224 terms

# Cardiovascular system

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For a given liquid moving inside the a tube with given resistance, the greatest change in energy occurs at the point of greatest resistance. Which vessels provide the highest resistance in the cardiovascular system (normally)?
Arterioles

Arterioles ARE the major determinant of <b>Total Peripheral Resistance (TPR)</b>.

TPR - is the total resistance (R) to blood flow presented by the entire systemic vasculature.

• MAP in the equation is MAP-CVP in reality but since the value of CVP is negligible, it is not part of the equation.
The blood pressure in the venous system is affected by what two factors?
1. Vein compilance (C)
2. Volume change (dV)

C = ΔV/δP (δP is the change in transmural pressure)
Main function of blood
delivery of oxygen and other nutrients to systemic tisseus and the removal of metabolic byproducts.
CO
• Cardiac Output = Blood flow per unit time (avg Q)
Cardiac Output = Stroke volume (SV) x Heart rate (Hr)

SV- Volume pumped by the heart per beat.
MAP
Mean aortic pressure
(T/F) Heat is 2 Pulsatile pumps functioning in <i>series</i>.
True

• Avg flow out of LV is the <u>same</u> as pumped by RV since pumps are in series.

• Sys pressure is <i>slightly</i> higher than pulmonary due to <u>higher systemic resistance</u>.
The pressure in systemic system is _________ pulmonary system.

a. higher than
b. lower than
c. the same as
a. Higher than

REASON ► ↑ systemic <i>resistance</i>.
Q
symbol for <b>blood flow</b>
VR
Venous Return - the blood retruning to the Right Atrium (RA).

★ Numerically, <b>VR = CO</b> ★
Blood flow <i>between</i> organs are in __________ where as blood flow<i> within</i> an organ could be in _________.
Blood flow <i>between</i> organs are in <b>parallel</b>where as blood flow<i> within</i> an organ could be in <b>series</b>.
What is the main factor determining how much of CO each organ receives?
the resistance (R) of blood flow to that specific organ.
Vascular bed
A convenient way to describe the <u>totality</u> of all blood vessels within a given tissue or organ.

• Vascular bed of each organ is in <i>parallel</i> with the vascular beds of other organs.
How is the value of Q changes for brain and heart in response to exercise? what about the CO?
CO ↑ increases

Q for brain ↓
Q for heart remains unchanged.
Vascular Smooth Muscle (VSM) is present in walls of all vessels <b>EXCEPT</b>:
capillaries
Overall vessel "stiffness" (compliance, C) depends on what 2 factors:
Compliance - the ease with which a blood vessel (or cardiac chamber) can be expanded (diameter or volume increased) when its P<SUB>TM</SUB> is increased.

1. Collagen/Elastin ratio (elastic modulus of the wall)
2. W/r<SUB>i</SUB>ratio

W = Wall's thickness
E = Elastic modulus of the wall

» keep in mind vessles that have higher VSM are more capable of ↓ the r<SUB>i</SUB> value and thus ↑↑ the resitance (R) and also the W is thicker.
Why do venous vessels have higher compliance (C) than arteries?
they have thinner walls (smaller W) and larger radius (larger r<SUB>i</SUB>) which means the W/r<SUB>i</SUB> ratio is smaller.
How is "fine tuning" of blood flow achieved?
by terminal arterioles which are distal segments of arteriole that gaurd entrance to capillaries.
Intravascular pressure / blood pressure
is the sum of (1) (2) and (3)

1) Cardiac pumping
2) Blood volume
3) Gravity

• Usually expressed in mmHg
Perfusion pressure
MAP = Mean aortic pressure
CVP = Central vein pressure. CVP is the input pressure to the RA/RV and affects CO.
What is the normal range for Central Vein Pressure (CVP)
1-5 mmHg
If the "frictional" resistance (R) of vessel ↑, what happens to the flow of blood?
decreases.

R - frictional resistance
ΔP - is the change in pressure.
What are the typical values for blood volume?
Men - 6 L (80 ml/kg)

Female - 5 L (70 ml/kg)

other- venous blood holds ~2/3 of the systemic blood volume.
What are the typical values for the following:

a. Plasma volume
b. Interestitial fluid
c. Cellular fluid
a. Plasma volume → ~ 3.5 L
b. Interestitial fluid → ~ 12 L
c. Cellular fluid → ~ 35 L
the SPECIFIC Blood flow resistance of a blood vessel can be expressed in the equation:
K - constant (128/π)
L - Length of the vessel
η - Blood's viscosity*
D - diameter of the <i>lumen</i> <b>(Dominant factor)</b>

* Viscosity is a measure of the <i>friction</i> experienced by adjacent layers of blood as it moves along the vessel. <i>Viscosity = (Shear stress/Shear rate)</i>

★ This is the more <span style="color: #ff0000;">specific</span> equation describing the resistance. the general equation is R=(ΔP/Q).
Transmural pressure (P<SUB>TM</SUB>) is defined as:
» Pressure applied to the walls of the vessel in a radial direction.
» Difference in P<SUB>i</SUB> and P<SUB>e</SUB>.
ΔP vs. P<SUB>TM</SUB>
ΔP is Pressure loss along the vessel length
In a vessel with an area of A, and a given amount of blood flow per unit of time (Q), the relationship between the Q and blood velosity (U) is expressed:
The relationship between U and Q is <u>inverse</u>.
» Velocity is also <u>inverse</u> to Area
The force required to flow blood of certain viscosity inside the vessles is known as:
Shear stress (τ). It is proportional to the difference in blood velocity, u, between adjacent layers of blood.

