White Blood Cell Disorders

Chapter 12 White Blood Cell Disorders



I. Benign Qualitative White Blood Cell Disorders

A. Pathogenesis

1. Defects in leukocyte structure

• Example—membrane fusion defect in Chédiak-Higashi syndrome (refer to Chapters 1 and 2)


Qualitative WBC defects: defects in structure and function



2. Defects in leukocyte function

a. Leukocyte adhesion defect

• Example—deficient selectin or CD11a/CD18 (refer to Chapter 2)

b. Phagocytosis defect

• Example—decreased opsonins in Bruton’s agammaglobulinemia (refer to Chapters 2 and 3)

c. Microbicidal defect

• Example—deficiency of myeloperoxidase (refer to Chapter 2)


Qualitative WBC defects: unusual pathogens, “cold” abscesses, frequent infections


B. Clinical findings

1. Unusual pathogens (e.g., coagulase-negative Staphylococcus)

2. Frequent infections and growth failure in children

3. Lack of an inflammatory response (e.g., production of “cold” abscesses)

4. Severe gingivitis


Job’s syndrome is an autosomal recessive disorder of neutrophils, characterized by abnormal chemotaxis leading to “cold” soft tissue abscesses due to Staphylococcus aureus. Patients have red hair, a leonine face, chronic eczema, and increased IgE (hyperimmune E syndrome).




Job’s syndrome: defect in chemotaxis; ↑ IgE


C. Unusual benign leukocyte reactions

1. Leukemoid reaction

a. Absolute leukocyte count usually >50,000 cells/mm3

• May involve neutrophils, lymphocytes, or eosinophils


Absolute count = % leukocytes × total WBC count


b. Etiology

(1) Perforated appendicitis (neutrophils)

(2) Whooping cough (lymphocytes)

(3) Cutaneous larva migrans (eosinophils)

c. Pathogenesis

• Exaggerated response to infection


Leukemoid reaction: benign, exaggerated leukocyte response


2. Leukoerythroblastic reaction (Fig. 12-1)

a. Immature bone marrow cells enter the peripheral blood.

b. Pathogenesis

(1) Bone marrow infiltrative disease

(2) Examples—fibrosis, metastatic breast cancer

image

12-1: Leukoerythroblastic reaction. The solid arrow shows a tear drop RBC. Immature myeloid cells are also present in a nucleated RBC (interrupted arrow).


(From Naeim F: Atlas of Bone Marrow and Blood Pathology. Philadelphia, WB Saunders, 2001, Fig. 4-10B.)



Leukoerythroblastic reaction in woman > 50 years of age: usually due to breast cancer metastatic to bone


c. Peripheral blood findings

(1) Myeloblasts, progranulocytes

(2) Nucleated RBCs, tear drop RBCs (if fibrosis is present)

II. Benign Quantitative WBC Disorders

A. Disorders involving neutrophils

1. Neutrophilic leukocytosis

a. Absolute neutrophil count > 7000 cells/mm3 (see Fig. 2-12)


Neutrophilic leukocytosis: neutrophil count > 7000 cells/mm3


b. Etiology

(1) Infection (e.g., acute appendicitis)

(2) Sterile inflammation with necrosis (e.g., acute myocardial infarction)

(3) Drugs (e.g., corticosteroids)

c. Pathogenesis

(1) Increased bone marrow production or release of neutrophils

(2) Decreased activation of neutrophil adhesion molecules

(a) Fewer neutrophils adhere to endothelial cells

(b) Examples—corticosteroids, catecholamines, lithium

2. Neutropenia

a. Absolute neutrophil count < 1500 cells/mm3

Neutropenia: neutrophil count < 1500 cells/mm3


b. Etiology

(1) Aplastic anemia

(2) Immune destruction

• Example—systemic lupus erythematosus (SLE)

