SLIDE NO.3

1. Cardiovascular system
What you will learn:
Anatomy of heart structure, rhythmic excitation, myogenic heart,
specialized tissue, ECG – its principle and significance, cardiac cycle, heart
as a pump, blood pressure, neural and chemical regulation of all above.

2. They are self-contracting, autonomically regulated and must continue
to contract in rythmic fashion for the whole life of the organism. Hence
they have special features.
The cells are Y shaped and are shorter and wider than skeletal muscle
cells. They are predominatly mononucleated. The arrangement of actin
and myosin is similar to skeletal striated muscle.
Some of the cardiac muscle cells are auto-rhythmic, i.e they contract
even in the absence of neuronal innervation (known as pacemaker cells).
Intercalated disks are located between cardiac muscles cells. These
contain gap junctions which provide communicating channels between
cells.The intercalated disks allows waves of depolarisations to sweep
across the cells thus synchronising muscle contraction.
Cardiac muscles
Depolarisation of cardiac muscle cells differs from that of other muscle
cells.Repolarisation takes much longer to occur and thus cells cannot be stimulated at
high frequency. The advantage is that cardiac muscle are prevented from going into
tetanus.

4. Skeletal muscle vs. Cardiac muscle

5. Skeletal muscle vs. Cardiac muscle
Transmission electron microscopy

6. Heart muscle is a SYNCYTIUM of many Cardiac Myocytes

8. Differences in concentration of ions on opposite sides of a
cellular membrane leads to a voltage called membrane potential

9. • Na+-K+ ATPase pump used for maintaining the large excess of Na+
outside the cell and the large excess of K+ ions on the inside.
• This unbalanced charge transfer contributes to the separation of charge
across the membrane. The sodium-potassium pump is an important
contributor to action potential produced by nerve cells.
This establishes two concentration gradients
Leak of more potassium ions (more permeable; Na+-K+ leak channels) to
diffuse across the membrane, down the concentration gradient that was
established by the ATPase, creating a charge separation, and thus a voltage,
across the membrane.

10. + + + + + + + + + + + + + + + + + + +
K+
- - - - - - - - - - - - - - - - - - - -
Na+
3Na+
2K+
More positive
Positive charge
less positive
Negative charge
All membranes have Na+-K+ channels or pumps (AT)
ATP
Na+
K+
Na+-K+ leak channels
Deficit of positive on inside: gives negative potential to inside of cell membranes
-90mV: resting membrane potential

11. Relatively static membrane potential of quiescent cells is called the
resting membrane potential (or resting voltage), as opposed to the
specific dynamic electrochemical phenomena called action potential and
graded membrane potential.
RESTING MEMBRANE POTENTIAL
-90mV on the inside of the fibre
AT of Na+ and K+ thro the membrane: SODIUM POTASSIUM PUMP
OUT
IN
3Na+
2K+
Electrogenic
Pump: more +ve out and -ve in leaving a deficit of +ve on inside
Hence -ve Potential inside the membrane

13. In physiology, an action potential is a short-lasting event in which the
electrical membrane potential of a cell rapidly rises and falls, following a
consistent trajectory.
Action potentials occur in several types of animal cells, called excitable cells,
which include neurons, muscle cells, and endocrine cells, as well as in some plant
cells. In neurons, they play a central role in cell-to-cell communication.
In other types of cells, their main function is to activate intracellular
processes.
In muscle cells, for example, an action potential is the first step in the chain
of events leading to contraction. In beta cells of the pancreas, they provoke
release of insulin. Action potentials in neurons are also known as "nerve
impulses" or "spikes", and the temporal sequence of action potentials
generated by a neuron is called its "spike train". A neuron that emits an action
potential is often said to "fire".
Action Potential

14. Action potentials are generated by special types of voltage-gated ion channels embedded in a
cell's plasma membrane. These channels are shut when the membrane potential is near the
resting potential of the cell, but they rapidly begin to open if the membrane potential
increases to a precisely defined threshold value.
When the channels open, they allow an
inward flow of sodium ions,
which changes the electrochemical gradient,
which in turn produces a further rise in the membrane potential.
This then causes more channels to open,
producing a greater electric current, and so on.
The process proceeds explosively until all of the available ion channels are open, resulting in a
large upswing in the membrane potential.
The rapid influx of sodium ions causes the polarity of the plasma membrane to reverse,
and the ion channels then rapidly inactivate.
As the sodium channels close,
sodium ions can no longer enter the neuron, and they are actively transported out of the
plasma membrane.
Potassium channels are then activated, and there is an outward current of potassium ions,
returning the electrochemical gradient to the resting state.
After an action potential has occurred, there is a transient negative shift, called the after
hyperpolarization or refractory period, due to additional potassium currents. This is the mechanism which
prevents an action potential traveling back the way it just came.
Action Potential

