alterations of leukocyte, lymphoid, and tic function

8/3/2019 Alterations of Leukocyte, Lymphoid, And tic Function

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Alterations of Leukocyte, Lymphoid, and Hemostatic Function

LeukocytesLeukocytosis

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 (


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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 drugreactions; hypersensitivity reactions, dermatologic disorders (ex. Atopic

dermatitis, eczema, pemphigus). Eosinophilic scleroderma-like diseases, and

eosinophilic-myalgia syndrome (EMS), which is associated with ingestion oftryptophan, 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 immediatetype, 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 bacterialinfections, 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

LymphocytesLymphocytosis

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.


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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 ofgenital, 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 onsetof 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 increasedincidence 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 leadsto complication s of bleeding, anemia and infection.

Increases with age, peaking in the 6th decade.

Risk factors: exposure to radiation, benzene, and chemotherapy.


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Hereditary: Down syndrome, Fanconi aplastic anemia, Bloom syndrome, ataxia-

telangiectasis, trisomy 13, Wiskott-Aldrich syndrome, and congenital X-linkedagammaglobulinemia.

Chronic Lymphocytic Leukemia

Advance slowly and insidiously without warning

Malignant transformation and progressive accumulation of monoclonal Blymphocytes 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 goutyarthritis. 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% ofthose 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 inurine.

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. Bonedestruction contributes to development of hypercalcemia.

Alterations in Lymphoid Function


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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 byproliferation 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 benign-appearing 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 associatedwith 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


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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 extensivemarrow replacement.

alterations of leukocyte, lymphoid, and tic function

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