Histology of arteries, veins and lymphatics

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The histology of blood vessels and lymph vasculature is the study of the minute structure of the cells, tissues and organs of arteries, veins, and lymphatics in relation to their function. (Lippincott Williams & Wilkins, 2006)[1] The ‘structure-function’ relationship between different vessels and vessel components make up the circulatory system.

Contents

Structures of the human circulatory vessels

Figure 1: A diagram of a blood vessel showing the three main layers. (Slomianka, L., 2006).[2]

Circulatory blood vasculature consists of the arterial system, the venous system, and the network of capillaries between them. The lymph vascular system, also part of the circulatory system, is a network of vessels responsible for draining excess extravascular fluid, lymph, to the blood circulatory system and lymph nodes. (Young, B. et al. 2006)[3]


The whole circulatory system is mostly constituted by three structures:

  • The tunica intima is an inner lining around the lumen of the vessel, comprising of simple squamous epithelial cells. These are supported by a subendothelial layer consisting of a basement membrane and delicate collagenous tissue. (Young, B. et al. 2006)[3]
  • The tunica media is a predominantly smooth muscular layer (Young, B. et al. 2006)[3] between the tunica intima and tunica adventitia, with varying amounts of connective tissue (CT) and elastic fibres. (University of Ottawa, nd.)[4]
  • The tunica adventitia is an outer supporting tissue layer mainly containing CT fibres (collagen). (Young, B. et al. 2006)[3]


The thickness and components of these layers [especially the media and adventitia (School of Osteopathic Medicine (SOM), nd.)][5] may vary greatly depending on the size and type of vessel. (University of Ottawa, nd.)[4]

Table 1: Variations in the structures of different blood vessels. (adapted from SOM, nd.)[5]

Intima Media Adventitia
Large (elastic) artery Thick fine fibro-elastic connective tissue (FECT), occasional smooth muscle, internal elastic membrane present but inconspicuous Thickest, mixed irregular FECT, muscle layers with occasional prominent elastic lamina Thin, dense
Muscular (distributing) artery Thin, fine, FECT, prominent internal elastic membrane Thickest, 8-40 circular smooth muscle layers Thick (often equal to media), external elastic membrane present
Small artery Thin, internal elastic membrane present Thickest, 8-40 circular smooth muscle layers Thick(often equal to media), external elastic membrane present
Arteriole Thin, internal elastic membrane present 1-2 layers circular, Very thin FECT, smooth muscle
Capillary Endothelium only Absent Basement Membrane
Venule Endothelium only Absent, or occasional pericyte, or incomplete muscle layer Basement membrane or very thin fine FECT
Small or Medium Vein Thin inconspicuous internal elastic membrane Circular smooth muscle, (thinner arterial counterpart) Thicker than media, dense, irregular FECT, occasional muscle
Large Vein Thin, internal elastic membrane present Poorly developed, dense irregular, FECT, occasional smooth muscle. Thickest, prominent longitudinal bundles of smooth muscle and dense irregular FECT


Table 2: Artery versus Vein (adapted from SOM, nd.)[5]

Artery Vein
Small lumen relative to wall thickness Large lumen relative to wall thickness
More elastic and muscle tissue More collagenous CT (looser). Less elastic and muscular tissue. Thin, irregular wall.
Tunics with clearer boundaries. Arterial walls are more uniform and regular in structure Tunics lack apparent boundaries. More variations in venous wall structure.
Postmortem (after death) contraction often forces blood from lumen Lack of postmortem contraction often leaves blood in lumen
Valves absent Valves may be present



The arterial system

Figure 2: Human aorta - three distinct layers: Tunica Intima(I), Tunica Media(M), Tunica Adventitia(A).

