WBC Disorders
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White Blood Cells
o Granulocytes (i.e., neutrophils, eosinophils, and basophils)
o Monocyte and macrophage lineage
 Both are derived from the myeloid stem cell in the bone marrow and circulate in
the blood
o Lymphocytes
 T lymphocytes (T cells) and B lymphocytes (B cells) originate in the bone marrow
and migrate between the blood and the lymph
Hematopoiesis
o 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
 From the Book: T h e l i f e s pa n o f wh i t e b l o o d c e l l s i s re l a t i v e l y s h o rt s o t h at
c o n s t a n t r e n e wa l i s n ec es s a r y t o m a i nt a i n n o rm a l b l o od l e v e l s . A n y c o n di t i o n s
t h a t d e c r e a s e t h e a v a i l a b i l i t y o f s t em c e l l s o r h em at o po i e t i c g r o wt h f ac t o rs
p r o d u c e a d e c r e a s e i n wh i t e b l o o d c e l l s .
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Growth and Reproduction of WBC’s
o The growth and reproduction of different stem cells is controlled by multiple
hematopoietic growth factors or inducers
o The life span of WBCs is relatively short; constant renewal is necessary to maintain
normal blood levels
o Conditions that decrease availability of stem cells or hematopoietic growth factors
produce a decrease in WBCs
Components of the Lymphatic System
o Lymphatic Vessels
o Lymph Nodes
o Spleen
o Thymus
Function of the Lymphatic System
o Drain lymph fluid from specific areas of the body
o Filter particular matter such as bacteria and cancer cells
Neutropenia
o Definition: N e u t r o p e n i a r ef e r s s p ec i f i c a l l y t o a d ec r e as e i n n e ut r o p h i l s
o Causes
 Accelerated removal of WBC’s
 Drug-induced granulocytopenia
 Pg 183
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Periodic or cyclic neutropenia
Neoplasms involving bone marrow
 Cause if you slow down your bone marrow, you slow down production
of WBC’s, including neutrophils.
Felty’s Syndrome
 Increased destruction of neutrophils in the spleen
Idiopathic
 No known cause
S/S
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Initially, those of bacterial or fungal infections
 Malaise, Chills, Fever, Extreme weakness and fatigue
 Reduced white blood cell count
Infectious Mononucleosis
o Definition
 Self-limited lymphoproliferative disorder
o Causes and Characteristics
 Caused by the B-lymphocytotropic EBV (Epstein-Barr virus), a member of the
Herpes Virus family; transmitted in saliva
 Characterized by fever, generalized lymphadenopathy, sore throat (often
severe) , and the appearance in the blood of atypical lymphocytes and several
antibodies
 Highest incidence in adolescents and young adults (cause they are making out
all the time!)
 Treatment is symptomatic and supportive
Neoplastic Disorder of Hematopoietic and Lymphoid Origin
o Include somewhat overlapping categories (and they represent the most important of
the White cell disorders). They r e p r es e n t s ol i d t um o r s d e r i v e d f r om n e o p l as t i c l ym p h o i d
tissue cells
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Lymphomas
 Hodgkin’s disease
 non-Hodgkin’s lymphoma
 The leukemias
 The plasma cell dyscrasias -multiple myeloma
Clinical Features of these guys
 Largely determined by:
 Site of origin
 Progenitor cell from which they originated
 Molecular events involved in their transformation into a malignant
neoplasm
Hodgkin’s Disease info
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H o d g k i n l ym p h o m a i s a t y pe o f c a nc e r c h a r ac t e r i z e d by R e e d - S t e r n b e r g c el l s
t h a t b e g i n s a s a m a l i g n a nc y i n a s i n g l e l ym p h n o d e a nd t h e n s p r e a ds t o
c o n t i g u o u s l ym p h n o d es
Symptoms of Hodgkin’s Disease
 Stage A
 Lack constitutional symptoms
 Painless lymph node enlargement, usually just one node or a small
group of nodes is getting bigger
 Stage B
 They have the constitutional symptoms
 Significant weight loss, fevers, pruritus and or night sweats
 Advanced Stages
 Fatigue and anemia
 Liver, lungs, digestive tract, and CSN may be involved
Diagnosis of Hodgkin’s Disease
 Reed-Sternberg cell present in a biopsy specimen of lymph node tissue
 They have to make sure that cell is present before they know it’s for
sure Hodgkin’s
 Computed tomography (CT) scans of the chest and abdomen
 To assess for involvement of different lymph nodes
 A bipedal lymphangiogram
 May detect small structural changes in the nodes the CT scan missed
 A positron emission tomography (PET) imaging
 A bilateral bone marrow biopsy
Non-Hodgkin’s Lymphoma Info
 N o n - H o d g k i n l ym p h om as r ep r e s e n t a g r o u p o f h e t e r o ge n e o u s l ym p h oc y t i c
c a n c e r s t h a t a r e m ul t i c e nt r i c i n o r i gi n a n d s p r e a d t o v ar i o u s t i s s u es t h r o u g h o u t
t h e b o d y , i n c l u d i n g t h e b o ne m a r r o w.
