Alterations of Leukocyte, Lymphoid, and Hemostatic Function Leukocytes

Leukocytosis Leukocyte count higher than normal; normal protective response to physiological stressors. Causes: o Invading microorganisms o Strenuous exercise o Emotional changes o Temperature changes o Anesthesia o Surgery o Pregnancy o Some drugs, hormones and toxins May also be caused by pathologic conditions (malignancies and hematologic disorders) Leukopenia Leukocyte count decreased (<1000/mm increased risk for infection, < 500/mm, very serious life-threatening infections occur) Causes: o Radiation o Anaphylactic shock o Systemic lupus erythematosus o Certain chemotherapeutic agents Granulocytosis Increased numbers of circulating granulocytes Often described as neutrophilia (neutrophils the most numerous of granulocytes) Occurs in early stages of infection or inflammation Confirmed when absolute neutrophil count exceeds 7500/uL When count more than 100,000/uL (usually seen only in myelocytic leukemia), blood viscosity increases, thrombus or occlusion may occur Shift-to-the-left: microscopic detection of disproportionate numbers of immature leukocytes in peripheral blood smears. Occurs when demand for circulating neutrophils exceeds the supply, marrow begins to release immature neutrophils and other leukocytes into the blood). Shift-to-the-right: infection or inflammation diminishes and granulopoiesis replenishes circulating granulocytes. Neutropenia Reduction in circulating neutrophils, <2000/uL (2.0) o Mild:1.0-1.5u/L o Moderate: 0.5-1.0/uL o Severe: <0.5/uL Causes: severe or prolonged infections when granulocyte production does not keep up with demand; decreased neutrophil production or ineffective

granulopoiesis; reduced neutrophil survival caused by increased turnover or use, and abnormal neutrophil distribution and sequestration. Classified as primary (congenital or acquired) or secondary Eosinophilia Absolute increase (>450/uL) in total numbers of circulating Eosinophils. Causes: allergic disorders (type 1) associated with asthma, hay fever, and drug reactions; hypersensitivity reactions, dermatologic disorders (ex. Atopic dermatitis, eczema, pemphigus). Eosinophilic scleroderma-like diseases, and eosinophilic-myalgia syndrome (EMS), which is associated with ingestion of tryptophan, and a relationship between EMS and fibromyalgia syndrome. Eosinopenia Decrease in circulating numbers of Eosinophils Causes: migration of Eosinophils into inflammatory sites, Cushing syndrome, stress caused by surgery, shock, trauma, burns, or mental distress. Basophilia Increase in circulating basophils Causes: response to inflammation and hypersensitivity reactions of the immediate type, Myeloproliferative disorders (CML and myeloid metaplasia) Basopenia (also known as basophilic leukopenia) Decrease in circulating basophils Causes: hyperthyroidism, acute infection, and long-term therapy with steroids. Decrease may also be seen during ovulation and pregnancy. Monocytosis Increase in circulating monocytes Causes: most commonly occurs with neutropenia associated with bacterial infections, particularly in the late stages or recovery stage, may also indicate marrow recovery from agranulocytosis, chronic infections such as TB and SBE, and may be found with MI and correlates with myocardial damage. Monocytopenia Decrease in the number of circulating monocytes (rare) Causes: hairy cell leukemia and prednisone therapy

Lymphocytes
Lymphocytosis Increase in lymphocytes Causes: acute bacterial infections (rare) and acute viral infections (most commonly) particularly with EBV Lymphocytopenia Decrease in lymphocytes Causes: abnormalities of lymphocyte production associated with neoplasias, immune deficiencies, destruction by drugs, viruses or radiation. Diseases associated with: AIDS, caused by human immunodeficiency virus being cytopathic for T-helper lymphocytes.

Infectious Mononucleosis
Acute, self-limiting neoplastic lymphoproliferative clinical syndrome. Acute infection of B lymphocytes (B cells) Most common agent: Epstein-Barr virus (EBV) Affects young adults between ages 15-35, peak incidence 15-19 Primary route of transmission saliva, virus also present in mucosal secretions of genital, rectal, and respiratory tract as well as blood. Begins with widespread invasion of B lymphocytes, all of which possess EBV receptor sites. Sites of invasion initially oropharynx, nasopharynx and salivary epithelial cells with simultaneous spread to the lymphoid tissue and B cells. Monospot test is limited in evaluation because other infections and toxoplasmosis also produce heterophilic antibodies. The percentage of individuals with IM who have heterophilic antibodies in their blood increases relative to the time of onset of symptoms. Some individuals do not produce heterophilic antibodies and children under age 4 years do not produce heterophilic antibodies.

