Hematologic Function: Leukocyte and Lymphoid Alterations

Alterations of Leukocyte and Lymphoid Function

Overview

• This section covers alterations in leukocyte and lymphoid function.

Alterations in Leukocyte Function

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

Quantitative Alterations Defined

• -cytosis: Above normal.
• -penia: Below normal.
• White blood cell count normal range: 5,000 - 10,000/mm3.
• Leukocytosis and leukopenia may involve all or a specific type of white blood cell.
• Leukocytosis: Above normal white blood cell count; a normal protective response to physiologic stress (infection, strenuous exercise, temperature changes, emotional changes, surgery, pregnancy, some drugs).
• Leukopenia: Below normal white blood cell count; may be due to radiation, anaphylactic shock, autoimmune disorders, immune deficiencies, and some drugs like glucocorticoids and chemotherapy; increases infection risk.

Granulocytes

• Types: 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:
    • 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).

Granulocytes Continued

• 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.

Agranulocytes Continued

• Lymphocytosis:
  • Acute viral infections (Epstein-Barr).
  • Rare in bacterial infections.
• Lymphocytopenia:
  • Altered lymphocyte production.
  • Neoplasms.
  • Immune deficiencies.
  • Lymphocyte destruction (drugs, radiation, viruses like HIV, autoimmune, heart failure and other acute illnesses related to increased cortisol).

Infectious Mononucleosis

• B-lymphocyte infection, acute, self-limiting.
• Transmission: Saliva (personal contact).
• Incubation: 30-50 days.
• 85% of cases caused by Epstein-Barr virus (EBV); 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 the blood.
• Excessive accumulation of malignant leukocytes.
• Overcrowding of bone marrow leads to 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 factors (ionizing radiation, previous chemotherapy), genetic mutations, and other diseases (HIV, Hepatitis C).

Leukemias: Acute vs. Chronic

• 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); these pass through the glomerulus and damage renal tubular cells.

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: Enlarged painless lymph node in the neck.
  • Large, multinucleated or bilobular nucleus.
  • Adenopathy, mediastinal mass, splenomegaly, and abdominal mass.
  • Prognosis is good if treated, but with systemic symptoms such as fever (with or without infection), itchy skin, and fatigue, the prognosis is more likely poor.

Hodgkin Lymphoma Continued

• Systemic symptoms: Fever (with or without infection), itchy skin, fatigue; indicate a poor prognosis.
• Occurrence: Both children and adults, but most common in early adulthood (20s-30s) and later adulthood (60s-70s).
• Non-Hodgkin Lymphomas:
  • Types: B-cells, T-cells, NK-cells.
  • Can be slow-growing or 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.

Non-Hodgkin Lymphoma Continued

• 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.

Splenic Function Continued

• 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 bloodstream.