Lymphatics Learning Objectives

Explain the function and components of the lymphatic system.

The lymphatic system is a network of structures that function to support the cardiovascular and immune systems.

The lymphatic system consists of:

Lymph - fluid found in lymph vessels and lymphatic organs
Lymph vessels - transport lymph
Lymphatic organs - made up of lymphatic tissue; Specialized reticular connective tissue that contains lymphocytes (B cells and T cells)
- Primary lymphatic organs: sites of stem cell mitosis & immunocompetence
  - Red bone marrow - where lymphocytes are generated
  - Thymus gland
- Secondary lymphatic organs & tissues:
  - Lymph nodes and nodules
  - Tonsils

Functions of the lymphatic system include:

Fluid balance - excess interstitial fluid is absorbed and transported back to the venous system through lymphatic vessels
Fat absorption - transportation of dietary lipids, large proteins, and vitamins from the GI tract to the liver for processing
- These dietary materials are too large to enter the bloodstream
Immunity - involvement of white blood cells

Describe lymph and the general pathway it takes from body tissues to the heart.

Lymph is a clearish-white fluid that is similar to blood plasma. Most components of blood plasma filter through the capillaries into interstitial fluid. When lymphatic capillaries absorb excess interstitial fluid, the fluid that is pulled into the lymphatic vessels is called lymph. Interstitial fluid and lymph are very similar in makeup, with the main difference being location. Lymph contains water, lymphocytes, cellular debris, plasma proteins and other cells.

Blood plasma containing oxygen and nutrients is filtered out of the capillary bed and into the surrounding interstitial spaces. Interstitial fluid and waste products in the interstitium are reabsorbed into the capillary bed for venous return. The rate of filtration and reabsorption are not equal. The filtration rate out of the capillary bed is greater than the reabsorption rate into the capillary bed. This creates an excess of interstitial fluid within the interstitium; the lymphatic system balances this. Typically, the lymphatic vessels will absorb the excess fluid so that the overall balance is net zero.

The pathway of lymph begins in specialized lymph capillaries that are interwoven within blood capillaries. The lymph capillaries are closed at one end and located between tissue cells. When the volume of the interstitial fluid becomes too high and causes the pressure to increase, the excess fluid makes its way into the lymphatic capillaries.

The lymph capillaries unite to form larger lymphatic vessels. The vessels are similar to veins, but have thinner walls and are harder to see with the naked eye. Superficially, just deep to the skin, the lymph vessels generally follow the same route as veins. Deep lymph vessels, around the viscera, tend to follow the path of arteries.

Lymph nodes are located at intervals along the lymph vessels and are encapsulated masses of lymphatic tissue and lymphocytes. In some areas of the body, lymph nodes can be found in clusters of varying sizes.

As lymphatic vessels exit lymph nodes, they unite to form lymph trunks. Major lymph trunks are located in specific regions of the body, including the lumbar, intestinal, bronchomediastinal, subclavian and jugular regions.

Trunks unite to form either the right lymphatic duct or the thoracic duct. The right lymphatic duct receives lymph from the right side of the head, neck, and thorax, as well as the entire right upper limb. The thoracic duct receives lymph returned from the left side of the head, neck, and thorax, as well as the whole left upper limb and all regions below the diaphragm.

The lymphatic duct drains into the right venous angle, while the thoracic duct drains into the left venous angle.

Discuss the role of the lymphatic system with edema.

Edema (swelling) occurs when the lymphatic system isn’t properly assisting in the reabsorption of interstitial fluid. This can happen due to an overwhelming increase in filtration of interstitial fluid, or the filtration rate may be normal but the lymph capillaries aren’t absorbing efficiently.

In general, edema is a sign of physiological dysfunction, and can either be contained locally or diffuse throughout the body. Lymphedema is edema that is specifically caused by a lymphatic dysfunction.

Explain the mechanism behind the different types of immunity.

Immunity is the ability to fend off disease, and can be categorized into innate immunity and acquired immunity.

