Nonmalignant Disorders of Granulocytes and Monocytes

Differentiate between quantitative and qualitative disorders of granulocytes.
- Examples depend on the primary function of the affected WBC.
Differentiate between acute, intermediate, and chronic neutrophilia.
Define leukemoid reaction and distinguish between leukemoid reactions and CML.
Recognize eosinophilia, basophilia, and monocytosis in blood smears and match with causes.
Define neutropenia and list at least 4 causes.
Describe and recognize 3 types of abnormal nuclear morphology in neutrophils:
- Hypersegmentation
- Pelger-Huёt anomaly (hyposegmentation)
- Pyknotic nucleus
Describe and recognize 4 types of abnormal cytoplasmic morphology in neutrophils:
- Toxic granulation
- Döhle bodies
- Ehrlichia
- Vacuoles
Describe 4 inherited neutrophil disorders with characteristic neutrophil morphology:
- May-Hegglin anomaly
- Chediak-Higashi syndrome
- Alder-Reilly inclusions
- Chronic Granulomatous disease (CGD)
Explain why inherited abnormalities of neutrophils can also appear in monocytes.
List at least 3 mechanisms causing qualitative granulocyte disorders.
Describe lipid functions in the human body and the importance of corresponding enzymes.
General characteristics of Lipid/Lysosomal Storage Diseases (LSDs) with diagnostic tests for confirmation.
Match enzyme deficiencies with typical abnormal cells for LSDs:
- Gaucher’s Disease
- Niemann-Pick Disease
- Tay-Sach’s Disease
Differentiate between Glycosaminoglycan/Mucopolysaccharidosis disorders and Histiocytosis disorders.

Quantitative Disorders: Increase or decrease in leukocyte counts, often due to infections.
Qualitative Disorders: Defective killing ability of leukocytes.
Toxic challenges can affect granulocytes; cell type affected depends on infection.
- Bacterial infections affect neutrophils.
- Viral infections affect lymphocytes.
- Parasitic infections affect eosinophils.
Laboratory tests: CBC, WBC differential, ESR, Bone Marrow aspirations for suspected malignancies.

Leukocytosis: Increase in leukocyte concentration in peripheral blood.
Leukocytopenia: Decrease in total leukocyte count.
Nonmalignant leukocytosis is common, caused by:
- Increased immature cell movement from bone marrow.
- Increased mobilization from maturation-storage compartments.
- Decreased movement of mature cells into tissues.

Definition: Absolute neutrophil count > 7.0 imes 10^9/L.
Factors affecting concentration:
- Bone marrow production and release.
- Neutrophil migration into tissues.
- Circulating vs. marginating neutrophils.
Types of Neutrophilia:
1. Immediate Neutrophilia: Redistribution from marginal to circulating pool (e.g., from stress).
2. Acute Neutrophilia: Occurs 4-5 hours after a pathological stimulus.
3. Chronic Neutrophilia: Follows acute neutrophilia as the bone marrow releases younger cells.
Associated conditions:
- Bacterial infections (most common): Absolute neutrophil count > 10-19 imes 10^9/L.
- Severe infections may lead to neutropenia (e.g., typhoid fever).

Leukemoid Reaction: Extreme neutrophilia (WBC count > 30 imes 10^9/L), resembles CML but lacks Philadelphia chromosome (Ph+).
Clinical parameters:
- Leukocyte alkaline phosphatase (LAP) score increased in leukemoid reaction but decreased in CML.
- Spleen size normal in leukemoid reaction, generally enlarged in CML.

Definition: Absolute count > 0.6 imes 10^9/L.
Causes:
- Allergy and asthma (most common).
- Parasitic infections, particularly helminths.
- Drug hypersensitivity reactions.
- Chronic inflammatory states and some malignancies.

Definition: Absolute count > 0.15 imes 10^9/L.
Features in CML and specific viral infections.
Basophilia can signify other conditions such as ulcerative colitis and polycythemia vera.

Definition: Absolute count > 0.8 imes 10^9/L.
Associated with chronic infections, inflammatory diseases, and certain malignancies.

Definition: Absolute neutrophil count < 1.5 imes 10^9/L.
Caused by:
- Decreased bone marrow production.
- Increased cell loss due to infections or immune mechanisms (e.g., anti-leukocyte antibodies).
- Pseudoneutropenia from sampling errors.

Increased Neutrophilia: Inflammatory conditions, infections, physical stimuli, and some malignancies.
Decreased Neutrophilia: Bone marrow damage, hypersplenism, starvation, and certain drugs.

Nuclear Abnormalities: Hypersegmentation, Pelger-Huёt anomaly, pyknotic nucleus.
Cytoplasmic Abnormalities: Toxic granulation, Döhle bodies, Ehrlichia, vacuoles.

May-Hegglin Anomaly: Characterized by Döhle body-like inclusions and large platelets.
Chédiak-Higashi Syndrome: Large granules in leukocytes leading to frequent infections.
Alder-Reilly Inclusions: Mucopolysaccharides in neutrophil granules.
Chronic Granulomatous Disease (CGD): Neutrophils can phagocytize but can't kill due to oxidative burst defects.

Overview: Caused by enzyme deficiencies leading to lipid accumulation in lysosomes.
Types of LSDs: Gaucher's Disease, Niemann-Pick Disease, Tay-Sach’s Disease with specific enzyme deficiencies.

Rare diseases where specific enzyme deficiencies prevent degradation of mucopolysaccharides.
Characterized by various symptoms, organomegaly, skeletal abnormalities, and specific WBC features.

Not an enzyme deficiency but causes similar symptoms with increased histiocytes affecting immune response.

Presented a case of Niemann-Pick disease with hepatosplenomegaly and abnormal cell findings.

Laboratory tests crucial in identifying leukocyte disorders and confirming diagnoses through enzyme assays and blood smears.
Diagnostic characteristics for Gaucher's, Niemann-Pick, and other LSDs highlighted.