Midterm paper

PCB3702L Intermediate Human Physiology Dr. Lisa Brinn

Cardiovascular Lab Supplemental Resource

• Basic Design of the Cardiovascular System

A. Systemic circulation- to/from all organs of the body except lung alveoli

B. Pulmonary circulation- to/from lung alveoli

• Organization of the Heart

A. Heart

1. Hollow organ about the size of a fist

2. Located in thoracic cavity

3. Lies mostly to the left

B. Pericardium

1. Protects and anchors the heart

C. Heart – chambers

1. Four chambers total that create two pumps

2. Can be dividing into right and left

a. 2 atria

b. 2 ventricles

3. Right side of the heart

a. Serves pulmonary circuit (blood leaves through the pulmonary trunk)

4. Left side of the heart

a. Serves systemic circuit (blood leaves through aorta)

5. Top two chambers

a. Atria

b. Great vessels

1) Right (blood enters the heart through these veins)

i. Superior vena cava

ii. Inferior vena cava

2) Left (blood enters the heart through these veins)

i. Pulmonary veins

6. Bottom two chambers

a. Ventricles

b. Great vessels

PCB3702L Intermediate Human Physiology Dr. Lisa Brinn

1) Right (blood leaves the heart through this artery)

i. Pulmonary trunk

2) Left (blood leaves the heart through this artery)

i. Aorta

7. Heart – valves

a. Ensure one way flow of blood

1) Right

i. Right atrioventricular valve or Tricuspid

ii. Pulmonary semilunar valve

2) Left

i. Left atrioventricular valve or Bicuspid or mitral

ii. Aortic semilunar valve

PCB3702L Intermediate Human Physiology Dr. Lisa Brinn

D. Blood flow through the heart

8. Blood comes from systemic circuit into the right atrium from the

superior and inferior vena cava

9. From the right atrium blood flows through the tricuspid valve to the

right ventricle

10. The right ventricle will pump blood through the pulmonary semilunar

valve into the pulmonary trunk

11. Blood goes to the lungs to get oxygenated

12. Blood comes back to the heart via the pulmonary veins

13. Pulmonary veins deliver blood into the left atrium

14. From the left atrium blood travels through the bicuspid valve into the

left ventricle

15. Left ventricle pumps blood out of the aortic semilunar valve and into the

aorta

16. Aorta helps distribute blood of the systemic organs of the body

PCB3702L Intermediate Human Physiology Dr. Lisa Brinn

• Cardiac Muscle Tissue and the Cardiac Conduction System

A. Cardiac muscle tissue – structure

1. Interconnected cells act as a functional syncytium

2. Gap channels allow cardiac cells depolarize and contract at the same time

B. Heart muscle shares properties with both skeletal and smooth muscle

C. Conduction system

Cardiac muscle does not require any external stimulation to contract. Contractions

occur because action potentials within cardiac muscle itself are spontaneously

generated on a periodic basis. This built-in rhythm is termed autorhythmicity.

Cardiac muscle, as a functional syncytium, consists of two types of muscle fibers:

autorhythmic fibers and contractile fibers. Autorhythmic fibers, also known as

pacemaker cells, spontaneously generate action potentials. They account for only a

very small number of cells in the functional syncytium and are usually grouped

together. Because autorhythmic fibers contain essentially no myofibrils, they are

unable to contract. Contractile fibers constitute the great majority of cells in the

functional syncytium. They have the necessary myofibrils to contract but do not have

the ability to initiate action potentials. Instead, they become excited and then contract

together in response to action potentials conducted to them from autorhythmic fibers

via gap junctions.

