White Blood Cell Disorders

Granulocytes

• - Multilobar nuclei
• - Phagocytic cells
• - Granules are present in the cytoplasm
• - Neutrophils, eosinophils, and basophils
• (in order of total amount of all WBC's)

Granulocytes

• - Basophils (less than 1% of all WBC's)
• -r/t mast cells
• - contain heparin and histamine
• - respond to allergic or hypersensitivity rxn's
• - Eosinophils (1-3% of all WBC's)
• - increase in number during allergic rxn
• - detoxify agents associated with allergic rxn
• - also respond to parasitic infections - attach to parasite and release hydrolytic enzymes
• - Neutrophils (60-65% of all WBC's)
• - most abundant WBC ***
• - polymorphonuclear leukocytes
• - maintain normal host defenses against bacteria, viruses and fungi
• - first on site ***
• - migrate into the tissues during inflammation

Agranulocytes

• - Lack cytoplasmic granules
• - Lymphocytes and monocytes **

Lymphocytes

• - 30% of all WBC's
• - originate in the bone marrow
• - recognize an antigen
• - active in the immune response
• 3 types
• 1. B lymphocytes
• 2. T lymphocytes
• 3. Natural killer cells

B Lymphocytes

• - form antibody producing plasma cells
• - humoral mediated immunity

T Lymphocytes

• - differentiate in the thymus
• - activate other cells of the immune system (T helper cells)
• - cell mediated immunity

Natural Killer Cells

• - destroy foreign bodies
• - innate (natural) immunity

Monocytes/Macrophages

• - 3-8% of all WBC's
• - contain lysosomal enzymes
• -travel from the bone marrow to tissues
• - during inflamm. they act as macrophages and destroy bacteria and tissue debris
• -activate lymphocytes by presenting an antigen to the T cells

Lymphoid Tissue

• - lymphatic vessels, lymphoid tissue, lymph node, spleen, and thymus
• - B lymphocytes differentiate into plasma cells that then produce antibodies
• - T lymphocytes differentiate into CD4 T helper cells and CD8 cytotoxic cells

Normal WBC Count

• * 4,500 - 10,500 cells
• - Leukopenia - reduction in the number of WBC's in the blood (ie. some diseases)
• - Leukocytosis - increase in the # of WBC's in the blood (ie. infection)

Neutropenia

• - Abnormally low level of neutrophils
• Causes:
• - drugs (side effect)
• - autoimmune disease
• - neoplasms

Congenital Neutropenia

• - Cyclic --- begins in infancy and lasts for decades
• - occurs every 21 days and lasts usually about 2-3 days
• - impaired feedback regulation of granulocyte production and release

Acquired Neutropenia

• - Aplastic anemia
• - Chemotherapy and radiation
• - Suppression of the bone marrow stem cells
• - Autoimmune disorders
• - Infections

Clinical Features of Neutropenia

• - Risk of infection
• - Mouth and skin infections
• - Most frequent infection site is the respiratory tract ***
• - Fever
• - Inflamm. response may be absent *

Infectious Mononucleosis (MONO)

• - Self-limiting lymphoproliferative disorder caused by the Epstein-Barr virus (EBV)
• - Mostly seen in adolescents and young adults
• - Kissing disease *
• - EBV infects about 90% of all people
• - Spread through oral secretions
• PATHO:
• - Spreads to the oropharyngeal lymphoid tissues - B lymphocytes
• - B cells house the EBV and produce heterophil-antibody which is used to dx EBV
• - CD8 cytotoxic cells and NK cells control the proliferation of EBV
• - Humoral and cellular immunity limit the # of infected B cells
• - once infected the person remains infected (asymptomatic) and some people shed the disease (few)

Clinical Course - Mono

• - Incubation period 4-8 weeks
• - malaise, anorexia, chills
• - fever, pharyngitis and swollen lymph nodes
• - hepatitis and splenomegaly
• - increased WBC's ----- 60% are lymphocytes
• - heterophil antibodies appear 2nd and 3rd week
• - tx is supportive

Leukemia

• - malignant neoplasms of cells derived from myeloid or lymphoid tissue cells
• - leukemic cells can infiltrate the liver, spleen, lymphoid tissue and other organs of the body
• - most common cause of cancer in children :( !

