricles during isovolumic ventricular
contraction
b. End Systolic Volume: remaining blood after ejection during isomvolumic ventricular
relaxation
c. Ejection Fraction: Stroke Volume (SV) / EDV
i. Indicates contractile function of heart
d. Stroke Volume: EDV ESV
e. Pulse Pressure: Systolic Blood Pressure (SBP) Diastolic Blood Pressure (DBP)
f. Mean Arterial Blood Pressure (MABP): DBP + 1/3 Pulse Pressure
i. Average value of pulsatile pressure that exists in arteries

8. Identify phases of cardiac cycle as described on pressure-volume loop:

a. A-C: ventricular filling
b. C-D: Isovolumetric Contraction
c. D-F: Ventricular systole
d. F-A: Isovolumetric Filling

9. Effects of valvular disorders on blood flow pattern and PV loop (cardiac cycle):
a. Heart Murmurs can be identified by 7 characteristics:
i. Timing (systole of diastole)
ii. Shape
iii. Location
iv. Radiation
v. Intensity
vi. Pitch
vii. Quality
b. Murmurs when valve should be fully open (narrow valve opening, doesnt open right)
i. Stenotic valve
c. Murmurs when valve should be fully closed (leaky valves, doesnt close right)
i. Insufficient
ii. Regurgitant
iii. Incompetent
d. Aortic Stenosis:
i. Aortic valve does not open completely
ii. Occurs during ventricular systole
iii. Ejection sound is due to aortic valve leaflets
1. Sound is not normal S1
2. Sound ends before normal S2
iv. Results in:
1. Large pressure gradient between Left Ventricular Pressure and Aortic
Pressure during systole
2. Elevated ESV and reduced SV
3. Left Ventricular hypertrophy
4. Myocardial dysfunction
5. Arrhythmias
6. Left heart failure

e. Mitral Stenosis
i. Mitrial valve does not open completely
ii. Has Opening Snap Murmur: mitral valve opens earlier than normal due to
higher left atrial pressure
iii. Occurs during ventricular diastole: passive filling of left ventricle
iv. Reduced left ventricular filling reduced EDV and SV
v. Increased blood volume in left atrium increased left atrial pressure
1. Increase in left atria pressure could cause:
a. Pulmonary hypertension
b. Pulmonary edema
c. Right heart failure
d. Atrial hypertrophy
e. Dilation of atrial chamber
vi. Atrial enlargement abnormal electrical activation of atrial chamber and
fibrillation
vii. Atrial Fibrillation reduced cardiac output blood remains in atrial
chamber
1. Stagnant blood in chamber could lead to thrombosis or stroke, if
thrombus blocks vasculature going to brain

viii. LAP is higher than usual because opening is narrower (Wiggers diagram)
ix. LAP higher than LVP in gray areas, should be about even (Wiggers diagram)
x. Lower EDV and stroke volume seen in Pressure-Volume Loop

f. Mitral Insufficiency/Regurgitation:
i. Occurs when mitral valve is leaky backflow from left ventricle in left
atrium during systole
ii. Has Holostolic Murmur: sound throughout whole systole S3 sound
iii. Blood flows into left atrium during systole volume overload in left atrium
iv. Increased left atrium pressure results in:
1. Taller v wave
2. Increased pulmonary pressure edema
3. Left ventricular hypertrophy and dilation
4. Increased EDV

Regulation of Cardiac Output:

1. Define and calculate cardiac output
a. Cardiac Output: volume of blood pumped by ventricles per unit of time (mL/min)
b. CO = Stroke Volume (ml/min) * Heart Rate (beats/min)
c. Q (CO) = P (MABP) / R (total peripheral resistance)

2. List factors that control cardiac output. Which factors are cardiac factors, which are
coupling.
a. Cardiac Output regulated by 4 factors:
i. Preload: initial stretching of single cardiac myocyte prior to contraction
ii. Afterload: pressure that chambers of heart must generate in order to eject
blood out of heart
1. Consequence of aortic pressure (for left ventricle)
2. Pulmonary artery Pressure (for right ventricle)
iii. Heart Rate: number of action potentials or cardiac cycles per unit of time
iv. Contractility: instinsic ability of heart to contract
1. Independent of preload and afterload
2. Also called Inotropy (level of Ca2+ in cytoplasm of muscle cell)
3. Level of Ca2+ determines contractions
4. Can change number of myofilaments (actin/myosin) more filaments
mean greater force of contraction
b. Coupling Factors: involves functional coupling of heart and blood vessels
i. Preload
ii. Afterload
c. Cardiac Factors: intrinsic to heart and modulated by neural and hormonal stimulation
i. Heart Rate
ii. Contractility
d. Cardiac Output is function of Heart Rate and Stroke Volume

