Physl 212 Cardiovascular

MAP = TPR x CO

- MAP = mean arterial pressure

- CO = cardiac output

- TPR = total peripheral resistance, determined by total arteriolar resistance

CO = HR x SV

CO-Cardiac output, amount of blood pumped by each ventricle in one minute

HR-Heart rate

SV-Stroke volume, amount of blood pumped out of each ventricle during systole

SV = EDV - ESV

End-diastolic volume (EDV) -amount of blood in each ventricle at the end of ventricular diastole

End-systolic volume (ESV) -amount of blood in each ventricle at the end of ventricular systole

Stroke volume -volume of blood pumped out of each ventricle during systole, ~70 - 75 mL

Poiseuille's equation

R = resistance to blood flow

η = viscosity of blood

l = length of vessel

r = radius of vessel (raised to fourth power)

Applies to laminar blood flow

F = ∆P/R

we have to maintain F, If R decreases as we go from large artery to many arterioles and F is constant

ΔP must decrease

F = flow

∆P = pressure difference between two fixed points

R = resistance to flow

Compliance = ∆Volume/ ∆Pressure

∆P that occurs with ∆V is greater if the compliance of the vessel is lower

Pulse pressure = systolic pressure - diastolic pressure

Diastolic pressure-minimum blood pressure at end of ventricular diastole

Systolic pressure-maximum blood pressure during ventricular systole

Ejection Fraction (EF) = SV/EDV

Stroke volume-volume of blood pumped out of each ventricle during systole

End-diastolic volume (EDV)-amount of blood in each ventricle at the end of ventricular diastole

What is hemodynamics?

Pressure gradient (not absolute pressure) creates blood flow

contraction of heart chambers

blood on the walls of the blood vessels and heart chambers

Flow and resistance to flow can affect pressure

What factors determine the resistance to blood flow?

Viscosity

friction between molecules of a flowing fluid

Length and diameter

determines amount of contact between moving blood and stationary wall of vessel

transitional and turbulent flow

How do the factors affect the resistance to blood flow (Poiseuille's equation)?

R = resistance to blood flow

η = viscosity of blood

l = length of vessel

r = radius of vessel (raised to fourth power)

Applies to laminar blood flow

What are the functions of the cardiovascular system?

To deliver oxygen and nutrients and remove waste products of metabolism

Fast chemical signaling to cells by circulating hormones or neurotransmitters

Thermoregulation

Mediation of inflammatory and host defense responses against invading microorganisms

Describe the path of blood flow in the body and through the pulmonary and systemic circuits.

Pulmonary circulation

-Blood to and from the gas exchange surfaces of the lung

-Blood entering lungs

-poorly oxygenated blood

-Blood leaving lungs

-oxygenated blood

Systemic circulation

-Blood to and from the rest of the body

-Blood entering tissues

-oxygenated blood

-Blood leaving tissues

-poorly oxygenated blood

What is serial versus parallel blood flow?

Series flow

-Blood must pass through the pulmonary and systemic circuits in sequence

Parallel flow

-Each organ supplied by different artery

-Independently regulate flow to different organs

Exception

-digestive organs and liver are in series

List the layers of the pericardium. What are the functions of the layers?

fibrous sac surrounding the heart and roots of great vessels

(1) Fibrous pericardium - Serous pericardium

(2) Parietal

(3) Visceral

Pericardial cavity

- Pericardial fluid decreases friction

-Stabilize heart in its cavity

-Protection from mechanical traumas and infection

-Limits overfilling of chambers

-Prevents distension

List the layers of the heart wall. Describe the structure and function of each.

Epicardium (visceral pericardium)

- Covers outer surface of heart

protecting the heart, producing factors that help the cardiac cells properly develop, and ensuring proper response to cardiac cell injury.

Myocardium

-Muscular wall

-Cardiac muscle cells (myocytes), blood vessels, nerves

-responsible for the contractile function of the cardiac pump.

Endocardium

-Endothelium covering inner surfaces of heart and heart valves

-barrier between cardiac muscles and the bloodstream and contains necessary blood vessels

Why is the wall of the left ventricle thicker than the right ventricle?

The left ventricle has to endure more pressure than the right ventricle

• What is the structure of a myocyte?

Branched ("Y") and joined longitudinally

Striated, one nucleus per cell, many mitochondria

What are intercalated disks?

Dense bands containing intercellular junctions that link adjacent cells mechanically and electrically

What specialized junctions are found at intercalated disks? What are their functions?

