Cardiovascular physiology

I. Functional Anatomy and Histology of the Heart

A. Myocardial Structure
The myocardium consists of columns of striated muscle fibres.

Each fibre includes an outer membrane (sarcolemma) surrounding

numerous longitudinally arranged myofibrils.

The sarcomere is the functional unit of the myocardium, limited

longitudinally by Z lines.

The sarcoplasm contains mitochondria, fat, and glycogen.

B. Functional Heart Divisions and Anatomy

The Left Heart: Acts as a pressure pump, pumping blood at a high
pressure.

The Right Heart: Acts as a volume pump, pumping a large volume of blood
at a low pressure.

Fibrous Skeleton: Formed of four rings of dense connective tissue to which

both atrial and ventricular muscles are attached.

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 Ventricular Muscle Layers: Formed of 3 layers: inner/outer spiral layers
(running in opposite directions) and a thick transverse middle layer.

Ventricular Thickness and Shape:

Left Ventricle is 3 times as thick as the right.

Left Ventricle is spherical in cross-section; the Right Ventricle is oblong.

Left Ventricular Aid: Contraction of the LV pulls on the outer free wall
of the RV, aiding its contraction. (acute diseases that affect contraction
of the right ventricle are not fatal)

Valve Type Cusps Key Functional Feature

Cusps are attached via chordae tendineae to

Atrio-
Tricuspid (3), papillary muscles, which prevent the valves from
Ventricular
Mitral (2) everting into the atria during ↑ ventricular
(A.V.)
pressure.

They are not attached to papillary muscles; their

Aortic (3), pocket-like shape prevents eversion. Aortic valve
Semilunar
Pulmonary (3) opens at 80 mmHg (LV P); Pulmonary valve
opens at 10 mmHg (RV P).

C. Functional Histology of Cardiac Muscle

Cardiac muscle is striated (similar to skeletal) and acts involuntary as a
functional syncytium (similar to smooth).

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 Functional Syncytium: Firm end-to-end connections between muscle
fibres (intercalated discs) have low electrical resistance, allowing
excitation spread. The heart forms two syncytia: atrial and ventricular
(functional syncytium).

Ordinary Contractile Fibres: Shorter, smaller, highly vascularised, many

mitochondria, and form a branching network.

D. Specialized Cardiac Muscle

1. The nodal or automatic pacemaker fibers: "For initiation of cardiac
impulse".

They differ from the ordinary cardiac muscle fibers: a. Smaller. b. Less
striated. c. Contain less glycogen.

They form gap junction with the ordinary fibers, which allows the
ions to pass with relative ease. Thus, it allows the spread of excitation
wave between the nodal and the ordinary fibres.

They are located in two areas of the heart

Feature Sino-Atrial Node (SAN) Atrio-Ventricular Node (AVN)

Post. wall of Rt. atrium, Rt. side of interatrial septum

Location below and medial to SVC at the junction of atria and
opening. ventricles.

Highest rhythm 90/min.

Rhythm Lower rhythm 60/min.
(Pace maker).

Rt. Vagus nerve and Lt. Vagus nerve and

Nerve Supply
sympathetic. sympathetic.

2. The specialized conducting fibres: "For propagation of cardiac impulse".

They are larger in diameter than the ordinary muscle fibre.

They are present in the AV bundle of His, its branches, and Purkinje
network.

1. The AV bundle of His is continuous with the AVN: It is the only

connection between atria and ventricles.

2. It breaks into two branches, right and left bundle branches, one for
each ventricle-that run down in the interventricular septum under
the endocardium to the apex of the heart, where they are reflected
upwards along the lateral wall of the ventricle to the heart base.

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 3. Each branch gives many small branches (Purkinje network) to the
ventricular muscle fibres. They pass from endocardium to
pericardium.

AVN has the slowest rate of conduction, while Purkinje fibers have the
fastest rate of conduction

II. Cardiac Properties

A. Excitability (Electrical Activity)
Definition: The ability to respond to an adequate stimulus, resulting in an
action potential followed by contraction.

Excitability is due to resting membrane potential (RMP), for ordinary

fibres: -90 mV.

