“OVIDIUS” UNIVERSITY OF CONSTANTA
FACULTY OF MEDICINE
MEDICINE (IN ENGLISH LANGUAGE)
DR. RAZVAN CHIRICADR LOREDANA PAZARA
GRADUATE:ASHRAF UMAR WAQAS
“OVIDIUS” UNIVERSITY OF CONSTANTA
FACULTY OF MEDICINE
MEDICINE (IN ENGLISH LANGUAGE)
Comorbidities in Acute Coronary Syndrome and Their Influences on Enzymatic Profiles
DR. RAZVAN CHIRICA
DR LOREDANA PAZARA
GRADUATE:ASHRAF UMAR WAQAS
Table of Contents
General PartPage 4-
Anatomy of the heartPage 6-18
Physiology of the heartPage 19-29
Cardiac EnzymesPage 30-32
ACS and related comorbiditiesPage 33-43
Special PartPage 44-70
Irrespective of advances in medical research which have raised public awareness of the risk factors involved, the frequency of cardiac disease is increasing at an alarming rate. Our hearts are put through abusive and destructive sequences of poor lifestyle decisions such as diet, lack of physical activity or smoking and regardless of all the constant pressure and misuse they still manage to fulfil their function. However, due to the gravity of everything the we put them through it does have a toll on their functionality over time.
Acute coronary syndrome (also referred to as ACS) is a syndrome which is generally associated with three common clinical manifestations which are unstable angina (38%), ST elevation myocardial infarction – STEMI (30%) and non-ST elevation myocardial infarction – N-STEMI (25%). There are many enzymes whose levels are in conjunction to the status of the heart hence are involved as specific markers for cardiac disease or injury and their levels are affected in the manifestations mentioned above. Also, being one of the most important organs in the body, when compromised, the heart can in tandem lead to or proceed alongside malfunction/damage of other organs and systems. In ACS, many comorbidities can occur such as renal disease, pulmonary disease, gastrointestinal disease, haematological disease or cancer and these can concurrently affect the levels of cardiac enzymes.
The key cardiac enzymes are, creatine kinase muscle/brain (CKmb/CPKmb), troponin I (TnI) and troponin T (TnT). In this study it will be investigated and discussed how comorbidities which exist alongside ACS can affect the levels of these enzymes. The link between the two factors is highly important as diagnostic criteria can be affected, potentially leading to misdiagnosis and treatment error.
The objective of this study is to investigate ACS, causes, risk factors involved, different types of ACS, diagnosis of ACS, comorbidities associated with ACS, relations with cardiac enzymes and markers and factors for physicians to keep in mind to avoid misdiagnosis.
The opening topic of discussion will be basic anatomy and physiology of our Heart, moving on to the pathology in ACS. This study will be aided by patient data from Spitalul Clinic Judetean, Constanta, Romania using a patient pool of more than 50 patients.
Anatomy of the Heart
The heart is an organ built of muscular fibres forming into a pyramidal shape. The heart is located in the middle of the chest between the lungs and slightly to the left of the sternum. A double layered membrane called the pericardium surrounds the heart. It carries pericardial fluid which acts as a lubricant preventing friction between the two membranes. The heart is encapsulated by the adjoining ribs and costal cartilages which act as a protective barrier for all organs found in the thorax.
The heart itself consists of four chambers separated by a sternum into the right and left heart. Both the right and left heart are split into two chambers each – a superior one called and atrium and an inferior one known as a ventricle. Both sides of the heart, regardless of their anatomical and physiological similarities have completely unique roles in their respective circulatory pathways. Both atria receive venous blood. They then weakly contract, filling both ventricles, which in turn contract more powerfully which forces blood out into the major arterial trunks and around the body.
The right atrium receives unoxygenated venous blood from the Superior Vena Cava and Inferior Vena Cava, alongside its own venous blood supply from the Coronary Sinus. This blood is then pumped across the Tricuspid valve and enters the Right Ventricle. The valve then closes upon contraction of the Ventricle. Blood is ejected from the right ventricle through the pulmonary valves and into both left and right pulmonary arteries. The pulmonary arteries carry the blood to the lungs where it binds with oxygen becoming oxygenated. Pulmonary veins then transport the oxygenated blood to the left heart.
The left atrium receives oxygenated blood from the pulmonary veins. The left atrium contracts pushing blood through the mitral valve and into the left ventricle. The left ventricle has very muscular walls which then contract, and blood leaves the heart at high pressure through the aortic valve and into the ascending aorta, into systemic circulation and the coronary arteries. Due to blood being pumped at higher pressure from the left ventricle compared to the right ventricle, the ejection phase is shorter.
The Right AtriumThe inferior vena cava and coronary sinus enter the inferior posterior wall of the right atrium and the superior vena cava enters the superior posterior wall of the right atrium. An anterior-medial facing orifice separates the right atrium from the right ventricle. This orifice is covered by the tricuspid valve. The pulmonary valves separate the ventricle and pulmonary artery and indicate the end of the ventricle.
