Etiology and Pathophysiology for Disorders of WBC’s
Decreased White Blood Cells (Leukopenia)
I.
Drug-Induced Causes:
A. Antitumor antibiotics
B. Alkylating agents –nitrogen mustards
C. Antimetabolites – methotrexate
D. Anti-inflammatory drugs – phenylbutazone
E. Psychotropics and antidepressants – clozapine, imipramine
F. Antimicrobial agents – sidovudine (AZT, Retrovir), trimethoprim-sulfamethoxazole (Bactrim)
II. Hematologic Disorders:
A. Aplastic anemia
B. Fanconi anemia
C. Leukemia
D. Myelodysplastic syndrome
III. Autoimmune Disorders
A. Systemic lupus erythematosus (SLE)
B. Felty’s syndrome
C. Rheumatoid arthritis (RA)
IV. Infections:
A. Viral – hepatitis, influenza, HIV, measles
B. Fulminant bacterial infection – typhoid fever, military tuberculosis
C. Parasitic
D. Rickettsial
V. Other:
A. Severe sepsis
B. Bone marrow infiltration:
1. Leukemia – proliferation of myeloblasts, immature lymphocytes, mature
neoplastic granulocytes, or mature-appearing lymphocytes in the bone
marrow, resulting in decreased production of all blood cells.
2. Lymphomas – malignant neoplasms originating in the bone marrow and
lymphatic structures resulting in the proliferation of lymphocytes but can
result in leucopenia due to treatment, ultimate dysfunction of the bone
marrow and hypersplenism. Classified as Hodkins or Non Hodgkins. (See
Below)
3. Multiple Myeloma – neoplastic plasma cells infiltrate the bone marrow and
destroy bone, thus decreasing white blood cells. (See below)
C. Hypersplenism: increased sequestration and filtration of all blood cells
1. Hereditary hemolytic anemias
- Sickle cell anemia
- Thalassemia
2. Autoimmune Cytopenias
- Acquired hemolytic anemias
- Immune thrombocytopenia
3. Infections and Inflammations
- Bacterial – endocarditis
- Mycobaterial – tuberculosis
- Spirochetes – syphilis, Lymes disease
- Viral infections – hepatitis, HIV, Mononucleosis, cytomegalovirus
- Parasitic infections – malaria, toxoplasmosis
- Rickettsial infections – Rocky mountain spotted fever, typhoid
- Fungal infections – histoplasmosis
- Auto immune – SLE, RA
4. Infiltrative Disease:
- Leukemia
- Lymphomas
- Polycythemia vera
- Multiple myeloma
- Other neoplasms
5. Congestions:
- Cirrhosis
- Heart failure
- Portal or splenic vein thrombosis
D. Nutritional deficiencies – cobalamin, folic acid
E. Transfusion reactions
F. Hemodialysis
Major Disorders Affecting White Blood Cells:
1. Leukemia: types
a. Acute Myelogenous
- Uncontrolled proliferation of myeloblasts
- Hyperplasia of the bone marrow
- Normal hematopoietic cells replaced by leukemic myeloblasts
- Infiltration of other organs and tissues
- 85% of acute leukemias in adults
b. Acute Lymphocytic
- Immature lymphocytes proliferate in bone marrow
- Crowding out of normal bone marrow cells
- Most common in children; 15 of acute leukemia in adults
c. Chronic Myelogenous Leukemia
- Proliferation of mature neoplastic granulocytes in bone marrow
- Excess granulocytes move into the peripheral blood and infiltrate the
liver and the spleen
- Distinctive chromosome called Philadelphia chromosome
- Progresses from chronic to blastic phase
d. Chronic Lymphocytic Leukemia
- Proliferation and accumulation of inactive, small mature-appearing
lymphocytes, usually the B cell.
- Infiltrate the bone, liver and spleen
- Lymph nodes enlarge cause enlargement resulting in paralysis and
pain
- Most common leukemia of adults
e. Hairy Cell Leukemia
- Proliferation of primarily B lymphocytes in the bone marrow
- Cells have a “hairy” appearance
- Spleen sequesters a large number of normal cells resulting in
splenomegaly
- May infiltrate the liver
2. Lymphomas: Neoplasms originate in the bone marrow and lymphbatic system
resulting in the proliferation of lymphocytes. Two types:
a. Hodgkin’s Lymphoma
- Giant, multi-nucleated cells called Reed-Sternberg cells located in the
lymph nodes.
- Twice as prevalent in men than women
- Can be caused by interacting factors: Epstein-Barr infection, genetic
predisposition and exposure to environmental toxins
- Destroys normal structure of lymph nodes
- Arises from single location and remains confined to nodes for a long
time
- Can infiltrate to lungs, liver and spleen
b. Non Hodgkin’s Lymphoma
- A heterogeneous group of neoplasms that usually involve B or T cells
that proliferate in the lymph nodes
- All forms involve lymphocytes arrested in various stages of
development
- Can spread quickly to the liver, bone marrow, CNS, lungs
3. Multiple Myeloma
a. Neoplastic plasma cells infiltrate the bone marrow and destroy the bone
b. If untreated, client will live about 2 years
c. Twice as common in men than women
d. Develops after 40 years of age
e. Could be caused by genetic factors, exposure to organic chemicals such as
benzene, herbicides and insecticides as well as viral infection.
f. The malignant plasma cells infiltrate the bone and produce excessive amounts of
abnormal immunoglobin called myeloma protein or M protein.
g. Excessive cytokines are also produced that help destroy bone
h. Normal plasma cells are reduced causing decreased immune response
i. Bence Jones proteins are produced by the myeloma celss
j. This process causes destruction and dysfunction of the bone marrow, bone itself,
kidneys, spleen, lymph nodes, liver and heart muscle.