1. Collection of modified muscle cells (nodal/pacemaker)

2. Initiate and conduct action potentials to other cells

3. Do not contribute significantly to contractile forces

4. Starts at the superior wall of the right atrium

5. Continues through the apex of the heart and myocardium of the ventricles

6. Structures include:

a. Sinoatrial (SA) node

b. Atrioventricular (AV) node

c. Atrioventricular (AV) bundle (Bundle of HIS)

d. Right and left bundle branches

e. Purkinje fibers

PCB3702L Intermediate Human Physiology Dr. Lisa Brinn

D. Contractile cells – constitute the great majority of cells in the functional syncytium

1. Produce forces, but do not spontaneously depolarize

2. Produce action potentials in response to signals from the nodal cells

3. Excitation contraction coupling – has similarity to both skeletal and smooth

muscle

4. Cardiac muscle has a long refractory period

E. The autorhythmic fibers of the heart have two important functions:

1. They act as a pacemaker, setting the rhythm of electrical excitation that

causes contraction of the heart.

2. They form the conduction system, the pathway that rapidly delivers action

potentials throughout the heart muscle. Action potentials are able to be

conducted throughout the heart by the conduction system because gap

junctions connect the components of the conduction system to each other and

to the contractile fibers of the heart. The conduction system ensures that

cardiac chambers become stimulated to contract in a coordinated manner,

which makes the heart an effective pump. As you will see later in the chapter,

problems with the conduction system can result in arrhythmias (abnormal

rhythms) in which the heart beats irregularly, too fast, or too slowly.

PCB3702L Intermediate Human Physiology Dr. Lisa Brinn

Cardiac action potentials propagate through the conduction system in the following

sequence:

I. Cardiac excitation normally begins in the SA node, when SA node cells spontaneously

depolarize to threshold by producing a pacemaker potential (described shortly). Once

threshold is reached, an action potential is generated and then propagates throughout

both atria. Following the action potential, the atria contract.

II. The action potential propagates from the atria to the atrioventricular (AV) node.

III. From the AV node, the action potential enters the AV bundle (bundle of His). This

bundle is the only site where action potentials can conduct from the atria to the

ventricles. Recall that elsewhere the fibrous skeleton of the heart electrically insulates

the atria from the ventricles.

IV. After propagating along the AV bundle, the action potential enters both the right and

left bundle branches.

V. From the bundle branches, the action potential propagates to the Purkinje fibers,

which in turn conduct the action potential beginning at the apex of the heart to the

remainder of the ventricular myocardium. Then the ventricles contract, pushing the

blood upward toward the semilunar valves.

Autorhythmic fibers can initiate their own action potentials because they have unstable

resting membrane potentials. The membrane potential starts at about −60 mV and

then spontaneously depolarizes to threshold (−40 mV), at which point an action

potential is generated. After repolarization, the membrane potential again starts to

depolarize and the cycle repeats. The spontaneous depolarization to threshold that

occurs in an autorhythmic fiber of cardiac muscle is known as a pacemaker potential.

The first half of the pacemaker potential is caused by (1) the closure of voltage-gated

K+ channels that were open during the repolarizing phase of the previous action

potential and (2) the opening of F-type channels (so-named because they have funny

or unusual properties), which are mainly permeable to Na+ ions. Closure of the voltage-

gated K+ channels decreases movement of K+ out of the cell (K+ has a higher

concentration in the sarcoplasm than in extracellular fluid); opening of the F-type

PCB3702L Intermediate Human Physiology Dr. Lisa Brinn

channels increases movement of Na+ from extracellular fluid (which has a higher Na+

concentration) into the sarcoplasm. The combined effects of these channel activities

cause the membrane potential to start drifting slowly above −60 mV. Before the

membrane potential reaches threshold, however, the F-type channels close and a new

set of channels open: T-type voltage-gated Ca2+ channels (T for transient because

they remain open for only a relatively short period of time). Opening of the T-type

voltage-gated Ca2+ channels causes the second half of the pacemaker potential. When

these channels open, Ca2+ enters the cell because the Ca2+ concentration is higher in

extracellular fluid than in the sarcoplasm. The influx of Ca2+ depolarizes the membrane

even further, eventually bringing it to threshold. Once threshold is reached, an action

potential occurs.

Pacemaker potentials and action potentials in an autorhythmic cardiac fiber.

