Cardiovascular System PDF

Basic science underpins clinical medicine The cardiovascular system The cardiovascular system, also known as the circulatory system, is a complex network of organs and vessels responsible for transporting blood, oxygen, nutrients, and hormones throughout the body. The three principal components...

Basic science underpins clinical medicine The cardiovascular system The cardiovascular system, also known as the circulatory system, is a complex network of organs and vessels responsible for transporting blood, oxygen, nutrients, and hormones throughout the body. The three principal components that comprise the circulatory system are: - The heart (the pump), - The blood vessels or vascular system (set of interconnected tubes) - The blood (a fluid connective tissue containing water, solutes, and cells that fills the tubes). BLOOD is composed of formed elements (cells and cell fragments) suspended in a liquid called plasma. More than 90% of PLASMA is water, but dissolved in it there are also a large number of proteins, nutrients, metabolic wastes, and other molecules being transported between organ systems. The plasma proteins constitute most of the plasma solutes by weight and can be classified in 3 major groups: The albumins and the globulins which have many overlapping functions, and Fibrinogen which play an important role in clotting (when fibrinogen and other clotting proteins are removed from the plasma, serum is obtained) The BLOOD CELLS are: - The leukocytes (white blood cells) which are involved in immune defenses and include neutrophils (engulf microbes by phagocytosis), eosinophils (fight off invasions by eukaryotic parasites releasing toxic chemicals), monocytes (circulate in the blood and develop into macrophages), macrophages (engulf virus and bacteria), basophils (secrete the anticlotting factors heparin at the site of infection to help the circulation flushing out the infected site and lymphocytes (T cells and B cells which protect against specific pathogens by directly killing them or by secreting antibodies into the circulation) - Platelets which are circulating cell fragments involved in maintaining homeostasis and blood clotting  - The erythrocytes (red blood cells), which are produced by the bone marrow, are involved in gas transport, carrying oxygen taken in by the lungs and carbon dioxide produced by the cells. They contain large amounts of the protein hemoglobin to which oxygen and carbon dioxide reversibly combine (oxygen binds to iron atoms in the hemoglobin molecules). The hematocrit is defined as the percentage of blood volume that is erythrocytes. It is measured by centrifugation (spinning at high speed) of a sample of blood. The erythrocytes are forced to the bottom of the centrifuge tube, the plasma remains on top, and the leukocytes and platelets form a very thin layer between them called the buffy coat. The hematocrit is normally about 45% in men and 42% in women. The HEART plays a central and vital role in the circulatory system, ensuring the continuous flow of blood through the body. It consist of: - 4 chambers: 2 atria (upper chambers) and 2 ventricles (lower chambers) that work in coordination to ensure efficient blood circulation - 4 valves: Semilunar valves that prevent backflow of blood from arteries to ventricles during ventricular diastole (relaxation). → Aortic valve: located between left ventricle and aorta → Pulmonary valve: located between right ventricle and the pulmunary artery (trunk) Atrioventricular (AV) valves that prevent backflow of blood from ventricles to atria during ventricular systole (contraction) but do not control valve opening and closing → Tricuspid valve: located between right atrium and right ventricle → Bicuspid (or mitral) valve: located between left atrium and left ventricle Both are anchored by chordae tendinae - Walls: Endocardium: Is the innermost layer of the heart that lines chambers and valves. It is composed of endothelial cells (or endothelium), which rest on a thin layer of connective tissue. It is continuous with the lining of the blood vessels entering and leaving the heart. Myocardium: Is the middle and thickest layer and it is composed of cardiac muscle tissue (striated with sarcomeres) with cells containing numerous mitochondria, forming the bulk of the heart mass Is responsible for the contraction of the heart, generating the force needed to pump blood throughout the circulatory system. The gap junctions between cells allows action potential to spread rapidly from cell to cell Epicardium: Is the outermost fibrous layer, directly covering the surface of the heart and surrounding the myocardium Pericardium: Protective layer (fibrous sac) that surround the entire heart. The loosely fitting superficial part of this sac is the fibrous pericardium, while the tough, dense connective tissue layer protects the heart, anchors it to surrounding structures, and prevents overfilling of the heart with blood. Between the epicardium and