Alterations of Leukocyte and Lymphoid Function Notes

Alterations of Leukocyte and Lymphoid Function

Alterations in Leukocyte Function

• Quantitative Alterations
  • Decreased production in bone marrow
  • Accelerated destruction of circulating WBC
  • Response to infections
• Qualitative Alterations
  • Disruption in function
  • Decreased phagocytosis: granulocytes, monocytes, macrophages
  • Lymphocytes may lose ability to respond to antigens
  • Examples: Infectious mononucleosis, blood cancers like leukemia and multiple myeloma

Quantitative Alterations

• -cytosis: Above normal
• -penia: Below normal
• White blood cell count
  • Normal range: 5,000 - 10,000/mm3 (per cubic millimeter)
• Leukocytosis: Above normal white blood cell count
  • Normal protective response to physiologic stress like infection, strenuous exercise, temperature changes, emotional changes, surgery, pregnancy, and some drugs.
• Leukopenia: Below normal white blood cell count
  • Below normal response that may be due to radiation, anaphylactic shock, autoimmune disorders, immune deficiencies, and some drugs like glucocorticoids and chemotherapy.
  • Increased infection risk

Granulocytes

• Basophils, eosinophils, neutrophils
• Neutrophilia (granulocytosis)
  • Early stages of infection or inflammation
• Neutropenia (agranulocytosis)
  • Severe prolonged infections
  • In the absence of infection:
    • Decreased neutrophil production
    • Decreased neutrophil survival
    • Abnormal neutrophil distribution/sequestration
  • Sources may include:
    • Congenital immunodeficiencies
    • Hematologic disorders
    • Anorexia/starvation
    • Secondary deficiencies of malignancy, chemotherapy, immunosuppressive drugs
• Eosinophilia
  • Allergic disorders
  • Parasitic infections
  • Increased Tryptophan ingestion
  • Fibromyalgia Syndrome
• Eosinopenia
  • Migration of eosinophils to inflammatory site
  • Hypercortisol secretion (Cushing syndrome)
• Basophilia
  • Inflammation
  • Immediate hypersensitivity reactions
  • Myeloproliferative disorders
• Basopenia (basophilic leukopenia)
  • Hyperthyroidism
  • Acute infections
  • Hypercortisol (exogenous)
  • Ovulation/pregnancy

Agranulocytes

• Monocytosis
  • Bacterial infections
  • Chronic infections
  • Myocardial damage (Acute myocardial infarction)
• Monocytopenia
  • Rare
• Lymphocytosis
  • Acute viral infections – Epstein-Barr
  • Rare in bacterial infections
• Lymphocytopenia
  • Altered lymphocyte production
  • Neoplasms
  • Immune deficiencies
  • Lymphocyte destruction
  • Drugs, radiation
  • Viruses, HIV
  • Autoimmune
  • Heart failure and other acute illnesses related to increased cortisol

Infectious Mononucleosis

• B-lymphocytes infection
• Acute, self-limiting
• Transmission
  • Saliva (personal contact)
• Incubation: 30-50 days
• 85% of cases - Epstein-Barr virus
  • B cells have an EBV receptor site
• Other viral causes:
  • Cytomegalovirus (CMV), hepatitis, influenza, HIV
• Signs and symptoms:
  • Fever
  • Sore throat
  • Cervical lymphadenopathy
  • Increased Lymphocyte count
  • Atypical lymphocytes
• Serious complications are infrequent (<5%)
  • Splenic rupture is the most common cause of death

Leukemia

• Malignant disorder of the bone marrow and usually but not always the blood
• Excessive accumulation of malignant leukocytes
• Overcrowding of bone marrow
• Decreased production of normal hematopoietic cells
• Chromosome abnormalities are a common precipitating factor in the majority of leukemias
• Gene mutations stimulate cell growth pathways that block normal cell apoptosis.
• Risk factors include:
  • Environmental - ionizing radiation, previous chemotherapy
  • Genetic mutations - recognized to run in families
  • Other diseases - HIV, Hepatitis C

Leukemias

• Acute leukemia
  • Presence of undifferentiated or immature cells, usually blast cells
• Chronic leukemia
  • Predominant cell is more differentiated but does not function normally
• Frequency varies at different ages and is more common in adults than children.
• Incidence is higher in males.
• Remission and survival have increased.

Myelomas

• Proliferation of hematopoietic cells (bone marrow)
• Solitary or multifocal tumors (multiple myeloma)
• Malignant plasma cells produce abnormally large amounts of immunoglobulin (Bence-Jones proteins)
  • Pass through the glomerulus and damage renal tubular cells

Multiple Myeloma

• Multiple myeloma causes increased osteoclastic bone destruction
• Clinical manifestations
  • Cortical (outer) and medullary (inner) bone loss
  • Skeletal pain
  • Recurring infections - decreased humoral immune response

Lymphadenopathy

• Enlarged lymph nodes that become palpable and tender
• Local lymphadenopathy
  • Drainage of an inflammatory lesion located near the enlarged node
• General lymphadenopathy
  • Malignant or nonmalignant disease

Malignant Lymphomas

• Proliferation of malignant lymphocytes
• Hodgkin lymphoma
  • Hodgkin and Reed-Sternberg cells in the lymph nodes from B-cell lymphocytes
  • Classic finding is an enlarged painless lymph node in the neck
  • Large, multinucleated or bilobular nucleus
  • Adenopathy, mediastinal mass, splenomegaly, and abdominal mass
  • If treated, prognosis is good, but with symptoms such as fever (with or without infection), itchy skin, and fatigue, the prognosis is more likely poor.
  • Systemic symptoms include fever (with or without infection), itchy skin, and fatigue
  • Occurrence:
    • Early adulthood 20s - 30s
    • Later adulthood 60s - 70s
• Non-Hodgkin lymphomas
  • Types:
    • B-cells
    • T-cells
    • NK-cells
  • Slow-growing
  • Fast-growing – aggressive
  • Occurrence
    • Males affected more than females
    • Rare in children
    • Median age at diagnosis is 67
    • May be associated with AIDS-related cancers
  • Clinical Manifestations – similar to Hodgkin lymphoma
    • Enlarged painless nodes
    • Mediastinal involvement - cardiac
    • Extranodal involvement
      • Retroperitoneum, spine, GU tract, abdomen, and thyroid
    • Hepatomegaly, splenomegaly
    • Leg edema

Alteration in Splenic Function

• Spleen functions overlap with many other organs and systems.
• Health can be maintained without the spleen.
  • Although this can lead to a higher risk for infection.
• Enlarged spleen can be normal or related to an underlying abnormal condition.
• Enlargement can lead to spleen overactivity.
• Hypersplenism leads to widespread abnormality of all types of blood cells.
• Red and white blood cells and platelets can be sequestered in the spleen leading to their decreased availability in the blood stream.