The tubular heart or primitive heart tube is the earliest stage of heart development. From the inflow to the outflow, it consists of sinus venosus, primitive atrium, the primitive ventricle, the bulbus cordis, truncus arteriosus, it forms from splanchnic mesoderm. More they form from endocardial tubes, starting at day 21. Embryology at Temple Heart98/heart97a/sld018 Embryology at Temple Heart98/heart97a/sld019
Heart development refers to the prenatal development of the human heart. This begins with the formation of two endocardial tubes which merge to form the tubular heart called the primitive heart tube, that loops and septates into the four chambers and paired arterial trunks that form the adult heart; the heart is the first functional organ in vertebrate embryos, in the human, beats spontaneously by week 4 of development. The tubular heart differentiates into the truncus arteriosus, bulbus cordis, primitive ventricle, primitive atrium, the sinus venosus; the truncus arteriosus splits into pulmonary artery. The bulbus cordis forms part of the ventricles; the sinus venosus connects to the fetal circulation. The heart tube elongates on the right side and becoming the first visual sign of left-right asymmetry of the body. Septa ventricles to separate the left and right sides of the heart; the heart derives from embryonic mesodermal germ-layer cells that differentiate after gastrulation into mesothelium and myocardium.
Mesothelial pericardium forms the outer lining of the heart. The inner lining of the heart and blood vessels, develop from endothelium. In the splanchnopleuric mesenchyme on either side of the neural plate, a horseshoe-shaped area develops as the cardiogenic region; this has formed from cardiac myoblasts and blood islands as forerunners of blood vessels. By day 19, an endocardial tube begins to develop in each side of this region; these two tubes grow and by the third week have converged towards each other to merge, using programmed cell death to form a single tube, the tubular heart. From splanchnopleuric mesenchyme, the cardiogenic region develops cranially and laterally to the neural plate. In this area, two separate angiogenic cell clusters form on either side and coalesce to form the endocardial tubes; as embryonic folding continues, the two endocardial tubes are pushed into the thoracic cavity, where they begin to fuse together, this is completed at about 22 days. At around 18 to 19 days after fertilisation, the heart begins to form.
This early development is critical for prenatal development. The heart is the first functional organ to develop and starts to beat and pump blood at around day 21 or 22; the heart begins to develop near the head of the embryo in the cardiogenic area. Following cell signalling, two strands or cords begin to form in the cardiogenic region As these form, a lumen develops within them, at which point, they are referred to as endocardial tubes. At the same time that the tubes are forming other major heart components are being formed; the two tubes migrate together and fuse to form a single primitive heart tube, the tubular heart which forms five distinct regions. From head to tail, these are the truncus arteriosus, bulbus cordis, primitive ventricle, primitive atrium, the sinus venosus. All venous blood flows into the sinus venosus, contractions propel the blood from tail to head, or from the sinus venosus to the truncus arteriosus; the truncus arteriosus will divide to form pulmonary artery. The central part of cardiogenic area is in front of the neural plate.
The growth of the brain and the cephalic folds push the oropharyngeal membrane forward, while the heart and the pericardial cavity move first to the cervical region and into the chest. The curved portion of the horseshoe-shaped area expands to form the future ventricular infundibulum and the ventricular regions, as the heart tube continues to expand; the tube starts receiving venous drainage in its caudal pole and will pump blood out of the first aortic arch and into the dorsal aorta through its polar head. The tube remains attached to the dorsal part of the pericardial cavity by a mesodermal tissue fold called the dorsal mesoderm; this mesoderm disappears to form the two pericardial sinuses the transverse and the oblique pericardial sinuses, which connect both sides of the pericardial cavity. The myocardium thickens and secretes a thick layer of rich extracellular matrix containing hyaluronic acid which separates the endothelium. Mesothelial cells form the pericardium and migrate to form most of the epicardium.
