L2. Development of the Heart PDF
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Ammar B Humaidi, Rana Sayed
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This document provides a detailed overview of the development of the heart, from its initial formation to the development of the heart chambers. It covers various aspects of heart development, including the formation of the cardiogenic region, the heart tubes, looping, and the formation of the atrioventricular and interventricular canals.
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02 Anatomy Dr. Mubarak Bidmos Development of the heart 18th January 2020 Ammar B Humaidi Rana Sayed This document resorted to: 1. “Development of the Heart” Lecture Slides. 2. “Langman’s Medical embryology 13th”. 3. “Pathophysiology of Heart Disease 6th”. Greetings future doctors, in this sheet we w...
02 Anatomy Dr. Mubarak Bidmos Development of the heart 18th January 2020 Ammar B Humaidi Rana Sayed This document resorted to: 1. “Development of the Heart” Lecture Slides. 2. “Langman’s Medical embryology 13th”. 3. “Pathophysiology of Heart Disease 6th”. Greetings future doctors, in this sheet we will go through the development of the heart which is the main component the cardiovascular system. It’s truly incredible how some embryonic tissue goes through all the complex stages of development that take place so accurately to ultimately give rise to the heart, the fist sized structure, that potentially starts beating at the 4th week of conception to continue beating and constantly pumping the blood throughout the whole body for many years and decades that one lives! Indeed, that is the creation of Allah, {}فتبارك هللا أحسن الخالقين. Overview: This sheet comprises the following concepts: ① an introduction to the development of the heart, ② formation of the cardiogenic region and the angioblastic cords, ③ formation of the two heart tubes and their fusion to a single tube, ④ the parts of the single heart tube, ⑤ the looping of the heart, ⑥ the formation of the AV canal, the IV foramen and the endocardial cushion, ⑦ the septation of the common atrium, ⑧ the atrial septal defects,⑨ the sinus venosus and the fate of its components, ⑩ the ventricular septum, and ⑪ the VSDs. Anatomical Orientations and Planes (revisited): Let us recall the terminologies that describe the anatomical orientation and the body planes. Appreciate the illustrations (Fig.1) below to have a quick view. You can also watch the suggested video. Notice that for the embryo, we use ‘cranial’ instead of superior, ‘caudal’ instead of inferior, ‘ventral’ instead of anterior, and ‘dorsal’ for posterior. Human Anatomy: Anatomical Position, Orientation & Directional Terms, and Body Planes 2 Figure 1. The anatomical orientation and planes Introduction to the Development of the Heart: ▪ The cardiovascular system is an extremely important system. Its formation begins during the third week of the embryonic development as the primordial heart and vascular system appears. ▪ Interestingly, the cardiovascular system is the first system to function in the embryo. The reason being is that by the third week of gestation, the nutrient and gas exchange needs of the rapidly growing embryo (the growth of the simple bilaminar disc to a more complex trilaminar structure and so forth) can no longer be met by simple diffusion alone, and the tissues have to rely on a more efficient circulatory system to deliver these substances over long distances. ▪ The cardiovascular system develops from two sources: 1. Splanchnic Mesoderm: Recall that there are three component of the mesoderm layer; paraxial mesoderm, intermediate mesoderm, and the lateral plate mesoderm. The latter will be further divided into two parts by the appearance of the intraembryonic coelom in-between of them. Those two parts are intraembryonic somatic mesoderm and the intraembryonic splanchnic mesoderm, the one which is of our interest (Fig.2). Figure 2. Components of the mesoderm 2. Neural Crest Cells: Also recall that one of the three layers of the trilaminar disc is the ectoderm. It forms neural folds and hence neural groove. At the apices of the neural folds, we have cells called neural crest cells and that’s where they come from (Fig.2). Formation of Angioblastic Cords: Looking at the embryo from the ventral aspect (having the yolk sac removed and the yellow part resembling the endoderm) (Fig.3), we can see ‘blood islands’ as the cells in the intraembryonic splanchnic mesoderm (IESM) transform into lots of blood cells and structures that will eventually form the heart. With time, the islands unite to form a region known as the cardiogenic region/area. As the development continues, some mesenchymal cells in the cardiogenic area will form the angioblastic cells, which later form two longitudinal cell clusters known as angioblastic cords found in the IESM (Fig.5A). When taking a sagittal section of the embryo (Fig.4), we can actually see the development of the cardiovascular system occurring at the cranial end of the embryo. Blood islands Figure 3 Figure 4 3 Formation of Two Heart Tubes: ▪ With time, the