Within the media is an extensive multi-layer of smooth muscle mixed with elastic laminae(E), which is stained black.(UNSW Medicine, nd.).[6]

The arterial system distributes blood from the heart to capillary beds throughout the body. There are three main types of arteries:

  • Elastic arteries, consisting of the major distribution vessels including the aorta, brachiocephalic trunk, common carotid, subclavian arteries and most of the large pulmonary arterial vessels.
  • Muscular arteries are main distributing branches such as the radial and femoral arteries.
  • Arterioles supply the capillary beds. (Young, B. et al. 2006)[3]



Different specialisations of the artery walls contribute to the maintenance of pressure during ventricular contractions of the heart (systole) and its subsequent recoil during ventricular relaxation (diastole). This regulates blood supply to target tissues. (Slomianka, L., 2006)[2]

Figure 3: Elastic Artery: Aorta. Red: Smooth muscle in tunica media, and cell cytoplasm. Blue: Collagen. Within tunica adventitia lies a nervi vasorum(N) and vasa vasorum(V).(UNSW Medicine, nd.)[6]

Elastic arteries

Elastic arteries are characterised by great elasticity. Their elasticity helps maintain laminar flow during large fluctuations in blood pressure. Arterial pressure is maintained by the stretching of the elastic laminae during systole and its recoil during diastole. (Slomianka, L., 2006)[2] This can be observed in the aorta.



The Aorta

The highly elastic nature of the aortic wall is distinguished from other blood vessels by the large amounts of elastic fibres, predominantly within the tunica media. Figure 2 displays three distinctive layers; tunica intima, a broad tunica media which contains most of the elastic fibres (bundles of protein called elastin), and the tunica adventitia.

Within its intima, it has a relatively thick subendothelial layer supporting the endothelium, containing scattered fibroblast cells and smooth muscle cells known as myointimal cells. (Young, B. et al. 2006)[3] Subendothelial thickness may increment with age or disease as myointimal cells accumulate lipid which may develop into atherosclerosis. (uOttawa, nd.)[4] The media is most extensive with multiple layers of concentric fenestrated sheets of elastin (figure2). (Young, B. et al. 2006)[3] Fenestrations are windows within the vessel walls, perpendicular to normal blood flow, which facilitate the diffusion of gas and nutrient exchange between blood and tissues. In the adventitia, relatively thin layers of collagenous tissue limits possible over-stretching of the elastic arteries and non-lamellae elastic fibres. Also present are the vasa vasorum (figure3), blood vessels that supply the adventitia and outer media (uOttawa, nd.)[4], and a nerve supply to the aorta, nervi vasorum. (George, T., 1998)[7] An inconspicuous internal elastic lamina (IEL) and external elastic lamina (EEL) separate the interna from the media, and the media from the adventitia respectively.(uOttawa, nd.)[4]



Muscular arteries

Muscular arteries, like elastic arteries, are the main distribution branches of the arterial system. They have a typical, thin intima and a prominent IEL.(uOttawa, nd.)[4] Concentrically arranged smooth muscle cells are frequently evident within the tunica media, along with few fine elastic fibres (figure5). Coarse elastic fibres are found between the collagen fibres within the tunica adventitia. The EEL is less prominent. (Slomianka, L., 2006)[2]. The smooth muscle of the arterial wall provides greater extensiveness of the vessel, regulates blood flow and is also a reflex force (contraction) against blood filling pressure. This reflex maintains varying amounts of steady blood supply into capillary beds. (Caceci, T., 2008)[8]



Arterioles

Deriving from small muscular arteries are large arterioles which gradually become small arterioles with no prominent boundary of change. This transition from large to small involves the loss of the IEL and the reduction of muscle layers within the media. (Young, B. et al. 2006)[3] The intima is thin with occasional bulges of endothelial cells into the lumen. The media comprises of as little as a single layer of smooth muscle. Arterioles receive both sympathetic and parasympathetic nerve signals with the smooth muscles regulating blood flow and pressure to their target tissue. (Slomianka, L., 2006)[2] The adventitia is not easily defined with its sheath of CT merging with surrounding CT. (Wiechmann, nd.)[9]

Capillaries

Figure 6: Capillary with visible endothelial cell nuclei. Note: Red Blood Cells (orange-brown) squeezing in capillaries.(Slomianka, L. 2006)[2]

Capillaries are tiny blood vessels that are part of the microcirculation. Their thin walls allow for gas and nutrient exchange via diffusion, and excretion of waste from the body. They are the most numerous class of vessels but its small diameter only allows one or two red blood cells through. (Caceci, T., 2008)[8]. Pericytes are present along various locations around endothelial cells of capillaries and of postcapillary venules. They participate in contractile functions and vessel reparation process. (Junqueira, L. C. et al., 2005)[10] There are three main types of capillaries:

  • Continuous capillaries (somatic) have an absence of fenestrations in their wall. They act as selective filters (Slomianka, L. 2006)[2] and are usually found where bulk exchange of material between blood and tissue is not required. (Caceci, T., nd.)[8]


  • Fenestrated capillaries (visceral) have fenestrations within the endothelium (Junqueira, L. C. et al., 2005)[10] allowing greater permeability. (Slomianka, L. 2006)[2]. This allows a rapid passageway for macromolecules smaller than plasma proteins. (uOttawa, nd.)[4]. The basement membrane is continuous and envelopes the fenestrated endothelium.