the pericardium there is the pericardial cavity, which contains the pericardial fluid that reduces friction as the heart moves - Cells: Cardiac cells: Make up the cardiac tissue and work to keep the heart pumping through involuntary movements thanks to their ability to generate electricity Pacemaker cells: Comprise a small population that spontaneously fire to trigger each heartbeat. BLOOD VESSELS play a major function in reglating blood pressure and in distributing blood flow to the various tissue. They can be divided into arteries, arterioles, capillaries, venules, and veins. The main blood vessels in the cardiovascular system are: the superior/inferior vena cava, the pulmunary artery and vein, and the aorta The walls of all blood vessels, except the very smallest, have three distinct layers, or tunics (“coverings”), that surround a central blood-containing space, the vessel lumen. - The innermost tunic is the tunica intima which contains the endothelium, the simple squamous epithelium that lines the lumen of all vessels. The endothelium is continuous with the endocardial lining of the heart, and its flat cells fit closely together, forming a slick surface that minimizes friction as blood moves through the lumen. In vessels larger than 1 mm in diameter, a subendothelial layer, consisting of a basement membrane and loose connective tissue, supports the endothelium. - The tunica media (in the middle), is made of smooth muscle cells and sheets of elastin arranged circularly. The activity of the smooth muscle is regulated by sympathetic vasomotor nerve fibers of the autonomic nervous system and a different chemicals. Depending on the body’s needs at any given moment, regulation causes either vasoconstriction (lumen diameter decreases as the smooth muscle contracts) or vasodilation (lumen diameter increases as the smooth muscle relaxes). The activities of the tunica media are critical in regulating circulatory dynamics because small changes in vessel diameter greatly influence blood flow and blood pressure. Generally, the tunica media is the bulkiest layer in arteries, which bear the chief responsibility for maintaining blood pressure and circulation. - The outermost layer of a blood vessel wall, the tunica externa (also called the tunica adventitia), is composed largely of loosely woven collagen fibers that protect and reinforce the vessel, and anchor it to surrounding structures. The tunica externa is infiltrated with nerve fibers, lymphatic vessels, and, in larger veins, a network of elastic fibers. - ARTERIES carry oxygenated blood away from the heart under high pressure The exception to this is the pulmonary arteries, which carry deoxygenated blood to the lungs to get oxygenated Their second major function, related to their elasticity, is to act as a “pressure reservoir” for maintaining blood flow through the tissues during diastole. The major coronary vessels that perfuse the heart are the Right Coronary Artery, the Left Coronary Artery, the Left Anterior Descending Artery and the Left Circumflex Artery If one of these vessel gets occluded, the blood flow to the heart stops and a heart attck occurs As they branch out, they become smaller and form ARTERIOLES, which have smooth muscle that enables them to regulate blood flow to specific tissues by controlling the diameter of their lumens, a process known as vasoconstriction (narrowing) or vasodilation (widening). Arterioles then deliver blood to capillaries - CAPILLARIES are the smallest but most numerous blood vessels. They connect arterioles to venules and play a crucial role in the exchange of oxygen, nutrients, and waste products between the blood and tissues (have intimate contact with tissue cells). This exchanges occur primarily through the thin capillary walls. Lipid soluble substances such as CO2, O2 and steroid hormones, easily diffuse across the plasma membrane and pass through the endothelial cells. On the other hand, substances insoluble in lipids such as glucose, amino acids and electrolytes, have to pass through fluid-filled pores within and between the endothelial cells. Large, non-lipid molecules such as plasma protein are excluded from passage. They are endothelial cells with no smooth muscle therefore they cannot regulate their own blood flow. Because of this they have what are called precapillary sphincters, small rings of smooth muscle located at the entrance of capillary beds. They play a crucial role in regulating blood flow into capillaries and, consequently, controlling the distribution of blood within tissues  The contraction or relaxation of these sphincters is a dynamic process that allows the body to adjust blood flow based on metabolic needs The lymphatic system recovers fluids that leak from the blood vessels VENULES are small veins connected to capillaries that then branch out to form bigger VEINS which are responsible for returning the deoxygenated blood back to the heart from the periphery (venous return) under lower pressure. The pulmonary