chords will be canalized (Fig.5B), meaning that lumen will appear within them and the chords will be transformed into paired endothelial tubes. Thus, they will make the two heart tubes that are the left and right heart tubes. ▪ Those tubes will be lying side by side and are joined by channels between them. ▪ As the embryo grows and bends cephalocaudally, it also folds laterally. This will gradually cause these two tubes to oppose one another and allow them fuse in a craniocaudal direction in the ventral midline, forming a single endocardial tube (Fig.4C) by day 22 (or late third week). Now, remember the intraembryonic coelom? That space now becomes the pericardial cavity. Figure 5. Transverse sections depict the two heart tubes and the lateral folding that cause them to fuse. The Single Heart Tube and Its Parts: ▪ As the tubular heart grows and elongates, it develops a series of alternative constrictions and dilatations (Fig.6A) and the tube will be divided into 5 distinct parts: 1. Truncus arteriosus: Continues cranially with aortic sac (discussed in a following sheet). This part forms the arteries such as the ascending aorta and the pulmonary trunk. 2. Bulbus cordis: Located between the truncus arteriosus and the primitive ventricle. 3. Primitive ventricle: The largest part. 4. Primitive atrium: It leads to ventricle through the atrioventricular (AV) canal. 5. Sinus venosus: The unfused part (thus has 2 parts, the right and left horns), and it receives blood from veins. So, the oxygenated blood (coming from the placenta through the umbilical vein) will enter the heart through the sinus venosus to pass through it and exit from the other side where the truncus arteriosus is located. ▪ Essentially, the Primitive circulation begins in the 4th week, whereby peristaltic waves move blood through the single heart tube. Figure 6. The primitive heart tube and its five dilations. A: day 22, no looping. B: day 26, the straight heart tube begins dextral looping. C: days 30-35, dextral looping is complete, and the four primitive heart chambers are apparent. AS= aortic sac, aa= aortic arch. Figure 7. The single heart tube components and their ultimate location. Details are discussed later. 4 Formation of Heart Loop: ▪ The continued growth and elongation of the tube within the confined (limited in area or volume) pericardial cavity will force the heart rube to bend/fold/loop on itself on day 23. ▪ The bulboventricular portion (includes the bulbus cordis and the primitive ventricle) grows faster than the rest of the heart. ▪ The cephalic portion (the truncus arteriosus and the bulboventricular portion) of the tube bends ventrally, caudally, and to the right. However, the caudal portion (the atrium and sinus venosus) shifts in a dorso-cranial direction and slightly to the left. As a result, primitive atrium and sinus venosus come to lie posterior and superior to the developing ventricles. See (Fig.6B, C) & (Fig.8). ▪ Normally, the heart loops to the right causing the apex of the heart to point to the left side placing the heart in its correct position. This is called dextral looping. Dextrocardia is a condition where the heart loops to the left instead of the right resulting in placing the apex of the heart on the right side of the body. Lateral view Figure 8. Formation of the cardiac loop. A. 22 days. B. 23 days. C. 24 days. D. Frontal view of the heart tube undergoing looping in the pericardial cavity. 5 Formation of Atrioventricular Canal and Interventricular Foramen: ▪ Initially, there is only a single atrium and a single ventricle since there is no septation between them. However, there is the junction between the ventricle and the atrium that remains narrow and forms the atrioventricular canal (Fig.9). ▪ This AV canal will later be divided into two by the endocardial cushion (discussed next). ▪ Similarly, the junction between the primitive ventricle and the bulbus cordis also remains narrow, protruding into the ventricle, Figure 9 giving rise to the interventricular foramen. ▪ Before the septa or the walls of the heart are formed, (Fig.10) shows how the single heart tube looks like. You can see that the truncus arteriosus is the cranial part, the primitive ventricle is lying ventral and inferior to the primitive atrium. Formation of Endocardial Cushion: ▪ Prior to septation or formation of the walls, the formation of the endocardial cushion takes place. ▪ This process is important for the subsequent formation of the atrial and ventricular septa as you will get to see shortly. ▪ So, this process begins as projections of tissue (endocardial cushion) appear on the dorsal (superior) and ventral (inferior) walls of the atrioventricular canal (Fig.11). The Figure 10 tissue projections approach each other (across the horizontal plane) and fuse, completing the formation of the endocardial cushion that divides the atrioventricular canal into two canals, the right and the left AV canals (Fig.12). Figure 11. Frontal view of the developing heart showing the formation of the endocardial cushion. Figure 12. Formation of the septum in the atrioventricular canal. From left to right, days 23, 26, 31, and 35. The initial circular opening widens transversely. 