Cardiac Anatomy, Histology & Function 2 PDF

CV2: Cardiac anatomy, histology and function 2 Lecturer: Yolanda Martinez Pereira (notes by Thalia Blacking) Learning objectives: 1. Describe the foetal circulation and the changes that occur during the postnatal transition 2. Describe the conducting system of the heart and understand its role in...

CV2: Cardiac anatomy, histology and function 2 Lecturer: Yolanda Martinez Pereira (notes by Thalia Blacking) Learning objectives: 1. Describe the foetal circulation and the changes that occur during the postnatal transition 2. Describe the conducting system of the heart and understand its role in the co-ordination of cardiac contraction. 3. Define the basic histological layers of tissues of the circulatory system and recognise the major features of each of these as they pertain to the heart. 4. Compare and contrast the functional and histological features of cardiac and skeletal muscle. 5. Recognise the levels of organisation within skeletal and cardiac muscle – myofibres, myofibrils and sarcomeres. 6. List and briefly describe the major components of the sarcomere. 7. Understand the histological appearance of the sarcomere. 8. Discuss mechanisms of muscle contraction – understand the prerequisites for the contractile process; describe the actin-myosin crossbridge cycle. Foetal circulation and the post-natal transition Until birth, the embryo / foetus is entirely reliant on the mother for nutrients / oxygen / removal of waste products. This occurs by diffusion until development of the placenta, which is responsible thereafter. As the lungs remain non-functional until the point of birth, the foetal circulation has several specific anatomical features: Foramen ovale – Permits flow of blood between right and left atria Ductus arteriosus – Permits flow of blood from pulmonary trunk to aorta (bypassing lungs) Ductus venosus – Permits blood returning from placenta to bypass liver Umbilical arteries transport blood to the placenta where it is oxygenated, then carried back to foetus by the umbilical vein. The ductus venosus allows much of the returning blood to bypass the liver on the way to the caudal vena cava. Here, it meets deoxygenated blood from the caudal part of the body (gut, kidneys, limbs) - but the two flows remain as distinct “columns” within the vessel without mixing. At the heart, the flows separate more or less precisely: Oxygenated blood: → RA → left atrium via the foramen ovale → left ventricle → aorta. Deoxygenated blood: → RA → RV along with that in the cranial vena cava (from the cranial part of the foetus). This is then conveyed via the pulmonary trunk towards the pulmonary circulation. Foetal lungs have no oxygenating capacity and the pulmonary circulation has high resistance (by contrast with that of the adult, where this is has low resistance in comparison with the systemic circulation). Thus, most blood is diverted to the aorta via the ductus arteriosus - but not before the origins of the coronary and subclavian / carotid vessels. Thus, mixing of the deoxygenated and oxygenated streams occurs primarily downstream of the point at which the brain and heart receive their blood supply. Alterations in blood flow at birth: Wall thickness / pressures generated by the right and left sides of the heart are equivalent in utero. At birth: Umbilical vessels rupture – loss of placental circulation Introduction of air into the lungs – decrease resistance and increased bloodflow within pulmonary  circulation Increased pulmonary venous return to left atrium Alterations in atrial pressures lead to closure of the “flap” of the foramen ovale Occlusion of ductus arteriosus – increased arterial oxygen tension, reduced pressure in its lumen, and reduced influence of placental prostaglandins promote its contraction and functional closure. Thickening of the intima over successive days leads to its anatomical closure Failure of the ductus to close – “patent ductus arteriosus” – is one of the more common congenital cardiac disorders seen in veterinary patients. Others include abnormal valve formation (e.g. aortic / pulmonic stenosis, atrioventricular valve dysplasia), disorders of septation (e.g. atrial septal defect such as patent foramen ovale, ventricular septal defect), conotruncal defects such as tetralogy of Fallot and disorders arising from abnormal development of the vasculature such as persistent right aortic arch. Co-ordination of cardiac contraction – the conducting system Cardiac function depends on the ability of the heart to contract in a co-ordinated manner. Cardiac action potentials are generated by the pacemaker cells of the sinoatrial node. Cardiomyocytes are connected by gap junctions that allow the spread of depolarisation from cell to cell, but this alone would not result in efficient propagation of impulses through the whole myocardium. A network of specialised conducting tissue allows depolarisation to spread more rapidly. The conducting tissue is located beneath the endocardium, with branches extending into the muscle layer. Branches help to transmit the cardiac action potential across the atria and towards the atrioventricular node. Transmission to the ventricles occurs only at this point, where the atrioventricular bundle (“bundle of His”) passes from the node through the fibrous platform. The bundle divides into bundle branches (left and right) which run down the septum before breaking up into a network of Purkinje fibres at the apex – these continue, subendocardially, up the walls of the ventricles, sending branches into the myocardium. The trabecula septomarginalis (RV) also contains conducting tissue & may provide a “short circuit” between septum and ventricular wall. Histology of the Heart Circulatory System – common basic structure: Inner lining – Tunica Intima (sometimes “interna”): endothelium (simple squamous epithelium) & associated basement membrane; subendothelial connective tissue Intermediate muscular* layer – Tunica Media (*Layer most variable between components of system - e.g. capillaries – absent muscular layer vs. heart – almost entirely composed of this muscular layer) Outer supporting layer – Tunica Adventitia (sometimes “externa”) – may include vasa vasorum, small arteries which sustain the