Exposure to antigen through a break in the skin or mucosa results in antigen being taken up by an antigen-presenting cell and carried via lymphatic channels to the nearest lymph node. Lymph channels course throughout the body except for the brain and the bones. Lymph enters the node through the afferent vessel and leaves through an efferent vessel. As antigen-presenting cells pass through lymph nodes, they present antigen to lymphocytes residing there. Lymphocytes in a node are constantly being replaced by antigen-naïve lymphocytes from the blood. They are retained in the node via special homing receptors. B cells populate the lymphoid follicles in the cortex; T cells populate the paracortical regions. When a B cell encounters an antigen to which its surface immunoglobulin can bind, it stays in the follicle for a few days and forms a germinal center where the immunoglobulin gene is mutated in an effort to make an antibody with higher affinity for the antigen. The B cell then migrates to the medullary region, differentiates into a plasma cell, and secretes immunoglobulin into the efferent lymph.
When a T cell in the node encounters an antigen it recognizes, it proliferates and joins the efferent lymph. The efferent lymph laden with antibodies and T cells specific for the inciting antigen passes through several nodes on its way to the thoracic duct, which drains lymph from most of the body. From the thoracic duct, lymph enters the bloodstream at the left subclavian vein. Lymph from the head and neck and the right arm drains into the right subclavian vein. From the bloodstream, the antibody and T cells localize to the site of infection.
Lymphadenopathy may be caused by infections, immunologic diseases, malignancies, lipid storage diseases, or other disorders of uncertain etiology (e.g., sarcoidosis, Castleman’s disease; Table 50-1). The two major mechanisms of lymphadenopathy are hyperplasia, in response to immunologic or infectious stimuli, and infiltration, by cancer cells or lipid- or glycoprotein-laden macrophages.
TABLE 50-1 DISEASES ASSOCIATED WITH LYMPHADENOPATHY
APPROACH TO THE PATIENT Lymphadenopathy
HISTORY Age, occupation, animal exposures, sexual orientation, substance abuse history, medication history, and concomitant symptoms influence diagnostic workup. Adenopathy is more commonly malignant in origin in those over age 40. Farmers have an increased incidence of brucellosis and lymphoma. Male homosexuals may have AIDS-associated adenopathy. Alcohol and tobacco abuse increase risk of malignancy. Phenytoin may induce adenopathy. The concomitant presence of cervical adenopathy with sore throat or with fever, night sweats, and weight loss suggests particular diagnoses (mononucleosis in the former instance, Hodgkin’s disease in the latter).
PHYSICAL EXAMINATION Location of adenopathy, size, node texture, and the presence of tenderness are important in differential diagnosis. Generalized adenopathy (three or more anatomic regions) implies systemic infection or lymphoma. Subclavian or scalene adenopathy is always abnormal and should be biopsied. Nodes >4 cm should be biopsied immediately. Rock-hard nodes fixed to surrounding soft tissue are usually a sign of metastatic carcinoma. Tender nodes are most often benign.
LABORATORY TESTS Usually lab tests are not required in the setting of localized adenopathy. If generalized adenopathy is noted, an excisional node biopsy should be performed for diagnosis, rather than a panoply of laboratory tests.
Pts over age 40, those with scalene or supraclavicular adenopathy, those with lymph nodes >4 cm in diameter, and those with hard nontender nodes should undergo immediate excisional biopsy. In younger pts with smaller nodes that are rubbery in consistency or tender, a period of observation for 7–14 days is reasonable. Empirical antibiotics are not indicated. If the nodes shrink, no further evaluation is necessary. If they enlarge, excisional biopsy is indicated.
Just as the lymph nodes are specialized to fight pathogens in the tissues, the spleen is the lymphoid organ specialized to fight bloodborne pathogens. It has no afferent lymphatics. The spleen has specialized areas like the lymph node for making antibodies (follicles) and amplifying antigen-specific T cells (periarteriolar lymphatic sheath, or PALS). In addition, it has a well-developed reticuloendothelial system for removing particles and antibody-coated bacteria. The flow of blood through the spleen permits it to filter pathogens from the blood and to maintain quality control over erythrocytes (RBCs)—those that are old and nondeformable are destroyed, and intracellular inclusions (sometimes including pathogens such as Babesia and Plasmodium) are culled from the cells in a process called pitting. Under certain conditions, the spleen can generate hematopoietic cells in place of the marrow.
The normal spleen is about 12 cm in length and 7 cm in width and is not normally palpable. Dullness from the spleen can be percussed between the ninth and eleventh ribs with the pt lying on the right side. Palpation is best performed with the pt supine with knees flexed. The spleen may be felt as it descends when the pt inspires. Physical diagnosis is not sensitive. CT or ultrasound are superior tests.
Spleen enlargement occurs by three basic mechanisms: (1) hyperplasia or hypertrophy due to an increase in demand for splenic function (e.g., hereditary spherocytosis where demand for removal of defective RBCs is high or immune hyperplasia in response to systemic infection or immune diseases); (2) passive vascular congestion due to portal hypertension; and (3) infiltration with malignant cells, lipid- or glycoprotein-laden macrophages, or amyloid (Table 50-2). Massive enlargement, with spleen palpable >8 cm below the left costal margin, usually signifies a lymphoproliferative or myeloproliferative disorder.
TABLE 50-2 DISEASES ASSOCIATED WITH SPLENOMEGALY GROUPED BY PATHOGENIC MECHANISM
Peripheral blood RBC count, white blood cell count, and platelet count may be normal, decreased, or increased depending on the underlying disorder. Decreases in one or more cell lineages could indicate hypersplenism, increased destruction. In cases with hypersplenism, the spleen is removed and the cytopenia is generally reversed. In the absence of hypersplenism, most causes of splenomegaly are diagnosed on the basis of signs and symptoms and laboratory abnormalities associated with the underlying disorder. Splenectomy is rarely performed for diagnostic purposes.
Individuals who have had splenectomy are at increased risk of sepsis from a variety of organisms including pneumococcus and Haemophilus influenzae. Vaccines for these agents should be given before splenectomy is performed. Splenectomy compromises the immune response to these T-independent antigens.
For a more detailed discussion, see Henry PH, Longo DL: Enlargement of Lymph Nodes and Spleen, Chap. 59, p. 465, in HPIM-18.