Chapter 24 Notes: Disorders of White Blood Cells and Lymphoid Tissues

Chapter 24: Disorders of White Blood Cells and Lymphoid Tissues

Formed Elements of Blood

  • Red blood cells
  • Platelets (megakaryocytes)
  • Granulocytes: Neutrophils, eosinophils, and basophils.
  • Monocyte and macrophage lineage: Both are derived from the myeloid stem cell in the bone marrow and circulate in the blood.
  • Lymphocytes:
    • T lymphocytes (T cells)
    • B lymphocytes (B cells)
    • Originate in the bone marrow and migrate between the blood and the lymph.

Hematopoietic Tissue

  • Myeloid tissue
    • Bone marrow
  • Lymphoid tissue
    • Nodes
    • Thymus
    • Spleen

Hematopoiesis

  • White blood cells are formed partially in the bone marrow and partially in the lymph system.
  • They are formed from hematopoietic stem cells that differentiate into committed progenitor cells.
  • These in turn develop into the myelocytic and lymphocytic lineages needed to form white blood cells.
  • RBCs and platelets are formed in the marrow and released into circulation.

Growth and Reproduction of White Blood Cells

  • The growth and reproduction of different stem cells are controlled by multiple hematopoietic growth factors or inducers.
  • The life span of WBCs is relatively short; constant renewal is necessary to maintain normal blood levels.
  • Conditions that decrease availability of stem cells or hematopoietic growth factors produce a decrease in WBCs.

Diseases of Deficient Blood Cell Production

  • Leukopenia: Deficiency of leukocytes
  • Aplastic anemia: Anemia, thrombocytopenia, and agranulocytosis
  • Neutropenia: Granulocytopenia

Causes of Neutropenia

  • Accelerated removal
  • Drug-induced granulocytopenia
  • Periodic or cyclic neutropenia
  • Neoplasms involving bone marrow
  • Idiopathic neutropenia occurring in the absence of other disease or provoking influence
  • Felty syndrome

Signs and Symptoms of Neutropenia

  • Malaise
  • Chills
  • Fever
  • Extreme weakness and fatigue
  • Initially, those of bacterial or fungal infections
  • Reduced white blood cell count

Question #1

  • The suffix –penia refers to a decrease in number.

Infectious Mononucleosis

  • Definition: Self-limited lymphoproliferative disorder
  • Causes and Characteristics:
    • Caused by the B-lymphocytotropic EBV, a member of the herpes virus family; transmitted in saliva
    • Characterized by fever, generalized lymphadenopathy, sore throat, and the appearance in the blood of atypical lymphocytes and several antibodies
    • Highest incidence in adolescents and young adults
    • Treatment is symptomatic and supportive.

Neoplastic Disorder of Hematopoietic and Lymphoid Origin

  • Represent the most important of the white cell disorders
  • Include somewhat overlapping categories:
    • Lymphomas (Hodgkin disease and non-Hodgkin lymphoma)
    • Leukemia
    • Plasma cell dyscrasias (multiple myeloma)

Clinical Features of Neoplasms

  • Largely determined by:
    • Their site of origin
    • The progenitor cell from which they originated
    • The molecular events involved in their transformation into a malignant neoplasm
  • Chromosomal aberrations:
    • Deletions
    • Polyploidy
    • Translocations
    • Hyperploidy
    • Inversions

Question #2

  • Which of the following is NOT a chromosomal aberration?
    • Regression

Hodgkin Disease and Non-Hodgkin Disease

  • Hodgkin disease
    • Lymphoma arises in a single node or chain of nodes.
    • Reed-Sternberg cells are present.
    • Reed-Sternberg cells are derived from B lymphocytes.
  • Non-Hodgkin disease
    • Lymphoma originates at extranodal sites and spreads to anatomically contiguous nodes.
    • Reed-Sternberg cells are not present.

Symptoms of Hodgkin Disease

  • Stage A: Lack constitutional symptoms
  • Stage B: Significant weight loss, fevers, pruritus, or night sweats (40% of persons with Hodgkin disease)
  • Advanced Stages: Fatigue and anemia; liver, lungs, digestive tract, and CNS may be involved.

