CVS physiolgy.pptx. Good document for physiology studies

Good file for learning the CNS under physiology

1. CIRCULATORY SYSTEM BY DR. ANDAMBI

2. Circulatory System The circulatory system was discovered by William Hervey (English Physician ) in 1628 Most physicians of the time felt that the lungs were responsible for moving the blood around throughout the body.  Its the body's transportation system that moves substances to and from the cells /tissues and heart It is broadly divided into 2 categories :- Open – Has no vessels Found amoung invertebrates i.e insects, myriapods e.g centipedes, arachnid e.g spiders, crustaceans e.g crabs. The heart pumps blood( hemolymph) into an open cavity called a hemocoel. Closed – found in vertebrates Found in vertebrates Heart pumps blood in a closed circuit of vessels made of 2 circuits i.e pulmonary and systemic circuits. It consists of heart, blood vessels and blood(cardiovascular system Chambers – Two(2) – 1 atrium and 1 ventricle i.e Fish Three (3) – 2 atrium and 1ventricle i.e Amphibians, Reptiles Four (4) – 2 atrium and 2 ventricles –like in human beings Cardiovascular system

3. What is human cardiovascular System? It consists of a closed circuit/network of structures that pump (by heart ) and deliver( using vessels ) blood to the body tissues/organs and back to the heart The components include :- The cardiac (the heart) – Muscular pumping device that pumps blood into the circulation. It generates the force required to circulate the blood to all the tissues in the body. The vasculature (vessels) – arteries, capillaries and veins) That circulate/distribute blood to and from cells/tissues/organs Blood Carry substances

4. The heart Learning objectives To appreciate basic steps of heart formation(Embryology) To appreciate the structure of the heart(Anatomy ) To understand cardiac muscle structure (histology) To appreciate the electrical activity of individual myocytes, including resting membrane potentials and action potentials. To appreciate the way action potentials are generated and conducted throughout the heart.(conducting system) . To be able to describe the way electrical activity of the heart is measured using the electrocardiogram (ECG). To understand the sequence of contraction and relaxation of the heart(cardiac cycle). To appreciate the amount of blood pumped from the heart to circulation per cycle(SV) and minute(CO) plus factors affecting it.

5. The heart -Embryology First functional organ to develop Develop from splanchnic layer of lateral plate mesoderm (cardiogenic area) Starts of as cluster of cells which are stimulated by endoderm beneath to form blood islands The islands organize into angioplastic cords The cords at the cardiogenic area canalize to form 2 cardiogenic tubes After lateral folding of embryo the 2 tubes fuse in craniocaudal direction to form single endocardial heart tube The tube forms 5 dilatations namely:- Sinus venosum Common(primitive) atrium Common (primitive )ventricle Bulbus cordis Proximal 1/3 – forms smooth part of rt ventricle Middle 1/3(conus cordis) – forms smooth outflow traccts Distal 1/3 (Truncus arteriosis ) - forms AA & PT Bulbus and ventricles grows faster leading to looping ( bulboventricular looping) Bulbus cordis and truncus loop ventrally & inferiorly Primitive Atrias and sinus venosus shifts dorsally and upwards The last step is partitioning into chambers, aortic and pulmonary outflow

6. The work of the heart in one life is equivalent to lifting 30 tons to the top of Mount Everest The busy and hard working heart! The Heart Definition - A specialized muscular organ Site – Middle mediastinum of thoracic cavity Size – clenched fist, Measurements -12 x 8 x 6 cm (L X W x T) Weight – 250-350 grams Shape – inverted cone/pyramid Orientation- apex inferior lateral, and base points towards right shoulder Layers – endocardium , myocardium and pericardium Parts – 4 chamber separated by septa and communicating through 4 valves Function – pump It receives blood from low pressure venous side and pumps it to high pressure arterial side The pumping requires rhythmic relaxation and contraction of chambers The rhythm is at a rate of 70-80 cycles or beats/m, 108,000 beats/day, 40million beats/year, 3billion beats/lifetime It pumps 70mls(1/2 cup /beat, 5L/min

7. CARDIAC MUSCLE- Structure Found only in the heart and is made of muscle cell called cardiomyocyte. Cardiomyocyte is striated but slightly different from skeletal muscle . Smaller (20 -100 um), shorter and broader . It is branched and interconnected/joined by intercalated discs which provides. Structural connection through desmosomes Electrical/physiological connection through gap junctions (pores made up of proteins called connexion ) – allow ions to pass An impulse initiated in one of the cardiac muscle fibers is conveyed to all the muscles, and the heart contracts as a functional syncytium (i.e., as if one big muscle). – atrias contracting before venticles hence 2 syncytium (Atria & ventricle) Has single centrally located nucleus More mitochondria – for work Less Endoplasmic reticulum, fewer and larger T-tubules Ca2+ also influxes from ECF reducing storage need In contrast to skeletal muscle it requires extracellular calcium for contraction Supplied by autonomic system(sympathetic and sympathetic) Like the other muscles it contains protein filaments of actin and myosin that slide past one another shortening (contraction) or lengthening (relaxation) Its contraction is stimulated by neural or chemical stimuli The muscle fibers are of 2 types: Contractile fiber/cell - found in atrial & ventricular muscles Conductive/excitatory nodal muscle fibers( auto- rythimic cells)- found in conductive system – conduct impulse

