Cardiovascular Physiology Continued Education Program Physiology 2 Cardiovascular Physiology Functional anatomy & Cardiac Properties Presented by: Dr. Shaimaa Nasr Amin Lecturer of Medical Physiology

Physiological Anatomy

The cardiovascular system is composed of : 1- A central pump; the heart 2- The blood vessels. The aim of this pumping is to provide adequate blood flow to every cell of the body.

The heart can be viewed functionally as two pumps with the pulmonary and systemic circulations situated between the two pumps

The pulmonary circulation is the blood flow within the lungs that is involved in the exchange of gases between the blood and alveoli. The systemic circulation is comprised of all the blood vessels within and outside of organs excluding the lungs.

Chambers of the heart : The right side of the heart Right atrium (RA) Right ventricle (RV) The right side of the heart Left atrium (LA) Left ventricle (LV) The left side of the heart

The unit of structure of the cardiac muscle is the cardiac muscle fiber or cardiac myocyte.

Cardiac myocytes has the following features: They are striated. Its length is about 100 micrometer long and 25 micrometer in diameter. Cardiac myocytes form a branching network of cells that are connected to each other through specialized cell membrane structures called intercalated discs.

Cardiac Muscle as a Syncytium Intercalated discs; they are actually cell membranes that separate individual cardiac muscle cells from one another.

Cardiac Muscle as a Syncytium At each intercalated disc the cell membranes fuse with one another to form permeable gap junctions that allow rapid diffusion of ions.

Cardiac Muscle as a Syncytium The heart actually is composed of two syncytiums: the atrial syncytium and the ventricular syncytium.

Cardiac Properties

Cardiac Properties 1-Autorhythmicity 2-Conductivity 3-Excitability 4-Contractility

Cardiac Properties 1-Autorhythmicity Automaticity is the ability of the heart to initiate its own contraction independent of external stimuli. Rhythmicity means that the heart can beat regularly. Both automaticity and rhythmicity are due to the pacemaker action potentials that are generated spontaneously and regularly.

Cardiac Properties 1-Autorhythmicity Pacemaker cells are present in SA node, AV node and Purkinje fibers. Cells of the SA node are the normal pacemaker of the human heart.

Cardiac Properties 1-Autorhythmicity SAN produce action potentials at a rate of about 105/min. High rate of SA node cells suppresses other pacemaker tissues (overdrive suppression). The rate of action potential generation by the SA node cells can vary (60 and 200/min) under various normal conditions.

Cardiac Properties 1-Autorhythmicity If the SA node cells fail for any reason, then the AV node cells will take over as their natural rate is about 60/min. which is faster than Purkinje cells rate of about 40/min.

Cardiac Properties 1-Autorhythmicity Factors that affect the rate of discharge of SA node: 1-Autonomic nerves activity: Sympathetic activity increases the rate of SA node discharge and consequently increases the heart rate (tachycardia). Increased heart rate is termed positive chronotropy. Parasympathetic (vagal) activity decreases the rate of SA node discharge and consequently decreases the heart rate (bradycardia). Decreased heart rate is termed negative chronotropy.

Cardiac Properties 1-Autorhythmicity Factors that affect the rate of discharge of SA node: 2-Catecholamines level in blood: increases SA node firing rate 3-Body Temperature: Rise of body temperature increases the rate of charge of SA node(10 beats/min for every one degree rise of body temperature). 3-Extracellular K+ level: Hypokalemia causes tachycardia.Hyperkalemia causes bradycardia. 4-Ca++ channel blocker drugs causes bradycardia.  

Cardiac Properties 1-Autorhythmicity 2-Conductivity 3-Excitability 4-Contractility

Cardiac Properties 1-Conductivity Spread of action potentials within the heart occurs by direct electric conduction from cell to cell. This is made possible due to the presence of gap junctions at the intercalated discs between different cardiac cells.

Cardiac Properties 1-Conductivity The velocity of conduction between cells depends on: 1-Electrical resistance between cells. This depends on the number of gap junctions at intercalated discs. 2-The speed of upstroke of action potential. Slow upstroke (e.g. in SA node and AV node) makes conduction slower.

Cardiac Properties 1-Conductivity Action potentials generated at SA node is conducted through the atrial myocytes at a velocity of 0.5 m/sec. However, special conduction tracts known as internodal bundles transmit action potentials directly from SA node to AV node at a faster speed of 1 m/sec.

Cardiac Properties 1-Conductivity Conduction within the AV node is slow (0.05 m/sec). This slow conduction is due to: 1-There are few gap junctions between AV node cells. 2-The upstroke of action potential in AV node cells is slow (slow response action potential).

Cardiac Properties 1-Conductivity Slow Conduction within AV node is important for two reasons: 1-It delays arrival of action potential from atria to ventricles for about 0.1 sec. This gives the atria enough time to finish their contraction and empty their blood into the ventricles before ventricular contraction begins.

Cardiac Properties 1-Conductivity Slow Conduction within AV node is important for two reasons: 2-In addition, in some disease conditions the rate of generation of action potentials in the atria becomes very rapid. The low conduction velocity at AV node helps to limit the frequency of impulses that can travel from atria through the AV node and activate the ventricle.

Cardiac Properties 1-Conductivity Action potentials leaving the AV node enter the base of the ventricle at the bundle of His and then follow the left and right bundle branches to the left and right ventricles. Conduction within Bundle of His and its branches is rapid (2 m/sec.).