★ The spatial gradient in velocity is called <b>velocity gradient</b> or <b>shear rate</b>.
What is another name for velocity gradient?
Shear rate
For a given fluid (blood) moving inside vessels, where do you have the highest <i>velocity</i>?
At the center

» The velocity at the walls of the vessels is ~ 0 but the <b>shear stress is greatest</b>.
Shear stress (τ) is maximum at the __________ and minimum at the ______.
Maximum at the <b>vessel walls</b>
Minimum at the <b>center</b>.

NOTE: Shear stress causes endothelial cells to release NO which leads to vasodialiton.
Unit for viscosity:
Centipoise (cP)
What happens to the shear stress at the walls of a vessel if the diameter of the vessel ↑.
It will decrease.
(T/F) Average Blood velocity (U) varies considerably throughout the vasculature.
True

In aorta, U<SUB>AA</SUB> is ~20 cm/sec.
In capillaries, U<SUB>cap</SUB> is ~ 0.05 cm/sec.
This is 400:1 range!

» The velocity ↓ due to combined effects of an <i>↑ in number (n) of parallel vessels from aorta to capillaries</i> and the <i>★ large cross sectional area of the capillary network</i>.
★ Main reason (REMEMBER: <span style="color: #ff0000;">U = Q/A</span>)
What is the equation that best explains the velocity of blood across the capillaries.
(1) is the general equation
(2) is considering multiple vessels (such as in capillaries).
• Q = CO since there is no change in the heart rate.
What are two factors affecting blood viscosity:
1. Hematocrit (Hct) - directly but <u>not</u> proportional
2. Temperature - Blood η ↑ ~ 2% per 1°C ↓ in blood temp.

★ normal Hct = <b>37-47</b>
Shear rate
The relative velocities in laminar flow of parallel adjacent layers of a fluid body under shear force. In other words, it is the velocity <u>difference</u> between <u>adjacent </u>molecules.
At ____ shear rates, viscosity (η) increases.

a. low
b. high
a. low

» Normally, average shear rates (~U/D) are sufficient to prevent blood viscosity from becoming abnormally high.
» <u>RBC Rouleaux</u> occur at low shear rate as well.
At ____ shear rate, Rouleaux RBCs are formed.

a. low
b. high
a. low

<b>Explanation:</b> Rouleaux grow at <i>low</i> shear rates in the presence of <b>plasma fibrinogen</b> and <b>globulins</b>, which somewhow foster shear rates, η also ↑ when fibrinogen concentration ↑.
Is the shear rate larger at the wall of the vessels or at the center.
At the center because the D would be very small at the center. CONFIRM this!
(T/F) As the shear rate ↑, viscosity (η) ↓.
True
Viscosity of blood is the highest at:

a. Vena Cava
b. Vein
c. Capillaries
d. Arterioles
e. Artery
a. Vena Cava
b. Vein
c. Capillaries
d. Arterioles ✓
e. Artery
As the velocity ↑, viscosity _______.

a. increases
b. decreases
b. decreases
Increase in which of the following causes an decrease in <i>viscosity (η)</i>?

a. ↑ Hct
b. ↑ Shear stress
c. ↑ Shear rate
d. ↓ temp.
e. cell sphering
f. ↑ blood fibrinogen
g. ↓ velocity
h. ↓ Diameter
a. ↑ Hct
b. ↑ Shear stress
c. ↑ Shear rate ✓
d. ↓ temp.
e. cell sphering (or cell hardening)
f. ↑ blood fibrinogen
g. ↓ velocity
h. ↓ Diameter ✓
(T/F) Low shear rates promote adherence of wbc to endothelium, further increasing viscosity.
True
Resistance in Series
The total R is greater than individual R
Resistance in parallel
The total is LESS than any individual R
P<SUB>c</SUB>
Mid-capillary pressure

3 ways to calculate

4) is the Apprixmate for predicting relative amount and direction of changes in capillary pressure.

» QR = ΔP = pressure loss
» Q= (MAP-P<SUB>v</SUB>)/(R<SUB>A</SUB> + R<SUB>V</SUB>)
» P<SUB>A</SUB> = MAP = 95 mmHg
» P<SUB>V</SUB> = 5 mmHg
Considering the general partitioning concept, If arterioles only constrict: what happens to Q and P<SUB>c</SUB>?
Both your Q and Mid-Capillary pressure would decrease.

CORRECTION: the denominator of (2) should say: Ra + Rv
Considering the general partitioning concept, If venules only constrict: what happens to Q and P<SUB>c</SUB>?
1) Mid-Capillary pressure would increase
2) Q would decrease.
Considering the general partitioning concept, If both arterioles and venules constrict, but R<SUB>A</SUB> changes more than R<SUB>V</SUB>, what happens to Q and P<SUB>c</SUB>?
1) Mid-Capillary pressure would decrease
2) Blood flow also would decrease
Considering the general partitioning concept, If only arterioles dilate: what happens to Q and P<SUB>c</SUB>?
1) Mid-Capillary pressure would increase
2) Blood flow would increase
(T/F) compliance concept: Less pressure increase for the same amount of volume change means a greater compliance.
True

compliance is the <b><i>slope</b></i> of Volume vs. Pressure graph.
Which of the following would ↑ as the result of ↓ compliance of aorta?

a. aortic systolic pressure
b. aortic pulse pressure
Both a and b will ↑

» The compliance ↑ by age which is one reason why older people suffer from hypertension more.
Laplace's Law (For thin walls)
Basic form: an <i>equilibrium radius</i> (r) occurs if tension in a wall (T) just balances effects of the distending tendensies of the transmural pressure (P<SUB>TM</SUB>).

