CV lecture one1.) Electrophysiology

a. Action potentials & conduction velocity differs within the heart

b. Compared to other tissues the heart has a relatively long AP and Refractory period

2.) Phase zero, the upstroke of the action potential is: ( see graph on page 3)

a. Relatively fast in Atrial myocytes, Ventricular myocytes, and conduction fibers

b. Relatively slow in SA & AV node

i. This is essential for ventricular filling

3.) Membrane potentials

a. Na & Ca are in higher concentration outside the cell & K is higher in the cell

b. Phase 4:

i. Ventricles, Atria, & His-Purkinje system

1. Stable Resting membrane potential (-90 mv)

2. Potential is determined by K, which has the highest conductance

3. Na plays a minor role, because it is not very permeable

4. Current is Ik1c. Phase 0 the Upstroke

i. Transient increase in Na conductance=> Na influx

d. Phase 1

i. Transient repolarization

ii. due to (1) decreased Na conductance ( inactivation gates are closing) and (2) the concentration and charge gradients favor K outflow

e. Phase 2

i. Plateau

ii. Due to increase in Ca conductance & decrease K conductance

1. L type Ca channels

iii. These forces oppose each other

f. Phase 3

i. Repolarization

ii. Ca conduction decreases & K increases

iii. Outward Ik repolarizes the cell

4.) Slow response (SA & AV)

a. Phase 4 in SA & AV nodal cells

1. Resting membrane is not stable (max is -65mv)

2. Ik1 is very low or absent

3. If , a Na current, is responsible for the spontaneous depolarization ( automaticity) of the SA node4. If is turned on by repolarization ensuring that a new AP is always generatedb. Phase 0

i. is due to a Ca current, not Na

1. T-type Ca Channels

ii. not as rapid or sharp as in other cardiac tissue

c. Phase 1 & 2 are absent

d. Phase 3 due to outward K current

5.) Conduction velocity trend: Purkinje > ventricles(atria> SA (AV

a. Conduction velocity depends on the size of the inward current during the AP upstroke & cable properties

b. Length of the AP does not matter

6.) Frequency of firing

a. SA>AV>His-Purkinje

7.) Activation Sequence of Heart

a. SA=> Left and Right atria via intermodal tracts=>AV node=>Bundle of His=>Purkinje systems

8.) The SA normally serves as the pace maker

a. AV node & His-Purkinje are latent pace makers

b. The fastest rate of phase four depolarization determines what myocardial component will act as the pace maker

c. Under normal circumstances: fastest-SA>AV> His-Purkinje-slowest

d. Ways to change pace maker activity

i. Alter (1) phase four rate of depolarization (2) max negativity of phase four (3) threshold potential

ii. Lecture Examples:

1. Sympathetic Stimulation increases SA phase 4 depolarization

2. Parasympathetic (vagal) stimulation decreases SA phase 4 depolarization

3. Drugs can decrease SA depolarization, by increasing the threshold potential ( see graph pg 10)

a. Ex: Quinidine 4. A reduction of Ca current in slow response cells can also influence automaticity (graph pg 15)a. Normally the Ca current is activated at the end of phase 4 depolarization and accelerated the rate of diastolic depolarization

b. Decreases in extracellular Ca or use of Ca antagonist decreases the amplitude and slope of the slow diastolic depolarization in the SA node

9.) Factors affecting AP

a. Amplitude, Rate of change ( dVm/dt) phase 0, Resting membrane potential

10.) Lecture Examples AP

a. Timing of AP

i. APs that occur too early (A) will induce very small nonpropagated responses. APs that occur early (B) in the relative refractory period have smaller amplitudes and les steep upstroke slopes than those occurring later in the refractory period. The conduction of APs early in the refractory period is also relatively slow. If conduction is too slow=> conduction block. (see graph pg 8)

b. Tetrodotoxin blocks Na channels (see graph of bottom on pg 11)

1. Decreases the amplitude & rate of rise of AP by decreasing Na current

2. Additionally the notch, which represents Ito, the transient outward K current during phase 1 repolarization one decreases and eventually disappears with higher doses on Tetrodotoxin

3. transforms fast AP (purkinje) into a slow AP (SA)

c. Increase in extracelluar K concentration (see graph of bottom on pg 12, pg 300 of book)

i. Occurs in patients with coronary artery disease

1. Diminished blood flow to the myocardium results in reduced Na-K pump activity=> (intracellular Na and ( extracelluar K

ii. Graph A is normal

iii. B-E:

1. As extracelluar K is increased=> less polarized membrane potential=> easer to reach threshold

2. As a result amplitude, duration, and steepness of the APs all diminish=> decreased conduction velocity

3. In Graph D & E the membrane voltage reaches the point were all fast Na channels are inactivated=>cell behaves as slow response cell

d. L type Ca Channels

i. Norepinephrine, increases Ca conductance during the plateau (sympathetic)

ii. ACH decreases Ca conductance during plateau (parasympathetic)

iii. Enhancement of Ca influx through L type receptors by isoproterenol (graph pg13)

1. L is for long lasting, these channels open during the upstroke at about -20mV and stay open throughout the plateau

iv. Ca channel antagonist (see graph pg 14)

1. verapmil, amlodipine, & diltiazem

2. Decrease ca current=> diminish length of plateau=> decreased myocardiac contraction force

11.) Relationship btwen CV and AP

a. Conduction velocity along the fiber varies with the amplitude of to AP and the rate of change of the potential (dVm/dt) during phase 0. The amplitude of the AP = the potential difference between the fully depolarized and fully polarized regions of the cell interior.

Random:

Cardiac glycosides inhibit the Na-K pump=> intracellular accumulation of Na=> decreases the activity of the Ca/Na exchange pump

CV 2 ElectrocardiographyEKG = electrocardiogram (ECG or EKG)

Measures the sum of all electrical forces at the level of the persons skin using electrodes

Direction and magnitude of the deflections on the EKG depend on how the electrical forces are aligned with respect to a set of specific reference axes

Electrical current flows from negative to positive charge

Upward wave = current flowing towards the positive end of the skin electrode

Downward wave = current flowing away from the positive end (twds neg end) of skin electrode

Current Vectors:

When current is flowing parallel in the same direction as the lead ( max pos. increase on EKG

When current is flowing parallel in the opposite direction of the lead ( max neg. increase on EKG

When current is flowing at an angle toward the positive end of the lead ( some positive increase on EKG

When current is flowing at an angle away from the positive end of the EKG ( some negative decrease on EKG

When current is flowing perpendicular to lead ( flat line

When there is no current ( flat line

EKG Leads 12 total leads, 6 on limbs and 6 on chest (precordial leads) 6 limb leads:

3 standard or bipolar (have a positive and negative direction)

Lead I = R arm to L arm

Lead II = R arm to L leg

Lead III = L arm to L leg

3 augmented or unipolar (have only a positive direction)

aVR = from body wall twds R arm

aVL = from body wall twds L arm

aVF = from body wall twds L foot

the limb leads only detect cardiac vectors on the frontal plane of the body

the normal average mean electrical axis is approximately +60

the magnitude of the deflection reflects how parallel the electrical force is to the axis of the lead being examined

6 chest/precordial leads: all unipolar (have only a positive direction) From R to L: V1, V2 (straight down), V3, V4, V5, V6 (straight towards L side of body) V1 and V2 = record mainly electrical activity of right ventricle

V3 and V4 = record mainly electrical activity of the septum

V5 and V6 = record mainly electrical activity of the left ventricle

The chest leads detect cardiac activity in a horizontal plane

Electrical Conduction

Normal beat starts at the SA node (junction of RA and SVC)

Electrical propagation through the heart: SA node ( atria ( AV node ( common bundle ( bundle branches ( Purkinje fibers ( ventricles

