# Lecture 7: The Lymphatic System

## Anatomy and Physiology II

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## Learning Objectives

By the end of this lecture, students will be able to:

1. Describe the structure and function of the lymphatic system
2. Explain how lymph is formed and transported
3. Describe the structure of lymph nodes and their role in immune surveillance
4. Identify and describe the major lymphoid organs: thymus, spleen, tonsils, Peyer's patches, and MALT
5. Explain the relationship between the lymphatic and cardiovascular systems

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## Lecture Content

### I. Overview of the Lymphatic System

The lymphatic system is a one-way drainage network that returns excess interstitial fluid to the bloodstream. It serves three major functions. First, it recovers approximately 3 liters per day of excess interstitial fluid that is not reabsorbed at the venular end of capillary beds, returning it to the blood as lymph. Second, it houses immune cells in lymphoid organs and tissues where they can filter lymph and blood to detect and respond to pathogens. Third, it absorbs dietary fats through specialized lymphatic capillaries called lacteals in the small intestine, transporting fat-laden lymph (chyle) containing chylomicrons. Unlike the cardiovascular system, the lymphatic system is not a closed circuit; it begins as blind-ended capillaries in the tissues and eventually drains into the venous system.

### II. Lymphatic Vessels

#### Lymphatic Capillaries

Lymphatic capillaries are blind-ended, thin-walled vessels found in nearly all tissues, with notable exceptions including bone marrow, the central nervous system, and avascular tissues. They are slightly larger than blood capillaries and have a unique structural feature: their endothelial cells overlap loosely, acting as one-way minivalves. When interstitial fluid pressure rises, the overlapping flaps are pushed open and fluid enters the capillary. When pressure inside the capillary exceeds pressure outside, the flaps close and prevent backflow. This design makes lymphatic capillaries highly permeable, admitting proteins, cell debris, pathogens, and even cells that blood capillaries would exclude. **Lacteals** are specialized lymphatic capillaries in the intestinal villi that absorb dietary lipids.

#### Lymphatic Collecting Vessels

Collecting vessels receive lymph from the capillaries and are structurally similar to veins, with three tunics, though their walls are thinner. They contain numerous valves, even more than veins, to prevent backflow. Along their course, lymph passes through a series of lymph nodes where it is filtered and monitored by immune cells.

#### Lymphatic Trunks and Ducts

Collecting vessels converge into larger lymphatic trunks named for the regions they drain: jugular trunks (head and neck), subclavian trunks (upper limbs), bronchomediastinal trunks (thorax), intestinal trunk (abdomen), and lumbar trunks (lower limbs and pelvis). These trunks ultimately drain into two main ducts. The **right lymphatic duct** drains the right arm and the right side of the head and thorax, emptying into the right subclavian vein. The **thoracic duct** (left lymphatic duct), which is the larger of the two, drains the remaining three-quarters of the body. It begins at the cisterna chyli, a dilated sac in the abdomen at the level of L1-L2, and ascends to empty into the left subclavian vein at its junction with the left internal jugular vein.

#### Lymph Transport Mechanisms

The lymphatic system has no pump of its own, so lymph flows at low pressure, driven by several passive mechanisms. The skeletal muscle pump compresses lymphatic vessels during movement. The respiratory pump creates pressure changes during breathing that propel lymph. Rhythmic contractions of smooth muscle in the walls of lymphatic vessels provide intrinsic propulsion. Pulsation of nearby arteries compresses adjacent lymphatic vessels. Valves throughout the system prevent backflow. Exercise significantly increases lymph flow, and the total daily return of lymph to the blood is approximately 3 liters.

<image>A full-body anterior view showing the lymphatic drainage system. Panel A: The major lymphatic vessels, trunks, and ducts labeled — the thoracic duct running from the cisterna chyli upward along the vertebral column to drain into the left subclavian vein, and the right lymphatic duct draining into the right subclavian vein. The body is color-coded to show the drainage territory of each duct (right lymphatic duct in one color for the right upper quadrant, thoracic duct in another color for the remaining three-quarters of the body). Panel B: An enlarged view of a lymphatic capillary showing overlapping endothelial cells acting as minivalves, with arrows demonstrating fluid entry from the interstitial space. Anchoring filaments connecting to surrounding tissue are shown. Panel C: A cross-section of a lymphatic collecting vessel showing the three tunics, valve leaflets, and direction of lymph flow.</image>

### III. Lymph Nodes

Lymph nodes are small, bean-shaped organs measuring 1 to 25 mm in diameter, clustered along lymphatic vessels. The body contains approximately 600 lymph nodes, with major clusters in the cervical, axillary, inguinal, mesenteric, and mediastinal regions.

#### Structure

Each node is surrounded by a fibrous capsule that sends inward extensions called trabeculae. The node is divided into an outer **cortex** and an inner **medulla**. The cortex contains **follicles**, which are dense clusters of B lymphocytes. Within active follicles, **germinal centers** serve as sites of B cell proliferation during an immune response. The **paracortex** (deep cortex) is predominantly populated by T lymphocytes and dendritic cells. The **medulla** contains **medullary cords**, strands of lymphoid tissue housing B cells, T cells, plasma cells, and macrophages, interspersed with **medullary sinuses**, channels through which lymph percolates and macrophages line the walls. A supporting network of reticular fibers and reticular cells provides structural scaffolding throughout.

