Externally, each breast has a raised nipple, which is surrounded by a circular pigmented area called the areola. The nipples are sensitive to touch, due to the fact that they contain smooth muscle that contracts and causes them to become erect in response to stimulation.

Internally, the adult female breast contains 15 to 20 lobes of glandular tissue that radiate around the nipple. The lobes are separated by connective tissue and adipose. The connective tissue helps support the breast. Some bands of connective tissue, called suspensory (Cooper’s) ligaments, extend through the breast from the skin to the underlying muscles. The amount and distribution of the adipose tissue determines the size and shape of the breast. Each lobe consists of lobules that contain the glandular units. A lactiferous duct collects the milk from the lobules within each lobe and carries it to the nipple. Just before the nipple, the lactiferous duct enlarges to form a lactiferous sinus (ampulla), which serves as a reservoir for milk. After the sinus, the duct again narrows and each duct opens independently on the surface of the nipple.

Mammary gland function is regulated by hormones. At puberty, increasing levels of estrogen stimulate the development of glandular tissue in the female breast. Estrogen also causes the breast to increase in size through the accumulation of adipose tissue. Progesterone stimulates the development of the duct system. During pregnancy, these hormones enhance further development of the mammary glands. Prolactin from the anterior pituitary stimulates the production of milk within the glandular tissue, and oxytocin causes the ejection of milk from the glands.

Surface Anatomy

The breast is located on the anterior thoracic wall. It extends horizontally from the lateral border of the sternum to the mid-axillary line. Vertically, it spans between the 2nd and 6th intercostal cartilages. It lies superficially to the pectoralis major and serratus anterior muscles.

The breast can be considered to be composed of two regions:

• Circular body – largest and most prominent part of the breast.
• Axillary tail – smaller part, runs along the inferior lateral edge of the pectoralis major towards the axillary fossa.

At the centre of the breast is the nipple, composed mostly of smooth muscle fibres. Surrounding the nipple is a pigmented area of skin termed the areolae. There are numerous sebaceous glands within the areolae – these enlarge during pregnancy, secreting an oily substance that acts as a protective lubricant for the nipple.

Anatomical Structure

The breast is composed of mammary glands surrounded by a connective tissue stroma.

Mammary Glands

The mammary glands are modified sweat glands. They consist of a series of ducts and secretory lobules (15-20).

Each lobule consists of many alveoli drained by a single lactiferous duct. These ducts converge at the nipple like spokes of a wheel.

Connective Tissue Stroma

The connective tissue stroma is a supporting structure which surrounds the mammary glands. It has a fibrous and a fatty component.

The fibrous stroma condenses to form suspensory ligaments (of Cooper). These ligaments have two main functions:

• Attach and secure the breast to the dermis and underlying pectoral fascia.
• Separate the secretory lobules of the breast.

Pectoral Fascia

The base of the breast lies on the pectoral fascia – a flat sheet of connective tissue associated with the pectoralis major muscle. It acts as an attachment point for the suspensory ligaments.

There is a layer of loose connective tissue between the breast and pectoral fascia – known as the retromammary space. This is a potential space, often used in reconstructive plastic surgery.

Vasculature

Arterial supply to the medial aspect of the breast is via the internal thoracic artery (also known as internal mammary artery) – a branch of the subclavian artery.

The lateral part of the breast receives blood from four vessels:

• Lateral thoracic and thoracoacromial branches – originate from the axillary artery.
• Lateral mammary branches – originate from the posterior intercostal arteries (derived from the aorta). They supply the lateral aspect of the breast in the 2^nd 3^rd and 4^th intercostal spaces.
• Mammary branch – originates from the anterior intercostal artery.

The veins of the breast correspond with the arteries, draining into the axillary and internal thoracic veins.

Lymphatics

The lymphatic drainage of the breast is of great clinical importance due to its role in the metastasis of breast cancer cells.

There are three groups of lymph nodes that receive lymph from breast tissue – the axillary nodes (75%), parasternal nodes (20%) and posterior intercostal nodes (5%).

