1. Histology
Lecture 1

2. Circulatory System
Function and Parts

3. The Circulatory System
Is the main transport system in which substances are carried from one part of the body to another in a variable size tubes called vessels. We have:
Blood circulatory system: in which O2, CO2, nutrients, cells of immune system, hormones,...etc. are transported to various parts of the body.
Lymphatic circulatory system: which drain the extra-cellular fluid from the tissue returning it to the blood circulatory system after their passage through lymph nodes.

4. Major Components Pump (heart) Network of tubes Blood
Continuously circulates blood
Network of tubes
Arteries- blood away from heart
Veins- blood back to the heart
Blood
Fluid that fills the circulatory system

5. Function Transport materials needed by cells
Oxygen
Glucose
Remove waste materials from cells
Carbon dioxide
urea

6. Heart: to pump the blood.
The Blood Circulatory System is formed of the following structures:
Heart: to pump the blood.
Arteries: series of vessels that carry blood from the heart to the tissues and they become smaller and smaller as they branch until they end in the capillaries.
Capillaries: diffuse network of thin tubules that anastomose with each others & through their wall the exchange of O2 & nutrients between blood & tissues occur.
Veins: series of vessels that will carry blood from the tissues to the heart.

7. In general the Blood Circulatory System is divided into:
Macrocirculation: vessels more then 0.1 mm. in diameter.
Microcirculation: vessels only visible by microscope. The vessels of the microvasculature are particularly important because of its participation in the process of exchange of materials between blood & tissues.

8. Three Kinds of Blood Vessels
Arteries – Carries blood away from the heart
Veins – Carries blood back to the heart
Capillaries – Delivers low-oxygen blood to veins (Smallest)

9. General structure of blood vessels
All blood vessels have common general structural features.
The composition of each blood vessel wall depend on the physiological requirement of the body, so pulmonary artery (low pressure system) have thinner walls then the systemic arteries (high pressure system) such as renal and carotid arteries.
The walls of all the blood vessels are composed of three identifiable layers named: tunica intima, tunica media, tunica adventitia.
In the smallest blood vessels (capillaries & venules) these 3 tunics are greatly simplified.
There are no absolute criteria to distinguish between large arteries, medium size arteries and arterioles because blood vessels constitute a continuous system & generally the basis of classification are the size and tissue composition of the vessel.

10. Histology of Blood Vessels
Tunica interna or intima (endothelium + c.t.)
Tunica media (muscle + c.t.)
Tunica externa or adventitia (thick layer of c.t.)

11. Tunics of the blood vessel wall:
 1. Tunica Intima:
consist of a layer of highly specialized cells called endothelial cells that line the vessel’s interior surface, These cells rest on a basal lamina.
Beneath these cells is the sub endothelial layer which consist of loose connective tissue that may contain some smooth muscle cells.
In arteries the T. intima is separated from the T. media by the internal elastic lamina (membrane) which is composed of elastic fibers & has fenestrae (gabs) that allow substances to diffuse and nourish the deeper cells in the blood vessel wall, this membrane is very obvious in the muscular arteries and arterioles.
The intima often appears wrinkled in section due to contraction of the smooth muscle cells present in the subendothelial layer (particularly true in arteries).

12. 2. Tunica Media: Is the middle layer in the blood vessel wall.
Composed mainly of smooth muscle cells reinforced with layers of elastic & reticular fibers that are found between the muscle cells.
In larger arteries a thin external elastic lamina often separates the media from the adventitia.
In capillaries & post capillary venules the media is replaced by cells called Pericytes.
The media is: particularly prominent in arteries, relatively indistinct in veins and non existent in very small vessels.
So in vessels near the heart & receiving the full thrust of the systolic pressure the elastic tissues in the media are very well developed so called elastic arteries, while in the muscular arteries & arterioles the elastic fibers will be gradually replaced by smooth muscle fibers leaving only the internal and external elastic laminae.

13. 3. Tunica Adventitia:
The outer layer of the blood vessel.
Composed mainly of collagen and elastic fibers & few smooth muscle cells.
Smooth muscle cells are particularly prominent in the adventitia of veins.
The adventitia is the most prominent layer in the wall of the veins.
The adventitia will gradually become continuous with the connective tissues surrounding the organ through which the vessel pass.

14. ***Within the T. adventitia we can notice:
1. Vasa Vasorum: (vessel of a vessel) these are very small blood vessels found in the tunica adventitia, they branch profusely here & they also send branches to the outer parts of the T. media to supply them with blood. The vasa vasorum are found in the adventitia of larger blood vessels because their wall is too thick & cannot be nourished by diffusion from the wall only. Vasa vasorum are more frequent in veins then in arteries which could be due to lack of O2 & nutrient materials in the venous blood. Vasa vasorum can arise as branches from the same artery they supply or from neighboring artery.
2. Lymphatic capillaries.
3. Autonomic nerves: that innervate the smooth muscle cells of the media, most blood vessels that contain smooth muscles in their wall are supplied by sympathetic nerve fibers (called vasomotor nerves) these nerve fibers leads to constriction of blood vessels.

