Chapter 24 Disorders of White Blood Cells and Lymphoid Tissue

Overview of White Blood Cell Disorders

White blood cells (WBCs) are primarily formed in the bone marrow, where myeloid cells develop.
WBCs circulate through the bloodstream and mature in lymphoid tissues such as lymph nodes, the thymus, and the spleen.
The primary role of neutrophils is to respond to infections, acting as the first line of defense against pathogens.
Neutrophils are crucial in non-neoplastic disorders, particularly in the context of infections and inflammatory responses.
The normal range of leukocytes in the blood is between 5,000 to 10,000 cells/mm³, with neutrophils being the most affected in leukopenia.
Understanding the formation and function of WBCs is essential for diagnosing and treating various hematological disorders.

Leukopenia refers to a decrease in the absolute number of leukocytes, often affecting neutrophils.
Neutropenia is defined as having fewer than 1,000 neutrophils/mL, while agranulocytosis indicates a virtual absence of neutrophils.
- Common causes of neutropenia include drug-related factors (e.g., chemotherapy), autoimmune diseases (e.g., lupus), infections, and hematologic malignancies.
- The clinical implications of neutropenia include increased susceptibility to infections, necessitating prompt medical intervention.
Regular monitoring of blood counts is crucial for patients at risk of neutropenia.

Hematologic neoplasms include leukemias, lymphomas, and plasma cell dyscrasias, affecting blood, bone marrow, and lymph nodes.
Leukemia is characterized by the proliferation of immature blood cells, leading to a crowded bone marrow environment.
Lymphomas are classified into Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), with distinct pathophysiological features.
Plasma cell dyscrasias, such as multiple myeloma, involve the abnormal proliferation of plasma cells producing monoclonal antibodies.
The classification of these neoplasms is based on the cell type involved (B-cell, T-cell, or NK-cell) and the disease's acute or chronic nature.
Understanding the types of hematologic cancers is essential for effective diagnosis and treatment planning.

In non-Hodgkin lymphomas, cancerous WBCs proliferate uncontrollably, leading to the suppression of normal blood cell development.
Hodgkin lymphoma is marked by the presence of Reed-Sternberg cells, which are indicative of the disease.
The pathophysiology of leukemias involves the diffuse replacement of bone marrow with immature neoplastic cells, leading to systemic symptoms.
Chromosomal abnormalities, such as translocations, play a significant role in the development of various hematologic malignancies.

Non-Hodgkin lymphoma
- B cell, T cell or NK cell origin
- Arise in Lymphocytes- peripheral lymphoid tissue
- Etiology- chromosomal translocation, Epstein Barr virus, H. Pylori
- Originates at extra nodal sites and spreads to contiguous nodes
- can be indolent (slow-growing) or aggressive
- Symptoms range from painless lymphadenopathy (in retroperitoneum, mesentery, pelvis) to systemic signs like fever and night sweats.
Hodgkin lymphoma typically presents with painless lymphadenopathy, often in the neck or supraclavicular area( above the level of diaphragm) enlargement single node or a group of nodes(single or chain)
- B lymphocytes
- Etiology: carcinogen exposure, virus, genetic
- Red Sternberg cells (two nuclei)
- Bimodal Early adulthood (15-40 years) & older adulthood (>55 years)
- chest discomfort, cough, dyspnea, fatigue, anemia
- Mediastinal masses are common in Hodgkin lymphoma and may be detected in Xray

Leukemias present with symptoms related to bone marrow infiltration, including anemia, neutropenia, and thrombocytopenia.
- Derived from hematopoietic stem cells→ immature cells that can develop into all types of blood cells
Acute leukemias (ALL and AML) often have a sudden onset, with symptoms like fatigue, fever, and easy bruising. ALL→ Children
AML→ Caused by the proliferation of undifferentiated (blast) myeloid cells in the bone marrow.
- the growth of myeloid blast cause the rduction of the production of normal blood cells.
- Manifestaitos. bleeding from thrombocytopnea. frequent infection- lack of wbcs
Chronic leukemias (CLL and CML) may have a more insidious onset, with symptoms developing over time, including lymphadenopathy and splenomegaly.
The Philadelphia chromosome is a hallmark of chronic myelogenous leukemia (CML), indicating a specific genetic mutation.
Diagnosis involves blood tests, bone marrow aspiration, and cytogenetic analysis to identify specific leukemic cell types.
Understanding the clinical features of leukemias is essential for timely diagnosis and management.

CLL

more common in adults -Hypogammaglobulinemia(increased risk of infection)

CML

Philadelphia Chromosome is present -Blast cell crisis

Hematologic neoplasm arising in B lymphocytes
Causes proliferation of abnormal plasma cells in bone marrow-> synthesis of abnormal Immunoglobulins (Igs)
Leads to bone destruction, bone marrow failure, renal failure, neurological complications
The abnormal Igs and fragments are referred to as monoclonal proteins or M-proteins (Bence Jones proteins)

genetic change in the cells that cause change in the normal apoptosis- cells don’t die and start replicating

Leukostasis

Condition in which circulating blast count is markedly elevated
Increases blood viscosity→ predispose for emboli or thrombus
Predisposes to emboli, occlusion of vessels
Treat with plasma apheresis(blood goes out of the body into the machine to get rid of the blasts cells) , chemotherapy

Hyperuricemia

Increased breakdown of purine secondary to leukocyte cell death from chemotherapy
Uric acid= renal complications