Interiorly, the right atrium consists of two spaces which are divided by a crest called the crista terminalis. Beginning anterior to the opening of the superior vena cava, on roof of the right atrium, it continues down the lateral wall to the inferior vena cava. In the space anterior to the crista terminalis ridges can be found called the musculi pectinate (pectinate muscles).
On the external portion of the right atrium, the separation is indicated by a vertical groove which extends from the right of the superior vena cava to the right of the inferior vena cava. This groove is called the sulcus terminalis cordis, posterior to which is found the vena cava sinus which is responsible for blood emptied by both the superior and inferior vena cava.
The venae cordis minimae (smallest cardiac veins) which drain venous blood from the myocardium into the right atrium are spread along the exterior wall of the right atrium.
The right atrium is separated internally from the left atrium by the interatrial septum which faces anterior and slightly towards the right side. The interatrial septum contains a depression known as the fossa ovalis (oval fossa). This is a remnant of a thin fibrous sheet which covered the foramen ovale during fetal development.
The posterior part of the atrium receives blood inflow via the four pulmonary veins. The walls found in this area are smooth compared to the anterior half which contains pectinate muscles. Unlike the right atrium there is no crest to separate them.
Like the right atrium, the left atrium and ventricle are separated by an orifice which houses a vale, in this case it being the mitral valve.
Also, Like the right atrium the fossa ovalis is found on the interatrial septum.
Right VentricleBlood enters the right ventricle from the right atrium through the tricuspid valve.
Multiple irregular, muscular structures can be found on the walls of the inflow portion of the right ventricle which are called trabeculae carneae. They can form two shapes, ridges or bridges. Papillary muscles can also be found which are only attached at one end, with the other end acting as point of adjoining for tendon-like cords known as chordae tendineae. Chordae tendineae connect to papillary muscles and to the tricuspid valve on either end and act as anchors for the valves.
The intraventricular septum is a thick muscular layer which separates the right ventricle from the left. The superior portion of the intraventricular septum is surrounded by a thin membranous layer.
Left VentricleThe left ventricle is found anterior to the left atrium. It receives blood from the left atrium through the mitral valve. The left ventricle has a conical shape which is longer than the right ventricle. Consisting of the thickest layer of myocardial muscle it is ready made for pumping high pressure blood out from the heart. Similarly, to the right ventricle, trabeculae carneae, and chordae tendineae are present. Papillary muscles are also found but only an anterior and posterior one.
right66802000Four valves are found in the heart, each separating a chamber of the heart from the preceding area of blood flow preventing backflow. These valves are called the aortic, pulmonary, tricuspid and mitral valves.
Aortic ValveThe aortic valve separates the left ventricle from the ascending aorta. It consists of three semilunar cusps which have their loose ends projecting superiorly into the ascending aorta. This shape forms sinuses on the superior side which fill after blood is pushed through the valve and force the them shut, preventing backflow. The blood from these sinuses is also forced into the coronary arteries which supply the heart muscle.
Pulmonary ValveThe pulmonary valve which is found in between the right ventricle and the pulmonary artery comprises of three semilunar cusps (anterior, right and left) again with loose ends which face the lumen of the pulmonary artery.
Like the aortic valve, the cusps are concave and form sinuses on the superior end and the mechanism prevents backflow.
Tricuspid ValveThe tricuspid opens during right atrial contraction and closes during ventricular contraction. It has three cusps (anterior, posterior and septal). Chordae tendineae which arise from the papillary muscles attach to the loose ends of the cusps. Contraction on the chordae tendineae prevents inversion of the cusps into the atrium.
Closing of the valve during ventricular contraction is via the same mechanism as in the other valves.
Mitral ValveThe mitral valve is found between the left atrium and ventricle in the atrioventricular orifice. It is made from two cusps (anterior and posterior) therefore is a bicuspid valve. Similar to the tricuspid valve in the right heart the mitral valve has the same mechanism of preventing back flow with the aid of the chordae tendineae.
The anterior part of the heart is formed predominantly by the right heart which curves slightly, covering the entire left portion of the heart. The tricuspid valve and pulmonary valves are widely separated by the right ventricle and due to being set in different planes. The posterior aspect is composed generally from the left heart. The base of the heart consists of the left atrium and left ventricles form the tip of the heart called the apex. The mitral valve and aortic valve are located closely together as the left ventricle is narrow.
The right and left coronary arteries arise from the ascending aorta in the anterior and posterior sinuses. Coronary ostia can be found on different levels. An oblique inverted crown is formed by the arteries. The main arteries and their major their major branches are usually located sub pericardial, however some may be found in grooves and concealed by overlaying myocardium.
The dominant artery gives branches to the posterior interventricular artery. It supplies the posterior aspect of the ventricular septum and also some of the posterolateral wall of the left ventricle. In 60% of cases the right coronary artery is the dominant one. There may be an increased number of anastomoses in some pathological conditions such as coronary artery disease or chronic hypoxia.
Coronary arteries vary in their diameter with the possibility of being between 1.5mm to 5.5mm, with them increasing in diameter until the age of 30 years.