Reflected by 3 major deflections on the EKG P wave, QRS complex, and T wave

SA and AV node have slow response

Repolarization of the atria are hidden in QRS during depolarization of ventricles (dont see it)

P wave = atrial depolarization

QRS complex = ventricular depolarization

T wave = ventricular repolarization

EKG on frontal plane

PhysiologyWaveVector Direction (frontal plane)

1) impulse origin and atrial depolarizationP wave

2) septal depolarizationQ wave

3) apical and early ventricular depolarizationR wave

4) late ventricular depolarizationS wave

5) repolarizationT wave

EKG on the horizontal plane QRS is mainly negative in V1 and positive in V6

V3 and V4 are isoelectric transition electrodes the up and down portions of the QRS are equal

Interpreting the EKG Paper moves at a constant speed of 25mm/sec

Thick lines occur every 5mm, thin lines occur every 1mm

X-axis is time ( 5 large boxes = 1 sec (1 large box = .2sec, 1 small box = .04sec)

Y-axis is voltage ( 1.0mV produces a deflection of 10mm (each small box represents .10mV and each large box is .5mV)

EKG Analysis1) Voltage calibration

In some cases of hypertrophy or bundle branch blocks, QRS complexes are larger than normal ( recording is made at standard voltage ( 1.0mV = 1 large box (instead of normally where 1.0mV = 2 large boxes)2) Rhythm

Normal rhythm is called the SINUS RHYTHM, which has 4 components:

Every P wave is followed by a QRS complex

Every QRS complex is preceded by a P wave

The P wave is upright in leads I, II, and III

The PR interval is greater than 0.12sec (three small boxes)3) Rate

Normal rate is between 60-100 beats/min

There are three methods for calculating rate

Count the number of mm between 2 consecutive QRS complexes to use the equation: Memorize the value that corresponds to HR of each sequential large box after the first QRS peak 1st = 300, 2nd = 150, 3rd = 100, 4th = 75, 5th = 60, 6th = 50 (use this to estimate the HR depending on where the next QRS peak is) Count the number of QRS sequences between a 3 second interval and multiply by 20

This is particularly useful for determining irregular HR4) Intervals (PR, QRS, QT)

PR = from the beginning to P to the beginning of Q (normal = 0.12-0.2 sec)

QRS = from beginning of Q to end of S (normal < 0.1 sec)

QT = from beginning of Q to the end of T (normal = 0.3-0.4 sec)

5) Mean QRS Axis

EKG represents the average electrical activity

QRS axis is usually -30 to +90

QRS axis is primarily upwards in leads I and II

If it is not, the axis is abnormal (not +60) and should be determined from the limb leads by finding the most isoelectric limb lead, then looking at the lead perpendicular to it ( the mean axis points to the positive pole of that lead if it is a +QRS

6) Abnormalities

Look for variance in voltage, rhythm, rate, interval durations, and axis and combine with variances in shape of the wave forms

Atrial Enlargement RA enlargement P wave has double bump with left side of bump (which represents the RA) larger than the right side (represents the LA)

LA enlargement P wave had double bump with right side of bump larger than left side

Sinus Bradycardia APs originate at SA at slow pace ( slowing of HR

All complexes are normal and evenly spaced but the rate is 100bpm Wandering Atrial Pacemaker impulses orginate from varying points in atria Variation in P wave contour, PR intervals, PP and thus RR intervals, normal QRS and T

Wolff-Parkinson-White (preexcitation) Syndrome impulses originate at SA node and preexcite peripheral conduction system and ventricular muscle via bundle of Kent without delay at the AV node After normal delay at AV node, also get impulses via regular route ( double depolarization

P wave is immediately followed by short delta wave, producing slurred upstroke on wide QRS w/short or no PR interval

First-Degree Heart Block fixed but prolonged PR interval P wave precedes each QRS complex, PR interval is uniform but >0.2sec

Second-Degree Heart Block (Mobitz 1/Wenckebach) progressive worsening of PR interval with intermittent dropped beats Starts with good rapid conduction across the crest of the AV node and normal PR intervals ( conduction gets worse and PR gets longer until conduction fails and QRS is dropped, then the AV node recovers and PR goes back to normal (continuous cycles of this)

Third-Degree (complete) AV Block no relationship between P and QRS, ARS rate slower than P rate Impulses orginate at SA node and below the AV node block Junctional Rhythm atria and ventricles depolarize independently, QRS less frequent, regular at 40-55/min but normal in shape

Idioventrical Rhythm atria and ventricles depolarize independently, QRS less frequent, regular at 20-40/min but with wide and abnormal shape

AV dissociation no relationship between P and QRS ( QRS is faster than P slower supraventricular rhythm and rapid ventricular rhythm ( P waves less frequent than QRS and totally unrelated

Bundle Branch Blocks R ventricular block extra vector of depolarization on the R side (R), wide QRS, longer time

L ventricular block extra vector of depolarization on the L side (R), widening of QRS and R

*when reading an EKG, find the most isoelectric lead and use the one perpendicular to it to get your info!

Cardiac Cycle CV Lecture 3

I) Cardiac Cycle is composed of two parts (more in IV)

A) Diastole: relaxation and filling of the heart

B) Systole: contraction and emptying of the heart

II) The heart has four separated chambers

A) Two atria

B) Two ventricles

C) Valves prevent back flow of blood

1) Atrium separated from ventricle by an atrioventricular valve

(a) Right = tricuspid valve

(b) Left = mitral (aka bicuspid) valve

2) Ventricle separated from arteries by semilunar valves

III) Right side of heart

A) Blood from venae cavae to the right atriumB) From right atrium through the tricuspid to the right ventricleC) Right ventricle through the semilunar valve to the pulmonary arteryD) Same deal on left side, with different names of valvesvenae cavae ( right atrium ( (tricuspid valve) ( right ventricle ( (semilunar valve)

(

(body

pulmonary artery

( Blood Flow Through the Heart

(aorta

lungs

(

(aortic semilunar valve ( left ventricle ( (mitral valve) ( left atrium ( pulmonary vein

IV) Cardiac cycle and ElectrocardiogramsA) Diastole1) Isovolumetric relaxation Looks like end of systole, but actually beginning of diastole(b) Semilunar valves and AV valves closed(i) Pressure in ventricles is higher than pressure in atria(ii) Pressure in ventricles is lower than pressure in aorta(iii) Aorta > Ventricle > Atria(c) No volume change(d) Pressure starts to decrease in ventricle(e) Transient increase in atrial pressure = dicrotic notch, imp. to blood pressure measurement2) Passive filling(a) Atria start to fill with blood from venae cavae(i) Pressure increases a little(ii) AV valves open(iii) Rapid filling of ventricles(b) Both atria and ventricles are relaxed(i) Blood is filling in the atria(ii) Blood is also entering the ventricle through the open AV valve, reduced filling(c) Pressure in left atria slightly higher than in left ventricle(d) Volume rises in the ventricle3) Atrial Contraction(a) End of Diastole = Atrial depolarization(b) SA node fires action potential(i) Depolarization and contraction of atria(ii) P wave(c) Atria contract and send more blood to ventricles, end filling increase in ventricular volume4) Three phases of filling: rapid, reduced, end(a) filling of ventricles depends on frequency of contraction (because it occurs during diastole)(b) increasing frequency of contraction (heart rate) gives same end diastolic volume

(i) decrease volume in ventricles if heart of >200 beats per minute

(ii) athletes have a lower heart rate because contraction is more forceful still sending same amount of bloodB) Systole1) Isovolumetric contraction(a) Wave of depolarization travels(i) Delay at AV node(ii) Travels through conduction system(b) Ventricular contraction (i) QRS complex = depolarization of ventricles(ii) Pressure increase in ventricles Ventricle pressure higher than atrial pressure Atrioventricular valves close (prevent back flow) Pressure has not reached/surpassed pressure in the aorta