Categories of Non-Hodgkin Lymphomas

  • Low-grade lymphomas: Predominantly B-cell tumors
  • Intermediate-grade lymphomas: Include B-cell and some T-cell lymphomas
  • High-grade lymphomas: Largely immunoblastic (B cell), lymphoblastic (T cell), Burkitt, and non- Burkitt lymphomas

Diagnosis of Hodgkin Disease

  • Reed-Sternberg cell present in a biopsy specimen of lymph node tissue
  • Computed tomography (CT) scans of the chest and abdomen to assess for involvement of mediastinal, abdominal, and pelvic lymph nodes
  • A bipedal lymphangiogram to detect structural changes in the lymph nodes too small to visualize on CT scan
  • A positron emission tomography (PET) imaging
  • A bilateral bone marrow biopsy may be performed if disease is disseminated.

Staging of Non-Hodgkin Lymphomas

  • Disease
  • BONE MARROW BIOPSY
  • BLOOD STUDIES
  • CHEST AND ABDOMINAL CT SCANS
  • NUCLEAR MEDICINE STUDIES
  • CYTOLOGIC EXAMINATION OF THE CEREBROSPINAL FLUID

Treatment for Hodgkin and NHL Types

  • Radiation
  • Combination chemotherapy
  • For NHL only:
    • Adjuvant radiation therapy
    • Monoclonal antibodies
  • Depends on the histologic type, stage of the disease, and clinical status of the person

Leukemias

  • Definition: Malignant neoplasms arising from the transformation of a single blood cell line derived from hematopoietic stem cells
  • Classification according to cell lineage:
    • Lymphocytic (lymphocytes)
    • Myelocytic (granulocytes, monocytes)

Chronic Leukemias

  • Definition: Malignancies involving the proliferation of well- differentiated myeloid and lymphoid cells
  • Types of chronic leukemia:
    • Chronic lymphocytic leukemia (CLL)
    • Chronic myelogenous leukemia (CML)

Classification of Leukemia Types

  • Acute lymphocytic (lymphoblastic) leukemia (ALL): Both involve immature lymphocytes and their progenitors in the bone marrow, the spleen, lymph nodes, CNS, and other tissue.
  • Chronic lymphocytic leukemia (CLL)
  • Acute myelogenous (myeloblastic) leukemia (AML): Both involve the pluripotent myeloid stem cells in bone marrow and interfere with the maturation of all blood cells.
  • Chronic myelogenous leukemia (CML)

Goals of Treatment for CML

  • A hematological response characterized by normalized blood counts
  • A cytogenetic response demonstrated by the reduction or elimination of the Ph chromosome from the bone marrow
  • A molecular response confirmed by the elimination of the BCR-ABL fusion protein

Criteria for Remission of ALL and AML

  • Less than 5% blasts in the bone marrow
  • Normal peripheral blood counts
  • Absence of cytogenetic abnormalities
  • Return to preillness performance status

Factors Affecting the Likelihood of Achieving Remission

  • Age (most significant prognostic variable)
  • Type of leukemia
  • Stage of the disease at time of presentation

Leukemic Cells

  • Are immature and poorly differentiated
  • Proliferate rapidly and have a long life span
  • Do not function normally
  • Interfere with the maturation of normal blood cells
  • Circulate in the blood stem
  • Cross the blood–brain barrier
  • Infiltrate many body organs

Warning Signs Complications of Acute Leukemia

  • Signs
    • Fatigue
    • Pallor
    • Weight loss
    • Repeated infections
    • Easy bruising
    • Nosebleeds
    • Other types of hemorrhage
  • Complications
    • Leukostasis
    • Tumor lysis syndrome
    • Hyperuricemia
    • Blast crisis

Multiple Myeloma

  • Definition: A plasma cell dyscrasia characterized by expansion of a single clone of immunoglobulin -producing plasma cells and a resultant increase in serum levels of a single monoclonal immunoglobulin or its fragments
  • Main sites involved: The bones and bone marrow
  • Proliferation and activation of osteoclasts that lead to bone resorption and destruction
  • Pathologic fractures
  • Hypercalcemia