McCane 30. Leukocyte Disorders and Neoplasms

Alterations of Leukocyte and Lymphoid Function

• Disorders involving leukocytes range from leukopenia to leukocytosis.
• Many hematologic disorders are malignancies or act like them which affects leukocyte production.

Alterations of Leukocyte Function

• Leukocyte function is affected by too many or too few white cells, or defective cells.
• Quantitative disorders such as infections and leukemias, are a result of decreased production or accelerated destruction.
• Qualitative leukocyte disorders consist of disruptions of leukocyte function.
• Phagocytic cells may lose their phagocytic capacity.
• Lymphocytes may lose their capacity to respond to antigens.
• Other leukocyte alterations include infectious mononucleosis and cancers of the blood-leukemia and multiple myeloma.

Quantitative Alterations of Leukocytes

• Leukocytosis is a leukocyte count higher than normal.
• Leukopenia is a count lower than normal
• Can affect all or specific cell types for a variety of physiologic conditions and alterations.
• Leukocytosis occurs as a normal protective response to physiologic stressors, such as infection, strenuous exercise, emotional changes, temperature changes, anesthesia, surgery, pregnancy, and some drugs, hormones, and toxins.
• Also caused by pathologic conditions, such as malignancies and hematologic disorders.
• Leukopenia is never normal and is defined as an absolute blood cell count less than 4000 cells/µL.
• Leukopenia is associated with a decrease in the number of neutrophils, which increases the risk for infection.
• Absolute neutrophil count (ANC) is calculated by multiplying the white blood cell count by the percent of band and segmented neutrophils.
• ANC is classified as mild (1000 to 1500 cells/µL), moderate (500 to 1000 cells/µL), or severe (<500 cells/µL).
• Possibility for life-threatening infections is high when the ANC is less than 500/µL.
• Leukopenia can be caused by radiation, anaphylactic shock, autoimmune disease, immune deficiencies, and exposure to certain drugs such as glucocorticoids and chemotherapeutic agents.

Granulocytes and Monocytes

• Increased numbers of circulating granulocytes and monocytes are primarily a response to infection.
• Increased numbers also occur as a result of myeloproliferative disorders that increase stem cell proliferation in bone marrow.
• Decreased numbers occur when infectious processes draw them out of the circulation and into infected tissues faster than they can be replaced.
• Decreases also can be caused by disorders that suppress marrow function.
• Granulocytosis an increase in the number of granulocytes.
• Neutrophilia is another term that may be used to describe granulocytosis because neutrophils are the most numerous of the granulocytes.
• Neutrophilia occurs in the early stages of infection or inflammation and is established when the absolute neutrophil count exceeds 7500/μL.
• Stored neutrophils are approximately 20 to 40 times greater in number than circulating neutrophils.
• Release and depletion of stored neutrophils from the venous sinuses stimulate granulopoiesis to replenish neutrophil reserves.
• When the demand for circulating mature neutrophils exceeds the supply, the marrow begins to release immature neutrophils into the blood.
• Premature release of the immature white cells is responsible for the phenomenon known as a shift-to-the-left or leukemoid reaction.
• This refers to the microscopic detection of disproportionate numbers of immature leukocytes in peripheral blood smears.
• Neutropenia is a condition associated with a reduction in the number of circulating neutrophils.
• Clinically, neutropenia exists when the neutrophil count is less than 2000/µL.
• The absolute neutrophil count reflects not only the degree of neutropenia but also the risk for infection.
• A reduction in the number of neutrophils can occur in severe, prolonged infections when production of granulocytes cannot keep up with demand.
• Severe neutropenia, granulocytopenia (less than 500/μL) or agranulocytosis (complete absence of granulocytes in blood), is usually secondary to arrested hematopoiesis in the bone marrow or massive cell destruction in the circulation.
• Chemotherapeutic agents used to treat hematologic and other malignancies cause generalized bone marrow suppression.
• Several other drugs and large doses of ionizing radiation cause agranulocytosis, which occurs rarely but carries a high death rate (10% to 50%).
• Clinical manifestations of agranulocytosis include recurrent and persistent life-threatening infection leading to septicemia, general malaise, fever, tachycardia, and ulcers in the mouth.
• If untreated, sepsis caused by agranulocytosis results in death within 3 to 6 days.
• Other causes of neutropenia, in the absence of infection, may be decreased or reduced neutrophil production, and abnormal neutrophil distribution and sequestration.
• Congenital defects in neutrophil production include cyclic neutropenia and neutropenia with congenital immunodeficiency diseases, as well as multiple syndromes.
• Primary acquired neutropenia is associated with multiple conditions, for example, hypoplastic anemia or aplastic anemia, leukemia, lymphomas and myelodysplastic syndrome.
• Reduced neutrophil survival and abnormal distribution and sequestration are usually secondary to other disorders.
• Neutropenia occurs in a variety of immunologic disorders, particularly systemic lupus erythematosus, rheumatoid arthritis, Felty and Sjögren syndromes, splenomegaly, and drug-related causes.
• Eosinophilia is an absolute increase (more than 450/μL) in the total numbers of circulating eosinophils.
• Allergic disorders associated with asthma, hay fever, and drug reactions, as well as parasitic infections are often cited as causes.
• Hypersensitivity reactions and the normal defense against parasites trigger the release of eosinophil chemotactic factor of anaphylaxis (ECF-A) from mast cells, attracting eosinophils to the area.
• Tissues with abundant mast cells, such as the respiratory and gastro- intestinal tracts, are particularly common sites for eosinophil invasion.
• Eosinophilia may also be associated with dermatologic disorders, such as atopic dermatitis, eczema, and pemphigus. Decreased numbers of eosinophils, eosinopenia, generally is caused by migration of eosinophils into inflammatory sites.
• It also may be seen in Cushing syndrome and as a result of stress caused by surgery, shock, trauma, burns, or mental distress.
• Basophilia-an increase in circulating numbers of basophils, in the blood, is rare and is usually secondary to arrested infection.
• Generally is a response to inflammation and immediate hypersensitivity reactions.
• Basophils contain histamine that is released during an allergic reaction.
• Levels increase also in myeloproliferative disorders, such as chronic myeloid leukemia and myeloid metaplasia.
• Basopenia also known as basophilic leukopenia, a decrease, in circulating numbers of basophils is seen in hyperthyroidism, acute infection, and long-term therapy with steroids.
• Decrease in the number of basophils may be seen during ovulation and pregnancy.
• Monocytosis is an increase in numbers of circulating monocytes.
• Monocytopenia is rare, and not much is known about this condition because of the small numbers of monocytes generally present in the blood.

