Physiology of the Heart - Cardiac Properties

Physiology of the Heart - Cardiac Properties

• Rhythmicity (automaticity) describes the heart's ability to generate regular electrical impulses independently of nervous control, enabling it to beat autonomously.

• Rhythmic cells found in the Sinoatrial Node (SAN), Atrioventricular Node (AVN), and Purkinje fibers exhibit automaticity.

• The intrinsic firing rate varies: SAN discharges at 90/min, AVN at 60/min, and Purkinje at 30/min.

• Rhythmic cells are characterized by spontaneous discharge, unstable membrane potential without a resting membrane potential (RMP), the absence of a plateau phase, higher permeability to Na+ and Ca++, a firing level of -40 mV, and a peak action potential (AP) of +10 mV.

Ionic Bases

• The membrane potential in rhythmic cells spontaneously decreases from -60 mV to -50 mV due to Na+ influx.

• At -50 mV, transient Ca++ channels (T-type) open, causing Ca++ entry and further depolarization to the firing level of -40 mV.

• The Prepotential represents the combined phases of membrane potential decrease and transient Ca++ channel activity.

• At -40 mV, long-lasting Ca++ channels (L-type) open, causing further depolarization, while transient Ca++ and Na+ channels close until +10 mV.

• Repolarization occurs due to K+ outflow through K+ channels, along with the closure of L-type Ca++ channels.

• At -60 mV, inactivation of K+ channels stops K+ efflux.

• The slope of the prepotential determines heart rate and an increased slope increases heart rate (tachycardia) while a decreased slope lowers it (bradycardia).

Factors Affecting Heart Rate

• Tachycardia results from sympathetic stimulation, catecholamines, increased temperature, hypokalemia (↓ K+), and thyroxin.

• Bradycardia results from parasympathetic stimulation, acetylcholine, calcium channel blockers (CCB), and hyperkalemia (↑ K+).

• Normal resting heart rate ranges from 70-80 bpm due to vagal tone.

Conductivity

• Conductivity refers to the ability of cardiac muscle to transmit excitation waves.

• The excitation wave originates in the Sinoatrial Node (SAN), proceeds through the internodal pathways to the atria, causing atrial contraction and ejection of blood to the ventricles.

• The wave reaches the Atrioventricular Node (AVN), delaying transmission. Then it moves via the Atrioventricular bundle and bundle branches to the Purkinje fibers and ventricular muscle, leading to ventricular excitation, contraction, and blood ejection to the aorta and pulmonary artery.

• Conduction rates vary such that the atrial pathway conducts at a rate of 1 m/sec.

• The AV node (AVN) conducts at 0.05 m/sec.

• The Bundle of His conducts at 1 m/sec.

• The Purkinje fibers conduct at 4-5 m/sec.

• The ventricular muscle conducts at 1 m/sec.

Conduction at the AV Node

• Slow conduction at the AV node (0.05 m/sec) is attributed to the presence of few gap junctions.

• Slow conduction at the AV node allows both atria to excite and contract, emptying blood into ventricles, and prevents abnormal atrial rhythms from reaching the ventricles.

Conduction at the Purkinje Fibers

• Rapid conduction at the Purkinje fibers (4-5 m/sec) is due to many gap junctions.

• Rapid conduction at the Purkinje fibers allows both ventricles to contract as a unit to eject blood.

Excitability and Action Potential in Cardiac Muscle

• The resting membrane potential (RMP) of ordinary cardiac muscle fibers is -90 mV, similar to skeletal muscle.

• The action potential is composed of five phases (0-4).

• Phase 0: Rapid depolarization from -90 mV to +20 mV, caused by Na+ influx through fast Na+ channels.

• Phase 1: Small rapid repolarization to +10 mV due to inactivation of Na+ channels, and K+ and Cl- efflux.

• Phase 2: Plateau where repolarization slows, the membrane potential is around zero mV for 200 msec due to a balance between Ca++ influx through long-lasting Ca++ channels and Na+ influx with K+ efflux.

• Phase 3: Rapid repolarization to RMP due to closure of long-lasting Ca++ channels, inactivation of Na+ channels, and activation of K+ channels.

• Phase 4: Resting membrane potential (RMP) at -90 mV due to selective permeability and Na-K pump activity.

