COMPARATIVE MORPHOLOGICAL ORGANIZATION OF THE HUMAN LYMPHATIC SYSTEM AND LABORATORY RATS

COMPARATIVE MORPHOLOGICAL ORGANIZATION OF THE HUMAN LYMPHATIC SYSTEM AND LABORATORY RATS

Pavel Varaksa

Associate Professor, Candidate of Biological Sciences, Federal State Budgetary Institution National Medical Research Center of Oncology named after N.N. Blokhin» of the Ministry of Health of Russia,

Russia, Moscow

Elena Grigorieva

Doctor of Biological Sciences, Federal State Budgetary Institution National Medical Research Center of Oncology named after N.N. Blokhin» of the Ministry of Health of Russia,

 Russia, Moscow

Anna Smirnova

Candidate of Biological Sciences, Federal State Budgetary Institution National Medical Research Center of Oncology named after N.N. Blokhin» of the Ministry of Health of Russia,

Russia, Moscow

Nikolay Kireenko

Postgraduate student, dermatologist, cosmetologist,

 Russia, Moscow

ABSTRACT

The authors conducted studies to identify and clarify the patterns of the lymphatic system in an adult laboratory rat in a comparative aspect with a human to identify points of violation when extrapolating data obtained during a radiopharmaceutical study.

Keywords: lymphatic system, lymph node, lymph vessel, rat lymph system, human lymph system

The lymphatic system is perhaps the most poorly understood area of anatomy. Lymphatic vessels are small transparent channels that are concentrated near the surface of the skin and mucous membrane of the digestive canal, where they collect and transport tissue fluid to the lymph nodes, where an immune response is triggered to fight foreign agents. In addition to their role in the immune response, lymph nodes can serve as a pathway for cancer metastasis. Thus, understanding the anatomy of the lymphatic system is of paramount importance for prediction cancer metastasis and to perform proper dissection of lymph nodes in cancer patients.

Figure 1. Groups of lymph nodes in an adult rat. Nodes located dorsally are demonstrated by reflecting muscles and internal organs (Nicholas L. Tilney, 1971)

Figure 2. Common distribution of lymph nodes in adult human

The distribution of lymph nodes in rats was well shown (Fig. 1). There may be intraspecific and intra-breed differences in the number of nodes and their topography. The nodes are usually very small (1-4 mm) and difficult to visualize in adipose or other tissues. They are usually grayish in color and elongated or round. The largest lymph nodes, as a rule, are mesenteric and mandibular nodes. Other nodes commonly used for histological studies include popliteal, axillary and iliac.

Human lymph nodes are present in typical external locations, including the organs of hematopoiesis and immune protection of the cervical (cervical), axillary and inguinal regions, as well as internal localizations, including the thoracic, paraaortic and mesenteric regions (Fig. 2). In humans, lymph nodes vary in size from 0.5 to 2 cm. Even in healthy people, only superficially located lymph nodes are often probed.

Figure 3. Diagram of the microstructural organization of the lymph node

Since the size of rat lymph nodes is very small, conventional histological sections may differ in their structural organization. For example, slices taken either in the sagittal or frontal plane will show areas of the cortex, paracortex and brain area of various sizes. Thus, although these manifestations are normal, they can mimic the lesions observed in old rats, as well as in experimentally induced pathologies.  Typical changes in the structure when changing the histological section through the node are shown in Figure 4.

The size of the lymph node separation depends on the plane of the section. The capsule is thin, with underlying subcapsular sinuses. In young rats, the bark contains follicles and several small germ centers. Often the germ centers are not visible.  When germ centers are present, they usually contain centrocytes, centroblasts, and follicular dendritic cells with sensitive macrophages of the body and remnants of apoptotic cells. Larger germ centers indicate a reaction to antigenic stimuli.

Since human lymph nodes are much larger than those of a rat, it is much easier to perform a complete cross-section of a human node for examination using light microscopy. Like a rat, human lymph nodes surrounded by a denser capsule of connective tissue. Under the capsule is the cortex of the lymph node, which contains primary and secondary follicles of B cells. Secondary follicles contain germ centers, and multiple germ centers can be seen in the reactive lymph node (Fig. 4). Even in young people, the germ centers are surrounded by a well-formed mantle zone (Fig. 4B).  The germinal center and the mantle zone usually show polarity, with the thicker part of the mantle zone facing the crust, and the thin part facing the central part of the node.

Under the thin part of the mantle zone there is a dark zone of the germinal center, which consists mainly of centroblasts, while at the opposite pole of the lymph node there is a light zone, which contains a larger number of centrocytes, T-cells and dendritic cells. It should be noted that at high power, the germ center centroblasts can be mistaken for atypical if they are considered outside the context of the rest of the lymph node, since they may contain multiple mitotic figures, apoptotic corpuscles and activated cells characterized by a high ratio of nucleus and cytoplasm, vesicular chromatin and protruding nucleoli (Fig. 4D). Sometimes you can see the marginal zone surrounding the mantle zone of the follicle, but it is less developed than those observed in other organs, such as the spleen or lymphoid tissue associated with the mucous membrane (MALT). There is a paracortical (interfollicular) zone between the follicles. This zone usually contains small reactive T-lymphocytes. When stimulated, IDCs present antigens to neighboring lymphocytes. In stimulated by antigen (reactive) lymph nodes, a mixture of small lymphocytes and abundant IDCs is called nodular paracortical hyperplasia and appears spotty at low power (Fig. 4C). In the central part of the lymph nodes, open sinuses are visible. In various reactive states, these sinuses can be filled with histiocytes, a phenomenon called sinus histiocytosis.

Figure 4. Histological organization of lymph nodes of rat (left) and human (right). (A) Overview of the capsule of the lymph node, germ centers (GC) and interfollicular (paracortical) lymphocytes. (B) The germinal center with the adjacent mantle zone (MZ). (C) paracortical/ interfollicular zone with hyperplasia in the human lymph node. Pay attention to the germinal center on the right edge of the human figure. (D) Close-up of germ center cells with mitotic figures, apoptotic bodies and macrophages (Piper M. Treuting, 2012)

Thus, it can be concluded that the lymph nodes of rats are very small compared to those of humans, and therefore their microstructural organization depends on the cross-sectional plane. It is worth noting that lymph nodes in young rats do not have well-developed germ centers, whereas germ centers are observed in humans at any age.

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