Intrauterine Development: Blood & Cardiovascular

• The lecture is about intrauterine development, specifically the early development of blood, the heart, and the vascular system.
• By the end of this lesson, students should be able to describe the main processes involved in the general development of the cardiovascular system (CVS).
• Students should also be able to describe the origin, initial development, and formation of blood vessels.
• Students should be able to identify the primordial cells/tissue of the CVS and link them to their final derivatives.

Blood: Early Development

• Blood cell development begins as early as the 7th day of embryonic life
• The 1st wave of primitive hematopoietic and endothelial cell development happens by day 14 of gestation because of signals to the extraembryonic, endodermal yolk sac.
• Results in the formation of primitive erythroid cells (EryP), megakaryocytes, macrophages, and the endothelium.
• EryP helps in the formation of blood islands
  • Central cells: erythroid and myeloid cells
  • Peripheral cells: endothelial cells
• Blood islands fuse to form vascular channels that span throughout the yolk sac.
• Once in circulation, the EryP cells are enucleated by the fetal liver and macrophages clear the nuclei.
• A second group of cells in the form of HPP-CFC (highly proliferative, multipotent progenitor colony forming cells) also form in the yolk sac.
• HPP-CFC initiates formation of cells of the definitive erythroid lineage from the first wave of definitive hematopoiesis
  • Develops into erythroid/myeloid progenitors
  • Bridges the transition between primitive erythropoiesis and hematopoietic stem cell (HSC) derived erythropoiesis

Hematopoiesis

• The migration of cells begin to colonize the liver, which is the next definitive site of hematopoiesis during gestation.
• The second wave of definitive hematopoiesis replaces primitive hematopoiesis and the first wave of definitive hematopoiesis.
• Hematopoietic stem cells (HSC) emerge from a specialized hemogenic endothelium of aorta's ventral wall, para-aortic splanchnopleure.
• HSC Colonize:
  • Fetal liver by the 7th week of gestation, begins to differentiate
  • Spleen around week 20, produces red cells for a brief period
  • Bone marrow around the same time
• By the end of the 3rd trimester of development, the marrow of specific bones becomes the essential hematopoietic organ.
• The liver and spleen will cease erythropoiesis.
• In postnatal life, definitive erythropoiesis originates from the marrow.

Cardiovascular System: Initial Development

• Development starts in the 3rd week of intrauterine life.
• Mesoderm cells travel through the primitive streak to the embryo's head to form a horseshoe-shaped cellular aggregation
  • This forms the Primary heart field > Heart tubes
• Concurrently, the primitive pericardial cavity forms lateral to each tube.
• At the inferior end, each endocardial tube connects to the vitelline vein that arises from the yolk sac.
• Mesoderm cells also form a pair of longitudinal vessels, the dorsal aortae.
• Lateral folding transforms the embryo into a cylindrical shape.
• The two endocardial tubes fuse to become the primordial heart tube.
• The left and right vitelline veins fuse to become the sinus venosus, which becomes the inflow tract.
• The aortae fuse to form the aortic sac, which becomes the outflow tract.
• The primitive pericardial cavities fuse around the heart tube to form the pericardial cavity.
• The heart tube remains attached to the pericardial cavity by a sheet of mesoderm called the dorsal mesocardium.
• The heart tube has two layers:
  • The inner endothelial lining
  • The outer (later middle) cardiac myoblasts
• Cardiac myoblasts form myocardium
• Some myocardial cells in the sinus venosus begin to produce rhythmic electrical discharge.
• Mesenchymal cells of the dorsal mesocardium form the proepicardial organ
  • Proliferates, migrates over the myocardium to form the epicardium

Craniocaudal Folding

• Craniocaudal folding, also known as head-tail or longitudinal folding, characterizes the development of the heart in week 4.
• The cylindrical embryo folds down along its length, pushing the heart down toward the chest.
• By week 4 the heart tube reaches the thorax and blood can be seen traveling through the heart tube.

The Heart Tube

• Sections of the heart tube:
  • Sinus venosus: left and right sinus horn bring in blood.
  • Primitive atrium becomes the left and right atria.
  • Primitive ventricle forms the left ventricle (atrioventricular sulcus).
  • Bulbus cordis forms the right ventricle, and outflow tracts for both ventricles (Bulboventricular sulcus).
  • Truncus arteriosus: Located at the top of the heart tube, it pumps blood through the aortic sac into an early version of the circulatory system.

Looping and Partitioning

• Looping changes the heart tube from being straight to a C-shape.
• Mesoderm proliferates on the anterior and posterior walls of the atrioventricular canal (anterior/posterior endocardial cushion).
• Cushions divide the heart into:
  • Left atrioventricular canals
  • Right atrioventricular canals
• This forms leaflets of the mitral and tricuspid valves.

Development Of Major Arteries

• The aorta develops through the division of the truncus arteriosus.
• Two endocardial cushions appear on the right-superior and left-inferior walls.
• The cushions grow with a spiraling trajectory, wrapping around each other.
• This forms the aorticopulmonary semilunar valves.
• Arteries of the head, neck, and pulmonary arteries develop from five aortic arches:
  • 1st arch: maxillary artery.
  • 2nd arch: stapedial artery.
  • 3rd arch: two common carotid arteries, internal carotid arteries
  • 4th aortic arch:
    • Left 4th arch: aortic arch.
    • Right 4th arch: right subclavian artery.
  • 6th arch: pulmonary arteries, ductus arteriosus

Development of the Venous and Conducting System

• The venous system develops from the sinus venosus.
• The right sinus horn enlarges and becomes the smooth-walled part of the right atrium (superior, inferior vena cavae).
• The left sinus horn shrinks and persists as the coronary sinus, and oblique vein of the left atrium.
• A special group of myocardial cells in the wall of the sinus venosus organize to synchronize their electrical discharge (pacemaker centers).
• Cells in wall of sinus venosus form the sinoatrial node.
• Cells in the atrioventricular septum form the atrioventricular node.
• Cells in the interventricular septum form the bundle of His.
• The rest of the ventricular myocardium, comes from modified cardiac myocytes, and will become Purkinje fibers.

Vasculogenesis and Angiogenesis

• Vasculogenesis and angiogenesis are the fundamental by which new blood vessels are formed.
• Vasculogenesis Definition:
  • Differentiation of endothelial precursor cells, or angioblasts, into endothelial cells and the de novo formation of a primitive vascular network.
• Angiogenesis Definition:
  • Growth of new capillaries (new blood vessels that lack a fully developed tunica media) from preexisting blood vessels either via sprouting or intussusception
• Angioblasts (aka vasoformative cells) are the embryonic tissue from which blood vessels arise.
• Blood vessels first appear in several scattered vascular areas developed simultaneously between the endoderm and mesoderm.
• The earliest embryonic vessels arise independently in the mesenchyme of the yolk sac wall, chorion, and embryonic disc.
• The angioblasts aggregate as cords which canalize by a process which includes intracellular vacuolation.
• The subsequent extension of the network occurs via:
  • in situ formation of new vessels,
  • sprouting and fusion of established neighboring vessels and
  • invading angioblasts from other regions
• As capillaries mature, a basement membrane is established, containing:
  • collagen IV
  • laminin,
  • nidogen/entactin
  • heparan sulphate proteoglycan and
  • a variable amount of fibronectin