Right coronary artery
Beginning from the right coronary aortic sinus, the right coronary artery is usually singular, however in some cases there may be up to four of them. It continues anteriorly between the right auricle and pulmonary trunk, from where it reaches the atrioventricular groove. It moves inferiorly in the groove, bending around the right acute cardiac border into the posterior aspect of the groove. It terminates upon reaching the crux of the. At this point it forms an anastomosis with the circumflex branch of the left coronary artery.
The right coronary artery and its branches supply the right atrium, right ventricle, the atrioventricular septum and portions of the left heart. The first branch is the right conus artery which branches anteriorly on the pulmonary conus and superior aspect of the right ventricle. In some cases, it can form an anastomosis with the left coronary branch of the anterior descending artery. This creates a spherical anastomosis around the outflow tract called the annulus of Vieussens.
The first portion of the right coronary artery gives arise to the anterior atrial and ventricular branches. The right marginal artery reaches the apex. Between the right border and the crux, up to three ventricular branches arise from the second segment of the right coronary artery. They supply the diaphragmatic surface of the right ventricle. The posterior interventricular artery is situated in the interventricular groove and is normally singular.
The sinoatrial node is supplied by the atrial branch which is spread to the myocardium of both atria. In the majority of cases, it begins from the anterior atrial branch of the right coronary artery. It passes back in the groove between the auricle and the aorta, branching around the base of the superior vena cava to supply the right atrium. The ramus cristae terminalis passes through the Sino-atrial node.
The posterior interventricular branch supplies the posterior interventricular septum. The largest posterior septal artery arises from the inverted loop at the crux. It supplies the atrioventricular node in the majority of cases. The atrial myocardium is supplied by the small atrioventricular branches arising from the ventricular branches of the right coronary artery.
Left coronary artery
Being larger than the right coronary artery, the left coronary artery supplies more of the myocardium. It supplies almost the complete left ventricle and left atrium. Most of the interventricular septum is supplied by the left coronary artery. Major branches are the circumflex and anterior interventricular arteries which are situated between the left auricle and the pulmonary trunk.
The anterior interventricular artery is an extension of the left coronary artery. It descends in the interventricular groove, reaching and ending at the apex, or sometimes meeting the posterior interventricular branch of the right coronary artery.
Left anterior ventricular arteries may divide in many branches at a ninety-degree angle crossing the ventricle anterior and diagonally to the anterior ventricular artery. A conus artery which branches from the anterior interventricular artery, anastomoses with the conus from the right coronary artery, the aorta and vasa vasorum. The anterior septal branches exit the anterior interventricular artery and inverse to the septum, supplying its anterior two thirds.
The circumflex artery extends around the left cardiac terminating on the left side of the crux. The circumflex gives rise to the left marginal artery which supplies a large portion of the left ventricle alongside the anterior and posterior branches of the circumflex. The left atrium is supplied by the anterior, posterior and lateral branches of the circumflex artery.
The sinoatrial node is supplied from a branch of the anterior circumflex. Encompassing the superior vena cava, a large branch passes directly through the node. The atrioventricular node is supplied by an artery which arises in close proximity to the crux.
The heart drains via the coronary sinus with its leading branches, the anterior cardiac veins and the small cardiac veins. The coronary sinus returns blood for all portions of the heart excluding the anterior segment of the right ventricle (drained by via the anterior cardiac veins) and small portions of both atria. Small cardiac veins also referred to as Thebesiuis’ veins also drain into the right atrium and ventricle.
The coronary sinus is located in the posterior atrioventricular groove between the left atrium and ventricle and it enters the heart between the inferior vena cava and the atrioventricular orifice. It is two to three centimetres in length. Most of the cardiac veins drain into the right atrium via the coronary sinus. The semilunar valve of the coronary sinus barriers its opening into the atrium. Branches include the great, small and middle cardiac veins, the posterior vein of the left ventricle and the oblique vein of the left atrium.
Great cardiac vein
Beginning at the apex, it rises upwards, then passing posteriorly and entering the coronary sinus. It receives the branches of the marginal vein alongside branches from the left atrium and both ventricles
Middle cardiac vein
The middle cardiac vein begins at the apex and inverts in the posterior interventricular groove, also terminating in the coronary sinus.
Small cardiac vein
Being situated in the posterior atrioventricular groove between the right atrium and right ventricle, it receives blood from the posterior of both the right atrium and ventricle. It drains into the coronary sinus.
Anterior cardiac veins
There may be up to five in number which drain the anterior part of the right ventricle. They ascend, crossing the right aspect of the atrioventricular groove, terminating in the right atrium. They drain into a subendocardial collecting channel.
The subendocardial, myocardial and sub pericardial plexuses are formed by the lymph trunks. The subendocardial and myocardial plexuses drain into the sub pericardial plexus. The left and right collecting trunks are formed for the efferent vessels of the sub epicardial plexus. Vessels from the right and left ventricles drain into three left trunks. At the atrioventricular groove, they are combined with a large vessel from the diaphragmatic surface of the left ventricle. This then ascends between the pulmonary artery and the left atrium, terminating at the inferior tracheobronchial node. The right trunk receives afferents from the right atrium, right border and right diaphragmatic surface of the right ventricle. It ascends in the atrioventricular groove. Finally, it ends in a brachiocephalic node.
