BIO 1150 - Chapter 12
Leukopenia
A decrease in WBC count below 4,000/uL is leukopenia, which is a general term that describes a decrease in all types of WBCs. Leukopenia increases the risk of infection, decreases signs of infection, and diminishes healing ability. Filgrastim (NeupogenR) is a stimulant of the bone marrow that can increase leukocyte synthesis, specifically neutrophils.
Chronic Myelogenous Leukemia (CML)
A disorder characterized by an overproduction of mature myeloid cells in the bone marrow 95% have Philadelphia chromosome; translocation between chromosome 9 and 22
Multiple Myeloma
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.
leukemoid reaction
A leukemoid reaction is leukocytosis in excess of 50,000/µL caused by conditions other than leukemia.
Treatment of ALL
Bone marrow transplantation from a tissue-matched sibling and chemotherapy are commonly used treatments.
Multiple Myeloma
Bone pain, especially in the back, is a common complaint at diagnosis. It is a result of lytic destruction and the formation of plasmacytomas. Lytic lesions are rounded, punched-out areas of bone found most commonly in vertebra, the skull, ribs, humerus, and femur.
bands
immature neutrophils are called bands
Chemotherapy Treatment Side Effects
Chemotherapy attacks ALL rapidly dividing cells: GI, mucosa, skin, hair, and all blood cells. Anorexia Nausea Vomiting Hair loss Infections (immunosuppression) Fever Bleeding and bruising
Treatment of Multiple Myeloma
Chemotherapy followed by autologous stem cell transplantation
Laboratory Tests for Hematologic Cancer
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 (also known as bone marrow biopsy) Fluorescence in-situ hybridization (FISH) is used to analyze cells for chromosome defects (such as the Philadelphia chromosome translocation between chromosome 9 and 22.
Eosinophils
Eosinophils are WBCs, mainly released during allergy and parasitic infection
Multiple Myeloma
It can arise in three different forms: 1-monoclonal gammopathy of undetermined significance (MGUS)(benign) 2-smoldering multiple myeloma 3-active, highly destructive MM
Complication of Treatment Tumor Lysis Syndrome
It results from rapid cell destruction of a large number of tumor cells all at once. The lysed cells release their intracellular contents into the surrounding tissues and circulation, causing hyperuricemia (from purine breakdown), hyperkalemia, and hyperphosphatemia with secondary hypocalcemia. The uric acid crystals can cause damage to the glomeruli and nephron tubules, causing renal failure.
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. The cancerous WBCs increase to excess numbers and they crowd and suppress development of the other blood cells in the bone marrow.
B and T Lymphocytes
Lymphocytes make up 20% to 35% of circulating WBCs. There are two main types of lymphocytes: B lymphocytes (B cells) and T lymphocytes (T cells). 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.
Lymphocytopenia
Lymphocytopenia, a decrease in lymphocytes, is a result of a decreased production in the bone marrow because of an acquired or inherited immunodeficiency.
Lymphocytosis
Lymphocytosis is an increase in lymphocytes within the bloodstream, most commonly caused by infection.
Lymphoma
Lymphoma is the most common type of blood cancer in the United States. Lymphoma falls into one of two major categories: Hodgkin's lymphoma (HL, previously called Hodgkin's disease) Non-Hodgkin's lymphoma (NHL) Non-Hodgkin's lymphomas account for 83% of lymphoma cases, with HL accounting for the other 17%.
Myelodysplastic Syndrome (MDS)
MDS is a term used for 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. The patient suffers deficient numbers of all blood cells or one type of blood cell: WBCs, RBCs, or platelets.
Macrophages
Macrophages function within the innate immune system and are the first responders in defense against an antigen
polymorphonuclear leukocytes
Mature neutrophils
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.
Diagnosis of CLL
The hallmark of CLL is lymphocytosis with a WBC count of greater than 20,000/uL. The bone marrow is infiltrated with characteristic small lymphocytes.