Desmosomes

-Anchor cells together in tissues subject to considerable stretching

-Mechanically couple cells

Gap junctions

-Communicating junctions

-Transmembrane channels linking adjacent cells

-Electrically couple heart cells

• Name the four valves of the heart. What is the function and structure of each?

AV valves

-Between atria and ventricles

-prevent backflow of blood into atria when ventricles contract

-valve Left AV (bicuspid or mitral)

-Left AV valve - Two leaflets (cusps)

valve Right AV (tricuspid) valve

-Right AV valve - Three leaflets (cusps)

2)Arterial (Semilunar)Valves

-Between the ventricle and artery

3)Pulmonary valve

-Pulmonary trunk, right ventricle

4)Aortic valve

-Aorta, left ventricle

-Prevent the backflow of blood from the arteries into ventricles when ventricles relax

what is the function of the AV valve apparatus?

Prevents eversion of av valves into atria during ventricular contraction

Valves open from pressure gradients

How do valves open and close?

Forward gradients open valves

Backward gradients close valves

What is the cardiac skeleton? What is its function(s)?

Fibrous skeleton of the heart

-Dense connective tissue

-Separates atria from ventricles

-Electrically inactive

- Support for heart

Coronary circulation

Blood through tissues of the heart

Coronary arteries

originate at aortic sinuses at base of ascending aorta

Coronary veins

drain into the coronary sinus, which empties into the right atrium

Coronary sinus

collection of veins joined together to form a large vessel that collects blood from the myocardium of the heart

Systole (contraction)

Myocardial blood flow almost ceases

Diastole (relaxation)

Myocardial blood flow peaks

What are the two types of myocytes? What are their functions?

Contractile cells

-mechanical work of pumping, propel blood

do not initiate action potentials

Conducting cells

-initiate and conduct the action potentials responsible for contraction of the contractile myocytes (1 % of myocytes)

few myofibrils

Describe the spread of excitation from the SA node to the rest of the heart.

SA node

Internodal pathways

Atrial myocardium

AV node

Bundle of His

Right and left bundle branches

Purkinje fibers

Ventricular myocardium

Why is the SA node important?

Cardiac pacemaker

Initiates action potentials

Pacemaker potential

-Closing of K+ channels, Na+ entering through F-type channels and Ca2+ entering through T-type channels

Depolarization phase

- L-type channels open at threshold and Ca2+ slowly enters cell.

Repolarization phase

-Opening of K+ channels and closing of L-type Ca2+ channels. K+ exits through K+ channels

What is the role of the AV node?

100 msec delay

Delay ensures atria depolarize and contract first

Describe the changes in membrane permeability that underlie the action potential in a ventricular muscle cell

K+ permeability, then Na+ permeability, and then Ca2+ permeability

What ions/ion channels are involved in each phase of contraction of a ventricular muscle cell

Stable resting phase

- K+ leak channels

depolarization

-opening of fast voltage gated Na+ channels to threshold

Notch

- transient opening of K+ channels

Plateau

-Ca2+ entering through L-type channels and slow opening of K+ channels to repol the cells

Repolarization

-Opening of K+ channels and closing of Ca2+ channels

What is the pacemaker potential and how does it occur?

Slow depolarization to threshold

Regular spontaneous generation of action potentials

Slow depolarization to threshold

Regular spontaneous generation of action potentials

ECG

electrocardiogram

Relate the different waves (P, QRS, and T) to the atrial and ventricular action potentials.

P

- atrial depolarization

QRS

-ventricular depolarization

T

- ventricular repolarization

Describe the sequence of events leading to excitation-contraction coupling in cardiac muscle (contraction and relaxation)

Excitation

opening of plasma membrane L type Ca2+ and T tubules

Flow of Ca2+ into cytosol

Ca2+ binds to Ca2+ receptors

Opening of Ca2+ channels intrinsic to these receptors

Flow of Ca2+ into cytosol

Cytosolic Ca2+ increases

Contraction of muscle cells

Describe the structure of a myocyte

Sarcolemma

-cell membrane of muscle cell

Sarcoplasmic reticulum

-stores calcium ions for contraction

Striated

T-tubules (Transverse-tubules)

-invaginations of sarcolemma; transmit depolarization of membrane into interior of muscle cell

What is the refractory period?