The instigation of the cardiac cycle is said to be myogenic. It begins in the sinoatrial node. The autonomic nerves affect the nodal tissues, their extensions, on coronary vessels and also on the atrial and ventricular musculature. The autonomic nerves control the rate and force and ouput. The cardiac branches of the vagus are parasympathetic and they possess both afferent and efferent fibres. The same is true for the sympathetic branches, apart from the superior cervical sympathetic ganglion. This is totally efferent. Sympathetic fibres accelerating the heart and dilate the coronary arteries. The vagal fibres slow the heart and constrict the coronary arteries.
The preganglionic cardiac sympathetic axons begin from neurones that are situated in the interomediolateral segment of the upper five thoracic spinal segments. They may either synapse at the upper thoracic sympathetic ganglia or they rise to synapse in the cervical ganglia. The sympathetic cardiac nerves are formed by the postganglionic fibres.
The preganglionic cardiac parasympathetic axons begin from neuornes in the dorsal vagal nucleus or in close proximity to the nucleus ambiguous. They continue as vagal branches and synapse in the cardiac plexus and also the atrial walls. The intrinsic cardiac neurones are only found in the atria and interatrial septum. They are mostly in the subepicardial connective tissue which is located near the sinoatrial node and the atrioventricular node. The intrinsic ganglia form complex circuits for the local neuronal control of the heart.
The cardiac plexus is formed together by the autonomic. It has two parts: the superficial part, which is located between the aortic arch and the pulmonary trunk, and the deep part which is located between the aortic arch and the tracheal bifurcation. The plexuses have ganglion cells which are found in the atrial tissue and along the supply of branches of the plexus. Their axons are postganglionic parasympathetic. Passing through the cardiac plexus are the cholinergic and adrenergic fibres. These are mostly located in the sinoatrial node and atrioventricular nodes. Adrenergic fibres supply the coronary arteries and cardiac veins. There is a plexus of nerves that have cholinesterase, adrenergic transmitters and neuropeptide Y in the subendocardial parts of all the chambers and in the cusps also.
Cardiac Conduction System
Formed from a group of specialised muscle cells, the cardiac conduction is responsible of sending signals to the heart muscle resulting in contraction. The key components of the conduction system are the SA node, AV node, bundle of His, bundle branches, and Purkinje fibres. Functioning by electrical activity a current is produced which can be seen on an ECG/EKG.
It is spherical in shape and is lies at the point between the right atrium that is from the embryonic venous sinus and the atrium proper. It is enclosed by a plaque of sub pericardial fat. The sinoatrial node is an anatomical pacemaker which begins the sequence of cardiac activity. It sends impulses which travel around the atria causing them to contract. From there, the signal travels to the AV node, through the bundle of His, down the bundle branches, and through the Purkinje fibres, causing the ventricles to contract.
Atrioventricular NodeThis is located on the atrial aspect of the atrioventricular septum. The atrioventricular node is stimulated by the electrical impulse which is carried from the sinoatrial node. Upon excitation it sends impulses through the bundle of his, continuing through the purkinje fibres resulting in ventricular contraction.
Bundle BranchesThe right bundle branch is found to the right of the interventricular septum and continues towards the apex of the right ventricle, where it splits and forms the purkinje fibres.
Similarly, to the right bundle branch, the left bundle branch is found to the left of the interventricular septum, descending to the apex of left ventricle terminating as the purkinje fibres
Both bundle branches carry electrical impulses which are part of the system responsible for ventricular contraction.
Physiology of the Heart
Three types of muscle can be found in the heart, atrial muscle, ventricular muscle and excitatory, conductive muscle fibres. The atrial and ventricular muscles have a similar contraction to skeletal muscle however the duration is longer. Excitatory conductive fibres contain specialised cardiac which are able to spontaneously create and spread action potentials through the heart, allowing it to beat in a normal rhythm. This is known as automaticity.
Cardiac muscle fibres are striated and consist of myofibrils containing actin and myosin filaments. These filaments slide over each other during contraction and return to normal during relaxion. The cardiac muscle also contains intercalated discs which separate muscle cells from each other. The intercalated disks are surrounded by cell membranes which combine, and form communication junctions known as gap junctions. These facilitate the rapid diffusion of ions. Being a syncytium means easy ionic movement in the intracellular fluid allowing action potentials to move from one cardiac muscle cell to the next. There are two syncytia in the heart, atrial and ventricular. Action potentials are only conducted via the atrioventricular bundle, which separates heart into two syncytia. This is what allows the heart rhythm to work in sync with the atria contracting first, followed by the ventricles.
An action potential is an electrical potential, associated with the passage of impluses across membranes of a muscle or nerve cells. Due to their electric characteristics, action potentials are measured in millivolts. They range from -85millivolts to +20millivolts, with the average being 105millivolts. Action potentials begin with an initial spike, which lasts 0.2 seconds followed by rapid repolarization. The action potential is propagated by sodium (quick) and calcium (slow) channels opening. Brief opening of multiple sodium channels causes a huge influx of sodium ions into the muscle fibres. Upon closing, repolarization occurs during which calcium channels open for a longer duration allowing influx of both calcium and sodium ions. The long timing causes the plateau during which there is an even balance of exchange of both calcium and potassium ions. By maximum 0.3 seconds calcium channels close resulting is ceased influx of calcium and sodium ions. An increased permeability for potassium ions returns the membrane to its resting potential.
