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Chapter 24: Disorders of White Blood Cells and Lymphoid Tissues

Formed Elements of Blood

Red blood cells

Platelets (megakaryocytes)

Granulocytes (i.e., 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) and 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

Neutropenia

Granulocytopenia

Aplastic anemia

Anemia, thrombocytopenia, and agranulocytosis

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

Initially, those of bacterial or fungal infections

Malaise

Chills

Fever

Extreme weakness and fatigue

Reduced white blood cell count

Question #1

The suffix –penia refers to a _____________ in number.

increase

stasis

decrease

Answer to Question #1

C. decrease

Rationale: In hematology neutropenia, granulocytopenia and others refer to decreased circulating cells.

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?

Deletions

Polyploidy

Translocations

Regression

Hyperploidy

Answer to Question #2

D. Regression

Rationale: Regression is not a type of chromosomal change.

Hodgkin Disease and Non-Hodgkin Disease

Non-Hodgkin disease

Lymphoma originates at extranodal sites and spreads to anatomically contiguous nodes.

Reed-Sternberg cells are not present.

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.

Symptoms of Hodgkin Disease

Stage A

Lack constitutional symptoms

Stage B (40% of persons with Hodgkin disease)

Significant weight loss, fevers, pruritus, or night sweats

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

Depends on the histologic type, stage of the disease, and clinical status of the person

Types

Radiation

Combination chemotherapy

For NHL only

Adjuvant radiation therapy

Monoclonal antibodies

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)

Chronic lymphocytic leukemia (CLL)

Both involve immature lymphocytes and their progenitors in the bone marrow, the spleen, lymph nodes, CNS, and other tissue.

Acute myelogenous (myeloblastic) leukemia (AML)

Chronic myelogenous leukemia (CML)

Both involve the pluripotent myeloid stem cells in bone marrow and interfere with the maturation of all blood cells.

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