RMP is due to selective permeability and Na-K pump

Cardiac myocyte (ordinary, non-pacemaker) action potential

Components:

a. Depolarization: [partial & complete] + reversal of polarity + 20 mV.

(phase 0)

b. Repolarization: It is triphasic.

Rapid and small. (phase 1)

Plateau : slow repolarization (phase 2)

Rapid and large repolarization (phase 3)

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 Action Potential
Change Ionic Basis
Phase

Rapid increase to +20 mV

Phase 0 (partial, complete & Opening of fast Na+ channels (↑
(Depolarization) reversal of polarity) permeability to Sodium).
Threshold is at -60 mV

Inactivation of fast Na+ channels.

Phase 1 Rapid and small
Small outflow of K+
(Initial Repolarization) repolarization.
Entry of chloride ions

Repolarization slows Balance between small inflow of

Phase 2 down forming a plateau Ca++ & Na+ (via slow Long lasting;
(Plateau) (membrane potential near L-type Ca++& Na+ channels) and
0 mV). small outflow of K+.

Phase 3 Delayed ↑ in K+ efflux (delayed

Large rapid drop to RMP.
(Rapid Repolarization) rectifier K+ channels).

Duration: Atrium 150 msec (short plateau); Ventricle 300 msec (long
plateau).

Relation between Mechanical Response & action potential:

Mechanical response lasts 1.5 times as long as action potential.

Contraction (Systole) starts 2 msec after depolarization and reaches its

maximum by the end of the plateau.

Relaxation (Diastole) starts with the large rapid phase of repolarization,

repolarization is completed by the end of the first 1/2 of diastole.

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 B. Excitability Changes and Refractory Periods

Period Excitability Coincides with Significance

Prevents tetanus;
Depolarization +
Absolute Refractory 0% (no response protects from any
plateau (whole
Period (ARP) to any stimulus) ectopic focus
systole)
firing at this time

Gradual return
Threshold
Relative Refractory from 0 to 100%; Phase 3 (first half of
stimulus = no
Period (RRP) strong stimulus : diastole)
response
weak response

Stimuli can
Second half of
Supernormal Period Excitability slightly produce
diastole, after AP
(vulnerable period) > normal ventricular
ends
fibrillation (fatal)

Relation between electrical, excitability, and mechanical changes:

Systole Diastole

Starts shortly after

Coincides with phase 3 of
depolarization (phase 0) and
Timing repolarization (lasts for double
ends by the end of the plateau
the period of phase 3)
(phase 2).

A.R.P. (absolute refractory

R.R.P. (relative refractory
period; excitability 0%) : heart
Excitability period; ↓ excitability between
cannot be tetanized
0% & 100%)
(continuous contraction).

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 C. Rhythmicity (Automaticity)
Definition: The inherent ability of the heart to INITIATE REGULAR
IMPULSES continuously independent of nervous connections (Myogenic
Property; present in a completely isolated or denervated heart)

Cause: The presence of PREPOTENTIAL in automatic cells (SAN and AVN),

which have an “unstable RMP”.

Rate:

Sino atrial node : 90/minute (pacemaker).

Atrio-ventricular node : 60/minute.

Purkinje fibre : 30/minute.

Differences in electrical activity between automatic vs ordinary cardiac

myocytes:

There is UNSTABLE resting membrane potential called the

PREPOTENTIAL (pace maker potential) starts at -55-65 mV.

There is no plateau in the action potential.

Nodal (pace-maker, specialized) action potential ~ Prepotential

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 Prepotential Phase Mechanism / Ionic Basis

Starts at -60 mV; opening of "funny" channels (slow

inward Na+ current).
Phase 4 (Slow Diastolic
Upon reaching -50 mV, transient (T-type) Ca++
Depolarization)
channels open : Ca++ influx : depolarizing the cell to
the -40 mV firing level.

Opening of long-lasting (L-type) Ca++ channels (Ca++

Phase 0 (Depolarization) influx) responsible for depolarization. (rate is slower
than ordinary fibres).