Action potentials spread to the cardiac muscle membrane to the transverse tubules, reaching the internal aspect of the cardiac muscle fibres. This causes the sarcoplasmic reticulum to release calcium ions into the sarcoplasm, which diffuse into myofibrils and catalyse the reaction between actin and myosin resulting in muscle contraction. The concentration of calcium ions found in extracellular fluid determines the strength of the contraction.
Cardiac muscle contraction lasts almost the same duration as the action potential, ending just milliseconds after the cessation of the action potential. In atrial muscle it lasts 0.2 seconds and in ventricular muscle, 0.3 seconds.
This represents all the events that occur from the commencement of one heartbeat to the beginning of the next. The duration of the cardiac cycle is a reciprocal of the heart rate. For example, if the heart rate is 74 beats per minute, 60/74 = 0.81 seconds per beat. This means if the heart rate increases the duration of the cardiac cycle will decrease ad vice versa. E.g. a decrease in the heart rate to 55 beats per minute, would be calculated by 60/55 = 1.09 seconds therefore an increased duration of the cardiac cycle. Atrial systole is the period of contraction of ventricles which happens between the first and second heart sounds. Diastole is the period or relaxation during which the heart refills with blood. The beginning of each cardiac cycle begins with excitation of the sinoatrial node, which results in generation of an action potential. Impulses travel from the sinoatrial node across both atria then to the atrioventricular node. This causes the atria to contract and in total takes slightly longer than 0.1 seconds. Upon excitation the atrioventricular node sending its own impulses down the bundle of his, through the purkinje fibres and to the ventricles causing them to contract.
center1932305002838455656580Figure SEQ Figure * ARABIC 11:The Cardiac Cycle
Figure SEQ Figure * ARABIC 11:The Cardiac Cycle
The AtriaBlood flows into the atria via the superior and inferior vena cava and the pulmonary veins. The atria accept the blood flow from the great veins. Atrial contraction is only responsible for approximately 20% of the received blood flow as approximately 80% of the blood flows straight through the mitral valve and into the ventricles, before contraction takes place. As a result of this if there is atrial dysfunction the patient will normal at rest however may be have exacerbated condition upon effort.
The VentriclesThe ventricles fill with blood during diastole through open valves. These valves close during systole allowing blood to fill in the atria. After systole, in the first third of diastole, there is rapid filling of the ventricles.
Systole is split into three main phases. The isovolumic contraction phase occurs after ventricular contraction. The pressure inside the ventricles rises rapidly. This leads to the closure of the atrioventricular valves. After a further 0.02 to 0.03 seconds, enough pressure has built up in the ventricles to push the aortic and pulmonary valves open against the pressures in the aorta and pulmonary artery. However, there is no emptying in this period. There is only contraction but no shortening of the muscle fibres.
The second period is that of ejection. Once the left ventricular pressure has risen over 80mm Hg, and the right ventricular pressure is above 8mm Hg, the ventricular pressures cause the opening of the semilunar valves. Blood then leaves the ventricles. 70% of the blood that was in the ventricles is ejected during the first third of the ejection period. This is called the period of rapid ejection. The other 30% is emptied during the last two thirds. This phase is called the period of slow ejection.
The final phase is isovolumic relaxation in which the ventricles suddenly relax, after systole. This causes the pressure in the right and left ventricles to decrease briskly. Due to the increased pressures in the aorta and pulmonary artery, blood is pushed back towards the ventricles. Blood is prevented re-entering the ventricles by the closure of the aortic and pulmonary valves. The ventricular muscle relaxes for a further 0.03 to 0.06 seconds. The ventricular volume remains the same and this is called the period of isovolumic relaxation. It is during this phase that the intraventricular pressures revert to the diastolic level and then the atrioventricular valves open.
End-Diastolic and Systolic volume
During diastolic filling of the ventricles, the volume of blood inside each ventricle equates to 110 to 120ml. This is called the end-diastolic volume. When the ventricles empty in systole, the volume of blood inside the ventricles reduces by 70ml. This is the stroke volume output. The end-systolic volume is the amount of blood that is left in the ventricles after contraction. This is 40 or 50ml. The portion of the end-diastolic volume that is ejected is called the ejection fraction. This is normally 60%. The normal values at each interval varies, depending on the amount of blood that enters the heart and the amount that is ejected. In the normal heart, the end-systolic volume can be as low as 10 to 20ml and the end-diastolic volume can be 150 to 180ml. The stroke volume output can be increased by more than 100%, when needed.
Preload and AfterloadPreload is the end diastolic volume that stretches the right or left ventricle of the heart to its greatest dimensions under variable physiologic demand. Afterload is the pressure against which the heart must work in order to eject blood during systole.
Rhythmical excitation of the heart
The heart produces electrical impulses which are conducted throughout its tissue in a rhythmical manner. Ventricular contraction is preceded one sixth of a second by atrial contraction. The hearts conduction system controls atrial and ventricular contraction.