The skin of the breast also receives lymphatic drainage:

• Skin – drains to the axillary, inferior deep cervical and infraclavicular nodes.
• Nipple and areola – drains to the subareolar lymphatic plexus.

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It is encased in a weak outer connective tissue capsule which allows for protection and also the expansion of the organ and is subdivided into many smaller internal sections termed lobules. The spleen has an anterior and posterior segment and rests on the upper pole of the left kidney and tail of the pancreas. The spleen has 3 distinct borders: superior, inferior, and intermediate. The superior border of the spleen has a notch on the anterior end.

The spleen has 2 surfaces, the visceral and diaphragmatic. The latter surface is convex and smooth, whereas the former surface is concave and irregular with several imprints. The most concave imprint on the spleen is a resultant of the fundus of the stomach. The left kidney leaves an imprint on the intermediate and inferior borders. The colic imprint is from the splenic flexure of the colon.

The tail of the pancreas leaves an impression between the hilum and colic impression sites. The splenic hilum is found on the inferomedial aspect of the gastric imprint. The splenic hilum contains nerves, splenic vessels, and also contains attachments for the splenorenal and gastrosplenic ligaments. It is roughly the size of an individual’s fist, measuring about 10 cm to 12 cm (about 3.94 to 4.72 in) and weighing about 150 g to 200 g (about 5.29 oz to 7.05 oz).

Structure and Function

The spleen has several functions, including the filtering of blood, removing microbes and inadequate red blood cells (RBCs), producing white blood cells (WBCs), and antibody synthesis. It is important to note, that while the spleen does have a wide range of functions, it is not a vital organ. Individuals can survive without a spleen as other organs of the body, such as the liver, can adapt in its absence to serve just about the same functions.

The spleen consists of 2 different tissue types, termed white pulp and red pulp, with each tissue type serving unique functions. White pulp is composed of periarteriolar lymphoid sheaths (PALS) and lymphatic nodules. The white pulp tissue is involved with the production and maturity of WBCs, particularly lymphocytes (types B and T) and thereby the production of antibodies. The red pulp is composed of splenic sinusoids (wide blood vessels) and cords/threads of connective tissue. The red pulp tissue is involved more so with the filtering aspect of the blood. The red pulp removes old, damaged, and/or useless red blood cells. Contained within the red pulp are also WBCs, particularly phagocytes (macrophages in particular) which destroy microorganisms such as viruses, bacteria, and fungi.

The red pulp also acts as a storage area for WBCs and platelets, which are typically released to injury sites to aid in healing and inflammation regulation or to assist in blood loss compensation. The white and red pulp regions are separated by a border known as the marginal zone which functions as a filter, filtering pathogens out of the blood and into the white pulp.   

Embryology

Mesenchymal cells are the source from which the spleen is derived from, which are located between the tiers of the dorsal mesogastrium as early as the fifth and sixth weeks of fetal development. The characteristic shape of the spleen is something which occurs early in the fetal period. The rotation of the stomach during embryonic development causes the left mesogastrium surface fusion with the peritoneum above the left kidney and the resultant dorsal attachment of the lienorenal ligament. The yolk sac wall and near dorsal aorta are the sources of the cells needed for the hemopoietic function of the spleen. By the second trimester, the spleen is capable of both RBC and WBC generation.

Blood Supply and Lymphatics

As previously mentioned, the spleen is an organ of high vascularity. The splenic artery primarily supplies the organ arterially, entering the splenic hilum near the middle of the visceral surface. The splenic artery branches off of the celiac trunk and runs within the splenorenal ligament, lateral and across the superior pancreatic aspect. Upon approaching the spleen, the splenic artery divides into 5 branches which supply blood to different regions of the organ.

The result of this is vascular segmentation of the spleen as the 5 sub-branches do not anastomose. The splenic vein allows for the venous drainage of the spleen. It also runs from the hilum and runs posteriorly to the pancreas and later joins with the superior mesenteric vein to constitute the portal vein. The spleen is a major organ of the lymphatic system, and as such contains lymphatic vessels not necessarily in proper splenic tissue, but rather some arisen from the capsule region.