The heart tube is formed by the endocardium, the inner endothelial lining of the heart, the myocardial muscle wall, the epicardium that covers the outside of the tube. The heart tube continues stretching and by day 23, in a process called morphogenesis, cardiac looping begins; the cephalic portion curves in a frontal clockwise direction. The atrial portion starts moving in a cephalic ally and moves to the left from its original position; this curved shape approaches the heart and finishes its growth on day 28. The conduit forms the atrial and ventricular junctions which connect the common atrium and the common ventricle in the early embryo; the arterial bulb forms the trabecular portion of the right ventricle. A cone will form the infundibula blood of both ventricles; the arterial trunk and the roots will form the proximal portion of the aorta and the pulmonary artery. The junction between the ventricle and the arterial bulb will be called the primary intra-ventricular hole; the tube is divided into cardiac regions along its craniocaudal axis: the primitive ventricle, called primitive left ventricle, the trabecular proximal arterial bulb, called the primiti
The pulmonary circulation is the portion of the circulatory system which carries deoxygenated blood away from the right ventricle of the heart, to the lungs, returns oxygenated blood to the left atrium and ventricle of the heart. The term pulmonary circulation is paired and contrasted with the systemic circulation; the vessels of the pulmonary circulation are the pulmonary veins. A separate system known as the bronchial circulation supplies oxygenated blood to the tissue of the larger airways of the lung; the earliest human discussions of pulmonary circulation date back to Egyptian times. Human knowledge of pulmonary circulation grew over centuries, scientists Ibn al-Nafis, Michael Servetus, William Harvey provided some of the first accurate descriptions of this process. Deoxygenated blood leaves the heart, goes to the lungs, re-enters the heart. From the right atrium, the blood is pumped into the right ventricle. Blood is pumped from the right ventricle through the pulmonary valve and into the main pulmonary artery.
The pulmonary arteries carry deoxygenated blood to the lungs, where carbon dioxide is released and oxygen is picked up during respiration. Arteries are further divided into fine capillaries which are thin-walled; the pulmonary vein returns oxygenated blood to the left atrium of the heart. The oxygenated blood leaves the lungs through pulmonary veins, which return it to the left heart, completing the pulmonary cycle; this blood enters the left atrium, which pumps it through the mitral valve into the left ventricle. From the left ventricle, the blood passes through the aortic valve to the aorta; the blood is distributed to the body through the systemic circulation before returning again to the pulmonary circulation. From the right ventricle, blood is pumped through the semilunar pulmonary valve into the left and right main pulmonary arteries, which branch into smaller pulmonary arteries that spread throughout the lungs; the pulmonary circulation loop is bypassed in fetal circulation. The fetal lungs are collapsed, blood passes from the right atrium directly into the left atrium through the foramen ovale: an open conduit between the paired atria, or through the ductus arteriosus: a shunt between the pulmonary artery and the aorta.
When the lungs expand at birth, the pulmonary pressure drops and blood is drawn from the right atrium into the right ventricle and through the pulmonary circuit. Over the course of several months, the foramen ovale closes, leaving a shallow depression known as the fossa ovalis. A number of medical conditions can affect the pulmonary circulation. Pulmonary hypertension describes an increase in resistance in the pulmonary arteries Pulmonary embolus is a blood clot from a deep vein thrombosis that has lodged in the pulmonary vasculature, it can cause difficulty breathing or chest pain, is diagnosed through a CT pulmonary angiography or V/Q scan, is treated with anticoagulants such as heparin and warfarin. Cardiac shunt is an unnatural connection between parts of the heart that leads to blood flow that bypasses the lungs. Vascular resistance Pulmonary shunt The discovery of pulmonary circulation has been attributed to several scientists over the years. In much of modern medical literature, the discovery is credited to English physician William Harvey.