The Sino-Atrial Node
The Sino-atrial node is a strip of specialized cardiac muscle, located in the superior posterolateral wall of the right atrium. The fibres found in the Sino-atrial node connect directly with the atrial muscle fibres. As a result, any an action potential originating from the node can swiftly distribute across the atrial muscle wall. It is also responsible for maintaining the rate of the heartbeat.
Automatic rhythmical discharge occurs in the Sino-atrial node due to its ability of self-excitation. The resting membrane potential for the sinus node is -55 to -60 millivolts, whereas the ventricular muscle fibres have a resting membrane potential of -85 to -90 millivolts. Due to the leaky cell membrane of the sinus node, calcium and sodium ions can enter. The cardiac muscle has fast sodium channels, slow sodium-calcium channels and potassium channels. The rapid upstroke of the action potential seen in the ventricular muscle is because of the opening of the fast sodium channels which leads to the huge influx of sodium ions. The plateau is due to the slower opening of the sodium-calcium channels. This lasts for 0.3 seconds. The last stage is the opening of the potassium channels. This allows the exit of huge amounts of potassium ions out of the fiber. The membrane potential then returns to its resting level.
At the resting potential on the sinus nodal fiber, at -55 millivolts, the fast sodium channels are inactivated. Only the slow sodium-calcium channels are able to open to cause an action potential. Therefore, the action potential takes longer to develop than the ventricular muscle. Also, in comparison to the ventricular muscle, it takes longer for the negative resting level to be achieved after the action potential.
Self-excitation of the sinus node fibres
There is a high concentration of sodium ions in the extracellular fluid and some sodium channels are also open. This results in an influx of sodium ions inside. In between heart beats, there is a gradual rise of the resting membrane potential due to the sodium ions. Once the potential reaches the threshold of -40 millivolts, the sodium-calcium channels become activated, resulting in an action potential. The leaking of calcium and sodium ions results in self-excitation of the sinus node. Sometimes deactivation of the sodium-calcium channels and opening of potassium channels can lead to the sinus node fibres not being depolarised. At the end of an action potential potassium channels begin to close. Leaking sodium and calcium ions results in an overshoot. There is a rise in the resting potential until it reaches the threshold for discharge at -40 millivolts. This is the complete process of self-excitation defined by the action potential, recovery from the action potential, hyperpolarization occurring upon termination of the action potential and the return of the resting potential to its threshold value.
Atrial muscle fibres are connected to the ends of the sinus node fibres hence atrial muscle fibres receive any action potential originating from the sinoatrial node. This is the path by which the action potential travels through the cardiac muscle and to the atrioventricular node. The anterior interatrial band passes through the anterior walls of the atria to the left atrium. Part of the anterior, the middle and posterior internodal pathways bend through the atrial walls ending at the atrioventricular node.
The atrioventricular node is located behind the tricuspid valve, in the posterior wall of the right atrium. When the atrioventricular node receives impulses from the atria, there is a delay before the impulse being transmitted to the ventricles. This allows adequate time for blood to empty from the atria into the ventricles before ventricular contraction. Impulses leaving the atrioventricular node enter the atrioventricular bundle, and then pass to the ventricles. Bundle of His
The bundle of his is a group of specialised heart muscle cells for conduction of electrical impulses, which are transmitted from the atrioventricular node to the fascicular branches via the bundle branches. Purkinje fibres are the next step in the chain which provide conduction to the ventricles, resulting in contraction of the cardiac muscle.
Beginning from the atrioventricular node, impulses pass the bundle of his and the atrioventricular bundle continuing into the ventricles via the Purkinje fibres. They are specialised for rapid transportation of impulses due to hyperpermeability of the gap junctions, resulting in increased velocity.
Both left and right bundle branches are branches of the bundle of his, which are both located along the right and left side of the interventricular septum respectively. As the branches continue downwards they divide into smaller fascicular branches which surround the ventricles.
Cardiac activity in the heart can also be detected at the surface of the body by the use of carefully placed electrodes. These electrodes which are placed in several positions over the aspect of the heart, detect electrical activity, polarisation, depolarisation and produce a recording called and Electrocardiogram (ECG).
An ECG machine operates by recording the electrical changes on a moving strip of boxed paper. The paper which is marked by calibration lines, is used as a guide to monitor the duration and electrical changes. The paper speed runs usually at 25 mm/second, therefore in horizontal movement each large box equals 0.2 seconds. The 0.2 second segments are divided into five smaller intervals, each representing 0.04 seconds. Vertical movement represents voltage intensity. 2 large boxes represent 1 mV therefore each small box represents 0.1mV.
The HR can be determined from the ECG. If the interval between two successive beats from the time calibration line is 1 second, then the HR is 60 bpm. It is usually estimated by counting the number of large squares between two successive R intervals.
HR = 300/number of large boxes between RR interval
ECG Leads Limb leads either be Bipolar or Unipolar. Unipolar means that the ECG is recorded from one electrode. Bipolar means use of two electrodes on different sides of the heart. A lead is a combination of two wires and their electrodes to complete a circuit between the body and the ECG.
