Cardiovascular System PDF

Cardiovascular system Friday, November 15, 2024 6:15 PM CARDIAC CONDUCTION SYSTEM The heart originates from cardiac pacemaker cells that...

Cardiovascular system Friday, November 15, 2024 6:15 PM CARDIAC CONDUCTION SYSTEM The heart originates from cardiac pacemaker cells that generate spontaneous action potentials. Pacemaker cells, have the responsibility of setting the rhythm and the pace of the heartbeat. SA node 60-100/min ( establishes what's known as normal sinus rhythm ) == main pacemaker AV node and bundle of his 40-60/min Purkinje fibers 30-40/min Initiation of cardiac electricity activity Interventricular septum Signal pathway Pacemaker cells : Purkinje fibers In right atrium Close to the superior vena cava SA node has high intrinsic rate and causes spontaneous depolarization Action potential spread from right to left AV node receives action potential from the SA node Don't have stable resting membrane ( RMP about -60 mV ) Internodal pathway : ( transmit signal from SA node to AV node ) Bechman (posterior internodal pathway ) Wenckeback ( middle internodal pathway ) Thorel ( anterior internodal pathway ) AV Node Delay: Delay: ~0.1 milliseconds. Purpose: Allows atria to contract fully before ventricles contract. ↠ Without delay: Atria and ventricles would contract simultaneously, disrupting blood flow. Conduction Velocities: Fastest: Purkinje fibers and Bundle of His. Middle: SA node. Slowest: AV node Contractile Myocardial Cells (Non-pacemaker cells): Function: Generate force for heart contractions. Structure: Contain actin, myosin, troponin (C, T, I), and tropomyosin for contraction. RMP: -90 mV to -95 mV (stable). Pacemaker cells : No resting potential ( no plateau = no true RMP ) Spontaneous depolarization and repolarization Rising phase is slow Non-pacemaker cells : True resting potential ( plateau ) == Flat RMP Prolonged sharp depolarization Rising phase is Fast Electrophysiological mechanism of pacemaker cells in the heart 1. Funny Sodium Channels (HCN) ( slow depolarization ) ○ Slow Na⁺ influx raises membrane potential from -60 to -55 mV ( depolarization threshold ) 2. T-Type Calcium Channels ( transient type and helps membrane potential to reach the threshold ) ○ Open at -55 mV, causing Ca²⁺ influx, raising potential to -40 mV. 3. L-Type Calcium Channels ( depolarization ) long lasting ○ Rapid Ca²⁺ influx from -40 mV to +40 mV 4. Repolarization: ○ K⁺ channels open; K⁺ efflux, resetting membrane potential (-90 mV ) Phases of Action Potential in Cardiac Contractile Cells (myocardial cells ) Phase 0 - Rapid depolarization : Na+ influx ( -90 mV → +10 mV ) Phase 1 - Initial repolarization : K+ efflux ( +10 mV → 0 mV ) Phase 2 - Plateau : L-type Ca2+ influx , K+ efflux ( 0 mV → +10 mV ) Phase 3 - Repolarization : K+ efflux ( +10 mV → -90 mV ) Phase 4 - Resting potential : K+ rectifier channels stay open ( -90 mV ) -70 PS : phase 1 and phase 2 are only present in the contractile cells not in pacemaker cells ECG Correlation 1. PR interval : Atrial depolarization + AV node delay ( PR segment ) == pushing blood from atrium to ventricle 2. QRS Complex: Ventricular depolarization / atrial repolarization == pumping blood from ventricles into the aorta and pulmonary artery 3. T Wave: Ventricular repolarization ( recovery phase ,preparing for the next heartbeat ) Propagation of depolarization in ventricular myocytes muscle cells of the ventricles that contract to pump blood out of the heart. When a myocyte becomes depolarized (positively charged inside), it triggers neighboring cells to depolarize by passing the electrical charge through the gap junctions. Gap junctions channels Gap Junctions + Desmosomes = Intercalated Discs: Allow electrical activity to spread from pacemaker cells to contractile cells. Enable heart muscle to contract as a single unit. We have 6 types Allow ions to pass easily when open Very tight RyR2 Phospholamban: Enhances calcium release from the sarcoplasmic reticulum. And activates the cAMP-PKA pathway. PKA phosphorylates phospholamban, which reduces its inhibition of the SERCA pump in the Sympathetic nervous system sarcoplasmic reticulum. Enhanced SERCA activity pumps more calcium into the sarcoplasmic reticulum, increasing calcium 1. Activation : Norepinephrine (NE) or Epinephrine (Epi) binds to beta-1 adrenergic receptors in the heart. availability for the next contraction. 