15. NERVE ACTION POTENTIAL
Transmission of nerve signals ----- action potential (AP)
AP: rapid changes in membrane potential, which spreads long the nerve fibre
-90mV (Negative potential) ---------> positive potential
Resting
Action
0
+35
overshoot
-90
polarized
Membrane
permeable to Na+
Na+ channels close
K+ channels open
Diffusion of K+

16. Depolarisation of cardiac muscle cells differs from that of other muscle cells.
Repolarisation takes much longer to occur and thus cells cannot be stimulated at high
frequency. The advantage is that cardiac muscle are prevented from going into tetanus.
Action Potential of Cardiac Muscle
Spontaneous depolarization

17. Action potential causes
ventricular contraction to last
15times longer than skeletal
muscle
-85mV to +20mV

18. 4: resting membrane potential;
diastole
0: rapid depolarization (opening of
fast Na+ channels and inward movt.
of Na+)
1: inactivation of fast Na+ channels
(K+, Cl- out)
2: “ plateau ” balance b/w inward
Ca++ and outward K+ (slow)
3: “ rapid repolarization ” Ca++
channels close; K+ perm. incr.; K+
out, net outward positive current
(loss of positive charge);
4: cells repolarize (-85-90mV) and
resting membrane potential is
achieved

19. Long Action Potential of Cardiac Muscle and Plateau
AP is caused by opening of fast
sodium channels; Na+ enters
skeletal muscle from ECF
(FAST). Channels close and
repolarization occurs
Permeability of K+ does not
decr
Skeletal Muscle Cardiac Muscle
1. Fast Na+ channels
2. Slow Ca++ channels (Ca-Na channels);
remain open for 1/10th of a sec; slow;
large Ca-Na+ flows into cardiac
muscle; prolonged depolarization and
hence plateau
3. Ca ions activate muscle to enter into
contractile phase
4. Permeability of K+ ions decr
(5X);outflux prevented; prevents
early return of AP plateau
5. Channels close; influx of Ca and Na+
cease, K+ permeability incr and rapid
loss of K from cardiac muscle returns
membrane pot----end of AP
0.3-0.5m/sec: velocity of signal conduction of excitatory AP along A-V muscle fibre

21. Refractory Period of cardiac Muscle
Cardiac muscle is refractory to restimulation
RP: that interval of time during which a normal cardiac impulse cannot re excite
an already excited area of cardiac muscle
1 2 3
sec
contraction
Normal refractory period of ventricle is 0.25-0.30 sec
Relative RP: (0.05sec) muscle is difficult to excite but can be with a
strong excitatory signal
Early premature contraction
Late premature contraction

22. Refractory Period of
cardiac Muscle

23. Automaticity of Cardiac Muscle
It means that it is self-exciting. (You could also call it "myogenic" tissue.
Meaning a tissue able of creating its own excitement.) This is in contrast
with skeletal muscle, which requires either conscious or reflex nervous
stimuli for excitation.
The heart's rhythmic contractions occur spontaneously, although the
rate of contraction can be changed by nervous or hormonal influences,
exercise and emotions. For example, the sympathetic nerves to accelerate
heart rate and the vagus nerve decelerates heart rate.

24. The rhythmic sequence of contractions is coordinated by the sinoatrial (SA) and
atrioventricular (AV) nodes.
The sinoatrial node, often known as the cardiac pacemaker, is located in the
upper wall of the right atrium and is responsible for the wave of electrical
stimulation that initiates atrial contraction by creating an action
potential.
Once the wave reaches the AV node, situated in the lower right atrium,
it is delayed there before being conducted through the bundles of His and
back up the Purkinje fibers, leading to a contraction of the ventricles.
The delay at the AV node allows enough time for all of the blood in the
atria to fill their respective ventricles.
In the event of severe pathology, the AV node can also act as a pacemaker;
this is usually not the case because their rate of spontaneous firing is
considerably lower than that of the pacemaker cells in the SA node and
hence is overridden.
Automaticity of Cardiac Muscle

27. Aa
Aa

29. Cyt
SERCA
Sarcolemma
ICa
Ca
Ca
3Na
SR
RyR
3Na
Ca
T-Tubule
Na
Na
Na
Na
Ca
NCX
NCX
ATP
2K
ATP
PLB/SLN
AP
(Em)
[Ca]i
Contraction
3Na
2K
ATP
by D.M. Bers
Ca2+ Ion transport in Muscle
SERCA: Sarco/Endoplasmic Reticulum Ca2+ ATPase
SLN: Sarcolipin; PLB: Phospholamban