Lead 1 is placed with the positive terminal on the left arm and the negative terminal on the right arm. The point where the terminal connects to the left arm is electropositive and the right arm is electronegative.
Lead 2 is placed with the positive terminal on the left leg and negative terminal on the right leg.
Lead 3 is placed with the positive terminal on the left leg and the negative terminal on the left arm
Einthoven’s Triangle – This is a triangle which is drawn around the heart illustrating the two upper limbs and the left leg as its apex’s.
Einthoven’s Law –
Lead I potential + Lead III potential = Lead II potential
If a 3 lead ECG records simultaneously the sum of the potentials in leads I and III equals the potential in lead II.
Augmented Unipolar Leads
There are 3 leads connected, 2 are negative and 1 is positive. The aVR lead is when the positive terminal is connected to the right arm. The remaining 2 negaitive leads are – aVL which is when it’s connected to the left arm and aVF which is connected to the left leg. The recording from the aVR lead is inverted.
Precordial (Chest) Leads
These are the six standard chest leads which are connected at different points on the anterior chest wall. They are referred to as V1, V2. V3, V4, V5 and V6. They record the electrical potential in the respective cardiac muscle lying below.
7416803169920Figure SEQ Figure * ARABIC 22:Precordial Lead placement
Figure SEQ Figure * ARABIC 22:Precordial Lead placement
737235147701000V1 and V2 – QRS complexes is these leads are recorded as negative. This is because the chest electrode in these leads is closer to the base of the heart, than to the apex. As the base of the heart is more electronegative during ventricular depolarisation, the recording is negative. In leads V3-V6, the QRS complexes are positive as the electrodes are closer to the apex, which is the direction of electro positivity during most of depolarisation.
In a normal patient an ECG recording has a baseline, a P wave, QRS complex and a T wave.
The P wave is the first wave found on an ECG. In a normal patient it is a wave which moves in a positive direction and represents atrial depolarisation. Atrial depolarisation results in atrial systole. The voltage of the P wave is between 0.1-0.3 mV.
The PR or PQ interval represents the period from the beginning of the P wave to the beginning of the QRS complex. It represents the beginning of excitation of the atria, and beginning of excitation of the ventricles. This normally lasts between 0.12-0.21 seconds.
The QRS complex represents the structure produced on the ECG by a combination of the Q, R and S waves which occur in rapid succession. The Q wave is a negative deflection present shortly following the P wave. It represents depolarisation of the interventricular septum. The Q wave is immediately followed by R wave. The R wave is a positive wave which represents early ventricular depolarisation. Following this, the S wave is a negative wave which signifies the final depolarization of the ventricles, at the base of the heart. The QRS complex is usually 1-1.5 mV from the top of the R wave to the bottom of the S wave.
The ST segment begins from the end of the QRS complex to the beginning of the T wave. It represents the isoelectric period when the ventricles are in between depolarization and repolarization. There are significant changes found in the ST segment during myocardial infarctions. This segment usual lasts between 0.05-0.15 seconds.
The T wave is a positive wave which represent ventricular repolarization. The T wave voltage is between 0.2-0.3 mV.
Cardiac enzymes are proteins which vary in quantity based on the health of the cardiac muscle. They are used as biomarkers to assist in assessment of heart function. Their levels in the blood can be significant in diagnosis of cardiac conditions. There are many different cardiac enzymes, each of which responds in a different way in different conditions. The cardiac enzymes are –
Creatine Kinase (CKmb)
Lactate Dehydrogenase (LDH)
Pro-brain Natriuretic Peptide
Glycogen Phosphorylase Isoenzyme BB
Many of these markers are unspecific so are not definitive for diagnosis therefore the focus in this study will be on the more sensitive markers. The enzymes which provide a high level of specificity are Tropinin I, Troponin T and CKmb.
Troponins (I and T)
Troponins are proteins which are found in cardiac muscle fibres, therefore are also referred to as cardiac troponins I and T (cTnT and cTnI). They can also be found in skeletal muscle. Troponin T is binds to tropomyosin forming a troponin-tropomyosin complex. Troponin I binds to actin filaments. During initiation of muscular contraction, calcium binds to the troponin-tropomyosin complex resulting in production of muscular force. Troponins are released into the blood stream during myocardial injury, being specific indicators for ischemia. This results in an increase in troponin levels and elevated serum levels indicate heart disorders such as myocardial infarction. Troponins are currently accepted as the most specific test when looking at an acute coronary syndrome, however care must be taken in regards to diagnosis as Troponin I can also be raised in other diseases such as chronic renal failure.
The normal range for troponins is less than 0.1ug/|L. If this value exceeds 2.0ug/L myocardial infarction is to be suspected. Levels generally rise around 12 hours after onset.
Creatine Kinase Muscle/Brain (CKmb/CPKmb)
Creatine kinase (CK) is an enzyme which acts a catalyst in a reversible reaction, converting creatine into phosphocreatine (PCr) by transferring one phosphate from adenosine triphosphate (ATP) to CK.