vein is the only exception since it carries oxygenated blood to the heart to get delivered to the rest of the body. Are composed of the same 3 layers as the arteries, but they have thinner walls, less elastic tissue and less smooth muscle. They are capacitance vessels sincethey have a larger internal diameter (less rigid so can hold more blood) Veins are able to carry out their functions thanks to 3 mechanisms: - Skeletal muscle pump: When muscles contract during activities such as walking or exercising, they squeeze the nearby veins, pushing blood back toward the heart. This action helps propel blood against gravity and assists in venous return. - Respiratory pump: During inhalation, the diaphragm contracts, and the thoracic cavity expands, causing a decrease in thoracic pressure. This decrease in pressure helps draw blood into the thoracic veins, including the vena cava, aiding venous return to the heart. - Venous valves: Medium and large veins also have one-way valves that prevent the backflow of blood. These valves ensure that blood moves unidirectionally toward the heart. The rapid flow of blood throughout the body is produced by pressures created by the pumping action of the heart. This type of flow is known as BULK FLOW because all constituents of the blood move together. Cardiovascular system function is impacted by the endocrine, nervous, and urinary systems. The circulatory system forms a closed loop, so that blood pumped out of the heart through one set of vessels returns to the heart by a different set. Therefore the CIRCULATION in the cardiovascular system can be broadly categorized into two main circuits: - The left side of the heart is the pump for systemic circulation, which carries oxygen-rich blood from the left ventricle through all the organs and tissues of the body (except the lungs) and then to the right atrium. - On the other hand, the right side of the heart is the pump for pulmonary circulation, which carries oxygen-poor blood from the right ventricle to the lungs and then to the left atrium. More particularly the pathway of blood through the heart is a carefully coordinated flow: In booth circuits, blood vessels carry the blood and are collectively termed microcirculation  HEARTBEAT COORDINATION Lecture 4 The heart is a dual pump in that the left and right sides of the heart pump blood separately, but simultaneously, into the systemic and pulmonary vessels. Efficient pumping of blood requires that the atria contract first, followed almost immediately by the ventricles. Contraction of cardiac muscle, like that of skeletal and many smooth muscle, is triggered by depolarization of the plasma membrane. Gap junctions interconnect myocardial cells and allow action potentials to spread from one cell to another. This initial depolarization normally arises in a small group of conducting-system cells (that determine the heart rate) called the sinoatrial (SA) node, located in the right atrium near the entrance of the superior vena cava. The action potential then spreads from the SA node throughout the atria and then into and throughout the ventricles. SEQUENCE OF EXCITATION The SA node is normally the pacemaker for the entire heart. Its depolarization generates the action potential that leads to depolarization of all other cardiac muscle cells. Electrical excitation of the heart is coupled with contraction of cardiac muscle, therefore, the discharge rate of the SA node determines the heart rate, the number of times the heart contracts per minute. The action potential initiated in the SA node spreads throughout the myocardium, passing from cell to cell by way of gap junctions. Depolarization first spreads through the muscle cells of the atria, with conduction rapid enough that the right and left atria contract at essentially the same time. The spread of the action potential to the ventricles involves a more complicated conducting system, which consists of modified cardiac cells that have lost contractile capability but that conduct action potentials with low electrical resistance. The link between atrial depolarization and ventricular depolarization is a portion of the conducting system called the atrioventricular (AV) node, located at the base of the right atrium. The action potential is conducted relatively rapidly from the SA node to the AV node through internodal pathways. The propagation of action potentials through the AV node is relatively slow (requiring approximately 0.1 sec), a delay that allows atrial contraction to be completed before ventricular excitation occurs. After the AV node has become excited, the action potential propagates down the interventricular septum. This pathway has conducting-system fibers called the bundle of His, or atrioventricular bundle. The AV node and the bundle of His constitute the only electrical connection between the atria and the ventricles. Except for this pathway, the atria are separated from the ventricles by a layer of nonconducting connective tissue known as the