Blood vessel histology
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 and histology of blood vessels. Additionally, clinical concepts associated with the vascular system will also be addressed.
- Histological layers
- Arteries and derivatives
- Veins and derivatives
- Vasa vasorum
- Clinical significance
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.
A great way to consolidate your knowledge of blood vessel histology is quizzing yourself! Get started with our blood vessel diagrams and artery and vein quizzes.
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.
There is an easy way to remember the main layers of a blood vessel. Just use a mnemonic! ' LIMA' will help you recall the following structures:
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.
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.
Students often focus on red blood cells when discussing the constituent cells circulating in the vascular network. However, blood vessels also carry leukocytes (white blood cells) that respond to infections as well as local injury. When cells are damaged (irrespective of the cause), resident phagocytes detect the damaged cells and release chemokines that attract more leukocytes from the microcirculation (chemotaxis). As a part of this inflammatory response, the blood vessels dilate in order to allow more white blood cells to gain access to the damaged site. Additionally, the epithelial cells of the blood vessels contract, creating spaces in the blood vessel wall through which leukocytes can migrate toward the injured tissue.
It is possible for an inflammatory cascade to be established in the walls of the vessels. This disorder is referred to generally as a vasculitis. The insulting factor may be infectious in nature (classically a Pseudomonas infection if bacterial, or Aspergillus if fungal) or non-infectious. The non-infectious subtypes are usually variants of an autoimmune characterized by any of the following:
- Immune complex deposition demonstrated in Systemic Lupus Erythematosus
- Antineutrophil cytoplasmic antibodies, which can be drug induced
- Antiendothelial cell antibodies, demonstrated in Kawasaki disease
- Autoreactive T-lymphocytes found in Giant Cell Arteritis.
Pathologically, damage to the blood vessels either by vasculitis or from malignant hypertension (for example) can result in fibrinoid necrosis. This is a special form of necrosis characterized by leakage of protein (such as fibrin) into the vessel wall. Consequently, the vessels appear bright pink on histological examination.
Atherosclerosis is a disorder of the arterial vessels characterized pathologically by narrowing of the vessel lumen as a result of plaque deposition within the vessel wall. This should not be confused with arteriosclerosis, which refers to a general hardening and stiffening of arterioles and capillaries. Atherosclerosis is a subtype of arteriosclerosis and is often a complication of hyperlipidaemia that affects medium to large sized arteries, such as the coronary arteries (blood supply to the heart) or abdominal aorta.
There is widespread speculation surrounding the initiating factors behind atherosclerosis. However, one theory suggests that disruption of the endothelium of the vessel provides a nidus for lipoproteins (usually low density lipoprotein [LDL]) to accumulate in the tunica intima of the vessel. There are several confirmed insulting agents that can lead to endothelial damage. These include cigarette smoking, hypercholesterolemia and hypertension. Once in the intima, LDL becomes oxidized and will subsequently be engulfed by circulating macrophages. These macrophages are recruited to the site of injury and after engulfing the lipoproteins, they become foam cells.
At this point the lesion is known as a fatty streak and can be seen in patients in mid adolescence. In an attempt to prevent extravasation of blood, platelets accumulate at the site of endothelial injury and release more inflammatory mediators. The inflammatory markers promote the accumulation of more macrophages along with smooth muscle cells. The smooth muscle cells secrete extracellular matrix that (along with the smooth muscle cells and macrophages) form a fibrous cap. The core of the lesion may become necrotic and calcify. The plaque grows intraluminally, which can result in occlusion of the vessel. Furthermore, the plaque may become unstable and rupture, which would lead to embolization of plaque particles. The clinical manifestations of atherosclerosis depend on the vessels that are affected:
- Lesions of the coronary arteries would result in acute coronary syndrome (unstable angina, stable angina, ST-segment elevated myocardial infarction, non-ST segment elevated myocardial infarction, sudden cardiac death).
- Lesions of the mesenteric vessels can manifest as ischaemic bowel disease (acute or chronic mesenteric ischaemia, or ischaemic colitis).
- Lesions of the peripheral arteries (more commonly lower limb) will manifest as peripheral artery disease (characterized by lipodermatosclerosis, hair loss, nail changes and punched out ulcers).
Typically, blood flows from arteries through capillary beds then to veins. There is a gradual decrease in intraluminal pressure progressing from arteries to veins. However, there are instances in which there are direct communications between arteries and veins. This abnormality is known as an arteriovenous (AV) fistula.
An AV fistula is often the result of surgically anastomosing an artery with a vein to facilitate dialysis of patients with chronic renal disease. However, there are cases of congenital AV fistulas that can arise at any point in the circulatory network. In iatrogenically created AV fistulas, there is hypertrophy of the tunica media that results in arterialization of the vein. This maturation process requires about three months before the access site can be used for dialysis. The maturation ensures that the vein becomes thick enough to tolerate repeated needle sticks.
Vitamin C deficiency
Ascorbic acid (vitamin C) participates in a myriad of reactions within the body. Humans are unable to synthesize ascorbic acid and consequently depend on exogenous sources for this vitamin. One very important role of vitamin C is that it participates in the synthesis of collagen. Therefore, deficiency in vitamin C would result in underproduction of collagen. Recall that collagen is the chief component in the tunica adventitia of blood cells. This is the underlying cause of the bleeding of the gums seen in patients with scurvy.