The Cardiovascular System: The Heart: Part B 18 The Cardiovascular System: The Heart: Part B

Heart Valves Heart valves ensure unidirectional blood flow through the heart (prevent backflow) Atrioventricular (AV) valves lie between the atria and the ventricles AV valves prevent backflow into the atria when ventricles contract Chordae tendineae anchor AV valves to papillary muscles Semilunar valves prevent backflow of blood into the ventricles Aortic semilunar valve lies between the left ventricle and the aorta Pulmonary semilunar valve lies between the right ventricle and pulmonary trunk

The conductive system The heart is an autonomic system that can work without neural stimuli – an intrinsic conduction system. The autonomic function of the heart results from: The pacemaker function – Autorhythmic cells The conductive system that transfer those impulses throughout the heart Two types of cardiac muscle cells that are involved in a normal heartbeat: Specialized muscle cells of the conducting system Contractile cells

Cardiac Muscle Contraction Depolarization opens voltage-gated fast Na+ channels in the sarcolemma Reversal of membrane potential from –90 mV to +30 mV Depolarization wave causes release Ca2+ that causes the cell contraction Depolarization wave also opens slow Ca2+ channels in the sarcolemma Ca2+ surge prolongs the depolarization phase (plateau)

Contractile Cells In skeletal muscle and neurons, an action potential falls back to Resting Membrane Potential (RMP) within 1-2 msec, but in cardiac muscle, slow calcium channels remain open longer (after sodium channels close), prolonging the depolarization of the cell. As long as the action potential is in its plateau and calcium is entering the myocytes, the myocytes contract. These plateaus are more pronounced in the ventricles. Cardiac muscle has an absolute refractory period of 250 msec, compared with 1–2 msec in skeletal muscle. The cardiac muscle must return completely to resting potential before it can be contracted again. As a result, the heart can not go through tetanus contraction.

Action potential in contractile cardiac muscle cells

Heart Physiology: Electrical Events Intrinsic cardiac conduction system A network of noncontractile (autorhythmic) cells that initiate and distribute impulses to coordinate the depolarization and contraction of the heart Have unstable resting potentials/ pacemaker potentials (they constantly depolarized slowly towards AP – hyperpolarization closes K+ and opens Na+) At threshold, Ca2+ channels open Ca2+ influx produces the rising phase of the action potential Repolarization results from inactivation of Ca2+ channels and opening of voltage-gated K+ channels

Heart Physiology: Sequence of Excitation Sinoatrial (SA) node (pacemaker) Generates impulses about 75 times/minute (sinus rhythm) Depolarizes faster than any other part of the myocardium Atrioventricular (AV) node Smaller diameter fibers; fewer gap junctions Delays impulses approximately 0.1 second Depolarizes 50 times per minute in absence of SA node input

Heart Physiology: Sequence of Excitation Atrioventricular (AV) bundle (bundle of His) Only electrical connection between the atria and ventricles Right and left bundle branches Two pathways in the interventricular septum that carry the impulses toward the apex of the heart Purkinje fibers Complete the pathway into the apex and ventricular walls AV bundle and Purkinje fibers depolarize only 30 times per minute in absence of AV node input

The upper part of the heart (the 2 atria) is insulated from the lower part Electrical excitation can pass from the atria to the ventricles only at the AV node

Extrinsic Innervation of the Heart Heartbeat is modified by the ANS Cardiac centers are located in the medulla oblongata Cardioacceleratory center innervates SA and AV nodes, heart muscle, and coronary arteries through sympathetic neurons Cardioinhibitory center inhibits SA and AV nodes through parasympathetic fibers in the vagus nerves

Electrocardiography (ECG or EKG) Body fluids are good conductors which allows the record of the myocardial action potential extracellularly EKG pairs of electrodes (leads) one serve as positive side of the lead and one as the negative Potentials (voltage) are being measured between the 2 electrodes EKG is the summed electrical potentials generated by all cells of the heart and gives electrical “view” of 3D object (different from one action potential) EKG shows depolarization and repolarization

Electrocardiography EKG is made of waves and segments Waves are deflections above or below baseline Three waves P wave: depolarization of SA node QRS complex: ventricular depolarization (Atrial repolarization record is masked by the larger QRS complex) T wave: ventricular repolarization Segments are sections of baseline between waves