6 Septation of the Common Atrium: The septation of both, the common atrium and the common ventricle is a very crucial concept to understand, because there are many potential congenital heart defects that result from inadequate septal formation. So, let’s discuss the atrial septum first. Formation of Septum Primum: From the roof of the single (common) atrium, a ridge of tissue appears as a crescentic structure and grows downwards approaching the endocardial cushion. This growing structure is known as the septum primum (Fig.13A). As the septum primum advances, it leaves a large Perforations opening known as the ostium primum between the crescent-shaped leading Ostium edge and the endocardial primum cushion. As this process of B approaching the endocardial A C cushion progresses, the Ostium secundum ostium primum gets smaller and smaller (Fig.13B). Before they actually fuse, perforations appear at the cranial end of the septum F D E primum (Fig.13C). Figure 13. Formation of the atrial septum. The arrows in F indicate the Those perforations ultimately direction of blood flow from R to L across the fully developed atrial septum. coalesce to form the ostium Septum primum = green, septum secundum = blue. secundum, preserving a pathway for blood flow between the atria (the R to L shunt). The ostium primum now fuses with the endocardial cushion (Fig.13D). Following closure of the ostium primum, a second, more muscular membrane, the septum secundum, begins to develop immediately to the right of the superior aspect of the septum primum (Fig.13E) This septum secundum grows towards the endocardial cushions, and its free edge overlaps the ostium (foramen) secundum (Fig.13F). As the septum secundum eventually fuses with the endocardial cushions, the fusion remains partial, leaving an oval-shaped opening known as the foramen ovale (Fig.13F). The superior edge of the septum primum then gradually regresses (and disappears), leaving the lower part to act as a “flap-like” valve that allows only right-to-left flow through the foramen ovale. Notice that the development is occurring in a way that there is always an opening between the atria. This is because the right atrium of the fetus gets the oxygenated blood coming from the placenta and hence does not have to pump it to the lungs, yet it has to be directed (shunted) to the left atrium under the pressure gradient to be pumped to the systemic circulation. That’s why it is important to have a foramen within the septum separating the atria. 7 Atrial Septum: Before and After Birth: Before birth, as explained earlier, the connection between the atria allows passage of blood from the right to the left. This happens under the pressure gradient. The valve of the foramen ovale (that used to be the inferior part of the septum primum) would allow the passage of the blood in one, R to L, direction (Fig.14A). However, after birth, the pressure of the left atrium increases, and it causes the valve of the oval foramen to be pressed against the septum secundum. The result is the obliteration of the oval foramen and the Right atrium is separated from the left atrium (Fig.14B). Atrial Septal Defects (ASDs): Ostium Primum Defect (Fig.15): ▸ This defect results from the failure of septum primum to fuse with the endocardial cushions (may be due to abnormal development of the cushion). ▸ Since the closure of ostium primum is defected, it is located on the lower part of the atrial wall. ▸ The fossa ovalis (obliterated foramen ovale in an adult) appears normal in these cases. ▸ It is common in patients with Down Syndrome (the down part is open). Ostium Secundum Defect: ▸ The most common atrial septal defect. ▸ Can result from: ❖ Excessive resorption of septum primum (Fig.16A): meaning that the part of it that should normally form the valve of the foramen ovale is overly degenerated, leaving the foramen ovale to be partially or completely open. ❖ Inadequate development of the septum secundum (Fig.16B): if the septum secundum is not adequately formed, the normally occurred separation of atrium will be disrupted. The defect can also be a result of a combination of both of the aforementioned causes. Figure 14 Figure 15 A B ▸ The opening is located in the central (or cranial) part of the atrial Figure 16 septum. ▸ The case and severity differ depending on the size of the abnormal opening and the amount of L to R shunting that occurs. For small openings, they can spontaneously fuse and close if small enough or the symptoms may be delayed even till age of 30 years. Some other cases may need immediate surgical approach or heart transplant if they are severe with larger openings and complex defects. 