#### Lymph Flow Through a Node

Lymph enters a node through several afferent lymphatic vessels at the convex surface, flowing into the subcapsular sinus. From there, it percolates through cortical sinuses, the paracortex, and medullary sinuses, where macrophages phagocytize debris and pathogens and lymphocytes survey for foreign antigens. Filtered lymph exits via one or two efferent lymphatic vessels at the hilum (the concave surface). Because lymph passes through multiple nodes before returning to the blood, it undergoes thorough filtration and immune surveillance.

#### Functions

Lymph nodes serve two primary functions: filtering lymph by using macrophages to remove debris, pathogens, and cancer cells, and activating immune responses when lymphocytes encounter antigens. Lymphadenopathy, the swelling of lymph nodes, is a clinical sign indicating an active immune response or underlying disease.

<image>A cross-sectional diagram of a lymph node. Panel A: Overall structure showing the fibrous capsule, trabeculae extending inward, cortex with follicles (containing germinal centers in lighter shading), paracortex (labeled as T cell zone), medulla with medullary cords and sinuses, afferent lymphatic vessels entering at the convex surface, and efferent lymphatic vessel exiting at the hilum along with blood vessels. Arrows trace the flow of lymph from afferent vessels through subcapsular sinus, cortical sinuses, medullary sinuses to efferent vessel. Panel B: A magnified view of a follicle germinal center showing proliferating B cells, follicular dendritic cells presenting antigens, and differentiating plasma cells migrating toward medullary cords.</image>

### IV. Other Lymphoid Organs and Tissues

#### Thymus

The thymus is a bilobed organ in the superior mediastinum, posterior to the sternum. It is largest and most active during infancy and childhood, then gradually involutes (shrinks) after puberty and is progressively replaced by adipose tissue. Each lobe is divided into lobules with a densely packed **cortex** containing immature T lymphocytes (thymocytes) and a lighter-staining **medulla** with fewer, more mature T cells and distinctive thymic (Hassall's) corpuscles.

The thymus is the site where T lymphocytes mature and undergo selection, learning to distinguish self from non-self through positive and negative selection. Only about 2% of thymocytes survive this rigorous screening to emerge as self-tolerant, MHC-restricted T cells. A blood-thymus barrier prevents premature exposure of developing T cells to circulating antigens. Unlike lymph nodes, the thymus does not filter lymph and is not directly connected to lymphatic vessels.

#### Spleen

The spleen is the largest lymphoid organ, located in the left upper quadrant of the abdomen. It is about the size of a fist (approximately 12 cm long), richly vascularized, and dark red-purple in color. It is surrounded by a fibrous capsule with internal trabeculae.

The spleen contains two functional regions. **White pulp** consists of lymphoid tissue surrounding small central arterioles. It contains T cells in the periarteriolar lymphatic sheaths (PALS) and B cells in follicles, and it conducts immune surveillance of blood-borne antigens. **Red pulp** consists of a network of splenic sinusoids and splenic cords (cords of Billroth) filled with macrophages, red blood cells, and other blood cells. The red pulp filters blood by removing old or damaged erythrocytes and platelets, phagocytizing pathogens and debris, and serving as a reservoir for blood (especially platelets and monocytes). In the fetus, the spleen is also a site of hematopoiesis.

**Splenectomy** (surgical removal of the spleen) increases susceptibility to certain encapsulated bacterial infections, particularly those caused by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. Patients who have undergone splenectomy receive vaccinations and may require prophylactic antibiotics.

#### Tonsils

The tonsils form a ring of lymphoid tissue around the pharynx known as Waldeyer's ring. The **palatine tonsils** are the largest and sit on each side of the posterior oral cavity. The **pharyngeal tonsil** (adenoid) occupies the posterior wall of the nasopharynx. **Lingual tonsils** are located at the base of the tongue, and **tubal tonsils** sit near the auditory tube openings. All tonsils contain lymphoid follicles with germinal centers and function as a first line of immunological defense, trapping and responding to pathogens that enter through the mouth and nose. Tonsillitis, inflammation of the tonsils, results from recurrent infection.

#### Mucosa-Associated Lymphoid Tissue (MALT)

MALT refers to diffuse collections of lymphoid tissue in the mucous membranes throughout the body. **Peyer's patches** are aggregated lymphoid nodules in the wall of the ileum that monitor intestinal bacteria and prevent pathogens from breaching the intestinal wall. Specialized M cells (microfold cells) in the overlying epithelium sample antigens and deliver them to underlying immune cells. **BALT** (bronchus-associated lymphoid tissue) provides immune surveillance in the respiratory tract. **GALT** (gut-associated lymphoid tissue) includes Peyer's patches, the appendix, and diffuse lymphoid tissue in the gut wall. The appendix, once considered vestigial, contains abundant lymphoid tissue and is thought to serve as a reservoir for beneficial gut bacteria.

### V. Clinical Correlations

**Lymphedema** is the accumulation of lymph in tissues due to blocked or damaged lymphatic vessels. It may result from surgery (such as lymph node removal during cancer treatment), radiation therapy, or parasitic infection (filariasis, which can cause elephantiasis). The condition produces chronic swelling, usually in a limb. **Lymphoma** is cancer of lymphoid tissue and comes in two major forms: Hodgkin lymphoma, characterized by the presence of Reed-Sternberg cells and often curable, and non-Hodgkin lymphoma, a diverse group of lymphoid cancers. Cancer cells can also spread through lymphatic vessels to lymph nodes and beyond, a process called **metastasis via lymphatics**. The **sentinel lymph node biopsy** technique identifies the first node receiving drainage from a tumor site, helping to determine whether cancer has spread.

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