Development of Blood Vessels

Development of Blood and Blood Vessels

New blood vessels are formed from endothelial stem cells, which give rise to the endothelial cells that line the vessels.

Learning Objectives

Describe the development of blood vessels and blood

Key Takeaways

Key Points

  • Endothelial stem cells (ESCs) are found in the bone marrow and give rise to endothelial progenitor cells (EPCs), which differentiate along a specific cell developmental pathway.
  • Endothelial cells give rise to the thin-walled endothelium that lines the inner surface of blood vessels and lymphatic vessels.
  • Hematopoietic stem cells are multipotent cells that give rise to erythrocytes ( red blood cells ), megakaryocytes/platelets, mast cells, T-lymphocytes, B-lymphocytes, dendritic cells, natural killer cells, monocytes/macrophages, and granulocytes.
  • Formation of new blood vessels occurs by two different processes: vasculogenesis and angiogenesis.
  • Vasculogenesis is the formation of a vascular network from mesodermal progenitor cells. It requires differentiation of endothelial cells from hemangioblasts and then organization into a primary capillary network.
  • Angiogenesis occurs when new vessels are built from preexisting blood vessels.

Key Terms

  • endothelial stem cells: One of three types of stem cells found in bone marrow. They are multipotent, which describes the ability to give rise to many cell types, whereas a pluripotent stem cell can give rise to all types.
  • hematopoietic stem cells: Multipotent stem cells that give rise to all the blood cell types from the myeloid (monocytes and macrophages, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes/platelets, and dendritic cells), and lymphoid lineages (T-cells, B-cells, and NK-cells).
  • vasculogenesis: The formation and development of the vascular system, including the formation of blood vessels from endothelial cells.

Endothelial stem cells (ESCs) are one of three types of stem cells found in bone marrow. They are multipotent, which describes the ability to give rise to many cell types, whereas a pluripotent stem cell can give rise to all types. ESCs have the characteristic properties of a stem cell: self-renewal and differentiation. They give rise to endothelial progenitor cells (EPCs), intermediate stem cells that lose potency. Progenitor stem cells are committed to differentiating along a particular cell developmental pathway. ESCs will eventually produce endothelial cells (ECs), which create the thin-walled endothelium that lines the inner surface of blood vessels and lymphatic vessels.

As part of the circulatory system, blood vessels play a critical role in transporting blood throughout the body. Consequently, ECs have unique functions such as fluid filtration, homeostasis, and hormone trafficking. Formation of new blood vessels occurs by two different processes: vasculogenesis and angiogenesis. The former requires differentiation of endothelial cells from hemangioblasts and then organization into a primary capillary network. The latter occurs when new vessels are built from preexisting blood vessels.

The lineages arising from the EPC and the hematopoietic progenitor cell (HPC) form the blood circulatory system. Hematopoietic stem cells can undergo self-renewal and give rise to erythrocytes (red blood cells), megakaryocytes/platelets, mast cells, T-lymphocytes, B-lymphocytes, dendritic cells, natural killer cells, monocyte/macrophage, and granulocytes. In the beginning stages of mouse embryogenesis, commencing at embryonic day 7.5, HPCs are produced close to the emerging vascular system. In the yolk sac ‘s blood islands, HPCs and EC lineages emerge from the extraembryonic mesoderm in near unison. This creates a formation in which early erythrocytes are enveloped by angioblasts, and together give rise to mature ECs. This led to the hypothesis that the two lineages come from the same precursor, termed hemangioblast. Even though there is evidence that corroborates a hemangioblast, the isolation and exact location in the embryo has been difficult to pinpoint. Some researchers have found that cells with hemangioblast properties have been located in the posterior end of the primitive streak during gastrulation.

This diagram indicates multipotential hematopoietic stem cell (hemocytoblast), common myeloid progenitor, common lymphoid progenitor, small lymphocyte, natural killer cell (large granular lymphocyte), T lymphocyte, B lymphocyte, plasma cell, myeloblast, mast cell, erythrocyte, megakaryocyte, thrombocyte, basophil, neutrophil, eosinophil, monocyte, and macrophage.

Simplified hematopoiesis: Blood cellular components are differentiated from hematopoietic stem cells.