8. CELL MEMBRANE POTENTIALS ion channels and pumps The cell membrane is a lipid bilayer that intrinsically has low permeability to charged ions Charged ions leave or enter the cell through channels or pumps spanning the cell membrane Channels Ungated = always open e.g cl Voltage gated = open due to voltage difference e.g Na+, K+, Ca+ Ligand/receptor gated = open when hormone or neurotransmitter binds to receptor. E.g Ca Pumps(active transport) Primary pumps – use energy e.g Na-K pump, Ca pump Secondary – use energy produced by primary pump e.g Na – Ca exchanger, Na-H exchanger Membrane potentials in cells are determined primarily by three factors: The concentration of ions on the inside and outside of the cell; The permeability of the cell membrane to those ions (i.e., ion conductance ) through specific ion channels The activity of electrogenic pumps (e.g., Na + /K + -ATPase and Ca ++ transport pumps ) that maintain the ion concentrations across the membrane. These channels and pumps regulate ionic concentrations across cell membranes and determine membrane potential

9. Concentrations of charged ions Cardiac cells, like all living cells, have different concentrations of ions across the cell membrane. The most important of which are Na + , K + , and Ca ++   There are also negatively charged proteins and nucleic acid within the cell to which the cell membrane is impermeable. In a cardiac cell, the concentration of K + is high inside the cell and low outside. Therefore, there is a chemical gradient for K + to diffuse out of the cell. The opposite situation is found for Na + and Ca ++ where their chemical gradients (high outside, low inside concentrations) favor an inward diffusion.   

10. Nernst potential for K To understand how a membrane potential is generated, first consider a hypothetical cell in which K + is the only ion across the membrane other than the large negatively charged proteins inside of the cell. Because the cell has potassium channels through which K + can move in and out of the cell, K + diffuses down its chemical gradient (out of the cell) As K + (a positively charged ion) diffuses out of the cell, it leaves behind negatively charged proteins.  This leads to a separation of charges across the membrane and therefore a potential difference across the membrane. Experimentally it is possible to prevent the K + from diffusing out of the cell. This can be achieved by applying a negative charge to the inside of the cell that prevents the positively charged K + from leaving the cell. The negative charge across the membrane that would be necessary to oppose the movement of K + down its concentration gradient is termed the equilibrium potential for K + (E K ; Nernst potential ). The resting potential for a ventricular myocyte is about -90 mV, which is near the equilibrium potential for K + when extracellular K + concentration is 4 mM.

11. CELL MEMBRANE POTENTIALS Resting Membrane Potentials By convention, the outside of the cell is considered 0 mV. if a voltmeter is used to measure voltage across the cell membrane (inside versus outside) of a cardiomyocyte, it will be found that the inside of the cell has a negative voltage of -90 mV with respect to the outside of the cell (which is referenced as 0 mV). Under resting conditions, this is called the resting membrane potential .

12. Action Potentials With appropriate stimulation of the cell, this negative voltage inside the cell (negative membrane potential) may transiently become positive owing to the generation of an action potential . Action potentials occur when the membrane potential suddenly depolarizes and then repolarizes back to its resting state(brief change of membrane potential) The two general types of cardiac action potentials include Non pacemaker Contracting cell/fiber. Triggered by depolarizing currents from adjacent cells. Pacemaker Conducting cell/fiber. Capable of spontaneous action potential generation Both types of action potentials in the heart differ considerably from the action potentials found in neural and skeletal muscle cells One major difference is the duration of the action potentials. Typical nerve, duration is about 1 ms. Skeletal muscle cells = 2-5 ms ventricular muscle= 200 to 400 ms Another difference between cardiac and nerve and muscle action potentials is the role of calcium ions in depolarization These differences among nerve, skeletal muscle, and cardiac myocyte action potentials relate to differences in the ionic conductances responsible for generating the changes in membrane potential.

13. Non-pacemaker(contracting) cells Action Potentials Includes atrial, ventricular and punkinje fibers. The AP divided into five numbered phases. Phase 4(polar state) – True Resting membrane potential The cell is positive outside and negative inside at -90mv Reflects a high potassium conductance Phase 0 = rapid depolarization Opening of fast sodium gated channels leading to rapid influx of sodium(increase Na+ conductance gNa ) Accompanied by a fall in potassium conductance ( gK ); Voltage changes from -90 to + 20 mv Phase 1= initial/partial /temporary repolarization to + 10 to 0mv At + 10 mv Na+ channels close and special type of K channel/ transient open allowing some K+ to leave(efflux) the cell. Phase 2 = plateau – balance between ca+ influx and k+ efflux At 0 mv long lasting ( L-type ) Ca ++ channels open and Ca++ moves in the cell ( increase in slow inward calcium conductance ( gCa ) ). Are major calcium channels in cardiac and vascular smooth muscle. open when the membrane potential depolarizes to about –40 mV. They are opened by membrane depolarization (they are voltage-operated ) and remain open for a relatively long duration. Are blocked by classical L-type calcium channel blockers (verapamil) Phase 3 - Repolarization Ca ++ channels close and delayed rectifier K+ channels open through which K+ leaves the cell Many of the antiarrhythmic drugs that are used to treat cardiac arrhythmias have their action on sodium, calcium and potassium channels.

14. Refractory Period The time interval in which a second contraction cannot be triggered is referred to as the refractory period of that muscle . The cardiac muscle has a long refractory period compared with skeletal muscle because of the plateau phase of the action potential. The longer duration of cardiac action potential (i.e., refractory period) is beneficial. In ventricle = 0.25 to 0.35 sec and In atria= 0.15 sec. Enables the heart to have adequate time to fill and eject blood. Prevent sustained (tetanic) contraction of the muscle. Many antiarrhythmic drugs alter the ERP, thereby altering cellular excitability.  For example, drugs that block potassium channels (e.g., amiodarone, a Class III antiarrhythmic ) delay phase 3 repolarization and increases the ERP.  Drugs that increase the ERP can be particularly effective in abolishing reentry currents that lead to tachyarrhythmias .