(3) Septic shock

c. Pathogenesis

(1) Decreased production

(2) Increased destruction

• Destruction by complement, macrophages

(3) Activation of neutrophil adhesion molecules

(a) Increase the number of neutrophils adhering to endothelium

(b) Example—endotoxins

B. Disorders involving eosinophils

1. Eosinophilia (Fig. 12-2A)

a. Absolute eosinophil count > 700 cells/mm3
image

12-2: Normal morphology of eosinophil (A), basophil (B), lymphocyte (C), and monocyte (D). The cytoplasm of an eosinophil (A) is packed with reddish-orange granules that do not cover the nucleus. The cytoplasm of a basophil (B) is packed with large purplish black granules that cover the usually bilobed nucleus. The cytoplasm of a small lymphocyte (C) is scant and surrounds a nucleus that is usually round (sometimes indented) and contains condensed nuclear chromatin. The cytoplasm of a monocyte (D) is grayish blue and contains many fine azurophilic granules and one or more clear vacuoles. The nucleus is large, eccentrically located, and either round, kidney- or horseshoe-shaped (monocyte in the picture), or lobulated.


(From Wickramasinghe SE, McCullough J: Blood and Bone Marrow Pathology. London, Churchill Livingstone, 2003, Fig. 1-1.)



Eosinophilia: eosinophil count > 700 cells/mm3


b. Etiology

(1) Type I hypersensitivity reaction

• Examples—bronchial asthma, reaction to penicillin, hay fever

(2) Invasive helminthic infection

(a) Examples—strongyloidiasis, hookworm infection

(b) Pinworms and adult ascariasis do not have eosinophilia (noninvasive).

(3) Polyarteritis nodosa

(4) Addison’s disease (cortisol deficiency)


Eosinophilia: type I hypersensitivity, invasive helminths, hypocortisolism


c. Pathogenesis

(1) Release of eosinophil chemotactic factor from mast cells

• Type I hypersensitivity reaction

(2) No sequestering of eosinophils in lymph nodes

• Example—hypocortisolism

2. Eosinopenia; etiology:

a. Hypercortisolism

• Examples—Cushing syndrome, corticosteroids


Eosinopenia: hypercortisolism


b. Corticosteroids sequester eosinophils in lymph nodes.

C. Disorders involving basophils; basophilia

1. Absolute basophil count > 110 cells/mm3 (Fig. 12-2B)

2. Etiology

• Chronic myeloproliferative disorders (e.g., polycythemia vera)


Basophilia: consider myeloproliferative disease


D. Disorders involving lymphocytes

1. Lymphocytosis

a. Absolute lymphocyte count > 4000 cells/mm3 in adults or >8000 cells/mm3 in children (Fig. 12-2C)


Lymphocytosis: lymphocyte count > 4000 cells/mm3 (adult); >8000 cells/mm3 (child)


b. Etiology

(1) Viral

• Examples—mononucleosis, cytomegalovirus (CMV)

(2) Bacterial

• Example—whooping cough

(3) Drugs

• Example—phenytoin

(4) Graves’ disease

c. Pathogenesis

(1) Increased production

(2) Decreased entry into lymph nodes

• Example—due to lymphocytosis-promoting factor produced by Bordetella pertussis

2. Atypical lymphocytosis

a. Etiology

(1) Infection

• Examples—mononucleosis, viral hepatitis, CMV infection, toxoplasmosis

(2) Drugs (e.g., phenytoin)

b. Pathogenesis

(1) Antigenically stimulated lymphocytes

(2) Prominent nucleoli and abundant blue cytoplasm


Atypical lymphocytes: antigenically stimulated


3. Infectious mononucleosis

a. Caused by Epstein-Barr virus (EBV)


Atypical lymphocytosis: EBV, CMV, viral hepatitis, phenytoin


b. Pathogenesis

(1) Primarily transmitted by kissing

• EBV initially replicates epithelial cells in oropharynx.

(2) Infection spreads to B cells in lymph nodes

(a) Attaches to CD21 receptors on B cells.


B cells have CD21 receptor sites for EBV.


(b) Causes B-cell proliferation and increased synthesis of IgM antibodies

(c) Virus remains dormant in B cells.

• Recurrences may occur.

c. Clinical findings

(1) Severe fatigue

(2) Exudative tonsillitis

(3) Hepatosplenomegaly

• Danger of splenic rupture in contact sports

(4) Generalized painful lymphadenopathy

(5) Rash develops if treated with ampicillin.