Period of time in which a new action potential cannot be initiated

Absolute Refractory Period

-~ 250 msec

-No response to another stimulus

-Inactivation of Na+ channels

-Prevents tetanus

What are the different phases of ventricular systole

-ventricular contraction and blood ejection

-Isovolumetric ventricular contraction

-all heart valves closed, blood volume in ventricles remains constant, pressures rise. Muscle develops tension but cannot shorten

Ventricular ejection

-pressure in ventricles exceeds that in arteries, semilunar valves open and blood ejected into the artery

- Muscle fibers of ventricles shorten

Stroke volume

-volume of blood ejected from each ventricle during systole

What are the different phases of ventricular diastole

ventricular relaxation and blood filling

Isovolumetric ventricular relaxation

-all heart valves closed,

-blood volume remains constant, pressures drop

Ventricular filling

-AV valves open, blood flows into ventricles from atria.

-Ventricles receive blood passively (atria are relaxed)

Passive ventricular filling

-majority of ventricles

-Atria contract at the end of ventricular filling

End-diastolic volume (EDV)

amount of blood in each ventricle at the end of ventricular diastole

End-systolic volume (ESV)

amount of blood in each ventricle at the end of ventricular systole

Stroke volume

volume of blood pumped out of each ventricle during systole

Cardiac output

the product of heart rate (HR) and stroke volume (SV)

Understand the pressure-volume curve

How does the left ventricular pressure curve differ from the right ventricular pressure curve?

The right ventricle develops lower pressures than the left ventricle during systole

Describe the effect of sympathetic and parasympathetic innervation on the heart.

Sympathetic innervation →

atria

- increases contractility

ventricles

-increases contractility

SA node

- increase HR and rate of depol

AV node

- increases conduction

- decreases nodal delay

Parasympathetic innervation →

atria

- decrease contractility

SA node

- decrease HR and rate of depolarization

AV node

- increase nodal delay

- decreases conduction

How do the sympathetic systems affect heart rate, stroke volume, and cardiac output?

Increased sympathetic activity

-Increase heart rate

-↑ the slope of the pacemaker potential

-Increase HR

-Increases F-type and T-type channel permeability

How do the parasympathetic systems affect heart rate, stroke volume, and cardiac output?

Increased parasympathetic activity

-Decrease heart rate

-↓ the slope of the pacemaker potential

-Decrease HR

-Decreases F-type channel permeability

-Hyperpolarizes cells (↑ K+ permeability)

How does SNS alter pacemaker potential

increases the slope

How does the PNS alter pacemaker potential

Decreases the slope

What is the relationship between cardiac output, stroke volume and heart rate?

CO = HR x SV

What are the principles of the Frank-Starling mechanism?

Relationship between EDV and SV

Main determinant of cardiac muscle fiber length

-degree of diastolic filling

-preload

Increase filling → increase EDV → increase cardiac fiber length → greater force during contraction and greater SV

What is preload?

tension or load on myocardium before it begins to contract or amount of filling of ventricles at the end of diastole

How does EDV alter the SV?

EF = SV/EDV

increase EDV - greater SV

Describe the effects of the sympathetic system on cardiac muscle during contraction and relaxation.

SV is greater at any given EDV

-Ventricular ejection fraction is the fraction of the end-diastolic -ventricular volume ejected

Ejection Fraction (EF) = SV/EDV

- More rapid contraction and a more rapid relaxation

Through what mechanisms does the sympathetic system affect contractility?

What is afterload?

tension (or arterial pressure) against which the ventricles contract

Describe how the pressures change in the arteriole and systemic circuits as the distance from the heart increases. Where does the largest pressure drop occur?

-MAP decreases as distance from heart increases

-Largest drop in pressure occurs across the arterioles

Systolic pressure

maximum blood pressure during ventricular systole

Diastolic pressure

minimum blood pressure at end of ventricular diastole

Pulse pressure

systolic - diastolic

What is mean arterial pressure? How does it change along the circulatory system?

pressure driving blood into tissues averaged over cardiac cycle

What are two functions of the arterioles?

1. Regulate blood flow to organs

-Capillary beds

2. Determine MAP

-Resistance vessels

What is the difference between intrinsic (local controls) and extrinsic factors that alter the basal tone of arterioles?

Extrinsic

-factors external to the organ or tissue

-whole body needs (MAP); nerves and hormones

Intrinsic

-local controls

-organs and tissues alter their own arteriolar resistances

-independent of nerves or hormones

Give examples of extrinsic factors altering the basal tone of arterioles.