15. Pacemaker(conducting) Cells Action Potentials Generation of Rhythmic Impulse The cells include i.e SAN, AVN, bundle cells punkinje fibers They cannot maintain a stable RMP. Every time these cells reach their RMP after depolarization, there is a slow leak of positive ions into the cell, raising the potential toward threshold and triggering another action potential They generate regular spontaneous AP of 3 phases Phase 4- pace maker potential - 60 mv. Gradually becomes less negative by slow leak of positive ions in At first(at -60mv) the Na+ moves in through funny Na+ channels Later(at -55mv) some ca+ moves in though funny(T-type-transient) ca+ channels Phase 0 - depolarization At -40mv more Ca+ moves in through open L-type Ca channels moving potential upto +40 Phase 3 - repolarization ca+ channels closes at + 40 and K+ channels open resulting in K+ to move out of the cell. At end of repolarization K+ closes

16. Pace marker cells The rhythm of the heart is normally determined by a pacemaker site (SAN). The SAN generates an impulse at rate of 100-110 AP/beats per min. This intrinsic rhythm is strongly influenced by autonomic nerves by decreasing or decreasing slope of phase 4 hence reducing or increasing time required to reach threshold Sympathetic – increase HR by increasing funny channels activity Parasympathetic / vagal tone " reduces HR by reducing funny channels activity and increasing K +  permeability hence hyperpolarization The rate of SA nodal firing can be altered by: Changes in autonomic nerve activity Circulating hormones Serum ion concentrations Cellular hypoxia Drugs Abnormal cardiac rhythms can occur if The SA node fails to function normally (e.g., sinus bradycardia or tachycardia ) Impulses are not conducted from the atria to the ventricles through the AV node (termed AV block ) Abnormal conduction pathways are followed (e.g., accessory pathways between atria and ventricles) Other pacemaker sites within the atria or ventricles (e.g., ectopic pacemakers ) trigger depolarization Maximal Heart Rate = 220 beats/min − age in years

17. Conducting Tissue/system of the Heart It is a network that initiates ,conducts and distributes electrical Impulses within the cardiac muscles. It has modified/specialized cardiac muscle cells called nodal cells Bi-nucleated More gap junctions Fewer actin and myosin – contract less Auto- rythimic (nodal) cells Make up 1 % of cardiac mass Are self excitable/create / pacemake ) and conduct APs without neural stimulation).- Serve as a pacemaker to initiate APs provide a conduction system The components of the conducting system are as shown Sinoatrial node(SAN) Internodal pathways/fibers and interatrial pathway Atrioventricular node(AVN) Bundles of His Right & Left Bundle branches Punkinje fibers.

18. Conducting system SAN - pacemaker located in posterior wall of RA at junction of SVC at stria terminalis Small, flattened, ellipsoid strip of specialized cardiac muscles about 3 x 15 x 1mm. The fibers of this node have Almost no contractile muscle filaments Small ,elongated cells with fewer striations Creates potentials at 60-80 /min(highest of the other tissues ), hence sets the pace/rate of heart beat Innervated by sympathetic (raises HR) and parasympathetic (reduces HR) The sinus nodal fibers connect directly with the atrial muscle fibers hence makes muscles to contract as a functional syncytium. Internodal pathways – anterior, middle and posterior plus Bachmann’s bundle The impulse spread in atrial muscles by cell-to-cell conduction at a speed of 0.5 – 1 m/s Takes 0.03s from SAN to AVN AVN – has few gap junctions, and small diameter fibers hence slow conduction The atria and ventricle are separated by a non-conducting band called the annulus fibrosus – functioning as electrical insulator , auchor for valves and muscles AVN is the only electrical connection between Atria and ventricle Its located in the inferior-posterior region of the interatrial septum behind TV attachment Speed of transmission 0.05m/s hence slows down transmission by 0.09secs It slows the impulse conduction considerably (to about 0.05 m/sec) thereby allowing sufficient time for complete atrial depolarization and contraction (systole) prior to ventricular depolarization and contraction Bundle of His(AV bundle) – extension of AV node)- Further slowing at A-V bundle system(0.04s) It takes 0.16 secs for impulse started at SAN to reach the ventricular muscles The slow conduction in AVN and bundle is caused mainly by diminished numbers of gap junctions between successive cells. Bundle branches – right and left Punkinje fibers Conduct at a speed of 4m/s Spreads signals throughout the ventricle – from apex to base

19. Excitation-Contraction Coupling The term “excitation-contraction coupling” refers to the mechanism by which the action potential causes the myofibrils of muscle to contract Steps Action potential spread along the sarcolemma to the T-tubules (transverse tubules) Calcium enters the cell through Long acting (L)-voltage gated Ca+ channels a dyhdroperidine receptor (DHR) Ca+ induces Ca+ release from sarcoplasmic reticulum (S.R.) Local release causes Ca2+ spark then Summed Ca2+ sparks create a Ca2+ signal. Calcium binds to troponin unblocking binding sites on actin . Myosin heads attach to actin hence sliding passed each other (contraction) Calcium unbinds troponin and the binding sites on actin become blocked again by tropomyosin hence muscle relaxes Ca2+ is pumped back into the sarcoplasmic reticulum for storage and . Rest of ca2+ is exchanged with Na+. Cardiac muscle contracts when calcium levels in cytosol rises above 100mmol 20% of calcium required for contraction enters the cell during plateau phase. The rest is released from rough endoplasimic reticulum where it is stored bound to calsequetrin