Other sources credit Spanish physician Michael Servetus and Arab physician Ibn al-Nafis with the discovery. However, the first descriptions of the cardiovascular system came before these men; the earliest known description of the role of air in circulation was produced in Egypt in 3500 BCE. At this time, Egyptians believed that the heart was the origin of many channels that connected different parts of the body and transported air as well as urine and the soul; the Edwin Smith Papyrus, named for American Egyptologist Edwin Smith who purchased the scroll in 1862, provided evidence that Egyptians believed that the heartbeat created a pulse that transported the above substances throughout the body. A second scroll, the Ebers Papyrus emphasized the importance of the heart and its connection to vessels throughout the body and described methods to detect cardiac disease through pulse abnormalities. However, despite their knowledge of the heartbeat and pulse, the Egyptians attributed the movement of substances throughout the vessels to air that resided in these channels, rather than to the heart's force.
The Egyptians knew that air played an important role in circulation, but they did not yet have a concept for the precise role of the lungs. The next addition to the human understanding of pulmonary circulation came with the Ancient Greeks; the physician Alcmaeon proposed that the brain, not the heart, was the connection point for all of the vessels in the body. He believed that the function of these vessels was to bring the air to the brain. Empedocles, a philosopher, proposed a series of pipes impermeable to blood but continuous with blood vessels which carried the pneuma throughout the body, he proposed. The physician Hippocrates developed the view that the liver and spleen produced blood, which traveled to the heart to be cooled by the lungs that surrounded it. Hippocrates described the heart as having two ventricles connected by an interventricular septum, he depicted the heart as the connecting point for all the vessels of the body and proposed that some vessels
The dorsal aortae are paired embryological vessels which progress to form the descending aorta. The paired dorsal aortae arise from aortic arches; each primitive aorta anteriorly receives the vitelline vein from the yolk-sac, is prolonged backward on the lateral aspect of the notochord under the name of the dorsal aorta. The dorsal aortae give branches to the yolk-sac, are continued backward through the body-stalk as the umbilical arteries to the villi of the chorion; the two dorsal aortae combine to become the descending aorta in development. Embryology at Temple Heart98/heart97a/sld017 Embryology at UNSW Notes/git cardev-009—Embryo Images at University of North Carolina
The aorticopulmonary septum is developmentally formed from neural crest the cardiac neural crest, separates the aorta and pulmonary arteries and fuses with the interventricular septum within the heart during heart development. In the developing heart, the truncus arteriosus and bulbus cordis are divided by the aortic septum; this makes its appearance in three portions. Two distal ridge-like thickenings project into the lumen of the tube, it divides the distal part of the truncus into two vessels, the aorta and pulmonary artery, which lie side by side above, but near the heart the pulmonary artery is in front of the aorta. Four endocardial cushions appear in the proximal part of the truncus arteriosus in the region of the future semilunar valves. Two endocardial thickenings—anterior and posterior—develop in the bulbus cordis and unite to form a short septum; the septum grows down into the ventricle as an oblique partition, which blends with the ventricular septum in such a way as to bring the bulbus cordis into communication with the pulmonary artery, through the latter with the sixth pair of aortic arches.
The actual mechanism of septation of the outflow tract is poorly understood, but is recognized as a dynamic process with contributions from contractile and extracellular matrix interactions. Misalignment of the septum can cause the congenital heart conditions tetralogy of Fallot, persistent truncus arteriosus, dextro-Transposition of the great arteries, tricuspid atresia, anomalous pulmonary venous connection. Aortopulmonary septal defect This article incorporates text in the public domain from page 514 of the 20th edition of Gray's Anatomy https://web.archive.org/web/20071009000046/http://isc.temple.edu/marino/embryology/Heart98/abnorm_text.htm
The atrium is the upper chamber through which blood enters the heart. There are two atria in the human heart – the left atrium connected to the lungs, the right atrium connected to the venous circulation; the atria receive blood, when the heart muscle contracts they pump blood to the ventricles. All animals with a closed circulatory system have at least one atrium; the atrium used to be called the "auricle", that term is still used to describe this chamber in, for example, the Mollusca, but in humans that name is now used for an appendage of the atrium. Humans have a four-chambered heart consisting of the right atrium, left atrium, right ventricle, left ventricle; the atria are the two upper chambers. The right atrium receives and holds deoxygenated blood from the superior vena cava, inferior vena cava, anterior cardiac veins and smallest cardiac veins and the coronary sinus, which it sends down to the right ventricle which in turn sends it to the pulmonary artery for pulmonary circulation; the left atrium receives the oxygenated blood from the left and right pulmonary veins, which it pumps to the left ventricle for pumping out through the aorta for systemic circulation.
