Chapter 16 Benign WBC disorders

Chapter 16
Benign White Blood Cell Disorder

​Granulocytes

• From: Myeloid stem cells

• Types: neutrophils, eosinophils, basophils, and monocytes
  

​Lymphocytes

• From: Lymphoid stem cells

• Type: Lymphocyte

​Two types of Leukocytes

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Granolyocytes are formed by ​

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, while lymphocytes are formed by​

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​WBC Type	​Normal percentage	​Function(s)
​Neutrophils	​50-70% in adults	​The first line of defense is engulfing bacteria and fungi through phagocytosis at the infection site. Mediate inflammatory
​Eosinophils	​2-4%4​WBC	​Destruction of parasites and allergic response regulator (hypersensitivity).
​Basophils	​1-2% in adults	​Inflammation response due to granules being histamine, response to allergy, and hypersensitivity response.
​Monocytes	​2-9% in adults	​Phagocytosis and antimicrobial of bacteria, digestion of debris, tissue repair and initiate/regulate an immune response

​Granulocytes

​Lymphocytes

​WBC type	​Normal percentage	​Function
​Lymphocytes	​20-40%	​Hummorial and Cell-Mediated Immunity

Match

Match the function and white blood cell

• Neutrophil

• Lymphocyte

• Monocyte

• Eosinophil

• Basophil

defense, bacteria and fungi by phagocy

adaptive immune response and antibody production

phagocytosis and antigen presentation

defense against parasites and allergic reactions

release of histamine and inflammatory response

• defense, bacteria and fungi by phagocy

• adaptive immune response and antibody production

• phagocytosis and antigen presentation

• defense against parasites and allergic reactions

• release of histamine and inflammatory response

Neutrophils

Cytoplasmic in Mature Neutrophils

​Cytoplasm Granules	​Seen with	​Contents
​Primary (azurophilic, non-specific)	​Light microscope	​Myeloperoxidase, lysozyme, α-Defensin, Bactericidal/permeability-increasing protein, Serine proteases, and acid hydrolases
​Secondary (Specific)	​Light microscope	​Lactoferrin, lysosome, gelatinase, collagenase, histaminase, herapinase, neutrophil gelatinase-associated lipocalin, signal regulatory protein alpha, transcobalamin 1 and 111, and plasminogen activator
​Tertiary	​Electron microscope	​Gelatinase, lysozyme, and alkaline phosphate

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All the cytoplasmic content contains ​

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, while only secondary and tertiary content have a common content, such as ​

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. Other types of cytoplasmic content in primary (azurophilic) are ​ ​

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and ​

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; in ​

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, lactoferrin and collagenase are present, and tertiary alkaline phosphate.

​
NEUTROPHIL
Phagocytosis function

​Migration and Diapedesis	​Recognition and Opsonization	​Ingestion, killing, and digestion
​Locomotion (random): Nondirectional neutrophils in the marginating pool along the endothelium vessel are the site of injury or infection by the chemoattractant, forming a concentration gradient. Chemokinesis: Nondirectional acceleration of migration speed due to chemoattractants Chemotaxis: Directional penetration of tissue with the help of chemoattractant guidance.	​Neutrophils have a membrane receptor that aids in indirect/direct recognition and attachments to microbes.	​Intracellular: Pseudopods extend around microbes, firing a vacuole in the neutrophil cytoplasm, while cytoplasmic granules migrate to fuse and destroy and digest microbes. Extracellular: Webs or traps that combat infections. However, it can contribute to pathogenesis from autoimmunity and inflammation

Key Terms
Quantitative

Qualitative

Neutrophilia

Neutropenia

​

​Disorders of Neutrophil Function

Match

Match term with definition

• Qualitative Disorder

• Quantitative Disorder

• Neutrophilia

• Neutropenia

• Leukocytosis

A disorder characterized by the quality of the blood cells

A disorder characterized by the quantity of blood cells

An increase in neutrophils in the blood

A decrease in neutrophils in the blood

An increase in white blood cells in the blood

• A disorder characterized by the quality of the blood cells

• A disorder characterized by the quantity of blood cells

• An increase in neutrophils in the blood

• A decrease in neutrophils in the blood

• An increase in white blood cells in the blood

• Exceeds 7.7X10⁹/L

• Leukomoid reaction: toxic granulation, vacuolization, Dohle bodies,

• Increase in neutrophil and immature cells neoplastic (CML or chronic myloeproliferative disorders.