20. ELECTROCARDIOGRAM (ECG)

21. An Overview of the Electrocardiogram As the heart undergoes depolarization and repolarization , the electrical currents that are generated spread not only within the heart, but also throughout the body. This electrical activity generated by the heart can be measured by an array of electrodes placed on the body surface( limbs and chest). The changes are transcribed onto graph paper to produce an electrocardiogram (commonly known as an ECG). The instrument used to record the electrical changes is called an electrocardiograph. How is ECG taken The six chest leads (V1 to V6) “view” the heart in the horizontal plane. The information from the limb electrodes is combined to produce the six limb leads (I, II, III, aVR , aVL , and aVF ), which view the heart in the vertical plane. The information from these 12 leads is combined to form a standard electrocardiogram.

22. Direction of wave form The direction of the deflection on the ECG depends on whether the electrical impulse is travelling towards or away from a detecting electrode. Impulse travelling directly towards the electrode produces an upright (“positive”) deflection relative to the isoelectric baseline Impulse moving directly away from an electrode produces a downward (“negative”) deflection.

23. Recording of ECG Waves. The repeating waves of the ECG represent the sequence of depolarization and repolarization of the atria and ventricles. The ECG is recorded at a speed of 25 mm/sec (5 large squares/sec), and the voltages are calibrated so that 1 mV = 10 mm (2 large squares/10 small squares) in the vertical direction. Therefore, each small 1-mm square represents 0.04 sec (40 msec ) in time and 0.10 mV in voltage. Because the recording speed is standardized, one can calculate the heart rate from the intervals between different waves. An ECG consists of a set of waves: the P wave , a QRS complex ,and a T wave

24. Waves of ECG P wave Represents Depolarization of the atria Impulse travelling in atria muscles . Duration 2-3 small squares (0.08-0.12s) Amplitude Rarely exceeds 21/2 small squares (0.25 mV) Because atrias have relatively less muscle mass. Direction of wave Upright in leads I and II and inverted in lead aVR A negative P wave in lead I may be due to incorrect recording of the ECG ,(transposition dextrocardia , or abnormal atrial rhythms. PR interval Isoelectric line after P wave Represents time between atria l depolarization and ventricular depolarization Measured from the beginning of the P wave to the first deflection of the QRS complex Impulse travels in AVN, Bundle of His & Bundle branches Ranges between 3-5 small squares ( 0.12 – 0.20 s) Prolonged PR may mean bundle block QRS Represents depolarization of the ventricles Duration 1.5 - 2.5 small squares (0.10 s) normally 0.06 to 0.1 seconds, Greater voltage changes than the P wave because the ventricles have more muscle mass than the atria. If the QRS complex is prolonged (greater than 0.1 seconds), conduction is impaired within the ventricles ST segment - isoelectric period when the entire ventricle is depolarized Corresponds to the plateau phase of the ventricular action potential QT interval – ventricular depolarization and depolarization. Corresponds to action potential duration T wave – phase 3 represents repolarization of the ventricles Lasts longer than depolarization Atrial diastole does not show up on an ECG as an independent event because the voltage changes are masked by the QRS complex.

25. ECG Amplitute The amplitude of the waveform recorded in any lead may be influenced by The myocardial mass. The net vector of depolarisation . The thickness and properties of the intervening tissues The distance between the electrode and the myocardium. Patients with ventricular hypertrophy have a relatively large myocardial mass and are therefore likely to have high amplitude waveforms In the presence of pericardial fluid, pulmonary emphysema, or obesity, there is increased resistance to current flow, and thus waveform amplitude is reduced.

26. Cardiac Cycle Is the sequence of mechanical and electrical events that occur with one heartbeat A heart beat is divided into two phases and 7 sub-phases: Systole - Contraction and ejection from chamber Diastole – relaxation and filling of a chamber Normal heart rate of 75 beats/minute, Whereas each beat/cycle is about .8secs/ 800 milliseconds . Systole lasts about 270 milliseconds Diastole for about 530 milliseconds .

27. phase 1 – atrial systole Electrical vents Atrial depolarization, P wave on ECG takes 0.05 sec Mechanical events Atria muscle contracts following depolarization Atria pressures exceeds ventricular pressure AV valves open, aortic and pulmonic closed Blood moves from atria, across the open AV valves, and into the ventricle Accounts for 10-20 % of LV filling The movement of blood across a narrow valve causes turbulence producing 4 th heart sounds S 4 vibration of the ventricular wall during atrial contraction when mm are hypertrophied Retrograde atrial flow back into the vena cava and pulmonary veins is impeded by the inertial effect of venous return and by the wave of contraction throughout the atria, which has a “milking effect .

28. Phase 2 – isovolumetric contraction Duration – 0.02-0.03 sec Electrical vents Ventricles start depolarizing Mechanical events AV valves closes when ventricular pressure rises to approximately 5mmhg causing Closing produces 1 st heart sound H1 (~0.04 sec) Semilunar valve still closed(All valves closed) No movement of blood Ventricular muscle build tension though no change in length. Ventricular pressures increases LV -From 5 to the level of aortic pressure (after-load) i.e 80 mmhg RV- From 0 to 10 mmhg No change in ventricular volume No heart sound is heard

29. Phase 3 – rapid ejection Duration – 0.1 sec Electrical vents Ventricles still depolarizing Mechanical events Ventricular muscle contracts and reduces in length Ventricular pressures rises above arterial pressure LV- slightly > 80mmhg RV -slightly > 8 mmhg Aortic and pulmonary valves open Blood pours out of ventricles Approximately 60-70% of blood(stroke volume No heart sound heart sounds are ordinarily heard.