Homeostatic Imbalances Defects in the intrinsic conduction system may result in Arrhythmias: irregular heart rhythms Uncoordinated atrial and ventricular contractions Fibrillation: rapid, irregular contractions; useless for pumping blood

Homeostatic Imbalances Defective SA node may result in Ectopic focus: abnormal pacemaker takes over If AV node takes over, there will be a junctional rhythm (40–60 bpm) Defective AV node may result in Partial or total heart block Few or no impulses from SA node reach the ventricles

(a) Normal sinus rhythm. (b) Junctional rhythm. The SA node is nonfunctional, P waves are absent, and heart is paced by the AV node at 40 - 60 beats/min. (c) Second-degree heart block. Some P waves are not conducted through the AV node; hence more P than QRS waves are seen. In this tracing, the ratio of P waves to QRS waves is mostly 2:1. (d) Ventricular fibrillation. These chaotic, grossly irregular ECG deflections are seen in acute heart attack and electrical shock. Figure 18.18

Autorythmic cells - ectopic pacemakers Autorythmic cells of the SA node (pacemaker) may be replaced by ectopic pacemakers Ectopic pacemakers – other parts in the heart that can induce beating The ectopic pacemakers may become dominant: If their rythmicity increased The pacemaker is inhibited/blocked The conduction system pathways are blocked First to take over will be the AV node

Heart Sounds Two sounds (lub-dup) associated with closing of heart valves First sound occurs as AV valves close and signifies beginning of systole Second sound occurs when SL valves close at the beginning of ventricular diastole Heart murmurs: abnormal heart sounds most often indicative of valve problems

Cardiac Cycle Cardiac cycle - The period between the start of one heartbeat and the beginning of the next. refers to all events associated with blood flow through the heart During the cycle, each of the four chambers goes through Systole – contraction of heart muscle Diastole – relaxation of heart muscle An average heart beat (HR)/cardiac cycle is 75 bpm. That means that a cardiac cycle length is about 0.8 second. Of that 0.1 second is the atrial contraction, 0.3 is the atrial relaxation and ventricular contraction. The remaining 0.4 seconds are called the quiescent period which represent the ventricular relaxation

Phases of the Cardiac Cycle Ventricular filling — takes place in mid-to-late diastole AV valves are open 80% of blood passively flows into ventricles Atrial systole occurs, delivering the remaining 20% End diastolic volume (EDV): volume of blood in each ventricle at the end of ventricular diastole

Phases of the Cardiac Cycle Ventricular systole Atria relax and ventricles begin to contract Rising ventricular pressure results in closing of AV valves Isovolumetric contraction phase (all valves are closed) In ejection phase, ventricular pressure exceeds pressure in the large arteries, forcing the SL valves open End systolic volume (ESV): volume of blood remaining in each ventricle

Phases of the Cardiac Cycle Isovolumetric relaxation occurs in early diastole Ventricles relax Backflow of blood in aorta and pulmonary trunk closes SL valves and causes dicrotic notch (brief rise in aortic pressure)

Cardiodynamics Movements and forces generated during cardiac contractions End-diastolic volume (EDV) – the amount of blood in each ventricle at the end of ventricular diastole (before contraction begins) End-systolic volume (ESV) - the amount of blood remains in each ventricle at the end of ventricular systole

Cardiodynamics Not all blood ejected Normal Adult 70 ml / beat Stroke volume (SV) – The amount of blood that leaves the heart with each beat or ventricular contraction; EDV-ESV=SV Not all blood ejected Normal Adult 70 ml / beat Ejection fraction – The percentage of end-diastole blood actually ejected with each beat or ventricular contraction. Normal adult 55-70% (healthy heart)

Stroke Volume and Cardiac Output Cardiac output (CO) – the amount of blood pumped by each ventricle in one minute. Physiologically, CO is an indication of blood flow through peripheral tissues Cardiac output equals heart rate times stroke volume; Normal CO: Approximately 4-8 liters/minute CO Cardiac output (ml/min) = HR Heart rate (beats/min) X SV Stroke volume (ml/beat)