• Shift to left: increased number of metamyelocytes and band forms

• Secondary reactive: infections, tissue necrosis, stress, smoking, pregnancy, acute bleeding, metabolic, etc.

Quantitative
Neutrophilia Neutropenia

• Age, race, less than 2.5 x10⁹/L

  Mild, moderate, and severe categories.

• Acquired: by transient conditions caused by extrinsic factors

  -Viral

  -Medications (penciling, ibuprofen, procainamide, Fenty etc.

  -immune-mediated (alloantibody or antibody)

• Secondary: aplastic anemia, bone marrow malignancy, B12, and folate deficiency

• Congenital as chronic or intermediate

  -Cyclic Nuetrponia

• Chronic benign neutropenia

Categorize

Options (19)

Shift to left

Increased white blood cell count

Presence of immature neutrophils

Bacterial infection

Inflammatory response

Stress response

Tissue necrosis

Decreased white blood cell count

Bone marrow suppression

Autoimmune disorders

Chemotherapy effects

Viral infections

Hypersplenism

Congenital neutropenia

Chronic: more than 24 genes affecting myeloid or hemopoietic regulation

Neonatal alloimmune after mother senstilozation to fetal antigens

Organize these options into the right categories

Neutrophilia

Neutrophenia

​Qualitative
Bacterial infections are caused by hereditary function. Functional defects can be acquired or inherited by the classification phagocytosis/killing defects, granule and structure-function, defects affecting chemotaxis and motility, and adhesion defects

​Chediak-Higashi Syndrome	​Chronic Granulomatous Disease	​Myeloperoxidase Deficiency	​Leukocyte Adhesion Deficiency
​Rare autosomal Lysosomal storage disease Caused by LYST gene Large granules Characteristics: recurrent bacterial infection, occulutaneous albinism, progressive neurological disorders, and platelet bleeding	Heterogenous, X-linked recessive Attributed to failure in activation of respiratory burst (little to no superoxidase)-ineffective killing NADPH oxidase mutation Characteristics: recurrent, life-threatening bacteria and fungus infection spread to organs and tissues	​Inherited disorder of phagocytosis The formation of hypochlorous acid affects phagocytosis, killing Usually, secondary disorder' Autosomal recessive in MPO gene	​ ​Autosomal recessive Mutation in CD18 Glycoproteins B2

​Qualitative
Disorders of neutrophil morphology
Acquired

​ ​Hypersegmentation	​ ​Hypogranularity	​Pseudo-Pelger Huet
​Six or more nuclear lobes Larger than normal Megaloblastic anemia Myeloid malignancies (AML, myelodysplastic syndromes)	​​Bilobed or no lubulatation Exceptionally coarse and condensed nuclear chromatin Pelger Huet Myeloid malignancies (AML, myelodysplastic syndromes)	​Drug-induced or leukemia ​Bilobed or no lubulatation <30% total neutrophil count Myeloid malignancies (AML, myelodysplastic syndromes)

​Qualitative
Disorders of neutrophil morphology
Inherited

​Alder-Reilly Anomaly	​May-Hegglin Anomaly
​	​

• ​Prominent dark stain

• Course cytoplasmic granules (azurophilic)

• Autosomal recessive
  

• ​Large Blue stain inclusion
  (precipitated mucopolysaccharide)

• Autosomal dominant
  
  

Eosinophils

Key term
Eosinophilia: more than 0.5x10⁹ cells/L

Facts

• Causes are categorized as neoplastic, reactive, and idiopathic

• Allergic reaction is a common cause of reactive eosinophilia.

• Other reactive esonphlia are parasite infection, skin disorders (even and atopic dermatitis), allergic (asthma), inflammatory disorders (celiac disease. IBS), and pulmonary disorders (pneumonia and cystic fibrosis).

• Acquired secondary eosinophilia: mild to moderate eosinophilia is a compensatory bone morrow mechanism in response to the tissue demand increase for eosinophils, disappears after the disease is resolved, and sometimes no known cause in mild or moderate cases after blood work is done.

