Upgrade to remove ads
Only $2.99/month

White Blood Cell Disorders

Terms in this set (94)

Production of White Blood Cells
bone marrow begins with pluripotent stem cells called myeloid and lymphoid cells

Granulocyte and monocytes cells are derived from myeloid stem cells and lymphocytes from lymphoid stem cells
Pluripotent Stem Cells
undeveloped, precursor cells in the bone marrow

All blood cells arise from these during the process of hematopoieisis

These precursor cells can become ANY type of blood cell
Blast Cells
immature precursor cells for each cell line

From the stage, each type of WBC begins to differentiate and mature along a committed cell line
B Lymphocytes
cells that mature to an extent in bone marrow and then develop into plasma cells which are antibody-producing cells within lymphoid tissue
T Lymphocytes
cells that continue the maturation process mainly within the thymus gland, where they become:
-T helper cells (CD4)
-Cytotoxic T cells (CD8)

These cells then move into lymphoid tissue for proliferation
Lymphoid Tissue Examples
Tonsils
Thymus
Spleen
Thoracic Duct
Cervical Lymph Nodes
Red Bone Marrow
B Lymphocytes produce _________.
immunoglobulins
Monocytes
type of WBC when further differentiated that perform phagocytosis and engulf antigens

Make up 3-7% of circulating WBCs

When they leave circulation and enter tissue, they mature into macrophages, which are found in large quantities in the spleen and other organs
Macrophages
first responders in defense against an antigen and function w/i the innate immune system
A macrophage can move _________ the capillary to engulf and capture and antigen and the macrophage uses its many lysosomal enzymes to digest the _________.
out
antigen
B and T Lymphocytes
Make up 20-35% of circulating WBCs

2 main types of lymphocytes:
-B Lymphocytes
-T Lymphocytes

Lymphocytes are part of the adaptive immunity

After exposure to an antigen, lymphocytes recognize, target, and have memory for specific antigens

They endow the body with long-term immunity
Granulocytes
WBCs w/ chemical containing granules in their cytoplasm

Granules contain powerful digestive enzymes capable of killing microorganisms and then catabolizing debris during phagocytosis

There are 3 types of granulocytes:
-Eosinophils
-Basophils
-Neutrophils
Neutrophils
first responders to an infection, stressful event, pr inflammatory reaction

Make up 60-70% of the WBCs in circulation

Antigens, epinephrine, and corticosteroids stimulate generation and release of neutrophils in the bloodstream

Polymorphonuclear Leukocytes
Polymorphonuclear Leukocytes
mature neutrophils

Have a segmented, multilobed nucleus, as opposed to immature neutrophils, which have a bandlike nucleus
Segs
mature neutrophils
Bands
immature neutrophils
"Shift to the Left"
if a laboratory test indicates a high number of bands in circulation symbolizing an infection

In severe acute infection or inflammation, the bone marrow cannot keep up with the body's need for mature neutrophils, so it releases BANDS
REALLY immature neutrophils/blasts in circulation can be a sign of cancer like _________>
leukemia
Purulent Exudate
pus

Whitish-green colored discharge from a site of injury that contains dead neutrophils, INFECTIOUS MATERIAL, and cellular debris
Eosinophils
WBCs mainly released during allergy and parasitic infection
Basophils
generates and released by the bone marrow in response to many inflammatory reactions, particularly parasitic infection
Leukocytosis
a rise in WBC count above 11,000 uL
Leukemoid Reaction
leukocytosis in excess of 50,000/microliters caused by conditions other than leukemia
Leukopenia
decrease in WBC count lower than 4,000/microliter

A decrease in ALL types of WBCs

Increases the risk for infection, decrease signs of infection, and diminishes healing ability

Filgrastim is a stimulant of the bone marrow that can increase leukocyte synthesis, specifically neutrophils
Leukopenia: Pharmacologic Treatment-
Hematopoietic Agents (HA)
Granulocyte-Colony Stimulating Factor
-Filgrastrim (Neupogen)
-Sargramostin (Leukine)
-Pegfilgrastim (Neulasta)
Filgrastrim (Neupogen)
leukopoietic growth factor produced by recombinant DNA technology

MOA= promotes proliferation, differentiation and activation of cells that make granulocytes

Indications= malignancies, chemo-induced leukopenia, patients undergoing bone marrow transplantation, harvesting of hematopoietic stem cells, chronic neutropenis

Given IV/SC

Adverse Effects=
-Bone Pain
-Leukocytosis
Sargramostin (Leukine)
growth factor

Accelerates bone marrow recovery after transplant

Increased production of:
-Neutrophils
-Macrophages
-Eosinophils

IV infusion

Adverse Effects=
-Diarrhea
-Weakness
-Rash
-Malaise
-Bone pain
-Leukocytosis
-Thrombocytosis
Pegfilgrastim (Neulasta)
long-acting derivative of filgrastin