In 1917, Florence Sabin first observed that the development of blood vessels and red blood cells in the yolk sac of chick embryos occur in close proximity and time. Then in 1932, Murray detected the same event and coined the term hemangioblast. Further evidence to corroborate hemangioblasts comes from the expression of various genes such as CD34 and Tie2 by both lineages. The fact that this expression was seen in both EC and HPC lineages led researchers to propose a common origin.

Fetal Circulation

Fetal circulation includes the blood vessels within the placenta and the umbilical cord that carry fetal blood.

Learning Objectives

Distinguish fetal circulation from postnatal circulation

Key Takeaways

Key Points

  • In the fetus, oxygen exchange and nutrients are obtained from the mother through the placenta and the umbilical cord rather than the lungs.
  • The placenta functions as the respiratory center for the fetus as well as a site of filtration for plasma nutrients and wastes, since the circulatory system of the mother is not directly connected to that of the fetus.
  • The uterine arteries carry oxygenated blood to the placenta.
  • Fetal hemoglobin has a higher affinity for oxygen than adult hemoglobin, thus allowing diffusion of oxygen from the mother’s circulatory system to the placenta. There, oxygen diffuses to the chorionic villus, an alveolus-like structure in the umbilical vein.
  • In the fetus, most blood flows through an opening between the right and left atrium (the foramen ovale ) directly into the left atrium from the right atrium, thus bypassing pulmonary circulation.

Key Terms

  • uterine arteries: An artery that supplies blood to the uterus in females.
  • placenta: A vascular organ present only in the female during gestation. It supplies food and oxygen from the mother to the fetus and passes back waste. It is implanted in the wall of the uterus and links to the fetus through the umbilical cord, and is expelled after birth.
  • chorionic villus: Villi that sprout from the chorion in order to give a maximum area of contact with the maternal blood.

Fetal circulation is the circulatory system of a human fetus, often encompassing the entire fetoplacental circulation that also includes the umbilical cord and the blood vessels within the placenta that carry fetal blood. The fetal circulation works differently from that of born humans, mainly because the lungs are not in use. The fetus obtains oxygen and nutrients from the mother through the placenta and the umbilical cord.

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Fetal circulation: This diagram illustrates the human feto-placental circulatory system.

The core concept behind fetal circulation is that fetal hemoglobin has a higher affinity for oxygen than adult hemoglobin, which allows a diffusion of oxygen from the mother’s circulatory system to the fetus. The circulatory system of the mother is not directly connected to that of the fetus, so the placenta functions as the respiratory center for the fetus as well as a site of filtration for plasma nutrients and wastes. Water, glucose, amino acids, vitamins, and inorganic salts freely diffuse across the placenta along with oxygen. The uterine arteries carry oxygenated blood to the placenta, which then permeates the sponge-like organ. Oxygen then diffuses from the placenta to the chorionic villus, an alveolus-like structure, from which it is carried to the umbilical vein.

Blood from the placenta is carried to the fetus by the umbilical vein. About half of this enters the fetal ductus venosus and is carried to the inferior vena cava, while the other half enters the liver proper from the inferior border of the liver. The branch of the umbilical vein that supplies the right lobe of the liver first joins with the portal vein. The blood then moves to the right atrium of the heart. In the fetus, there is an opening between the right and left atrium (the foramen ovale), and most of the blood flows through this hole directly into the left atrium from the right atrium, thus bypassing pulmonary circulation. Blood then flows into the left ventricle and is pumped through the aorta into the body. Some of the blood moves from the aorta through the internal iliac arteries to the umbilical arteries and re-enters the placenta, where carbon dioxide and other waste products from the fetus enter the maternal circulation. Some of the blood entering the right atrium does not pass directly to the left atrium through the foramen ovale, but enters the right ventricle and is pumped into the pulmonary artery. In the fetus, there is a special connection between the pulmonary artery and the aorta called the ductus arteriosus, which directs most of this blood away from the lungs.

At birth, when the infant breathes for the first time, there is a decrease in the resistance in the pulmonary vasculature, which causes the pressure in the left atrium to increase relative to the pressure in the right atrium. This leads to the closure of the foramen ovale, which is then referred to as the fossa ovalis. Additionally, the increase in the concentration of oxygen in the blood leads to a decrease in prostaglandins, causing closure of the ductus arteriosus. These closures prevent blood from bypassing pulmonary circulation, and therefore allow the neonate’s blood to become oxygenated in the newly operational lungs.

