CVS: Basic and Advanced Concepts PDF

BHCS2001, 2013 & 2018 CVS: Basic and Advanced Concepts Dr Nicola King  Learning Outcomes 1. Be able to describe the importance of pressure in the CVS 2. Revise the cardiac cycle 3. Revise Starling’s law of the heart and its relationship to filling pressure 4. Unde...

BHCS2001, 2013 & 2018 CVS: Basic and Advanced Concepts Dr Nicola King  Learning Outcomes 1. Be able to describe the importance of pressure in the CVS 2. Revise the cardiac cycle 3. Revise Starling’s law of the heart and its relationship to filling pressure 4. Understand the effect of sympathetic activation and exercise on the pressure volume loop 5. Be able to describe the adjustments made in response to orthostasis  Pressure profile Resistance vessels across the R = (P1 – P2) / flow Pressure, mmHg circulation. regulate arterial pressure cause of clinical hypertension - a very important Venous pressure figure! 5–10mmHg Slow capillary flow Mean Facilitate velocity exchange cm/s Velocity (cm/s) = Flow (cm3/s) Big capillary area Area (cm2) Total cross-sectional area (cm2) es s riole illari ries ntr s Vein Arte Arte L ve Cap Haemodynamics: arterial pressure pulse Measurement of Blood Pressure Summary of Ventricular Cycle Mitral v. Aortic v. Aortic v. Mitral v. closes opens closes opens Atrial Ventricular systole Ventricular diastole systole Iso- Iso- Filling vol. Ejection vol. Filling cont. relax. 0 0.17 s 0.35 s 1 second  Ventricular volume changes Mitral v. Aortic v. Aortic v. Mitral v. closes opens closes opens Atrial Ventricular systole Ventricular diastole systole Iso- Iso- Filling Ejection Ejection fraction Filling vol. vol. Atrial = SV / EDV cont. relax. boost Normal value 2/3rd or more; lower values in heart failure. SV, 80 ml EDV 120 ml Rapid Slow Rapid Slow ESV, 40 ml ejection ejection filling filling 0 0.17 s 0.35 s 1 second 7 Cycle of pressure changes in atria, L ventricle & aorta Mitral v. Aortic v. Aortic v. Mitral v. closes opens closes opens Atrial Ventricular systole Ventricular diastole systole Iso- Iso- Filling vol. Ejection vol. Filling cont. relax. Incisura Aorta Left atrium Left ventricle 0 0.17 s 0.35 s 1 second  Recap  Pressure does not fall uniformly across the vascular system. Where does the biggest change occur and why does this happen?  Which valves are open during isovolumetric relaxation?  During what phase of the cardiac cycle does the greatest change in ventricular volume occur?  During what phase of the cardiac cycle does the rapid rise in ventricular pressure occur? The pressure–volume loop (left ventricle) Ejection Area = Stroke work (Pressure x volume = work) Isovolumetric Isovolumetric relaxation contraction Filling 10 Timing of valves, heart sounds & ECG Mitral v. Aortic v. Aortic v. Mitral v. closes opens closes opens Atrial Ventricular systole Ventricular diastole systole Iso- Iso- Filling vol. Ejection vol. Filling cont. relax. 1 2 Mitral & tricuspid closure Pulmonary v. closure Aortic v. closure 11  Central venous pressure J = Collapse jugular vein M = Manubriosternal angle A = right atrium a = Atrial contraction C = bulging of AV valves into atrium on closure X = atrial relaxation V = atrial filling – pressure rise, Vent systole Y = Av valves open, atrial pressure drop Hodder Arnold / An Introduction to Cardiovascular Physiology © 2010 J. Rodney Levick  Cardiac control Cardiac output = heart rate x stroke volume of one ventricle e.g. rest, 70 /min x 70 ml = 5 litres/min exercise, 180/min x 120 ml = 22 litres/min  Starling’s law of the heart (1914) ‘The energy of contraction - - - is (Arterial pressure proportional to the muscle fibre length at rest. Stroke held constant) volume (human) b lim Plateau ml i ng 70 e nd c As Normal, rest 5 10 15 Hodder Arnold / An Central venous pressure (mmHg) Introduction to Cardiovascular Physiology © 2010 J. The ’ventricular function curve’ or ‘Starling curve’ Rodney Levick  Laplace’s law - relates wall tension to