Innate immunity

Born with it; No prior exposure to pathogen/antigen required
Body’s first line of defense
- Skin and mucous membranes act as a physical protective barrier
- Fever and inflammation
Generalized, not specific to a certain antigen
- No memory component

Acquired (adaptive) immunity

Built up over time; Prior exposure to antigen required, or inherited
Specific to a certain antigen
- Has a memory function
- Previous exposure required
Involves the formation of antibodies
- Antibodies (immunoglobulins) - act in different ways to facilitate an immune response

Understand the role of lymphocytes in acquired immunity. Discuss the role of antigens in an immune response and how antibodies are generated.

The lymphatic system functions as part of the acquired immune system, as lymphocytes are the modulators of acquired immunity. T cells and b cells are the two main types of lymphocytes.

T cells and B cells recognize pathogens, microbes, toxins, and cancer cells. These chemical substances that are recognized as foreign by the immune system are called antigens. When antigens are detected in the body, antigen presenting cells engulf them and break them down into fragments. They then present a fragment on their plasma membrane. T helper cells detect the antigen and activate other cells to fight it.

There are two types of acquired immunity, and thus two pathways for T helper cells to proceed with the immune response:

Humoral immunity

Antibody mediated immune response
- Antibodies are generated in response to presence of antigens (antigen = antibody + generator)
Pathway:
- T helper cell presents an antigen to a B lymphocyte (B cell) with a matching receptor
  - B cells are activated
- B cells differentiate into plasma cells
- Plasma cells produce antibodies with the same receptor shape for the specific antigen
  - Plasma cells are the only cell in the body that produces antibodies
- Some of the B cells become long-lived memory B cells
  - Initiates a stronger response against same antigen in the future

Cellular immunity

Cell-mediated immune response
- Functions through the direct actions of T lymphoblasts (T cells)
Pathway:
- T helper cells activate cytotoxic T cells that have a matching receptor on their surface
- Cytotoxic T cells directly destroy pathogens by releasing cell-killing (cytotoxic) chemicals and causing them to rupture
- Some cytotoxic T cells will differentiate into T memory cells
  - Initiates a stronger response against same antigen in the future
- Regulatory T cells turn off (regulate) an immune response by suppressing T cells
  - Important for prevention of autoimmunity (immunity against one’s self)

Discuss how HIV affects the immune system.

Human Immunodeficiency Virus (HIV) is a retrovirus that attacks T helper cells. T helper cells are the key to acquired immunity; without a sufficient number of T helper cells, the ability of the body to launch an acquired immune response is diminished. As an individual continues to live with this level of immunodeficiency, a certain threshold can be crossed that leads to acquired immunodeficiency syndrome (AIDS), the syndrome that is caused by an HIV infection. There are no specific parameters that indicate when AIDS will occur as a result of HIV, but clinically, a few factors are used to determine when that transition has occurred. The main indicator is the level of T helper cells in the body is below 200 cells/ml, as measured through a blood test. The other indicator is an increase of opportunistic infections, which are illnesses that occur more frequently and severely in people with HIV.

HIV may be transmitted through bodily fluids, such as blood, semen, vaginal fluids or rectal fluids. Today, this infection is manageable if caught and treated early. With current treatments, HIV doesn't always lead to AIDS, and many people who are HIV positive live a full life.

Explain primary versus secondary lymphatic organs and tissues

Lymphatic organs and tissues can be found across the body, and are categorized into primary lymphatic organs, and secondary lymphatic organs and tissues, based on their functions.

The primary lymphatic organs are where stem cells undergo mitosis, develop, and mature in order to become immunocompetent. Immunocompetence is the ability to conduct an immune response. These organs include red bone marrow and the thymus.

The secondary lymphatic organs and tissues are sites where immune responses are carried out, and these organs and tissues are the lymph nodes, lymph nodules, and the spleen.

Discuss the location and functions of red bone marrow.

Red bone marrow is also known as hemopoietic connective tissue or myeloid tissue. This primary lymphatic organ functions in the formation of blood cells. Red bone marrow contains two types of stem cells: myeloid stem cells (myelo- = marrow) and lymphoid stem cells.