Aging and the Cardiovascular System

The health of the myocardium can become impaired with age as the arteries narrow or become clogged due to atherosclerosis.

Learning Objectives

Assess the changes to the cardiovascular system associated with aging

Key Takeaways

Key Points

  • Cardiac output and heart rate decrease with age as the heart muscle becomes less efficient.
  • High blood pressure (hypertension) is another common occurrence in old age which leads to a weak, overworked ventricle and may cause congestive heart failure.
  • The heart valves may become thickened by fibrosis, leading to heart murmurs and less efficient pumping.
  • Arrhythmias (irregular heartbeat) occur when the cells of the conduction pathway become less efficient.

Key Terms

  • fibrosis: The formation of excess fibrous connective tissue in an organ.
  • atherosclerosis: The clogging or hardening of arteries or blood vessels caused by plaques (accumulations of fatty deposits, usually cholesterol).
  • congestive heart failure: A syndrome marked by weakness, edema, and shortness of breath, caused by the inability of the heart to circulate the blood adequately to the lungs and other tissues.

The heart muscle becomes less efficient with age, with a decrease in both maximum cardiac output and heart rate. However, resting levels may remain more than adequate.

Global Cardiovascular Changes

The health of the myocardium depends on its blood supply, and with age there is greater likelihood that atherosclerosis will narrow the coronary arteries. The heart loses about one percent of its reserve plumbing capacity every year after we turn 30. Changes in blood vessels that serve brain tissue reduce nourishment to the brain, resulting in the malfunction and death of brain cells. By the time we turn 80, cerebral blood flow is 20% less and renal blood flow is 50% less than at age 30. As we age, our heart goes through certain structural changes: the walls thicken, weight increases, valves stiffen and are more likely to calcify, and the aorta, the major vessel carrying blood out of the heart, enlarges.

Infarcation Development

High blood pressure (hypertension) causes the left ventricle to work harder. The ventricle muscle may enlarge and outgrow its blood supply, thus becoming weaker. A weak ventricle is not an efficient pump, potentially leading  to congestive heart failure. This process may be slow or rapid. Acute myocardial infarction (AMI or MI), commonly known as a heart attack, is a disease that occurs when the blood supply to a part of the heart is interrupted, causing death of heart tissue.

Atherosclerosis can lead to an MI, the leading cause of death for both men and women all over the world. The term myocardial infarction is derived from myocardium (the heart muscle) and infarction (tissue death). Atherosclerosis, the deposition of cholesterol on and in the walls of the arteries, narrows the lumen, decreases blood flow, and forms rough surfaces that may cause intravascular clot formation.

The phrase heart attack sometimes refers to heart problems other than MI, such as unstable angina pectoris and sudden cardiac death. With aging, the integrity of the endothelium lining the blood vessels and coronary arteries is reduced, increasing he likelihood of plaque formation and infarct development.

Arrhythmias and Fibrosis

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Reticular Fibers: High magnification micrograph of senile cardiac amyloidosis (brown) and fibrosis (yellow). Movat stain (black = nuclei, elastic fibers; yellow = collagen, reticular fibers; blue = ground substance, mucin; bright red = fibrin; red = muscle). Autopsy specimen.

Arrhythmias are also more common with increasing age as the cells of the conduction pathway become less efficient. Some are life-threatening medical emergencies that can result in cardiac arrest. In fact, cardiac arrythmias are one of the most common causes of death en route to hospitals.

Other arrhythmias may be merely uncomfortable, causing minor symptoms like palpitations. These can also be caused by atrial/ventricular fibrillation, wire faults, and other technical or mechanical issues in cardiac pacemakers/defibrillators. Still others may be asymptomatic, but predispose the patient to a potentially life-threatening stroke or embolism.

The heart valves may also become thickened by fibrosis, leading to heart murmurs and less efficient pumping. In the elderly, ventricular diastolic stiffness can lead to pulmonary circulatory congestion. Aortic stenosis and aortic insufficiency elevate left ventricular preload to the point where it becomes stiff and noncompliant, common in people ages 75 and older. These elevated pressures are transmitted to the pulmonary vasculature and lead to pulmonary edema.