YAW BBL Cardiovascular System Lecture 4 PDF

Dr Yasser Abdel-Wahab (Module Coordinator) WEEK 4 YAW Introductions to Anatomy and Physiology of Cardiovascular System By Dr. Yasser Abdel-Wahab, Diabetes Research Group, Saad centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Coleraine Campus (Email: y.abdel-wa...

Dr Yasser Abdel-Wahab (Module Coordinator) WEEK 4 YAW Introductions to Anatomy and Physiology of Cardiovascular System By Dr. Yasser Abdel-Wahab, Diabetes Research Group, Saad centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Coleraine Campus (Email: [email protected]) Aims are: '”To give an overview of the Anatomy and Physiology of Cardiovascular System. Lecture Outlines: 1. The organisation of the cardiovascular system (CV) 2. Overview of the Heart 3. Overview of the Vascular System 4. Blood flow around CVS 5. Heart Beat & Heart Dynamics 6. Blood vessels and hemodynamic The Intended Learning outcomes are:  To have an overview of the structure of cardiovascular system.  Give an overview of the heart, the heart valves, blood flow through the heart and pulmonary circuit  Appreciate the differences between nodal cells and conducting cells and describe the components and functions of the conducting system of the heart  Identify the electrical events associated with a normal electrocardiogram and associate these events with the cardiac conduction system.  Identify the heart dynamics and define stroke volume, heart rate cardiac output and describe the factors that influence these variables  Explain how adjustments in stroke volume and cardiac output are co-ordinated and the role of positive and negative inotropic agents and the nervous system in the control of the heart  Give an overview of the cardiovascular system and how and where fluid and dissolved materials enter and leave the cardiovascular system.  Explain the mechanisms that regulate blood flow through arteries, capillaries and veins and factors that regulate Blood pressure. 1  Dr Yasser Abdel-Wahab (Module Coordinator) Cardiovascular System Cardiovascular terminology:  Cardiovascular system: is the circulatory system which comprises the heart and blood vessels. The system carries nutrients and oxygen to the tissues of the body and removes carbon dioxide and other wastes from them. Cardio means (heart) is the centre of cardiovascular system and Vascular (refer to blood vessels).  At rest the heart pumps 30 times its own volume each minute (i.e. 5 litres of blood to the lungs and the same to the rest of the body).  The heart circulates blood through approximately 100,000 km of blood vessels. The Heart Location and size of heart Cone-shaped. Same size as closed fist. The heart has 4 chambers; 2 atria and 2 ventricles Mediastinum: The heart rest on the Diaphragm near middle of the thoracic cavity which extends between the Sternum (chest bone) anteriorly and vertebral column in the back between two lungs. About 2/3 of the heart lies on the left of the body’s midline The heart has: Apex: formed from the tip of the left ventricle Base: opposite to apex and it forms the upper and posterior margin of the heart; it is broader than being flat like the base of a pyramid Position of the heart 2  Dr Yasser Abdel-Wahab (Module Coordinator) Exterior anatomy of the heart: Pericardium: It is a triple-layered bag that surrounds and protects the heart. It confines the heart to its position to the mediastinum. It is formed from: (1) Outer fibrous pericardium; tough inelastic fibrous connective tissue. (2) Inner serous pericardium; thinner more delicate membrane that forms double layers around the heart and formed of: (1) Outer parietal layer and (2) Inner visceral layer (epicardium). Anatomy of heart wall: The heart is approximately 12 cm long, 9 cm width at its broadest point and 6 cm thick. The heart wall consists of the following: The outer most layer (epicardium) or visceral layer of serous pericardium. Middle layer (myocardium); cardiac muscle makes the main bulk of the heart (involuntary, striated). Inner layer (endocardium); thin layer of endothelium that provides the smooth lining for the inside of the heart and covers the valves of the heart. Three distinct layers: (1) Epicardium; (2) Myocardium; (3) Endocardium 3  Dr Yasser Abdel-Wahab (Module Coordinator) Overview of heart: Major internal components: Heart divided into four hollow chambers: – Two on left. – Two on right. – Upper chambers (called atria) Thin walled, receive blood returning