Derivatives of myeloid stem cells include erythrocytes, thrombocytes, granular leukocytes, monocytes and macrophages.

Lymphoid stem cells give rise to T cells, natural killer cells, and B cells, which give rise to plasma cells. Immature T cells migrate from the red bone marrow to the thymus where they will mature and become immunocompetent. B cells can fully mature in the red bone marrow, and concentrate in the lymph nodes throughout the body upon release.

Red bone marrow is found in the flat bones of the axial skeleton (skull, scapulae, sternum, ribs, pelvis, and vertebral bodies), and in the ends of long bones.

Discuss the features, location and functions of the thymus. Explain how immature T cells become immunocompetent.

The thymus gland, a primary lymphatic organ, is situated between the great vessels of the heart and the sternum, within the mediastinum. The bulk of the stroma of the thymus is made up of thymic epithelial cells. It’s a bilobed, capsulated organ with the capsule enclosing each lobe separately. Extensions of the capsule, called trabeculae, project inward, dividing the lobes into lobules. Each lobule has a cortex and a medulla.

The cortex contains thymocytes, which are immature T cells, as well as dendritic cells and macrophages. Dendritic cells and epithelial cells help T cells to mature.

In the cortex, thymocyte selection takes place. Thymocyte selection is a maturation process for immature T cells, which enables them to recognize and respond to major histocompatibility complexes/MHC (positive selection) and avoid autoimmune responses (negative selection). Only 2% of all thymocytes survive selection.

Positive selection is a process that ensures thymocytes will respond appropriately to several cell surface molecules that are used as a training tool. These special cell surface molecules, called major histocompatibility complexes, act to ensure reactivity and specificity for the thymocytes.

Negative selection ensures that thymocytes don't react with the body’s own proteins.

If a thymocyte fails either part of the selection process, which is 98% of them, it undergoes apoptosis, or cell death. If a thymocyte survives, they leave the cortex of the thymus and enter the medulla.

The medulla contains more mature T cells, and there is an increased presence of antigen presenting cells (dendritic cells and macrophages). When it’s time, T cells are released from the medulla for circulation throughout the body.

The thymus reaches its maximum size around puberty, then undergoes involution throughout the rest of the individual’s life. As the thymus diminishes in size, it’s replaced by adipose tissue; a small portion of active thymic tissue will persist into adulthood.

Discuss the location, structure, and functions of lymph nodes. Describe lymph flow through a lymph node.

Lymph nodes function as a filter of lymph. Foreign substances brought into the node are trapped within the sinuses; macrophages destroy them via phagocytosis, and B cells and T cells destroy others through an immune response. The filtered lymph then leaves the node.

There are about 600 lymph nodes, on average, scattered throughout the body along lymph vessels, usually found in groups that are named for their location.

Lymph is carried to the nodes via afferent lymphatic vessels that open into the convex surface of the node. Lymphatic vessels utilize valves to ensure unidirectional flow of lymph into the nodes.

Lymph nodes are encapsulated, and deep to the capsule is the subcapsular sinus. Deep to the subcapsular sinus is a cortex that is divided into inner and outer parts. The outer cortex contains naive, inactivated (germinal) B cells, which remain naive until activated. The inner cortex contains T cells and dendritic cells. The dendritic cells are antigen presenting cells that present an antigen to T cells, causing the T cells to proliferate. These newly formed T cells then migrate from the lymph node to areas of the body where there is an active immune response.

Lymph flows through the outer and inner cortices into the medulla, which contains medullary sinuses. Within the medullary sinuses are mature B cells, plasma cells, and macrophages.

From the medullary sinuses, lymph drains out of the lymph node through 2-3 efferent lymph vessels, which drain the lymph from the hilum of the node. Since there are fewer efferent lymph vessels carrying lymph out of the node than afferent vessels, a bottleneck is created, and flow through the lymph node is slow. This allows more time for the lymph to be filtered within the node.