» So as the radius ↑, the tension ↑.
» <i><u>stable</i></u> radius when transmural pressure is balanced by wall tension.
LaPlace's Law (modified)
σ - Wall stress
P - pressure (Transmural)
W - Wall thickness

Stress that the wall experiences depends directly on the product of transmural pressure and the ratio of the radius to wall thickness.
How is stress (σ) differs from Tension (T)?
σ- force/area - arises from forces acting on an area
T- force/length- applies to thin wall structure.
Bachmann's bundle
Originates in the sinoatrial node and is the only tract that conducts action potentials to the left atrium.
Internodal tracts
The portion of the cardiac conduction system between the SA node and the AV node.
Purkinje Fibers
<u>Modified</u> cardiac muscle fibers - transition into muscle cells via <i><u>gap junction</i></u> cell-cell conduction.
• Fast conduction speed
What is the correct sequence of Depolarization in the heart?
Septum from Left to Right → Apex → Endo → Epi → Posterior Base → Last myocytes to deplorize are in epicardium and LV posterior base → Fully depolarized.
5 phases (Φ) of fast response AP (FRAP)
Φ0 - Upstroke or rapid deplorization (to +20 mv)
Φ1 - early <u>rapid</u> replorization
Φ2 - Plateau
Φ3 - replorization
Φ4 - resting membrane potential* (-80 mv)

* this phase is NOT stable for <i>slow</i> response APs and continuously deplorizes.

» the term slow/fast response mainly describes rate of change of the AP Φ0 which in atrial and ventricular muscle and in the His-Purkinje conducting system is <b>~2 msec</b> hence- fast response.
Which of the following experiences a slow response?

a. SA node
b. Atrial muscle
c. Atrioventicular
d. Bundle branch
e. Purkinje fibers
f. Ventricular muscles
a. SA node ✓
b. Atrial muscle
c. Atrioventicular ✓
d. Bundle branch
e. Purkinje fibers
f. Ventricular muscles
(T/F) Some ion channels that are open during fast response are NOT open during slow response.
True.
(T/F) Cells of the SA node have lower threshold and therefore reach it faster than all the other cells.
False,

The threshold is not lower, the recovery is faster.
What is the resting cell potential for <b>slow</b> response cells of SA and AV node?
-60 mv and the threshold is <b>-40 mv. </b>
Which is not a characteristic of slow-response APs.

a. prolonged activation/deactivation times
b. longer excitability recovery
c. Lower threshold
d. More unstable Φ4
e. Lower absolute resting membrane potential
f. slower upstroke
a. prolonged activation/deactivation times
b. longer excitability recovery
c. Lower threshold ✓
d. More unstable Φ4
e. Lower absolute resting membrane potential
f. slower upstroke
(T/F) Gap junctions are example of non-specific channels.
true
What three factors determine the whole cell ion current flow through a specific ion channels?
1. membrane potential (V<SUB>m</SUB>)
2. Ion concentration gradient across the membrane
3. <i>Probability of open state of the ion channels</i>
What factors determine the whole cell ion current for a constant ion concentration gradient at a fixed membrane potential?
number of functional ion channels in the membrane (N) <b>x</b> the probaility of the open-state of these channels <b>x</b> single open channel current I<SUB>S</SUB>.
Which of the following factors will change by change in V<SUB>m</SUB>?

a. # functional ion channels in the memb. (N)
b. probability of open-state of the channels
c. single open channel current I<SUB>S</SUB>
a. # functional ion channels in the memb. (N) → constant
b. probability of open-state of the channels ✓
c. single open channel current I<SUB>S</SUB> ✓
Increased the activity of IK<SUB>Ach</SUB> causes:
» Hyperplorizes the membrane
» ↓ rate of spontaneous deplorization (Φ4) of slow response APs (SRAP).
Which of the three types of potassium channels you would expect NOT to be open during Φ4?

a. IK<SUB>1</SUB>
b. IK
c. IK<SUB>Ach</SUB>
a. IK<SUB>1</SUB> → open during Φ4 to maintain resting membrane potential in <i>atrial, His-Purkinje</i>, and <i>ventricular</i> fibers.

b. IK ✓ → increased during <B>Φ2</B> causing replorization (<b>Φ3</b>).

c. IK<SUB>Ach</SUB> → ↓ rate of spontaneous deplorizaiton in SRAP.
In which direction is the "net component" of IK<SUB>1</SUB> during Φ4?
has a net component directed <b><u>outward</u></b>.
What are the two types of Ca⁺⁺ channels?
L (long lasting)
T (Transient)
IK<SUB>1</SUB>
» helps maintain resting membrane potential in artrial, His-Purkinje, and ventricular cells.

» Its activity is a function of both V<SUB>m</SUB> and [K⁺]<SUB>o</SUB>.