Relationship between Action Potential and Mechanical Response

• Contraction starts just after the beginning of depolarization and reaches its maximum by the end of the plateau phase.

• Repolarization coincides with the first half of relaxation (diastole).

• Systole coincides with the period of depolarization until the end of the plateau.

• Diastole coincides with the period of rapid repolarization and continues in rest, because the mechanical response lasts one and a half times as long as action potential.

Relationship between Action Potential and Excitability Change

• The absolute refractory period coincides with the period of depolarization until the end of the plateau, during which excitability is lost.

• The relative refractory period coincides with the period of rapid repolarization, during which excitability is weak.

Relationship between Action Potential and ECG

• The QRS complex coincides with depolarization.

• The S-T segment coincides with the plateau.

• The T wave coincides with rapid repolarization.

Contractility (Excitation-Contraction Coupling)

• Contractility refers to the cardiac muscle's ability to contract and pump blood, beginning with the excitation of a cardiac wave.

• Excitation leads to Ca++ entry inside the cardiac muscle.

• Ca++ entry into the sarcoplasm triggers the release of a large amount of Ca++ from the sarcoplasmic reticulum through the Ca++ release channel.

• Ca++ binds to troponin-C, causing tropomyosin to uncover the active site of actin.

• Interaction between actin and myosin, followed by their sliding, leads to contraction.

• Removal of Ca++ from the sarcoplasm leads to relaxation.

Factors Affecting Contractility

• All or none rule: cardiac muscle contracts or does not contract at all.

• Increasing stimulus intensity beyond threshold will not change the strength of contraction, while stimulation below threshold will produce no response.

• Tetanus, a sustained contraction, cannot occur in cardiac muscle due to the long absolute refractory period (ARP), which coincides with systole.

Length-Tension Relationship

• The force of contraction of the heart is directly proportional to the initial length of the cardiac muscle fiber within limits (Starling's Law).

• Increasing the initial length of the cardiac muscle fiber increases the force of contraction, up to a certain length called L max, where all myosin cross-bridges bind to the active site of actin.

• Increasing length above L max decreases the force of contraction.

Force-Velocity Relationship

• The initial velocity of shortening of cardiac muscle is inversely related to the load moved during contraction.

• Increasing the load carried by the muscle decreases the initial velocity of shortening, and decreasing the load increases it.

Staircase Phenomenon

• Applying repeated stimuli to the cardiac muscle within a short time causes a staircase effect with the 2nd contraction stronger than the first and the 3rd stronger than the 2nd.

• The staircase effect continues until a new level of contraction is reached, attributed to increased Ca++ ions and failure of reuptake due to Ca++ pump weakness.

Inotropic State

• Inotropic state refers to the ability of cardiac muscle to develop force (contract).

• The contractile state can be increased (+ve inotropic) or decreased (-ve inotropic).

• Positive inotropic factors include sympathetic stimulation (ẞ1-adrenergic), catecholamines, glucagon hormone, digitalis, and xanthines/caffeine.

• All positive inotropic factors act through increasing Ca++ in the sarcoplasm.

• Negative inotropic factors include parasympathetic stimulation, acetylcholine, hypoxia (due to ischemia), calcium channel blockers (CCB), anesthetics, and anti-arrhythmic drugs.

Cardiac Output (CO)

• Cardiac output (CO) is the volume of blood pumped by each ventricle per minute. The normal CO is 5 L/min.

• The cardiac index (CI) is the volume of blood pumped by each ventricle per minute per square meter of body surface area. The normal CI is 3.2 L/min/m².

• Cardiac output is calculated as Stroke Volume (SV) x Heart Rate (HR).

• Normally: CO = 70 beats/min heart rate x 70 ml stroke volume = 5 L/min

• The cardiac output depends on heart rate and stroke volume.

• Stroke volume (SV) is the volume of blood pumped by each ventricle per beat.

• Stroke volume is calculated as End Diastolic Volume (EDV) - End Systolic Volume (ESV).

• Normally: SV = 135 ml EDV - 65 ml ESV = 70 ml.

• End Diastolic Volume (EDV) is the volume of blood in the ventricle at the end of diastole.

• End Systolic Volume (ESV) is the volume of blood in the ventricle at the end of systole.

Ejection Fraction (EF)

• Ejection Fraction (EF) is the fraction of the EDV that is ejected with each beat, such that EF = Stoke volume / End diastolic volume x 100.