interventricular septum. Within the interventricular septum, the bundle of His divides into right and left bundle branches, which separate at the bottom (apex) of the heart and enter the walls of both ventricles. These pathways are composed of Purkinje fibers, which are large-diameter, rapidly conducting cells connected by low-resistance gap junctions. The branching network of Purkinje fibers conducts the action potential rapidly to myocytes throughout the ventricles. The rapid conduction along the Purkinje fibers and the diffuse distribution of these fibers cause depolarization of right and left ventricular cells to occur nearly simultaneously and ensure a single coordinated contraction. Actually, though, depolarization and contraction do begin slightly earlier in the apex of the ventricles and then spread upward. The result is an efficient contraction that moves blood toward the exit valves. CARDIAC ACTION POTENTIAL AND EXCITATION OF THE SA NODE The mechanism by which action potentials are conducted along the membranes of heart cells is similar to that of other excitable tissues like neurons and skeletal muscle cells. It involves the controlled exchange of materials (ions) across cellular membranes, however, different types of heart cells express unique combinations of ion channels that produce different action potential shapes. In this way, they are specialized for particular roles in the spread of excitation through the heart MYOCARDIAL CELL ACTION POTENTIAL As in skeletal muscle cells and neurons, the resting membrane is much more permeable to K+ than to Na+, therefore, the resting membrane potential is much closer to the K+ equilibrium potential than to the Na+ equilibrium potential. 1) Because of this, the depolarizing phase of the action potential is due mainly to the opening of voltage-gated Na+ channels, resulting in the entry of sodium ions that depolarize the cell and sustains the opening of more Na+ channels in positive feedback fashion. 2) However, unlike other excitable tissues, the reduction in Na+ permeability in cardiac muscle is not accompanied by immediate repolarization of the membrane to resting levels. Rather, there is a partial repolarization caused by a special class of transiently open K+ channels, and then the membrane remains depolarized at plateau for a prolonged period. This continued depolarization occurs because K+ permeability declines below the resting value due to the closure of the K+ channels that were open in the resting state, and because there is a large increase in the cell membrane permeability to Ca2+. 3) In myocardial cells, membrane depolarization causes voltage-gated Ca2+ channels in the plasma membrane to open, which results in a flow of Ca2+ ions down their electrochemical gradient into the cell. These channels open much more slowly than do Na+ channels, and, because they remain open for a prolonged period, they are often referred to as L-type Ca2+ channels (L = long lasting). The flow of positive Ca ions into the cell just balances the flow of K ions out of the cell keeps the membrane depolarized at the plateau value (200-300 milliseconds) 4) Ultimately, repolarization does occur as potassium moves out. This is due to the inactivation of the L-type Ca2+ channels and the opening of another subtype of K+ channels, which open in response to depolarization (but after a delay) and close once the K+ current has repolarized the membrane to negative values.  NODAL CELL ACTION POTENTIAL There are important differences between action potentials of cardiac muscle cells and those in nodal cells of the conducting system. The SA node cell does not have a steady resting potential but, instead, undergoes a slow depolarization known as pacemaker potential which brings the membrane potential to threshold, at which point an action potential occurs. Three ion channel mechanisms contribute to the pacemaker potential. - The first is a progressive reduction in K+ permeability. The K+ channels that opened during the repolarization phase of the previous action potential gradually close due to the membrane’s return to negative potentials. - Second, pacemaker cells have a unique set of channels that, unlike most voltage-gated ion channels, open when the membrane potential is at negative values. These nonspecific cation channels known as F-type conduct mainly an inward, depolarizing Na+ current - The third pacemaker channel is a type of Ca2+ channel known as T-type that opens only briefly but contributes inward Ca2+ current and an important final depolarizing boost to the pacemaker potential. Although SA node and AV node action potentials are basically similar in shape, the pacemaker currents of SA node cells bring them to threshold more rapidly than AV node cells, which is why SA node cells normally initiate action potentials and determine the pace of the heart. 