Effect inotropy – effect on contractility of the heart Effect chronotropy – effect on HR Effect dromotropy – effect on the conductive velocity Sympathetic stimuli has a positive effect (increase) all Parasympathetic stimuli has a negative effect (decrease) all

Autonomic Nervous System Regulation In healthy conditions, parasympathetic effects dominate and slows the rate of the pacemaker from 80-100 bpm to a 70-80 bpm. The binding of Ach to muscarinic receptors (M2) inhibit NE release (mechanism by which vagal stimulation override sympathetic stimulation) Sympathetic nervous system is activated by emotional or physical stressors Norepinephrine causes the pacemaker to fire more rapidly (and at the same time increases contractility) Parasympathetic nervous system opposes sympathetic effects Acetylcholine hyperpolarizes pacemaker cells by opening K+ channels The heart at rest exhibits vagal tone (parasympathetic)

Autonomic Nervous System Regulation Atrial (Bainbridge) reflex: a sympathetic reflex initiated by increased venous return Stretch of the atrial walls stimulates the SA node Also stimulates atrial stretch receptors activating sympathetic reflexes

Effects on SA node The effect of the ANS on the heart is by changing the permeability of the conducting system cells. Ach released by the parasympathetic neurons slow the depolarization rate and extend slightly the repolarization. This decreases the HR The NE released by the sympathetic neurons binds to beta–1 receptors, leading to the opening of calcium ion channels. That increases the depolarization rate and shortens the repolarization period. Threshold is reached more quickly and HR increases

Chemical Regulation of Heart Rate Hormones Epinephrine from adrenal medulla enhances heart rate and contractility Thyroxine increases heart rate and enhances the effects of norepinephrine and epinephrine Intra- and extracellular ion concentrations (e.g., Ca2+ and K+) must be maintained for normal heart function

Homeostatic Imbalances Tachycardia: abnormally fast heart rate (>100 bpm) If persistent, may lead to fibrillation Bradycardia: heart rate slower than 60 bpm May result in grossly inadequate blood circulation May be desirable result of endurance training

Regulation of Stroke Volume SV = EDV – ESV Three main factors affect SV Preload Contractility Afterload

Regulation of Stroke Volume Preload The amount of tension on a muscle before it begins to contract. The preload of the heart is determined by the EDV. In general, the greater the EDV the larger is the stroke volume : EDV-ESV=SV These relationships is known as the Frank-Starling principle/Sterling’s law of the heart : The force of cardiac muscle contraction is proportional to its initial length The greater the EDV the larger the preload

Factors Affecting stroke volume - Preload/EDV Stroke volume is the difference between the EDV and ESV. Changes in either one can change the stroke volume and cardiac output: The EDV volume is affected by 2 factors: The filling time – duration of ventricular diastole; depends on HR – the faster the HR the shorter is the available filing time The venous return – changes in response to several changes: cardiac output, blood volume, peripheral circulation etc.

EDV increase (preload increased) Diastolic filling increased EDV increase (preload increased) Cardiac muscle stretch increased Force of contraction increased Ejection volume increased

Regulation of Stroke Volume Contractility Force of ventricular contraction (systole) regardless of EDV Positive inotropic agents increase contractility Increased Ca2+ influx due to sympathetic stimulation Hormones (thyroxine and epinephrine) Negative inotropic agents decrease contractility Increased extracellular K+ Calcium channel blockers

Regulation of Stroke Volume Afterload The amount of resistance the ventricular wall must overcome to eject blood during systole (influenced by arterial pressure). The greater is the afterload, the longer is the period of isovolumetric contraction (ventricles are contracting but there is no blood flow), the shorter the duration of ventricular ejection and the larger the ESV – afterload increase – stroke volume decrease Hypertension increases afterload, resulting in increased ESV and reduced SV

Congestive Heart Failure (CHF) Progressive condition where the CO is so low that blood circulation is inadequate to meet tissue needs Caused by Coronary atherosclerosis Persistent high blood pressure Multiple myocardial infarcts (decreased blood supply and myocardial cell death) Dilated cardiomyopathy (DCM) – heart wall weakens and can not contract efficiently. Causes are unknown but sometimes associated with toxins (ex. Chemotherapy), viral infections, tachycardia and more