• Normally, the ejection fraction is 55-75%.

• Importance: Assessment of contractility.

Variations of Cardiac Output

• Cardiac output is unchanged during sleep and moderate changes in external temperature.

• Cardiac output is increased during excitement (50-100%), exercise (300%), exposure to high temperature, eating (30%), epinephrine secretion, end of pregnancy, inspiration, and shifting from standing to recumbent position.

• Cardiac output is decreased during sitting or standing from lying position, rapid arrhythmia, and heart failure.

Control of Cardiac Output

• Heart Rate (HR): An increase of HR up to 200/min (e.g., during exercise) increases CO.

• Change of Preload: Preload determines muscle length before contraction.

• Ventricular preload is determined by EDV, which depends on venous return.

Starling's Law

• The more the end diastolic volume, the greater the force of contraction (within limits).

• An increase in EDV (preload) leads to an increase in SV, with a consequent increase in CO.

• Preload is mainly affected by venous return, which increases filling of ventricles, increases EDV, increases myocardial contractility, increases SV, and increases cardiac output.

Factors Affecting Ventricular Preload

• Increased venous return will increase preload.

• Decreased ventricular compliance decreases preload, as in myocardial infarction.

• Increased heart rate above 200/min decreases preload due to shortening of diastole, decreasing ventricular filling.

Effect of Afterload on SV

• Afterload is the load against which the ventricle contracts and ejects blood. The main afterload for the left ventricle is the aortic pressure.

• Increased afterload leads to decreased SV and CO, while decreased afterload leads to increased SV and CO.

Effect of Contractility (Inotropic State) on SV

• Positive inotropics increase contractility, ejecting more blood, increasing SV and CO.

Cardiac Reserve

• Cardiac reserve is the difference between cardiac output under ordinary circumstances and its maximum capacity for pumping blood.

• In normal young adults, cardiac reserve is 300%.

• Cardiac reserve is assessed by low-dose dobutamine stress echocardiography.

Mechanisms for modifying cardiac output

• Positive chronotropic condition (heart rate reserve)

• During rest: HR = 70 bpm

• During exercise: HR = 200 bpm

• Limitation: diastolic period is shortened

• Positive preload

• (EDV reserve)

• During rest: = 135 ml

• During exercise: increase venous return, ventricular filling and higher force of contraction

• Decrease afterload during exercise

• Resulting in decreased total peripheral resistance

• Positive inotropic conditions

• (ESV reserve)

• During rest: = 65 ml

• During exercise: sympathetic stimulation lead to increased force of contraction decreasing ESV leading to increased SV and COP

• Limitation: Amount of blood

• increaseForce of contraction causes higher SV and therefore COP

• Cardiac hypertrophy

• Cardiac hypertrophy may be Physiological or Pathological.

• Venous oxygen reserve:during rest

• O2 content in each 100 ml arterial blood:20 ml

• O2 content in each 100 ml venous blood:15 ml

• *- Thus blood supply to tissue = 5 ml 02

• During exercise: Blood supply to tissue increase up to 12 ml

Enzymes

• Enzymes are catalysts of chemical reactions, mostly globular proteins, and are essential for life as they occur at rates sufficient for life.

• An apoenzyme or apoprotein require a cofactor and together this is known as a holoenzyme.

• Cofactors may be inorganic including metal ions (e.g., zinc in carbonic anhydrase) and iron-sulfur clusters or organic which are prosthetic groups or coenzymes

• Coenzymes released from the enzyme's active site during the reaction, such as NADH, NADPH, and adenosine triphosphate.

Examples of Coenzymes

• Hydrogen carriers, such as NAD, NADP, FAD, FMN, HEAM, lipoic acid, glutathione, vitamin C, and CoQ.

• Isoenzymes (isozymes) catalyze the same reactions at different rates, have different affinities to substrates, and consist of multiple polypeptide chains.

Examples of Isoenzymes

• Lactate dehydrogenase (LDH) enzyme, formed of 4 polypeptide chains (H, M) existing as 5 isozymes, with isozyme 1 present in cardiac muscle, increasing in myocardial infarction and isozyme 5 present in the liver, increasing in hepatitis and liver diseases.

