20.6 Development of Blood Vessels and Fetal Circulation

Development of Blood Vessels

Formation of Blood Vessels

The cardiovascular system is one of the first organ systems to develop in the embryo, and it arises from embryonic mesoderm, one of the three primary germ layers formed during gastrulation (the others being ectoderm and endoderm).

The cell lineage that builds blood vessels follows a specific path:

1. Hemangioblasts are multipotent stem cells derived from mesoderm. They give rise to two key cell lines: hematopoietic stem cells (which produce blood cells) and angioblasts.
2. Angioblasts are endothelial cell precursors. They migrate, proliferate, and differentiate into the endothelial cells that line the inner walls of blood vessels.
3. These angioblasts organize into a primitive vascular plexus, which is the embryo's first rough network of small blood vessels.

Two distinct processes build the vascular system:

• Vasculogenesis is the de novo formation of blood vessels from angioblasts. This is how the primitive vascular plexus first forms. Think of it as building vessels from scratch.
• Angiogenesis is the formation of new blood vessels from pre-existing ones. It works through sprouting of new branches or splitting of existing vessels (called intussusceptive angiogenesis). This process expands and remodels the primitive plexus into a mature vascular network.

Angiogenesis is stimulated by vascular endothelial growth factor (VEGF), which is produced when tissues experience hypoxia (low oxygen). Wherever tissue needs more oxygen, VEGF signals new vessels to grow toward it.

Regulation of Blood Vessel Development

• Hypoxia-inducible factor (HIF) is a transcription factor activated under low-oxygen conditions. It drives the production of VEGF and other angiogenic factors, promoting new vessel formation to increase oxygen delivery. HIF is the upstream signal; VEGF is the downstream effector.
• Embryonic stem cells can differentiate into the cell types involved in blood vessel formation, making them a potential resource for tissue engineering and regenerative medicine approaches to vascular disorders.

Fetal Circulation

The fetal circulatory system is built around one central fact: the placenta, not the lungs, handles gas exchange. Because the fetal lungs are collapsed and fluid-filled, the circulatory system uses three shunts to route blood away from the lungs and toward the placenta.

Fetal Circulatory Shunts

Each shunt serves a specific bypass function:

1. Ductus venosus shunts oxygenated blood from the umbilical vein directly to the inferior vena cava, bypassing the liver. This allows oxygen-rich blood from the placenta to reach the fetal heart and brain quickly.
2. Foramen ovale is an opening that shunts oxygenated blood from the right atrium to the left atrium, bypassing the pulmonary circulation. This sends more oxygenated blood into the systemic circulation rather than to the non-functional lungs.
3. Ductus arteriosus shunts blood from the pulmonary artery to the aorta. The majority of right ventricular output enters the systemic circulation through this route, further diverting blood away from the lungs and helping maintain high pulmonary vascular resistance.

Fetal vs. Adult Circulation

• Oxygenation

  1. In the fetus, the umbilical vein carries oxygenated blood from the placenta to the fetus, and the umbilical arteries (two of them) carry deoxygenated blood back to the placenta. The lungs play no role in gas exchange.
  2. In adults, blood is oxygenated in the lungs and returns to the left atrium via the pulmonary veins.

• Blood flow patterns

  1. Fetal circulation uses shunts (ductus venosus, foramen ovale, ductus arteriosus) to preferentially direct oxygenated blood to the brain and heart.
  2. Adult circulation has no shunts. Blood flows through the pulmonary and systemic circuits in series.

• Placental circulation

  • Present only in the fetus; responsible for gas exchange, nutrient transfer, and waste removal.

• Pulmonary circulation

  • Minimal in the fetus because the lungs are non-functional. In adults, all blood from the right ventricle passes through the lungs for oxygenation.

• Fetal hemoglobin

  • Fetal blood contains fetal hemoglobin (HbF), which has a higher oxygen affinity than adult hemoglobin (HbA). This is what allows the fetus to efficiently extract oxygen from maternal blood at the placenta, where oxygen levels are relatively low compared to inhaled air.

Cardiovascular Transition at Birth

At birth, the newborn transitions from placental gas exchange to breathing air. This triggers a rapid series of cardiovascular changes:

1. The lungs inflate with the first breaths, and pulmonary vascular resistance drops sharply. Blood flow to the lungs increases dramatically.
2. The umbilical cord is clamped and cut, stopping placental circulation. This removes the low-resistance placental circuit and raises systemic vascular resistance.
3. Increased left atrial pressure (from increased pulmonary return) pushes the flap of the foramen ovale closed. It eventually fuses to become the fossa ovalis.
4. Rising blood oxygen levels cause the smooth muscle of the ductus arteriosus to constrict. It closes functionally within hours and becomes the ligamentum arteriosum over several weeks.
5. The ductus venosus closes as umbilical blood flow ceases and becomes the ligamentum venosum.

These changes establish the adult-type circulation, where the pulmonary and systemic circuits operate fully in series with no shunts.