1) The depolarizing phase is caused not by Na+ but rather by Ca2+ influx through L-type Ca2+ channels. These Ca2+ currents depolarize the membrane more slowly than voltage-gated Na+ channels, and one result is that action potentials propagate more slowly along nodal-cell membranes than in other cardiac cells. 2) As in cardiac muscle cells, the long-lasting L-type Ca2+ channels prolong the nodal action potential, but eventually they close and K+ channels open and the membrane is repolarized. The return to negative potentials activates the pacemaker mechanisms once again, and the cycle repeats. Thus, the pacemaker potential provides the SA node with automaticity, the capacity for spontaneous, rhythmic self-excitation (independent of the nervous system) The slope of the pacemaker potential (how quickly the membrane potential changes per unit time) determines how quickly threshold is reached and triggers the next action potential. THE ELECTROCARDIOGRAM The electrocardiogram (ECG, also abbreviated EKG) is a tool for evaluating the electrical events within the heart. When action potentials occur simultaneously in many individual (contractile) myocardial cells, negative and positive currents (depolarization an repolarization events) are conducted through the body fluids around the heart and can be detected by recording electrodes at the surface of the skin. 12 different leads look at different aspects of the heart, however, usually 3 lead can accurately monitor heart rate and regularity. They are placed in what is known as the Einthoven Triangle, where - Lead I measures the electrical difference between the right arm (negative electrode) and the left arm (positive electrode). - Lead II measures the electrical difference between the right arm (negative electrode) and the left leg (positive electrode). - Lead III measures the electrical difference between the left arm (negative electrode) and the left leg (positive electrode). The triangle is formed by connecting these three leads, creating an equilateral triangle where the heart lies in the center. The electrical activity of the heart is projected along these axes, and the sum of the potentials in each lead (I + III = II) follows Einthoven's law. The triangle helps interpret the frontal plane of heart electrical activity, providing essential information in diagnosing heart conditions The ECG paper is broken into different sized boxes and squares to represent time (horizonally) and voltage (vertically). This is vital when determining if an ECG is normal or abnormal In a ECG the first deflection, the P wave, corresponds to current flow during atrial depolarization. The second deflection, the QRS complex, occurring approximately 0.15 sec later, is the result of ventricular depolarization. The final deflection, the T wave, is the result of ventricular repolarization. Atrial repolarization is usually not evident on the ECG because it occurs at the same time as the QRS complex. More particularly the PR Interval goes from the start of Atrial Depolarisation to the Start of Ventricular Depolarisation (0.12–0.20 seconds which means 3–5 squares) The ST Segment is the period at which both ventricles are completelydepolarised and ready to depolarised. If there is a delay, the voltage goes up and the R peak will result much more higher than usual, meaning that a massive heart attck will occur) The QT Interval is the time for both ventricular depolarization and repolarization to occur (0.33–0.42 seconds which means approx. 8-10 squares) In conclusion the ECG is not a direct record of the changes in membrane potential across individual cardiac muscle cells, but is a measure of the currents generated in the extracellular fluid by the changes occurring simultaneously in many cardiac cells. By using these methods, you To accurately determine the heart rate and assess the regularity of the heart rhythm, which helps in diagnosing cardiac conditions, differnt methods can be used. Each method is based on measuring the R-R interval, which is the distance between consecutive R-waves, representing ventricular contraction. - Six-Second Method: Count the number of R-waves in a 6-second interval (30 large boxes) and multiply by 10 to get the heart rate in bpm. In this case 4 x 10 = 40 bpm (person has bradichardia) - Heart Rate Calculator Rulers: Specialized rulers designed to measure heart rate based on the distance between R-waves. You have to match the QRS complex with the number and will get the reading - R-R Method: The number of large squares (5mm boxes) between two R waves is measured. The heart rate is calculated by dividing 300 by the number of large squares between the R-waves. In this case there are 5 boxes between the R waves, therefore 300/5 = 60 bpm - Digital Method: Many modern ECG machines have a built-in heart rate calculator that automatically detects the R-R intervals and provides the heart rate digitally. In ECG analysis, different are the aspects that have to be checked: - P waves: Are they presents? Are they regular? Is there one P wave for each QRS complex? Are the P waves upright or inverted? (depends if there are issues with SA