Cardiac Properties 1-Conductivity The bundle branches divide into an extensive system of Purkinje fibers that conduct the impulses at high velocity (about 4 m/sec) throughout the ventricles. This rapid conduction velocity allows the action potentials to reach all ventricular myocytes almost at the same time.

Cardiac Properties 2-Conductivity Effect of autonomic nervous system on conductivity: 1-Sympathetic stimulation increases the rate of conduction (positive dromotropic effect). 2-Parasympathetic stimulation decreases the velocity of conduction (negative dromotropic effect).

Cardiac Properties 1-Autorhythmicity 2-Conductivity 3-Excitability 4-Contractility

Cardiac Properties 3-Excitability It is the ability of cardiac muscle to respond to a threshold stimulus by developing an action potential followed by contraction.

Cardiac Properties 3-Excitability -This action potential occurs when the cardiac myocyte is rapidly depolarized from resting membrane potential (-90 mV) to a threshold membrane potential; the firing level (about -65 mV). -This depolarization occurs by cell-to-cell conduction of depolarizing potential.

Cardiac Properties 3-Excitability This action potential is composed of the following five phases: Phase 4: This is the resting membrane potential.  Phase 0: It is the rapid upstroke of the action potential from resting value to a positive value of about +20 mV. Phase 1: is a rapid small initial repolarization caused by inactivation of fast Na+ channels and opening of special type of K+ channels and Cl- channels. Phase 2: (plateau) During this phase, membrane repolarization slows down and membrane potential is sustained around zero mV. Phase 3: This is the rapid repolarization phase.

Cardiac Properties 3-Excitability

Cardiac Properties 3-Excitability Relationship between Action potential and contraction in cardiac myocyte Contraction starts just after the beginning of action potential. Contraction reaches maximum by the end of plateau (phase 2). Repolarization (phase 3) coincides with the first half of relaxation

Cardiac Properties 3-Excitability Excitability changes during action potential: 1-The effective (absolute) refractory period: During phases 0, 1, 2, and part of phase 3, the cell is refractory to initiation of new action potentials (unexcitable). 2-The relative refractory period: Supra-threshold stimuli are required to elicit actions potentials. It coincides with phase 3 of action potential. 3-The supernormal period: It occurs during the late part of phase 3. During this period the myocyte can respond to a weaker stimulus. It is also known as the vulnerable period.

Cardiac Properties 3-Excitability The long refractory period occupies the whole period of contraction and early part of relaxation. This prevents the heart from developing sustained, tetanic contractions like those that occur in skeletal muscle. Such sustained contraction is not suitable for the pumping function of the heart.

Cardiac Properties 1-Autorhythmicity 2-Conductivity 3-Excitability 4-Contractility

Cardiac Properties 4-Contractility Contraction is called systole and relaxation is called diastole. Membrane depolarization initiates the process of excitation-contraction coupling.

Cardiac Properties 4-Contractility Excitation contraction coupling:

Cardiac Properties 4-Contractility Excitation contraction coupling: 1-Membrane depolarization leads to opening of L-type Ca++ channels present in sarcolemma and T-tubules. This leads to entry of small amount of Ca++ inside the myocyte. This increases Ca++ concentration in local region just inside the sarcolemma.

Cardiac Properties 4-Contractility Excitation contraction coupling: 2-This Ca++ is sensed by the “feet” of the calcium release channel in the terminal cisterns of the sarco-endoplasmic reticulum (known as “ryanodine-sensitive calcium release channel” or “ryanodine receptor RyR”).

Cardiac Properties 4-Contractility Excitation contraction coupling: 3-This triggers the release of large amount of Ca++ from the sarcoplasmic reticulum. This is known as “Calcium-induced Calcium release”.

Cardiac Properties 4-Contractility Excitation contraction coupling: 4-Ca++ binds to Troponin-C and starts the steps of interaction between actin and myosin leading to contraction. 5-As the action potential ends, Ca++ release decreases.

Cardiac Properties 4-Contractility Excitation contraction coupling: 6-Relaxation starts when calcium is removed and its concentration in the cytoplasm decreases and it dissociates from Troponin-C. This leads to inhibition of the interaction between actin and myosin and subsequent relaxation.

Cardiac Properties 4-Contractility Ca++ plays a main role in determining the force with which the cardiac myocyte contracts (known as contractility or inotropic state). Under resting condition Ca++ release inside the myocyte is not maximal.

Cardiac Properties 4-Contractility If more Ca++ is available in the cytoplasm, cardiac myocyte contracts with greater force (known as positive inotropic state). If less Ca++ is available lower contractility is observed (known as negative inotropic state).

Cardiac Properties 4-Contractility Regulation of Contractility (inotropic state) of cardiac myocytes A- Positive inotropic mechanisms: 1- Stimulation of beta- adrenergic receptors 2- Glucagon hormone 3- Increased extracellular Ca++ concentration 4- Drugs (Digitalis, Xanthines).

Cardiac Properties 4-Contractility Regulation of Contractility (inotropic state) of cardiac myocytes A- Negative inotropic mechanisms: 1- Hypoxia of the myocytes 2- Activation of muscarinic receptors (M2 receptors). 3- Adenosine 4- Drugs (calcium channel blockers).