Physiology of the cardiovascular system Part 1

Transcription

1 Physiology of the cardiovascular system Part 1 Physiological properties of the cardiac muscle automacy and rhythmicity, conductivity, excitability, contractility. The cardiac cycle. Heart sounds. Arterial pulse. Regulation of the cardiovascular system. Practical tasks Physiological properties of the cardiac muscle Auscultation of the heart sounds Examination of the arterial pulse Experiments on an isolated heart Katarína Babinská MD, PhD, MSc, Institute of Physiology CU, Bratislava

2 Transmembrane potential electrical potential exists across the membranes of almost all cells in the body - also in the cardiac muscle cells electrode out oscilloscope shows a potential difference = transmembrane potential a cell electrode in resting membrane potential - unstimulated cell - shows a straight line action potential - after stimulation shows a curve with a typical shape mv 0 t (ms) mv Changes of the potential are due to ion flows

3 Physiological properties of the cardiac muscle Activity 1: List the physiological properties of the cardiac muscle (in both English and Greek terminology) and define them in 1 sentence. 1. Automacy and rhythmicity (Chronotropy) ability of the cardiac muscle cells (sinus node) to generate spontaneously action potentials at a regular pace (= self-excitation) 2. Conductivity (Dromotropy) ability to transmit the excitation generated in the sinus node to all the heart muscle fibres in a pre-defined pattern via a specialised conducting system 3. Excitability (Bathmotropy) ability of the cardiac muscle cells to respond to the incoming excitation by AP - when the stimulus arrives to the cardiac muscle cells it causes their depolarization 4. Contractility (Inotropy) capability of the cardiac muscle to respond to a stimulus by contraction

4 1. Automacy and rhythmicity (Chronotropy) ability of the cardiac muscle to generate spontaneously action potentials at a regular pace (= self-excitation) Sino-atrial (SA) node (sinus node) generator of electric activity of the heart small strip of cardiac cells in superior/postero/lateral wall of the right atrium (close to the opening of vena cava superior) cells capable of self-excitation at regular intervals (normally /min) from SA node the excitation is spread to all cardiac muscle cells, therefore SA node = the heart pacemaker (the only normal pacemaker)

5 Mechanism of the sinus nodal rhytmicity Activity 2: Draw and describe the curve of transmembrane potential in the sinus node (names of the periods, ion changes, voltage, duration). mv Sinus node unquiet cells instant changes in transmembrane potential - no real resting membrane potential ( straight line ) - minimum value: -55 mv t (ms) Curve of transmembrane potential in sinus node

6 Phases of the transmembrane potential in the sinus node 1. Spontaneous diastolic depolarization (SDD, praepotential) - a slow increase of the transmembrane potential (from -55 mv to a less negative value) - without any external stimulus!!! -at the beginning Na + ions leak through the funny channels into the cardiac muscle cells - membrane is untight for Na + (cause slow depolarization) -later T-type of Ca 2+ voltage gated channels are activated (at about -50 mv) -due to higher concentration in ECF the Ca 2+ ions move slowly in concentration gradient inwards (slow depolarization proceeds) -these channels are specific for the pacemakers!!! Curve of transmembrane potential in sinus node

7 2. Depolarization after the threshold -40 mv is reached a steep rise in transmembrane potential occurs allowed by opening of the L-type Ca 2+ voltage gated channels Ca ++ ions move from extracellular space (in concentration gradient) into the cells and cause depolarization of the sinoatrial cells overshoot to positive values (transpolarization) Curve of transmembrane potential in sinus node

8 3. Repolarization - Ca 2+ channels get inactivated - K + channels open - K + moves outwards - the transmembrane potential returns to its minimum value Curve of transmembrane potential in sinus node

9 Positive and negative chronotropic effect Baseline Positive Negative

10 2. Conductivity (Dromotropy) Activity 3: Draw a scheme of heart and indicate how the action potential is spread to the atria and ventricles. - excitation travels from the sinus node to all the heart muscle fibres in a predefined pattern via a specialised conducting system The cardiac muscle includes - working myocardium (main function: contraction/pumping) - conduction system (main function: fast transmission of action potentials)

11 Conduction pathways include: excitation of the atria from the SA node to all muscle cells of atria 1. from a muscle cell to the neighbouring ones via gap junctions (0,3 1 m/s) 2. interatrial bundles anterior, middle, posterior (1 m/s) cardiomyocytes specilized on conductivity (from SA node to the AV node) excitation of the ventricles - AV node the only pathway from atria to ventricles (because atria and ventricles are separated by a non-conductive fibrous tissue) SA node to AV node (velocity 1 m/s) : through the A-V node (0,03 m/s) bundle of Hiss (2 m/s) right and left bundle branch (Tawara branches) Purkinje fibres (2-4 m/s) cardiac muscle cells (0,3 m/s)

