- Moayyad Al-Shafei

-Waseem Abu Obidah

-Faisal Mohammed

- 4

Last time we have introduced the conduction system of the heart, which is

composed of a modified cardiac muscle cells. They are modified:

1- Anatomically: By lacking the contractile proteins (actin and myosin), and by

having a rounded instead of rectangular shapes.

2-Physiologically: they are leaky to sodium, have a special channels called leaky

sodium channels which allow sodium to diffuse according to its concentration

gradient.

Also we mentioned the components of this system (the SA node, AV node, bundle

of His, bundle branches, and Purkinje fibers.) and how they differ from each other

in their:

a-Intrinsic rate (the number of impulses- action potentials- generated per

minute) as follows: SA node 70-80/min, AV node 40-60/min and Purkinje fibers

15-40/min.

The cells of this system are autorythmic cells: this means that they can discharge

(generate an action potential) without a stimuli from external innervation.

b- Conduction rate (It is the speed at which an

impulse propagates) as follows:

-SA node: slow speed of conduction.

- Ventricular and Atrial muscle: Moderate speed of

conduction.

- AV node: slowest speed of conduction.

- Purkinje fibers: Fastest speed of conduction.

*The numbers are not for memorization, they are only

to give you an indication about the difference between

the components of the conduction system.

Notes:

- The conduction is unidirectional, due to refractory periods (anything recently

repolarized won’t be depolarized again for a while, so the wave can't go back).

- Why the conduction rate in the AV node is the lowest? To assure that the atria

and ventricles will not contract at the same time; atria contract and finish their

contraction then ventricles are able to contract and this is mediated through AV

node which delays the impulse.

- The conduction rate is the fastest in the Purkinje, 4m /sec, due to their higher

number of gap junctions and larger diameter and low resistance, to make sure

that ventricles will receive the impulse at the same time and contract at the same

time as a one unit, otherwise, each ventricular fiber contracts dependent from

the others, this is called ventricular fibrillation which is lethal and the physician

should interfere to relief the condition.

** don’t mix the last 2 concepts with each other as they are completely different.

How does the heart work?

1-The SA node drives the heart as a

pacemaker, due to its highest intrinsic

activity in comparison to others, and

anything else is considered ectopic.

2-Some believe that the internodal

bundles (between the AV node and the

SA node) conduct the impulses from

the SA to the AV nodes (But the doctor

believes that the impulse is conducted

via the muscles of the atria).

3-The impulse is then conducted through the bundles (bundle of his and its

bundle branches) till reaching the Purkinje fibers which finally spread it through

the ventricular muscles.

- Think of this system as train having a multiple carts, and of course the cart with

the highest rate leads, so:

-The atria and the ventricles contract at the rate of the SA node (pacemaker)

that is 70-80, meaning that the Purkinje fibers also work at this rate.

What about the AV and Purkinje intrinsic rates? Their intrinsic rates are

suppressed by the highest SA rate, this is called over drive suppression.

- Normally SA node has the highest rate, and once it is destructed, the rate of

the AV node will drive the heart rate (ectopic pacemaker-any pacemaker other

than the SA is ectopic-).

- If the AV node is not normal (a condition called AV block), the impulse will not

reach the ventricles. And within 15-30 seconds, the Purkinje fibers will generate

the impulses which drive the ventricles. (Here, atria and ventricles contract at

different rates as they are separated from each other via fibrous tissue septa),

this point will be explained later in this sheet.

- We said that the pacemaker can generate action potential intrinsically, and

this action potential is different from the cardiac one as we will see:

1-Phase 4

-The resting potential will be less negative reaching -60, and does not reach-90.

And the cause behind this lesser negativity is that the cell membranes of the sinus

fibers are naturally leaky to sodium and calcium ions, and positive charges of the

entering sodium and calcium ions neutralize some of the intracellular negativity.

-At -60 millivolts, Leaky channels conduct slow inward sodium increasing the

potential to a less negative value, at -50 millivolts another type of channels open

called T-type calcium channels (transient ca channels), as ca enters through these

channels it also increases the potential, so the passing of calcium and sodium

through these channels contribute to the slow depolarization phase until reaching

the threshold -40 millivolts.

-This is the longest phase of SA node action potential.

-This phase is a determinant to the heart heart.

2-Phase 0 (depolarization)

-Occurs due to opening of L-type calcium channels (long lasting calcium

channels). These channels open at threshold of -40 millivolts.

3-Phase 3 (repolarization)

-Occurs due to increased permeability and efflux of K ions.

4-There is no phase1 (partial repolarization) nor phase 2 (plateau)

- This cycle continues. Remember that we said that it occurs intrinsically without

any stimulation. SO, what are the effects of the ANS on the cardiac physiology?!