(iii) Volume stays the same end diastolic volume still

2) Ventricular ejection

(a) Pressure in ventricle surpasses pressure in aorta

(i) Semilunar valves open, blood enters aorta

(ii) Volume in ventricle decreases

(b) Ventricles repolarize T wave No further contraction

(i) Pressure in ventricle falls

(ii) Semilunar valves close, prevents backflow to ventricles

(c) Maximum ejection of blood

(i) End diastolic volume remains in ventricles

(ii) End systolic volume End diastolic volume = stroke volume

(iii) 135 ml 65 ml = 70 ml ejected with each contraction

3) P wave atrial depolarization, QRS complex ventricular depolarization, T wave ventricular repolarization (U waves, not always seen, may represent repolarization of Purkinje Fibers, prominent in hypokalemia)

Basically, look at and understand slide 5: events of the cardiac cycle. A comparable picture can be found on p. 149 of Costanzos Physiology (3rd ed.) with explanations from p. 148 -151Cardiovascular System Lecture 4: Hemodynamics and Flows

I. Velocity, Flow and Cross-sectional Area

a. the cardiovascular system is arranged in series and parallel circuits

b. the cardiovascular system attempts to maintain constant flow

i. velocity will vary inversely with cross sectional area

v=Q/A

c. cross-sectional area is greatest in capillaries followed by venules/veins

d. velocity decreases as cross-sectional area increases

i. though the cross sectional area is greatest in the capillaries, the largest drop in pressure occurs between the arteries and arterioles

1. this is because there are far more capillaries arranged in parallel than arterioles, and thus the total resistance is much less for capillariesthis concept will be explored shortly

e. since the cross-sectional area increases as we proceed through the circulatory system (from aorta to arteries to arterioles to capillaries), velocity decreasesII. Relationship between Velocity and Pressure

a. total pressure = lateral pressure + dynamic(or kinetic) pressure

b. effect of velocity on dynamic component of pressure can be estimated from the eqn.:

Pdyn=(v2/2

i. in most arterial locations, the dynamic pressure will be a negligible fraction of total pressure

ii. at sites of constriction/obstruction, dynamic pressure may increase significantly

c. pressure falls linearly with length along the tube (vessel)

d. lateral pressure will decrease in areas where velocity increases, i.e., lateral pressure in narrow sections will be less than the lateral pressure in wider sections

III. Relationship between Pressure and Flow

a. Poiseuilles Law: applies to steady laminar flow of newtonian fluids

i. N.B. not ACTUALLY applicable to CV system, because flow is pulsatile, vessels are not rigid cylinders, and blood is not newtonian

b. Poiseuilles Law describes the flow of fluids through tubes in terms of flow, pressure, dimensions of tube, and viscosity of liquid

c. Equation:

Q = ( (Pi Po) r4 / 8(l

d. flow through the tube will increase as pressure gradient is increased; flow will decrease as either viscosity or length increases; radius is critical because it is raised to 4th power; flow is directly proportional to radius

e. at this point, his lecture goes into a number of slides indicating many of the relationships indicated above; basically, understand the equation and how changing any of the variables will affect the others

IV. Resistance to Flow

a. similar to Ohms Law for electrical circuits: R= E / I

b. for fluid dynamics:

R = Pi Po / Q = 8(l / r4 (c. vessel diameter is principal determinant of resistance

i. this makes sense, since the resistance will be inversely proportional to the radius to the 4th power; other factors will not have such a major effect

ii. arterial occlusion has a large effect on flow: if the radius of an artery (with P=120mmHg) is decreased by 20%, flow will drop from 100ml/min to 41ml/min and it will take a P=293mmHg to restore normal flow

d. Total resistance in a series arrangement equals the sum of individual resistances

i. Rt = R1 + R2 + R3 +

e. Total resistance in a parallel arrangement equals the sum of reciprocals of individual resistances:

i. 1/ Rt = 1/ R1 + 1/ R2 + 1/ R3 +

f. thus, total resistance in parallel arrangement will be less than similar resistance in series arrangements

g. Advantages to parallel arrangement of resistors:

i. can regulate flow to certain destinations

ii. total resistance is less than the resistance of any one resistor

iii. impact of changes in resistance of a few vascular beds on blood pressure is minimized

iv. optimizes gas and substrate distribution dynamics

V. Laminar Flow and Turbulence

a. turbulent flow occurs when fluid does not flow in definite laminae (layers), but rapid mixing occurs (this will happen in blood)

b. in turbulent flow, the pressure drop is approximately proportional to the square of flow rate (compared to first order in laminar flow)

i. i.e., a heart will have to pump harder if turbulent flow develops

c. laminar vs. turbulent flow is determined by the Reynolds number NR using the following equation:

NR = (Dv/(d. NR < 2000, flow is laminar

e. 3000 > NR > 2000, flow is transitional

f. NR > 3000, flow is turbulent

VI. Apparent Viscosity of Blood

a. viscosity may vary considerably as a function of dimension and flow

b. apparent viscosity is used as a derived value of blood viscosity obtained under particular conditions

c. apparent viscosity varies as a function of hematocrit

d. apparent viscosity increases exponentially as hematocrit risesPhysiology Cardiovascular Lecture 5: Arterial Blood Pressure

Arterial Blood Pressure:

Small diameter vessels have a high resistance (ex. Arterioles).

Blood pressure drops a lot at the level of the arterioles.

Elasticity the ability of the blood vessels to deform under stress and then recoil back to their original shape.

Large arteries have high elasticity (lots of elastin fibers in the walls) makes them very efficient hydraulic filters.

Reduces the workload of the heart

With old age ( elasticity and work load of the heart .

Hydraulic filtering and Work:

A. Continuous pump = constant Pressure (P) and Flow (Q)

B. Intermittent pump with rigid tube = larger increase in P and Q with opening and closing of pump. This system works harder and P .

C. Intermittent pump with Compliant walls = Constant P and Q

Energy is stored in the wall of the tube ( allows for constant P and Q, outflow doesnt change.

This is like our circulatory system ( but b/w B + C, because our arteries are not infinitely distensible.

Arteries as Pressure Reservoir:

Systole ventricular contraction ( part of the energy is used to distend arteries, and part to expel blood into aorta.

Diastole ventricular filling ( pressure in the aorta moves blood back towards ventricles, but it is stopped by the semilunar valves.

Dichrotic notch aortic valve closure produces a brief period of retrograde flow from aorta back to the valve, there is a slight decrease in aortic P which creates this extra hump.

Loss of Elasticity in Arteries:

Systole the volume of blood equal to the entire stroke volume must flow through capillaries ( but, if no distension in arteries:

When arteries are rigid, none of the SV can be stored in the arteries, walls are not compliant.

Diastole flow through the capillaries stops during diastole ( rigid arteries cant recoil appreciably ( cant keep constant flow ( intermittent flow results.

Low hydraulic filtering requires more energy.

Increased Energy requirement in a Rigid Conduit:

More energy and O2 is required in a rigid (low hydraulic filter) system ( plastic tubing vs. native aorta.

Compliance

Compliance (C, capacitance) describes the volume of blood the vessel can hold at a given pressure.

Compliance is related to distensibility.

C = V/P

Veins are the most compliant ( can hold the largest volume of blood at low pressure (unstressed volume) Arteries ( much lower compliance, hold much less blood and at higher pressures (stressed volume), most elastic. in compliance of veins ( causes redistribution of blood b/w veins (unstressed volume) and arteries (stressed volume).