30. Phase 4 – reduced ejection Duration – 0.2 sec Electrical vents Ventricles still depolarizing Mechanical events Ventricular Muscle start to relax Ventricular pressure falls to just equal to arterial pressures Aortic and pulmonary valves still open and AV valves closed Outward flow still occurs owing to kinetic (or inertial) energy 30-40% of blood flows/ejected in the last 2/3 of ejection No heart sound heart sounds are ordinarily heard.

31. Phase 5 – isovolumetric relaxation Duration – 0.03 -0.06sec Electrical vents Ventricular repolarization (QRS) Mechanical events Ventricular muscle continues relaxing Ventricular pressure falls below arterial pressures Semilunar valve closes 2 nd heart sound produced by closing/snapping of the Semilunar valves Now semilunar valves closed when AV valves are still closed ( All valves closed ) No blood flow in or out of the ventricular chambers

32. Phase 6 – rapid filling Duration – 0.11 sec Electrical vents Ventricular repolarization (QRS) continues Mechanical events Ventricular muscle relax continuously. Ventricular pressures falls to equal or lower than atrial pressures AV valves open, semilunar valves closed Blood flows rapidly into the ventricles accounting for 70% of filling A Third Heart Sound (S3) may be audible during ventricular filling, due to tensing of chordae tendineae and the AV ring.

33. Phase 7 – reduced filling – diathesis Duration – 0.22 sec Electrical vents Ventricular repolarization (QRS) continues Mechanical events All chambers in relaxation Ventricular pressures equal to atrial pressures AV valves open, semilunar valves closed The filling is by direct flow from veins to ventricles and flow due to atrial contractions(20%)

34. The graphical representation of Phases

35. FUNCTIONAL VOLUMES OF THE HEART End diastolic volume (EDV) Volume of blood within either ventricle after full relaxation Stroke volume (SV) Volume of blood ejected in a single contraction End systolic volume ESV) Volume of blood within the ventricle after the end of full contraction Ejection fraction Proportion of end diastolic volume that is ejected in a single contraction expressed as a percentage Cardiac output Is the amount/volume of blood pumped out of either ventricle in one minute. Cardiac reserve Is the extra Cardiac output during exercise

36. CARDIAC OUTPUT Cardiac output is the volume of blood pumped out of the heart per min and its a function of stroke volume(EDV-ESV=70mls) and heart rate (72 BPM) = 5-6 litres Stroke volume is the volume of blood pumped out of the heart with each beat and its determined by end-diastolic volume (EDV)/pre load minus end-systolic volume ESV/afterload (=70mls). Variations in Cardiac output can be produced by changes in heart rate or stroke volume End systolic volume (ESV)/afterload is determined by peripheral resistance and contractility . Peripheral resistance is determined by viscosity of blood and tone of the vessels i.e constricted or dilated. Contractility is determined by muscle size which depends Sympathetic nervous system Hormones –T3 and T4, glucagon Drugs – digitalis , dopamine , epinephrine Age, gender, exercise,

37. Factors that determine EDV End diastolic volume/pre-load/stretch is determined by venous return and degree of stretch of cardiac muscle (muscle compliance). Venous return is determined by Venous valve integrity – Backflow of blood in veins of the limb, especially when standing, is prevented by valves. Pumping action of skeletal leg muscles – The contraction of skeletal muscles surrounding the deep vein compresses them pushing blood towards the heart Venous constriction(sympathetic tone) Filling time Respiratory pump During inspiration, the expansion of the chest creates a negative pressure within the thorax assisting flow of blood towards the heart. In addition when the diaphragm descents during inspiration the increased intra abdominal pressure pushes blood towards the heart.   Muscle elasticity/compliance depends on age, gender, intergrity and heart size Frank-starling law – the greater the stretch the greater force of contraction

38. Regulation of heart rate Intrinsic regulation Based on the automaticity of cardiac muscle cells The SAN sets the pace which then controls the rest of the cardiac musculature Extrinsic regulation Regulated by factors external to cardiac musculature Endocrine Catecholamines – adrenaline Thyroid hormones – T3 and T4 Neural regulation Control by autonomic nerves system Parasympathetic - -chronotropic action Sympathetic - + chronotopic action Ions - ca ++ - + chronotropic , K+ - inhibits Temperature r

39. Circulatory systems& Heamodynamics

40. WHAT IS CIRCULATION? Circulation is the movement of fluid(blood or lymph) to and from the cells of body and back to the heart. There are two (2) types of circulatory system. Cardiovascular circulatory system Lymphatic circulatory system

41. Lymphatic Circulation Fluid filtered at the capillaries find itself surrounding cells as tissue/interstitial fluid 90 % of the tissue fluid is absorbed by capillaries back to circulation The excess tissue fluid of about 10 % (3L/d) is absorbed by lymphatic vessels as lymph The lymph moves through a network of channels/vessels and nodes that filter lymph This vessels are blind ended, thin walled valved structures and finally drains into the venous system Function of lymphatic system Absorbs some tissue fluid Absorbs fats from the digestive system Filters tissue fluid of dead cells, bacteria , viruses, fungi Fight infections Its an filtered in capillary ends back to the heart