to heart Right atrium-receives blood from the systemic (body) circuit. Left atrium- collects blood from the pulmonary (lungs) circuit. – Lower chambers (called ventricles) Force blood out of heart into arteries. Right ventricle- discharges blood into pulmonary circuit. Left ventricle - ejects blood into systemic circuit. Interatrial septum – Separates right from left atrium. Interventricular septum – Separates right from left ventricle. Atrioventricular orifice – Opening through which atrium corresponds with corresponding ventricle. – Guarded by atrioventricular (AV) valve. Atrioventricular (coronary) sulcus – Groove separating atria from ventricles. Overview of heart: Sectional view 4  Dr Yasser Abdel-Wahab (Module Coordinator) Valves of the heart: During contraptions of the chambers of the heart, a portion of blood is pushed into a ventricle or out of the heart through an artery. To prevent the back flow of the blood during cardiac contraction, the heart requires valves The heart consists of two types of valves: Atrioventricular valves: a) Tricuspid (three cusps or flaps) and b) Bicuspid (mitral). Semilunar valves: a) Pulmonary and b) Aortic. Valve Location Function Triscupid valve Right Prevents blood from moving from right atrioventricular ventricle into right atrium during ventricular orifice contraction Pulmonary valve Entrance to Prevents blood from moving from pulmonary pulmonary trunk into right ventricle during ventricular trunk relaxation Bicuspid (mitral) Left Prevents blood from moving from left ventricle valve atrioventricular into left atrium during ventricular contraction orifice Aortic valve Entrance to Prevents blood from moving from aorta into aorta left ventricle during ventricular relaxation Overview of the vascular system: Network of blood vessels Extend between heart and peripheral tissues. Subdivided into: – Pulmonary circuit: Carries blood to and from gas exchange surfaces of lungs. – Systemic circuit: Transports blood to and from rest of body. Each circuit begins and ends at heart; blood travels through circuits in sequence. Arteries (efferent vessels) Carry blood away from heart. Veins (afferent vessels) Carry blood to heart. Capillaries (exchange vessels) Connect the smallest arteries and veins. Thin walls allow exchange of dissolved gases, nutrients and wastes between blood and surrounding tissue. 5  Dr Yasser Abdel-Wahab (Module Coordinator) Some key features of arteries and veins: ARTERIES: VEINS: Receive blood under great pressure from the Receive blood at low pressure from capillaries. heart (ventricles) after cardiac contraction (systole). Veins have valves along their length which Aorta and arteries have elastic walls and stops blood from possibly flowing backwards. the ability to expand in diameter to stop them rupturing on receipt of blood following Muscular contraction also assists blood flow ventricular contraction - this is termed compliance through veins. Then during ventricular relaxation the artery walls return to normal size (by elastic recoil). Analogy is blood being added to balloon below: After contraction lots of blood fills space (artery) and balloon On relaxation, surplus blood held in balloon returns to space (artery) as heart rests Comparisons between arteries and veins: Redraw 6  Dr Yasser Abdel-Wahab (Module Coordinator) Arterial blood supply to the heart: - Blood flows through the heart, but the heart also needs a rich blood supply to supply nutrients and gases to working muscles. - Blood supply to the heart comes from Coronary arteries which gives rise to right and left Coronary arteries. Furthermore, right coronary artery gives rise to posterior inter-ventricular artery and left gives rise to anterior inter- ventricular and circumflex arteries. This in turn gives rise to small arterioles and arterial capillaries. - Coronary artery disease (CAD) often arising due to atherosclerosis can reduce blood flow and cause coronary ischemia. Blockages can sometimes be successfully removed surgically. Blood flow through heart (pulmonary circuit & systemic Circuits): A pumping heart drives blood around a network of blood vessels comprising of two separate ‘circuits”: pulmonary and systemic, connected by the heart, and following one complete sequence Head and upper limbs Lungs Pulmonary Circuit Systemic Circuit Digestive tract Kidneys Trunk and lower limbs 7  Dr Yasser Abdel-Wahab (Module Coordinator) Blood flow through heart and pulmonary circuit: The right