However, the lymphatic vessels of the spleen are solely efferent lymphatic vessels, with the spleen acting analogously to a large lymph node supplying lymph material to neighboring nodes such as the pancreaticosplenic lymph nodes.

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The thymus is made up of immature T cells called thymocytes, as well as lining cells called epithelial cells which help the thymocytes develop. T cells that successfully develop react appropriately with MHC immune receptors of the body (called positive selection,) and not against proteins of the body, (called negative selection).

The thymus is largest and most active during the neonatal and pre-adolescent periods. By the early teens, the thymus begins to decrease in size and activity and the tissue of the thymus is gradually replaced by fatty tissue. Nevertheless, some T cell development continues throughout adult life.

Structure

The thymus is an organ that sits beneath the sternum in the upper front part of the chest, stretching upwards towards the neck. In children, the thymus is pinkish-gray, soft, and lobulated on its surfaces. At birth it is about 4–6 cm long, 2.5–5 cm wide, and about 1 cm thick. It increases in size until puberty, where it may have a size of about 40–50 g, following which it decreases in size in a process known as involution.

The thymus is made up of two lobes that meet in the upper midline, and stretch from below the thyroid in the neck to as low as the cartilage of the fourth rib. The lobes are covered by a capsule. The thymus lies beneath the sternum, rests on the pericardium, and is separated from the  aortic arch and great vessels by a layer of fascia. The left brachiocephalic vein may even be embedded within the thymus. In the neck, it lies on the front and sides of the trachea, behind the sternohyoid and sternothyroid muscles

Functions of the Thymus

T cell maturation

The thymus facilitates the maturation of T cells, an important part of the immune system providing cell-mediated immunity. T cells begin as hematopoietic precursors from the bone-marrow, and migrate to the thymus, where they are referred to as thymocytes. In the thymus they undergo a process of maturation, which involves ensuring the cells react against antigens (“positive selection”), but that they do not react against antigens found on body tissue (“negative selection”). Once mature, T cells emigrate from the thymus to provide vital functions in the immune system.

Each T cell has a distinct T cell receptor, suited to a specific substance, called an antigen. Most T cell receptors bind to the major histocompatibility complex on cells of the body. The MHC presents an antigen to the T cell receptor, which becomes active if this matches the specific T cell receptor. In order to be properly functional, a mature T cell needs to be able to bind to the MHC molecule (“positive selection”), and not to react against antigens that are actually from the tissues of body (“negative selection”).

Positive selection occurs in the cortex and negative selection occurs in the medulla of the thymus. After this process T cells that have survived leave the thymus, regulated by sphingosine-1-phosphate. Further maturation occurs in the peripheral circulation. Some of this is because of hormones and cytokines secreted by cells within the thymus, including thymulin, thymopoietin, and thymosins.

Positive selection

T cells have distinct T cell receptors. These distinct receptors are formed by process of V(D)J recombination gene rearrangement stimulated by RAG1 and RAG2 genes. This process is error-prone, and some thymocytes fail to make functional T-cell receptors, whereas other thymocytes make T-cell receptors that are autoreactive. If a functional T cell receptor is formed, the thymocyte will begin to express simultaneously the cell surface proteins CD4 and CD8.

The survival and nature of the T cell then depends on its interaction with surrounding thymic epithelial cells. Here, the T cell receptor interacts with the MHC molecules on the surface of epithelial cells. A T cell with a receptor that doesn’t react, or reacts weakly will die by apoptosis. A T cell that does react will survive and proliferate. A mature T cell expresses only CD4 or CD8, but not both. This depends on the strength of binding between the TCR and MHC class 1 or class 2. A T cell receptor that binds mostly to MHC class I tends to produce a mature “cytotoxic” CD8 positive T cell; a T cell receptor that binds mostly to MHC class II tends to produces a CD4 positive T cell.