i. Heart Rate is determined by Rate of Depolarization of Pacemaker cells

ii. Rate of depolarization:
1. Slowed down by Parasmpathetic
2. Faster by Sympathetic
iii. Sympathetic affects contractibility
iv. Stroke Volume is determined by Ventricular Force of Contraction
v. Force of Contraction influenced by Contractility and Frank-Starling
1. Frank Staling varies with Venous Return

3. Demonstrate how changes in preload affect the pressure-volume loop, stroke volume
and cardiac output:
a. In Pressure-Volume Loop, preload is at point of EDV
b. Passive stretch of left ventricle at end of filling determined by venous return
c. Factors that affect Preload:
i. Vascular Resistance: capillary bed resistance to flow and venous vascular
resistance
ii. Venous Capacitance: volume of blood stored in venous circulation
iii. Ventricular Filling Time
d. Lower EDV = lower force of contraction
e. Filling of blood determines force of contraction
f. If increased preload:
i. EDV
ii. Stroke Volume
iii. Cardiac Output
g. Preload can be measured clinically by parameters:
i. Right ventricular preload
ii. Right atrial pressure
iii. Thoracic venae cava pressure
iv. Central venous pressure
h. Each ventricular contraction maintains relationship: Venous Return (VR) = CO

4. Describe relationship between preload and Frank Starling relationship of heart:

a. Frank Starling: based on length-tension relationship of single cardiac cell.
i. Volume of blood ejected by ventricle depends on volume of blood present in
ventricle at end of diastole.
ii. Venous returns increase = EDV increase = SV increase
iii. EDV and SV increase linearly until very high levels of EDV reached

5. Demonstrate how changes in afterload affect pressure volume loop, stroke volume, and
cardiac output:
a. Afterload: during contraction
b. Factors that affect afterload:
i. Volume of blood in arterial circulation
ii. Pressure in aorta at onset of ejection
iii. Compliance of aorta
iv. Size of aortic valve
c. When afterload (aortic pressure) is increased:
i. Pressure against which the ventricle contracts is much
greater
ii. Larger pressure increases resistance to ejection of blood
more blood remaining in left ventricle higher endsystolic volume (ESV)
d. If afterload is increased, pressure that heart has to generate is increased.
e. Ultimately, heart cannot pump all the blood out ESV increases
i. Stroke volume is shortened, thus EDV will move up to restore SV

6. Demonstrate how changes in contractility affect pressure volume loop, stroke volume,
and cardiac output
a. Contractility: increase in myofilaments or inotropic state due to:
i. Alteration in cardiac performance that involves contractile proteins
ii. Intracellular calcium concentration during Excitation Contraction Coupling
b. Altered with following agents:
i. Sympathetic stim:
1. Epinephrine/Norepinephrine
2. Isoproterenol (acts on 1-AR receptors)
ii. Positive Inotropic Drugs:
1. Digitalis (Na-K ATPase blocker)
a. Cell increases in intracellular Na concentration
b. Causes cell to now reserve mode and pump Na out, Ca in
c. Ca increases inside increase force of contraction
iii. Negative Inotropic Drugs: (reduce Ca levels)
1. Toxins
2. General Anesthetics
3. Ach
4. -adrenergic receptors blocking drugs (propranolol)
c. Contractility enhanced when heart is able to increase force and pressure along systole:
i. Ejection of greater blood volume
ii. Shift in active tension curve to left
iii. Greater Stroke Volume
d. Positive Inotropic Drug enhanced contractibility Increase in Frank Starling
Curve

7. Identify effect of heart rate in cardiac output

a. When Heart Rate increases with a given Stroke Volume, Cardiac Output increases

Work of the Heart:

1. Direct Relationship between Cardiac Output and Preload by using cardiac function
curves
a. Cardiac Function Curve: demonstrates direct relationship between central venous
pressure (right atrial pressure) on cardiac output (frank-starling law)
b. Beyond 4 mm HG, cardiac output will reach steady state (plateau)
i. Before 4 mmHg, there is linear increase in cardiac output
c. Increase preload in green area of curve = increase cardiac output
d. Red Zone: heart has maximum volume
i. Despite increase in right atrial pressure, Cardiac Output has maxed out