node) Do all the P waves look alike? (if not, there is a conduction issue) Is the P– R Interval >0.12 and < 0.20 seconds? - QRS complex: Do all the QRS complexes look alike? What is the QRS duration? Are there any ST segment changes? Is it normal, elevated (heart attack) or depressed (usually because of previous damages) ? The regularity of the heart rhythm is an important aspect that can help identify underlying cardiac conditions. Here’s how regularity is classified: - Regular: The time between consecutive R-waves (R-R intervals) is consistent. Seen in normal sinus rhythm, where the electrical impulses originate from the sinoatrial (SA) node at regular intervals. Another example is sinus bradychardia, where the electrical impulse still originates from the sinoatrial (SA) node, which keeps the time interval between each beat (R-R interval) the same, resulting in a regular rhythm, even though it is slower (below 60 beats per minute because of a delay between the Sa node and the AV node) Sinus tachycardia is a regular rhythm as well. It is characterized by a heart rate that is faster than normal (above 100 beats per minute), but the rhythm remains consistent, meaning that the R-R intervals are equal, and the pattern is uniform, with each P wave followed by a QRS complex. Supraventricular Tachycardia (SVT) is also generally regular. In SVT, the heart rate is very fast, usually over 150 beats per minute, but the rhythm itself is regular, meaning that the time interval between each heartbeat remains constant. SVT originates above the ventricles, however, instead of spreading, it goes back to the Bundle of His, creating a loop. Ventricular Tachycardia (VT) is also classified as regular. This arrhythmia is characterized by a rapid heart rate originating from the ventricles, with a consistent rhythm. VT can be stable (with a pulse) or unstable (without a pulse) If the patient is not responsive, immediate intervention is often required to try and reset the heart: SHOCKABLE - Regularly Irregular: There is an irregularity in the rhythm, but it follows a pattern. - Irregularly Irregular: No consistent pattern to the R-R intervals. This is characteristic of atrial fibrillation (AFib), where the atria contract in a completely uncoordinated manner, leading to an irregular ventricular response. As a result, the R-R intervals on the ECG are uneven, and P waves are absent or replaced by erratic fibrillatory waves. It is usually solved using medications Premature Ventricular Complexes (PVCs) are also considered irregularly irregular. PVCs occur when there is an early contraction of the ventricles, followed by a compensatory pause which disrupts the normal rhythm of the heart. The R-R intervals become uneven, indicating the irregular nature of the rhythm. Ventricular fibrillation is also irregularly irregular. In VF, the ventricles quiver ineffectively rather than contracting in a coordinated manner, leading to a chaotic and disorganized electrical activity. VF is a life-threatening condition that can result in cardiac arrest, and immediate medical intervention is required: SHOCKABLE.  Asystole (unusual) is characterized by a complete absence of electrical activity in the heart, resulting in no contractions of the heart muscle, therefore leading to a flatline on the electrocardiogram (ECG). The ECG will show a straight line, indicating the absence of P waves, QRS complexes, or any other heart activity. As such, it is classified as irregularly irregular, but more accurately, it represents no rhythm at all: NOT SHOCKABLE Pulseless Electrical Activity (PEA) is a condition where there is organized electrical activity on the ECG, but the heart does not produce a pulse or adequate blood pressure (usually followin ga trauma) It is considered irregularly irregular in nature because, while there may be some electrical patterns, they do not correspond to effective cardiac contractions: NOT SHOCKABLE EXCITATION-CONTRACTION COUPLING The small amount of extracellular Ca2+ entering through L-type Ca2+ channels during the plateau of the action potential triggers the release of a larger quantity of Ca2+ from the sarcoplasmic reticulum through the ryanodine receptor channels. Ca2+ activation of thin filaments and cross-bridge cycling then lead to generation of force, just as in skeletal muscle. Contraction ends when Ca2+ is returned to the sarcoplasmic reticulum and extracellular fluid. Since the amount of Ca2+ released from the sarcoplasmic reticulum in cardiac muscle during a resting heartbeat is not usually sufficient to saturate all troponin sites, the number of active cross-bridges (and thus the strength of contraction) can be increased if more Ca2+ is released from the sarcoplasmic reticulum (as would occur, for example, during exercise). REFRACTORY PERIOD OF THE HEART Cardiac muscle is incapable of undergoing summation of contractions like that occurring in skeletal muscle This inability is the result of the long absolute refractory period of cardiac