Describe the structure and function of lymphatic nodules including MALT and Waldeyer’s ring of tonsils.

Lymphatic nodules differ from lymph nodes, because they are not encapsulated, and therefore not as confined. They are collections of aggregated lymphatic tissue that are located throughout the lamina propria of mucous membranes. Due to their location within mucous membranes, lymphatic nodules are referred to as mucosa-associated lymphatic tissue (MALT). Within MALT, there are a lot of antigen presenting cells and lymphocytes.

MALT can be scattered across broad regions of the body, and a specific region of MALT is named for its location. For example MALT of the bronchi is called BALT, B for bronchi.

MALT can also be organized into more condensed regions; there are organized collections of lymphoid tissue in the distal portion of the ileum called Peyer’s patches. Peyer’s patches are important for immune responses in relation to food absorption through the intestinal walls.

Waldeyer’s ring of tonsils is another example of organized MALT. There are five tonsils that form a ring around the naso- and oropharynx, including the pharyngeal tonsil (adenoid), tubal tonsils, palatine tonsils (THE tonsils), and lingual tonsil. This organized collection of lymphatic tissue associated with the pharynx provides an opportunity for any pathogens that are ingested or inhaled to be brought into direct contact with the lymphatic system before further entering the body.

Inflammation of the palatine tonsils is known as tonsillitis, which is typically the result of a viral infection, but can also be from a Group A Strep infection.

Discuss the location, structure, and functions of the spleen.

The spleen is the largest single mass of lymphoid tissue in the body. This organ is tucked way up in the left upper quadrant of the abdomen, inferior to and directly in contact with the diaphragm. It is encapsulated, and has various impressions on its surface, caused by surrounding organs and structures.

It’s made up of two distinct portions, white pulp and red pulp. White pulp is immediately adjacent to the arteries and is where immune responses are generated within the spleen.

Red pulp surrounds the white pulp, and is cardiovascular in function (cardiovascular = red!). Macrophages within the red pulp work to eliminate red blood cells as they reach the end of their life cycle. The spleen is also the site of storage for up to ⅓ of the body’s supply of platelets, and is one of the organs active in hemopoiesis during fetal development.

Understand the basis of lymphadenopathy.

Lymphadenopathy refers to lymph nodes that are of abnormal size and/or consistency, and this can be a sign of infection. This can be systemic across the body, or localized. “Swollen glands,” as used colloquially, is fairly common and doesn’t indicate any specific pathologies. It could be a sign that the body is fighting off a very minor virus, or a more severe infection or malignancy. During a medical exam, clinicians palpate along known areas of lymph node clusters to feel for enlargement.

Lymphadenitis is the most common type of lymphadenopathy, and is characterized by painfully enlarged and inflamed lymph nodes.

Explain metastasis. How do lymph nodes relate to this process? Describe the pathways of metastasis.

Metastasis is the spread of malignancies. With malignancies, lymph nodes are often enlarged, firm and fixed, but are often painless. The malignancy may be a lymphoma (cancer of the lymph nodes), or it could be a metastasis into the lymph nodes from another area.

There are three pathways for the spread of cancer cells:

Transcoelomic - spread along a membrane or surface barrier
- Ex: spread along the peritoneum
Hematogenous - tumor cells from the primary tumor spread to other areas of the body through the bloodstream
- Typically through venous circulation
- Typical metastasis of sarcomas (mesenchymal) & renal carcinoma
Lymphogenous - tumor cells from the primary tumor spread to other regions of the body through lymph circulation
- Typical metastasis of carcinomas (epithelial)

Define the principal groups of the lymphatic system. Understand which regions of the body the right lymphatic duct and thoracic duct drain.

The pattern of lymphatic drainage can be grouped by region, and the main groups are the head and neck, the thorax, the upper limbs and axilla, the abdominopelvic region, the viscera, and the lower limbs.