2. Inverse Relationship Between Preload and Cardiac Output using vascular function
curves
a. Vascular Function Curve: demonstrates inverse effect of central venous pressure
on venous return
b. High Right Atrial Pressure + Low venous return = Low Cardiac Output

c. Venous return back to heart depends on pressure gradient, dependent on changes

in vascular system
i. Normal Peripheral Pressure: 7 mmHg
ii. Central Venous Pressure:
1. < 7: blood will flow in
2. > 7: blood will not flow in
d. As right atrial pressure increases, venous return decreases
e. As right atrial pressure falls below 0, intrathoracic pressure is higher collapse
of veins and a plateau of venous return
f. Factors that affect venous return:
i. Difference between peripheral and central venous compartment
ii. Veins are compliant changes in blood volume in periphery can alter
peripheral venous pressure venous return can be altered
iii. Decrease in peripheral venous pressure results in:
1. Blood loss by hemorrhage
2. Loss of body fluid through sweating, diarrhea, vomiting
3. Venodilation (decreased sympathetic stim)
iv. Increase in peripheral venous pressure may result from
1. Blood transfusion
2. Fluid retention in kidneys
3. Increase in circulating blood vlume
4. Venoconstriction (increased sympathetic stim)
5. Venous compression
6. Exercise
7. Wearing elastic stockings (elderly wear them to increase pressure)

3. Define Mean Circulatory Pressure

a. Mean Circulatory Pressure: volume of blood in total systemic circuit when heart
is in cardiac arrest and no blood is flowing through the system
b. Occurs at x-intercept: Cardiac Output and Venous Returns are = 0, at 7 mmHg
c. Can be affected by changes in:
i. Circulating blood volume

ii. Venous reserve

iii. Venous tone (contriction/dilation)

4. Significance of Equilibrium Point of cardiac function and venous return curves

a. Equilirbium Point (steady state): cardiac output and venous return is equal and
stabilized
b. Eq. Point is at 5 L/min, 2 mmHg
5. How changes in inotropy, blood volume, and total peripheral resistance affect cardiac
function curve, venous return curve, and point of intersection of curves
a. Positive Inotropic Effect
i. Higher Cardiac Output
ii. Increased Venous Return
b. Negative Inotropic Effect:
i. Lower Cardiac Output
ii. Reduced Venous Return

c. Change in Blood Volume or Venous Reserve (compliance) shift in vascular

function curve
i. Increased Blood Volume: at same right atrial pressure, higher venous
return, higher CO
ii. Decreased Blood Volume: at same RAP, reduced venous return, lower CO

d. Changes in Total Peripheral Resistance (TPR) shifts both Cardiac Function and
Venous Return Curves
i. Deals with PQR relationship
ii. Deals with both veins and arteries, thats why both curves shift
iii. Increase in TRP: (vasoconstriction)
1. Reduced blood ejected
2. Reduced CO
3. New equilibrium has same pressure, decreased CO
iv. Increased R in PQR, leads to reduced CO and venous return

6. Relationship between stroke work and cardiac energy consumption

a. Stroke Work: work done by ventricles to eject blood into aorta, in terms of
contraction and pressure
i. Work: force * distance
ii. Work: volume * pressure
iii. Volume = stroke volume (affected by contractility)
iv. Pressure = Mean Arterial Blood Pressure (MABP)
v. Stroke Work = Stroke Volume * Mean Arterial Blood Pressure
vi. Area under the curve of pressure-volume loop curve

b. Cardiac Minute Work:

i. Power of the heart
ii. Cardiac Minute Work = Cardiac Output * MABP
c. Stroke Work and Cardiac Minute Work can be divided into 2 part:
i. Pressure Work (aortic pressure)
ii. Volume Work (cardiac output or stroke volume)
1. Force of contraction dictated by EDV
2. More volume = more force it has to generate
d. Energy consumption of Heart = Myocardial Oxygen Consumption (MVO2)
i. Directly correlates with stroke work and cardiac minute work
ii. Factors increasing MVO2:
1. Heart Rate (consumes more ATP)
2. Inotropy (increase ATP in order to increase circuit pump)
3. Afterload (to overcome pressure, more force has to generate,
more ATP)
4. Preload (affects much less than first 3) (dictates initial rate, not as
much ATP needed)
7. Compare energy cost of cardiac work in terms of pressure and volume work
a. Pressure work consumes more energy than volume work
b. Heart has to work much harder to overcome changes in pressure