atrium receives non-oxygenated blood from systemic circuits via Superior and inferior Vena Cavae. The blood passes via Tricuspid valve into right ventricle. From the right ventricle, blood passes through the pulmonary valve into the pulmonary trunk and into the Right and left Pulmonary arteries into the lung to be oxygenated. The oxygenated blood leaves the lungs via Pulmonary veins into the left atrium and from the Left atrium via Bicuspid valve into left ventricle. From the left ventricle it passes through aortic valve towards Aorta and distributed via the system circuit. Blood from systemic circuit Blood to systemic circuit Vena cavae Aorta Aortic valve Right atrium Tricuspid valve Left ventricle Right ventricle Bicuspid valve Pulmonary valve Left atrium Pulmonary trunk Pulmonary arteries Pulmonary veins Lungs Summary: The valves of the heart are: The two circuits of the cardiovascular TRICUSPID system are: ………………………………… PULMONARY ………………………………… PULMONARY ………………………………… BICUSPID ………………………………… SYSTEMIC ………………………………… AORTIC ………………………………… 8  Dr Yasser Abdel-Wahab (Module Coordinator) Heart Beat and ECG: Heartbeat: Coordination of heartbeat made possible by: Gap junctions: Allow spread of action potential from one muscle cell to the next throughout heart Specialized conducting system: Facilitates rapid and coordinated spread of excitation. A B Redraw Cardiac muscle cells involved in heartbeat: Contractile cells – Produce powerful contractions propelling blood. – Action potential stimulates contraction. Specialized (non-contracting) cells – Nodal cells Establish rate of cardiac contraction. Cell membranes depolarize spontaneously. Generate action potentials at regular intervals. Depolarize at different rates. Normal rate of contraction established by those reaching threshold first - pacemaker cells. – Conducting cells Distribute contractile stimulus to myocardium. Electrically connect sinoatrial (SA) nodal cells to atrioventricular (AV) nodal cells. 9  Dr Yasser Abdel-Wahab (Module Coordinator) Cardiac autorhythmic cells: During embryonic development ~ 1% cardiac cells become autorhythmic (self- excitable) cells. Autorhythmic fibres – Act as pacemaker, setting rhythm for entire heart. – Form conduction system. Pacemaker and action Ion movements during an action State of ion channels during potentials and pacemaker potential pacemaker and action potential 20 Membrane potential (mV) 0 -20 -40 -60 This diagram shows the pacemaker and action potentials of the cardiac muscle, the ion movements during an action and pacemaker potential; the state of ion channels during pacemaker and action potential. Action potential in cardiac muscle: It is composed of 3 phases: (1) Rapid Depolarization: (a) Causes: Na+ entry; (b) Duration: 3-5msec and (c) End with: Closure of Voltage-gated (fast) sodium channels. (2) Rapid Plateau: (a) Causes: Ca+ entry; (b) Duration: ~175msec and (c) End with: Closure of slow calcium channels. (3) Repolarization: (a) Causes: K+ loss; (b) Duration: 75msec and (c) End with: Closure of slow potassium channels. 10  Dr Yasser Abdel-Wahab (Module Coordinator) Depolarization of plasma membrane (“excitation”) Excitation-contraction coupling in cardiac muscle: - Action potential of cardiac muscle results Opening of voltage-regulated in depolarization of plasma membrane calcium channels (“excitation”). - Opening of voltage-regulated calcium Channels. Calcium influx into cell - Calcium influx into the cells which accounts for 10% of the increase in intracellular Calcium and also stimulate the release of Stimulation of Calcium calcium release from induced Calcium from sacroplasmic reticulum which sarcoplasmic calcium Accounts for 90% of the increase in intracellular reticulum release Calcium. The increase in intracellular Calcium concentration 10% 90% Will lead to cardiac muscle contration. Increase in intracellular calcium concentration Contraction Components of cardiac conduction system and impulse conduction trough the heart: Sinoatrial (SA) node Atrial syncytium Junctional fibres Atrioventricular (AV) node AV bundle Right and left bundle branches Purkinje fibres Ventricular syncytium Step 1: SA node activity and atrial activation begin, time=0 Step 2: Stimulus spread across the atrial surfaces and reaches AV node, time: 50 msec. Step 3: There ia a delay at AV node. Atrial contraction begins, time= 150 msec. Step 4: The impulse travel along the interventricular septum within the AV bundle at the bundle branches to Purkiniji fibres and via the moderator band, to the papillary muscles of the right ventricles, elapsed time= 175 msec. Step 5: The impulse is distributed by Purkinije fibres and relayed throughout the ventricular myocardium. Atrial contraction is completed and ventricular contraction begins. 