internal pressure; too big is bad! P T If the RADIUS of the heart dilates excessively, and if ACTIVE TENSION has reached the plateau, R then the systolic PRESSURE generated by the contraction will FALL. 2T P [for a sphere] This reduces the STROKE VOLUME. R So, TREAT a dilated heart to reduce its distension Hodder Arnold / An Introduction to and thereby IMPROVE CARDIC OUTPUT Cardiovascular Physiology © 2010 J. Rodney Levick  What governs central venous pressure (CVP)? VOLUME OF BLOOD in the circulation reduced in haemorrhage DISTRIBUTION OF BLOOD between central and CVP peripheral veins. Sympathetic nerve activity regulates peripheral venous tone Gravity Standing ‘pools’ venous blood in legs, reducing CVP & stroke volume Movement (walking etc) operates the calf muscle pump, so raises CVP and stroke volume. Hodder Arnold / An Introduction to N.B. Venous return does NOT control cardiac output; Cardiovascular it IS the cardiac output !!! Physiology © 2010  Central venous pressure (CVP)  Right atrial pressure (RAP) How are  Right ventricle end-diastolic pressure (RVEDP) RV and  LV Right ventricle end-diastolic volume (RVEDV)  stroke Right ventricle end-diastolic fibre length  STARLING’S volumes Right ventricle energy of contraction LAW OF THE HEART  kept RV stroke volume  equal? Pulmonary blood volume and pressure  Pulmonary vein pressure, filling left atrium  Left atrial pressure (LAP)  Left ventricle end-diastolic pressure (LVEDP)  Left ventricle end-diastolic volume (LVEDV)  Left ventricle end-diastolic fibre length STARLING’S  LAW OF THE Left ventricle energy of contraction HEART  17 Left ventricle stroke volume  Recap  The closure of which valves produces the second heart sound?  What equation relates cardiac output to heart rate and stroke volume?  What does Starling’s law of the heart describe?  What happens if a heart over distends?  Name a determinant of central venous pressure  The ‘pump function curve’ – a high arterial pressure impairs outputPump-function curves Normal Stroke volume (ml) Wvalue 80 2 Starling 4 effect 3 1 Heart Normal failure heart 0 100 200 Mean arterial pressure (mmHg) Effect of sympathetic nerves on LV pressure 160 1. Faster ejection, increased dP/dtmax Stimulated, Left ventricle pressure (mmHg) increased contractility 2. Shorter ejection time Control 0 Time 3.Smaller end-diastolic volume, due to increased ejection fraction (>70%) 20 Family of ventricular function curves (Starling curves) ility 1-adrenoceptors 140 rct a – sympathetic nerve NAd t c on m) – adrenaline s ed pis – dopamine or stroke work (ml x mmHg) e a t ro – isoprenaline c r n o In e i ( + v Stroke volume (ml) rug e g d igoxin d 70 Lying Inotropic c tility Standing o n tr a o ma c E he r u c ed AILUR at Red ART F artery E y = H oronar c e.g 0 5 10 Diastolic filling pressure, EDP (mmHg) 21  How contractility alters the P–V loop Sympathetic stimulation; bigger stroke volume, 120 higher arterial pressure, bigger stroke work (PxSV), bigger ejection fraction. Left ventricle pressure (mmHg) 80 But smaller end-diastolic volume limits the size of the SV SV increase (Starling L.O.H.) Passive pressure– volume curve of ventricle 0 40 120 ESV EDV Volume of blood in left ventricle (ml) How contractility & the Starling effect combine. Optimal rise Sympathetic in SV due to stimulation; combined bigger stroke effect volume,of: 120 sympathetic higher drive arterial pressure, (reduced bigger strokeESV) work (PxSV), Starling bigger lawfraction. ejection of heart Left ventricle pressure (mmHg) (increased EDV) 80 Exercise: But smaller rise end-diastolic in filling pressure volume limits the due to peripheral size of the veno- SV SVconstriction increase (Starling L.O.H.) & muscle pump Passive pressure– volume curve of ventricle 0 40 120 ESV EDV Volume of blood in left ventricle (ml) Orthostasis creates a low cardiac filling pressure CVP CVP 0 mmHg 10 mmHg 3 mmHg 10 mmHg Venous Distribution of venous blood distension