CK + ATP = PCr + ADP
As this this a reversible reaction and PCr can bind with ADP to produce ATP, PCr acts as an energy reserve in tissues which have a high consumption of ATP. Thus, CK plays an important role in cardiac, skeletal, smooth muscle contractility and generation of blood pressure. CKmb is generally found in cardiac muscle hence it may be used as a cardiac marker. Its levels reflect the amount of damage in CK-rich tissues.
Practically, the use of CKmb in the diagnosis of chest pain has been superseded by troponin tests, however in many countries it remains as a specific diagnostic criterion. In general, the levels of CKmb will increase in result of damage to tissues with a high CK content therefore its levels are raised in myocardial infarction. However, the levels may also be increased is other conditions such as myocarditis, rhabdomyolysis or acute kidney injury, indicating low specificity when compared to troponins.
In myocardial injury the serum value of CKmb will exceed the normal range which is 5-25iu/L.
ACS and related comorbidiesAcute Coronary Syndrome (ACS)
A syndrome is a group of medical signs and symptoms which have a relation or correlation with a specific disease. Situations such as obstruction or stenosis can lead to a decreased blood flow in coronary arteries, resulting in a reduced supply of oxygen called cardiac ischemia. In ischemia the lack of oxygen leads to reduced cellular metabolism and irreversible cell damage. As this is taking place in the coronary arteries and the symptoms are present for a short period of time, this process can be defined as acute coronary syndrome (ACS).
Atherosclerosis is an accumulation of fatty deposits on the interior lumen of a blood vessel is known as a plaque (or atheroma). Plaques have a tenancy to rupture and which can lead to adherence of blood cell and formation of a blood clot also referred to as a thrombus. Thrombi can cause constriction in the area where they are present or dislodge and travel to a smaller blood vessel where they get stuck, causing obstruction, which is called an embolus. These obstructions lead to inadequate or absence of blood flow.
In terms of ACS there is either plaque build-up, a thrombus or an embolus present in one or multiple coronary arteries. There is two possible scenarios from this position. In the case of incomplete blockage or stenosis, there is inadequate blood flow, however little amounts are still present. Consequently, there is still little amounts of oxygen present is cells, which leads to reduced or improper function of cardiac muscle. This is called unstable angina which can be reversible. The other possibility is complete obstruction leading to absence of oxygen resulting in cell death and necrosis. Cell death is irreversible and causes a myocardial infarction.
Age – in general women aged above 55 and men aged above 45 have an increased risk of acute coronary syndrome.
High blood cholesterol – an increase in cholesterol increases the chances of plaque build-up in blood vessels.
Hypertension – high blood pressure increases the chances of developing atherosclerosis.
Unhealthy Diet – a diet high in lipids and cholesterol increases the risk of atherosclerosis.
Smoking – smoking damages artrial walls and increases the chances of atherosclerosis.
Lack of exercise – irregular physical activity can raise blood pressure resulting in atherosclerosis.
Signs and Symptoms
As the principal cause of ACS is ischemia, the most common symptom is retrosternal chest pain of a compressive nature. In many cases the chest pain will radiate to the left shoulder, the neck and left angle of the jaw. Radiation from the shoulder to the fingertips may also be present in certain cases. Dyspnoea, sweating, nausea and vomiting may also be associated in many patients. Even though chest pain is the main symptom present attention must be paid in situations such as diabetes in women where pain is absent.
The three common clinical manifestations in ACS are unstable angina (38%), ST elevation myocardial infarction – STEMI (30%) and non-ST elevation myocardial infarction – N-STEMI (25%). Stable angina is not classified as an ACS as it is triggered upon exertion and resolves at rest, which is the opposite of unstable angina which often occurs spontaneous in a resting patient.
Unstable Angina is a type of angina pectoris which can have an unprompted occurrence even without physical exertion. It is characterised by retrosternal chest pain, possibly radiating to the left shoulder, limb, neck, jaw and lasting greater than 20 minutes. The pain is relieved by administration of nitroglycerine. Differential from N-STEMI may be difficult and is solely dependent on the levels of cardiac markers as ECG changes may be present in either scenario. In unstable angina cardiac enzymes are not increased, whereas in N-STEMI there is an increase. This is the key to differential between the two possible pathologies. Upon initial presentation they may be indistinguishable as cardiac enzymes levels may not raise for up to 12 hours. Management includes nitroglycerine, an antiplatelet and anticoagulant.
Myocardial infarction occurs due to ischemia of heart muscle. The pain experienced carrys the same characteristics as those in unstable angina. There are two types of myocardial infarction which are named and distinguished based on their ECG presentations. In an STEMI the ST segment on the ECG is raised, hence the name ST elevation myocardial infarction. On the other hand, in N-STEMI there is no ST elevation. In both cases cardiac enzymes levels are elevated. ECG changes are immediately present in STEMI, allowing prompt diagnosis and treatment when compared to NSTEMI which is undistinguishable from unstable angina during its early hours of onset.
-19494594043500A simple way to differentiate is between the 3 manifestations is unstable angina consists of neither ECG or enzyme changes, N-STEMI only presents enzyme changes and STEMI shows both ECG and changes in cardiac enzymes.
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