Negative selection

T cells that attack the body’s own proteins are eliminated in the thymus, called “negative selection”. Epithelial cells in the medulla and dendritic cells in the thymus express major proteins from elsewhere in the body. The gene that stimulates this is AIRE. Thymocytes that react strongly to self antigens do not survive, and die by apoptosis. Some CD4 positive T cells exposed to self antigens persist as T regulatory cells

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Each node contains T lymphocytes, B lymphocytes, and other immune cells. They are exposed to the fluid as it passes through the node, and can mount an immune response if they detect the presence of a pathogen. This immune response often recruits more inflammatory cells into the node – which is why lymph nodes are palpable during infection.

Lymph fluid enters the node through afferent lymphatic channels and leaves the node via efferent channels. Macrophages located within the sinuses of the lymph node act to filter foreign particles out of the fluid as it travels through.

Lymph nodes are kidney or oval shaped and range in size from 0.1 to 2.5 cm long. Each lymph node is surrounded by a fibrous capsule, which extends inside a lymph node to form trabeculae. The substance of a lymph node is divided into the outer cortex and the inner medulla. These are rich with cells. The hilum is an indent on the concave surface of the lymph node where lymphatic vessels leave and blood vessels enter and leave,

Lymph enters the convex side of a lymph node through multiple afferent lymphatic vessels and from here flows into a series of sinuses. After entering the lymph node from afferent lymphatic vessels, lymph flows into a space underneath the capsule called the subcapsular sinus, then into cortical sinuses, After passing through the cortex, lymph then collects in medullary sinuses. All of these sinuses drain into the efferent lymph vessels to exit the node at the hilum on the concave side.

Location

Lymph nodes are present throughout the body, are more concentrated near and within the trunk, and are divided into groups. There are about 450 lymph nodes in the adult. Some lymph nodes can be felt when enlarged (and occasionally when not), such as the axillary lymph nodes under the arm, the cervical lymph nodes of the head and neck and the inguinal lymph nodes near the groin crease. Most lymph nodes lie within the trunk adjacent to other major structures in the body – such as the paraaortic lymph nodes and the tracheobronchial lymph nodes.

There are no lymph nodes in the central nervous system, which is separated from the body by the blood-brain barrier. Lymph from the meningeal lymphatic vessels in the CNS drains to the deep cervical lymph nodes.

Cells

Subdivisions

A lymph node is divided into compartments called nodules (or lobules), each consisting of a region of cortex with combined follicle B cells, a paracortex of T cells, and a part of the nodule in the medulla. The substance of a lymph node is divided into the outer cortex and the inner medulla. The cortex of a lymph node is the outer portion of the node, underneath the capsule and the subcapsular sinus. It has an outer part and a deeper part known as the paracortex. The outer cortex consists of groups of mainly inactivated B cells called follicles. When activated, these may develop into what is called a germinal centre. The deeper paracortex mainly consists of the T cells. Here the T-cells mainly interact with dendritic cells, and the reticular network is dense.

The medulla contains large blood vessels, sinuses and medullary cords that contain antibody-secreting plasma cells. There are fewer cells in the medulla.

The medullary cords are cords of lymphatic tissue, and include plasma cells, macrophages, and B cells.

Cells

In the lymphatic system a lymph node is a secondary lymphoid organ. Lymph nodes contain lymphocytes, a type of white blood cell, and are primarily made up of B cells and T cells. B cells are mainly found in the outer cortex where they are clustered together as follicular B cells in lymphoid follicles, and T cells and dendritic cells are mainly found in the paracortex.

There are fewer cells in the medulla than the cortex. The medulla contains plasma cells, as well as macrophages which are present within the medullary sinuses.

As part of the reticular network, there are follicular dendritic cells in the B cell follicle and fibroblastic reticular cells in the T cell cortex. The reticular network provides structural support and a surface for adhesion of the dendritic cells, macrophages and lymphocytes. It also allows exchange of material with blood through the high endothelial venules and provides the growth and regulatory factors necessary for activation and maturation of immune cells.

There are fewer cells in the medulla than the cortex. The medulla contains plasma cells, as well as macrophages which are present within the medullary sinuses.