30. Cyt
Ca
RyR
T-Tubule
3Na
Ca
Na
Sarcolemma
NCX AP
(Em)
[Ca]i
Contraction
SERCA
ATP NCX
Na 3Na Na
3Na
2K
ATP
PLB/SLN
ICa
SR
by D.M. Bers
Ca
Na
Ca
Ca2+ Ion transport in Muscle
SERCA: Sarco/Endoplasmic Reticulum Ca2+ ATPase
SLN: Sarcolipin; PLB: Phospholamban

32. Heart Valves Produce One-way Blood Flow
Atrioventricular(AV) valves –prevent backflow of blood into the atria when
the ventricles contract.
1. bicuspid valve –between left atrium and left ventricle
2. tricuspid valve –between the right atrium and right ventricle

33. Heart Valves Produce One-way Blood Flow
Semi lunar Valves
– prevent backflow of blood into the ventricles when the ventricles
relax.
1. aortic valve –at entrance to aorta
2. pulmonary valve –at entrance to pulmonary trunk
The semilunar valves also have cusps, which catch blood as it flows back toward
the ventricle during ventricular systole.
“dubb”

34. The heart pumps by squeezing,
compressing and pressurizing the blood
which then flows down the pressure
gradient. The heart’s valves force the
blood to go in one direction and prevent
(when working properly) backward flow.

36. 3D reconstruction of the heart as viewed from the apex towards the valves, image flipped 180° relative to illustration
above. Pulmonary valve not visible, leaflets of the tricuspid and aortic valves only partly visible. To the left two images in
2D from the same dataset, showing tricuspid and mitral valves (above) and aortal and mitral valve (below).
Tricuspid and mitral valve
aortic valves
aortal and mitral valve
Tricuspid

37. Terms:
DIASTOLE-the relaxation phase; unless otherwise specified refers to
left ventricle, but each chamber has its own diastole;
refers to filling of blood
SYSTOLE-the contraction phase; unless otherwise specified refers to
left ventricle, but each chamber has its own systole.
CARDIAC CYCLE
the sequence of events from the beginning of one heartbeat to
the beginning of the next
Each cycle is initiated by the spontaneous generation of AP in the
SINO ATRIAL NODE. AP travels from here to atria and AV
bundle into the ventricles (delay of 0.1 sec)
The frequency of the cardiac cycle is described by the heart rate.

38. Each beat of the heart involves five major stages
The first two stages, often considered together as the "ventricular filling"
stage, involve the movement of blood from atria into ventricles. Action of
valves relating to them
The next three stages involve the movement of blood from the ventricles
to the pulmonary artery (in the case of the right ventricle) and the aorta
(in the case of the left ventricle). Action of valves relating to them
CARDIAC CYCLE

39. The first, "late diastole", is when the semi lunar valves close, the
atrioventricular (AV) valves open, and the whole heart is relaxed.
The second, "atrial systole", is when the atrium (R and L) contracts, the
AV valves open, and blood flows from atrium to the ventricle.
The third, "isovolumic ventricular contraction", is when the ventricles
begin to contract, the AV and semilunar valves close, and there is no
change in volume.
The fourth, "ventricular ejection", is when the ventricles are empty and
contracting, and the semilunar valves are open.
During the fifth stage, "Isovolumic ventricular relaxation", pressure
decreases, no blood enters the ventricles, the ventricles stop contracting
and begin to relax, and the semi lunar valves close due to the pressure of
blood in the aorta.
CARDIAC CYCLE

40. Throughout the cardiac cycle, blood pressure increases and decreases.
The cardiac cycle is coordinated by a series of electrical impulses that are
produced by specialized heart cells found within the sinoatrial node and the
atrioventricular node.
CARDIAC CYCLE
The sino-atrial node sends out electrical waves of excitation to both atria, and
it is prevented from flowing into the ventricles by strands of non-conducting
fibrous tissue situated laterally from the tricuspid/bicuspid valves to the septum.
These waves of excitation travel towards the septum and into the atrio-
ventricular node, where they are held for roughly 0.1 seconds. They are then
discharged down the bundle of his, then down the purkinje tissue, which are both
situated inside the septum. The waves flow down towards the apex of the heart
and are then discharged into the ventricles, causing them to contract (ventricular
systole) This creates the well known beat of the heart.
The cardiac muscle is composed of myocytes which initiate their own contraction without help of
external nerves (with the exception of modifying the heart rate due to metabolic demand). Under
normal circumstances, each cycle takes approximately one second.

42. Major Events in The Cardiac Cycle
1) quiescent period- period when all chambers are at rest and filling.
70% of ventricular filling occurs during this period. The AV valves
are open, the semi-lunar valves are closed.
2) atrial systole- pushes the last 30% of blood into the ventricle. BP in
atria rises and pushes blood into ventricles (atrial kick) [P wave:
depolarization; due to SA node]
3) atrial diastole- atria begin filling. This occurs nearly simultaneously
with the next event…
4) ventricular systole- ventricles contract, first closing the AV valves
and causing the first heart sound then the semi lunarvalves open
permitting ventricular ejection of blood into the arteries.
5) ventricular diastole- As the ventricles relax the semi lunarvalves
close first producing the second heart sound, then the AV valves
open allowing ventricular filling.