PCB3702L Intermediate Human Physiology Dr. Lisa Brinn

In an autorhythmic cardiac muscle fiber, an action potential consists of a depolarizing phase

and a repolarizing phase. The depolarizing phase of the action potential is caused by the

opening of L-type voltage-gated Ca2+ channels (L for long-lasting because they open for a

relatively long period of time). When these channels open, additional Ca2+ enters the cell,

and the membrane potential rises above threshold to a positive value. (Recall that in neurons

and skeletal muscle fibers, the depolarizing phase of the action potential is due to the influx

of Na+ through voltage-gated Na+ channels.) The repolarizing phase of the action potential

in an autorhythmic cardiac muscle fiber is caused by (1) the closure of L-type voltage-gated

Ca2+ channels and (2) the opening of voltage-gated K+ channels. Opening the voltage-

gated K+ channels allows K+ ions to leave the cell, which decreases the membrane potential

back to around −60 mV. Once an action potential is generated in an autorhythmic fiber, it

spreads to the contractile fibers of cardiac muscle via gap junctions.

On their own, autorhythmic fibers in the SA node would initiate an action potential about

every 0.6 second, or 100 times per minute. This rate is faster than that of any other

autorhythmic fibers. Because action potentials from the SA node spread through the

conduction system and stimulate other areas before the other areas can generate an action

potential at their own, slower rate, the SA node acts as the natural pacemaker of the heart.

Action potentials from the autonomic nervous system (ANS) and blood-borne hormones

(such as epinephrine) modify the timing and strength of each heartbeat, but they do not

establish the fundamental rhythm. In a person at rest, for example, acetylcholine released by

the parasympathetic division of the ANS slows SA node pacing to about every 0.8 second or

75 action potentials per minute. Hence, the resting heart rate is about 75 beats per minute.

If the SA node becomes damaged or diseased, the AV node can pick up the pacemaking task.

With pacing by the AV node, however, heart rate is slower, only 40 to 60 beats per minute. If

activity of both nodes is suppressed, the heartbeat may still be maintained by the AV bundle,

a bundle branch, or Purkinje fibers. These fibers generate action potentials very slowly, about

20 to 35 times per minute. At such a low heart rate, blood flow to the brain is inadequate.

PCB3702L Intermediate Human Physiology Dr. Lisa Brinn

Unlike autorhythmic fibers, contractile cardiac muscle fibers have a stable resting membrane

potential of about −90 mV. This value is a result of the fact that resting contractile fibers are

highly permeable to K+ ions and not very permeable to other ions. So the resting membrane

potential stabilizes around the K+ equilibrium potential of −90 mV. When a contractile

cardiac muscle fiber is depolarized to threshold by an action potential initiated by an

autorhythmic fiber, it produces its own action potential. The action potentials that occur in

contractile cardiac muscle fibers consist of four phases: a depolarizing phase, initial

repolarizing phase, plateau phase, and final repolarizing phase.

An action potential in a contractile cardiac muscle fiber.

PCB3702L Intermediate Human Physiology Dr. Lisa Brinn

Depolarizing Phase

During the depolarizing phase, fast voltage-gated Na+ channels open. These channels are referred to

as fast because they open very rapidly in response to a threshold-level depolarization. Opening of

these channels increases the membrane permeability to Na+ ions, allowing Na+ to flow into the cell.

This produces a rapid depolarization that increases the membrane potential to about +20 mV.

Initial Repolarizing Phase

Within a few milliseconds, the fast Na+ channels automatically inactivate, reducing the membrane

permeability to Na+. As a result, Na+ inflow decreases. Of the several different types of voltage-gated

K+ channels present in a contractile cardiac muscle fiber, a subset known as fast voltage-gated K+

channels* opens at this time, allowing K+ ions to leave the cell. The closure of fast voltage-gated Na+

channels and the opening of fast voltage-gated K+ channels cause the initial repolarizing phase of the

action potential. During this phase, the membrane potential begins to decrease.