42. Cardiovascular Circulation Is the movement of blood from and to the heart through blood vessels.

43. Two pathway/routes of cardiovascular circulation. Systemic circulation Pulmonary circulation

44. FUNCTION OF VASCULAR SYSTEM The circulatory/vascular system serves two basic functions: Distribution/Transport of blood and its constituents from & to heart. Exchange of substances in blood with body tissues: i.e Nutrients, fluid/water , electrolytes, wastes, hormones, gases ( oxygen, carbon dioxide) e.t.c

45. What are blood vessels? The blood vessels are a closed system of conduits that carry blood from and to the heart.

46. TYPES OF BLOOD VESSELS. The arteries are further classified as elastic arteries, muscular arteries, and arterioles. Blood vessels are of three types: arteries , capillaries , and veins Veins are divided into venules and veins

47. FUNCTIONAL MORPHOLOGY Arteries and veins have three layers( tunica ) in their walls The layers/tunica are Intima/interna Endothelium Squamous epithelium Controls vessel permeability – exchange Plays role in hemostasis , inflammatory response and angiogenesis Promotes laminar blood flow Elastic lamina/fibers ), media/middle Has smooth muscles , elastic and collagen fibers Help in varying size of vessels lumen Externa / adventia (connective tissue ) Capillaries Wall made of single layer of endothelial cells and basement membrane. Types are Continuous – Gaps of 10nm E.g muscles, brain Fenestrated Gaps of 20 - 100nm E.g kidney , endocrine glands Sinusoidal Gaps of 600 – 3000 nm E.g liver , bone marrow

48. Functional morphology of Arteries Aorta and large arteries Have large amount of elastic tissue for stretching during systole and recoiling during diastole to allow for continuous flow of blood with the heart beat. Arterioles Their walls contain less elastic tissue and more smooth muscles The smooth muscles are innervated by autonomic nervous system allowing for significant reduction ( constriction) and increase ( dilatation ) in diamater The changes in diameter/caliber affect the resistance to blood flow small changes in their caliber cause large changes in the total peripheral resistance. Arterioles affects blood distribution(flow) and blood pressure.

49. Function of Capillaries Exchange of substances Nutrients, waste molecules, gases, water, electolytes Sphincter muscles, called precapillary sphincters , encircle the entrance to each capillary Not all capillary beds are open or in use at the same time. Most capillary beds have a shunt that allows blood to move directly from an arteriole to a venule (a small vessel leading to a vein) when the capillary bed is closed.

50. Function of veins & venules Collect & Carry blood from the capillary beds to the heart. Act as a blood reservoir. At any given time, more than half of the total blood volume is found in the veins and venules There are no valves in the very small veins, the great veins, or the veins from the brain and viscera.

51. Blood Flow Blood flow means simply the movement of blood from one point to another in the circulation. Blood always flows from areas of high pressure to areas of low pressure In our body blood flows from the heart to arteries to capillaries ,veins then back to the heart along a pressures gradient. The flow in the arteries is initiated by high ventricular force/pressure during systole/contraction which is maintained by recoil of arteries. Pressure is venous system is by compression of veins by muscular contraction and negative pressure in the thoracic cavity.

52. Types of Flow Laminar= Layered Flow. Turbulent- Non-layered flow. Occurs when Rate of blood flow becomes too great, Passes by an obstruction in a vessel. Makes a sharp turn, or It passes over a rough surface Reynolds number. D x Vel x d/ Vis

53. Determinants of Blood Flow Blood flow through a blood vessel is determined by two factors: pressure gradient and resistance The pressure gradient (or perfusion pressure) driving flow through an organ is the arterial minus the venous pressure. Which is the force that pushes the blood through the vessel, Vascular resistance is impediment to blood flow through the vessel Omns law

54. Resistance. Blood flow through organs (as well as through the entire systemic circulation) is determined largely by changes in resistance because arterial and venous pressures are normally maintained within a narrow range by various feedback mechanisms. Therefore, it is important to understand what determines resistance in individual vessels and within vascular networks Three factors determine the resistance (R) to blood flow within a single vessel: Vessel length(L),= directly proportional to vessel length. Blood viscosity Plasma =1.8x water Whole blood = 3-4x water(coz of RBC& proteins) Diameter (or radius, r) of the vessel. Blood viscosity normally does not change much; however, it can be significantly altered by changes in hematocrit and temperature and by low flow states. Vessel radius is the most important factor determining resistance to flow.

55. Methods for Measuring Blood Flow Blood flow can be measured by cannulating a blood vessel, but this has obvious limitations. Various devices have been developed to measure flow in a blood vessel without opening it. Electromagnetic flow meters Doppler flow meters. plethysmography

56. Velocity of Blood Flow Because the same volume(5L) of blood must flow through each segment of the circulation each minute, the velocity of blood flow is inversely proportional to vascular cross-sectional area In capillaries (0.05 cm/sec) whereas Aorta is 50cm/s The velocity of blood flow is slowest in the capillaries. What might account for this?

57. Why is velocity slow in cappilaries ? Each time an artery branches, the total cross-sectional area of the blood vessels increases, reaching the maximum cross-sectional area in the capillaries(6300). Conversely, blood flow increases as venules combine to form veins, and velocity is faster in the venae cavae than in the smaller veins.

58. What is the benefit of slow flow in cappillaries ? The slow rate of blood flow in the capillaries is beneficial because it allows time for the exchange of gases in pulmonary capillaries and for the exchange of gases and nutrients for wastes in systemic capillaries

59. Velocity of blood leaving and returning to heart. The cross-sectional area of the two venae cavae is more than twice that of the aorta, and the velocity of the blood returning to the heart remains low compared to the blood leaving the heart. In a resting individual, it takes only a minute for a drop of blood to go from the heart to the foot and back again to the heart! Blood pressure causes blood flow because blood always flows from a higher to a lower pressure difference.