Lymphocytes

• Quantitative alteration of lymphocytes occurs when lymphocytes are activated by antigenic stimuli, usually microorganisms.
• Lymphocytosis is an increase in the number or proportion of lymphocytes in the blood.
• Rare in acute bacterial infections and occurs most commonly in acute viral infections particularly those caused by the Epstein-Barr virus (EBV), a causative agent in infectious mononucleosis.
• Lymphocytopenia is a decrease in the number of circulating lymphocytes in the blood.
• It may be attributable to abnormalities of lymphocyte production and destruction by drugs, viruses, or radiation.
• Major problem in acquired immunodeficiency syndrome (AIDS) in which the human immunodeficiency virus (HIV) is cytopathic for T helper lymphocytes.

Infectious Mononucleosis

• Infectious mononucleosis (IM) is a benign, acute, self-limiting, lymphoproliferative clinical syndrome characterized by acute viral infection of B lymphocytes (B cells).
• Associated with several human tumors.
• Most common etiologic agent is EBV, a ubiquitous, lymphotrophic, gamma-group herpesvirus. EBV approximately accounts for 85% of all IM causes.
• Early infections cause EBV thus they are usually asymptomatic and provide immunity.
• IM may arise when the infection occurs during adolescence or later.
• Symptomatic IM usually affects young adults between ages 15 and 35. The peak incidence is between 15 and 24 years.
• Transmission of EBV is usually by saliva through personal contact.
• The disease begins with widespread infection of B lymphocytes, all of which possess receptors for EBV.
• The virus initially infects the oropharynx, nasopharynx, and salivary epithelial cells with later spread to the lymphoid tissue and B cells.
• In the immunocompetent individual, unaffected B cells produce antibodies (IgG, IgM, IgA) against the virus.
• Concomitantly, there is a massive activation and proliferation of cytotoxic T cells (CD8) directed against EBV-infected cells.
• The pharyngitis most often causes the individual to seek treatment.
• IM is usually self-limiting and fatigue may last for 1 to 2 months after resolution of the infection.

Evaluation and Treatment

• Evaluation and management of IM. As the condition progresses generalized lymph node enlargement may develop, specifically spleen, lymph nodes, and liver.
• Splenomegaly is clinically evident 50% of the time and is demonstrated radiologically 100% of the time. Splenic rupture is rare (only 0.1% to 0.5% of all cases) and can occur spontaneously as a result of mild trauma.
• Other organ systems are rarely involved but such involvement may result in additional symptoms.
• In children, Reye syndrome also has been associated with infectious mononucleosis, or EBV infection. The blood of affected individuals contains an increased number of atypical lymphocytes.
• Medical intervention rarely required treatment is supportive and includes rest and alleviation of symptoms with analgesics.
• Ampicillin is contraindicated for infections in general and is also contraindicated when treating Mononucleosis because it causes a rash.
• Bed rest and avoidance of strenuous activity should be included in the therapy.
• The spleen is removed due to cases of Splenic Rupture, but this carries a risk of Overwhelming Postsplenectomy Infection(OPSI).
• It better to repair the spleen.
• Fatal IM also is expressed with the inherited X-linked lympho- proliferative (XLP) syndrome (Duncan disease) and leads to death.