12 Duration of the transmission of AP from SA node to myocardium first depolarization (and also contraction) the of atria occurs 0,00 s 0,03 s 0,16 s 0,22 s depolarization (and also contraction) of ventricles occurs with a time delay 0,17 s delay is caused by a slow transmission through the AV-node 0,19 s 0,18 s the delay allows for efficient function of the heart as a pump first contract the atria slightly later contract the ventricles

13 Gradient of cardiac automacy not only the cells of SA node, also other parts of the conduction system are capable of self excitation - however at slower pace: atrio ventricular node Purkinje fibres 40 60/ minute 15 40/ minute - these also begin their self-excitation (at the same time as SA node) - normally they do not get self-excited because the action potential from SA node arrives here faster and causes their excitation - they produce potentials only in abnormal cases sino-atrial node = heart pacemaker (the only normal) ectopic (secondary) pacemakers other than S-A node - abnormal (e.g. junctional rhythm generated in AV node)

14 Cardiac muscle syncytium - cells connected by gap junctions - allow the transport of ions, i.e. transmission of AP from one cardiac muscle cell to another - all the cells of working myocardium are activated (and contracted) as one unit

15 3. Excitability (Bathmotropy) Activity 4: Draw and describe the curve of transmembrane potential in a cardiomyocyte of working myocardium (periods, ion changes, voltage, duration). phase 0 - depolarization opening of fast voltage gated Na + channels, Na + moves into the cardiac muscle cell transpolarization (upstroke) transmembrane potential: mv phase 1 - early repolarization fast Na + channels inactive, K channels open phase 2 - plateau opening of L type voltage gated Ca ++ channels (inflow if ions) channels open slowly and remain open for longer time than fast channels K channels remain open ms phase 3 - repolarization K + channels are open (K outflow) phase 4 - resting membrane potential ions are restored by pumps Curve of transmembrane potential in working myocardium

16 yes no Refractory periods in the cardiac muscle Absolute refractory period (ARP) period of action potential when cardiac muscle cells do not react to next stimulation at all in myocardium it has a long duration protection from: a/ tetanic contraction of the myocardium b/ premature depolarization (that would make the heart pump less effective the heart would have insufficient time to get filled with blood) Relative refractory period (RRP) follows the absolute refractory period - myocardium is more difficult to stimulate responds only to very strong excitatory signals Extrasystole abnormal premature stimulation resulting in systole ARP RRP extrasystole compensatory pause no no yes ms

17 The all or nothing principle the cardiac muscle operates according to the all or nothing principle insufficient stimulation (subthreshold stimulus) causes no contraction (no response) of a cardiac muscle fibre sufficient stimulation (threshold and suprathreshold stimulus) causes maximum contraction of a cardiac muscle fibre according to the all or nothing law operate both 1. individual cardiac muscle fibres - similarly to the skeletal muscle 2. the heart as a whole - in contrast to striated muscle because myocardium is a syncytium action potential is quickly transmitted to all heart muscle cells through gap junctions, thus they are activated in one time subtheshold threshold suprathreshold stimulus stimulus stimulus no response maximum maximum contraction contraction

18 4. Contractility (inotropy) excitation/contraction coupling

19 Neurotransmitters and drugs with effects on the heart Automacy and rhythmicity (chronotropy) - Positive chronotropic effect increased automacy (faster generation of AP) - Negative chronotropic effect decreased automacy (slower generation of AP) Conductivity (dromotropy) - Positive dromotropic effect faster conduction of the AP - Negative dromotropic effect slower conduction Excitability (bathmotropy) - Positive bathmotropic effect higher excitability of the cardiac muscle - Negative bathmotropic effect lower excitability of the cardiac muscle Contractility (inotropy) - Positive inotropic effect stronger contraction of the cardiac muscle - Negative inotropic effect weaker contraction of the cardiac muscle

20 The cardiac cycle The cardiac cycle is the series of events comprising a complete contraction and relaxation of the heart's four chambers: 1. filling of the ventricles (diastole of the ventricles) 2. period of isovolumic (isometric) contraction of the ventricles 3. period of ejection 4. period of isovolumic relaxation of the ventricles

21 1. Filling of the ventricles (ventricular diastole) starts after previous systole when ventricles relax intraventricular pressures fall below atrial pressures the AV valves open and ventricular filling begins (great pressure difference) the blood flow during ventricular filling generates the third heart sound (S3) - by tensing of chordae tendineae and AV ring during ventricular filling Filling of the ventricles has 3 periods: 1A. Rapid filling 1B. Slow filling 1C. Systole of the atria generates the fourth heart sound (S4) at the very end of the ventricular filling, the ventricular volumes are maximal = the end-diastolic volume (EDV) the left ventricular EDV is typically about 120 ml