The division of lymphatic drainage on the right and left sides is asymmetrical. The right lymphatic duct drains lymph from the right side of the head, neck, and thorax, and the entirety of the right upper limb. The thoracic duct will drain everything else: the left side of the head, neck and thorax, and the entirety of the left upper limb, abdomen, pelvis, and both lower limbs.

Describe the major distributions of lymph nodes and outline the lymphatic drainage in each principal body region.

Head and neck

Lymph flow through the head and neck passes through a series of lymphatic nodules, lymph node groupings, lymph vessels, and lymphatic trunks as it works its way inferiorly to the lymphatic ducts.

Waldeyer’s ring of tonsils is one of the first collections of lymphoid tissue in the pharynx that pathogens come into contact with, as they are inhaled or ingested through the naso- and oropharynx.

Lymph flows from the tonsils in the following pathway, from superior to inferior:

Walderyer’s ring of tonsils
Deep cervical lymph nodes - associated with internal jugular vein in the lateral neck
- 2 groups (divided anatomically by the intermediate tendon of the omohyoid m.):
  - Superior deep cervical lymph nodes
    - Includes the jugulodigastric node - positioned anterior to jugular v.
      - Larger than other nodes
    - Receives direct drainage from the tonsils, becomes enlarged in response to pathogens carried through lymph vessels
  - Inferior deep cervical lymph nodes
    - Include supraclavicular nodes - just superior to clavicle
      - Of particular interest clinically, as enlargement could indicate a serious, advanced disease
        Related to position near terminal lymph drainage at the lymphatic duct
Jugular trunk
Lymphatic duct

Superficial cervical lymph nodes collect lymph drainage from superficial regions of the head and neck, and are located along the external jugular vein. Lymph from these nodes drain into the subclavian trunk, which carries lymph to the duct.

As immune responses are mounted in the ring of tonsils or lymph nodes, inflammation may occur. Signs of infection in the ring of tonsils include enlargement, redness, and exudate (pus), as seen with strep throat. Enlargement of the lymph nodes may be palpated along the sides of the neck or just above the clavicle, and may even be visibly noticeable if severe enough.

Lungs

In the thoracic cavity, lymph is drained from the thoracic wall and organs. The lymphatic drainage from the lungs follows along the branching pattern of the bronchial tree and pulmonary vessels. Drainage isn’t active at the level of the alveoli, which is the most distal, smallest portion of the bronchial tree; it starts at the level of the bronchioles.

The pathway of pulmonary lymph drainage is as follows, from distal to proximal:

Pulmonary lymph nodes - located throughout the parenchyma of the lung
- Associated with larger (secondary and tertiary) bronchi
- Situated within the angles created by bronchial branching
Bronchopulmonary nodes - located at the hilum (entrance) of the lung
Tracheobronchial nodes - located at that junction of the trachea and main bronchi
- The bifurcation of the trachea into the main bronchi is the anatomical landmark that divides the tracheobronchial nodes into:
  - Inferior group (inferior to tracheal bifurcation)
    - Drains into superior group
  - Superior group (superior to tracheal bifurcation)
- Lymph from the bronchopulmonary nodes can drain into either the inferior or superior group
Bronchomediastinal trunks (left & right)
Lymphatic ducts

Understanding the lymph drainage pattern in the lungs is important for specialized health care professionals, as it helps guide the order of nodal biopsies when determining the extent of metastasis in the lung.

Breast & Axilla

Lymph is drained from the thoracic wall and breast in a predictable pattern. Drainage from the breast begins with the subareolar (lymphatic) plexus. From the subareolar plexus:

25% of lymph drainage is channeled medially to parasternal nodes and the contralateral breast,
75% of lymph is channeled to the axillary nodes, a collection of nodes and vessels that follow a specific pattern of drainage (proximal to distal), away from the breast:
- Pectoral nodes - located along the inferior border of pectoralis minor m.
- Central nodes
- Apical nodes - located at the apex of the axilla
  - Also collect lymph from the superficial forearm and arm

Subclavian trunk → lymphatic duct

Upper Limb and Axilla

In the upper limb, superficial lymphatic drainage follows the veins, and deep lymphatic drainage follows the arteries.

