WHITE BLOOD CELLS DISORDERS

There are five types of white blood cells in the peripheral blood,

•          granulated ( neutrophils, eosinophils, and basophils) , non granulated, monocytes and lymphocytes.

•          Formation of Blood Cells
All blood cells are derived from , pleuripotent blood stem cells, the stem cells has two properites, the first is self renewal (production of more stem cells), and the second is its proliferation and differentiation into progenitor cells, committed to one specific cell line.

•          Haematopoietic growth factors
Haematopoietic growth factors are glycoproteins which regulate the differentiation and proliferation of haematopoietic progenitor cells and the function of mature blood cells.

•          These factors including interleukin-3, IL-6,IL-11and stem cell factor, erythropiotein, thrombopiotein, and TNF.

•          Neutrophils
Neutrophils are small cells with a nucleus with 2-5 lobes has short life span 6-8 hours.

   Function of neutrophils:

•          The prime function of neutrophils is to ingest and kill bacteria, fungi and damaged cells.

•          Neutrophils are released into the circulation in response to stimuli e.g infections and corticosteriods therapy.

•          Neutrophil leucocytosis (neutrophillia)
A rise in the number of circulating neutrophils to >10x10⁹ occur in bacterial infections or as a result of tissue damage, pregnancy, during excersise and corticosteriod therapy.

•          Leukomoid reaction
Over production of white blood cells with many immature cells, may occur in severe infections, tuberculosis, malignant infiltration of bone marrow, hemorrhage and haemolysis.

Leucoerythroblastic anemia

•          Characterized by presence of nucleated red blood cells and white cell precursors in the peripheral blood.

•          Causes:

Bone marrow infiltration with metastatic carcinoma, myelofibrosis,myeloma,lymphoma, hemolytic, megaloblastic anemia.

•          Causes of neutrophil leucocytosis
Bacterial infection

•           Tissue necrosis in myocardial infarction

•          Inflammation

•          Corticosteriod therapy

•          Hematological , myelofibrosis, Leukomoid reaction, Leukoerythroblastic reaction

•          Pregnancy, excersise

•          Malignant (breast,bronchial-gastric)

•          Metabolic ,renal failure

•           Congenital, neutrophil adhesion deficiency.

•          Neutropenia and agranulocytosis
Neutropenia is defined as a circulating neutrophil count below 1.5x10⁹/l. Absence of neutrophil is called agranulocytosis.

Causes of Neutropenia:

A- Congenital : is rare in which there is a defect in maturation and release of neutrphils from the bone marrow  (Kostman’s syndrome, cyclic neutropenia every 2-3 weeks).

Acquired causes

•          Viral infections, severe bacterial infections (typhoid)., Felty’s syndrome, immune neutropenia and pancytopenia.

•          Leukemia, myelosuppressive drugs, antiviral drugs, hypersplenism.

•          Clinical features:
Infections may be frequent when neutrophil count is below 0.5 (severe neutropenia) and may be associated with septicemia and may be associated with pneumonia and septicemia.

•          Patients presented by glazed mucositis in the mouth and ulceration.

•          Disseminated infection are usually occurred with septicemia, fungemia and deep abscesses, local infections ,mouth, perianal, skin damage and vascular catheters.

Treatment

•          Antibiotics should be given as necessary to patients with severe neutropenia seem likely to have been caused by a drug.

•           all current drug therapy should be stopped.

•           Recovery of neutrophil count usually occurs after 10 days.

•           G-CSF is used to decrease the period of neutropenia after chemotherapy and haematopoietic transplantation.

•          Growth factors also used successfully in the treatment of chronic neutropenia.

•          Steroids and high dose intravenous immunoglobulins are used to treat patients with severe autoimmune neutropenia and recurrent infections.

•          Causes of neutrophil dysfunction
A-Congenital:

•          1-Leucocyte adhesion defect: autosomal recessive disorder impaired leukocyte tissue localization,locomotion,and endocytosis.

•          2-Hyper-IgE syndrome: the syndrome characterized by very high levels of IgE,impaired neutrophil locomotion,severe eczema with frequent staphylococcal secondary infections, abscesses and fungal infections.            

•          Shwachman’s syndrome
Exocrine pancreatic insufficiency and Pyogenic infections, defects in neutrophil migration.

•          Chronic granulomatous disease

•          This is a congenital defect of neutrophil and monocyte killing.

•          Clinical features:

•          Patients have chronic suppurative granulommas or abccess affecting skin, lymph nodes, liver, lung as well as osteomyelitis.

Treatment: Antimicrobial therapy, surgical measures, regular gamma interferon can reduce the frequency of infection.

•          Acquired neutrophil dysfunction
Causes:

•          Corticosteriods therapy, affect neutrophil function and cell mediated immunity.

Eosinophils

•          Eosinophils are slightly larger than neutrophils and are characterized by a nucleus with usually 2 lobes and deeply red cytoplasmic granules. The eosinophils plays a part in allergic responses and in the defense against infections with helminthes and protozoa.

•          Eosinophilia occur when the number of  eosinophils is >0.4x10⁹/l in the peripheral blood.

Causes of eosinophillia

•          1-Parasitic infections: Ascaris- hookworm

•          2-Pulmonary: bronchial asthma

•          3-Allergic: Allergic rhinitis, drug reaction, skin disorders, urticaria and eczema.

•          4-Malignant: Hodgkin’s disease, Sarcoidosis and hypogonadisim.

Monocytes

•          Monocytes are slightly larger than neutrophils, nucleus has variable shape rounded or lobulated .

•          Monocytosis >0.8x10⁹ in chronic bacterial infections such as tuberculosis, infective endocarditis, myelodysplasia.

Lymphocytes

•          Circulating lymphocytes are small cells, there are two main types T and B lymphocytes.

•          Lymphocytosis occurs when lymphocytic count >5x10⁹ in viral infections,EBV, HIV, chronic infections as tuberculosis and Toxoplasmosis, chronic lymphatic leukemia and lymphoma.

•          T- cell immunodeficiencies
1-Congenital:

•          A defect in thymic development associated with hypoparathyrodisim and cardiac defects. Patients presented with infections including mucocautaneous candidiasis and diarrhea.

•           Treatment: thymic transplant, thymic hormone.

•          Acquired:
1- Acquired immunodeficiency syndrome

•          The priming cellular receptor for HIV is the CD4 molecule.

•          The following cells in the immune system are affected:

•          A-CD4+ cells T lymphocytes

•          B-Monocytes

•          C-Macrophage 

•          2- Measles

•          3-Immunosuppressed drugs

•          4-Corticosteriods.

Combined T and B lymphocyte immunodeficiencies

•          1- Congenital:

•          A –Severe combined immunodeficiency:

•          Occurs in the first weeks of life, failure to thrive, absent lymphoid tissue, lymphopenia and hypogammaglobinemia.

•          Treatment :

•          BMT

•          Gene therapy.

•          B-Wiskott-Aldrich syndrome
Presented by eczema, thrombocytopenia.

•          Acquired lymphopenia:

•          1- Protein calorie malnutrition:

•          Very common cause of acquired combined immunodeficiency.

•          Measles is a major cause of death.

•          2-Immune deficiency of prematurity
Premature infants of 26 weeks gestation and under are now surviving and have several immunological deficiencies and problems.

•           Antibody continue to drop further after birth.

•          Neutropenia and impaired chemotaxis.

•          Disruption of host defense barriers e.g insertion of foreign bodies e.g catheters and  antibiotic therapy which reduces resistance produce severe infections.