Lymphoid Neoplasm, Leukemia

• Leukemia is a clonal malignant disorder of leukocytes in the bone marrow and usually, but not always, of the blood.
• A common feature of all forms of leukemia is an uncontrolled proliferation of malignant leukocytes, causing an overcrowding of bone marrow and the reduction of the production and function of normal hematopoietic cells.
• Thus leukemia has been termed an accumulation disorder, as well as a proliferation disorder.
• With increased understanding, the distinct divisions between leukemia and lymphoma have become indistinct or blurred.
• Many entities known as "lymphoma" that arise as a discrete tissue mass sometimes have "leukemic" presentations, and evolution to leukemia is not unusual during the progression of incurable lymphomas.
• The current World Health Organization (WHO) classification scheme uses morphologic, immunophenotypic, genotypic, and clinical features to group the lymphoid neoplasms into five broad categories. 1, Precursor B-cell neoplasms 2, Peripheral B-cell neoplasms 3, Precursor T-cell neoplasms 4, Peripheral T-cell and NK-cell neoplasms 5, Hodgkin the Lymphoma
• Most lymphoid neoplasms relate to stages of differentiation of the B-cell of T-Cell differentiation.
• Acute leukemia is characterized by undifferentiated or immature cells, usually a blast cell, and the onset of disease is abrupt and rapid with a short survival time.
• The predominant cell is more differentiated in the chronic leukemia, but does not function normally, with a relatively slow progression.
• There are four general types of leukemia: acute lymphocytic (ALL), acute myelogenous (AML), chronic lymphocytic (CLL), and chronic myelogenous (CML).
• Philadelphia chromosome was observed in persons with chronic myelogenous leukemia (CML) to stop to cause leukemic cells.

Acute Leukemias

• Acute leukemias consist of two types: acute lymphocytic leukemia (ALL) and acute myelogenous leukemia (AML).

• ALL is an aggressive leukemia too many blasts in the blood found and bone marrow and is lymphoblastic.

• AML is an aggressive growing cells white blood but non lymphoblastic cells in blasts.

• ALL commonly affects and causes related deaths.

• Although the exact cause of leukemia is unknown hereditary abnormalities increases of leukemia family members can reappear due to increased risk from cigarette smoke.

• In radiation there is an increasing level of high doses and concern due to subsequent risk to HIV infections and is accepted to be caused by lymphocyte virus-1.

• The chemotherapy AML the high frequency cancer

• All leukemias have a certain pathophysiology.

• All cell lymphomas of T CELL but do not cause ALL with genetic problems from B cell and T CELL.

• The Philadelphia Chromosome is the novel gene translocations in chromosomes for the fusion of BCT1 from chromosome 22 and that form ABLI from chromosome 9.

Chronic Leukemia

• Chronic lymphocytic leukemia (CLL) is a slow-growing type. In adults, there are too many lymphocytes found in the tissue. These cases of B Celli tumors are a type of lineage which was previously related.
• Acute leukemia is chronic ,are well differentiated and identified but most come with children or patients.
• The etiology ,CLL ,was unknown and familial suggested in family genetics.
• A close gene family members get CLL. First degree with family is of 3 fold the chance of having leukemia and 45 to 40 the age and then only are less of a chance.
• Exposure in CML is ionizing radiation.
• A cML was to depend after having a stem cell and was hetero depending of the stage and was a granulocyte monocyte .

Lymphadenopathy

• Lymphadenopathy is characterized by enlarged lymph nodes.
• Lymph node enlargement is caused by an increase in size and number of its germinal centers caused by proliferation of lymphocytes and monocytes or invasion by malignant cells.
• Normally, lymph nodes are not palpable otherwise Enlarged lymph nodes, often also has tenders on the skin and can be painful if touched.
• Localized lymph node swelling is indicated by Drainage, caused during the inflammatory or infectious process. Localized node also usually indicated if draining as well.

Malignant Lymphomas

• Cancers that develops in the lymphoid systems . Hodgkin lymphoma and non Hodgkins are the basic cells which originated . Some include B-cell/T-cell which are now used as names and were in 2 groups before.

• Lymphoma exhibits a significant geographic variation: that is, it is more prevalent in high economic places where lymphoma is seen more. In those cases more food comes in and other cases that caused the increase.

• Hodgkin are B Celli tumors. With classic systems and RS BCELL that may occur for years. So that more can help heal with the accurate diagnostics .It causes the release cell cytokines and produces Local sites and tumors that form .

• The RS transform for lymphoma . And the process that changes which cause remains as a mystery . The genes are defect ,and if one survives ,then they come together to create high function.

• Treatment includes the classification, medical history, and check examination . Progestic will be tested for and checked . That may include different lymph .

Non Hodgskins

• Are neoplasms arising from the tissues,with cells that can not create different genetic coding and cell . Risk factors that involve. The family with this has different changes. Factors including development and to treat from stem cell .

• Is described as expanding T , and is well described as B and is different from other cases. With that cases are the treatment.

Explore alterations in leukocyte numbers and types, including conditions like neutrophilia and infectious mononucleosis. Differentiate between precursor and peripheral lymphoid neoplasms, focusing on leukemia's pathological features. Understand factors influencing leukemia risk and genetic aberrations in AML.