Increased production of neutrophils

SC injection

Adverse Effect=
-Bone pain

Pegylated= delayed excretion by the kidneys
-1/2 Life increased to 17 hours
Neutrophilia
neutrophil predominance in the WBC count

Neutrophil count above 7,700/uL in patients with a total WBC of fewer than 11,000/uL
CBC with Differential
WBC count is measured using a lab test called a complete blood count with differential (breaks down WBCs):
-Basophils
-Eosinophils

Test measures total RBCs, hemoglobin (Hgb), hematocrit (Hct), platelets, total WBCs, and the percentage of each type of WBC present
WBC Total Count
5,000-10,000/mm3
Leukocytosis
increased WC
Leukopenia
decreased WBC
Neutropenia
decreased neutrophils
Agranulocytosis
marked decreased granulocytes
WBC Total Count
Indicates the degree of response to a pathologic process

Differential count will provide a more complete evaluation for specific diagnosis
Neutrophil count will be elevated with a huge _________ response or _________ infection.
inflammatory
bacterial
Total WBC Elevated
may cause one to conclude there is an inflammatory response
WBC: Differential-
Why is it reported in %?
an INCREASE in one type will always mean a DECREASE in another type even though number for second type of cell doe snot decrease
WBC w/ Differential
Granulocytes (Phagocytes):
-Neutrophils (50-67%)
-Eosinophils (0-3%)
-Basophils (0-2%)

Lymphocytes (24-40%)

Monocytes/Macrophages (4-9%)

DIFFERENTIAL ALWAYS ADDS UP TO 100%
Conditions Altering WBC's:
Leukocytosis
Leukopenia
Conditions that Alter WBCs resulting in Leukocytosis
Normal protective response to physiologic stressors (surgery, anesthesia)

All types of infection

Tissue necrosis

Inflammatory disorders
Conditions that Alter WBCs resulting in Leukopenia
Bone marrow depression

Drug toxicity

Autoimmune disease (Lupus)

Malignancies, Chemotherapeutic agents
WBC Differential with Bacterial Infection
elevated segmented neutrophils
WBC Differential with Virus
highly elevated lymphocytes
WBC Differential with Allergic reaction with Resultant Asthma Attack
elevated eosinophils
Primary Sign of Infection
Fever
Neutropenia
lack of sufficient number of neutrophils

Most frequent type of leukopenia

Diagnosed in patients with fewer than 1,500 neutrophils/uL

Increases susceptibility to infection and diminished the external signs of inflammation
Neutropenic Precautions
ANY temperature is IMPORTANT

Precautions:
-NO standing water
-NO fresh fruits/veggies
-NO sick guests
-Wash hands
Lymphocytes
Lymphocytosis
Lymphocytopenia
Lymphocytosis
an increase in lymphocytes within the bloodstream, most commonly caused by infection
Lymphocytopenia
a decrease in lymphocytes, which is a result of a decreased production in the bone marrow because of an acquired or inherited immunodeficiency
Infectious Mononucleosis
Self-limiting lymphoproliferative disorder
Caused by Epstein-Barr Virus (EBV)
Most prevalent in adolescence/ young adults
Main mode of transmission= EBV-contaminated saliva
Pathogenesis= atypical lymphocytes proliferative
Onset= insidious (slowly progressing)
Incubation= 4-8 weeks

Clinical Manifestations:
-Lymphadenopathy
-Hepatitis
-Splenomegaly

Labs:
-WBC HIGH (12,000-18,000) 95% lymphocytes

Acute Phase= 2-3 weeks

Some degree of debility/lethargy: 2-3 months

Treatment= symptomatic and supportive
Myelodyslastic Syndrome (MDS)
disorders of the stem cells in the bone marrow

All or part of bone marrow hematopoiesis is disorderly and ineffective and differentiation of all or one category of precursor stem cells into committed cell lines is impaired

Patient suffers deficient numbers of all blood cells or one type of blood cell:
-WBC
-RBC
-Platelets
Hematologic Neoplasms
types of cancers that affect blood, bone marrow, and lymph nodes

Malignancies that are either mainly located in the blood (leukemia) or in lymph nodes (lymphomas)
Hematologic Cancers
Leukemias and lymphomas cause similar pathophysiological conditions in the body

Nonfunctional, cancerous WBCs proliferate and overwhelm the bone marrow and other lymphoid tissue

Cancerous WBCs increase to excess numbers and they crowd and suppress development of the other blood cells in the bone marrow

Kids diagnosed w/ leukemia will be very pale & anemic w/low platelets results in lots of bruising

Excessive proliferation of cancerous blood cells in bone marrow will suppress the growth of healthy blood cells