11  Dr Yasser Abdel-Wahab (Module Coordinator) Summary: Two types of specialised (non-contracting) cells are: (1) Nodal cells (2) Conducting cells (3) The two nodes of the Cardiac conduction system are known as: (1) Sinoatrial (SA) Node (2) Atrioventricular (AV) Node Two types of specialised (non-contracting) cells are: Autorhythmic cells. The ions involved in action and pacemaker potentials are Na+, Ca++, K+ Electrocardiogram (ECG):  Electrical events occurring in the heart can be detected by electrodes on the surface of the body. Recording of cardiac electro-activity is called Electrocardiogram.  ECG allows to monitoring of performance of nodal activity (SA and AV), conducting activity, and contractile activity of the heart. +1 P wave:  Accompanies depolarization of the atria. QRS complex: + 0.5 Appears as ventricles depolarize. Ventricles begin contracting shortly Millivolts after peak of R wave. 0 T wave Indicates ventricular repolarization. - 0.5 Redraw Note: Of particular importance diagnostically is the amount of depolarization during the P wave and QRS complex, or changes in the T wave. P wave S wave R * This slide summarises the cardiac conduction accompanying the records of various components P P of ECG. Q S * Start of the P wave followed by PQ Segment and atrial contraction begins followed by Q wave, R wave PQ ST segment and S wave. segment R * ST segment develops and the formation of T wave, P P followed by the completion of ECG. Q S Atria contract Ventricles contract Q wave T wave R P P T Q Q S R wave Completion R R P P T 12 Q Q S  Dr Yasser Abdel-Wahab (Module Coordinator) Summary:  The five types of ECG waveS are P Q R S T waves.  The segment corresponds to atria contracting is PQ segment.  The segment corresponds to ventricle contracting is ST segment. Heart dynamics: The heart beats independently. However to maintain health and life, the body’s demands for oxygenated blood must influence heart dynamics. Heart dynamics: Cardiac output: The following equation identify the Cardiac Cardiac output = Stroke volume x Heart rate Output. (ml/min) (ml/beat) (beats/min) Stroke volume (SV) Volume of blood ejected by ventricle with each contraction, Typically 70 ml per beat. Heart rate (HR) Cardiac output = 70 x 72 Number of heartbeats per minute. (ml/min) (ml/beat) (beats/min) Typically 72 beats per minute. Cardiac output (CO) Volume of blood ejected from left (or right) ventricle into the aorta (or pulmonary trunk) each minute. During exercise cardiac output Cardiac output = 5040 ml/min = ~ 5 litres can increase to 30 - 35 litres/min. Major factors increasing heart rate and stroke volume:  Increase of the activity of sympathetic Activity of Plasma adrenaline Activity of parasympathetic sympathetic Nerves to the heart, increase in Plasma nerves to heart nerves to heart adrenaline and decrease in parasympathetic activity will lead to increase in Heart Rate (HR) and Heart rate cardiac output.  Increase of the activity of sympathetic Nerves to the heart, increase in Plasma Cardiac adrenaline and end-diastolic ventricular volume output will lead to increase in cardiac output and Heart Rate (HR). Stroke volume Activity of End-diastolic sympathetic Plasma ventricular nerves to heart adrenaline volume Regulation of stroke volume: Blood flow through heart At rest, heart pumps out 50 – 60 % of the total volume of blood in heart. Other 40 – 50 % remains in ventricles after each contraction, the end-systolic (ventricular) volume (ESV). 13  Dr Yasser Abdel-Wahab (Module Coordinator) End-diastolic (ventricular) volume (EDV) is the amount of blood in the ventricle immediately before contraction. EDV - ESV = Stroke volume (135 ml) (65 ml) (70 ml) Important factors regulating stroke volume: Preload – The stretch on the heart before it contracts. – The more the heart is filled during diastole (i.e. the greater the preload), the greater the force of contraction during systole (The Frank-Starling Law of the heart). Contractility – The forcefulness of contraction of individual ventricular muscle fibres. – Strength of contraction for any given preload. – Regulated by positive inotropic agents (increase contractility) and