Compliance of arteries as age ( walls become stiffer, less distensible, less compliant, hold less blood at any given arterial pressure.Elastance

Elastance is the tendency of arterial walls to recoil. Elastance = P/ (D/D)

D = max amount aorta distends, D = diameter

Elastance 1/Compliance (opposites). Elastance is greatest in arteries, smallest in veins. More elastic tissue leads to more elastic recoil. Mean Arterial Pressure, Pa

Pulse pressure = Systolic pressure Diastolic pressure

If all other factors are equal, magnitude of pulse pressure reflects Stroke Volume (volume of blood ejected from L ventricle on a single beat)

Largest pressure drop is at the level of the arterioles.

Pressure greatest in aorta, and decreases steadily to veins (lowest pressure)

Mean Pressure integral of Aortic P

Pa = Pd (diastolic P) + 1/3 Pulse Pressure

More weight is given to diastolic P because more time spent in this state.Factors that Determine Arterial BP

Physiological Factors 1) CO (HR x SV), 2) Peripheral Resistance Physical Factors Arterial blood volume, Arterial compliance Physiological factors modify physical ones, both modify arterial BP 1) Increasing CO increases BP

If instantaneously, Q doubles ( CO (b/c SV and HR), but P hasnt yet.

As reach steady-state, P to maintain constant flow Recall: Q = P/R As CO, rate of in BP is lower in younger adults ( arteries are more distensible and more compliant. 2) Increasing Peripheral resistance increases BP

If resistance in arterioles (by diameter), initial response is to flow, but get a build up of blood in the system, so BP to push more blood through arteries and maintain constant flow ( therefore P.Arterial Pulse pressure:

stroke volume

\

CO, Peripheral Resistance ( MEAN ARTERIAL PRESSURE

SV ( change in arterial volume, and arterial compliance ( PULSE PRESSURE (systolic P diastolic P)

1) SV ( in Pulse Pressure

a. compliance stays constant ( C = V/P, more energy stored, but no overall change.

b. BUTif low compliance (old age), a V will cause a much greater increase in PP.

2) Total Peripheral Resistance ( preferentially Systolic Pressure

a. Systolic P a lot more than diastolic P with in TPR b/c of in Compliance ( HYPERTENSION.

3) Compliance ( Pulse Pressure

a. lower compliance = syst. P a lot, diastolic P a little ( PP a lot

b. high compliance = pulse pressure very small

c. ARTERIOSCLEROSIS ( diameter of arteries, PP

4) Systolic Pressure as move further from heart

a. as move further/lower from heart ( due to distance and time travel of P wave, BP.

b. In ankle, see small deflection in P wave b/c blood being deflected back towards heart.

Measuring Arterial BP

Constrict artery (usually brachial) block flow of blood

1st sound as release air Korotkoff sound, ~ 120mmHg ( Systolic P

last sound ~80mmHg ( Diastolic P

Korotkoff sound turbulence of flow through small opening, meeting static column of blood causes the noise.

Physiology CV6-Regulation of Arterial Blood Pressure

Determinants of Blood Pressure:

Mean arterial pressure depends on cardiac output, and total peripheral resistance

Cardiac output=Hear Rate x Stroke Volume (CO=HRxSV)

CV6 is all about how these are controlled by our body, either via intrinsic or extrinsic mechanisms to control blood pressure under different circumstances.

Extrinsic: affects CO and TPR

Intrinsic: affects TPR at local levelMechanisms of extrinsic control from fastest to slowest:

Baroreceptors which mediate vascular reflex(NS control, PNS, SNS)

Chemoreceptors (peripheral and central)

Cardiopulmanory receptors

Humoral receptors (slowest, sometimes trigger effects via gene expression)Baroreceptors:

Located in the aortic arch and bifurcation of the carotid artery.

Sense STRECH in the aortic arch and carotids due to increased pressure. Do not directly sense pressure, and relay this information through the vagus nerve.

Sinus nerve from carotid sinus joins the glossopharangeal nerve, which is the ninth cranial pair.

Firing rate is proportional to strech. Therefore with high strech caused by high blood pressure the baroreceptors will fire more frequently, and less frequently with low blood pressure.

Baroreceptors adapt to circumstances. During chronic hypertension, baroreceptors adapt and change their set point, so normal firing rate is at higher than normal blood pressure. The baroreceptor reflex effectiveness is lost with chronic hypertensionChemoreceptors: primarily involved in breathing control

Peripheral: in aortic arch and bifurcation of carotids. Stimulated by a decrease in pO2, increase in pCO2, and decrease in pH

Primary: Causes an (sympathetic) arteriolar vasoconstriction in skeletal muscle, renal, and splanchnic vascular beds. Also a transient parasympathetic lowering of heart rate.

Secondary: increased ventilation, which independently decreases parasympathetic stimulation to the heart, resulting in an increased heart rate

Central: in medualla itself. Sensitive to pCO2 and pH. When flow to the brain decreases CO2 and pH increase. This causes sympathetic stimulation to many vascular beds and increases TPR. This redirects blood flow to the brain and increases arteriolar blood pressure which can be dangerous.

In close association with baroreceptors because they travel to the CNS via the same nerves (Vagus nerve, X) The meduallary cardiovascular center is made up from input from the glossopharangeal nerve, and the vagus nerve which end in the nuclei tractus solitarius (NTS) in the posterior part of the medulla along with other nuclei here such as the dorsal motor nucleus of the vagus nerve, and the nucleus ambiguous from the ninth and tenth cranial nerves.

Cardio Inhibitory area-made up of nucleus tractus solitarius (which is made up of the dorsal motor nucleus of the vagus and nucleus ambiguous)

Vasomotor area-in anterior part of medulla

Cardiac acceleratorExample: In the case of increased blood pressure, the bodys reflex is to decrease blood pressure. This is a baroreceptor reflex.

Baroreceptor(NTS(vasomotor area(inhibit C1 and A1 cells, inhibit cardiac accelerator (slows HR by inhibiting SNS)

C1 causes vasoconstriction through the SNS (Preganglionic ACh, postganglionic NE)

At the same time, parasympathetic activity is stimulated by the nucleus ambiguous and the dorsal motor nucleus of the vagus, further reducing HR. With an increase in blood pressure, baroreceptors from the aortic arch fire closer to the end of systole.

Sympathetic Nervous System Effects

Vasodialation of skeletal muscle increases oxygen supply

Preganglionic ACh release to muscarinic receptors on adrenal medulla causes EPI release. EPI binds to beta-1 receptors on blood vessels and causes vasodialation.

NE also released from adrenal gland in smaller proportions

2 sympathetic inputs to skeletal muscle to cause vasodialation

SNS releases ACh and NE

Adrenal Medulla releases EPI into circulation

Parasympatetic nervous system effects (ACh as neurotransmitter)

L vagus nerve mostly affects AV node

R vagus nerve mostly affects SA node

Decrease blood pressure and subsequently cardiac output at AV and SA node

Heart: decreases contraction, decreased SV, decreased BP

Blood vessels: vasodilation in salivary glands, GI organs, erectile tissue

Does not innervate skeletal muscle or skin. Effects there are under local control (ie metabolism), and due to activation/inactivation of SNS.

Cardiopulmonary receptors

Baroreceptors which are sensitive to low pressure, act in opposition to baroreceptors in aortic arch and carotid sinus.

Nerve terminals located in the pulmonary arteries, vena cavas, atria, and ventricles and muscles

Two types of atrial receptors: A and B

A receptors sense atrial contraction and depolarize

B receptors sense atrial volume and depolarize when the atria are filling

Ex: increase blood volume in atria

Short term response depends on the previous heart rate. If it was low before, it will increase; if it was high before it will decrease due to baroreceptors firing.