22 2. Isovolumetric contraction a rapid increase in myocyte tension and intraventricular pressure as intraventricular pressure exceeds atrial pressure - the AV valves close closure of the AV valves results in the first heart sound (S1) (the 1st sound is caused by the closing of the AV valves + vibration of the myocardium) ventricular pressure rises rapidly without a change in ventricular blood volume (no ejection occurs so far) ventricular blood volume does not change because all valves are closed during this phase ("isovolumic" or "isovolumetric )

23 3. Ejection when the intraventricular pressures exceed the pressures within the aorta and pulmonary artery, which causes the aortic and pulmonary valves to open pressure gradient propels blood into the aorta and pulmonary artery from their respective ventricles Pressures in the ventricles (systole) left ventricle 125 mm Hg right ventricle 25 mm Hg about 70 ml of blood are ejected = stroke (systolic) volume ejection fraction = systolic volume/ end-diastolic volume (normal value in the rest: 60 %)

24 4. Isometric (isovolumetric) relaxation the ventricles relax the intraventricular pressures fall (below in aorta and pulmonary artery) pressure in aorta and pulmonary artery exceeds the pressure in the ventricles the aortic and pulmonary valves abruptly close causing the second heart sound (S2) In diastole the pressures in the ventricles fall to left ventricle 0 mm Hg right ventricle 0 mm Hg end-systolic volume - the volume of blood that remains in a ventricle (50 ml in the left ventricle) left atrial pressure continues to rise because of venous return from the lungs.

25 Task: Auscultation of the heart sounds

26 Heart sounds heart sounds are the noises (sound) generated during the cardiac cycle (lub-dub) sounds are examined by - auscultation by a stethoscope - phonocardiography a curve is recorded the first sound (systolic) lub the first of the paired heart sounds, following the longer diastolic period generated by closing of AV valves (bicuspid and tricuspid) and vibrations of ventricular myocardium the second sound (diastolic) dub generated by closing of semilunar valves shorter duration and higher frequency than the first heart sound the third sound generated by blood flow into ventricles during the period of rapid filling the fourth sound generated by the systole of atria usually first and second sound are audible, the third and fourth rarely

27 Task: Auscultation of the heart sounds - examine in a quiet place - the patient may lie or sit 1st sound (is examined on 2 spots) A/ tricuspid valve 5 th intercostal space, parasternally on the right (left) B/ bicuspid valve 5 th intercostal space, medioclavicular line, left 2nd sound (is examined on 2 spots) A/ aortic valve 2 nd intercostal space, parasternally, right B/ pulmonary valve 2 nd intercostal space, parasternally, left - evaluate rhythm/accent (regular) - synchronisation (normally closing of 2 valves generates 1 synchonized sound) -the 3 rd and 4 th sounds are only sometimes audible mainly in children, young adults - examine when lying on the left side, slightly leaning to the front Murmurs - abnormal heart sounds produced by abnormal patterns of blood flow in the heart (e.g. due to defective heart valves)

28 Measurement of the arterial pulse

29 Arterial pulse - systole - ejection of blood from left ventricle into aorta - aorta and large arteries elastic type of arteries - rise in volume/pressure in aorta - distention of the aortic vessel wall diastole systole diastole Pulse (wave) - a wave of vibration of the vessel wall caused by ejection of blood during cardiac systole that is transmitted down the aorta and arteries -it can be plapated over superficial arteries - central pulse: carotid artery, a. femoralis (branches of aorta) - peripheral pulse: radial a., popliteal a., etc.

30 Arterial pulse a pulse wave Velocity of the pulse wave 1. is higher than velocity of the blood flow!!! 2. inverse association with arterial elasticity therefore increases with age (elasticity drops down due to atherosclerosis) 3. decreases with the diameter of the vessel - caused by closing of the aortic valve) more elastic less elastic

31 Measurement of pulse 1. by palpation - 2 (3) fingers are put over the artery (usually a. radialis, a. carotis) - can be determined by palpation of any artery 2. sphygmography registration of a pulse curve by an instrument - pulse is mostly measured/determined per 1 minute - if measured for 30 seconds - multiply by 2 - if measured for 15 seconds - multiply by 4 - most precise value is obtained by 1 min measurement (due to heart rate oscilations) Examination of pulse informs about: - the cardiac function (heart rate) - the function of vessels not palpable pulse probably no blood flow