As part of the reticular network, there are follicular dendritic cells in the B cell follicle and fibroblastic reticular cells in the T cell cortex. The reticular network provides structural support and a surface for adhesion of the dendritic cells, macrophages and lymphocytes. It also allows exchange of material with blood through the high endothelial venules and provides the growth and regulatory factors necessary for activation and maturation of immune cells.

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Your circulatory system consists of a pump (your heart) and a network of tubes that conduct blood throughout your body (your blood vessels). With each heartbeat, blood is forced into your arteries, which carry blood away from your heart and toward all of your tissues and organs. As your arteries travel farther from your heart, they divide into progressively smaller vessels called arterioles, which themselves divide into tiny, thin-walled, somewhat leaky vessels called capillaries.

As blood travels through your capillaries, oxygen, nutrients, and fluid are pushed into the surrounding tissues, and carbon dioxide and cellular wastes are retrieved. The blood then proceeds on its way, coursing into progressively larger vessels called venules and then into even larger veins, which finally return the blood to your heart. If the fluid that leaked into your tissues from your bloodstream remained there, your cells would soon drown in the excess. That’s where your lymphatic system picks up the ball.

Function of the Lymphatic System

Mingled among the blood capillaries throughout your body is another network of tiny, thin-walled vessels called lymphatic capillaries. Lymphatic capillaries are designed to pick up the fluid that leaks into your tissues from your bloodstream and return it to your circulatory system.

Nature has ingeniously devised your lymphatic and circulatory systems so the pressure in your blood capillaries is slightly higher than the pressure in your lymphatic capillaries. This pressure gradient from blood capillary to tissue to lymphatic capillary gradually moves fluid from your circulatory system to your lymphatic system, much like water in a river flows downhill.

Just like their neighboring blood capillaries, your lymphatic capillaries join into progressively larger tubes called lymphatic vessels, which transport the fluid from your tissues (this fluid is now called lymph) toward the center of your body. Eventually, the lymph is returned to your bloodstream through two large ducts in the upper central portion of your chest.

The largest of these lymphatic ducts, the thoracic duct, originates in your abdomen, where it collects lymph from your legs, intestine, and other internal organs. As it proceeds upward into your chest, the thoracic duct collects lymph from your thoracic organs, your left arm, and the left side of your head and neck.

The right lymphatic duct, which is much shorter than the thoracic duct, begins high in the right side of your chest. It collects lymph from the right side of your chest wall, your right arm, and the right side of your head and neck. The thoracic duct and the right lymphatic duct reintroduce lymph to your bloodstream through the large veins returning to your heart from your arms: the left and right subclavian veins.

Structure

The general structure of lymphatics is based on that of blood vessels. There is an inner lining of single flattened epithelial cells (simple squamous epithelium) composed of a type of epithelium that is called endothelium, and the cells are called endothelial cells. This layer functions to mechanically transport fluid and since the basement membrane on which it rests is discontinuous; it leaks easily.

The next layer is that of smooth muscles that are arranged in a circular fashion around the endothelium, which by shortening (contracting) or relaxing alter the diameter (caliber) of the lumen. The outermost layer is the adventitia that consists of fibrous tissue. The general structure described here is seen only in larger lymphatics; smaller lymphatics have fewer layers.

The smallest vessels (lymphatic or lymph capillaries) lack both the muscular layer and the outer adventitia. As they proceed forward and in their course are joined by other capillaries, they grow larger and first take on an adventitia, and then smooth muscles.

The lymphatic conducting system broadly consists of two types of channels—the initial lymphatics, the prelymphatics or lymph capillaries that specialize in collection of the lymph from the ISF, and the larger lymph vessels that propel the lymph forward.

Unlike the cardiovascular system, the lymphatic system is not closed and has no central pump. Lymph movement occurs despite low pressure due to peristalsis (propulsion of the lymph due to alternate contraction and relaxation of smooth muscle), valves, and compression during contraction of adjacent skeletal muscle and arterial pulsation.

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