Long term (maintain increased blood volume). Vasodilation in the kidney stimulates atrialnaturetic hormone release, and inhibits antidiuretic hormone release. This increases Na secretion, which increases H2O secretion, increases urine volume, and therefore lowers blood volume. Humoral receptors- this is control at the hormonal level, and is referring to the rennin/angiotensis system. See page 7 of Dr. Garcias lecture.

Decreased blood volume is sensed by the kidney

Juxtaglomerular cells release rennin.

Renin functions to transform angiotensinogen to angiotensin I. Angiotensin I is converted to the active form angiotensin II in the lungs and kidneys by ACE.

Angiotensin II functions to:

Release aldosterone from the adrenal gland which increases Na (and therefore water) reabsorption in the kidneys.

Affect Na/H transporter of kidney to retain sodium

Increase total peripheral resistance by affecting small vessels smooth muscle

Cause release of ADH

INCREASE BLOOD VOLUME, PRESSURE, AND SODIUM, brings system back to normal Intrinsic/local control- three things which can all act to modify TPR at the arteriole level.

1. Autoregulation by myogenic (heart contraction) effects, metabolic products, and endothelial products.

a. Autoregulation refers to the ability to maintain a constant flow when the pressure chages.

i. Increased pressure initially causes an increased flow, but smooth muscle relaxes and flow is returned back to normal

ii. Decreased pressure initially causes a decreased flow, but smooth muscle contracts and flow is returned back to normal

iii. These have effects on resistance! (know the effects)

b. Myogenic- explained by stretch receptors in plasma membranes of smooth muscle cells. Increased or decreased pressure causes the blood vessels to strech or relax, which is recognized by the stretch receptors. These will cause constriction or relaxation of muscle to maintain constant flow. 2. Active hyperemia (dilation of arteriolar smooth muscle) stimulated by metabolic and endothelial products during exercise

a. With moderate exercise cardiac output increases from 5L/min to approx. 12L/min

b. Blood vessels are arranged in parallel, so the body can divert blood flow to or away from different areas. Different tissues can receive the same or different proportions of the total cardiac output depending on the activity. For example during exercise skeletal muscle will receive a greater percentage of cardiac output. Blood flow to the brain is always constant. Therefore when cardiac output is increased, the percentage of total cardiac output which goes to the brain will be decreased. (see p. 10 of this lecture)3. Reactive hyperemia (increase of blood flow to an organ) by buildup of metabolic and endothelial products or waste, usually due to an oxygen debt.

a. Increased blood flow to a tissue in response to an oxygen debt

b. Important in heart following a transient ischemic episode (ischemia-lack of proper blood flow/oxygen supply)

Metabolites released following an ischemic episode

Lactate, adenosine, or potassium released from heart or skeletal muscle in an attempt to restore normal flow.

Shear stress on endothelial cells caused by blood flow causes NO to be released, this acts on smooth muscle and causes vasodilation

Other endothelial vasodilators: Prostaglandins, prostacyclin, PGE2

Endothelial vasoconstrictors: Thromboxanes, endothelin CV7 - MicrocirculationCapillaries branch from arterioles

Unlike the smooth muscle cell lining in arterioles, capillaries have endothelium that is important for the filtration of blood and the absorption of nutrients

Met arterioles branch from the arterioles

Some capillaries will still branch off of the arterioles but some will branch off of the met arteriole (see picture in lecture slide)

Precapillary sphincter- increased amount of smooth muscle where the arteriole becomes capillaries

This system regulates the nutritional flow to the organs

If nutrients are not needed, the sphincter will close, blood will go through the met arteriole and directly to the vein (it bypasses the capillaries) this way you are conserving nutrients/ gases for the areas in which they are needed

In contrast, active tissues which are in need of nutrients/ gases, the precapillary sphincter will relax so blood will flow through it to the capillaries

This system also regulates how much blood goes where

If youre older, there is less elasticity in the arterioles, they cannot vasodilate as much, which leads to decreased blood flow which leads to an oxygen debt which can lead to pain

The capillaries still need pressure in order to move the blood forward

How can they withstand this pressure with just thin layer of endothelium?

Law of Laplace!

Tension = pressure times radius (P X r)

Bigger radius = bigger tension

Tension is how much force needs to be applied to make the wall split

(capillaries are small and so there is little tension as opposed to the aorta for example)

Ex) aneurysm diameter increases therefore tension increases, more prone to break

Pinocytosis, diffusion and filtration are the three methods used for exchange of nutrients

Field pores- aqueous holes in the endolthelial wall that allow exchange

Plasma proteins are usually relatively large and stay in the blood

Pinocytosis- is the movement of larger proteins through the use of vesicles out of the capillaries

Ions/glucose/ amino acids- pass through the water pores- diffusion based on concentration gradient

O2, CO2 (lipid soluble) can cross the endothelial wall

Flow limited diffusion- the more flow you have in one tissue, the more flow of blood

The more open capillaries= greater blood flow

He then drew a graph explaining how on the arteriolar side of the capillaries there is a high concentration of molecules

You will see a decrease in the concentration of small molecules in the capillaries as you go from arteriolar to venous side because most of them are small enough to go into the tissues whereas the concentration of medium to large sized molecules will not decrease as much as more of them will stay in the capillary

Also, notice that some cells are farther from the capillary than usual and this leads to edema because the molecules do not reach the tissue cells and this leads to a build up of fluid in the interstitia

Endothelial lining has fenestrations where the endothelium is discontinuous

Fenestrations are bigger in kidney/intestine/liver, form= function!!

These organs are involved in filtration and absorption and thus need many fenestrations

In contrast, the brain has the blood brain barrier and thus has fewer fenestrations and a more continuous endothelium

Forces on capillaries

When resistance on the arteriolar side is reduced, pressure in the capillaries is increased and when vasodilation on the venous side occurs pressure in the capillary is also increased, this leads to a pressure gradient in the capillaries which favors filtration

(so high pressure in the capillaries favors filtration)

Oncotic pressure- proteins in the capillaries exert oncotic pressure which moves water down its gradient into the capillaries

Filtration- bring fluid out of the capillaries

Absorption- bring water into the capillaries

Ex) kidneys you have mostly filtration and in liver you have mostly absorption

Albumin is important for maintaining protein concentrations in capillaries which is key for maintaining oncotic pressure, without albumin, there is less movement of water into the capillaries and more risk for edema

Also, pressure increases on either arteriolar or venous side increases pressure in capillaries and this will increase filtration

Most of the fluid filtrated out is reabsorbed by the capillary

Whatever is not reabsorbed will move into lymphatic vessels and go back to the heart for recirculation

Lymphatic vessels have a thin cell lining, cells are not as tightly attached as in the endothelia, this makes lymphatic vessels more permeable, when excess fluid exists it goes into the lymphatic vessels and then becomes lymph

Lymphatic vessels- unidirectional flow back to the heart because of the presence of valves

In cases of burns, permeability of the capillaries increase, fluid builds up in the interstitial space, lymphatic vessels are not working properly and so they dont take up all the fluid properly

Decrease in the blood volume leads to a decrease in blood pressure

Less blood goes back to the heart which leads to decreased stroke volume and decreased cardiac output

The body responds by increasing heart rate/ BP

Two factors affecting venous return

Respiratory pump- in horizontal position, body is at atmospheric pressure but pressure in thorax is below that so you have a pressure gradient in your body

Cardiac pump- opening of the ventricles functions as a suction cup and sucks in more blood from the atria and the veins therefore increasing venous return

When you stand up, your blood pools at your feet and thus there is less blood going to your heart, your blood pressure will drop and so your body responds by increasing the heart rate and BP

This sympathetic stimulation increases the pressure in the capillaries as well which we know will increase filtration which is what leads to the swelling of ankles/ feet