Symptoms include:
-Anemia (Fatigue, Weakness, Pallor)
-Leukopenia (increased susceptibility to infection)
-Thrombocytopenia (increased susceptibility to bleeding and bruising)
-Bone pain (caused by proliferating cancerous blood cells that put pressure in marrow of bones)
Hematologic Cancer Symptoms
Anemia (Fatigue, Weakness, Pallor)

Leukopenia (increased susceptibility to infection)

Thrombocytopenia (increased susceptibility to bleeding and bruising)

Bone pain (caused by proliferating cancerous blood cells that put pressure in marrow of bones)
Physical Signs of Hematologic Cancers
Physical examination may reveal enlarged lymph nodes, splenomegaly, or both

An enlarged lymph node is the result of proliferative neoplastic cells

Splenomegaly is the result of excessive infiltration of neoplastic blood cells or excessive hemolysis performed by an overactive spleen
Lab Tests for Hematologic Cancers
Complete Blood Count (CBC) with differential is an important initial diagnostic test to identify which specific type of WBC is causing the neoplastic disorder

Bone marrow aspiration/biopsy

Fluorescence in-situ hybridization is used to analyze cells for chromosome defects
Bone Marrow Aspiration
aspiration of bone marrow through a large bore catheter into iliac crest
Stem Cell Transplants-
Allogeneic Hematologic Stem Cell Transplants
healthy bone marrow cells are harvested from a donor who has a MATCHING TYPE to the recipient

Treatment for hematologic cancers

When successful, the donor's healthy bone marrow cells replace the recipient's cancerous bone marrow

Bone marrow rejection occurs frequently
Stem Cell Transplants-
Autologous Hematologic Stem Cell Transplant
kind of transplant involves extraction of healthy hematopoietic stem cells from the patient and storage of the harvested cells in the freezer

Patient is then treated with high-dose chemotherapy with or without radiation to destroy the patient's malignant cells

After complete or partial bone marrow ablation, the patient's own stored healthy stem cells are returned to his or her body, where they replace the destroyed tissue and resume the patient's normal blood cell production

LESS RISK OF REJECTION
Umbilical Cord Stem Cells
being used as stem cell transplants for hematologic cancers with varying rates of success
Cord blood has a _________ concentration of hematologic stem cells than is normally found in adult blood.
higher
Two basic Categories of Cells within the Bone Marrow
Myeloid
Lymphoid
Myeloid Cells
myelocytic leukemias affect these cells
Lymphoid Cells
lymphocytic leukemias affect these cells
Acute Lymphocytic Leukemia (ALL)
Aggressive cancer that is most common in children

Philadelphia chromosome (PhC) is associated with chemotherapy-resistant disease

Stem cell precursors for T or B lymphocytes in the bone marrow do not function and DO NOT MATURE BEYOND THE LYMPHOBLAST stage

As the lymphoblasts become more numerous, there is less room for healthy WBCs, RBCs, and platelets, leading to anemia, susceptibility yo infection, and suppressed clotting

Lymph nodes also contain large numbers of lymphoblast cells, which crowd out healthy lymphocytes
Diagnosis of ALL
bone marrow biopsy demonstrates hypercellularity with predominately lymphoblasts

A bone marrow lymphoblast count of over 20% of total WBC is sufficient for a diagnosis of ALL
TRUE or FALSE

Seeing blasts in a bone marrow biopsy is very concerning.
True
Treatment of ALL
Bone marrow transplantation from a tissue-matched sibling

Chemotherapy
Chemotherapy Treatment Side Effects
Attacks ALL rapidly dividing cells:
-GI
-Mucosa
-Skin
-Hair
-All blood cells

Anorexia
Nausea
Vomiting
Hair loss
Infections (immunosuppression)
Fever
Bleeding and bruising
Chronic Lymphocytic Leukemia (CLL)
B cell lymphocyte malignancy is found in elderly individuals, with a median age at diagnosis of 70 years

Most common type of leukemia in the US and other Western countries

RARE in China
Chronic Lymphocytic Leukemia (CLL)
genetic changes are the fundamental cause

Any agent that can disrupt DNA upon exposure is considered an etiologic agent

Over 80% of patients with CLL have some type of chromosomal abnormality, with Trisomy 12 being the most common

Over 95% of CLL cases involve B cells that have failed to differentiate from precursor B cells into mature B cells in the bone marrow

In the peripheral blood, these cells resemble mature B cells, but they synthesize and release low levels of immunoglobulin (Ig), mutated Igs, or no Ig at all

They are referred to as B-CLL lymphocytes

There is constant proliferation of B-CLL precursor cells in the bone marrow

The accumulation of B-CLL cells results in crowding of the bone marrow and consequent decreased development of RBCs, WBCs, and platelets