The right atrium and right ventricle are referred to as the right heart and the left atrium and left ventricle are referred to as the left heart. The atria do not have valves at their inlets and as a result, a venous pulsation is normal and can be detected in the jugular vein as the jugular venous pressure. Internally, there are the rough pectinate muscles and crista terminalis of His, which act as a boundary inside the atrium and the smooth walled part of the right atrium, the sinus venarum derived from the sinus venosus; the sinus venarum is the adult remnant of the sinus venous and it surrounds the openings of the venae cavae and the coronary sinus. Attached to the right atrium is the right atrial appendage – a pouch-like extension of the pectinate muscles; the interatrial septum separates the right atrium from the left atrium and this is marked by a depression in the right atrium –the fossa ovalis. The atria are depolarised by calcium. High in the upper part of the left atrium is a muscular ear-shaped pouch – the left atrial appendage.
This appears to "function as a decompression chamber during left ventricular systole and during other periods when left atrial pressure is high". The sinoatrial node is located in posterior aspect of the right atrium, next to the superior vena cava; this is a group of pacemaker cells. The cardiac action potential spreads across both atria causing them to contract, forcing the blood they hold into their corresponding ventricles; the atrioventricular node is another node in the cardiac electrical conduction system. This is located between the ventricles; the left atrium is supplied by the left circumflex coronary artery, its small branches. The oblique vein of the left atrium is responsible for venous drainage. During embryogenesis at about two weeks, a primitive atrium begins to be formed, it begins as one chamber which over the following two weeks becomes divided by the septum primum into the left atrium and the right atrium. The interatrial septum has an opening in the right atrium, the foramen ovale which provides access to the left atrium.
At birth, when the first breath is taken fetal blood flow is reversed to travel through the lungs. The foramen ovale is no longer needed and it closes to leave a depression in the atrial wall. In some cases, the foramen ovale fails to close; this abnormality is present in 25% of the general population. This is known as an atrial septal defect, it is unproblematic, although it can be associated with paradoxical embolization and stroke. Within the fetal right atrium, blood from the inferior vena cava and the superior vena cava flow in separate streams to different locations in the heart, this has been reported to occur through the Coandă effect. In human physiology, the atria facilitate circulation by allowing uninterrupted venous flow to the heart during ventricular systole. By being empty and distensible, atria prevent the interruption of venous flow to the heart that would occur during ventricular systole if the veins ended at the inlet valves of the heart. In normal physiologic states, the output of the heart is pulsatile, the venous inflow to the heart is continuous and non-pulsatile.
But without functioning atria, venous flow becomes pulsatile, the overall circulation rate decreases significantly. Atria have four essential characteristics. There are no atrial inlet valves to interrupt blood flow during atrial systole; the atrial systole contractions are incomplete and thus do not contract to the extent that would block flow from the veins through the atria into the ventricles. During atrial systole, blood not only empties from the atria to the ventricles, but blood continues to flow uninterrupted from the veins right through the atria into the ventricles; the atrial contractions must be gentle enough so that the force of contraction does not exert significant back pressure that would impede venous flow. The "let go" of the atria must be timed so that they relax before the start of ventricular contraction, to be able to accept venous flow without interruption. By preventing the inertia of interrupted venous flow that would otherwise occur at each ventricular systole, atria allow 75% more cardiac output
Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of splitting. Vasculogenesis is the embryonic formation of endothelial cells from mesoderm cell precursors, from neovascularization, although discussions are not always precise; the first vessels in the developing embryo form through vasculogenesis, after which angiogenesis is responsible for most, if not all, blood vessel growth during development and in disease. Angiogenesis is a normal and vital process in growth and development, as well as in wound healing and in the formation of granulation tissue. However, it is a fundamental step in the transition of tumors from a benign state to a malignant one, leading to the use of angiogenesis inhibitors in the treatment of cancer; the essential role of angiogenesis in tumor growth was first proposed in 1971 by Judah Folkman, who described tumors as "hot and bloody," illustrating that, at least for many tumor types, flush perfusion and hyperemia are characteristic.