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Catergories of Non-Hodgkin’s 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’s, and nonBurkitt’s lymphomas
Staging of NHL (Non-Hodgkin’s Lymphoma) Disease
 Bone marrow biopsy
 Blood studies
 Chest and abdominal CT scans
 Nuclear medicine studies
 Cytologic examination of the cerebrospinal fluid
Manifestations of NHL
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Painless, superficial, lymphadenopathy
Noncontiguous nodal spread
Increased susceptibility to infections
 Hypogammaglobulinemia
 Poor, humoral response
Leukemias
o Definition
 Malignant neoplasms arising from the transformation of a single blood cell line
derived from hematopoietic stem cells
o Classification according to cell lineage
 Lymphocytic (lymphocytes)
 Myelocytic (granulocytes, monocytes)
o 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
o 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 pluri-potent myeloid stem cells in bone marrow and
interfere with the maturation of all blood cells
o Acute Leukemias
 Cancer of hematopoietic stem cells
 ALL – children 2 to 4 yrs, 85%
 AML – adults 60 to 65 peak,
 ALL - Immature precursor B and T cells
 AML – heterogeneous group of disorders, toxins, congenital (Down syndrome
associated leukemia)
o Warning S/S of Acute Leukemia
 Fatigue
 Pallor
 Weight loss
 Repeated infections
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 Easy bruising
 Nosebleeds
 Other types of hemorrhage
Criteria for Remission of ALL and AML
o Less than 5% blasts in the bone marrow
o Normal peripheral blood counts
o Absence of cytogenetic abnormalities
o Return to pre-illness performance status
Factors affecting the Likelihood of Achieving Remission
o Age (most significant prognostic variable)
o Type of leukemia
o Stage of the disease at time of presentation
Chronic Leukemias
o Definition
 Malignancies involving the proliferation of well-differentiated myeloid and
lymphoid cells
o Types of chronic leukemia
 Chronic lymphocytic leukemia (CLL)
 Insidious onset
 CLL – slow, asymptomatic at dx, lymphocytosis
o Progresses to fatigue, reduced exercise tolerance, enlargement
of superficial nodes, splenomegaly
o Fatigue may become severe, recurrent or persistent infections,
pallor, edema, thrombophlebitis, pain
 Chronic myelogenous leukemia (CML)
 Triphasic course – chronic, short accelerated, terminal blast crisis
 Initially, leukocytosis, c immature granulocytes, splenomegaly
 Followed by anemia, thrombocytopenia
o Fatigue, weakness, exertional dyspnea
 Constitutional sx – low grade fever, night sweats, bone pain, wt. loss
 Termial phase – blast cells, increased splenomegaly, and increased sx,
leukostasis
 Goals of Treatment for CML
o A hematological response characterized by normalized blood
counts
o A cytogenetic response demonstrated by the reduction or
elimination of the Ph chromosome from the bone marrow
o A molecular response confirmed by the elimination of the BCRABL fusion protein
 Multiple Myeloma
 Definition
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A plasma cell dyscrasia (problem, abnormality) 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
o The bones and bone marrow
 Pathogenisis
o Etiology – Genetic Chromosome 14, IgG loci
o Proliferation of malignant plasma cells
o Osteolytic bone lesions throughout
o Characterized by M protein (Ig_ or Ig _)
 And/Or BenceJones proteins in urine
o Cytokines
 Manifestations
o Bones and Marrow
 Osteoclastic activity  bone resorption, destruction
 Hyperviscosity of fluids  ameloid proteins  heart
failure and neuropathy
o Plasmacytomas in GI track and bone
 Cause of bone pain
o Bone destruction decreased RBC, WBC production 
anemias and infections
Increased Platelet Function/Hypercoagulability States (things that make your platelets go crazy
and work really, really well)
o Atherosclerosis
o Diabetes
o Smoking
o Elevated lipid and cholesterol
o Increased platelets
o Accelerated Activity of Clotting System
 Pregnancy, oral contraceptives, surgery, immobility, malignancy
Disseminated Intravascular Coagulation (DIC)
o Widespread coagulation and bleeding
o Complicaiton of many conditions
o Massive activation of coag sequence
 Reduced levels of anticoagulants
 Microthrombi, vessel occlusion, tissue ischemia
o Patho of DIC
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