c. Mechanical Energy = external work performed (stroke work) + oxygen

consumption
i. With increased afterload (hypertension/aortic stenosis) high pressures are
required to eject stroke volume
1. Oxygen consumption is increased
2. Mechanical efficiency is decreased
ii. Strenuous exercise increases cardiac output
1. Oxygen consumption increased (slightly compared to afterload)
2. Mechanical efficiency decreases (less than afterload
iii. Frank-Starling contributes to lower efficiencies in afterload and exercise
d. Left heart has to use more energy than right heart since left heart has 6 times more
pressure (120 compared to 25 mmHg) than right.
i. Left Ventricular Pressure Work > Right Ventricular Pressure Work
ii. Pressure Work increases ventricular thickness
iii. Work on right heart is 1/6 of left
1. Mean pulmonary pressure is 1/6 of aortic pressure
8. Law of LaPlace and how it relates to Pressure-overload/concentric hypertrophy and volumeoverload hypertrophy
a. Law of LaPlace (for a sphere):
i. Tension of wall is product of pressure and radius of chamber
ii. Tension is inversely related to thickness of wall
iii. T = (Pr)/(2H)
1. H = wall thickness
2. R = radius
3. T = wall tension
4. P = pressure
iv. With increased pressure or volume load, heart will undergo hypertrophy to
reduce wall stress
1. Increase blood volume = increase tension
2. Increase thickness = decrease tension
v. Explains how heart physiologically compensates for change in volume and
pressure above normal values
b. Cardiac Hypertrophy:

i. Due to excessive workload placed on heart

ii. Due to either excessive pressure load or excessive volme load
iii. Excessive preload = eccentric hypertrophy
1. Preload (Hypervolemia, Anemia
2. Eccentric hypertrophy (Myocyte lengthening)
a. Increased myofilaments = increased contractility
b. Sarcomeres added in series
iv. Excessive afterload = concentric hypertrophy
1. Afterload (resistance, impedance)
2. Concentric hypertrophy (myocyte thickening)
a. Sarcomeres added in parallel
v. Compensations (hypertrophy) works for short period of time
1. If they fail heart failure
vi. Hypertrophy can happen after exercise
1. Physiological: (good)
a. Increase in thickness of ventricular/chamber wall
b. In athletes
c. Changes are proportional
2. Pathological: (bad)
a. After exercise
b. Change in thickness/diameter
Hemodynamics:

Analyze factors that determine blood flow

o 3 Connective Loops for blood flow:
1st Loop: Cardiac Output (7200L/day)
2nd Loop:
Filtration (20 L/day)
Reabsorption (16-18 L/day)
Diffusion Exchange occurs here:
o 80,000 L of water/day is exchanging (3 L in body)
o Brain needs 20,000 g glucose per day
3 Loop: Lymph Flow (2-4 L/day)

o Poiseuille Equation:
Pressure from inlet to outlet (pressure gradient) determines driving force of
blood

Calculate hemodynamic resistance and conductance in series and parallel

For pulmonary circuit, input and output (pressure gradient) if from right
ventricle to left atrium
Q = cardiac outptut, blood flow, flow, etc

Dilated arteries = increased radius = decrease in resistance

In series: heart aorta capillaries
o Resistance is greater in series
In parallel: capillaries branch from arterioles and into venules

Evaluate quantitatively the consequences of changes in vessel diameter on blood flow

o Velocity = blood flow / total cross sectional area (pi*r^2)
o Thin vessel = greater velocity
o Thick = lesser velocity
o Application:

Aorta has larger vessel

Lungs have thinner vessels
Lungs have slower velocity than aorta because it has a greater total cross
sectional area. Lungs as a whole, since it has more vessels, will have a slower

velocity.