43. Heart diastole
Atrial systole
Heart systole
Ventricular systole
Atrial Pressure
a wave: atrial contraction;; AV valves open; RAP incr 4-6mm Hg
LAP incr 7-8 mm Hg
c wave: ventricles contract (V systole); backflow of blood in atria; incr in
ventricular pressure; AV valves closed, SLV open
v wave: end of contraction; slow flow of blood into atria from SVC/IVC (diastole);
AV valves open
Heart diastole
Atrial systole

44. V V V
middle stage of diastole during the cycle of a heartbeat

46. Electrocardiogram
P: spread of depolarization through atria
Atrial contraction
Rise in atrial pressure after P wave
After 0.016sec
QRS wave: electrical depolarization of ventricles
Initiation of contraction
Ventricular pressure rises
QRS rises slightly before ventricular systole
T wave stage of repolarization of ventricles (ventricular muscles relax;
occurs slightly before end of ventricular contraction)
P
Q
R
S
T

48. Cardiac Diastole
CD is the period of time when the heart relaxes after ventricular contraction
in preparation for refilling with circulating blood.
Ventricular diastole is when the ventricles are relaxing, while atrial diastole
is when the atria are relaxing. Together they are known as complete cardiac
diastole.
During ventricular diastole, the pressure in the (left and right) ventricles drops
from the peak that it reaches in systole. When the pressure in the left
ventricle drops to below the pressure in the left atrium, the mitral valve opens,
and the left ventricle fills with blood that was accumulating in the left atrium.
The isovolumic relaxation time (IVRT) is the interval from the aortic
component of the second heart sound, that is, closure of the aortic valve, to
onset of filling by opening of the mitral valve. Likewise, when the pressure in
the right ventricle drops below that in the right atrium, the tricuspid valve
opens, and the right ventricle fills with blood that was accumulating in the right
atrium.
During diastole the pressure within the myocardium is lower than that in aorta, allowing
blood to circulate in the heart itself via the coronary arteries.

52. AV open
SL close

53. AV open
SL close

54. Cardiac Cycle

55. Cardiac Output
The volume of blood per minute that the left ventricle pumps into the
systemic circulation
Depends on two factors:
1. Heart rate: rate of contraction i.e. number of beats per minute
2. Stroke volume: amount of blood pumped by left ventricle in each
contraction.
Average SV is 75ml in humans; heart rate is 70 beats per minute
cardiac output is 5.25 L/min (= to total vol of blood in body)
CO incrs during heavy excersise

56. Cardiac Output
Minute Volume= Heart Rate X Stroke Volume
Heart rate, HR at rest = 65 to 85 bpm (widest range usually quoted)
Each heartbeat at rest takes about 0.8 sec. of which 0.4 sec. is quiescent period.
Stroke volume, SV at rest = 60 to 70 ml.
C.O. at rest = 70 bpmX 70 ml/beat = 4900 ml/min/vent.
The heart can increase both rate and volume with exercise.
Rate increase is limited due to necessity of minimum ventricular diastolic period for filling.
Upper limit is usually put at about 220 bpm. Maximum heart rate calculations are usually
below 200.

57. SV / EDV = Ejection Fraction Normally around 50% at rest and will
increase during strenuous exercise in a healthy heart. Well trained
athletes may have ejection fractions approaching 70% in the most
strenuous exercise.
Preload-This is the pressure at the end of ventricular diastole, the
beginning of ventricular systole. It is roughly proportional to the End
Diastolic Volume (EDV), i.e. as the EDV increases so does the preload
of the heart.
Afterload- This is the pressure at the end of ventricular systole
and is related to the resistance to blood flow. It is roughly
proportional to the End Systolic Volume (ESV). When the peripheral
resistance increases so does the ESV and the afterload of the heart.
The difference between preload and afterload is a measure of
the hearts efficiency.
ADDITIONAL TERMS

58. Blood Flow ~ Δblood pressure
Resistance to
blood flow
Blood flow is directly proportional to the pressure gradient
over a section of a blood vessel, and inversely proportional to
the resistance to flow.
Resistance is produced by friction along the vascular wall, and
is increased with vasoconstriction, atherosclerosis, and
hypertension.

59. Arteries have blood
flowing at high velocity
and pressure and
maintain BP even when
heart is relaxed; thick
and elastic walls
Vein have thin walls
and blood flows at low
velocity and low
pressure and flows as a
result of skeletal
muscle action; contain
valves to move blood
towards heart

62. SYSTEMIC
AND
PULMONARY
CIRCULATION:
CARDIOVASCULAR
CIRCULATION