» Fully open during Φ4 and has a net component directed outward from the cell.
Which of the following is voltage gated?

a. IK<SUB>1</SUB>
b. IK
c. IK<SUB>Ach</SUB>
a. IK<SUB>1</SUB> (?)
b. IK ✓
c. IK<SUB>Ach</SUB> (ligand gated)
Parasympathetic stimulation of the heart opens which channels?
IK<SUB>Ach</SUB>

» Reduces rate of spontanous deplorization of SRAP
Which of the following Ca⁺⁺ is voltage gated?

a. I<SUB>Ca, L</SUB>
b. I<SUB>Ca, T</SUB>
both!
I<SUB>Ca, L</SUB>
» Activated on upstroke (Φ0) ~ -35 mv
» Contributes to Φ2 by balancing against outward flow of K⁺ through IK channels.
» triggers Ca⁺⁺ release from Sarcoplasmic reticulum
» Also causes SRAP Φ0
What two channels are involved in the <b>plateau</b> (Φ2) of the FRAP?
1. IK channels which allow K⁺ to rush out. → hyperplorization
2. I<SUB>Ca, L</SUB> that allow Ca⁺⁺ to rush in → deplorization

Together, they contribute to formation of plateau.
During the upstroke (Φ0) phase of FRAP, which of the following channels open up first?

a. I<SUB>Ca, L</SUB>
b. I<SUB>Ca, T</SUB>
a. I<SUB>Ca, L</SUB> → ~ -35 mv ✓
b. I<SUB>Ca, T</SUB> → ~ -30 mv
I<SUB>Ca, T</SUB>
» Transient inward Ca⁺⁺ current via voltage-gated channels.

» Activated during FRAP Φ0

» Also contributes to inward current to later part of Φ4 of SRAP.
Which channels are responsible for the initiation of Φ4 spontaneous deplorization in pacemaker cells (SRAP)
I<SUB>f</SUB> - Hyperplorization-activated (funny current) carried by Na⁺ in SA and AV nodal cells.
What two channels contribute to <b>slow diastolic deplorization</b>? also known as spontaneous Φ4 depolarization. (SRAP)
interaction between:

1 repolarizing current :
a. K⁺ (IK)
2 deplorizing currents:
a. Na⁺ (I<SUB>f</SUB>)
b. Ca⁺⁺ (I<SUB></SUB>CA)
Opening of which specific channel causes V<SUB>m</SUB> to "turn-the-corner" and initiate a slow diastolic deplorization in SRAP?
I<SUB>f</SUB> Na⁺⁺ channels. These channels open up at -50 mv
What happens at V<SUB>m</SUB> = -55 mv in a SRAP?
Inward calcium current (I<SUB>Ca-T</SUB>) is activated and it ↑, it accelerates the diastolic deplorization.**

I<SUB>Ca-L</SUB> opens up when threshold is reached <i>which causes the generation of upstroke of the AP</i>.

** I<SUB>Ca,T</SUB> open at -30 mv in FRAP
(T/F) There are no <b>fast</b> voltage gated sodium channels in SRAP.
true
What channels are responsible for the <b>rapid</b> deplorization that occurs in FRAP?
Fast voltage gated sodium channels.
» I<SUB>NA</SUB> is turned off by Inactivation gate during Φ0.
In FRAP, the fast voltage gated sodium channels close during Φ0 due to:
closure of Inactivating gates.
What happens during Φ0 phase of FRAP?
1. fast voltage gated sodium channels becom inactivated
2. Ca⁺⁺ (I<SUB>CA-L</SUB>) open up
3. I<SUB>K</SUB> also opens up
4. I<SUB>K1</SUB> closes
What causes entrance to Φ3 from plateau?
closure of Calcium channel and dominance of I<SUB>K</SUB> channels.
duration of plateau (Φ2) depends on:
relative amount of I<SUB>K</SUB> and I<SUB>CA</SUB>
The highest contraction force occurs during which phase of FRAP?
plateau (Φ2)
Time to reach threshold depends on what three factors?
1. rate of Φ4 deplorization (dVm/dt)
2. magnitude of the threshold potential
3. maximum negative diastolic potential.
What are the mechanisms involved in vagal and sympathetic changes of the heart rate?
<u>Vagal</u>- opening of IK<SUB>Ach</SUB> and reduction I<SUB>f</SUB> and I<SUB>CA</SUB> (FASTER)

<u>Sympathetic</u> - through secondary messangers c-AMP(β<SUB>1</SUB> receptors) → ↑ I<SUB>f</SUB> and I<SUB>CA</SUB> (SLOWER)
Cardiac dysrhythmia / Arrhythmia
is a term for any of a large and heterogeneous group of conditions in which there is abnormal electrical activity in the heart. The heart beat may be too fast or too slow, and may be regular or irregular. <B> ecopic impulses in the relative refractory period may trigger a reentrant iarrhythmia</b>.
(T/F) the AP generated during relative refractory period has shorter amplitude.
True

This is because not all Na⁺ channels have recovered yet.
What is the source of Electrocardiogram (EKG)?
Moving waves of <b>depolarization</b> activity
This depends on:

a) magnitude of 'source' membrane current and voltage changes

b) volume conductor electrical properties

c) position of the electrodes relative to the moving wave of the electrical currents and potential associated with depolarization and repolarizaiton.
The P-wave is due to:
arterial depolarization
The distance between P-wave and R-wave is the estimation of:
<b>Depolarization wave</b> (DW) transit time from

atria → ventricles.