muscle, defined as the period during and following an action potential when an excitable membrane cannot be re-excited. Because of the prolonged, depolarized plateau in the cardiac muscle action potential, the absolute refractory period of cardiac muscle lasts almost as long as the contraction (approximately 250 msec), and the muscle cannot be re-excited multiple times during an ongoing contraction THE CARDIAC CYCLE The orderly process of depolarization triggers a recurring cardiac cycle of atrial and ventricular contractions and relaxations that take place during one complete heartbeat (0.8 sec at rest). It consists of two periods, both named for events occurring in the ventricles: - The phase of ventricular contraction and blood ejection called systole (0.3 secs) and - The alternating period of ventricular relaxation and blood filling, known as diastole (0.5 secs) Audible noises, also known as heart sounds, generated by the functioning of the heart occur during the cardiac cycle. 1) It starts with ATRIAL SYSTOLE where the atria contract. Blood is forced through the AV valves (semilunar aew closed) into the ventricles, which are relaxed at this point. Atrial contraction tops off the blood in the ventricles, adding to the End-Diastolic Volume (EDV), the maximum volume of blood in the ventricles during the cardiac cycle. 2) In VENTRICULAR SYSTOLE the ventricles contract while the atria relax. It is also termed ISOVOLUMETRIC VENTRICULAR CONTRACTION, because even if the pressure in the ventricles rises to a value greater than the atrial pressure, the ventricular volume remains contastant because all valves (both AV and semilunar) are closed. This prevent backflow into the atria, ando also causes the production of the first heart sound (S1), a soft, low-pitched lub. 3) The pressure in the ventricles however keeps increasing and arrives at a point where exceeds that in the aorta and pulmunary trunk, leading to the opening of the pulmonary valve (right side) and aortic valve (left side). In this pahse maximum arterial pressure, also known as systolic pressure (SP) is reached As a result, blood is ejected from the heart in what is known as the VENTRICULAR EJECTION PERIOD. The right ventricle pumps deoxygenated blood into the pulmonary artery, sending it to the lungs, while the left ventricle pumps oxygenated blood into the aorta, sending it to the rest of the body. The volume of blood ejected from each ventricle is called the STROKE VOLUME (SV), while the amount of blood remaining in the ventricle after the ejection is called the end-systolic volume (ESV). Frank-Starling Law states that the stroke volume of the left ventricle will increase as the left ventricular volume increases due to the myocyte stretch causing a more forceful systolic contraction (Cardiac contractility) 4) In VENTRICULAR DIASTOLE (EARLY) after the blood is ejected, the ventricles relax. As the pressure in the ventricles drops, the semilunar valves close to prevent backflow from the arteries into the ventricles, producing the second heart sound (S2), a louder dup. At this time, the AV valves are also closed, therefore, no blood is entering or leaving the ventricles (ventricular volume is not changing) hence the name ISOVOLUMETRIC VENTRICULAR RELAXATION The closing of the aortic valve causes a temporary increase in pressure in the aorta, which results in a brief upward deflection in the arterial pressure also known as dirotic notch However this effect ends rapidly since the ventricular pressure falls lower than atrial pressure. 5) This change in pressure gradient then results in the opening of the AV valves, and VENTRICULAR FILLING occurs as blood starts to flow passively in from the atria, in what is called the VENTRICULAR DIASTOLE (LATE). Here the minimum arterial pressure, also called diastolic pressure (DP) is reached. Atrial systole will then follow again to complete the filling of the ventricles (EDV) Preload: The amount of stretch experienced by cardiac muscle, at the end of ventricular filling during diastole. Afterload: Resistance that the L ventricle must overcome to pump blood. The volume of blood each ventricle pumps as a function of time, usually expressed in liters per minute, is called the CARDIAC OUTPUT (CO). In the steady state, the cardiac output flowing through the systemic and the pulmonary circuits is the same. The cardiac output can be calculated by multiplying the heart rate (the number of beats per minute) and the stroke volume (the blood volume ejected by each ventricle with each beat). Therefore: CO = HR x SV BLOOD PRESSURE REGULATION involves a complex set of mechanisms that maintain the balance between blood flow and vascular resistance to ensure adequate oxygen and nutrient supply to tissues. It operates through short-term and long-term processes involving the nervous system, hormones, and the kidneys. SHORT-TERM REGULATION It involves the nervous system and responds quickly to changes in blood pressure, such as when you stand up