Proliferation of B-CLL cells also occurs in the lymph nodes and spleen, causing lymphadenopathy and splenomegaly
B-CLL Lymphocytes
contain excess proto-oncogene bcl 2

proto-oncogene bcl 2 is a suppressor of apoptosis (programmed cell death), resulting in long life for the B-CLL cells which allows for more time for mutation
Diagnosis of CLL
hallmark is lymphocytosis with a WBC count of greater than 20,000/uL

Bone marrow is infiltrated with characteristic small lymphocytes
Treatment of CLL
Tyrosine kinases cause unregulated growth of the cell, which leads to development of cancer

Tyrosine kinase inhibitors, such as imatinib are often effective treatment
Acute Myelogenous Leukemia (AML)
caused by the proliferation of undifferentiated (blast) myeloid cells in the bone marrow

Genetic mutations in the abnormal myeloid cells cause a change in the normal apoptosis
AML Symptoms
Anemia from lack of RBCs
Bleeding disorders from lack of platelets
Infections from neutropenia
Chronic Myelogenous Leukemia (CML)
disorder characterized by an overproduction of mature myeloid cells in the bone marrow

95% have Philadelphia chromosome

Translocation between chromosomes 9 & 22
CML 3 Phases
1- Chronic Phase where neutrophils begin to lose their differentiation

2- Accelerated phase where neutrophils are more undifferentiated and unable to function

3- Blast crisis phase, where myeloid blast cells do not differentiate at all
Symptoms of CML Blast Crisis
Signs:
-Decreased number of normal WBCs, RBCs, and platelets

Usual symptoms of Leukemia:
-Frequent infection
-Anemia
-Thrombocytopenia
-Fever
-Fatigue
-Weakness
-Bleeding
-Bone pain
CML Treatment
both treatable and curable

Because tyrosine kinase activity is needed for the action of PhC, drugs that inhibit this enzyme are used to treat CML

Tyrosine kinase inhibitors, such as imatinib (Gleevec), can induce a complete remission in over 90% of all patients treated
Lymphoma
most common type of blood cancer in the US

Falls into 1 of 2 categories:
-Hodgkin's
-Non-Hodgkin's

Chromosomal translocations are the genetic hallmark

Common translocation in NHL is the translocation of genes at 14q32 and 18q21 present in 85% of follicular lymphomas

Somepathogens that have been associated with the development of NHL include:
-HIV
-EBV
-Helicobacter pylori
-HTLV-1
-Hepatitis C
-Human Herpesvirus-8
Hodgkin's Lymphoma
develops from a specific abnormal B lymphocyte line
Non-Hodgkin's Lymphoma
derives from either abnormal B or T cells
Lymphoma Diagnosis
Patient or clinician often notices an enlarged, painless lymph node, which initiates further investigation

A lymph node biopsy is the mainstay of diagnosis
Reed-Sternberg (RS) Cells in HL
Class HL is diagmosed by the presence of RS cells int eh lymphoid tissue

The RS cells is a large malignant B cell with 2 nuclei that give the cell the appearance of owl's eyes
Multiple Myeloma
hematologic neoplasm that arises in B lymphocytes causeing proliferation of abnormal plasma cells in the bone marrow and consequent synthesis of abnormal Igs or Ig fragments

Arise in 3 Different Forms:
-1. Monoclonal gammopathy of undetermined significance (MGUS) (benign)
-2. Smoldering multiple myeloma
-3. Active, highly destructive MM

A generalized disorder that leads to bone destruction, bone marrow failure, renal failure, neurological complications, and amyloidosis

When one particular type of plasma cell proliferates abnormally, it causes an excess of its synthesized abnormal immunoglobulin and Ig fragments

The abnormal Igs and fragments are referred to as monoclonal proteins or M-proteins
Acute Multiple Myeloma
Increase in osteoclast activity (bone macrophages) that causes bone reabsorption at an accelerated rate

Osteoclastic activity is greater than osteoblastic activity, causing bone destruction and preventing bone formation

Vertebral bones collapse

Bone destruction causes serum hypercalcemia

Radiculopathy is a frequent neurological occurrence from compression of a nerve by a paravertebral plasmacytoma (neoplastic plasma cell tumor) in the lumbosacral area
Multiple Myeloma
bone pain, especially in the back, is a common complaint at diagnosis

Is a result of lytic destruction an the formation of plasmacytomas

Lytic lesions are rounded, punched-out areas of bone found most commonly in vertebra, the skull, ribs, humerus, and femur
Diagnosis of Multiple Myeloma
diagnosed having 10% or more plasma cells int eh bone marrow, the presence of M-proteins in the blood and urine, an organ or tissue damage as a result of the proliferation of the plasma cells

Plasmacytomas may be found of tissue biopsy
Plasmacytomas
tumors of plasma origin
Treatment of Multiple Myeloma
Chemotherapy followed by autologous stem cell transplantation
THIS SET IS OFTEN IN FOLDERS WITH...