negative inotropic agents (decrease contractility). Afterload – The pressure that must be exceeded before ejection of blood from ventricles can begin. – Sufficient pressure to force open semilunar valves. – When increased (e.g. elevated blood pressure, atherosclerosis), stroke volume decreases and more blood remains in ventricles at the end of systole. Positive inotropic agents (regulation of stroke volume): Often promote Ca2+ influx during cardiac action potentials, strengthening the force of muscle fibre contraction. Sympathetic stimulation – Noradrenaline (NE) released from postganglionic fibres binds receptors on cardiac muscle cell membrane. – Adrenaline (E) and NE released from adrenal medulla binds receptors on cardiac muscle cell membrane. – Stimulation of cardiac muscle metabolism. Hormones – Adrenaline (E) and noradrenaline (NE). – Glucagon. – Thyroid hormones. Increased extracellular Ca2+ concentration Drugs – Isoproterenol, dopamine, and dobutamine (via α- and β-receptor- mediated effects). – Digitalis (via blocking Ca2+ flux out of sarcoplasm). Negative inotropic agents (regulation of stroke volume): Sympathetic inhibition – Acetylcholine (ACh) released from vagus nerve binds receptors and hyperpolarizes cardiac muscle cell membrane. – Decreased heart rate (via effects on SA and AV nodes). – Reduction in force of contraction. 14  Dr Yasser Abdel-Wahab (Module Coordinator) Anoxia (oxygen deficiency) Acidosis (low pH) Increased extracellular K+ concentration Drugs – Propanolol, artenolol, and barbiturates (via α- and β-receptor-mediated effects). – Anaesthetics (e.g. halothane; via reduced intracellular Ca2+). – Regulation of heart rate: Autonomic innervation: Cardiovascular centre – Processes nerve impulses (input) to give definite responses (output) via sympathetic and parasympathetic nerves. Proprioceptors – Monitor position of limbs and muscles. – Upon movement sends increased input to cardiovascular centre. – Input is major stimulus for quick rise in heart rate at onset of physical activity. Chemoreceptors – Monitor chemical changes in blood. Baroreceptors – Monitor blood pressure in major arteries and veins. – Those in arch of aorta and carotid arteries detect changes in blood pressure, influencing blood pressure and heart rate. Regulation of heart rate: Chemical regulation: Depression of cardiac activity by: – Hypoxia (lowered oxygen level). – Acidosis (low pH). – Alkalosis (high pH). Major effects on heart exerted by: – Hormones Adrenaline (E) and noradrenaline (NE) (both from adrenal medulla) enhance efficiency of heart. E and NE increase heart rate (HR) and contractility. Thyroid hormones also enhance HR and contractility. – Ions Relative concentrations of K+, Na+ and Ca2+ have high impact on cardiac function; while excess K+ and Na+ have negative effects, moderate increases in Ca2+ speeds HR. Higher brain centres Sensory receptors Cerebral cortex Proprioceptors (monitor movement) Nervous system control of the heart Limbic system Chemoreceptors (monitor blood chemistry) Hypothalamus Baroreceptors (monitor blood pressure) This diagram summarises the nervous system control of the heart beats. Cardiac control centre in medulla oblongata Cardiac accelerator nerve Vagus (X) nerve (sympathetic) (parasympathetic) Increased rate of spontaneous Decreased rate of spontaneous depolarization in SA (and AV) depolarization in SA (and AV) node increases heart rate node decreases heart rate Increased contractility of atria 15 and ventricles increases stroke volume  Dr Yasser Abdel-Wahab (Module Coordinator) Summary:  Cardiac output = HR X SV  The three important factors regulate stroke volume are: (1) preload (stretch on heart before contraction), (2) contractility, (3) afterload (pressure that must be exceed before ejection of blood from ventricles can begin). Blood vessels and haemodynamics: (A) Model of the cardiovascular system & (B) Distribution of blood in the cardiovascular system: (A) (B) Elastic arteries Aorta Aortic valve Left of Arteriole with Mitral valve heart variable radius Pulmonary veins Lungs Capillaries Exchange Pulmonary of material with cells artery Right of Pulmonary Venules heart valve Tricuspid valve Venae cavae Veins Explanation for blood flow: Liquids and gases Vena cavae Capillaries Arterioles  Always flow down a pressure gradient (ΔP). Venules Arteries  Flow from regions of higher pressure to lower Veins Aorta pressure. Mean systemic blood pressure Blood flow  Relies on heart to maintain a pressure head.  