8 The Sinus Venosus (SV): After discussing the septation of the common atrium, we shall talk about the development of the right and left atria. The reason why the sinus venosus is presented in this part of the sheet is that this is the part which eventually contributes to the formation of the right atrium, as well as some other structures of the heart as we will see. Components of Sinus Venosus (Fig.17): It consists of two horns, the left and right sinus horns. Each of these horns receives blood from: ▸ Vitelline vein ▸ Umbilical vein ▸ Common cardinal vein B Figure 17 Derivatives of Right Sinus Horn (RSH): Initially, the sinuatrial junction (between the sinus venosus and the primitive atrium) is wide and in the midline (Fig.17B). However, with looping of the heart tube, the right horn becomes enlarged as well as the 3 veins associated with it (Fig.18). As the development goes on, the right sinus horn become a part of the right atrium, specifically the smooth-walled part. In other words, the RSH becomes incorporated into the right atrium forming the smooth walled part. This smooth-walled part of the right atrium is called sinus venarum (Fig.20), referring (by its name) to its origin which is the right horn of the sinus venosus. The right common cardinal vein becomes the superior vena cava, and the right vitelline vein becomes the inferior vena cava (Fig.20). Derivatives of Left Sinus Horn (LSH): As opposed to the right sinus horn, the left sinus horn gradually becomes smaller. The LSH contributes to the formation of the coronary sinus and the oblique vein of the left atrium (Fig.20). However, all the veins that used to drain in the LSH (Left vitelline, umbilical and cardinal veins) obliterate. Figure 18 Figure 19 9 Figure 20 Differentiation of the Left Atrium: The left atrium develops a bit differently since the LSH does not contribute to the left atrium formation as the RSH does to the right atrium. Initially, a single primordial pulmonary vein develops on the dorsal wall of the left atrium. This is the only vein that opens and drains into the left atrium at that stage (Fig.21A). As the heart develops and the left atrium enlarges, the pulmonary vein and its branches are incorporated into the wall of the left atrium. As a part of the development, the single opening of the pulmonary vein into the left atrium becomes two, and then 4 openings, all to be incorporated with the left atrium forming the smooth-walled part of it (Fig.21B). Only a small part of the primitive left atrium will remain in an adult’s left atrium as the left auricular appendage (Fig.21B). Auricular appendage Figure 21 The atrial septum descends from the roof of the primitive atrium, while the ventricular septum grows from the floor of the primitive ventricle. Formation of Ventricular Septum: Unlike the atrial septum which is formed from two parts (two septa), there is only one septum for the interventricular septum. Yet, although it is one septa, it has two components (presented shortly). Partitioning of Primordial Ventricle: The median muscular ridge or the primordial interventricular (Fig.22A) septum gradually grows from the floor of the primitive ventricle towards the fused endocardial cushions. The medial walls of the ventricles approach each other, forming that huge ridge in the midline known as the muscular part of the interventricular septum (Fig.22B). Muscular interventricular septum extends towards the fused endocardial cushions. A B Figure 22a Figure 22b 10 However, there is a space between the muscular interventricular septum and the endocardial cushion since they do not fuse, and the space is called the interventricular foramen (Fig.22B). This foramen allows the communication between the ventricles as this gap (foramen) connects between the left and right ventricles and the blood can flow from right to the left. Later on, the interventricular foramen has to be closed to avoid mixing of the blood. So, it will be closed by the development of the membranous part of the interventricular septum (Fig.23C). This membranous part is derived from three sources: ▸ The inferior part of the endocardial cushions (Fig.23A). B ▸ Right conotruncal ridges (Fig.23B). Figure 22b ▸ Left conotruncal ridges (Fig.23B). Ultimately, the primitive ventricle is separated into rough part of right and left ventricles. Figure 23 Ventricular Septal Defect: Since the membranous part of the ventricular septum is derived from three different sources, any underdevelopment or problems in any of those sources would cause defects in its formation. This is the reason why ventral septal defects are way more commonly seen at this part of the ventricular wall (septum). In other words, the membranous ventricular septum develops VSDs more often compared to other parts of the septum. Generally, VSDs are the most common type of congenital heart diseases with being more common in males. The small VSDs can close spontaneously. Large VSDs are associated with left to right shunting of the blood, causing serious consequences The main two types of the VSDs are the membranous VSDs (Fig.24) and the muscular VSDs (Fig.25); depending on the part of the septum defected. 11 Figure 24. The membranous VSD Figure 25. The muscular VSD Last but not least, here is a summary for each step: 1- Heart tube formation : 2- Formation of cardiac loop and its derivatives: 12 3- Atrial septal formation 4- Ventricular septal formation Don’t hesitate to contact Ammar / Rana regarding any clarification, concern or suggestion! 13