60. Blood Pressure Blood pressure is the force of blood against a blood vessel wall. You would expect blood pressure to be highest in the aorta. Why? Because the pumping action of the heart forces blood into the aorta. Systemic blood pressure decreases progressively with distance from the left ventricle. Blood pressure is lowest in the venae cavae because they are farthest from the left ventricle.

61. Systolic, diastolic and mean pressure Blood pressure fluctuates in the arterial system between systolic blood pressure and diastolic blood pressure. Certainly, we can correlate this with the action of the heart. More important is the mean arterial blood pressure (MABP). What might determine MABP? One factor is cardiac output (CO) In other words, the greater the amount of blood leaving the left ventricle, the greater the pressure of blood against the wall of an artery

62. Systolic, diastolic and mean pressure Another factor that determines blood pressure is peripheral resistance, which is the friction between blood and the walls of a blood vessel. All things being equal, the smaller the blood vessel, the greater the resistance and the higher the blood pressure.

63. Pressure changes along vascular network. Pressures (note the differences of systemic and pulmonary circulation) Aorta = 120/80mmhg Cappilaries – systemic 30 -10 mmhg mean =17 mmhg - pulmonary mean 7 mmhg .

64. Volumes of Blood in the Different Parts of the Circulation 84% = systemic circulation, 64% in veins, venules & venous sinuses 13% in arteries 7% in arterioles and capillaries 16 % = heart and lungs. 7 % Heart 9% pulmonary vessels

65. Evaluating Circulation Taking a patient’s pulse and blood pressure are two ways to evaluate circulation.

66. Pulse The surge of blood entering the arteries causes their elastic walls to stretch, but then they almost immediately recoil. This alternating expansion and recoil of an arterial wall can be felt as a pulse in any artery that runs close to the body’s surface, termed pulse points

67. Pulse It is felt by placing several fingers on the radial artery, or the common carotid artery, Normally, the pulse rate indicates the rate of the heartbeat. because the arterial walls pulse whenever the left ventricle contracts. The pulse is usually 70 times per minute, but can vary between 60 and 80 times per minute.

68. Blood Pressure Blood pressure is usually measured in the brachial artery with a sphygmomanometer, an instrument that records changes in terms of millimeters (mm) of mercury A blood pressure cuff connected to the sphygmomanometer is wrapped around the patient’s arm, and a stethoscope is placed over the brachial artery.

69. BLOOD EXCHANGE & CVS REGULATION BY DR . ANDAMBI

70. Capillary Exchange The primary function of the cardiovascular system is to ensure that blood reaches the capillaries where exchange of nutrients and waste products occur. The pumping of the heart sends blood by way of arteries to the capillaries.

71. Rate of exchange Mechanism of exchange include: Filtration Osmosis Diffusion Passive Active Vesicular transport – Pinocytosis/endocytosis

72. Movement of Fluid Across the Capillaries The movement of fluid across the capillaries is determined by the difference between The forces that pull/push the fluid out of the capillaries and Forces that pull/push the fluid into the capillaries. Such forces are a result of the processes of osmosis and filtration

73. Forces that pull fluid out of cappilary Interstitial fluid osmotic pressure The force tends to pull the fluid out of the capillaries into the interstitial compartment. This force is a result of the large particles present in the interstitial compartment. There are few particles, such as proteins, present in this compartment as they are removed quickly by the lymphatic capillaries. This force is, therefore, very small, only about 0.1–5 mm Hg.

74. Forces that push fluid out of cappilary Blood hydrostatic pressure This pressure is generated by the pumping action of the heart and is equivalent to the blood pressure in the capillaries. The hydrostatic pressure is comparable to the force that pushes water out of a leak in a garden hose; if the tap is opened further, more water gushes out of the leak. The blood hydrostatic pressure is about 35 mm Hg.

75. Forces that push fluid into of cappilary Interstitial hydrostatic pressure Tends to push the fluid back into the capillaries. This is the pressure of fluid between the cells. Normally, there is little fluid in the tissue spaces as they are removed by the lymphatic vessels. In the body, this pressure is negligible—about 0 mm Hg.

76. Forces that pull fluid into of cappilary Blood colloid osmotic pressure Created by the particles inside the blood that are unable to move out of the capillaries Endothelial wall of the capillaries is Permeable to water and some solutes Impermeable to larger particles. The plasma proteins are mainly responsible for this force, which is about 26 mm Hg.

77. NET MOVEMENT The net balance of all of these pressures determines whether fluid leaves or stays inside the capillaries. If the net pressure that pushes fluid out of the capillaries is more than the net pressure that pulls fluid in, fluid would move into the interstitial compartment (filtration). If the net pressure that pulls fluid into the capillaries is more than the net pressure that pushes the fluid out, fluid would move into the capillaries ( reabsorption )

78. TISSUE FLUID The internal environment of the body consists of blood and tissue fluid . Tissue fluid is simply the fluid that surrounds the cells of the body. The force tends to pull the fluid out of the capillaries into the interstitial compartment.

79. A capillary has an arterial end (contains arterial blood) and a venous end (contains venous blood). In between, a capillary has a midsection.

80. NET FLUID REABSORPTION About 85% of the fluid in the body that moves into the interstitial compartment moves back into the capillaries. The remaining fluid and the proteins that may have escaped into the interstitial compartment are removed by the lymphatic vessels and returned to the circulatory system. Everyday, about 3 liters of fluid are returned to the circulatory system by the lymphatic vessels. If excessive fluid accumulates in the interstitial compartment, it is termed edema.