Leukemias
Acute Lymphocytic Leukemia (ALL) Progressive neoplasm defined by the presence of >30% lymphoblasts in bone marrow or blood. Most common leukemia in children (80%) and most often occurs in first decade. Accumulation and proliferation disorder Immunotyping of leukemic blast cells allows for identification of subtypes: precursor B cell types, mature-B cell ALL, and T-lineage ALL. Philadelphia chromosome: most common genetic abnormality in adult ALL; the reciprocal translocation between chromosome 9 and 22 t. Develops at different rates in different locations, unique characteristic of ALL. Individuals in developed countries and in higher socioeconomic categories have an increased incidence of ALL. Prevention is almost impossible because there are no known causes. Acute Myelogenous Leukemia (AML) Abnormal proliferation of myeloid precursor cells, decreased rate of apoptosis, and an arrest in cellular differentiation. Bone marrow and peripheral blood characterized by Leukocytosis and a predominance of blast cells. Replacement of normal myelocytic cells, megakaryocytes and erythrocytes leads to complication s of bleeding, anemia and infection. Increases with age, peaking in the 6th decade. Risk factors: exposure to radiation, benzene, and chemotherapy.

Hereditary: Down syndrome, Fanconi aplastic anemia, Bloom syndrome, ataxiatelangiectasis, trisomy 13, Wiskott-Aldrich syndrome, and congenital X-linked agammaglobulinemia. Chronic Lymphocytic Leukemia Advance slowly and insidiously without warning Malignant transformation and progressive accumulation of monoclonal B lymphocytes that express CD5 and DC 23 molecules Major pathophysiologic deficit is failure of B cells to mature into plasma cells that synthesize immunoglobulins. Familial tendency with first-degree relatives having a 3 times greater risk of developing the disease. Rare in individuals less than 45 years of age, 95% of individuals are over age 50. Suppression of humoral immunity caused by reduction in normally functioning B cells is the most significant effect Anemia, thrombocytopenia and neutropenia present with over t CLL Symptoms: spleenomegaly, extreme fatigue, weight loss, night sweats, and low grade fever. Chronic Myelogenous Leukemia (CML) Myeloproliferative disorder Diagnostic marker: Philadelphia chromosome. Acute effects resemble those of acute leukemia but with more prominent and painful spleenomegaly. Hyperuricemia usually present and produces gouty arthritis. Infections, fever, and weight loss are common. Standard treatment: chemotherapy and allogenic stem cell transplant.

Myeloma
Multiple Myeloma (MM) Neoplastic proliferation of immunocytes (plasma cells) Most common of primary malignancies 15% pf detected myelomas More common in persons older that 40, males affected twice as much as females, blacks with higher incidence than whites Chromosome 13 abnormality is the most common alteration found in 86% of those affected. Molecular pathogenesis: chromosomal translocations, proto-oncongene mutations, and rarely inactivation of tumor-suppressor genes. Bence-Jones protein: unattached light chain protein passed through the kidney and excreted in urine. Most common initial symptom is pain, felt in single bone or the entire skeleton. Usual sites of pain are lower back, upper spine, pelvis, ribs, and sternum. Bone destruction contributes to development of hypercalcemia.

Alterations in Lymphoid Function

Lymphadenopathy Enlarged lymph nodes that become palpable and tender. Localized: usually indicates drainage of an inflammatory lesion located near enlarged node. Generalized: generally seen in presence of malignant or nonmalignant disease Reflects significant diseases more often in adults than in children. Caused by the increase in number of germinal center within the node caused by proliferation of lymphocytes or monocytes May also be caused by invasion of node by malignant cells or cells not normally present within node. Location and size important factors in diagnosing the cause, as well as age, gender, and geographic location.

Malignant Lymphomas
Hodgkin Lymphoma (HL) Presence of Reed-Sternberg (RS) cells surrounded by a background of benignappearing host inflammatory cells (necessary for diagnosis but not specific to HL Initial sign often enlarged painless mass found most commonly in the neck Also asymptomatic mediastinal mass on routine chest x-ray is not unusual. Cervical, axillary, inguinal and retroperitoneal lymph nodes are most commonly affected. Staging system used: The Cotswold Staging Classification System, four stages based on location and distribution of lymph node involvement, other organs involved, and location of any large masses. Staging based on medical exam and radiographic results. Lab findings include: elevated sedimentation rate, Leukocytosis, and Eosinophilia Treatment: high-dose chemotherapy with bone marrow or stem cell transplant. Non-Hodgkin Lymphoma Malignant transformation of lymphoid tissues, primarily lymph nodes. Five recognized chromosomal translocations exist that potentially set in motion the transformation or loss of critical oncogenes and tumor-suppressor genes. Multiple viruses are associated with development of NHL. Viruses associated with NHL: EBV, HYLV-1, HCV, and Kaposi sarcoma-associated herpes virus (KSHV) Progressive clonal expansion of B cells, T cells and/or natural killer (NK) cells. Classified as: low (indolent or slow-growing), intermediate or high grade. Symptoms: night sweats with elevated temperature, weight loss, cytopenia, hepatomegaly, spleenomegaly and weakness. Biopsy primary means for diagnosis. CT scans of neck, chest, pelvis, bone marrow aspirate necessary to identify treatment and prognosis. Burkitt Lymphoma

Most common type of NHL in children 2% of all lymphomas Occurs in children from east-central Africa and New Guinea Fast growing tumor and involves primarily the faw and facial bones EBV found in nasopharyngeal secretions American type usually involves the abdomen and is characterized by extensive marrow replacement.