Hematologic Neoplasms
The hematologic neoplasms are types of cancer that affect blood, bone marrow, and lymph nodes. These cancers are malignancies that are either mainly located in the blood (leukemia) or in lymph nodes (lymphomas).
Lymphoma Diagnosis
The patient or clinician often notices an enlarged, painless lymph node, which initiates further investigation. A lymph node biopsy is the mainstay of diagnosis.
Stem Cell Transplants Autologous hematologic stem cell transplant
This kind of transplant involves extraction of healthy hematopoietic stem cells from the patient and storage of the harvested cells in a freezer. The 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 destroyed tissue and resume the patient's normal blood cell production.
myeloid and lymphoid stem cells
To produce white blood cells (WBCs), the bone marrow begins with pluripotent stem cells called myeloid and lymphoid stem cells
Stem Cell Transplants Allogeneic hematologic stem cell transplants
Treatment for hematologic cancers Healthy bone marrow cells are harvested from a donor who has a matching tissue type to the recipient. These are called allogeneic hematologic stem cell transplants. When successful, the donor's healthy bone marrow cells replace the recipient's cancerous bone marrow. However, bone marrow transplant rejection occurs frequently.
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.
Umbilical Cord Stem Cells
Umbilical cord stem cells are also being used as stem cell transplants for hematologic cancers with varying rates of success. Cord blood has a higher concentration of hematologic stem cells than is normally found in adult blood.
CBC With Differential
WBC count is measured using a laboratory test called a complete blood count with differential (CBC with differential). The test measures total RBCs, hemoglobin (Hgb), hematocrit (Hct), platelets, total WBCs, and the percentage of each type of WBC present.
segs
Because of the shape of their nucleus, mature neutrophils are referred to as segs
Diagnosis of ALL
A bone marrow biopsy demonstrates hypercellularity with predominantly lymphoblasts. A bone marrow lymphoblast count of over 20% of total WBC is sufficient for a diagnosis of ALL.
CML Three 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
leukocytosis
A rise in WBC count above 11,000/uL is called leukocytosis.
Acute Myelogenous Leukemia (AML)
AML is 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. Symptoms: anemia from lack of RBCs, bleeding disorders from lack of platelets, and infections from neutropenia.
Acute Lymphocytic Leukemia (ALL)
Aggressive cancer that is most common in children Philadelphia chromosome (PhC) is associated with chemotherapy-resistant disease.
Pluripotent Stem Cells
All blood cells arise from a small number of undeveloped, precursor cells called pluripotent stem cells in the bone marrow during the process of hematopoieisis. These precursor cells have the potential to become any type of blood cell.
Hematologic Cancers 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)
B Lymphocytes
B lymphocytes mature to an extent in bone marrow and then develop into plasma cells, which are antibody-producing cells, within lymphoid tissue.
Basophils
Basophils are generated and released by the bone marrow in response to many inflammatory reactions, particularly parasitic infection.
Lymphoma
Chromosomal translocations are the genetic hallmark of lymphomas. A common translocation in NHL is the translocation of genes at 14q32 and 18q21 present in 85% of follicular lymphomas. Some pathogens that have been associated with the development of NHL include HIV, EBV, Helicobacter pylori, HTLV-I, hepatitis C, and human herpesvirus-8.
Reed-Sternberg (RS) Cells in HL
Classic HL is diagnosed by the presence of RS cells in the lymphoid tissue. The RS cell is a large malignant B cell with two nuclei that give the cell the appearance of owl's eyes.
Chronic Lymphocytic Leukemia (CLL)
Genetic changes are the fundamental cause of CLL. 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.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. B-CLL lymphocytes contain excess proto-oncogene bcl 2. This proto-oncogene bcl 2 is a suppressor of apoptosis (programmed cell death), resulting in long life for the B-CLL cells. 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. B-CLL lymphocytes contain excess proto-oncogene bcl 2. This proto-oncogene bcl 2 is a suppressor of apoptosis (programmed cell death), resulting in long life for the B-CLL cells. 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. The proliferation of B-CLL cells also occurs in the lymph nodes and spleen, causing lymphadenopathy and splenomegaly.