Sprouting angiogenesis was the first identified form of angiogenesis. It occurs in several well-characterized stages. First, biological signals known as angiogenic growth factors activate receptors on endothelial cells present in pre-existing blood vessels. Second, the activated endothelial cells begin to release enzymes called proteases that degrade the basement membrane to allow endothelial cells to escape from the original vessel walls; the endothelial cells proliferate into the surrounding matrix and form solid sprouts connecting neighboring vessels. As sprouts extend toward the source of the angiogenic stimulus, endothelial cells migrate in tandem, using adhesion molecules called integrins; these sprouts form loops to become a full-fledged vessel lumen as cells migrate to the site of angiogenesis. Sprouting occurs at a rate of several millimeters per day, enables new vessels to grow across gaps in the vasculature, it is markedly different from splitting angiogenesis because it forms new vessels as opposed to splitting existing vessels.
By intussusception known as splitting angiogenesis, a new blood vessel is created by splitting of an existing blood vessel in two. Intussusception was first observed in neonatal rats. In this type of vessel formation, the capillary wall extends into the lumen to split a single vessel in two. There are four phases of intussusceptive angiogenesis. First, the two opposing capillary walls establish a zone of contact. Second, the endothelial cell junctions are reorganized and the vessel bilayer is perforated to allow growth factors and cells to penetrate into the lumen. Third, a core is formed between the 2 new vessels at the zone of contact, filled with pericytes and myofibroblasts; these cells begin laying collagen fibers into the core to provide an extracellular matrix for growth of the vessel lumen. The core is fleshed out with no alterations to the basic structure. Intussusception is important, it allows a vast increase in the number of capillaries without a corresponding increase in the number of endothelial cells.
This is important in embryonic development as there are not enough resources to create a rich microvasculature with new cells every time a new vessel develops. Mechanical stimulation of angiogenesis is not well characterized. There is a significant amount of controversy with regard to shear stress acting on capillaries to cause angiogenesis, although current knowledge suggests that increased muscle contractions may increase angiogenesis; this may be due to an increase in the production of nitric oxide during exercise. Nitric oxide results in vasodilation of blood vessels. Chemical stimulation of angiogenesis is performed by various angiogenic proteins e.g integrins and prostaglandins, including several growth factors e.g. VEGF, FGF; the fibroblast growth factor family with its prototype members FGF-1 and FGF-2 consists to date of at least 22 known members. Most are single-chain peptides of 16-18 kDa and display high affinity to heparin and heparan sulfate. In general, FGFs stimulate a variety of cellular functions by binding to cell surface FGF-receptors in the presence of heparin proteoglycans.
The FGF-receptor family is composed of seven members, all the receptor proteins are single-chain receptor tyrosine kinases that become activated through autophosphorylation induced by a mechanism of FGF-mediated receptor dimerization. Receptor activation gives rise to a signal transduction cascade that leads to gene activation and diverse biological responses, including cell differentiation and matrix dissolution, thus initiating a process of mitogenic activity critical for the growth of endothelial cells and smooth muscle cells. FGF-1, unique among all 22 members of the FGF family, can bind to all seven FGF-receptor subtypes, making it the broadest-acting member of the FGF family, a potent mitogen for the diverse cell types needed to mount an angiogenic response in damaged tissues, where upregulation of FGF-receptors occurs. FGF-1 stimulates the proliferation and differentiation of all cell types necessary for building an arterial vessel, including endothelial cells and smooth muscle cells.
Besides FGF-1, one of the most important functions of fibroblast growth factor-2 is the promotion of endothelial cell proliferation and the physical organization of endothelial cells into tube-like struct