Basophils

Key term
Basophilia: more than 0.1x10⁹ cells/L

Facts

• It is uncommon to be isolated

• Chronic myelogenous leukemia (CML) is often the cause of basophilia

• Reactive conditions such as infections (chicken pox, influenza), inflammatory disorder (rheumatoid arthritis), allergies due to histamine, chronic renal disease, endocrine disease (diabetes and hypothyroidism), and exposure to radiation can cause basophilia.

• Indicative of malignancy process

Monocytes

Key term
Minocytosis: more than 1.0x10⁹ cells/L

Facts

• It contains very fine granules that destroy microbes

• Granules include lysozyme, collagenase, acid phosphate, and elastase

• Reactive conditions such as chronic infection (fungal bacterial and protozoal), autoimmune disease, splenectomy, and malignant hematological disorders (Hodgkin and Non-Hodgykin, and multiple myeloma)

• It can be found in chronic myelomonocytic leukemia (CMML), chronic myelogenous leukemia (CML), acute monocytic leukemia, and acute myelomonocytic leukemia (AMML).

Lymphocytes

Key term
Lymphocytosis: Increase in percentage of lymphocytes when performing WBC differential. The total number of lymphocytes present is calculated as a percentage of WBC overall.
Facts

• The predominance of lymphocytes after birth to childhood and return to neutrophil predominance in in adulthood

  Characteristics

​	​Reactive lymphocytes	​Resting small lymphocytes
​Size	​Large (9-30mm)	​Small (8-12mm)
​N:C Ratio	​Low to moerate	​High to moderate
​Cytoplasm amount	​Abundant	​Scant
​Cytoplamsic color	​coloress to dark blue	​colorless to light blue
​Nucleus shape	​round to irregular	​round
​Chromatin	​course to moderately fine	​coarse
​Nucleoli	​Absent to distinct	​absent
​Typing	​polyclonal	​polyconal

Categorize

Options (17)

Eosinophilia increase of eosinophils

Mild to moderate increase resolve once disease is

neoplastic, reactive, and idiopathic

Reactive: allergic rhinitis , pemphigus, bronchiectasis, vasulutides

Eosinophils play a key role in combating parasitic infections

Lymphocytosis is an increase in lymphocytes

They can be divided into B cells and T cells

Basophilia is an increase in basophils in the blood

Basophils are involved in the defense against parasites

Chronic myelogenous leukemia

Routine blood work can show no cause of eosinophilia

Granules being histamine causing allergies and inflammation

Reactive: Diabetes, Smallpox, collagen vascular disease. exposure to radiation, and urticaria

Monocytosis increase in monocytes

Granules: lipozyme, collagenase, acid phosphate, and elastase.

CML, CMML, AMML, and acute monocytic leukemia

Reactive: fungal and rickettsial infection, sarcoidosis, hemolytic anemia, acquired neutropenia

Organize these options into the right categories

Monocytes

Lymphocytes

Basophils

Eosinophils

Match

Match descriptions

• Large Size

• High to moderate N:C

• Abundant cytoplasm and colorless/dark blue

• Scant cytoplasm and colorless/ light blue

• Nucleus Irregular/ round and low to moderate N:C

Reactive Lymphocyte Size

Resting Lymphocyte Ratio

Reactive Lymphocyte cytoplasm

Resting lymphocyte cytoplasm

Reactive lymphocyte nucleus

• Reactive Lymphocyte Size

• Resting Lymphocyte Ratio

• Reactive Lymphocyte cytoplasm

• Resting lymphocyte cytoplasm

• Reactive lymphocyte nucleus

​Lymphocytosis
Reactive or malignant

​Reactive	​Malignant confused with reactive
​Vary in size and shape Immunophenotypic marker (polyclonal) Causes can be viral (adenovirus, herpes zoster, HIV, hepatitis), bacterial (whopping cough, tuberculosis, typhoid and paratyphoid fever), drug reaction recovering from acute infection and syphilis, malnutrition, etc.	​Granular blast and prompyncoytes Reactive lymphocytes have a blast, fine chromatinpominent nuclei, and less cytoplasm. Malignant are homogenous appearance

Lymphocytenepia
Key Term: Sever occurs when less than 1.0x10⁹ cells/L.

Facts

• Relative neutropenia and normocytic, normochromic anemia is present

• Causes include HIV, TB, myasthenia gravis, burns, renal disease, anesthesia and surgery, chemotherapy, nutritional deficiencies, and carcinoma.