Lymphocytic Leukemia

• - mutation of the lymphoid cell line
• - overproduction of abnormal immune cells
• -production of other cell types decreases

Myelocytic Leukemia

• - mutation of the myeloid cell line
• - overproduction of abnormal monocytes or granulocytes
• - production of other cell types decreases

Lymphocytic Myelocytic

• Myelocytic leukemia
• - mutation of the myeloid cell line
• - overproduction of abnormal monocytes or granulocytes
• - production of other cell types decreases
• Lymphocytic leukemia
• - mutation of the lymphoid cell line
• - overproduction of abnormal immune cells
• -production of other cell types decreases

Acute Leukemias

• - cancers of the hematopoietic progenitor cells *
• - sudden onset of s/s of depressed bone marrow fxn
• - ALL is more common
• - AML - mainly in adults

Acute Leukemias

• - ALL
• affects the pre-B and pre-T lymphocytes referred to as lymphoblasts *
• - AML
• affects myeloid precursor cells in the bone marrow - most are from acquired genetic mutations

Acute Leukemia - Manifestations

• - abrupt onset of s/s :
• fever low grade fever wt. loss night sweats bone pain* infections generalized lymphadenopathy *
• - more CNS involvement in ALL
• - leukostasis - extremely high circulating blast count which can lead to emboli and occlusion of the blood vessels (painful)
• - hyperuricemia - increased breakdown of purine secondary to leukemic cell death d/t chemotherapy * (dangerous)
• - dangers of hyperuricemia = increased risk for death
• increased risk for :
• - stroke
• - heart disease
• - liver failure
• - kidney failure

Acute Leukemia

• Dx : Blood and bone marrow studies
• Major tx: chemotherapy
• - bone marrow or stem cell transplant

CML

• - disorder of the pluripotent hematopoietic progenitor cell - granulocyte precursors are the dominant leukemic cell type
• - philadelphia chromosome
• - chronic phase
• - short accelerated phase
• - terminal blast crisis
• - * distinct chx : WBC count more than 150,000
• - tx: bone marrow transplant

Malignant Lymphomas

• - malignancies that arise in the peripheral lymphoid tissues
• - solid tumors
• - 2 groups: Hodgkin and Non-Hodgkin Lymphoma*
• - Both types associated with lymph node involvement, fever, fatigue, wt .loss, + growth of abnormal lymphoid cells and tissue

NHL

• - either t or b cell neoplasms
• - impairment of the immune system and infectious agents
• - seen in pts with HIV
• - can originate in the lymphoid tissue but is most commonly seen in the lymph nodes ---- ** originates in the extranodal sites first *
• - can spread to liver, spleen, and bone marrow

Mature B Cell Lymphomas (NHL)

• - Follicular lymphoma 1/3 of all adult NHL's
• - 1/3 develop into fast growing diffuse B-cell lymphoma
• ** Burkitt Lymphoma - most rapidly growing - evidence of previous EBV infection

NHL - Clinical Manifestations

• - indolent or aggressive stage
• - indolent stage - painless swollen lymph nodes
• - aggressive stage - painless swollen lymph nodes, night sweats, fever, wt. loss, and infections

NHL

• DX - lymph node bx
• TX -
• radiation if caught early enough and their is only a single node involved
• combo. of chemotherapy and radiation
• if CNS involvement, will receive cranial radiation !!!!

Hodgkin Lymphoma

• - Reed-Sternberg cell
• - Bimodal disease - seen in early adulthood and also in older adults
• - usually arises in a single node or chain of nodes
• - predictable spread
• - people who have had mono are at risk for Hodgkin lymphoma

HL - Clinical Manifestations

• - initial lymph involvement is above the diaphragm
• - mediastinal masses may cause chest discomfort and cough
• - itching and intermittent fevers

Multiple Myeloma

• - B - cell malignancy of the differentiated plasma cells
• - risks fx's:
• chronic immune stimulation autoimmune disorders & exposure to radiation
• - HIV infection
• - osteolytic bone lesions *
• - M protein *

Multiple Myeloma - Manifestations

• - bones & bone marrow
• - activation of osteoclasts
• - hypercalcemia and high rate of fractures - axial skeleton and long bones
• - renal involvement / insufficiency
• - bone pain common s/s ***

Multiple Myeloma

• DX :
• Classic Triad:
• - more than 10% plasma cells
• - lytic bone lesions
• - M protein spike
• TX :
• -chemotherapy
• -allogenic bone marrow transplant