Plateau Phase

The next phase of the action potential is the plateau, a period of sustained depolarization. It is due in

part to the opening of L-type voltage-gated Ca2+ channels. When these channels open, calcium ions

move from extracellular fluid into the cell. While this is occurring, fast voltage-gated K+ channels

close and slow voltage-gated K+ channels begin to open. The slow voltage-gated K+ channels† are so-

named because they are activated when the membrane initially depolarizes but are slow to open. They

are the same type of voltage-gated K+ channels found in neurons and skeletal muscle fibers. Because

the fast voltage-gated K+ channels are completely closed and the slow voltage-gated K+ channels are

only partially open, the membrane permeability to K+ is relatively low at this time. However, there is

just enough efflux of K+ through the slow voltage-gated K+ channels to balance the Ca2+ influx

through the L-type voltage-gated Ca2+ channels, causing the action potential curve to flatten out like

a plateau. The plateau phase lasts for about 0.2 sec, and the membrane potential of the contractile

fiber is close to 0 mV. By comparison, depolarization in a neuron or skeletal muscle fiber is much

briefer, about 1 msec, because it lacks a plateau phase.

Final Repolarizing Phase

During the final repolarizing phase of the action potential, the slow voltage-gated K+ channels fully

open. This increases the membrane permeability to K+, accelerating K+ outflow. At the same time, the

L-type voltage-gated Ca2+ channels close. This decreases the membrane permeability to Ca2+,

reducing Ca2+ inflow. The increase in K+ outflow and decrease in Ca2+ inflow rapidly restore the

membrane potential to −90 mV. Once the membrane potential reaches the resting level, the slow

voltage-gated K+ channels close.

PCB3702L Intermediate Human Physiology Dr. Lisa Brinn

D. Electrocardiogram - As action potentials propagate through the heart, they

generate electrical currents that can be detected at the surface of the body.

An electrocardiogram, abbreviated either ECG or EKG (from the German word

elektrokardiogram), is a recording of these electrical signals. The ECG is a

composite record of action potentials produced by all of the heart muscle

fibers during each heartbeat.

1. Records electrical signals of the heart

2. Consists of waves, intervals and segments

3. Can be read to provide clues for abnormalities

4. Composed of:

a. P wave

1) Represents depolarization of the atria

b. P-R interval

1) Represents the AV node delay

c. QRS complex

1) Represents ventricular depolarization

d. S-T segment

1) Depolarized state of the ventricular muscle

e. T wave

1) Represents ventricular repolarization

PCB3702L Intermediate Human Physiology Dr. Lisa Brinn

• The Cardiac Cycle

A. Has 5 phases

1. Passive ventricular filling

2. Atrial contraction

3. Isovolumetric ventricular contraction

4. Ventricular ejection

5. Isovolumetric ventricular relaxation

PCB3702L Intermediate Human Physiology Dr. Lisa Brinn

I. Passive Ventricular Filling - Our discussion of the cardiac cycle begins during the

period when both the atria and ventricles are in diastole. Atrial pressure is higher

than ventricular pressure (step 1) because the atria are filling with blood

returning to the heart by veins. As a result of the pressure difference, the

atrioventricular (AV) valves open, and blood flows from the atria into the

ventricles. This phase of the cardiac cycle is known as passive ventricular filling.

The term passive is used because no muscle contractions are involved. About

80% of ventricular filling occurs during this phase; the remaining 20% of

ventricular filling occurs during atrial contraction. It is worth mentioning that

the semilunar (SL) valves are closed at this time because aortic pressure is higher

than left ventricular pressure (step 2) and pulmonary trunk pressure is higher

than right ventricular pressure. At the end of atrial diastole, an action potential

arises in the SA node and then propagates throughout the atria, causing the atria

to depolarize. Atrial depolarization is indicated by the P wave on the ECG (step 3).