CV #8- Special Circulations

Coronary circulation

The force that is actually used to propel blood compresses the coronary vasculature on the heart itself, consequently:

Epicardial pressure (outside the cardiac muscle) < endocardial pressure (innermost layer)

When the heart is in systole (compression of heart muscle) endocardial blood flow drops to nearly zero

Flow increases during diastole as a result of local metabolite release (stimulated by O2 debt)

Myocardial oxygen balance flow chart (determinants of coronary perfusion)

Thus as metabolic demand increases ( coronary resistance decreases ( coronary perfusion increases

*Clinical tachycardia (rapid heart rate) decreases diastolic time period thus decreasing time for coronary perfusion ( increased metabolic demand

*SAME THING OCCURS WITH INCREASED SYMPATHETIC INNERVATION*

Reaction Hyperemia

Basically clamping the coronary artery and upon release you get a corresponding increase in perfusion to compensate for the blood flow lost during clamping

Local factors such as NO, Adenosine, and ATP sensitive K+ channels mitigate the response via prolonging K+ effusion ( shorter plateau of AP

As always, diffusion of O2 is flow limited (depends on number of capillaries and open/closed state)

Clinical: transient ischemia can be temporarily compensated for in the body via collateral circulation

Skin Circulation

Has arterio-venous (A-V) shunts (aka metarterioles)

Properties of A-V shunts

Thick muscular walls

Under sympathetic not metabolic control

Responds to reflex activation by temperature receptors

No reactive hyperemia

Means of conserving heat through metarteriole bypass route

Arterioles though, are under local control e.g. autoregulation and reactive hyperemia

Temperature control in skin (acts on the hypothalamus)

Cold: 0-15 degrees = vasoconstriction of arterioles and AV shunts

Below 0 = vasodilation

Warmth: vasodilation

Skeletal Muscle Circulation

Sympathetic innervations = vasoconstriction

Due to large vascular bed it is important for regulating blood pressure

Under neural and local factor control

Notice that skeletal muscle exhibits both active intrinsic vasodilation and extrinsic vasoconstriction while skin vessels exhibit only vasoconstriction (NO ACTIVE VASODILATION IN SKIN)

Cerebral Circulation

Regional blood flow is associated with regional neural activity

Little or no sympathetic influence

Local:

PaCO2 ( vasodilation across BBB

Acidic pH in CSF ( vasodilation

K+ ( seizure or hypoxia

Adenosine ( increased levels during seizure/hypoxia

Autoregulated between 60-160 mm Hg (but at this high pressure BBB is compromised)

Blood vessels in the brain exhibit reactive hyperemia

Gastrointestinal Circulation

25% of Cardiac Output to liver and 10% to SI

Control:

Sympathetic ( vasoconstriction

Local: metabolic

Adenosine: increases during arterial occlusion (enhances food absorption)

Gastrin/cholecystokinin increase blood flow during digestion

During congestive heart failure fluid accumulates in the right heart ( fluid from liver enter the abdominal cavity

Fetal Circulation

Lungs inactive (high R)

O2 tension low but Hb has higher O2 affinity due to the lack of 2,3 BPG

Fetal shunt:

RV ( Pulmonary artery via ductus arteriosis ( aorta

Blood gets to the fetus via the umbilical vein

Blood from RA ( LA via foramen ovale (R/L atrium work in parallel)

Summary of fetal blood circulation changes at birth:

CV9-Cardiac Dynamics and Regulation of Cardiac Output

2 Phases of Cardiac Cycle:

1.) Systole

Isovolumetric Ventricular Contraction

Ventricular Ejection

2.) Diastole

Isovolumetric Ventricular Relaxation

Ventricular Filling

Atrial Contraction

Pressure Profiles in the Blood Vessels

As blood flows through the systemic circulation, pressure decreases progressively because of resistance to blood flow.

Pressure HIGHEST(Aorta and Large Arteries

Pressure LOWEST( Venae Cavae

Largest decrease in pressure occurs across the arterioles because they are the site of highest resistance.

Mean Pressures in the systemic circulation:

Aorta: 100 mmHg

Arterioles: 50 mmHg

Capillaires: 20 mmHg

Vena Cava: 4 mmHg

Pressure Profiles in the Heart

Law of Laplace

Assumes shape of heart as a sphere to make conclusions about affect of geometry and tension on pressure

P = 2HT

r

P: Pressure

H: Thickness (height)

T: Tension

r: radius

In words, the Law of Laplace for a sphere states that the greater the thickness of the wall of the sphere (ie: the left ventricle), the greater the pressure that can be developed.

This is important in explaining why the left ventricular wall is thicker than the right ventricular wall because the left ventricular wall must develop a greater pressure to eject blood.

It is also important in seeing the compensatory affect

Ventricular wall thickness will increase if the ventricle has to pimp against increased aortic pressure (ie: hypertension).

Therefore, in systemic hypertension, the left ventricle will hypertrophy.

In pulmonary hypertension, the right ventricle hypertrophies.

Stroke Volume, Cardiac Output, and Ejection Fraction

1. Stroke Volume (SV)

Is the volume ejected from the ventricle on each beat.

Expressed by:

SV= EDV ESV

SV: Stroke Volume

EDV: End Diastolic Volume

ESV: End Systolic Volume

2. Cardiac Output (CO)

Expressed by:

CO = SV x HR

CO: Cardiac Output

SV: Stroke Volume

HR: Heart Rate

3. Ejection Fraction (EF)

Is the fraction of end diastolic volume ejected in each stroke volume.

Is related to contractility.

Is normally 0.55, or 55%.

Expressed by:

EF = SV

EDV

EF: Ejection Fraction

SV: Stroke Volume

EDV: End Diastolic Volume

4. Venous Return (VR)

Is equal to Cardiac Output!!

VR=CO

Expressed by:

VR = HR x LV

VR: Venous Return

HR: Heart Rate

LV: Loading Volume

Changes in Cardiac Output with Exercise

ParameterEffect

Heart Rate, HR((

Stroke Volume, SV(

Cardiac Output, CO((

Arterial Pressure( (slightly)

Pulse Pressure( (due to increased stroke volume)

Total Peripheral Resistance, TPR(( (due to vasodilation of skeletal muscle beds)

Arteriovenous 02 difference(( (due to increased O2 consumption)

Frank-Starling Relationship

Describes the increase in SV and CO that occur in response to an increase in VR or EDV.

Is based on the length-tension relationship in the ventricle:

(EDV cause (Ventricular fiber length, which produce (Tension developed.

Is the mechanism that matches CO to VR; the greater the VR, the greater the CO.

Changes in contractility shift the Frank-Starling curve up ((ed Contractility) or down ((ed Contractility).

Increases in contractility cause in increase in cardiac output for any level of right atrial pressure or EDV.

Decreases in contractility cause a decrease in cardiac output for any level of right atrial pressure or EDV.

Contractility

Is the intrinsic ability of cardiac muscle to develop force at a given muscle length.

Is also called inotropism.

Is related to intracellular [Ca2+].

Can be estimated by ejection fraction.

Positive inotropic agents produce increase in contractility.

Negative inotropic agents produce decrease in contractility.

What Causes Increase in Contractility? (aka What are Positive Inotropic Agents?)

1. Increased HR When more action potentials occur/unit time, more Ca2+ enters the myocardial cells during the AP plateaus, more Ca2+ is released from the SR, and greater tension is produced during contraction.

Examples of Increased HR:

Positive Staircase (Bowditch staircase): Increased HR increases the force of contraction in a stepwise fashion as the intracellular [Ca2+] increases cumulatively over several beats.

Postextrasystolic Potentiation: The beat that occurs after an extrasystolic beat has increased force contraction because extra Ca2+ entered the cells during the extrasystole.