Granulocytes
Granulocytes are WBCs with chemical-containing granules in their cytoplasm. Their granules contain powerful digestive enzymes capable of killing microorganisms and then catabolizing debris during phagocytosis. There are three types of granulocytes: eosinophils, basophils, and neutrophils.
Lymphoma HL vs. NHL
HL develops from a specific abnormal B lymphocyte line. NHL derives from either abnormal B or T cells.
Blast Cells
Immature precursor cells for each cell line are called blast cells. From the blast cell stage, each type of WBC begins to differentiate and mature along a committed cell line.
Acute Lymphocytic Leukemia (ALL)
In ALL, the 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 to infection, and suppressed clotting. Lymph nodes also contain large numbers of lymphoblast cells, which crowd out healthy lymphocytes.
"Shift to the Left"
In severe acute infection or inflammation, the bone marrow cannot keep up with the body's need for mature neutrophils, so it releases bands. If a laboratory test indicates a high number of bands in circulation, this is referred to as a "shift to the left."
Active Multiple Myeloma
Increase in osteoclast activity (bone macrophages) that causes bone resorption 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.
Monocytes
Monocytes make up 3% to 7% of circulating WBCs. When they leave the circulation and enter tissue, they mature into macrophages, which are found in large quantities in the spleen and other organs. Their primary function is phagocytosis.
Chronic Lymphocytic Leukemia (CLL)
Most common type of leukemia in the United States and other Western countries; however, it is rare in China and . B cell lymphocyte malignancy is found in elderly individuals, with a median age at diagnosis of 70 years.
Multiple Myeloma
Multiple myeloma (MM) is a hematologic neoplasm that arises in B lymphocytes, causing proliferation of abnormal plasma cells in the bone marrow and consequent synthesis of abnormal Igs or Ig fragments.
Diagnosis of Multiple Myeloma
Multiple myeloma is diagnosed as having 10% or more plasma cells in the bone marrow, the presence of M-proteins in blood and urine, and organ or tissue damage as a result of the proliferation of the plasma cells. Plasmacytomas, or tumors of plasma origin, may be found on tissue biopsy.
Two Basic Categories of Cells Within the Bone Marrow:
Myeloid cells: Myelocytic leukemias affect these cells. Lymphoid cells: Lymphocytic leukemias affect these cells.
Neutropenia
Neutropenia, which is the lack of sufficient number of neutrophils, is the most frequent kind of leukopenia. It is diagnosed in patients with fewer than 1,500 neutrophils/uL. Neutropenia increases susceptibility to infection and diminishes the external signs of inflammation
Neutrophilia
Neutrophilia is the term used for neutrophil predominance in the WBC count; it is defined as a neutrophil count above 7,700/uL in patients with a total WBC count of fewer than 11,000/uL.
Neutrophils
Neutrophils make up 60% to 70% of the WBCs in circulation. They are first responders to an infection, stressful event, or inflammatory reaction. Antigens, epinephrine, and corticosteroids stimulate generation and release of neutrophils in the bloodstream.
Purulent exudate
Purulent exudate, commonly called pus, is a whitish-green-colored discharge from a site of injury that contains dead neutrophils, infectious material, and cellular debris.
Chronic Myelogenous Leukemia (CML)
Symptoms of a blast crisis include all the usual symptoms of leukemia: Decreased number of normal WBCs, RBCs, and platelets Symptoms = frequent infection, anemia and thrombocytopenia, fever, fatigue, weakness, bleeding, and bone pain CML is 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 (GleevecR), can induce a complete remission in over 90% of all patients treated.
T lymphocytes
T lymphocytes continue the maturation process mainly within the thymus gland, where they become T helper (CD4) and cytotoxic T cells (CD8) and then move into lymphoid tissue for proliferation
lymphocytes from...
lymphoid stem cells
Granulocyte and monocyte cells are derived from...
myeloid stem cells
Mature neutrophils have a
segmented, multilobed nucleus, as opposed to immature neutrophils, which have a bandlike nucleus