when supine: (‘pooling’), high central blood volume, +500 ml high cardiac filling pressure, 90  transmural large stroke volume (Starling’s law) pressure, 90 mmHg inside (‘trans’ ‘mural’ = ‘across’ ‘wall’) 0 outside (atmos) Immediate consequence of a fall in CVP  right stroke  left ventricular volume filling pressure Starling  left stroke volume Starling law  CVP law  arterial pressure  cerebral blood flow Exacerbated by: Symptoms of cerebral warmth (venodilatation) underperfusion: bed rest dizziness alpha-adrenoceptor blocker zero gravity visual fade Changes in BP & heart rate following orthostasis Reduced pulse pressure Arterial blood 80 Raised pressure mean pressure (mmHg) 90 Heart Raised heart rate rate (min-1) (baroreflex) 60 0 2 minutes Let’s have a 10-minute Fidget Break  Learning outcomes  Be able to describe the reflex control of the cardiovascular system  Be able to describe the ionic basis of cardiac excitability  Be able to describe excitation contraction coupling  Be able to describe the signal transduction processes that regulate heart rate  Be able to describe the utility of the ECG cardiovascular reflexes, depressor & excitatory Sensory receptors – Arterial baroreceptors – depressor (to BP) – Cardiac stretch receptors – some depressor (mixed) – Arterial chemoreceptors – excitatory – Muscle work receptors – excitatory Central pathways – Medulla relay station (nucleus tractus solitarius) to: – Vagal motor neurons (nucleus ambiguus) – Presympathetic neurons (rostroventrolateral medulla, RVLM) Effects (via sympathetics/vagus-regulation) – Heart – rate, stroke volume (contractility) – Resistance vessels – TPR – Veins – CVP 29 29 Hodder Arnold / An Introduction to Cardiovascular Physiology © 2010 J. Rodney Levick Location of arterial baroreceptors & chemoreceptors Glossopharyngeal n. (IX) IX, glossopharyngeal Nodose ganglion of vagus (X) Nodose ganglion X, vagus Carotid sinus n. Internal carotid a. Carotid sinus n. External carotid a. Carotid body Carotid body (chemoreceptors) (chemoreceptors) Carotid sinus (baroreceptors) Carotid sinus (baroreceptors) Common carotid a. at base of Common carotid Thyroid a. internal carotid artery Left vagus (X) Right subclavian a. Depressor (aortic) n. Aortic arch baroreceptors Aortic baroreceptors Ascending aorta Aortic bodies Aortic bodies (chemoreceptors) (chemoreceptors) 30  Regulation of the baroreceptor response Reflex effects of baroreceptor unloading (low BP, reduced firing) e. g. after haemorrhage  sympathetic activity, vagal parasymp. activity  Heart rate & contractility, aiding the CO Arteriolar vasoconstriction, so  TPR Venoconstriction, supporting CVP and SV These 3 effects can restore mean blood pressure, or at least minimise how far it falls, since: BP = CO x TPR Hodder Arnold / An Introduction to Cardiovascular Physiology © 2010 J. Rodney Levick Further reflex effects of baroreceptor unloading Adrenaline secretion ( sympathetic drive to adrenal medulla) Vasopressin secretion from posterior pituitary Angiotensin II formation (due to sympathetic stimulation of renin secretion by kidneys) Plasma volume expansion capillary absorption, due to  P following vasoconstriction c of resistance vessels antidiuresis, due to renal action of vasopressin (ADH) 33 Arterial chemoreceptors: key facts Located in carotid BODIES (not sinus) & aortic bodies Stimulated by CO2, H+ and hypoxia  stimulated by asphyxia & by haemorrhage (unlike baroreceptors) Reflex effects: vasoconstriction (via  sympathetic activity) raise blood pressure (important in severe haemorrhage) preservation of cerebral blood flow 34 Hodder Arnold / An Introduction to Cardiovascular Physiology © 2010 J. Rodney Levick  Nucleus tractus Signal cardiac Cardiac pain pain: Cardiac reflexes solitarius angina, heart attacks Cardiac vagal afferents Spinothalamic Myelinated Unmyelinated tract Myelinated Unmyelinated venoatrial atrial/ventricular mechano- mechanoreceptors Spinal receptors cord Signal over-distension Signal CVP PA & filling of heart in diastole RA LA Sympathetic Sympathetic/vagal afferents, afferents, unmyelinated unmyelinated nociceptors nociceptors Ventricles 35  Recap  Where are the baroreceptors located?  