  • Discontinuous capillaries (sinusoidal) have both a fenestrated endothelial layer and an incomplete or absent basement membrane allowing maximum exchange of substances or even cells between bloodstream and organ. (Slomianka, L. 2006)[2]





The venous system

The systemic venous system is a low-pressure component responsible for returning blood from the capillary plexuses to the right atrium of the heart. A combination of smooth muscle contractions of the vein wall and external compressions of veins by skeletal muscle impels blood back to the heart against gravity. Valves, particularly within small and medium veins, prevent backflow of blood away from the heart. (Young, B. et al. 2006)[3]

Unlike blood vessels in the arterial system, these vessels are frequently more irregular in shape and may often appear 'floppy' due to a larger adventitia than media (which usually has most of the smooth muscle), fewer elastic tissue than arteries and a poorly developed or absent IEL.(uOttawa, nd.)[4]

Venules

Deriving from the capillary beds, postcapillary venules drain into collecting venules and then muscular venules. The structure of postcapillary venules is similar to that of large capillaries with endothelium, pericytes and no smooth muscle. Collecting venules are larger postcapillary venules. Muscular venules are even larger, having one or two layers of smooth muscle fibres in the media and devoid of elastic fibres in the intima. (Young, B. et al. 2006)[3]

Figure 10: A pocket-like valve in veins..(Slomianka, L. 2006)[2]

Veins

Small or medium sized veins have multiple bands of smooth muscle in the tunica media. Some veins may have longitudinal bundles of smooth muscle such as the veins of the ‘pampiniform plexus’ in the spermatic cord. (Slomianka, L. 2006)[2] The intima is thin while the adventitia is usually the thickest in veins, comprising of collagenous fibrous tissue. (Young, B. et al. 2006)[3] Veins also have pocket-like valves, usually with two pockets. These valves close by the filling of the pockets and hence prevent blood reflux. (Slomianka, L. 2006)[2]

Large veins (femoral and renal) have typical and very narrow intima. (uOttawa, nd.)[4] However, the media is substantially larger consisting of multiple layers of smooth muscle amongst layers of collagenous CT and scanty elastic fibres. The adventitia is broad and composed of collagen and vasa vasorum. There are no distinct elastic laminae in veins separating each structural layer as there are in arteries.(Young, B. et al. 2006)[3]


Figure 13: Vena Cava. Tunica intima(I), tunica media(M), tunica adventitia(A), Smooth Muscle(SM)(UNSW Medicine, nd.)[6]

Vena Cava

The inferior and superior venae cavae are the largest veins; returning deoxygenated blood from the whole body, except the lungs, to the right atrium of the heart. (Young, B. et al. 2006)[3] Blood pressure within the vena cava is much lower than that of the aorta and its wall is also thinner. The vena cava’s tunica intima and media is typical of veins. However, bundles of longitudinally arranged smooth muscle fibres are present amongst the collagen in the adventitia. This is more frequent within the walls of the inferior vena cava when contrasted with the superior vena cava. (Zhang, S., 2006)[11] Elastic fibres are scattered throughout all the layers. (Visual Histology, nd.)[12]









The lymph vascular system

The lymphatics are responsible for draining the excess fluid, lymph, from extracellular spaces and returning it to the blood vascular system. Lymph is drained by a system of tiny lymph capillaries which converge progressively to form larger lymphatic vessels. Larger lymph vessels acquire smooth muscles and valves before passing large ducts which empties lymph into the blood. Along the course of larger lymphatic vessels, lymph nodes screen for foreign materials and activated cells of the immune system and antibodies are introduced into the circulation. (Young, B. et al. 2006)[3]

