L4. Development of Great Vessels-1.pdf

04 Anatomy Dr. Mubarak Bidmos Development of Great Vessels 14th January 2020 Yazan Al-Dali Zahra Yousif 1 This document resorted to: 1. “Development of Great Vessels” Lecture Slides. 2. “Langman’s Medical Embryology 13th” Chapter 13. 3. “Pathophysiology of Heart Disease 5th” Chapter 16. Overview Thi...

04 Anatomy Dr. Mubarak Bidmos Development of Great Vessels 14th January 2020 Yazan Al-Dali Zahra Yousif 1 This document resorted to: 1. “Development of Great Vessels” Lecture Slides. 2. “Langman’s Medical Embryology 13th” Chapter 13. 3. “Pathophysiology of Heart Disease 5th” Chapter 16. Overview This sheet describes the ① formation of the aorticopulmonary septum and address its ②clinical significance. Then we will move to the development of the ③ systemic arteries and again mention the ④ common congenital defects that may occur. Lastly, we will talk about ⑤ Eisenmenger Syndrome. Aorticopulmonary Septum Formation Figure 1 From the previous anatomy lecture (sheet#2) we came to know about the formation of the Atrial Septum as well as the Interventricular Septum. Now we will be talking about the septum that will give rise to 2 major structures. However, before that lets have a quick recap on the heart tube. As the tubular heart grows and elongates, it develops a series of alternate constrictions and dilatations, creating the first sign of the primitive heart chambers; (Fig.1) A) Truncus Arteriosus B) Bulbus Cordis C) Primitive Ventricle D) Primitive Atrium E) Sinus Venosus Continued growth and elongation within the confined pericardial cavity force the heart tube to bend on itself on day 23. Then by day 28, the result of this looping is placement of the Atrium and Sinus Venosus above and behind the: ① Truncus Arteriosus, ② Bulbus Cordis and the ③ Ventricles (Fig.2). Figure 3 Figure 2 During the 5th week, neural crest cells-derived proliferation occurring in the bulbus cordis and truncus arteriosus creates a pair of protrusions known as the conotruncal ridges (Fig.3). These ridges fuse in the midline and undergo a 180° spiraling process, forming the aorticopulmonary septum (APS). This septum will divide the: 1) Truncus Arteriosus (TA)  Ascending Aorta.  Pulmonary Trunk. 2) Bulbus Cordis (BC)  Conus Arteriosus of the Right Ventricle (Fig.4).  Aortic Vestibule of the Left Ventricle (Fig.5). Figure 5 Figure 4 2 What could go wrong? Notice that the Aorticopulmonary Septum must be ① formed, ② spiralled and ③ situated in the midline (proper alignment). Any issue in any of the 3 will give rise to different pathological defects that originate from Truncus Arteriosus. 1- Persistent Truncus Arteriosus It is also called Common Truncus Arteriosus. This defect results when the conotruncal ridges fail to form completely or partially such that no division of the outflow tract of the heart occurs because of failure of formation or partial development of aorticopulmonary septum. This defect is always associated with membranous VSD. Because of the fact that the membranous part of the interventricular septum is formed from 3 sources; ① the right conotruncal ridge, ② the left conotruncal ridge and ③ the endocardial cushions, failure of formation of the conotruncal ridges (just like in our case) will also affect the formation of the membranous part of the interventricular septum resulting in Ventricular Septal Defect. All of this will result in an undivided truncus arteriosus (Fig.6) which will override both ventricles and receive blood from both sides. Hence, mixing oxygenated with deoxygenated blood giving rise to a cyanotic heart disease. Figure 6 2- Transposition of Great Vessels     This defect results when the aorticopulmonary septum fails to follow its normal spiral course and runs straight down. The spirality’s significance initially was that it divides the Bulbus Cordis & Truncus Arteriosus resulting in an anterolateral portion (outflow tract of Right Ventricle) and a posteromedial portion (outflow tract of Left Ventricle). Because of failure of spiraling (as in this case), the Aorta will originate from the Right Ventricle, and the Pulmonary Trunk will originate from the Left Ventricle. This switch in the major blood vessels will result in the following loop (Fig.7): Deoxygenated blood getting pumped from the Right ventricle into the Aorta and then to the rest of the body. This deoxygenated blood will return to the Right atrium  Right Ventricle and then gets pumped again back to the aorta and hence to the rest of the body. Looking at the opposite side’s loop, you have oxygenated blood getting pumped from the left ventricle into the pulmonary trunk and then to the lungs. This oxygenated blood will return to the Left atrium  Left Figure 7 Ventricle and then gets pumped back again to the Pulmonary Trunk and hence to the lungs again. Transposition of Great Vessels is the most common cause of severe cyanosis that 3 persists after birth 3- Tetralogy of Fallot This defect results from a single developmental defect; the failure of proper alignment of aorticopulmonary septum in the midline. An abnormal anterior displacement that will result in unequal division of the Truncus Arteriosus, giving rise to 4 cardiovascular alterations (Fig.8): A) Pulmonary Stenosis: Because the Aorticopulmonary septum did not divide the TA into equal