2. G-Protein Activation : The receptor activates the Gαs protein (stimulatory G-protein), which switches GDP to GTP. More calcium is released during systole, leading to stronger heart contractions (positive inotropic 3. Adenylyl Cyclase: Gαs stimulates adenylyl cyclase, an enzyme in the cell membrane. effect). 4. cAMP Production : Adenylyl cyclase converts ATP into cAMP (cyclic AMP), a second messenger. Blood Pressure Increase: Stronger contractions boost cardiac output, leading to increased blood 5. PKA Activation : cAMP activates Protein Kinase A (PKA). pressure. 6. Calcium Channel Action : PKA phosphorylates L-type calcium channels, increasing calcium influx into heart cells. 7. Effects on the Heart - Positive Chronotropic Effect : Faster heart rate (tachycardia) due to SA node stimulation. The SERCA pump (Sarcoplasmic Endoplasmic Reticulum Calcium ATPase) is a - Positive Dromotropic Effect : Faster electrical conduction speed through the AV node. vital protein found in the muscle cells, including those of the heart. It plays a - Positive bathmotropic Effect : Increase excitability of the heart muscle crucial role in maintaining the proper balance of calcium ions (Ca²⁺) within - Positive ionotropic Effect : Increase contractility of heart muscle cardiac cells, which is essential for muscle contraction and relaxation. ↑ Temperature == sympathetic nervous system activation Parasympathetic nervous system 1. Acetylcholine Release : The vagus nerve releases acetylcholine (ACh) onto the heart. 2. M2 Receptor Activation : ACh binds to M2 muscarinic receptors on the SA node and AV node of the heart. ↠ Beta-gamma complex connect to calcium channels 3. G-Protein Activation : M2 receptors are linked to an inhibitory GI protein ( beta-gamma complex ), which is activated by ACh. 4. Inhibition of Adenylyl Cyclase : Gαi inhibits adenylyl cyclase, reducing the production of cAMP. 5. Effects on Ion Channels : - Decreased cAMP reduces activity of L-type calcium channels, decreasing calcium influx. - Potassium channels are opened, increasing potassium efflux, which hyperpolarizes the cells (makes them less excitable). 6. Effects on Heart - Negative Chronotropic Effect: Slower heart rate (bradycardia) due to SA node suppression. - Negative Dromotropic Effect: Slower conduction speed through the AV node T3-T4 hyperthyroid ↠ ↑ HR T3-T4 hypothyroid ↠ ↓ HR Digoxin ( medication commonly used to treat heart failure and certain types of arrhythmias ) Inhibition of Na+/K+ ATPase Pump: Digoxin inhibits the Na+/K+ ATPase pump in the heart cells. This pump typically moves sodium (Na⁺) out of the cell and potassium (K⁺) into the cell. When digoxin blocks this pump, sodium accumulates inside the cell. This increase in intracellular sodium reduces the activity of another ion exchanger, the Na+/Ca²⁺ exchanger, which normally removes calcium (Ca²⁺) from the cell in exchange for sodium. As a result, intracellular calcium levels rise because less calcium is pumped out, leading to increased calcium availability for muscle contraction. Positive inotropic effect (increased force of contraction) Negative chronotropic effect (slowed heart rate) Negative dromotropic effect (slowed conduction through the AV node) Cardiac Output (CO) The cardiac output (CO) is the amount of blood the heart pumps per minute ( normal : 5L/min ) CO = SV×HR SV = Stroke Volume (the volume of blood pumped out of the heart with each contraction) HR = Heart Rate (the number of heart beats per minute) Stroke Volume (SV) Stroke volume (SV) is the amount of blood pumped out by the heart in one beat. It's determined by the difference between the end-diastolic volume (EDV) and the end-systolic volume (ESV) SV = EDV−ESV EDV = The volume of blood in the ventricles just before they contract (when the heart is full) ( normal : 120-130 mL ) ESV = The volume of blood remaining in the ventricles after contraction (after the heart has