Orange- depolarization
Gray - Isoelectric point / ST-segment
if a drug increases the duration of plateau phase (Φ2), which part of the EKG would appear longer?
S-T segment.

It correlates with the plateau phase.
The ______ complex reflects movement of the DW as it rapidly sweeps down the septum and depolarizes the ventricle, apex, lateral wall and base.
QRS
How does the level of Ca⁺⁺ changes in response to arrival of AP.
rises from ~0.1 μm to ~ 2μm in about 10 msec.

This is sufficient to activate some, but not all, of the potentially available cross bridges.
Ca⁺⁺ supplied for cardiac muscle contraction comes from two sources; SR stores (internal, ___%) and calcium current during Φ2 (external ____%).
Internal → 80%
External → 20%
What triggers release of Ca⁺⁺ from SR?
entry of Ca⁺⁺ into the cell. (Calcium-induced calcium release.)
Phospho•lamban
its a controlling protein which inhibits and thus regulates the SR-uptake via Ca-ATPase pump.

» NE and E ↓ the inhibitory effects of phospholambin therefore promote relaxation of the muscle.
the degree of stretch on the heart before it contracts.
» In the heart its due to the End Diastolic Volume (EDV).
» Force and Pressure developed by contraction depends DIRECTLY on the preload.

The force ↑ and the Length ↑.
Inotropic state
how forcefully the heart can contract. It is used interchangeably as contractility.

Contractility- myocardial force-generating and length shortening potential at a given preload.
Contratility depends on what factors?
» all the factors affecting muscle's contractile machinery, with Ca⁺⁺ being a major factor.
» Changes can be in either direction (+ or -)
»<b> + Inotropic</b> effects descibes increased force and rate
» <b>+ lusitropic</b> effect descibes enhanced relaxation features of the heart.
The intracellular calcium pool depends on what 3 factors?
1. Magnitude of I<SUB>ca</SUB>
2. Relative duration of Ca⁺⁺ influx (systole) and efflux (diastole)
3. on extracellular [Ca⁺⁺]

Calcium pool is the major factor determining the contractility.
If the inotropic effects increase, would you expect the heart to:
contract faster

If contractility is increased, V<SUB>max</SUB> and shortening velocity at all afterloads increase as illustrated in figure C
What are the effects of sympathetic stimulation of myocardium on the calcium pool?
it will ↑ it and hence it will also increase <i>contractility</i> → ↑ ventricular pressure AND ↑ <u>rate</u> of increase in ventricular pressure.
Clinically, how are we able to measure the cardiac contractility?
by measuring maximum of dp/dt= (dp/dt)<SUB>max</SUB> whcih is an index of the cardiac muscle V<SUB>max</SUB>.
Muscle contraction force and rate (contractility) affect ____ and _____.
Stroke Volume (SV) = EDP-ESP
Stroke Work (SW)

» Stork work is the work done by the heart per beat and it represents ~5-15% of total <i>internal</i> energy requirement.

» Pressure could be MAP

» SW is equal to the area of the P-V loop approximated by the product of SV and MAP
What is the <u>best</u> index of afterload?
stress in the LV wall that needs to be overcome by contracting muscle for muscle to shorten. But clinically, <b>aortic pressure is most often used as the afterload</b>.
What are the major factors determining the stroke volume? (3)
2. Contractility (done by sympathetic*)

* stimulation by sympathetic ↓ inhibition of phospholamban's inhibition of Ca⁺⁺ re-uptake, thus enhacning the calcium pool.

» one way to measure SV is EDV-ESV
What happens in general to the CO if the preload increases?
it will increase.

Increased preload means ↑ SV and we know that
What is the BEST index of preload?
End Diastolic Volume (EDV)
Peak isovolumic pressure
the linear increase in LV pressure and LV volume if the afterload is at its MAX (e.g. Aorta is clamped!). If the afterload is not at its max, then the relationship will not be linear.
What are the probable explanations for the fact that stretched ventricles contract faster?
• More optimum sarcomere length
• Increased sensivity to Ca⁺⁺
The SV for standing position is actually lower than for supine position, this can be contributed to:
Gravity. At standing position, the gravity lowers the amount of EDV or LVEDP and thus the SV would be lower as well.
Cardiac Function Curve (CFC)
plot of Stoke Volume (ml) vs. LVEDP (mmHg)
Increased contractility shifts the CFC _____.
upward resulting in a greater <b>SV</b> for any preload.
Physiological changes in contractility are mostly determined by which part of nervous system?
Sympathetic activity.
Positive inotropic drugs
drugs that ↑ contractility

» They often achieve this by increasing Ca⁺⁺ availability to <b>myocyte contractile machinery</b>.
The <i>true</i> afterload on the heart is proportional to the wall stress within the myocardium during its contraction.

practical afterload is the arterial pressure against which the heart must act.
Because the ventricle has to develop a greater pressure in the case of an increased afterload, more of the contraction process goes into raising the pressure than into ejecting blood.
How is SV maintained if contractilty decrease?
by increasing the EDV

Increased EDV will move the point along the S-F curve back up the the original value.
Atrial kick
the remaining 30% of blood that enters into the ventricles from the atrium during ventricular filling / 70% enters <u>passively</u> without muscle contraction from SA node
The decrease in volume of the ventricle prior to ejection is called:
There is no decrease in volume!