-*- An important note, the rate of the impulses depends on the slope of the Phase

4 (-60 to the threshold). Higher slope means less time to reach the threshold thus,

a higher rate (it makes sense!). Now what affects the slope? It is mainly the

permeability of the membrane for sodium, potassium and calcium. (Remember

what makes the membrane of the conduction system less negative than the

normal one. The same principle is applied here, the less the negativity, the shorter

time is needed to reach the threshold). Now we can understand the ANS effects

on the heart.

- I think also that we can understand the cause that makes the SA, AV nodes and

Purkinje different from each other in their rhythmic rates. It is due to their

difference in sodium permeability (sodium leakiness).

-We have both sympathetic and parasympathetic innervations, see the figure

during reading:

1. Sympathetic fibers from cardiac plexus which supply all the heart (ventricles

and atria). They release epinephrine and norepinephrine which:

a- Increase the rate (positive chronotropic effect) by

- Increasing the permeability to sodium(influx) and calcium and decreasing it for

potassium So, the resting membrane potential become less negative the

slow depolarization occurs faster (increasing the slope of phase 4) the rate

increases.

b- Increase the strength of contraction (positive inotropic effect) by

- Increasing the permeability to calcium. (It affects other contractile cells of the

heart not the SA node because SA node does not have contractile tissue).

c- Increase the rate of conduction (positive dromotropic effect)

2. Parasympathetic fibers, from vagus nerve (10th cranial nerve), which supply

only the atria (SA node and AV node), and do not affect the ventricles. They

release acetylcholine which:

a- Decreases the heart rate (negative chronotropic effect) by:

-Increasing the permeability for potassium (efflux) and decreasing it for sodium

and calcium So, the resting membrane potential becomes more negative

the slow depolarization occurs slower (decreasing the slope of phase 4) the rate

decreases.

b- Has a negative inotropic and dromotropic effects on the atria only.

c-Has no effect on the contractility of ventricles.

-*-In both types of stimulation (sympathetic or parasympathetic) the peak doesn't

change as it follows “the all or none principle”.

Ectopic pacemaker may result due to different situations we mentioned some of

them, but let’s revise:

-We said that the SA node drives the heart as a pacemaker, due to its highest

intrinsic activity, and anything else is considered ectopic. We said also that the

intrinsic rhythm of AV node and Purkinje fibers are suppressed by receiving the

faster rhythmic action potential of SA node. This is called overdrive

suppression.

-Ectopic pacemaker: pacemaker in an area other than the SA node; it can be

faster or slower in rate than the SA node. An examples of ectopic pacemakers:

1-Upon the stimulation (by pressurizing it locally, near the trachea) of the

vagus nerve we suppress SA node gradually (remember the effect of the

parasympathetic innervation). And after a while the SA and AV nodes rhythm

stops. After that, Purkinje fibers’ intrinsic rhythm starts because of the

absence of the overdrive suppression. But the reactivation of Purkinje fibers is

not direct; it may take 15 to 30 seconds to start. This process is called

ventricular escape.

2- Pathologically, when the conduction from SA to A-V nodes is blocked (A-V

block), During sudden onset of A-V block, sinus node discharge(impulse) does

not get transmitted to ventricles, and Purkinje fibers become the pacemaker

of heart beats because of the absence of the overdrive suppression. A-V block

results in a syndrome called “Stokes-Adams” syndrome. What we usually do

is that a new pacemaker (artificial) is implanted in A-V node, penetrating part

of A-V bundle or in the right ventricular muscle.

Electrocardiogram

This is a very important topic, because if anyone enters the hospital with a

chest pain or any cardiac symptom the 1st thing the doctor asks for is an ECG.

So what is the ECG?

-The electrical currents generated by cardiac muscle during depolarization

and repolarization spread into the tissues around the heart and are

conducted through the body fluids. A small part of this electrical activity

reaches the body surface, where it can be detected using a machine (contains

galvanometer and amplifier). The record produced is an electrocardiogram,

or ECG. (Alternatively, the abbreviation EKG is often used, because the

pioneers of this technique are German, and in their language cardio is written

with a k).

- ECG records the changes in the electrical activity, it has nothing to do with

the mechanical activity.

- ECG is recorded using a machine called the galvanometer that records

voltage difference and has 2 electrodes (bipolar) which are put on a surface

(muscle cell-But no one in this world or at least no one with a brain will accept

to have his chest opened just for an ECG!! - or body surface) and the potential

difference between these 2 points will be recorded.

- How much is the potential difference that occur in the heart?