portions, one of the major blood vessels must be bigger than the other. And in this case, a narrow Right Ventricular outflow will arise (narrow pulmonary trunk base). B) Right Ventricular Hypertrophy: Because the right ventricle will have to pump against higher resistance due to the obstruction of the pulmonary trunk’s stenosis, the R.V will hypertrophy. C) Ventricular Septal Defect: Due to the anterior malalignment of the membranous interventricular septum, a VSD will arise. Both contribute in making TOF the most common congenital Cyanotic heart disease. D) Overriding Aorta: Again, because the TA is divided into unequal portions, the Aorta will takeover (override) to the Right ventricle. Therefore, the base of the Aorta will be found lying on both ventricles. What does this mean? It means that the aorta will be receiving blood from both ventricles and yeah, just like you guessed, mixing of oxygenated and deoxygenated blood will happen resulting in cyanotic heart disease. Bottomline    Persistent Truncus Arteriosus Failure to form of APS Transposition of Great VesselsFailure of spiraling of APS Tetralogy of Fallot Failure of proper alignment of APS Figure 8 Before moving on to the next topic, let’s have a quick recap on the structures that will ultimately form from each segment from the single heart tube (Fig.9) -TA: Pulmonary Trunk & Ascending Aorta. -BC: Smooth parts of the Ventricles leading to the respective blood vessel. - PV: The Ventricles - PA: The Auricles - SV: Right Sinus HornSmooth wall of Right Atrium1 : Left Sinus HornOblique Vein of Left Atrium Coronary Sinus Figure 9 4 1 If you might be wondering where the smooth wall of the Left Atrium comes from, it’s from the Pulmonary Vein Vascular Development Blood Vessels development occurs by two mechanisms; 1- Vasculogenesis: Vessels arise by coalescence of angioblasts. 2- Angiogenesis: Vessels sprout from existing vessels. The major blood vessels are formed by Vasculogenesis, while almost all of the vascular system then forms by Angiogenesis. Once the process of Vasculogenesis establishes a primary vascular bed, additional vasculature is added by Angiogenesis, the sprouting of new vessels. This process is mediated by Vascular Endothelial Growth Factor (VEGF) which stimulates proliferation of endothelial cells at points where new vessels are to be formed. This is called preferential systematic development. 4 main channels will form (Please keep an eye on Figure 10 & 11 to understand): 1- Aortic Sac: Found cranial to the truncus arteriosus. 2- Right & Left Dorsal Aortae: Found on both sides of the Aortic Sac and is fused between T4 and L4 (as in it remains a pair of two dorsal aorta cranial to T4 and caudal to L4). 3- Pharyngeal Arch Arteries (PAA): 6 pairs of arches will connect the dorsal aortae to the aortic sac. 4- Intersegmental Arteries: Both dorsal aortae also give rise to seven pairs cervical intersegmental arteries laterally. The upper six of those anastomose (connect), while the last 7th intersegmental artery arise from the lateral aspect of the dorsal aortae cranial to T4. Figure 10 Please note that (Fig.10) does not actually represent what exactly happens in the Vascular development. Reason being that the 6 pairs of the PAAs usually develop but are never present at the same time, where serial appearance proceed in a craniocaudal direction. By the time the 3rd pair develops, the 1st pair has regressed. Aortic Arch Transformation into Fetal Pattern By week 8, the aortic arch pattern is transformed into the final fetal arterial pattern. The 6 pairs of the Pharyngeal Arch Arteries will become modified and some vessels regress completely. How did this happen? “Let’s start with what we know” Figure 11 5 Please understand the color coding on the figures, that will ease your understanding! 1. Division of the Truncus Arteriosus by the Aorticopulmonary septum divides the outflow channel of the heart into the Aorta and the Pulmonary Trunk. 2. The Aortic Sac then forms right and left horns, which subsequently give rise to the Brachiocephalic artery and the proximal segment of the Aortic Arch, respectively. Dorsal Aorta between 3rd & 4th PAA disappears 3. By day 27, most of the 1st PAA disappears, leaving behind a small portion that persists to form the Maxillary Artery1 4. Similarly, most of the 2nd PAA disappears, leaving behind a portion that will remain as the Hyoid & Stapedial2 Arteries. 5. Then the proximal part of the 3rd PAA Figure 12 forms the Common Carotid Artery, while the distal part joins the Cranial Dorsal Aorta to form the Internal Carotid Artery. Figure 12 Moreover, the External Carotid Arteries arise as outgrowth from the root of the Internal Carotid Artery. 6. The 4th PAA persists on both sides, but its ultimate fate is different on the right and left sides. On the left, it forms part of the proximal Arch of the Aorta (between the left common carotid and the left subclavian arteries). On the right, it forms the most proximal segment of the Right Subclavian Artery, while the distal part is formed by a portion of the caudal right dorsal aorta and the right 7th intersegmental artery. NOTE: The distal part of the Arch of Aorta is from the Caudal Left Dorsal Aorta. NOTE: The left 7th intersegmental artery forms the left subclavian artery. 