vasculogenesis_angiogenesis_and_cardiogenesis (1)
I. Expanded Discussion on the Formation of Blood Cells (Haematopoiesis)
Overview of Haematopoiesis
Definition: Dynamic and regulated process of blood cell formation occurring in various anatomical sites during embryonic and fetal development.
Phases of Haematopoiesis:
Mesoblastic (Yolk Sac) Period
Hepato-lienal (Liver and Spleen) Period
Medullary (Bone Marrow) Period
1. Mesoblastic (Yolk Sac) Period
Time Frame: Early embryogenesis (approximately day 10 in pigs, day 15 in ruminants, day 21 in horses).
Location: Blood islands in the yolk sac.
Main Cell Types: Primitive erythrocytes (nucleated red blood cells).
Process:
Haemangioblasts aggregate to form blood islands, which give rise to:
Haematopoietic Stem Cells (HSCs): Precursors for all blood cells.
Endothelial Cells: Essential for initial blood vessel formation.
Significance: Produces embryonic erythrocytes with nuclei and embryonic hemoglobin; adapted for oxygen transport from the placenta.
2. Hepato-lienal (Liver and Spleen) Period
Time Frame: Mid-gestation (around day 30 in pigs, day 35 in ruminants, day 40 in horses).
Location: Primarily in the liver, later in the spleen.
Main Cell Types:
Definitive erythrocytes (anucleated red blood cells).
Leukocytes including granulocytes and monocytes.
Megakaryocytes (predecessors of platelets).
Process:
As yolk sac activity declines, HSCs migrate to the fetal liver, becoming the primary site for blood cell production.
The spleen begins to contribute by producing lymphocytes and aiding in blood filtration and iron storage.
Notable Transition: Formation of definitive erythrocytes that are anucleated and contain adult hemoglobin, marking significant fetal development.
3. Medullary (Bone Marrow) Period
Time Frame: Late gestation (~day 50 in pigs, day 60 in ruminants, day 70 in horses).
Location: Bone marrow of long and flat bones.
Main Cell Types:
Erythrocytes, granulocytes (neutrophils, eosinophils, basophils), monocytes, macrophages, lymphocytes (T-cells and B-cells), and platelets.
Process:
Shift of haematopoiesis to bone marrow, which serves as a long-term organ for blood cell replenishment.
Key events include expansion of haematopoietic niches, increased mature immune cell production, and differentiation of lymphoid cells in lymphatic organs.
Post-Birth Changes: Haematopoiesis in the liver and spleen ceases, but can be reactivated in conditions like anemia (extramedullary haematopoiesis).
Regulation of Haematopoiesis
Controlled by various cytokines and growth factors:
Erythropoietin (EPO): Stimulates red blood cell production; produced by the kidneys.
Granulocyte Colony-Stimulating Factor (G-CSF): Promotes white blood cell development.
Thrombopoietin (TPO): Regulates platelet production from megakaryocytes.
II. Expanded Discussion on the Development of the Heart
Overview of Cardiac Development
Importance: The heart is the first functional organ, essential for oxygen and nutrient delivery.
The formation includes:
Primitive heart tube formation.
Folding and looping processes.
Septation into four chambers.
1. Early Formation of the Heart
Time Frame: Days 18–22 in pigs, 20–24 in ruminants, 22–26 in horses.
Tissue Origin: Splanchnic mesoderm in the cardiogenic field.
Key Population:
First Heart Field (FHF): Forms the left ventricle.
Second Heart Field (SHF): Forms the right ventricle, outflow tract, and atria.
2. Folding and Looping of the Heart Tube
Time Frame: Days 22–28 in pigs, 24–30 in ruminants, 26–32 in horses.
Key Process: Asymmetrical folding of the straight heart tube resulting in:
Cranial End: Forms bulbus cordis and primitive ventricles.
Caudal End: Forms primitive atria and sinus venosus.
Rightward Looping (D-looping): Essential for chamber alignment, regulated by genes such as NODAL and PITX2.
3. Chamber Formation and Septation
Time Frame: Days 28–50 in pigs, 30–55 in ruminants, 32–60 in horses.
Partitioning of the Atria:
Septum primum grows and foramen primum closes.
Formation of foramen secundum allowing blood flow.
Septum secundum forms to the right creating the foramen ovale for oxygenated blood to bypass lungs.
Partitioning of the Ventricles:
Muscular and membranous interventricular septa form.
Common Congenital Defects
Formation failure leads to ventricular septal defects (VSDs), a frequent congenital heart defect in domestic animals.
Formation of Atrioventricular Valves
Tricuspid and mitral valves form from endocardial cushions, separating atrial and ventricular blood flow.