Ventricular PRESSURE increases but both Mitral and aortic valve are closed and volume is <u><i>constant</i></u>. this is known as <b>isovolumic contraction</b> phase (<b>Phase 3</b>)
phase 4 of cardiac cycle
<b>Ejection</b>!

Ventricular pressure > aortic pressure
Ejection fraction (EF)
measurement of the volume percentage of left ventricular contents ejected with each contraction. <u> EF is the BEST indicator of pump function</b>.
What is the BEST indicator of the pump (heart) function?
Ejection fraction (EF)
S1 sound is associated with:
<i>Onset</i> of ventricular systole and the closing of the inlet valve.

S2 is associated with the onset of ventricular diastole and closing of the outlet valve.
Which of the heart sounds is associated with QRS curve on the EKG?
S1 which is associated with onset of ventricular systole and the closing of the inlet valve.
Peak RV and pulmonary artery pressures are about _________ in the LV and aorta.
1/5 that
What causes closure of the mitral valve?
↑ pressure in the LV.
(T/F) The ventricular pressure decreases immediately after aortic valve opens up.
False.

Volume drops immediately though.
What happens to aortic pressure as soon as aorta closes:
Begins to drop
The highest ventricular pressure occurs during what phase of Wiggers diagram
Ejection ~ 120 mmHg
(T/F) Any factor that ↑ wall tension or that increases the time over which the tension acts, increases energy need.
true
(T/F) difference (systolic-diastolic) is pulse pressure (PP)
True
What are the consequence of missed heart beats?
If heart beat is missed, the aortic volume is not replenished continuously, and thus peripheral 'runoff' causes a progressive decrease in BP.
Explain three ways in which Partial pressure (PP) can increase:
1. Increased rate of LV ejection
2. Increased stroke volume
3. Decreased aortic compliance
(T/F) if all other factors fixed: PP∝SV
True. but any SV, a greater PP results if <i>ejection rate</i> is greater since ~75% of SV occurs during early ventricular ejection.
↓ compliance means ____ systolic and diastolic.
Increased
What is the equation that best describes the effects of resistance on arterial pressure?
Where is the correct place fore measurement of BP on the arm?
level of the <i>right</i> Atria
Hydrostatic pressure
Hydrostatic pressure is the pressure exerted by a fluid at equilibrium due to the force of gravity.

If the arm hangs down, HP is added to the transducer.
MAP depends on three factors:
1. Cardiac output (CO)
2. Total Peripheral REsistance (TPR)
3. Vascular blood volume to vascular compliance (BV/C)
an ↑ in Blood volume (BV) tends to ____ MAP.
increase
If the compliance decrease in arterioles, what happens to the pulse wave/speed wave?
It will ↑↑ because wave-speed is inversely related to the square root of aortic compliance and is directly related to ejection rate. So stiffer arteries ~ higher speed

C<SUB>0</SUB> - Pulse wave "wave speed"
C - compliance

» Compliance is usually more important factor than ejection rate.
How would you describe a pulse at any point in artery?
is the algebraic sum of <u>forward transmitted pulses</u> and <u>reflected backward pulses</u>.
Vasomotion
Arrhythmic changes in arteriole diameter
The resistance in capillaries is generally______.

a. low
b. high
a. low

because capillaries are in parallel.
Name a few places/organs where you would find <b>discontinuous capillaries</b>?
Bone marrow
Spleen
Liver
Name a few organs where you would find fenestrated capillaries.
1. Kidney glomeruli
2. Intestinal mucosa
3. Endocrine Gland
What is the Fick's law for PS products?
(1) simple one-dimentional representation of diffuion processes

(2) Transcapillary exchange in a capillary network is directly which is DIRECTLY to <i><b>total</i></b> available capillary surface area and <i><b>overall</i></b> capillary permeability via the Permeability-surface area products.

T and C are tissue and capillary concentration
Trancapillary exchange in a capillary network is directly related to what 2 factors:
1. <i><b>total</i></b> available capillary surface area
2. <i><b>overall</i></b> capillary permeability via the Permeability-surface area products.
Pores between adjacent EC are _____ nm in diameter and ____% of the wall area.
~ 4 nm
~ 0.02%
A molecule with MW of 63,000 is considered:

a. small molecule
b. larger molecule
b. larger molecules

they are also called <i><b>diffusion limited</b></i>.
Very low capillary density means ______ rate of diffusion

a. lower
b. higher
a. lower
The <u>direction</u> and <u>amount</u> of fluid movement across capillary walls depends on:
Net filtration pressure ΔP<SUB>FILT</SUB>

P - pressure
π- Osmotic pressure

P<SUB>C</SUB>- P<SUB>T</SUB> = Transmural pressure
Filtration flow (Q<SUB>F</SUB>)
K<SUB>T</SUB> - depends on a tissue specific capillary <i>filtration coefficient.</i> » it has units of conductance and its <u>value varies with organ specific function</u>.
oncotic pressure
The osmotic pressure in the blood vessels due only to plasma proteins (primarily albumin) --> causes water to rush back into capillaries at end.

