MBChB Control of the Cardiovascular System - Year 1 PDF

Control of the Cardiovascular System MBChB Year 1 Dr Craig Lygate [email protected]  Functions of the CV system Transport of nutrients, oxygen, waste products around the body Thermoregulation (generally core to skin) Buffers body pH and electrolytes...

Control of the Cardiovascular System MBChB Year 1 Dr Craig Lygate [email protected]  Functions of the CV system Transport of nutrients, oxygen, waste products around the body Thermoregulation (generally core to skin) Buffers body pH and electrolytes Transport of hormones (e.g. adrenaline from adrenals) Assists in response to infection Note: must respond rapidly to changes in metabolic demand  Intended learning objectives By the end of this session you should be able to: - 1. Describe the sequence of the cardiac cycle 2. Describe how the heart initiates and conducts impulses 3. Identify the parts of the Electrocardiogram (ECG) 4. Describe the events which lead to contraction of the heart muscle  Basic cardiac anatomy Superior Pulmonary artery vena cava 120 25/10 /80 Pulmonary veins 0-4 8-10 Inferior vena cava 120/10 25/4 [Numbers are pressure in mmHg: systolic / diastolic]  Heart valves Valves ensure blood flow only occurs in one direction Opening and closing of a valve is determined by the pressure gradients across the valve (i.e. it is passive) Atrioventricular (AV) valves are between atria and ventricles Chordae tendinae and papillary muscles stop them opening under pressure – they have no role in valve opening Semilunar valves control blood movement into the exit arteries (aorta and pulmonary artery) Valve insufficiency (e.g. due to calcification or stenosis) causes regurgitation of blood, which can lead to heart failure Aortic regurgitation Cardiac function 6 The Cardiac Cycle Consists of systole (contraction) and diastole (relaxation) of the atria and then the ventricles Wiggers diagram Aortic pressure (AP) Left atrial pressure (LAP) LV Pressure (LVP) LV volume ECG Heart sounds 7 phases of cardiac cycle For an interactive version see: - 7 https://library.med.utah.edu/kw/pharm/hyperheart/  Phase 1: Atrial systole AV valves open; aortic & pulmonary valves closed LVEDP SA node initiates P wave on ECG Active filling to top-up ventricle: ‘a wave’ Contributes 10-40% of LV filling LVEDP = LV end-diastolic pressure S4 is due to blood turbulence during 8 atrial contraction  Phase 2: Isovolumetric contraction All valves closed QRS complex; LV depolarisation LV & papillary muscles contract AV valves close – S1 ‘lubb’ sound Rapid ↑P with no change in volume LV geometry becomes spherical 9  Phase 3: Rapid ejection Aortic & Pulmonary valves open LVP > aortic P → valve opens P difference only a few mmHg Max. outflow velocity occurs Atria continue to fill, but P dips due to atrial relaxation 10  Phase 4: Reduced ejection Aortic & Pulmonary valves open T- wave repolarisation LV muscle starts to relax Rate of ejection ↓ Atrial pressures gradually rise due to continuous venous return 11  Phase 5: Isovolumetric relaxation All valves closed Dicrotic notch - valve closing LVP ↓ rapidly LVP < aortic P → valve closes S2 short sharp ‘dupp’ sound Aortic P rebounds (dicrotic notch) and remains high due to elastic recoil and TPR LVESV = LV min. vol. (~50ml) 12  Phase 6: Rapid filling AV valves open; aortic & pulmonary valves closed Mitral valve opens LVP < atrial P → AV valves open LVP ↓ despite filling due to continued relaxation: creates diastolic suction And rapid, passive filling S3: due to filling turbulence is heard in young or if EDP high 13 Atrial P ↓ rapidly  Phase 7: Reduced filling AV valves open; aortic & pulmonary valves closed Passive filling almost complete ↓ pressure gradient = ↓ filling LVP ↑ with filling and LV become stiffer (less compliant) Prolonged phase at rest 14  Measuring systolic function Stroke Volume (ml) = End Diastolic Volume – End Systolic Volume - Amount of blood ejected with each beat (note: always some residual volume) Cardiac Output (L/min) = SV (L) x HR (min-1) Cardiac Index = CO/Body Surface Area Ejection Fraction (%) = SV / EDV x100 - Fraction of the End Diastolic Volume that is ejected - Used as a clinical indicator of cardiac contractility - Normal >60%; depressed 100 BPM) originating in the ventricle ‘Sustained’ if lasting >30s and can lead to fibrillation and death STEMI ST elevation is indicative MI Reflects injured