tissues of large vessels Heart – Intima = endocardium; Media = myocardium; Adventitia = epicardium 1) Myocardium Striated ultrastructural appearance - contractile machinery (similar to skeletal muscle). Majority (>75%) is contractile tissue – cylindrical, branched cardiomyocytes – plus intercellular supportive tissue, vessels, nerve fibres etc. Cardiac muscle has characteristics intermediate between skeletal and smooth. Like skeletal muscle, it is strong and energy-hungry. Like smooth muscle, it shows continuous activity initiated by inherent mechanisms, modulated autonomically & hormonally. In discussion of cardiac muscle and muscle in general, note some specific terminology: Cell membrane – “sarcolemma” – true plasma membrane plus outer polysaccharide layer. Invaginations of membrane - “t-tubules” - facilitate transmission of depolarisation through the muscle fibre. “Sarcoplasmic reticulum” – located around myofibrils (see on). SR is not quite analogous to endoplasmic reticulum – it has an additional critical role of Ca2+ ion storage / release (contractile mechanism). Cardiomyocytes – histological features: Long, cylindrical, branched cells. They have abundant mitochondria reflecting their constant requirement for ATP. Unlike skeletal muscle cells (see metabolism) they contain little glycogen and have limited glycolytic capacity in low O2 situations – hence the catastrophic effects of myocardial hypoxia. Adjacent cells are joined at intercalated discs (by contrast with skeletal muscle, whose cells merge to a multinucleate syncytium, the skeletal muscle fibre). Histologically, the characteristic pattern of branching distinguishes cardiac from skeletal muscle. Intercalated discs (visible using electron microscopy - darker staining lines between cells): a) Adherens junctions – attachment of sarcomere via actin to the cell membrane b) Desmosomes – strong intercellular connections c) Gap junctions – permit the spread of contractions (allows changes in membrane potential to spread from cell to cell) such that cardiac muscle acts as a functional syncytium Note the fine striations running perpendicular to the orientation of the cardiomyocyte. These are formed by components of the sarcomere – the basic contractile unit of cardiac and skeletal muscle. 2) Endocardium – Continuous with tunica intima of large blood vessels which enter and leave heart Single layer of flattened endothelial cells with basement membrane Subendothelial supporting tissue (blood vessels, nerves, conducting system branches) 3) Epicardium Visceral pericardium and the connective tissue layer deep to this – includes blood vessels (e.g. large subepicardial vessels such as coronary b.v. – the heart’s equivalent of vasa vasorum) and nerves. 4) Pericardium Recall that the true serous pericardium has two layers – the visceral layer, apposed to the heart, and the parietal layer, apposed to the thick fibrous pericardium. Conducting tissue Purkinje cells - specialised cardiomyocytes with few contractile proteins. Their primary function is conduction, not contraction. Valves Endothelial layer – continuous with that of the heart / great vessels A tough central fibrous sheet merges with the fibrous ring (annulus) at the margin of each valve. The  chordae tendineae of the mitral and tricuspid valves are also continuous with this fibrous sheet. Levels of organisation within skeletal and cardiac muscle: Within each myofibre are hundreds of myofibrils, cylindrical arrangements of contractile proteins. Each myofibril comprises a repeating series of sarcomeres. Myofibrils contain four major protein molecules within the sarcomere: -Actin -Tropomyosin - 2 strands of each arranged in a helix – the thin filament. -Troponin – a protein complex distributed along the thin filaments -Myosin - shaped like a 2-headed golf club, arranged in thick filaments parallel to thin filaments These are directly involved in the contraction mechanism, with actin and myosin the two primary contractile proteins. A fifth protein, titin, contributes to the stiffness / elasticity of muscle. The alternating light-dark banding pattern of the sarcomere can be appreciated at microscopy: z disc: Mark the boundaries of each sarcomere. Anchoring point for contractile proteins. i bands : Light bands spanning the z-disc, only thin filaments present (i = isotropic) a bands : Dark bands where thick and thin filaments overlap (a = anisotropic) [h zone : Relatively clear portion in centre of sarcomere – thick filaments only (actin doesn’t reach).] [m line : Disc of proteins stabilising position of filaments relative to each other.] Cardiac muscle contraction: actin-myosin crossbridge cycling Sliding of actin and myosin filaments relative to each other pulls together the ends of the sarcomere, shortening the myofibril and therefore the muscle fibre. Background: Depolarisation of the cardiomyocyte leads to the influx of calcium (see lecture on cardiac action potential), with further calcium release from the sarcoplasmic reticulum. Calcium binds to troponin-C leading to a conformation change in the troponin complex, which in turn changes the position of tropomyosin relative to actin. This exposes myosin binding sites, allowing the formation of actin-myosin crossbridges. In addition to an actin binding site, myosin heads have an ATP binding site and ATPase activity (so can split ATP to ADP+Pi, with release of energy).  When bound to ATP, the myosin head actually has poor affinity for actin such that ATP binding stimulates release of the actin-myosin bond formed during preceding crossbridge cycle. Without ATP binding, this “rigor state” is maintained – this underlies rigor mortis, muscle contraction / stiffness after death. Crossbridge cycle: 1. ATP binding to myosin releases the rigor state / actin-myosin crossbridge of previous cycle. 2. Hydrolysis of ATP to ADP + Pi allows myosin to bind actin (requires presence of Ca++ as above), as well as causing a slight straightening of the myosin head. 3. ADP and Pi are released with the energy produced leading to the power stroke – flexion of the myosin head that moves the thin fibre about 10nm in relation to the thick fibre. Binding of another molecule of ATP leads to release of the actin such that the cycle can begin again.