Correlate hemodynamic principles with alterations produced by disease processes

o Aortic Stenosis (coarctation):
Reduced diameter increased resistance
As a result body increases pressure gradient
Orginally: 120 mm Hg,
Now, due to stenosis: >120 mmHg
This allows blood pressure in legs to be normal
Initially, flow to legs is lower, but over time it is normal
Neural Control of Peripheral Circulation: (baroreceptors)

Understand neural regulation of peripheral circulation as a feedback mechanism

o Most examples in physiology are negative feedback
o Clotting = positive
When clot forms, more clot forms
o During Labor = positive
Release of oxytocin leads to more to be released

Analyze relations between carotid baroreceptors, cardiovascular centers and effectors

o Receptors for Cardiovascular system:
Carotid Sinus Baroreceptor (between internal/external carotid) (CN IX)
Aortic Arch Baroreceptor (below aortic arch) (CN X)
o Afferent Pathway: Nucleus Tractus Solitarius (NTS)
o Integration Center: (medulla)
Cardiac Decelerator (parasympathetic)
Ach is released in second synapse to act on SA node and heart rate
Cardiac Accelerator (sympathetic)
Increases contractility of muscle
Also acts on SA node to increase heart rate
Vasoconstrictor (sympathetic)

Understand role of sympathetic and parasympathetic nerves in regulation of blood

pressure
o Only sympathetic nerves directly control blood flow
o Sympathetic releases epinephrine/noradrenaline

o Receptors for Noradrenaline:

Alpha: constriction (sympathetic mainly constricts)
Beta: vasodilation
o Stimulation of sympathetic nerves at Lumbar 4 (controls legs):
Increase firing rate
If more alpha than beta receptors vasoconstriction (reduce vessels by 1/16)
o In Coronary Vessels: beta > alpha
Vasodilation when stimulated
Norepinephrine has greater tendency to constrict than epinephrine

Describe interaction between high and low blood pressure receptors (sensors)
o Carotid and Aortic Baroreceptors sense high blood pressure (between 70-80 mm Hg)
o If around 40 mm Hg, sensors will not sense it
o Body sets low pressure baroreceptors in atria
Sense -10 10 mm Hg
Atrial Pressure usually 0 mm Hg
Usually associated with changes in water content
Connected to neurons in spinal cord posterior pituitary
Posterior pituitary will either release more/less of ADH (vasopressin)
ADH controls secretion of water (more ADH = more water kept)
ADH acts on kidneys blood pressure diseases originate from kidney

Fight or Flight Reaction and Conundrum:

o In fight or flight reactions, neurons in hypothalamus initiate response via sympathetic
nerves
o Exception:
Sympathetic postsynaptic neurons can release Ach
Ach = vasodilation
Muscarinic receptors
Production of nitric oxide
o Skeletal muscles have both alpha, beta, muscarinic, H1, and H2 receptors
Vasoconstriction is normal response in skeletal muscles (alpha > beta)

Humoral Regulation of Circulation: (hormones)

Humoral Factors
o Norepinephrine: alpha/beta receptors
o ADH (vasopressin)
o Atrial Natriuretic Hormone
o Renin-Angiotensin System
o Kallikrein -Kinin System

Humoral regulation of blood pressure as a feedback mechanism

o Decrease in Arterial Blood Pressure Increase in renin Constriction of renal

arterioles Decrease in Renal Blood Flow and Filtration Rate Decrease renal
excretion of Na and water Increased Blood Pressure

Humoral regulation of blood pressure as a system with constrictor and dilator elements
o Renin-Angiotensin (aldosterone) System (RAS):
Angiotensin Angiotensin I Angiotensin II
First enzyme (angiotensin to angiotensin I): Renin
Second enzyme: ACE
Angiotensin II:
Vasoconstrictor
Works on 2 receptors: AT1 and AT2
If AT1 vasoconstriction
If AT2 vasodilation, nitric oxide produced
o Kallikrein-Kinin System (K-K):
Kininogen Kinins
Enzyme: Kallikrein
Kallikrein produced by pancreas
Most famous kinin = Bradykinin (vasodilation)
Involved in toothaches
o Kininase II and ACE both breakdown Bradykinin by removing
1 amino acid

Physiologic basis of action of angiotensin converting enzyme inhibitors and betablocking agents in control of hypertension
o ACE Inhibitors:
Prevents Angiotensin II decrease constriction
Prevents breakdown of Bradykinin increase dilation
o Beta-receptors:
More prevalent than alpha on kidneys
When Norepinephrine binds causes renin to be produced
Renin leads to vasoconstriction
However, beta receptors lead to vasodilation
More important to prevent vasoconstriction than increase vasodilation led
to creation of Beta-Blockers (propranolol)
o Ang-(1-7) is mainly found in brain leads to vasodilation