• Creatine kinase (CK), formed of 2 subunits (M, B) with CK-BB present in the brain that increase in brain tumors or infarctions, CK-MM in muscles that increase in muscle diseases, and CK-MB in cardiac muscles which increases in myocardial infarction.

Enzyme Activation

• Enzymes are activated through proteolysis from pepsinogen by HCL to pepsin, blood clotting factors being activated as prothrombin to thrombin and fibrinogen to fibrin.

• Metal ion activation may occur with the metal present in any position: (metal - enzyme - substrate), (enzyme - substrate, metal) or (enzyme - metal - substrate).

• Allosteric activation occurs when many enzymes contain another site other than the catalytic site named the allosteric site.

• Binding increases enzyme activity

• Covalent modification of the enzyme occurs by Phosphorylation and dephosphorylation of the enzymes which leads to change in its activity.

Enzyme Inhibition

• Enzyme Inhibition: can be A) Irreversible or B) Reversible (it may be either competitive or non competitive)

• Irreversible enzyme inhibition can be caused by factors producing denaturation (strong acids or bases), inhibitors of the sulfhydryl group (oxidizing agents or salts of heavy metals), antienzymes e.g α 1-antitrypsin deficiency which allows elastase to digest the pulmonary tissue in emphysema, and inhibition by removal of catalytic ions. EDTA prevents blood clotting and fluoride inhibits enolase enzyme of glycolysis.

• Reversible Enzyme Inhibition can be competitive by which there is structural similarity between the inhibitor and the substrate which affect affect the rate of the enzyme activity or Non Competitive Inhibition.

Non Competitive Inhibition:

• The Substrate and inhibitor bind different sites and increasing concentration of the substrate does not lead to change in the inhibitory process of the enzyme.

• Can be caused by Allosteric Inhibition when enzymes contain a site other than catalytic site. Binding to this site leads to change in the shape of the enzyme which doesn't favour the binding of the substrate as well as Feed Back Inhibition when The product inhibits the key enzyme or one of the substrates in the pathway.

Enzymes for Clinical and Biomedical Importance

• Specific enzymes are present in high concentration in certain organs and damage to certain organs may cause an elevation of enzymes useful in the diagnosis of certain diseases.

• The myocardium is rich in glutamate oxaloacetate transaminase „Lactate dehydrogenase and creatine kinase and any reduction of blood supply to the myocardium leads to an increase in those enzymes.

Diagnosis of myocardial infarction

• To diagnose myocardial infarction creatine kinase CK(MB ) is used along with glutamate oxaloacetate transaminase (GOT) and lactate dehydrogenase (LDH)

• The liver contains many enzymes but is is primarily for gluconeogenesis and lactate dehydrogenase for the anaerobic glycolysis.

• So, hpetitis is diagnosed mainly glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), alkaline phosphatase, and lactate dehydrogenase (LDH)

• The biliary tract contains many enzymes so obstructive jaundice show elevates alkaline phosphatase and gamma Glutamyl transferase (y GT). gamma Glutamyl transferase (y GT) is elevated in case of alcoholism and drug abuse also.

• The following enzymes may diagnose Pancreatitis : pancretic amylase and pancreatic lipase (it is also elevated in pancreatic duct obstruction).

• Acid phosphatase is an enzyme elevated in case of prostatitis and cancer prostate.

Great Vessels of the Thorax

• Ascending Aorta – arises from the left ventricle in 3rd left intercostal space, has 3 sinuses and lies in middle mediastinum. Anterior to pulmonary trunk, right lung, pleura and is posterior to left atrium, right atrium and SVC and to the left of the pulmonary trunk . Branches: Rt and Lt coronary.
• Arch of Aorta – starts at the 2 nd right costal cartilage, superior to Branches (brachiocephalic, Lt common carotid, Lt subclavian As) and Left brachiocephalic V. Inferior to division of pulmonary trunk, ligamentum arteriosum and Left main bronchus Ant to Left lung, pleura. Posterior to Trachea, esophagus and vertebral column. Branches: Brachiocephalic, Left Common Carotid, Left Subclavian, Thyroidae Ima
• Descending Aorta – starts at the Lt side of T4 vertebra Anterior Lt bronchus, Lt atrium , esophagus Vertebral column, Rt: esophagus : Lt lung & pleura and ends at the lower border of T12.
• Pulmonary Trunk – arises from Right Ventricle at the 3rd Lt costal cartilage. Anterior Left lung and pleura, ascending aorta, and Lt atrium. Distributes Right and Lt pulmonary As (caries deoxygenated blood to the lungs).N.B.:
• Ligamemtum arteriosum: fibrous band (embryological remnant) connecting arch of aorta & Lt pulmonary A causing shifting of blood from aorta