pumped out blood) ( normal : 50-70 mL ) QRS Phases: Electrocardiogram 1. Initial Downward Deflection (Q wave): Depolarization of the interventricular septum. he ECG measures potential differences between + and - electrodes that are generated by electrical 2. Sharp Upward Deflection (R wave): Depolarization moving currents emanating from the heart during global depolarization. and repolarizationlamban towards apex. 3. Return to Baseline (S wave): Final depolarization of ventricles. Waves P Wave: Represents atrial depolarization (electrical activity causing atrial contraction). QRS Complex: Represents ventricular depolarization (electrical activity causing ventricular contraction) ≈ 0.06-0.1s ↠ closely realted to mass of myocardial tissue Q Wave: The initial downward deflection. R Wave: The first upward deflection. S Wave: The following downward deflection. T Wave: Represents ventricular repolarization (recovery phase of the ventricles). U Wave (sometimes present): Thought to represent late repolarization of the Purkinje fibers. Intervals and Segments PR Interval: Time from the start of the P wave to the start of the QRS complex, reflecting the conduction time through the atria and AV node. QRS Duration: The width of the QRS complex, indicating the time taken for ventricular depolarization. QT Interval: Time from the start of the Q wave to the end of the T wave, representing the total time for ventricular depolarization and repolarization. ( involved in sudden cardiac death ) ST Segment: The flat section between the end of the QRS complex and the start of the T wave, representing the isoelectric period when the ventricles are depolarized. RR interval : crucial to know how frequent the ventricles depolarize Mean vector : The mean vector in an ECG refers to the average direction and magnitude of electrical activity during a specific phase of the cardiac cycle. Depolarization towards the + pole ↠ positive deflection on ECG Depolarization towards the - pole ↠ negative deflection on ECG The depolarization wave begins in the left bundle branch and activates the interventricular septum, propagating from left to right. The vector generated by this activity points toward the right ventricle This movement creates a small downward deflection down to the mean electrical axis , towards the - pole on ECG After the septum depolarizes, the wave travels rapidly through the Purkinje fibers, activating the left and right ventricles simultaneously The left ventricle, being larger and more muscular, contributes the dominant electrical activity. The mean electrical vector points downward and to the left, roughly aligning with Lead II. Travels towards the + pole ( positive deflection ) As the depolarization wave continues, it spreads throughout the ventricular walls, completing activation of both ventricles. The mean electrical vector begins to reorient slightly upward and toward the left, directed more toward the base line The electrical activity now moves away from the positive pole, toward the negative electrode. This creates a small downward deflection (S wave) on the ECG as the depolarization ends. Cardiac cycle The cardiac cycle consists of two main phases: systole (ventricular contraction) and diastole (ventricular relaxation). It describes the events that occur during one heartbeat, allowing blood to be pumped throughout the body. Systole (Ventricular Contraction) 1. Isovolumetric Contraction (Initial Phase of Systole) Definition: The ventricles contract without changing their volume because both mitral and aortic valves are closed. Key Features: ○ Left ventricular pressure increases. ○ Mitral valve closes to prevent backflow into the left atrium. ○ Volume remains constant; pressure builds up. ○ ECG Correlation: The QRS complex indicates ventricular depolarization, triggering this phase. ○ LVEDV (Left Ventricular End Diastolic Volume): Blood volume before ejection (~120 mL). 