Functional significance of nitric oxide signaling cascade in regulation of blood pressure

and flow
o Substances that activate eNOS (endothelial nitric oxide synthase)
Shear Stress
Ach
Histamine
Bradykinin
ATP
o eNOS is located in endothelial cells along with ACE

o Once activated, eNOS activates sGC (soluble guanylyl cyclase) which leads to
vasodilation

Regional Circulation:

Characteristics of autoregulation of blood flow

o Autoregulation of blood flow: Intrinsic ability of organs to maintain relatively
constant blood flow despite changes in pressure gradient
o Organs that can autoregulate:
Heart
Brain

Skeletal Muscle
Kidney
GI

Hypotheses and basis of autoregulation of blood flow

o Metabolic hypothesis:
pO2 is lower due to increased oxygen consumption
Adenosine is metabolic waste from food consumption, which is a vasodilator
pH is decreased (acidic)
o Myogenic Hypothesis
o Neither theory explains blood pressure well
o Blood flow is constant, but if taken at one interval there are fluctuations
Aorta + pulmonary artery: flow is always changing
Pulmonary Vein: not much change
IVC: cyclic activity

Factors responsible for functional and reactive hyperemia

o Functional Hyperemia:
Increased glucose after eating = increased GI blood flow
o Reactive Hyperemia:
Rush of blood after circulation is cut off from external factor
Ex: Sphygometer

Once it is pumped, hand turns pale (ischemia) b/c of lack of blood

flow. Once taken off, hand turns red due to faster blood flow

Specific properties of circulation in specific organs (skeletal muscle, GI, skin)

o Coronary Blood Flow:
Physical Determinants:
Aortic Pressure
Extravascular Compression
Main Regulators:
Metabolic factors (adenosine, pO2, pCO2, pH, VO2)
Role of sympathetic nerves VO2
Metabolism:
Fatty acids are important
Heart will consume any substrate in proportion to their plasma
concentration
o Cerebral Blood Flow:
Physical Determinants:
Aortic Pressure (blood and interstitial volume in fixed space)
Main Regulator:
Metabolic Factors (arterial pCO2, cerebrospinal pH
Neural regulation (???)
Metabolism:
Glucose is most important source, more than oxygen
Blood Brain Barrier:
Lowest capillary permeability in body
Facilitated diffusion for glucose and specific amino acids
Normal Cerebral Blood Flow at 10kPa (for bo th pCO2 and pO2) = 75 mmHg

Neurons not in direct contact with blood vessels, does it through glia
CO2 drives blood flow

Microcirculation:

Relative contribution of diffusion and convection to transport substance across

microvascular walls

o Main function of cardiovascular system: exchange of substance between blood and

tissue
o Diffusion (Ficks Equation):

Js = flux
dM = change in mass
dt = change in time
D = diffusion coefficient
A = area available for exchange
Increase density of capillaries = increase in A
Capillary density = # capillaries / mass of tissue
dC = change in concentration
P = permeability
F = flow
For PAdeltaC C is difference between inside and outside capillary
For FdeltaC, C is difference between two points within a capillary
o Convection (Starting Equation) deals with pressure differences

Jv = volume flux
Lp = hydraulic conductivity coefficient (how water/fluids exchange)
P = hydrostatic pressure (not permeability)
= osmotic reflection coefficient
0 = permeable, water
1 = impermeable, proteins
R = gas constant
T = temperature
C = concentration difference between outside and inside vessel
KFC = capillary filtration coefficient
Pc = pressure inside capillary
Pt= pressure in interstitium (tissue)
= osmotic pressure in plasma/tissue

Adaptive mechanisms of microcirculation in response to metabolic demands

o A: Normal
Blue Line = osmotic gradient
Down arrows = filtration of capillaries, inside to out
Upward arrows = tissues to capillary
Blood Pressure Control is seen in arterioles
Osmotic Pressure wants to pull blood
Blood Pressure wants to push blood out vessels into tissue
o B: Arteriolar Dilation (Exercise)
More filtration = physiological/functional edema
Explains heavy legs after exercising
o C: Arteriolar Constriction (hemorrhage)
Down arrow (filtration) decreases
Response is to increase filtration
o D: Decreased Plasma-Protein Concentration
Filtration increases edema