Lymph capillaries, lymph Vessels and lymph ducts

Unlike blood capillaries, lymphatic capillaries have greater permeability. The endothelial cell cytoplasm of lymphatics is extremely thin, the basement membrane is incomplete or absent and there is an absence of pericytes. (Young, B. et al. 2006)[3] They are irregularly shaped (Slomianka, L. 2006)[2] and do not contain erythrocytes (red blood cells). (SOM, nd.)[5] Lymph vessels are larger and contain valves which prevent the backflow of lymph. Due to the absence of smooth muscle, lymph is moved by surrounding tissue, and valves determine the directional flow. (Slomianka, L. 2006)[2] Lymph vessels merge to form lymph ducts which have some layers of longitudinal and transverse smooth muscle in the media. Lymph ducts empty the lymph into both sides of where the internal jugular and subclavian veins join. (Young, B. et al. 2006)[3]

Histopathology

There are many diseases associated with blood vessels such as atherosclerosis.

Atherosclerosis

Atherosclerosis is a generic term for vascular disease that usually involves thickening and loss of elasticity of arterial walls. This is usually characterized by formation of lipid-rich, fibrous plaques protruding into the lumen from the intima, calcification (calcium deposit) and ossification (forming bone) within the media although this is usually clinically insignificant, and disease of small arteries and arterioles. This results in arterial wall thickening with luminal narrowing which may cause downstream ischemic injury. (Cotran R.S. et al., 1999)[13]

Table 3: American Heart Association - Classification of human atherosclerotic lesions with histological classifications (adapted from Cotran R.S. et al., 1999)[13]



References

  1. Lippincott Williams & Wilkins (2006). Steadman’s Medical Dictionary (28th ed.). United States of America: Quebecor World.
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 Slomianka, L. (2006). Blue Histology - Vascular System. Retrieved August 10, 2008 from http://www.lab.anhb.uwa.edu.au/mb140/CorePages/Vascular/Vascular.htm
  3. 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 Young, B., Lowe, J. S., Stevens, A. & Heath, J. W. (2006). Wheaters’s Functional Histology (5th ed.). Philadelphia: Churchill Livingstone Elsevier.
  4. 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 University of Ottawa (nd.). Histology of the Blood Vessels. Retrieved August 13, 2008 from http://www.courseweb.uottawa.ca/medicine-histology/English/Cardiovascular/HistologyBloodVessels.htm
  5. 5.0 5.1 5.2 5.3 School of Osteopathic Medicine (nd.). Lab 7 Cardiovascular System Retrieved August 13, 2008 from http://www3.umdnj.edu/histsweb/lab7/lab7index.html
  6. 6.0 6.1 6.2 6.3 6.4 6.5 University of New South Wales (nd.). Blood vessels and atherosclerosis. Retrieved August 11, 2008 from http://web.med.unsw.edu.au/vslide/phase1/indexA3.asp
  7. George, T. (1998). Review Glossary. Retrieved August 15, 2008 from http://medinfo.ufl.edu/year1/histo/glossary.html#nervi_vasorum
  8. 8.0 8.1 8.2 Caceci, T. (2008). Cardiovascular System: Arteries and Veins. Retrieved August 15, 2008 from http://education.vetmed.vt.edu/curriculum/vm8054/labs/Lab12b/Lab12b.htm
  9. Wiechmann, A., Pillow, J. (nd.). Interactive Histology Atlas. Retrieved August 15, 2008 from http://w3.ouhsc.edu/histology/
  10. 10.0 10.1 Junqueira, L. C. & Carneiro, J. (2005). Basic Histology: Text & Atlas (11th ed.). United States of America: McGraw-Hill Companies. Retrieved August 15, 2008, from http://info.library.unsw.edu.au/cgi-bin/local/access/access.cgi?url=http://www.accessmedicine.com/lange.aspx
  11. Zhang S. (1999). An Atlas of histology. Retrieved August 12, 2008 from http://books.google.com.au/books?id=iuJ3mG85LSAC&printsec=frontcover&dq=histology+vena+cava+longitudinal
  12. Visual Histology (nd.) Chapter 10: The Circulatory System. Retrived August 15, 2008 from http://www.visualhistology.com/Visual_Histology_Atlas/VHA_Chpt10_The_Circulatory_System.html
  13. 13.0 13.1 Cotran, R.S., Kumar, V., Collins, T. (1999). Pathologic Basis of Disease (6th ed.). Philadelphia:W.B. Saunders Company.
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