Deep lymph from the forearm and arm are received by the axillary lymph nodes. The axillary lymph nodes are subdivided into (from distal to proximal):

Humeral nodular group - associated with the proximal aspect of the humerus
Central nodes - in the central region of the axilla
Apical nodes - located at the apex of the axilla
- Also collect lymph from the superficial forearm and arm

Lymph vessels from the apical nodes coalesce into the subclavian trunk, which flows into the duct.

Abdomen and Pelvis

Lymphatic drainage of the abdominopelvic cavity is ultimately collected in the cisterna chyli, the dilated origin of the thoracic duct within the abdomen. The cisterna chyli receives lymphatic drainage from the lower limbs, pelvis, abdominal viscera, and abdominal walls (everything below the diaphragm).

Common iliac nodes cluster around the common iliac arteries and receive a large portion of lymph drainage that is destined for the cisterna chyli. Specifically, drainage received by the common iliac nodes come from:

External iliac lymph nodes - along external iliac a.
- Receives lymph from abdominal and pelvic walls, and lower limb
Internal iliac lymph nodes - along internal iliac a.
- Receives lymph from the viscera of the pelvis

From the common iliac nodes, lymph flows through the lumbar trunk and the lateral aortic lymph nodes associated with the lumbar trunk. Lymph from the lumbar trunk then flows into the cisterna chyli.

Lymph from the abdominal viscera arrives at the cisterna chyli through the intestinal trunk. Lymph nodes and vessels throughout the GI tract and other abdominal organs follow the pathway of the arteries that supply the organs (lymph return from the spleen follows the splenic artery, etc). As lymph flows toward the midline near the aorta, the lymph vessels coalesce to form the intestinal trunk. The intestinal trunk usually drains directly into the cisterna chyli.

From the cisterna chyli, the thoracic duct ascends through the abdomen and thorax to the root of the neck where it will drain the collected lymph into the left venous angle.

Abdominal Wall

Lymphatic drainage of the abdominal wall has a different pattern based on its location relative to the transumbilical plane. The transumbilical plane is a conceptual transverse plane at the level of the umbilicus that divides the abdomen into upper and lower quadrants. The two groups of lymphatic drainage of the abdominal wall are delineated by this landmark.

Lymphatic vessels and nodes superior to this plane drain lymph superiorly to the axillary nodes. The right side drains into the right lymphatic duct, while the left side drains into the thoracic duct. The axillary nodes drain into the subclavian trunk, which carries lymph to the duct.

Lymphatic vessels and nodes inferior to the transumbilical plane drain into the superficial inguinal nodes that are located superficially in the femoral triangle. From there, lymph drains into the deep inguinal nodes, which are deeper within the femoral triangle. The drainage pathway continues to the external iliac nodes, located adjacent to the external iliac artery, then to the common iliac nodes. Lymph from the common iliac nodes proceeds to the lumbar trunk and cisterna chyli. Note that both the right and left sides ultimately drain to the thoracic duct.

Lower Limb

In the lower limb, superficial lymph drainage follows superficial veins, and deep lymph drainage follows the deep arteries and veins.

Superficial lymph drainage follows the pathway of the great saphenous vein and empties into the superficial inguinal nodes within the femoral triangle.

Superficial lymph that follows the pathway of the lesser saphenous vein drains lymph to the popliteal lymph nodes within the popliteal fossa before going deep and following the femoral vein and draining into the deep inguinal nodes.

Lymph collected by the superficial inguinal nodes then drain into the deep inguinal nodes, before flowing into the external iliac nodes.

Which trunks unite to form the lymphatic ducts? Which structures form the venous angles?

The jugular, subclavian, and bronchomediastinal trunks unite to form the ducts. On the right, they form the right lymphatic duct, and on the left, they form the thoracic duct. The ducts drain into the vicinity of the venous angles of their respective side to return lymph to the bloodstream.

The venous angles are formed by the union of the internal jugular and subclavian veins on each side in the root of the neck.

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