Mean Capillary Hydrostatic Pressure:

o
o
o
o
o

This pressure drives fluids out of capillaries

Highest at arteriolar end of capillary than venule
Pc is much more influenced by changes in Pv than Pa
R = radius
Compression of leg veins increased Pv increased Pc edema due to filtration

Calculate net movement of fluid and substances in microcirculation

Basis of altered microvascular permeability in disease

o If disease causes inflammation, bradykinin, histamines, platelet-activating factor, and
VEGF can be released to increase permeability

Main site of agents that alter microvascular flow and/or permeability

o Agents that affect Permeability
Bradykinin
Histamine
Platelet-Activating Factor
Vascular Endothelial Growth Factor
o All these agents above released in inflammation
o Main site of Action: Postcapillary Venules
o Permeability in Organs: (in order of lowest to highest permeability)
Brain (BBB)
Lung (must be kept dry)
Skeletal Muscle
Kidney (glomerulus)
Liver (sinusoids)

Factors involved in lymph formation and flow

o Flow of lymph is unidirectional
o Edema occus when volume of interstitial fluid exceeds capacity of lymphatics to
return it to circulation
Can be caused by:
Excess filtration
Block lymphatics
o Lymph flow depends on interstitial pressure (direct relationship)
As pressure increases, lymph flow also increases

Extra Info:

Internal anatomy of heart (mitral valve, tricuspid)

Leads:
o Bipolar Leeds (positive/negative ends)
o Einthovens Triangle: (3 leeds)
Right leg is used as ground

o Augmented Unipolar Limb Leeds: (3 leeds)

Electrical acivity is small
1 electrode is used to determine electrical activity, all positive
Central terminus is at center of heart (negatively charged)
o Precordial (Chest) Leeds (6 leeds)
Chest leads represent transverse section of heart
Limb Leeds (augmented & bipolar) represent frontal region of heart

Fibrillation:
o Atrial Fibrillation: chaotic activation of the atrial muscle
Heart Rate: > 350
No recognizable P waves, only f waves
o Ventricular Fibrillation: chaotic activation of ventricular muscle (more serious)
No recognizable QRS complex
Ventricular Arrest
Need to shock heart to stimulate malfunctioning nodes

Cardiac ECC:
o Ca2+ ions enter the L type channel
o Calcium causes more release of calcium from RyR2 receptor
o Calcium binds to troponin and allows myosin binding sites
o Calcium taken back to SR by Ca ATPase

Hypertension: (silent killer)

o Affects 1 billion people
o Leading cause of morbidity and mortality
o >20% Americans are hypertensive
o Major risk for coronary artery disease and heart attacks
o White Coat Syndrome: increased BP when visiting doctor
o 90-95% patients with hypertension, cause is unknown
o Secondary Hypertension: caused from another disease/disorder
o Increase in arterial blood pressure:
Increase in systemic vascular resistance (SVR) (vascular tone)
Increase in cardiac output (heart rate, stroke volume)

Continuity Principle: flow will remain constant (vA = k)

Reading Impulse Curve:
o Aorta has 120 mm Hg
o Tibia has 150 mmHg
o Even though tibia has a higher pressure, blood will not go from tibia to aorta
o Look for area under the curve (pressure energy/mean pressure)
Aorta = 100
Tibia = 90
Thus, blood will go from aorta to tibia
When finding blood pressure, set sphingometer to 0 atmospheric pressure
o Thus, when finding a patients blood pressure, its really an additional 760 mm Hg to
the sphingometer reading (ex: 760 + 120 if at the aorta)
Impedance is used to deal with a single vessel, not resistance
o Impedance is greater than resistance
Only way to calculate Mean Systemic Pressure (mean circulatory filling pressure) is to
measure this pressure half an hour after person is dead so Ach and NE is all released
If medulla cut, it will affect heart rate since cardiac center is in medulla
Vasopressin: constriction, elevation in BP
Atrial Natriuretic Hormone (peptide): decrease sodium reabsorption in kidneys decreases
blood pressure
Renin-angiotensin: associated with vasoconstriction
Angiotensin III: causes thirstiness
o Lack of risk of dry mouth
Plot Poiseuille equation (y axis: blood flow, x-axis: delta P) straight positively sloped line
o In autoregulation there is a period of leveling off called steady state