16. Endothelium:
Composed of highly specialized flattened cells called endothelial cells.
In routine histological section the cytoplasm of the endothelial cells cannot be seen so only the small flattened nuclei can be noticed.
A prominent feature of the endothelial cells is the presence of many pinocytotic vesicles in their cytoplasm which are involved in the process of transport of substances from one side of the cell to another. In addition the endothelial cells of the small blood vessels of the nervous system express certain transport proteins that are responsible for active transport of substances into the brain tissues.

17. Functions of endothelial cells:
Have a role in the transport of substances from and to blood vessels.
They are able to sense any change in blood pressure, O2 tension and blood flow by unknown mechanisms & they respond to these changes by secretion of substances that have a powerful effect on the tone of the vascular smooth muscle (endothiline, nitric oxide, prostaglandins…..) these substances will cause relaxation of the vascular smooth muscles leading to vasodilatation & so increase blood flow.
These cells are important for the control of blood coagulation process. Under normal conditions intact endothelial surface prevent blood clotting by secretion of certain factors that prevent formation of blood clot, however any damage to the endothelial surface will induce the aggregation of platelets & initiate a cascade of events leading to formation of fibrin from blood fibrinogen (called thrombus). This thrombus may enlarge in size until full obstruction of the vessel occur leading to death of the tissues.
Endothelial cells can be activated after any form of tissue injury or tissue damage, they become cuboidal & secrete substances that facilitate adhesion of lymphocytes & nutrophiles to the endothelial surface to help in their migration to the damaged tissues.

18. Specific structure of blood vessels The histological classification of blood vessels is made according to the size of the vessel & to the tissue composition so we have: Large size (elastic artery), Medium size (muscular artery), Arteriole, Capillary, Venule, Medium size vein, Large vein

19. Elastic arteries:
The largest arteries, they receive the main output of the left ventricle.
They include the Aorta & its main branches such as the carotid, subclavian & ranal arteries. Macroscopically these arteries have a yellowish color due to accumulation of elastin in their wall
Tunica intima is thicker then the intima of the muscular artery with thick sub-endothelial layer. Internal elastic lamina is present but it is difficult to be distinguished because it is very similar to the elastic laminae found in the media.
T. media is thick and highly developed contain many elastic laminae, in adult they reach up to 70 in no. & their no. increase with age. The elastic fibers are arranged around the vessel in order to counter act the tendency of the vessel to distend during systole. Return of the elastic fibers from the stretched to unstretched state will maintain a diastolic pressure of about mmHg. Between the elastic fibers of the media are smooth muscle cells & some reticular fibers.
Tunica adventitia relatively under developed, no external elastic lamina, contain some elastic & collagen fibers, contain vasa vasorum.

22. Muscular arteries: (medium size arteries)
Distal to the elastic arteries.
Most of the named arteries are muscular arteries.
The elastic arteries will gradually branch & become a muscular arteries by loosing most of their elastic laminae in the media leaving only two layers of elastic fibers which are the internal elastic lamina between T. intima & media & the external elastic lamina between the media & adventitia.

23. Muscular artery has the following features:
T. intima thinner then that of the elastic artery, consist of endothelial cells & very thin subendothelial layer. The internal elastic lamina is prominent.
T. media consist mainly of smooth muscle cells which make these vessels highly contractile (the diameter of the lumen is controlled by the autonomic nervous system). Few elastic fibers can be seen between the smooth muscle cells. The external elastic lamina is not well defined and often incomplete.
T. adventitia consist of loose connective tissue with adipose cells and contain lymphatic capillaries & vasa vasorum.
Muscular arteries varies in diameter from about 1 cm. close to their origin to about 0.5 mm., in the large muscular artery there might be 30 or more layers of smooth muscle cells whereas in the smallest muscular artery there are only 3 muscle layers.

25. Arterioles: Less then 0.5 mm in diameter with narrow lumen
T. intima consist of endothelial cells with very thin subendothelial layer
internal elastic lamina only found in the larger arterioles.
T. media is muscular & consist of one or 2 layers of smooth muscle cells. As the arteriole get smaller the smooth muscle cells become discontinuous (called met-arteriole) which will branch later on to form a network of capillaries.
No external elastic lamina.
T. adventitia is thin and insignificant.
The endothelial cells of the arterioles have a granules that contain a protein called Von Willebrand’s factor, which is regarded as part of the coagulation mechanism. Deficiency of this protein lead to impaired adhesion of platelets to the injured endothelium, a condition known as Hemophilia.

26. Capillaries:
Smallest blood vessel, about 5-10 µm. in diameter.
Receive blood from met-arteriole
Have a very thin wall & it is the major site of gaseous exchange from & to the tissues.
Capillary wall is formed of single layer of endothelial cells that are rolled in the form of a tube, these cells rest on a basement membrane. Occasional scattered contractile cells called pericytes are found external to the endothelial cells.
When cut transversely the wall of the capillary appear to be formed of a portion of one or more endothelial cells.
The nucleus of the endothelial cells cause the cell to bulge into the capillary lumen.
Pericytes:
Are mesenchymal cells with long cytoplasmic processes that partly surround the endothelial cells at various locations along the capillaries & small venules. Function of these cells:
The presence of actine & myocine filaments in their cytoplasm suggest that they have a contractile function.
After tissue injury these cells will proliferate & differentiate to form new blood vessels & connective tissue cells.