What happens if there is increased firing of the baroreceptors?  The secretion of which of the following is not increased following baroreceptor unloading?  Adrenaline  Vasopressin  Acetylcholine  Angiotensin II Central pathway regulating sympathetic outflow Cerebellum, Hypothalamus, Limbic system, Cortex M e d u lla Caudal ventro- CVLM lateral medulla RVLM Nucleus tractus Rostro-ventro- solitarius lateral medulla Bulbo- spinal Spinal transection fibres causes acute Sensory hypotension ganglia of IX & X IML Heart BP & blood Sympathetic vessels Baroreceptors ganglion 37  Cortex Hypothalamus/Limbic system Central pathways regulating vagal Medulla e.g. emotional faint parasympathetic Inhibitory input Inspiratory outflow to centre from inspiration pacemaker Nucleus centre sinus tractus tachycardia solitarius Nucleus ambiguus C o rte x Hy p oth a la mus /Limb ics yste m M e dula e.g.e motion Ins a lfa p in ire a t to c ntrre y tN ro s u ac lc le itta uu rs iu s s N uclie u s a mb guu s V pa ag r aly Se Ig a X n n & s g X o ry liaof fi bra es s mp ath etic B aro re ce pto rs Vagal parasympathetic Sensory fibres ganglia of IX & X BP Baroreceptors 38 Anatomy of the cardiac conduction system Bundle of His SA node Sub-endocardial Purkinje fibres Left bundle branch AV node Right bundle branch 39 Excitation-Contraction coupling in cardiac myocytes The arrival of an action potential, which penetrates deep into the myocyte through transverse tubules, triggers a sharp increase in the influx on calcium across the cell membrane through voltage gated calcium channels. Calcium binds to calcium release channels called ryanodine receptors which are located on the membrane of the sarcoplasmic reticulum. When calcium binds to the ryanodine receptors it stimulates release of calcium from the SR into the cytosol. This stimulates contraction, by binding to Troponin C, causing a conformational change, and  Ionic gradients govern cardiac excitability inward outward A variety of ion channels control inward and outward ionic fluxes, which determine action potential shape, height, duration  Cardiac conduction, action potentials and gap junctions Excitation is transmitted through the conduction system and myocardium by local currents acting ahead of the action potential. Internal current Conduction velocity is governed flows through the sarcoplasm and gap junctions by inward currents and gap of the intercalated disc. External current flows junctions (connexins) through the extracellular fluid. The currents Signal transduction pathways in a pacemaker cell and heart rate Altering the ionic environment can cause dangerous cardiac events Hypocalcaemia reduces myocardial contractility Extreme hypercalcaemia can arrest the heart in systole Hyperkalaemia can induce heart block and ventricular tachyarrhythmia/fibrillation Hypokalaemia induces arrhythmia in patients with existing cardiac dysfunction Ischaemia raises external [K+], and increases [H+]= compete with Ca2+ for TroPC binding site Hypoxia and ischaemia activate KATP channels, which  Recap  Where is the cardiorespiratory control centre located in the brain?  Describe the sequence of cardiac excitation  Describe the steps involved in excitation contraction coupling  What ion channel is responsible for the upstroke of the action potential?  What is an ECG ECG? (1 mV) -----+ ---+++ -+ ++ ++ ++++ Voltm ++ eterE calercdtiorog-raph - - - +++ +++ - - - Excitedm yocyte Restingm yocyte - - - + + + + + + + + + -- -- -- Excited myocyte Resting myocyte (100 mV) 46 Relation of Not detected ECG waves to action potentials of heart Intracellular Not detected recordings Endocardium Epicardium Extracellular recording PR interval Isoelectric ST segment