Introduction

The vascular system consists of multiple diverse blood vessels that extend throughout the body and circulate blood from the heart. The blood circulates in arteries to arterioles to capillaries, where the exchange of oxygen, nutrients, and other substances occurs. Blood is then returned to the heart from post-capillary venules to veins which successively enlarge and empty into the heart.[1]

Structure

The vascular system shares common histology however, there are key differences among the diverse system. Most blood vessel walls can be histologically organized by three layers: an inner tunica intima, a middle tunica media, and an outer tunica externa or adventitia. Each layer has a distinct cellular composition and supportive connective tissue.[2]

The inner tunica intima is composed of a single layer of endothelial cells, surrounding the inner vessel lumen. It is supported by an underlying basement membrane, which contains laminin, collagen IV and XVIII, von Willebrand factor, and perlecan. Underlying the endothelium and dividing the inner tunica intima from the tunica media is a thin layer of fibro-elastic connective tissue called the internal elastic laminae.[3][4]

The endothelium can be classified into three structural types depending on the continuity of endothelial cells: continuous, fenestrated, and discontinuous. Continous endothelium is present in most organs and the endothelial cells next to each other are bound together with tight junctions. Fenestrated capillaries have pores and are found in the glomeruli of the kidney, choroid plexus, intestinal tract, etc. Discontinuous endothelium is characterized by gaps between endothelial cells and is located in the liver, bone marrow, and spleen.[5] 

The tunica media is the middle layer of most blood vessel walls. It contains predominantly diagonally oriented smooth muscle cells and is supported by a basement membrane and extracellular matrix composed mostly of collagen and elastin fibers. It is separated from the tunica intima by the internal elastic lamina and from the outer adventitia by the external elastic lamina.[6]

The caliber of the blood vessel dictates the proportion of smooth muscle, elastin, elastic fibers, and collagen fibers within the vessel wall. In the case of the large arteries (i.e. the aorta), the tunica media is mostly composed of elastin and elastic fibers, with some smooth muscle cells interspersed. Medium and small size arteries have more smooth muscle cells. The smallest vessels of the vascular system are the capillaries. These vessels have a single layer of endothelial cells over a basement membrane. Histologically the capillary net is marked by a lack of smooth muscle.[3]

In general, small and medium veins have smooth muscle cells in the tunica media while large veins have more connective tissue. Some veins such as the ones located in the limbs contain valves that facilitate forward blood flow and avoid backflow.[3][6]

The outermost layer of the blood vessel wall is the adventitia. Its cellular components are mostly fibroblasts and myofibroblasts that are responsible for the synthesis of the fibro-elastic extracellular matrix that characterizes this layer.[7] Within the adventitia of larger vessels resides several critical structures including a blood vessel plexus or the vasa vasorum, unmyelinated nerve fibers, or the nervi vasorum and lymphatic vessels. These elements provide irrigation and innervation to the blood vessel wall.[6]

Function

The endothelial cells perform several critical actions including but not limited to: maintenance of the tunica intima, regulation of vascular tone, and promotion of antithrombotic activity.[6]

The differences in endothelial continuity are important to the transendothelial exchange between blood, plasma, and the interstitial space. In continuous capillaries, the tight junctions occlude the passage of large molecules, while fenestrated capillaries allow not only the exchange of water but also small solutes. Sinusoidal vessels have gaps between endothelial cells, making them highly permeable.[5]

As previously mentioned, the tunica media of the large vessels contains elastin and elastic fibers primarily. These fibers allow them to respond to pressure coming from the heart by expanding and contracting the wall. This activity is essential to mitigate oscillations in blood flow, allowing blood to reach smaller vessels. Medium and small-size arteries contain less elastic fibers and are rich in smooth muscle cells since they constrict and dilate to distribute blood to the capillary net.[6]

The capillaries are where the exchange of water, solutes, and other molecules occur. After blood exchange, deoxygenated blood passes from the capillary net to the postcapillary venules and later to larger veins and then back to the heart.

Histochemistry and Cytochemistry

Beyond the widely used hematoxylin and eosin histochemical and cytochemical staining, there are other stains useful for detecting specific components of the blood vessel wall. Especially for endothelium: CD34, CD31, endothelin, von Willebrand factor, and vimentin.[8]

Microscopy, Electron

Electron microscopy can help to differentiate specific cell components including but not limited to tight, gap, or adherens junctions, cytoplasmic filaments, basement membrane, and pericytes.[9]

Clinical Significance

The blood vessel is susceptible to numerous pathologies, including atherosclerosis, aneurysms, and pulmonary hypertension. 

The formation of atheromas is a key feature of atherosclerosis. Atheroma formation involves the deposition of lipids in the subendothelial space of arteries. These lipids are then phagocytosed by circulating macrophages, forming "foam cells." Foam cells then result in plaque formation. Smooth muscle cells also participate in the pathogenesis of atherosclerosis by synthesizing extracellular matrix proteins that form the cap of the plaque. The rupture of this coverage promotes thrombosis and may cause cardiovascular events, including myocardial infarctions and strokes.[10][11]

Aneurysms are focal dilatations of vessels secondary to medial thinning of arterial walls. Aneurysms occur because of a failure of structural proteins such as collagen and elastin in the media, resulting in focal regions of dilation. These areas are not structurally supported and can be clinically significant if they rupture. Abdominal aortic aneurysm rupture is associated with nearly a 90% mortality rate. The tunica media of the infrarenal aorta contains less collagen than that of the thoracic aorta, resulting in more infrarenal aortic aneurysms than thoracic aneurysms. The exact etiology of aneurysm formation is unclear.[10][12]

Pulmonary hypertension occurs when the mean pulmonary artery pressure reaches over 25 mmHg. Histologically, this is characterized by increased smooth muscle cells, which likely derive from other cell types such as endothelial cells, fibroblasts, and mesenchymal progenitor cells. There is also evidence of reduced arterial compliance of the arteries due to the increase of endothelial cells and extracellular matrix.[10]