★ Although Intravascular pressure ↓ along the length of a capillary, oncotoic pressure <u><b>stays constant</b></u>.
Which of the following will increase the absorption in the capillaries?

a. terminal arteriole vasoconstriction
b. terminal arteriole vasodilation
a. terminal arteriole constriction

the normal pressure is 35 mmHg
vasoconstriction can reduce the pressure to 20 mmHg at which you have full absorption in the capillaries
Vasodilation can increase pressure up to 50 mmHg at which point you have full filtration in capillaries.
What is the main force behind entry of interstitial fluid into lymphs?
↑↑ pressure in the surrounding tissue which will widen the overlap between EC.
lymphangions
lymphatic vessels empty to collecting ducts which have:
» Contain smooth muscle
» valves spaced at varying distances

The space between the valves are called <B>lymphangions</b>. They contract in a peristaltic-like pattern

disfunction can → lymphedema
What happens to Pc for each of the following:

a. if Venous volume ↑
b. if the venous vessles are compressed
c. there is obstruction in venous vessels (venous thrombosis)
d. Conjestive heart failure
it will increase in all the cases
hypoproteinemia
abnormally low level of protein in the blood which could be due to starvation.
it will decrease blood osmolarity and therefore promotes filtration rather than absorption.
What's the normal supine average pressure for RA and CVP?
~ 3-5 mmHg

prepheral veins/venules ~15 mmHg
(T/F) the hydrostatic pressure and TMP increases by 0.77 mmHg per 1 cm below the RA.
True
If the distance between the right atrium and the collpas point of jugular vein is 25 cm, what is would be the CVP?`
In collapsible vessels, such as veins, Q equals:
Q is proportional to P<SUB>U</SUB> - P<SUB>D</SUB>
In collapsible veins, the collaps first occurs at the closest to:

a. upstream
b. downstream
b. downstream

This is due pressure loss along the vessel.
point 1 in the graph
Flow-induced arterial vasodilation
mechanism for relaxing arteriolar smooth muscles that involves detection of shear stress by endothelial cells which release parcime inhibitors of contaction. I occurs by an increase in blood flow (Q)
Name two substances released by EC that alter tonicity of blood vessels:
1. Nitric oxide (NO) → vasoDILATOR
2. Endothelin (ET) → vasoCONSTRICTOR
Which neurotransmitter can act to both cause vasoconstriction and vasodilation?
Epinephrine

However the predominant effect in vessels with both α and β<SUB>2</SUB> receptors is <i>vasodilation</i>

e.g. skeletal muscles which have both receptor types.
Vasodilation due to lack of sympathetic activity is known as:
Widthdrawal of sympathetic tone
NE and E act on ____ receptors to cause vasoconstriction.
α

e.g. skin arterioles that only have α receptors
The arterioles in which of the following MOSTLY β<SUB>2</SUB> receptors?

a. skin
b. skeletal m.
c. Myocardial m.
a. skin → mostly α
b. skeletal m. → mixed
c. Myocardial m. → mostly β<SUB>2</SUB> ✓
» don't release NE or Ach.
» release NO and other substances
» effects are prominent in the GI vasculatur and in the penis.
Atrial Natriuretic peptide
hormone secreted by the heart when there is an increase in blood flow which increases sodium excretion. it dilates renal arterioles.
Three types of local control of blood flow
1. Autoregulation → blood flow maintenance despite changes in organ perfusion pressure.

2. Active hyperemia → Blood flow changes to meet current or changing metabolic demands

3. Reactive hyperemia → Blood flow increases to meet prior blood flow deficits
A change in blood flow to the stomach after eating a meal is an example of:

a. autoregulation
b. active hyperemia
c. Reactive hyperemia
b. active hyperemia
Myogenic Response
↑ stretch of the vessel wall due to changes in transmural pressure causes a reflex constriction and decreased stretch causes a reflex dilation. (interesting!)
In which of the following organs, <b>autoregulation</b> does NOT occur:

a. brain
b. kidney
c. lungs
d. cardiac muscles
e. skeletal muscles
a. brain
b. kidney
c. lungs ✓
d. cardiac muscles
e. skeletal muscles

note:
» Autoregulation only works for a certain pressure range. at pressure above or below this range, it does not work
» Its partially due to <i>myogenic effect</i> and partially to <i>vasodilator metabolites</i>.
Functional hyperemia
↑ in blood flow associated with an increased blood flow <i><b>demand</i></b> stemming from an increase in metabolic activity. (e.g. exercise)

AKA metabolic vasodilation and ACTIVE hyperemia
The reactive hyperemia flow peak and duration depends on:
amount of flow deprivation. the longer the deprivation time, the higher is the peak of the reactive hyperemia.
Reactive hyperemia depnds on:
short term → myogenic response (1-3 mins)
long term → vasodilator metabolite build-up within the tissue (after ~15 mins)
After _____ minutes of flow stoppage, hyperemic response is near maximal.
15 mins

If the flow stoppage is extended, hyperemia may NOT occur.
(T/F) For a long flow stoppage time, >>15 mins, the reactive hyperemia may not occur.
True

This impairment is related to <b>ischemia-reperfusion injury</b> that is in part due to damage caused by <u>oxygen-derived free radicals during ischemia</i> and to effects mediated by returning blood flow.
How is <B>heart rate</b> regulated?
by the action of:

Afferent → mechanical/chemical receptors
Efferent:
1. sympathetic activity (NE) ++
2. vagal activity (ACh) --
3. Hormones (NE,E) ++
Stroke volume is <u>largely</u> depends on _______ activity which alters the Ca⁺⁺ availability and changing cardiac contractility.
sympathetic

Example of negative feedback control include _____________ processes that target the maintenance of blood pressure.
baroreceptor

► found in :
» Carotid sinus / Aortic arch
» 'High' pressure - Arterial system
» 'Low' pressure - venoatrial system
► for <b>short term</b> BP control
The receptors in the <b>carotid body</b> respond to:
1. Hypoxemia (Low O₂) (not so sensetive)*
2. Hypercapnea (high CO₂) (Sensetive)
3. Acidosis (Low pH)

* only if it drops to 65-70 mmHg from a normal value of ~95 mmHg.