cells shifting baseline of ECG upwards  Intended learning objectives By the end of this session you should be able to: - 1. Describe the sequence of the cardiac cycle 2. Describe how the heart initiates and conducts impulses 3. Identify the parts of the Electrocardiogram (ECG) 4. Describe the events which lead to contraction of the heart muscle What happens in the cardiac muscle cells? Sarcomere (1.6 – 2.2µm) Cardiomyocyte Z line Z line Thick filament Thin filament 100µm Sarcomere Sliding filament theory: Cross-bridge formation generates active tension Excitation-contraction coupling: ↑[Ca 2+]i Myosin head: hydrolyses ATP required for actin and myosin cross bridge formation Mitochondria Myofibrils Troponin complex: Sarcomere TnI – inhibits actin-myosin binding 10µm TnC – conformational change with Ca2+ binding moves TnI from myosin binding site allowing cross-bridge Actin Tropomyosin formation = contraction Excitation-contraction coupling in cardiomyocytes Action potential causes membrane depolarisation Ca2+ enters via L-type calcium channels Ca2+-induced calcium release from sarcoplasmic reticulum (SR) amplifies signal Cross-bridge formation at myofilaments = contraction Removal of Ca2+ via sodium-calcium exchanger (NCX) and re-uptake into SR = relaxation Intrinsic contractility (inotropy) is determined by Ca2+ levels and myofilament sensitivity From Bers, DM (2002) Nature 415, 198-205  Regulation by Adrenoceptors Exist in α and β forms with subtypes of each Heart contains predominantly β1 on nodal tissue, conducting system and the myocardium Bind norepinephrine (NE) released by sympathetic nerves but also circulating adrenaline (epinephrine) Increases intracellular Ca2+ Effects are: - Positive inotropy (contractility) - Positive chronotropy (heart rate) - Positive dromotropy (conduction speed) - Positive lusitropy (relaxation) Agonists e.g. dobutamine can support the heart in acute decompensated heart failure β-blockers e.g. bisoprolol used in chronic heart failure to reduce workload Determinants of Ventricular Function Contractility (inotropy) Preload Afterload Stroke Volume Heart rate Cardiac Output 29 Afterload The load against which the heart has to work to eject blood Determined by aortic pressure, aortic compliance, and total peripheral resistance (TPR) E.g. hypertension or aortic stenosis increase afterload Failing heart sensitive to afterload since less able to generate higher pressures to open valves and eject blood Sarcomere (1.6 – 2.2µm) Preload Preload = myocyte stretch prior to contraction Markers: end-diastolic volume (EDV) or pressure (EDP) ↑ sarcomere length means more overlap between filaments allowing for more cross-bridge formation = ↑ force Determined by venous return, LV compliance & function Note: preload generates more force, but the “intrinsic contractility” (inotropy) is not altered  Preload: the Frank-Starling law ‘The heart contracts more forcefully during systole when it is filled to a greater extent during diastole’ Family of Frank-Starling Curves: (LV function) afterload or inotropy shifts curve down and to right afterload or inotropy shifts curve up and to the left (i.e. preload) Failing hearts have impaired F-S response due to ventricular dilation resulting in too much stretch and less filament overlap Example of the Frank-Starling mechanism Myocyte stretch results in ↑ force generation Higher venous return stretches myocytes, invokes the F-S mechanism and thereby increases force of ejection Important in balancing output of both ventricles on a beat- to-beat basis Arrythmia causes premature contraction, prolonging time to next beat Highlighted beat is more forceful due to the longer filling time (stretch due to ↑venous return invoking F-S mechanism) More blood is ejected and balance is returned  Summary Phases of the cardiac cycle using Wiggers diagram (Pressure, volume, ECG, heart sounds) Parameters of systolic function: CO = SV x HR Beat initiation & electrical conduction: SAN, AVN, purkinje, action potentials, gap junctions Normal ECG and examples of arrhythmia Both branches of the autonomic nervous system can affect cardiac function E-C coupling elevates intracellular calcium which activates filaments in the sarcomere to generate force (↑Ca2+ = positive inotropy) Function is modified by afterload and preload Preload ↑ force generation due to myocyte stretch i.e. Frank- Starling mechanism (inotropy unchanged)