32 Evaluation of the pulse examination 1. frequency normal / min bradycardia <60/ min (normal in sleep, trained people, abnormal causes: e.g. hypothyrosis, heart disease) tachycardia (pulsus frequens) >100/ min (normal in physical activity, stress, abnormal causes e.g. hyperthyrosis, heart disease) 2. rhythm regular / irregular In previous times also other qualities of the pulse were evaluated 3. amplitude large/small (magnus/parvus) 4. velocity of the pulse wave increase (celer/ tardus) 5. suppressibility (mollis easily suppressive, durus hardly suppressive) Task: a/ find the pulse over different arteries (carotid, radial, popliteal, dors. pedis, etc.) b/ measure the a pulse rate / min in a volunteer c/ evaluate if the pulse rate is: normal/abnormal, reular/irregular

33 Regulation of the cardiac function Autoregulation: Frank - Starling mechanism (law) Autonomic nervous system Norepinephrine (symp. neurotransmitter) Sympathetic mimetics (adrenergic effect) Stimulation of frequency contractility conductivity excitability Acetylcholine (neurotransmitter) Inhibition of: frequency conductivity Parasympatethic mimetics Parasympathetic lytics Sympatethic mimetics Sympathetic lytics Inhibitory effect (parasympathetic like) Simulation (delete parasymp. inhibition) Stimulation (sympathetic-like effect) Inhibition (delete sympathetic effect) Humoral regulation Epinephrine (hormone) Ions - calcium (Ca 2+ ) - potassium (K + ) Thyroxine Glucagon stimulatory effect all physiological properties contractility (the heart may stop in systole) automacy, batmotropy (heart may stop in diastole) - stimulates automacy (+ increases sensitivity to catecholamines, therefore other physiological properties are stimulated, too) Increased heart rate and force Effect of the temperature - higher body temperature stimulation (higher permeability of cell membranes to ions) - lower body temperature inhibition (lower permeability of cell membranes to ions)

34 Protocol Task: Sim Heart - Sim Heart is a simulation program that monitors the cardiac activity and the effects of cardio-active drugs - you will administer different cardioactive drugs to yor patient and monitor their effect - the cardiac action will be shown by a curve determined by its frequency and amplitude Evaluate (for each substance given) the effect of your treatment chages in frequency (heart rate chronotropy) changes in amplitude (strength) of the cardiac contraction - inotropy substance A substance B

35 Your patient need the following substances include A/ Neurotransmitters 1. sympathetic: epinephrine (adrenaline, Adr) stimulatory effect on the cardiac muscle (the cardiac muscle has mainly beta1 receptors) 2. parasympathetic: acetylcholine (ACh) generates inhibitory effect on the cardiac muscle B/ Calcium blockers - cardio-active drugs - calcium - decisive role in the electromechanical coupling of cardiac contraction - due to limited intracellular calcium storage the heart is dependent on the calcium flowing in from the extracellular space - calcium blockers like verapamil block the calcium channels

36 C/ Substances with competitive effect (antagonists, inhibition) the action of neurotransmitters can be suppressed by specific blockade of their receptors with appropriate receptor antagonists (competitive inhibition). atropine competes for the muscarinic a receptors and it is inhibitor of the ACh propranolol blocks the epinephrine action by binding to beta receptors, phentolamine binds to adrenergic alpha receptors D/ Cardiac glycosides (digitalis glycosides) - cardio-active drugs increase the force of heart contraction tendency to (e.g. strophantin) trigger arrythmias

37 5. Transfer the selected tube into the apparatus and preset the dose (100) 6. Start testing the effects of a substance by pressing the arrow down and arrow left - to stop testing press the STOP button 4. Choose the appropriate concentration: always Select a substance 1. Switch on 2. Change the settings Speed 1 cm/s Resolution 5mV/Div the curve of basal activity of the heart will appear

38 Protocol / Results - Indicate if the effect was positive (+), negative (-) or no change was observed (0) - Draw a curve of the change Substance Epinephrine Chronotropy Inotropy Curve Acetylcholine Verapamil Atropine Epinephrine, then add α blocker phentolamine Epinephrine, than add β blocker propranolol Strophantine

39 Task: Physio Ex Click PhysioEx Choose Exercise 6 Cardiovascular Physiology - Perform Activities 2, 3, 4,5 - You are not expected to perform the pre-lab or post-lab quiz - In menu always choose the option Experiment - Do the experiments according to the procedure on the left side - Answer also the questions - When ready, submit your data, go to Lab report and generate PDF (name it with your names) - PDF will be sent to you by , please complete it at home and bring next week to the practicals results/anwers to the questions will be discussed