Pressure gradient in blood vessels (mm Hg) Physiology of blood flow & pressure: Fluid pressure Force exerted by fluid on container. If fluid is not moving, exerts a force in all directions, termed hydrostatic pressure (HP). 16  Dr Yasser Abdel-Wahab (Module Coordinator) Diagrammatic explanation of Hydrostatic pressure (HP): F  P (Flow is directly proportional to the pressure gradient) Proportional to height of When fluid flows pressure falls water column with distance as energy is lost as friction Physiology of blood flow & pressure (Cont.): Circulatory pressure The pressure gradient in the cardiovascular system. Can be divided into three components: – Arterial (Blood) pressure (BP) Ranges from ~ 100 mm Hg to 35 mm Hg. – Capillary pressure Pressure within capillary beds. Ranges from ~ 35 mm Hg to 18 mm Hg. – Venous pressure Pressure within venous system. Pressure gradient from venules to right atrium ~ 18 mm Hg. Resistance and blood flow: Resistance Refers to opposition to blood flow. Principally results from friction between blood and walls of blood vessels. Depends on: – Total blood vessel length (usually constant). – Blood viscosity (usually constant). – Turbulence (usually negligible). – Average blood vessel radius (variable). For circulation to occur the pressure gradient must overcome the total peripheral resistance (resistance of entire cardiovascular system). F  1/R (Flow is inversely proportional to resistance) 17  Dr Yasser Abdel-Wahab (Module Coordinator) Equations determining blood flow: F  P (Flow is directly proportional to the pressure gradient) F  1/R (Flow is inversely proportional to resistance) F  P/R (Flow is directly proportional to the pressure gradient and inversely proportional to resistance) F  BP/PR (Flow is directly proportional to blood pressure and inversely proportional to peripheral resistance) F  1/r4 (Flow is inversely proportional to the fourth power of the vessel radius, derived from Poiseuille’s Law) Pressures within the systemic circuit: The peak blood pressure measured during ventricular systole – SYSTOLIC PRESSURE (SP) The minimum blood pressure measured at the end of ventricular diastole – DIASTOLIC PRESSURE (DP) SP – DP = Pulse Pressure (PP) Mean arterial pressure (MAP) is used to report a single blood pressure value: MAP = DP + (PP/3) Factors affecting blood pressure: This diagram summarises the various factors affecting blood pressure: Increased contraction of leg Increased blood volume Respiratory muscles (skeletal muscle (water retention) pump pump) Increased sympathetic Decreased Increased ratio of Increased Increased impulses & para- red blood cells to body venous catecholamines sympathetic blood plasma size return from adrenal medulla impulses (e.g. burns) (obesity) Decreased Increased Increased Increased Increased total blood vessel heart stroke volume blood blood vessel radius rate (preload) viscosity length (vasoconstriction) Increased Increased cardiac systemic vascular output resistance Increased mean 18 arterial pressure (MABP)  Dr Yasser Abdel-Wahab (Module Coordinator) Hormonal regulation of blood pressure: The following table summarizes the hormonal regulation of blood pressure Factor influencing blood pressure Hormone Effect on blood pressure CARDIAC OUTPUT Increased heart rate and force of Noradrenaline Increase contraction SYSTEMIC VASCULAR RESISTANCE Vasoconstriction Angiotensin II Increase Antidiuretic hormone Noradrenaline Adrenaline Calcitriol (active form of vitamin D) Vasodilation Atrial natriuretic peptide Decrease Adrenaline Parathyroid hormone BLOOD VOLUME Blood volume increase Aldosterone Increase Antidiuretic hormone Blood volume decrease Atrial natriuretic peptide Decrease Summary:  Blood flow relies on heart to maintain a pressure head  Force exerted in all directions when a fluid is not moving is called HYDROSTATIC PRESSURE  Resistance to blood flow depends on: (1) Total blood vessel length , (2) Blood viscosity , (3) Turbulence, (4) Average blood vessel radius. Reading List:  Martini FH & Nath JL, Fundamentals of Anatomy and Physiology, San Francisco, Pearson Benjamin Cummings. Martini’s Fundamentals of Anatomy and Physiology was specially selected for this module on the basis of the quality of the textbook, the inclusion of the valuable Fundamentals of Anatomy and Physiology. It comes with Interactive CD-ROM and supporting WWW site (freely accessible to students purchasing this text). 19