2. Ejection Phase Definition: Blood is ejected from the left ventricle into the aorta. Sub-Phases: ○ Rapid Ejection: Forceful ejection of blood; occurs early. ○ Reduced Ejection: Gradual, slower ejection; occurs later. Key Features: ○ Aortic valve opens as left ventricular pressure exceeds aortic pressure. ○ LVESV (Left Ventricular End Systolic Volume): Residual blood after ejection (~50 mL). ○ ECG Correlation: The T wave represents ventricular repolarization. Diastole (Ventricular Relaxation) 1. Isovolumetric Relaxation Definition: Ventricles relax without a change in volume as both aortic and mitral valves are closed. Key Features: ○ Aortic valve closes, preventing backflow from the aorta. ○ Pressure drops rapidly within the ventricle. ○ Ends when the mitral valve opens, allowing filling. 2. Filling Phase Definition: Blood flows into the ventricle from the left atrium. Sub-Phases: ○ Rapid Filling: Most blood enters passively. ○ Reduced Filling: Slower, gradual filling. Key Features: ○ 90% of filling occurs passively during diastole. ○ Atrial contraction contributes ~10%. ○ Atrial systole (P wave on ECG) ensures final ventricular filling. Additional Events in the Cardiac Cycle Heart Sounds S1 (Lub): Closure of mitral and tricuspid valves during isovolumetric contraction. S2 (Dub): Closure of aortic and pulmonary valves at the start of isovolumetric relaxation. ○ Splitting occurs when aortic valve closure precedes pulmonary valve closure. S3 Sound: When: Early diastolic filling (rapid filling phase). Normal in: Children. Pathological in Adults: Associated with dilated left ventricles (e.g., cardiomyopathy). S4 Sound: When: Late diastole, during atrial contraction. Cause: Blood being pushed into a stiff ventricle. Seen in: Older adults with hypertension or hypertrophic hearts. Ejection Fraction Definition: Percentage of blood ejected from the ventricle during systole. Normal Range: 55-60%. Low Values: Indicative of heart failure (can drop to 15%). Summary of Key Pressures and Volumes LVEDV (120 mL): Volume before contraction. LVESV (50 mL): Volume after ejection. Ejection Fraction: Measures efficiency of the heart’s pumping ability. ) (= ' At a given flow is directly related to resistance ∆# = % + ' A condition with double the resistance requires double the pressure gradient ( delta P ) to maintain the same flow (L) Increased body weight --> increases R (L) Decreased body weight --> decreases R ( r ) is high --> vasodilation ( r ) is low --> vasoconstriction ( if r decreases , R increase ) Laminar vs turbulent flow Turbulence occurs when the smooth, laminar flow is disrupted, usually due to high velocities, narrowed vessels, or irregularities like plaques. Turbulence causes vibrations that are heard as a "murmur" or 'bruit" Perfusion pressure = MAP - CVP: MAP (Mean Arterial Pressure): The driving force for blood flow. CVP (Central Venous Pressure): Pressure in the venous system ≈0 mmHg Neurohumoral determinants of arterial pressure : Autonomic nervous system : – Sympathetic vs parasympathetic effects – Baroreflexes Circulating catecholamines Renin-angiotensin-aldosterone system Anti-diuretic hormone Natriuretic peptides ( ANP , BNP ) Effects of Sympathetic Activation on Arterial Pressure ↑ SVR (Systemic Vascular Resistance) (vasoconstriction) ○ α-adrenergic receptors, coupled to Gq-protein and IP₃, signal transduction pathway in vascular smooth muscle. ↑ CO (Cardiac Output: ↑ HR and ↑ SV) ○ β-adrenergic receptors coupled to Gs-protein and cause an increase in cAMP in the heart. ○ Increased blood volume (through renal β-adrenergic receptor activation of RAAS) and cardiac preload. ↓ CO (Cardiac Output: ↓ HR and ↓ SV) ○ M2 receptors coupled Gi-protein and causes decrease in cardiac cAMP ○ Vasovagal syncope ( a common type of fainting (syncope) that occurs when the body overreacts to certain triggers, such as prolonged standing, stress, pain, or the sight of blood. It is caused by a sudden drop in heart rate (bradycardia) and blood pressure, which reduces blood flow to the brain, leading to temporary loss of consciousness.) Local Factors that Affect Blood Pressure Dilation ○ PGE/PGI2/PGF = Prostaglandins ○ NO (Nitric Oxide) ○ Endothelial ○ Relaxation ○ Vascular smooth muscle cell Contraction ○ Ang-II (Angiotensin II) ○ Ca²⁺ ○ Thromboxane ○ Bacterial endotoxins ○ Stress ○ Bradykinin ○ Trauma ○ Substance P ○ ACh (Acetylcholine) ○ Thrombin