Histology of the Vascular Network
It would be impossible to get blood to the predestined locations without the vascular pathways. Blood vessels form the extensive networks by which blood leaves the heart to supply tissue. Additionally, other blood vessels return from these tissues with oxygen poor blood back to the heart.
These tubular structures can be classified according to the:
- number of layers present
- thickness of the layers
- diameter of the vessel
- presence or absence of valves
This article will explore the embryology of blood vessels, the histological composition of these structures, and the four general classes of vessels. Additionally, clinical concepts associated with the vascular system will also be addressed.
The vascular pathway is a mesodermal derivative that proliferates by vasculogenesis and angiogenesis. The former refers to the differentiation of precursor angioblasts into endothelial cells and the subsequent de novo formation of blood vessels. On the other hand, the latter speaks to the formation of new blood vessels from preexisting vessels. While vasculogenesis is primarily an embryological process, angiogenesis persists into extrauterine life and is the mechanism by which new vessels are formed to bypass occluded arteries (i.e. formation of a collateral blood supply).
Around the third gestational week, fibroblast growth factor 2 (FGF2) binds to fibroblast growth factor receptors (FGFR) on mesodermal cells to induce differentiation of these cells into hemangioblasts. They aggregate in the walls of the yolk sac and form blood islands. The hemangioblasts will later become endothelial cells under the influence of vascular endothelial growth factor (VEGF) acting on vascular endothelial growth factor receptors (VEGF-R2). The endothelial cells join together in their characteristic tubular arrangement under the influence of VEGF acting on VEGF-R1 to form the blood vessels.
The remaining hemangioblasts within the vessel has two fates. Those located toward the periphery will differentiate into angioblasts (which will participate in angiogenesis), while those located in the center will differentiate into hematopoietic stem cells (which is the precursor for all blood cells). VEGF is the primary instigator behind angiogenesis, as they promote the differentiation of angioblasts into endothelial cells. It also guides these endothelial cells as the aggregate to form primitive blood vessels. New vessels will then branch from the primary vascular pathway toward their destination sites. Further maturation of these new vessels is mediated by platelet-derived growth factor (PDGF) as well as transforming growth factor beta (TGF-β). Differentiation of the vessels into arterial, venous and lymphatic derivatives also commences shortly after induction of angioblasts.
With haematoxylin and eosin stains, blood vessels can be easily observed on light microscopy. There are three distinct layers forming the walls of arteries and veins. The innermost layer is the tunica intima. This layer is lined by endothelium, which is comprised of simple squamous epithelial cells. Just deep to the endothelium are a basement membrane and a layer of subendothelial connective tissue that offers support to the overlying cells.
The middle muscular layer of the blood vessel is the tunica media. The muscle of this layer is smooth muscle that is fitted with alpha and beta adrenergic receptors. These receptors are innervated primarily by the sympathetic nervous system. Stimulation of the alpha receptors produces contraction of the smooth muscles. On the contrast, stimulation of the beta receptors produces dilatation of the vessels. Consequently, this allows for sympathetic regulation of blood pressure. Additionally, the smooth muscle layer also secretes extracellular matrix.
The outermost layer of the blood vessels is the tunica adventitia, also known as the tunica externa. This layer is primarily composed of type I collagen and elastic connective tissue (in arteries). This external layer is responsible for anchoring the vessels to adjacent organs.
Arteries and Derivatives
When compared to veins, capillaries and lymphatics, arteries are the largest of the vessels. The luminal diameter becomes progressively smaller as the vessels branch. Arteries can be classified based on the abundance of elastic fibres present in the walls. The larger vessels leaving the heart – namely the aorta, pulmonary trunk, common carotid, subclavian, vertebral and common iliac arteries – are elastic arteries.
These larger vessels contain two additional layers – the internal and external elastic laminae. The former is a wavy band of elastic fibers between the intima and media, while the latter is seen between the media and adventitia. The elastic arteries are designed to accommodate the high pressures generated by the heart.
The larger aforementioned vessels branch into medium-sized muscular arteries. These vessels have a larger quantity of smooth muscles in the intima when compared to their elastic counterparts. They are the most abundant arterial vessels throughout the body.
The muscular medium-sized arteries branch into smaller arterioles; which is the smallest division of the arterial network. The tunica media has far fewer muscle fibres.
For a quick recap: large arteries (e.g. aorta and pulmonary trunk) → medium-sized and small arteries (e.g. gastro-epiploic artery) → arterioles (e.g. vasa recta of the large intestines) → capillaries
Arterioles branch to form capillaries. These are the smallest vascular structures in the body that deliver blood at the level of the tissue. Capillaries are grouped based on the arrangement of the endothelium along the vessel walls. The capillary beds found in the Bowman’s capsule of the kidneys, in endocrine tissue and parts of the small intestine are perforated along the endothelial cells. This facilitates rapid molecular exchange between the luminal space of the capillary and the surrounding tissues. These are known as fenestrated capillaries.
In the bone marrow, liver and spleen, the capillaries either have incompletely formed (or completely absent) basement membranes underlying widely spaced endothelial cells. There are usually no gap junctions between these cells and the vessel allows for direct transportation from the vascular lumen to the surrounding cells. These tortuous and irregular vessels are called discontinuous (sinusoidal) capillaries.
The most commonly encountered capillaries are the continuous capillaries. The endothelial cells in these vessels are traditionally arranged; the cells are in close proximity with each other and fitted with gap junctions. Continuous capillaries are designed to isolate luminal content from the interstitial space. They are commonly encountered in the skin, muscle, connective tissue, nervous tissue and respiratory tract.
Veins and Derivatives
The terminal capillaries coalesce to form postcapillary veins. These post capillary veins then unite and form venules, which then progress to larger veins, which will return deoxygenated blood back to the heart. Veins possess all three tunics that are found in arteries. However, the tunica media is significantly thinner in veins when compared to arteries of roughly the same size.
Additionally, veins have wider lumen, which translate to them accommodating lower blood pressure than arteries. There are more veins in the circulatory system than there are arteries; and are loosely classified as small, medium and large veins. Another distinct feature of most veins (except the venae cavae, visceral organs and the central nervous system) is that they contain valves in the lumen. This prevents the backflow of blood in the low pressure venous system.
Finally, the lymphatic vessels are initially blind-ended tubular structures in the connective tissue stroma of various organs that collects lymph (excess interstitial fluid). The endothelial lining of lymph vessels and capillaries are thin enough to enhance their permeability, and consequently the uptake of lymph. Like veins, lymph vessels are also low pressure systems and as a result, they too contain valves to prevent reflux of lymph within the vessel. Additionally, there is no tunica media in lymph vessels, so they rely on surrounding skeletal muscles to promote the forward movement of fluid back to the primary circulation.
Lymph vessels eventually coalesce to form the thoracic duct and right lymphatic duct, which will then return lymph to the venous arm of the circulatory system. With the exception of bone and bone marrow, cartilage, the placenta, teeth and the thymus, lymph vessels are ubiquitous throughout the body.
In large vessels, it is difficult for nutrient in the lumen to diffuse to the intima and adventitia layers. These vessels require additional blood vessels to perfuse the outer layers. These structures are known as vasa vasorum. It should be noted that this phenomenon also occurs with some large nerves that cannot get all the required nutrients from simple diffusion from neighbouring arteries, so they require vasa nervorum for additional perfusion.