2. Sympathetic Stimulation

Sympathetic Stimulation is by catecholamines acting on (1 Receptors

Increases Contractility by Increasing the inward Ca2+ current during the plateau of each cardiac AP.

Catecholamines (ie: Norepinephrine) act on GPCRs. This Activates Adenyl Cyclase, which increases cAMP levels, which activate kinases (ie: PKA) to P-late enzymes (such as Phospholamban).

Sympathetic Simulation also increases the activity of the Ca2+ pump of the SR; this occurs by P-lation of Phospholamban.

As a result, more Ca2+ is accumulated by the SR, therefore more Ca2+ is available for release in subsequent beats.

3. Cardiac Glycosides (digitalis)

Increase force of contraction by inhibiting the Na+/K+ ATPase in the myocardial cell membrane.

As a result of this inhibition, intracellular [Na+] increases, diminishing Na+ gradient across the cell membrane.

Na+-Ca2+ exchange (a mechanism that takes Ca2+ OUT of cell) depends on the size of the Na+ gradient.

So, no Na+ gradients means no Ca2+ leaves the cell!

Increase in intracellular [Ca2+] good for contractility! What Causes Decrease in Contractility? (aka What are Negative Inotropic Agents?)

1. Parasympathetic Stimulation

Parasympathetic Stimulation is by ACh acting on Muscarinic Receptors.

Decreases Contractility by Decreasing the inward Ca2+ current during the plateau of each cardiac AP.

2. Decreases in pH (Acidosis), decreases force development and contractility.

NOTE: Vagal Effects predominate! There is quick on/off response of vagal effects and sympathetic affects in absence of vagal are strong.

Indices of Contractility

1.) Peak Rate of Pressure Rise (dP/dt)

2.) Peak Aortic Flow Velocity (dV/dt)

3.) Ventricular Ejection Fraction (SV/EDV)

Excitation-Contraction Coupling: Cardiac vs. Skeletal

NOTE: this is from previous exam, for more detailed explanation see notes from EXAM1

Basically, in Cardiac CICR predominates and in Skeletal VICR predominates.

CV Lecture 10: II. Cardiac Dynamics and Regulation of Cardiac Output

LECTURE OBJECTIVES:

1) Describe the Frank/Starling Law of the Heart and illustrate this graphically.

2) How are the length tension relationship and calcium sensitivity involved in the Frank/Starling Law of the Heart?

3) Define pre-load and afterload.

4) Show graphically how preload, afterload, and contractility affect variables such as ESV, EDV, ESP, and SV.

5) How do changes in myocardial contractility and blood volume produce a compensation in heart failure?

In the heart, inc [Ca] is graded while in skel it is all or none.

In the heart, there is no summation, but instead a modulation of response to [Ca] by phosphorylation of 1) phospholamban (to store more Ca in SR), 2) Ca pump (SERCA and on cell membrane) and 3) TnI (increases Ca sensitivity ( inc crossbridge formation).

(+) ionotropic ( inc. contractility

(-) ionotropic ( dec. contractility

SLIDE 4: Memorize positive and negative ionotropic agents. I dont think we need to know the source.

Frank-Starling law of the heart (aka cardiac length tension relationship):

Describes the increases in SV and CO that occur in response to increased venous return or EDV.

As you increase the length, you increase the force development (plateaus at a long lengths). At longer lengths, the heart contracts more forcibly producing more tension.

Increases in EDV cause an increase in ventricular fiber length, which produces an increase in developed tension.

It ensures that CO = venous return

Increased contractility cause an increase in CO or EDV

Decreased contractility cause a decrease in CO or EDV.

Cardiac muscle length range 1.8-2.4um.

As you increase the length, you increase myofibril sensitivity to Ca and you get more bang for your buck for the same amount of Ca. As you stretch the sarcomere, TnC will much more easily bind Ca ( inc force and cycling

Preload VOLUME of ventricular filling

Afterload PRESSURE exerted by blood leaving the heart

Valve will not open until the pressure in vent increases past the afterload pressure

a. pre-load/EDV

a. Mitral valve closes

b. Afterload/ESV

a. Aortic valve opens

c. Aortic valve closes

d. Mitral valve opens

a-b ( isovolumetric contraction

b-c ( ventricular ejection

c-d ( isovolumetric relaxation

d-a ( ventricular filling

Inc preload ( inc vent filling, inc EDV, and inc end-diastolic P. but NO CHANGE in afterload ( more forceful contraction ( inc ejection P ( inc ejection fraction ( inc SV

Inc afterload = inc aortic P ( must develop greater P in vent to overcome it ( inc ejection P, inc ESV, inc end-systolic P, ( dec SV.

B/c aortic P is higher, valve will close sooner ( inc ESV and ESP ( dec SV

In the 2nd beat, the system will compensate towards a more normal SV at the expense of a higher EDV leading to inc tension (T) on vent walls eventually causing vent hypertrophy and eventual dilated cardiomyopathy in the long term (heart failure)

Increasing symp stimulation of the heart leads to inc contractility ( inc vent P at any given EDV. There is a decrease in vent P at any EDV with heart failure and the system compensates by increasing symp stim to return vent pressure closer to normal.

Increased contractility ( inc endsystolic P ( inc SV ( dec ESV.

On the 2nd beat, same endsystolic P as beat one ( dec EDV ( dec ESV ( returns SV to normal.

SLIDE 24: understand how diseases affect pressure volume loops.

With exercise, you get (inc venous return ( inc EDV) and also (inc contractility ( dec ESV). Both work together to increase SV.

CV 11: III. Regulation of Cardiac Output and Cardiac Work

1. How do changes in Venous return affect cardiac output? What physiological mechanisms control venous return?

Venous return (VR) is the flow of blood back to the heart. Under steady-state conditions, venous return must equal cardiac output (CO) when averaged over time because the cardiovascular system is essentially a closed loop. Therefore in any conditions which may increase Venous Return (by increasing Central Venous Pressure) will cause an increase in Cardiac Output.Factors Affecting Venous Return:Muscle pump: A major mechanism promoting venous return during normal activity (e.g., walking, running) is the muscle pump system. Peripheral veins, particularly in the legs and arms, have one-way valves that direct flow away from the limb and toward the heart. Veins located within large muscle groups undergo compression as the muscles surrounding them contract, and they become decompressed as the muscles relax. Therefore, with normal cycles of contraction and relaxation, the veins are alternately compressed and decompressed (i.e., "pumped"). Muscle contraction propels blood forward through the open venous valves and impedes back flow in the muscle with closed venous valves. During muscle relaxation, the valves open and blood flows into and fills the venous segment, but only from the arterial side. The net effect is that the cycle of compression and relaxation propels the blood in the direction of the heart. Venous valves prevent the blood from flowing backwards, thereby permitting unidirectional flow thereby enhancing venous return. When a person is standing, postural muscles in the legs alternately contract and relax to keep the body in balance. This muscle activity promotes venous return and helps to maintain cardiac output.Respiratory pump: During inspiration, the chest wall expands and the diaphragm descends. This causes a negative pressure in the thorax (suction effect), which leads to expansion of the lungs and cardiac chambers. This expansion causes the intravascular and intracardiac pressures (e.g., right atrial pressure) to fall. As right atrial pressure falls during inspiration, the pressure gradient for venous return to the right ventricle increases, thus more blood returns to the heart. During expiration, the opposite occurs and the venous return is decreased. Inspiration causes an increase in venous return

Gravity: Gravitational forces significantly affect venous return and therefore cardiac output, and arterial and venous pressures. This is shown by the example of a person who is lying down and then suddenly stands up. As the person stands, gravity acts on the vascular volume so that blood accumulates in the lower extremities. Therefore, venous volume and pressure becomes very high in the feet and lower limbs when standing. This shift in blood volume decreases thoracic venous blood volume and therefore decreases central venous pressure. This change causes a decrease in right ventricular filling pressure (preload), leading to a decline in stroke volume by the Frank-Starling mechanism. When a person initially stands, cardiac output and arterial pressure decrease; The flow through the entire systemic circulation falls because arterial pressure falls more than right atrial pressure, therefore the pressure gradient driving flow throughout the entire circulatory system is decreased.