The membrane potential at the resting state is =-90 and in the overshot

(max) = +30 so there is a difference of almost {+30-(-90) = 120} at the level of

the heart!!

At the level of the skin it is going to reach 2-3 millivolt due to resistance, and

this is the cause behind using the amplifier as a part of the ECG machine.

The Principles of ECG

-When we discussed the topic of action potential, the graphs demonstrated

are monophasic. This means that the electrical activity is detected by placing

an electrode outside the cell and the other parallel inside the cell, and the

graph was all above the resting potential, because the positive ions get in the

cell throughout the process.

- ECG, however, measures in a biphasic manner by placing the both

electrodes outside the cell in two different points. The electrodes are put on

the surface of the body. Placing the electrodes directly on the surface of the

heart is not practical (although gives the best results), and may be done only

during heart surgeries.

Let’s apply some physic now, and discuss the following graph of biphasic

measurement:

First, when the whole muscle is in the resting state the difference equals

zero ((isoelectric line))

Then (during depolarization), the potential difference increases until

reaching its maximum value when the muscle is halfway in depolarization.

When the membrane is completely depolarized, the difference gets back to

zero (another (Isoelectric line).

****This wave is called the depolarization wave which is deflected upwards.

Note: depolarization wave doesn’t always mean an upward reflection this can

be changed and this depends in the arrangement of the 2 electrodes.

The membrane now is fully depolarized ( negative outside, positive inside),

so repolarization starts to happen and now charges outside the membrane

are becoming positive again(increase the pot difference) until reaching the

maximum level midway.

At last, after exceeding the midway it starts to decrease till reaching the

fully repolarized state (outside positive and recording is zero).

Normal ECG

-ECG records the change in the voltage (Y axis) plotted against time (X axis).

-This figure shows a normal EKG (it shows depolarization of the atrium,

depolarization and repolarization of the ventricles).

The waves of the electrocardiogram have the following represent:

1- P wave represents the depolarization of atria.

–Signals onset of atrial contraction

2- QRS complex represents ventricular depolarization

–Signals onset of ventricular contraction

3-T wave represents the repolarization of ventricles

NOTES

* These shifting waves of depolarization and repolarization bring about

alternating contraction and relaxation of the heart, respectively.

* The P wave is smaller than the QRS complex because the atria have a smaller

muscle mass than the ventricles and consequently generate less electrical activity.

*Cardiac cycle (heart beats): the time between a point and its next emergence (R

to the next R for example…). This means that you can calculate the heart rate out

of ECG (1 cycle = 1 beat).

* Note: this recording doesn’t stop. If the recording stopped and a continuous

straight line appeared this means this person is dead.

As we can see depolarization of both atrium and ventricles are shown but only the

repolarization (but it is deflected upwards) of the ventricle is shown. The

following figure solve the major 2 questions:

1- The 1st: Why doesn't repolarization of the atria appear?

It doesn't appear because it is masked by the QRS wave. Notice from the figure:

-Phase 0 of the atria (depolarization) → P wave

-It doesn’t appear as Phase 3 of the atria (repolarization) happens at the same

time as phase 0 (depolarization) of the ventricles(QRS wave).

2-The 2nd: Why does T wave (repolarization wave) is an upward deflection (just

like the depolarization wave and not the opposite)?

-Because repolarization starts retrospectively from the last depolarized site!!

-Depolarization starts from the endocardium to the epicardium and from the base

to the apex of the heart. While repolarization starts from the epicardium to the

endocardium and from the apex to the base of the heart (Endothelial area

depolarizes first, and pericardial area repolarizes first). But why?!

Going back to the ECG measurement section, you can see that depolarization and

repolarization both started from left to right, and their corresponding waves was

in opposite directions. If the repolarization started from the opposite side (like

what happens in the heart), both waves will be in the same direction. The

following figure shows the case here, compare it to the others in the

measurement section:

But why depolarization and repolarization don't start from the same area in the

heart?

- It could be a due to an intrinsic property of endocardial and epicardial muscles.

The endocardial muscles repolarization is a little bit longer than the epicardial

muscles.

- A more acceptable theory states the following:

Depolarization is always followed by systole (contraction) and repolarization is

followed by diastole (relaxation). So, when there is depolarization of the

ventricles, it is followed by contraction. And because the cells of the ventricle are

intermingled with each other, there is an increase in the force in the center. This

increased force in the center will affect mostly the endocardium. And because this

force presses too much on the endocardium, it delays repolarization by changing

the permeability of endocardial cells to ions thus, disturbing their balance which

in turn requires longer time to reestablish again to the extent that delays the

repolarization.(this will be discussed in more details in next sheet)