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

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
  • Derived from myeloid stem cells in bone marrow and circulate in blood.
• Lymphocytes
  • T lymphocytes (T cells) and B lymphocytes (B cells) originate in bone marrow and migrate between blood and lymph.

Hematopoietic Tissue

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

Hematopoiesis

• White blood cells form partially in bone marrow and partially in the lymph system.
• Formed from hematopoietic stem cells that differentiate into committed progenitor cells.
• Progenitor cells develop into 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

• Growth and reproduction of different stem cells are controlled by multiple hematopoietic growth factors or inducers.
• Lifespan 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

• Self-limited lymphoproliferative disorder
• Definition:
  • 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