81. Lymphatic Capillaries Lymphatic vessels are a one-way system of vessels. Notice that lymphatic capillaries have blind ends that lie near blood capillaries Lymphatic vessels have a structure similar to that of cardiovascular veins, except that their walls are thinner and they have more valves

82. What is lymph? The fluid carried by lymphatic vessels Has the same composition as tissue fluid. Why? Because lymphatic capillaries absorb excess tissue fluid at the blood capillaries.

83. Edema Edema is localized swelling that occurs when tissue fluid accumulates. Edema can be caused by several factors: An increase in capillary permeability; A decrease in the uptake of water at the venous end of blood capillaries due to a decrease in plasma proteins; An increase in venous pressure; or insufficientuptake of tissue fluid by the lymphatic capillaries. Another cause of edema is blocked lymphatic vessels. e.g filiariasis / elephantiasis. DO GIRAFFES DEVELOP EDEMA?

84. REGULATION OF THE CARDIOVASCULAR SYSTEM.

85. Regulation of the Cardiovascular System The ultimate objective of the cardiovascular system is to ensure that the tissue blood flow meets the demands for oxygen and nutrients at the right time and region This is achieved by manipulating the Cardiac output (output of the heart), Peripheral resistance (changing the diameter of resistance vessels), and Altering the amount of blood pooled in the veins.

86. REGULATAORY MECHANISMS Three regulatory mechanisms are involved : Local mechanisms, Neural mechanisms, and Endocrine mechanisms.

87. LOCAL MECHANISMS The tissues are able to regulate, to some extent, their own blood flow (a utoregulation). Autoregulation can be compared to the water supply to our houses. A pumping station pumps water to houses in a certain locality. However, individuals in each house are able to regulate the water according to their needs. Similarly, the heart pumps blood to the body, but each organ has the capacity to regulate the blood flow to it according to its needs.

88. How is autoregulation achieved? On short term basis it is brought about by the accumulation of “vasodilator substances.” or vasoconstrictor substances. On long term basis tissues can increase or decrease the number and length of blood vessels. New blood vessels may be formed ( angiogenesis) or blood vessels that are already present may be remodeled ( vascular remodeling).

89. Neurohumoral Control of the Heart and Circulation Autonomic nerves and circulating hormones serve as important mechanisms for regulating cardiac and vascular function. These mechanisms are controlled by sensors that monitor Blood pressure ( baroreceptors ), Blood volume(volume receptors), Blood chemistry( chemoreceptors ), and Plasma osmolarity ( osmoreceptors ).

90. NEURAL MECHANISMS The heart & blood vessels are innervated by the sympathetic nerves The nerves produce vasoconstriction in almost all tissue. Except skeletal muscle they produce vasodilatation. The sympathetic nerves are controlled by groups of neurons located in the medulla oblongata known as the vasomotor area or vasomotor center. The activity of the vasomotor center and, thereby, that of sympathetic nerves, is altered by many factors.

91. sensors Peripheral sensors such as baroreceptors are found in arteries, veins, and cardiac chambers. They have afferent nerve fibers that travel to the central nervous system, where their activity is monitored and compared against a “set point” for arterial pressure. Central Sense changes in chemistry

92. AUTONOMIC NEURAL CONTROL Autonomic regulation of cardiovascular function is controlled by Cerebral cortex. Hypothalamus Medulla –primary site Sensors

93. Function of different centers Regions within the medulla contain the cell bodies for the parasympathetic ( vagal ) and sympathetic efferent nerves. The hypothalamus plays an integrative role by modulating medullary neuronal activity, Higher centers, including the cortex, connect with the hypothalamus and medulla. The higher centers can alter cardiovascular function during times of emotional stress

94. NEUROHUMORAL CONTROL OF THE HEART AND CIRCULATION. Schematic representation

95. Adrenergic and muscarinic receptors in the heart and blood vessels.

96. ENDOCRINE MECHANISMS Many hormones in the circulation have an effect on blood pressure, volume, and flow. It is brought about by direct effect on the smooth muscles of blood vessels or on the kidney tubules. Example of hormones adrenaline and nonadrenaline Vasopressin or antidiuretic hormone Aldosterone angiotensin II

97. COMPENSATORY ADJUSTMENT The cardiovascular system must be able to adapt to changing conditions and demands of the body. For example During exercise Gravitational changes

98. During exercise Increased metabolic activity of contracting skeletal muscle requires large increases in nutrient supply (particularly oxygen) and enhanced removal of metabolic by-products (e.g., carbon dioxide, lactic acid) To meet this demand, blood vessels within the exercising muscle dilate to increase blood flow; however, blood flow can only be increased if the arterial pressure is maintained. Arterial pressure is maintained by increasing cardiac output and by constricting blood vessels in other organs of the body If these changes were not to occur, arterial blood pressure would fall precipitously during exercise, thereby limiting organ perfusion and exercise capacity

99. What happens when a person stands up? Gravitational forces cause blood to pool in the legs when a person assumes an upright body posture In the absence of regulatory mechanisms, this pooling will lead to a fall in cardiac output and arterial pressure, which can cause a person to faint because of reduced blood flow to the brain. To prevent this from happening, coordinated reflex responses increase heart rate and constrict blood vessels to maintain a normal arterial blood pressure when a person stands. The major compensation is caused by the stimulation of the carotid sinus and aortic arch baroreceptorswhen there is a slight drop in blood pressure. It is important to control arterial blood pressure because it provides the driving force for organ perfusion.

100. THE END