Nerves

-Sympathetic innervation

NE

-vasoconstriction (α-adrenergic receptors)

Sympathetic tone can be increased (vasoconstriction) or decreased (vasodilation) (in addition to vessel's intrinsic tone)

Regulating MAP - Noncholinergic, nonadrenergic nerves

NO

-vasodilation

Hormones

Epinephrine from adrenal medulla causes :

-vasoconstriction,(αadrenergic receptors)

-Vasodilation.(β2 -adrenergic receptors)

What changes occur in the pressure volume loop following a change in: contractility, preload and afterload

Increased slope of ESPVR with increased contractility

-ESV decreases

-Increased contractility results in increased SV

Increased preload (filling) results in increased SV

-Increase in EDV

-No change in ESPVR

Ventricle must generate more pressure to eject blood with an increased afterload

-SV decreases

-ESV increases

What does the width and area of the pressure volume curve represent?

Width = Stroke volume

Area = Stroke work

What are the different phases of the pressure volume loop

Discuss the key components of the left ventricular pressure-volume loop

Physiologically relevant hemodynamic parameters determined from these loops are:

-stroke volume

-cardiac output

-ejection fraction

-myocardial contractility

Pressure volume loops are generated by real-time measurement of pressure and volume within the left ventricle

What are the key components of the cardiac length-tension relationship?

What is contractility?

strength of contraction at any given EDV

What is the effect of a positive inotropic agent?

Positive inotropic agent

-catecholamines (Epi), exercise

-Increase contractility

-↑ Ca2+ increases contractility

1. Increased Ca2+ influx into cell and Ca2+ -induced Ca2+ release from SR

2. Increased sensitivity of the SR Ca2+ release channel Ca2+

3. Stimulate SERCA to increase SR Ca2+ stores for later release

4. Increased Ca2+ entry into the cell increases SR Ca2+ stores

What is the effect of a negative inotropic agent?

Heart failure

Decrease contractility

↓ Ca2+ decreases contractility

When the arterial baroreceptors increase or decrease their rate of firing, what changes in autonomic outflow occur and cardiovascular function occur?

Increase in MAP increases rate of firing of baroreceptors

• Decrease in MAP decreases rate of firing of baroreceptors

• Respond to changes in pulse pressure

Medullary cardiovascular center

-Medulla oblongata

-Receives input from baroreceptors

-Alters vagal stimulation (parasympathetic) to heart and sympathetic innervation to heart, arterioles and veins

Baroreceptors adapt to sustained changes in arterial pressure

What causes a change in firing of the arterial baroreceptors?

Rate of discharge is proportional to the mean arterial pressure

Describe the arterial baroreceptors.

Respond to mean arterial pressure and pulse pressure

Respond to changes in pressure when walls of vessel stretch/relax

Degree of stretching is directly proportional to pressure

• What is the difference between long-term regulation of blood pressure and short-term regulation of MAP?

Short-term regulation

-Seconds to hours

-Baroreceptors reflexes

-Adjusts cardiac output (CO) and total peripheral (TPR) resistance by ANS

Long-term regulation

Adjust blood volume

Restore normal salt and water balance through mechanisms that regulate urine output and thirst

How do changes in CO and TPR affect MAP?

MAP = CO x TPR

What is the relationship between MAP, CO and TRP?

- MAP = mean arterial pressure

- CO = cardiac output

- TPR = total peripheral resistance

determined by total arteriolar resistance

How does venous return affect the SV? (ie. Frank-Starling law)?

Increased venous return results in increased stroke volume through the Frank-Starling mechanism

The venous system is a low pressure system. What mechanisms aid in returning blood back to the heart

Smooth muscle in veins

-Innervated by sympathetic neurons

Skeletal muscle pump

-Compresses veins

-Venous pressure increases, forcing more blood back to heart

Respiratory pump

-Inspiration causes an increase in venous return

What mechanisms prevent the backflow of blood into capillaries?

Valves

-folds

-Prevent the backflow of blood to capillaries

What is the function of the venous system?

High capacitance vessels

-store large volumes of blood

Highly distensible at low pressures and have little elastic recoil

-Reservoir of blood

What is the difference between filtration and reabsorption?

Filtration

-movement of protein-free plasma from capillary to IF •

Reabsorption

-movement of protein-free plasma from IF to capillary

What pressures drive bulk flow

Which end of the capillary favors filtration

arterial end

Which end of the capillary favors absorption

venous end

hydrostatic pressure

the pressure within a blood vessel that tends to push water out of the vessel

colloid pressure

osmotic pressure produced by plasma proteins

Diffusion

movement of substance down its concentration gradient

Transcytosis

transport into, across, and then out of cell

bulk flow

The movement of a fluid due to a difference in pressure between two locations.

continuous capillaries

Exchange of water, small solutes, lipid-soluble material, no exchange of blood and plasma proteins