suddenly. - Baroreceptor Reflex: Is a key mechanism for maintaining short-term blood pressure homeostasis. Baroreceptors are stretch-sensitive receptors located in the carotid sinus and aortic arch. They detect changes in blood pressure based on how much the vessel walls are stretched With high blood pressure, an increased stretching of baroreceptors occurs, which sends signals to the brainstem (medulla oblongata). This leads to an increased parasympathetic activity (via the vagus nerve) and a decreased sympathetic activity, which ultimately results in the slowing of heart rate (bradycardia), dilation of blood vessels (vasodilation), and reduction of cardiac output (amount of blood pumped by the heart). With low blood pressure a decreased stretch in baroreceptors happens leading to a reduced signaling to the brainstem. This increases the sympathetic activity as well as the heart rate (tachycardia), the force of contraction, and vasoconstriction (narrowing of blood vessels), resulting in the increase of blood pressure to restore normal levels. - Chemoreceptor Reflex: Chemoreceptors located in the carotid and aortic bodies respond to changes in blood oxygen, carbon dioxide, and pH levels. Low oxygen (hypoxia) or high CO2 stimulate the chemoreceptors. At this point, signals are sent to the brainstem, which activates the sympathetic nervous system, causing increased heart rate, vasoconstriction, and elevated blood pressure to improve oxygen delivery. - Sympathetic Nervous System: It increases heart rate, as well as cardiac contractility (force of contraction) and constrict blood vessels, which raises peripheral resistance and blood pressure. LONG-TERM REGULATION It involves the kidneys and hormones. These mechanisms control blood volume and systemic vascular resistance. - RAAS system: The Renin-Angiotensin-Aldosterone System is a critical hormonal system that regulates blood pressure over time, particularly in response to low blood volume or low blood pressure. Angiotensinogen (produced by the liver) is converted by renin (secreted by the kidneys when blood pressure is low or when there's reduced blood flow to the kidneys) into angiotensin I, which in turn is converted into angiotensin II, a potent vasoconstrictor, by the angiotensin-converting enzyme (ACE) in the lungs. The angiotensin II has different effects: It increases peripheral resistance (vasoconstriction), raising blood pressure. Stimulates aldosterone release from the adrenal glands, which in turn increases sodium and water reabsorption by the kidneys, increasing blood volume and blood pressure. Stimulates ADH (antidiuretic hormone) that promotes water reabsorption in the kidneys, also increasing blood volume. - Aldosterone: Is produced by the adrenal cortex in response to angiotensin II or high potassium levels. It increases sodium reabsorption in the kidneys, which leads to water retention and increased blood volume, raising blood pressure. - Antidiuretic Hormone/ Vasopressin: ADH is released by the posterior pituitary gland in response to low blood volume or high plasma concentration. It increases water reabsorption in the kidneys, which raises blood volume and it has also a mild vasoconstrictor effect, increasing blood pressure. - Atrial Natriuretic Peptide: ANP is a hormone released by the atria of the heart when blood volume or pressure is too high. It promotes excretion of sodium and water by the kidneys, reducing blood volume. It also inhibits the RAAS and the release of renin, aldosterone, and ADH Causes vasodilation, reducing blood pressure. CLINICAL APLLICATION In CORONARY ARTERY DISEASE, changes in one or more of the coronary arteries cause insufficient blood flow (ischemia) to the heart. The result may be myocardial damage in the affected region, or even death of that portion of the heart (a myocardial infarction, or heart attack) Sudden cardiac deaths during myocardial infarction are due mainly to ventricular fibrillation, an abnormality in impulse conduction triggered by the damaged myocardial cells. A small fraction of individuals with ventricular fibrillation can be saved if emergency resuscitation procedures are applied immediately after the attack. This includes cardiopulmonary resuscitation (CPR) and defibrillation MEASUREMENT OF CARDIAC FUNCTION Human cardiac output and heart function can be measured by a variety of methods. - Echocardiography is a noninvasive technique that uses ultrasonic waves. It can detect the abnormal functioning of cardiac valves or contractions of the cardiac walls, and it can also be used to measure ejection fraction. - Cardiac angiography, also called angiogram, is usually performed for evaluating cardiac function and for identifying narrowed coronary arteries or blockages It requires the temporary threading of a thin, flexible tube called a catheter through an artery or vein into the heart. A liquid containing radio-opaque contrast dye is then injected through the catheter during high-speed x-ray videography. - The electrocardiogram