Brachiocephalic Veins

_ Begind: behind the medial end of clavicle by joining internal jugular and subclavian Veins _Short on the Right at 2.5 cm, Vertical. Relations are Righr phrenic. _Longer on left at 6cm, Obliquely horizontal Anterior- sternum, Posterior : Branches of aortic arch Inferior- arch of aorta

• SUPERIOR VENA CAVA
• *-**Begind: behind 1st Rt costal cartilage and is created by joining of 2 brachiocephalic Vs Relations are, Right: Rt phrenic. Contains B2 brachiocephalic veins and Azygos Veins
• End in: the Right atrium

Inferior vena cava

• Begins in thorax from diaphram around T8 vertebra _End in: 6th Rt costal cartilage
• PULMONARY VEINS 4 total, sup and inf Veins from each lung
• CARRIES OXXYGENATED BLOOD FROM LUNG To Left atrium

Histology of the Vascular System

• The vascular system includes arteries, veins, and arteriovenous connections.

• The wall of any blood vessel is formed of three layers, including the Tunica intima, Tunica media, and Tunica adventitia;

• Arteries are classified into Large arteries, Medium sized arteries, Small arteries (arterioles), and Meta-arteriols.

• Tunica media -Thick=:Fenestrated elastic membranes (40- 70 layer).with Smooth muscles in between.-EEL: ill defined -Mainly smooth muscles with many elastic fibers inbetween EEL:: may be present- One or 2 layers of smooth muscles replaced by pericytes in small arterioles, No EEL

• Tunica adventitia -elastic fibers rich in Present -elastic fibers -ewf may be present- absent

• Arteries that supply blood to capillaries are Called "Metarterioles" that connect terminal arterioles connect with capillaries" -Arteries that supply blood to capillaries Are surrounded by smooth muscles to act as *sphincters to control blood how to the capillaries. They carry blood from heart.

• *-STRUCTURE OF MEDIUM SIZED VEIN LIKE MEDIUM SIZED ARTERY**With some Differences

• ""Tunica intima has No int. EL."The ""Tunica media is thin."++"Tunica adventitiais very thick & longitudinal smooth muscle""

Arteries & veins Connections And Blood Capilliaries

• I-Blood Capillaries. II- Arterio venous anastomoses.
• Diameter: about 8m.*
• Lumen: narrow.*
• Structure*: It is formed of one layer of endothelial cells. Resting on basement layer
• Types*: 1-continuous (somatic capillaries)2- fenestrated (visceral) Sinusoidal capillaries

• Arteriovenous Anastomoses, These are dierct connections from arteriole Side branch that arise form an arteriole and is similair to a vanule.-Gloumrs, complacted bracnshng surrounded in a consitent structure

Physiology Arterial Blood Pressure ABP

• Arterial pressure of blood on arterial wall maximum is SBP about 1200 normally.The minimum is distolic to 70 m hg to mHg.-Pulse pressure is 50 mmHg normally 50mmHg.-Mean systemic Arteiral Pressure Is the average of the cycle MAPis

• Changes of age from the blood SBP systolic,DBP distotic Map arterial measures. Measuremnt-By cathter (invassive- By non sphg momerter (noninbasire

• Physicology of the variation ABP increase to loss if elasitciy-new8/4, four years as well Femals also hve low ABP until age 45-Race cause ABP chnages as well:

• Symphetic Emonotion increase ABP-SP ecersize too-Gravity to lower heart increase ABP, by 0.77 mmHg-Resperations cause

• Factiors which control ABP--CO increase SV and HR. IF HR is constant so Sv decreses ABP. if SV increase diaticyly pressure

• Each 1 to aboce heart to deceae ABP-Ealsicy buffer -volume is relation can affed Resistace- TPR too, "Nevers mechanism 1. reapud 2-Inter 3. low ""Cardiac Center: Cardio Pressore area and Center"" "Cardiothr Centre = Its heart heart, and reach sympaically."

• Recrptors the artialy that influence the artioanly process and ABP