The effects of gravity are compensated by sympathetic vasoconstriction of the veins and the use of the skeletal muscle pumps (specifically the valves).

Sympathetic Vasoconstriction: In blood vessels, sympathetic activation constricts arteries and arterioles (resistance vessels), which increases resistanceand decreases distal blood flow. Sympathetic-induced constriction of veins (capacitance vessels) decreases venous compliance and blood volume, and thereby increases venous pressure. The overall effect of sympathetic activation is to increase cardiac output, by increasing venous pressure.

Dr. Kenndy also makes mention of the hearts contractility and suction effect (as contraction increases, the suctions effect increases) as other factors that will increase central venous pressure and therefore cardiac output.

2. Show how the cardiac function curve is generated graphically and understand how changes in preload, contractility, and afterload alter the curve.

Contractility: Contractility is the intrinsic ability of cardiac muscle to develop force for a given muscle length.

An increase in Contractility = an elevated stroke volume at each End Diastolic Volume; and less End Diastolic Volume is required to generate a given Stroke Volume (Top line of the graph)

Preload: Preload is the muscle length prior to contractility, and it is dependent on ventricular filling (or end diastolic volume.) This value is related to right atrial pressure. The most important determining factor for preload is venous return.

An increase in Preload causes an increase in End Diastolic Volume and an increase in cardiac output. (he does not have a picture for this in lecture)

Afterload: Afterload is the tension (or the arterial pressure) against which the ventricle must contract. If arterial pressure increases, afterload also increases. Afterload for the left ventricle is determined by aortic pressure, afterload for the right ventricle is determined by pulmonary artery pressure.

An increase in Afterload causes a reduced stroke volume at each End Diastolic Volume; and an elevated End Diastolic Volume to achieve the same Stroke volume (bottom line of the graph.)

3. Calculate the Cardiac Output using the Fick Principle and determine the Cardiac Index

Fick Principle can be used to compute cardiac output (CO) indirectly from whole body oxygen consumption (VO2) and the mixed venous (O2ven) and arterial oxygen contents (O2art).

The principle states that the oxygen quantity delivered to the lungs in the pulmonary arteries plus the oxygen quantity added by the lungs must equal the amount carried away from the lungs in the pulmonary veins.

CO = VO2

_____________

(O2vein O2artery)

Cardiac Index = Cardiac Output (calculated from above)

M2 body surface area (typically 1.6 m2)

Normal range of cardiac index is 2.6 - 4.2 L/min per square meter.

If the CI falls below 1.8 L/min, the patient may be in cardiogenic shock.

4. How is Cardiac Minute calculated? What is meant by pressure work and volume work and which has a higher cost?

Cardiac Minute work is the rate of work in the cardiac muscle.

Cardiac Minute Work = Aortic Pressure X Cardiac Output

Pressure Work Volume Work

Development of PressureWork of Ejecting Blood

Pressure work is more expensive than volume work. This is measure by the oxygen consumption required by the heart to do each. The energy requiremens for pressure work are higher than those of volume work. More O2 is consumed to develop pressure gradient in the heart than is used to eject the blood in cardiac output

5. Use the Law of LaPlace to describe why a dilated heart has greater energy costsA dilated heart is caused by Cardio Myopathy which causes the thinning of the ventricular walls and therefore a lager radius.

An increase in Radius and End Diastolic volume ( Increases Tension ( creating a higher demand for ATP( therefore demanding more O2Meanwhile, a healthy heart has a comparatively smllaer radius and End Diastolic Volume which Lowers the tension, requires less ATP and therefore less O2

Circulation and Cardiac Output: CV12

Venous P affect R. Ventricle filling( affects CO (cardiac output)

If inc. VP (diff btn VC and peripheral venous pressure) from inc. R. Ventricle filling, ( inc. end diastolic volume( inc. CO

Venous compliance has (-) affect on VP, b/c relaxation of smooth muscle inc. stretchability, which dec. VP

If inc. Venous return (inc. blood flow to central vein), then will inc. VP

Venous SM contractility

Inc. total BV (blood volume)

Resp. movements will inc VP by dec. interthoracic pressure

Skeletal muscle pump- compresses veins( inc. blood flow b/c one way valves

Gravity- from lying to standing, venous pooling( less venous return

Ventricular compliance (low) can inc. VP

Atrial contractility inc. VP

HR when above 170 compromises time for vent. Filling, so (-) affect on VP

*Inc. CO( dec. BV for next, so has (-) affect on VP

if dec. CO, that inc. central VP or r. atrial pressure

where CO = 0, that is the (Pmc) mean circulatory pressure (7mm Hg for normal)

where heart is stopped, all the pressures can equilibrate (identical). Pressures in veins = arteries, etc.

Only two types of volumes in veins:

1) Unstressed- very little pressure being developed

2)Stressed- after 4L, each addition lead to rapid inc. in of pressure in veins

Observe changes in BV as it relates to central VP(venous pressure) see p.6

If inc. BV( curve shifts right(which inc. VP(also inc. Pmc (10.5)

venoconstriction

If dec. BV( curve shifts left(dec. VP(also dec. Pmc (5.2)

Venodilation

Pmc changes with changes in BV

BV dec. (e.g. hemorrhage)- no change in unstressed volume, but dec. in stressed volume, dec. Pmc

BV inc. (transfusion)- no change in unstressed volume, but inc. in stressed volume, inc. Pmc

Venoconstriction dec. unstressed volume, inc. Pmc

venodilation(syncope/blood pooling) inc unstressed volume, dec. Pmc

this is the same with change from going to reclining to standing position quickly-venous pooling(dec. Pmc

Sympathetic stimulation and Vascular Fxn

If inc. TPR (art. constriction)( shift left, dec. CVP, no change Pmc

If dec. TPR (art. dilation)( shift right, inc. CVP, no change Pmc

Cardiac fxn curve- (looks at VP affect on CVP)

Inc. CVP( inc. CO

Vascular fxn curve (looks at CO affect on CVP)

Inc. CO( dec. CVP, see slide 13!

Interaction of both curves( Cardiovascular Operating point- where at equilibrium. Tries to reestablish equilibrium.

Symp. Stimulation(inc contract(inc CO(dec. CVP

Hemorrhage (dec. BV(dec CO(dec CVP

Response to hemorrhage:

1)inc. symp. Stimulation(inc HR, contractility, CO

2)venosonstrict(inc. Pmc, inc. CVP

3)vasoconstrict(inc TPR(inc CO

Inc. in MAP (mean art. pressure)( dec. CO (because aortic valve cant open)

Inc. in TPR (hypertension)(inc. MAP (or afterload)(dec. CO, no change Pmc

Will always get a dec. CO, but CVP can dec/inc.

Heart Failure(dec. contractility(curve to right(dec. CO

Response: inc. BV(by retention of fluid (hypervolemia)(inc. CVP, Pmc. The compromise to get back to normal CO is the inc. in CVP!!!

Severe is more dec. in CO, and more inc. in CVP. CO is not normal, so there is more pressure to inc. BV further(leads to peripheral edema

On flip side, if can inc. symp. stimulation of veins(inc CO = Cardiac Reserve Happens in exercise( inc. symp, and inc. HR