II. Atrial Contraction - Atrial depolarization causes atrial systole. While the atria

are in systole, the ventricles remain in diastole. As the atria contract, atrial

pressure increases (step 4) and more blood is forced through the open AV valves

into the ventricles. Atrial contraction contributes a final 25 mL of blood to the

volume already in each ventricle (about 105 mL). The end of atrial systole is also

the end of ventricular diastole (relaxation). Thus, each ventricle contains about

130 mL at the end of its relaxation period (diastole). This blood volume is called

the end-diastolic volume (EDV) (step 5). Toward the end of atria systole, the

QRS complex appears on the ECG, marking the onset of ventricular

depolarization (step 6).

III. Isovolumetric Ventricular Contraction - Ventricular depolarization causes

ventricular systole. While the ventricles are in systole, the atria are in diastole. As

ventricular systole begins, pressure rises inside the ventricles and pushes blood

up against the AV valves, forcing them shut (step 7). For a brief moment, both

the AV and SL valves are closed. This phase of the cardiac cycle is referred to as

isovolumetric ventricular contraction (iso- = same). During this interval, cardiac

muscle fibers are contracting and exerting force but are not yet shortening. Thus,

PCB3702L Intermediate Human Physiology Dr. Lisa Brinn

the muscle contraction is isometric (same length). Moreover, because all four

valves are closed, ventricular volume remains the same (isovolumic).

IV. Ventricular Ejection - Continued contraction of the ventricles causes pressure

inside the chambers to rise sharply. When left ventricular pressure surpasses

aortic pressure at about 80 mmHg and right ventricular pressure rises above

pulmonary trunk pressure (about 20 mmHg), both SL valves open (step 8). At

this point, the ventricular ejection phase of the cardiac cycle begins. During this

phase, blood is pumped out of the heart. The left ventricle ejects about 70 mL of

blood into the aorta, and the right ventricle ejects the same volume of blood into

the pulmonary trunk. The volume remaining in each ventricle at the end of

systole, about 60 mL, is the end-systolic volume (ESV) (step 9). Stroke volume,

the volume ejected per beat from each ventricle, equals end-diastolic volume

minus end-systolic volume: SV = EDV − ESV. At rest, the stroke volume is about

130 mL − 60 mL = 70 mL (a little more than 2 oz). The percentage of the end-

diastolic volume that is ejected with each stroke volume is called the ejection

fraction (EF): EF = SV/EDV × 100. Under normal resting conditions, EF is about

54% (70 mL/130 mL × 100). Changes in stroke volume alter the ejection fraction.

Near the end of ventricular systole, the T wave appears on the ECG, marking the

onset of ventricular repolarization (step 10).

V. Isovolumetric Ventricular Relaxation - Ventricular repolarization causes

ventricular diastole. As the ventricles relax, pressure within the chambers falls,

and blood in the aorta and pulmonary trunk begins to flow backward toward the

regions of lower pressure in the ventricles. Backflowing blood catches in the

valve cusps and closes the SL valves (step 11). Rebound of blood off the closed

cusps of the aortic valve produces the dicrotic wave on the aortic pressure curve

(step 12). After the SL valves close, there is a brief interval when ventricular

blood volume does not change because all four valves are closed. This phase is

known as isovolumetric ventricular relaxation. As the ventricles continue to

relax, the pressure falls quickly. When ventricular pressure drops below atrial

pressure, the AV valves open (step 13), and another cardiac cycle repeats as

passive ventricular filling begins.

PCB3702L Intermediate Human Physiology Dr. Lisa Brinn

A. Heart sounds

6. First sound (S1)

a. Lubb

b. Louder and a bit longer

c. Caused by vibrations associated with the closure of the AV

valves

7. Second sound (S2)

a. Dupp

b. shorter and not as loud

c. Caused by vibrations associated with the closure of the AV

valves

• Cardiac Output

A. The volume of blood ejected per minute

B. Autonomic regulation – heart rate

1. Sympathetic effects

a. Release E and NE

1) Increase force of contraction

2) Increase heart rate

2. Parasympathetic effects

a. Release Ach

1) Decrease heart rate