► causes ↑ TPR which lead to BP
Aortic receptors vs. carotid receptors.
difference is in their location. they both detect stretch and distortion (baroreceptors)
Carotid receptors can:

a. detect increase in pressure
b. decrease in pressure
both. the system is bidirectional

They respond to:
» ↑ BP
» ↓ ejection rate and ↓ PP
Indicate each of the following EKG components to relationship of AP.

a. P
b. P-R
c. QRS
d. ST
e. T
f. QT
a. P → Deplorization
b. P-R → Atrial-Ventricular
c. QRS → ~ Upstroke
d. ST → ~ Plateau
e. T → Replorization
f. QT → ~ AP duration
(T/F) Afferent impulses originating in the reticular formation that converge on the vasomotr center cause BP changes induced by pain.
True
Baroreceptor
are sensors located in the blood vessels of several mammals. They are a type of mechanoreceptor that detects the pressure of blood flowing through them, and can send messages to the central nervous system to increase or decrease total peripheral resistance and cardiac output. Baroreceptors act immediately as part of a negative feedback system called the baroreflex
which receptors are activated in an individual hyperventilating due to exercise ?

a. baroreceptors
b. chemoreceptors
both
a. baroreceptors → regulation of bp
b. chemoreceptors → breathing regulation
Vasomotor center
found in the medulla oblongata. It exerts sympathetic control over blood vessels throughour the body by the remote control of the autonomic nervous system.
At what point (how low) does the chemoreceptors respond to low O₂?
when O₂ drops to about 65-70 mmHg from a normal value of ~95 mmHg
If the blood pressure drops to 59 mmHg (severe hemorrhage), which of the following is mainly involved in maintaining blood pressure?

a. chemoreceptor-driven vasoconstriction
b. baroreceptor-driven vasoconstriction
a because the baroreceptor low-end threshold for activation is ~65 mmHg.
<i>Central</i> Chemoreceptors are located in_____.
Medulla

very sensitive to ↓ pH in the surrounding CSF
High intracranial pressure activates which receptors?
» <b>Central chemoreceptors</b> which leads to a large ↑ in blood pressure accompanied by:

» A <b>baroreceptor</b> induced <i>reflex bradycardia</i>

THIS IS <b>CUSHING</b> reflex
<b>Cardiopulmonary Receptor<b> measure what?
they measure blood pressure in the venous system?

» They are <b>mechanoreceptor</b> / baroreceptor
» located near venoatrial junction (meylinated A and B fibers) OR diffusely scattered (non-myelinated) in atria and right ventricle.
bainbridge reflex
A second reflex pathway originating from the vascular system that keeps venous pressure low and preventing pooling of blood on the venous side of the circulation.

In response to high venous blood pressure it <b>selectively</b> ↑ SA/heart beat

► Sympathetic drive to heart <i>muscle</i> is NOT increased nor is TPR changed.
The LCA and RCA arise in the _________at root behind aortic valve cusps.
sinus of Valsalva

RCA mainly supplies RV and RA
LCA mainly supplies LV and LA but there is considerable overlap.
What is the mian route of drainage from the heart?
via coronary sinus into RA (95%)
~5% returns via anterior cardiac and thebesian vein.
a very small amount of coronary venous blood also flows back into the heart through very minute __ veins, which empty directly into <b>left</b> chambers.
Thebesian

► this way it bypasses the pulmonary circulation and the systemic circulation is diluted
What is the basal coronary flow?
~75 ml/min/100g

» a 5X increase may occur at maximum cardiac work.
At rest myocardial O₂ consumption is high _____ which is ~20X that of resting skeletal muscle!!
~8 mlO₂/100g
<i>Most</i> of blood flow into coronary arteries happen during which phase?

a. diastole
b. systole
a. diastole

flow <u>pattern</u>, especially in LCA, is due to systolic compression of arteriolar vessels within contracting myocardium.

Thus → arteriral inflow peaks during diastole as the ventricle relaxes and venous outlfow occurs during systole as intramyocardial forces compress veins.
What is the most important factor determining coronary blood flow (CBF)?
O₂ demand which means metabolic activity. Increased O₂ demand is met <b>ONLY</b> be adequately met by a blood flow increase.
(T/F) The lower end of the autoregulation range in human is ~50-70 mmHg depending on the myocardial region.
T
What happens if perfussion pressure drops below the autoregulation's lower end?
vasodilation is not demonstrated and flow would actually decrease since the reverse is exhusted.

In the graph: the amount of autoregulated flow (vertical position of 'plateau') changes with metabolic demand. how ever low range of regulatory range remains the same.
What is the anatomical gaurd against ischemia
Circle of willis
What is the basal cerebral flow
~50 ml/min/100g (Less than heart!)
What are the cerebral physiological vasodilators?
1. CO₂
2. K⁺