4. Development of the Outflow Tract
Time Frame: Days 35–55 in pigs, 40–60 in ruminants, 45–70 in horses.
Key Process: Conotruncal ridges develop to divide the outflow tract (common to both ventricles) into aorta and pulmonary artery.
Septation of the Truncus Arteriosus
Neural crest cells contribute to forming conotruncal ridges that create aorticopulmonary septum.
Formation of Semilunar Valves
Aortic and pulmonary valves develop as swellings in the truncus arteriosus.
5. Fetal Circulation and Postnatal Changes
Fetal adaptations that shunt blood away from the lungs include:
Foramen Ovale: Blood flow from right to left atrium.
Ductus Arteriosus: Connects pulmonary trunk to aorta.
Ductus Venosus: Bypasses the liver, directing blood to inferior vena cava.
At birth, changes trigger closure of these structures ensuring effective postnatal circulation.
III. Expanded Discussion on the Development of the Arterial System
Overview of the Arterial System
Originates from aortic arches and evolves into major arteries.
1. Early Formation
Time Frame: Third week of embryonic development in most domestic species.
Tissue Origin: Mesodermal cells form angioblastic cords differentiating into blood vessels.
2. Aortic Arch Development and Remodeling
Time Frame: Days 24–50 in pigs, Days 26–55 in ruminants, Days 28–60 in horses.
Adult Fates of Aortic Arches:
1st Arch: Part of maxillary artery (early regression).
2nd Arch: Contributes to stapedial artery (regression).
3rd Arch: Forms common carotids and internal carotid artery.
4th Arch: Forms aorta (left) and proximal right subclavian artery (right).
5th Arch: Rarely develops or disappears.
6th Arch: Forms proximal pulmonary arteries and ductus arteriosus.
3. Formation of Major Arteries
Includes arch, subclavian, carotid, and pulmonary arteries, crucial for developing adult circulation.
4. Development of Vitelline and Umbilical Arteries
Vitelline Arteries: Supply yolk sac and later form major gastrointestinal arteries.
Umbilical Arteries: Carry deoxygenated from fetus to placenta and regress postnatally.
5. Postnatal Changes in the Arterial System
Major adaptations occur as fetal circulation ceases, including closure of ductus arteriosus and regression of umbilical arteries.
6. Clinical Correlations and Congenital Defects
Malformations can lead to conditions like Persistent Right Aortic Arch (PRAA) and Patent Ductus Arteriosus (PDA), requiring early detection.
IV. Expanded Discussion on the Development of the Venous System
Overview of Venous System Development
Develops parallel to the arterial system with complex remodeling to form systemic, portal, and pulmonary veins.
1. Early Formation
Time Frame: Third week of development in domestic species.
Tissue Origin: Splanchnic mesoderm, with primary components being vitelline, umbilical, and cardinal veins.
2. Development of Vitelline Veins
Contributes to hepatic and portal circulation. Failure in remodeling can lead to portosystemic shunts.
3. Development of Umbilical Veins
Carry oxygenated blood from placenta; postnatally, they degenerate into ligaments.
4. Development of Cardinal Veins
Drains deoxygenated blood; remodels to form vena cavae:
Cranial Vena Cava: From right common and anterior cardinal veins.
Caudal Vena Cava: From right vitelline, subcardinal, and supracardinal veins.
5. Postnatal Changes in the Venous System
Closure and regression processes occur leading to functional adaptations.
6. Clinical Correlations and Congenital Venous Defects
Conditions like Persistent Left Cranial Vena Cava and Portosystemic Shunt (PSS) can arise from developmental failures.
V. Expanded Discussion on Fetal Circulation
Overview of Fetal Circulation
Unique system that maintains oxygen and nutrient delivery while bypassing non-functional organs.
1. Key Shunts in Fetal Circulation
Foramen Ovale, Ductus Arteriosus, and Ductus Venosus each serve to ensure proper bypassing of the lungs and liver.
2. Postnatal Changes
Significant changes occur at birth with the closure of shunts, affecting blood circulation efficiency.
3. Clinical Relevance
Conditions like Patent Foramen Ovale (PFO) and Patent Ductus Arteriosus (PDA) highlight the need for attention in neonatal care.
VI. Comparative Aspects in Domestic Animals
Variations exist in embryonic development timelines and functional adaptations among species including dogs, cats, horses, ruminants, and pigs, relevant for veterinary diagnostics.
VII. References
McGeady, T. A., et al. (2017). Veterinary Embryology (2nd ed.). Wiley-Blackwell.
Hyttel, P., et al. (2010). Essentials of Domestic Animal Embryology. Elsevier.