Opening of delayed rectifying K+ channels (outward

K+ movement with its electrochemical gradient)
Phase 3 (Repolarization)
Potential goes back to - 60 mV : now “funny current” is
activated and the whole cycle is repeated)

Importance of prepotential:

Prepotential is the cause of automaticity (rhythmicity) and ability to

generate impulses

The more rapid is the slope, the more will be the heart rate (firing level
is reached earlier)

SAN: rapid slope = rapid rate 90/minute.

AVN: slower slope = slow rate : 60/minute.

Factors affecting prepotential

Factors that ↓ K⁺
Factors that ↑ K⁺ Permeability
Permeability

Slope Rapid slope Slow slope

↑ Heart rate “+ve

Heart rate ↓ Heart rate “–ve chronotropic”
chronotropic”

Catecholamines, sympathetic
Acetylcholine, vagal stimulation,
stimulation, hyperthermia (↑
Examples digitalis, ↓ extracellular K⁺,
temperature), ↑ extracellular
cooling
K⁺

Pace Maker:

Definition: The part of the heart with the highest rhythm; SAN is the
normal pacemaker.

Evidence SA is the pacemaker:

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 Inhibition of SA node (by cooling or Ach) causes ↓ HR, while
stimulation of SAN (by warming or adrenaline) causes ↑ HR. (Doing
this to other parts has no effect)

D. Conductivity (Propagation of Impulse)

Definition: The spread of excitation wave from the SAN to all parts of the
heart.

Rates:

AV bundle, bundle branches, and Purkinje fibres have the HIGHEST

rate (4 m/s)

Cause : to excite the whole ventricle simultaneously for strong

contraction

AV node has the SLOWEST rate (0.05 m/s)

Reason for AVN Delay:

To delay ventricular contraction until atrial contraction is

complete

Protect the ventricles against high pathological atrial rhythms

(max conduction 150-200 impulse/min).

E. Contractility
Definition: The ability of the heart to pump blood against the peripheral
resistance

Excitation Contraction Coupling (Molecular Theory of Contraction):

Depolarization leads to contraction.

A. Muscle Proteins:

Protein Type Example Characteristics Role in Contraction

Myosin cross bridges

Cross bridges combine
(heads and arms).
Myosin with actin sites when
Contractile Active sites on actin
Actin Ca²+ binds to Troponin
covered by
C.
tropomyosin.

Relaxing Tropomyosin Troponin subunits: Troponin attaches

Troponin I : affinity for actin tropomyosin to active
T : affinity for sites of actin, preventing

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 tropomyosin myosin binding (resting
C : high affinity for state).
calcium

B. Tubular System:

1. Transverse (T) tubule: Invagination of the muscle membrane containing

extracellular fluid. AP spreads along T tubules to the interior. Wider
diameter in cardiac muscle than skeletal muscle.

2. Sarcoplasmic Reticulum (SR): Contains high concentration of Ca²+. Less

developed in cardiac muscle and does not store enough Ca²+ for full
contraction. Ends expand to form terminal cisternae contacting T tubules.

C. Molecular Mechanism of Contraction/excitation contraction coupling:

1. Action potential spreads along T-tubules.

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 2. Ca²+ influx occurs during plateau phase (through slow L-type channels).

Cardiac contraction depends mainly on extracellular Ca²+, unlike

skeletal muscle.

3. Inflow of Ca²+ stimulates release of Ca²+ from terminal cisternae of SR

(via Ryanodine receptors).

4. Free cytosolic Ca²+ increases.

5. Ca²+ binds to Troponin C, reacting with tropomyosin to uncover active

sites on actin.

6. Myosin cross bridges combine with active sites on actin, causing sliding,
which needs energy from ATP (Myosin acts as ATPase); contraction is an
active process.

7. Relaxation: Intracellular (cytosolic) Ca²+ falls : tropomyosin covers active

sites of actin : relaxation

Na+ Ca²+ exchanger : 2 Na+ exchanged for 1 Ca++. (electroneutral

exchange for Ca++ that entered from ECF)

Active reuptake of Ca²+ back to SR.

Factors affecting contractility:

1. All or none rule: The cardiac muscle contracts maximally or does not, at
all provided all factors are kept constant (functional syncytium).

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