Infectious mononucleosis: rash develops if patient placed on ampicillin


d. Laboratory findings

(1) Atypical lymphocytosis

(a) Usually more than 20% of the total WBC count

(b) Atypical lymphocytes are antigenically stimulated T cells (Fig. 12-3).

(2) Positive heterophil antibody test

(a) Initial screening test

(b) Detects IgM antibodies against horse (most common), sheep, and bovine RBCs

image

12-3: Peripheral blood with atypical lymphocytes. The lymphocytes are large and have abundant blue-gray cytoplasm. Nuclei are irregular and have dark chromatin with inconspicuous nucleoli.


(From Naeim F: Atlas of Bone Marrow and Blood Pathology. Philadelphia, WB Saunders, 2001, Fig. 13-1.)



Heterophile antibodies: IgM antibodies directed against horse, sheep, bovine RBCs


(c) Sensitivity 87%, specificity 91%

(3) Antiviral capsid antigen (VCA) antibodies

(a) High sensitivity and specificity

Anti-VCA-IgG/IgM: excellent test if screening test is negative


(b) Develops early in the infection

(c) Persists for life

(4) Anti-early antigen (EA) antibodies

• Increased with chronic infections

(5) Anti-Epstein Barr nuclear antigen (EBNA) antibodies

(a) High sensitivity and specificity

(b) Develops late in the infection

(c) Persists for life

(6) Increased serum transaminases from hepatitis

• Jaundice is rare.

4. Lymphopenia

a. Absolute lymphocyte count < 1500 cells/mm3 in adults or <3000 cells/mm3 in children


Lymphopenia: lymphocyte count < 1500 cells/mm3 (adult); <3000 cells/mm3 (child)


b. Etiology

(1) HIV


Lymphopenia in HIV: lysis of CD4 helper T cells by the virus


(2) Immunodeficiency

(a) DiGeorge syndrome (T-cell deficiency)

(b) Severe combined immunodeficiency (B- and T-cell deficiency)

(3) Immune destruction (e.g., SLE)

(4) Corticosteroids (apoptosis)


Corticosteroids produce neutrophilic leukocytosis, eosinopenia, and lymphopenia.


(5) Radiation

• Lymphocytes most sensitive cells to destruction by radiation (refer to Chapter 6)

c. Pathogenesis

(1) Increased destruction

• Examples—lysis CD4 helper T cells by HIV; apoptosis by corticosteroids; immune destruction (SLE)

(2) Decreased production

• Example—Bruton’s agammaglobulinemia

E. Disorders involving monocytes; monocytosis

1. Absolute monocyte count > 800 cells/mm3 (see Fig. 12-2D)

2. Etiology

a. Chronic infection

• Examples—tuberculosis, subacute infective endocarditis


Monocytosis: chronic infection, autoimmune disease, malignancy


b. Autoimmune disease

• Examples—rheumatoid arthritis, cirrhosis

c. Malignancy

• Examples—carcinoma, malignant lymphoma

3. Pathogenesis

• Response to chronic inflammation or malignancy

III. Leukemias (Acute and Chronic)

A. Epidemiology

1. Malignant diseases of bone marrow stem cells

• May involve all cell lines


Leukemia: malignant transformation of marrow stem cells


2. More common in males than females

3. Risk factors

a. Chromosomal abnormalities

• Examples—Down syndrome, chromosome instability syndromes

b. Ionizing radiation

• Example—nuclear plant explosion

c. Chemicals

• Example—benzene for myeloid leukemia

d. Alkylating agents

• Particularly busulfan

e. Chronic myeloproliferative diseases

• Example—polycythemia vera

f. Paroxysmal nocturnal hemoglobinuria

g. Cigarette smoking

h. Immunodeficiency diseases

• Example—Wiskott-Aldrich syndrome

4. Age ranges for common leukemias

a. More common in adults than children

b. Newborn to 14 years old

(1) Acute lymphoblastic leukemia (ALL)

(2) Most common leukemia in children

(3) Most common cancer in children


ALL: most common leukemia and cancer in children


c. Persons 15 to 39 years old

• Acute myeloblastic leukemia (AML)

Related posts:

  1. Skin Disorders
  2. Vascular Disorders
  3. Genetic and Developmental Disorders
  4. Red Blood Cell Disorders

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Jun 25, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on White Blood Cell Disorders

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