7. The 5th PAA either never forms or forms incompletely and then regresses. 8. The 6th PAA gives off an important branch that grows toward the developing lung bud. On the right side, the proximal part of the 6th PAA forms the proximal segment of the right pulmonary artery. The distal portion of 6th right PAA degenerates. On the left side, the proximal part of the 6th PAA forms the proximal segment of the left pulmonary artery. The distal portion of 6th left PAA will form the Ductus Arteriosus. 6 1 The external carotid artery divides into 2; the superficial temporal and the maxillary artery. The middle ear consists of 3 bones; the Malleus, Incus & Stapes. The stapedial artery is a small artery supplying the stapedius muscle which is responsible for stabilizing the stapes bone when loud sounds enter the ear. 2 It is important to note that one of the changes that occur along with the alterations in the aortic arch system is what happens to the position of the Recurrent Laryngeal Nerve. But before mentioning the change, let’s understand the neuroanatomy of this nerve :’) The Recurrent Laryngeal Nerve (RLN) is a branch of the Vagus nerve (Cranial Nerve X) that supplies almost all the intrinsic muscles of the larynx. There are 2 RLNs; the Right Recurrent Laryngeal Nerve (RRLN) and the Left Recurrent Laryngeal Nerve (LRLN). Initially, these nerves supply the 6th PAA. When the heart descends, they hook around the 6th PAA and ascend again to the larynx, which accounts for their recurrent course. On the right side (Fig.13), when the distal part of the right 6th PAA and the 5th PAA disappear, the Right Recurrent Laryngeal Nerve moves up and hooks around the right subclavian artery (which comes from the right 4th PAA). Figure 13 On the left side (Fig.14), the Left Recurrent Laryngeal Nerve does not move up because the distal part of the 6th PAA persists as the ductus arteriosus, which later closes and forms the ligamentum arteriosum. Figure 14 Arterial System Defects 1- Patent Ductus Arteriosus (PDA) Under normal conditions (Fig.15 left heart), the Ductus Arteriosus (DA) is functionally closed through the contraction of its muscular wall shortly after birth to form the ligamentum arteriosum. In this case, Patent Ductus Arteriosus, the DA fails to close (Fig.15 right heart). This will lead to an increased blood flow to lungs because blood is being pushed from the descending aorta (higher pressure) to the left pulmonary artery (lower pressure). Hence, an Figure 15 increase in the pulmonary blood vessels’ pressure will happen. Consequently, the patient will have pulmonary hypertension that will lead to pulmonary edema.  Clinical features of PDA: ① Dyspnoea (difficulty in breathing), ② fatigue, ③ anorexia (eating disorder), ④ poor weight gain and ⑤ machinery murmur (continuous murmur). 7 2- Coarctation of the Aorta   In this defect, the aortic lumen narrows in the descending aorta distal to the origin of the left subclavian artery. It can happen anywhere in the descending aorta (thoracic or abdominal), but is more common in the Thoracic part. The reason for this coaractation is unknown, it happens sporadically. It is classified into 3 (Fig.16); A- Preductal= Coarctation before the Ductus Arteriosus. B- Juxtaductal= Coarctation next to the Ductus Arteriosus. C- Postductal= Coarctation after the Ductus Arteriosus. Figure 16 Complications include ① hypertension, ② left heart failure (L.V pumping against higher resistance) and ③ renal failure (because of oligemia). When the coarctation is present, the ① pulses, ② temperature and the ③ pressure in the upper limb are all higher & greater when compared to the lower limbs. The reason is because in all 3 types, the coarctation (narrowing) is after the 3 branches of the Arch of the Aorta, which basically means that more blood will be pumped to these branches that supply the upper limbs when compared to the amount of blood reaching the lower limbs. 3- Eisenmenger Syndrome This syndrome is a complication of any untreated congenital cardiac defect with intracardiac communication (Fig.17). A- In any heart defect, the pressure in the systemic circulation (Left side of the heart) is higher than the pulmonary circulation (Right side of the heart), hence the blood flows from the left side to the right side, a LR shunt. B- However, if not treated, with time this difference in pressure will reverse. Looking at the pulmonary circulation blood vessels’ lumen, after continuous overflow of blood, the walls of the smooth muscle in Figure 17 the tunica media will enlarge. The mechanism by which increased pulmonary flow causes this condition is unknown. Overtime, the vessels become thrombosed, the resistance of the pulmonary vasculature rises. Hence, an increase in the pulmonary pressure. A state of equilibrium between the pulmonary and the systemic pressure will happen and here only a bidirectional mixing of blood between the existing shunt will take place. C- As the lumen of the Pulmonary circulation decrease even more, an increase in the pulmonary pressure that will exceed the systemic pressure will happen and this will lead to a RL shunt; which is Eisenmenger Syndrome. It is characterized by ① Pulmonary hypertension, ② reversal of blood flow and ③ Cyanosis. 8 Don’t hesitate to contact Yazan Al-Dali/ Zahra Yousif regarding any clarification, concern or suggestion!