HEMA WBC Anomalies PDF

Leukocytes Louis John R. Bejo, RMT, MSPH Function: Defense mechanism.  Leukocytes A.k.a. White Blood Cells Derived its name from being relatively colorless compared to red blood cells. (Rodak) The major component of “buffy coat” (white in color) hence,...

Leukocytes Louis John R. Bejo, RMT, MSPH Function: Defense mechanism.  Leukocytes A.k.a. White Blood Cells Derived its name from being relatively colorless compared to red blood cells. (Rodak) The major component of “buffy coat” (white in color) hence, White blood cells  Leukocytes Romanowsky stain – Light microscope 5 to 6 types of leukocytes Flow Cytometry At least 10 different types  Leukocytes Granulocytes Agranulocytes Neutrophil Monocyte Eosinophil Lymphocyte Basophil  Leukocyte Staining Granulocytes are a group of leukocytes with cytoplasmic granules and lobulated or segmented nuclei. Eosinophils = granules are basic proteins that stain with acid stains (eosin). Basophils = acidic granules that stain with basic stains (methylene blue). Neutrophils = granules that react with both acidic and basic stains which give them pink to lavender color;  Mononuclear cells/Agranulocytes Nuclei: round, oval, indented or folded.  Leukocyte Population Factors: Sex Age Activity Time of the day Ethnicity WBC reacting to stress, being consumed, or being destroyed Enough production Granulocytes Neutrophils Neutrophils Kinetics: Once in the blood divided randomly into Circulating Neutrophil Pool (CNP) and Marginated Neutrophil Pool (MNP). MNP neutrophils are loosely localized to the walls of capillaries in tissues such as liver, spleen and lung. MNP and CNP neutrophils are almost equal in number and shows no difference in functions. Neutrophils in blood have a half life of 7 hours. Kinetics: MNP are allowed to enter tissues through diapedesis, tissues that do not migrate into the tissues will undergo apoptosis and will be removed by splenic macrophages. Their lifespan in the tissues are variable if they are responding to infection or inflammation. (if they are functioning = longer half life; if not = half life is measured in hours). Functions: Part of the innate(non-specific) immune system. Can activate the complement system. Major function is phagocytosis and destruction of foreign materials and microorganisms. The process involves seeking(chemotaxis, motility and diapedesis) and destruction (phagocytosis and digestion).  Killing and Formation of Digestion Neutrophil Phagocytosis Ingestion Extracellular (Oxygen in/dependent) Traps  Primary (Azurophilic) Secondary (Specific) Granules Granules Formed during promyelocyte Formed during myelocyte and stage. metamyelocyte stage. Last to be released (exocytosis). Third to be released. Neutrophil Granules Secretory Granules (Secretory Vesicles) Tertiary Granules Formed during band and Formed during metamyelocyte segmented neutrophil stages. and band stages. First to be released(fused to Second to be released. plasma membrane). Eosinophils Eosinophils Kinetics: Once in the blood have a circulating half-life of roughly 18 hours. The tissue destination of eosinophils under normal circumstances appear to be underlying columnar epithelial surfaces in the respiratory and gastrointestinal and genitourinary tracts. In the tissues, eosinophils can live from 2 to 5 days. Functions: Eosinophils have multiple functions: Compound exocytosis Piecemeal degranulation Can be an Antigen presenting cells (APCs) Can induce Type 1 or 2 immune response Regulate Mast cell formation through the release of major basic protein (MBP). Eosinophil production is increase in helminthic infection. Destroys tissue-invading helminthes and prevents reinfection. A hallmark of allergic disorders (asthma) Eosinophils on allergic reactions: Can cause airway inflammation. Also been implicated in airway remodeling (increase airway wall thickness) through eosinophil-derived fibrogenic growth factor. Eosinophil accumulation in the gastrointestinal tract occurs in allergic disorders such as food allergy, allergic colitis, and inflammatory bowel disease (Crohn’s disease and ulcerative colitis). Basophils Basophils Kinetics: Basophil kinetics is poorly understood because of their very small numbers. Recent study suggests that a mature basophil is 60 hours (due to anti- apoptotic pathways). Functions: Previously regarded as “poor relatives of mast cell” and minor players in allergic inflammation. Like mast cells, they have IgE receptors (Ab commonly see in allergic reactions). Contains histamine in its secondary granules. Along with eosinophils, they are involve in control of helminth infections.  Mast Cells They are not considered as leukocytes. They are tissue effector cells of allergic responses and inflammatory reactions. They have several phenotypic and functional similarities with basophils and eosinophils. Their precursors came from BM but they mature in the peripheral blood or tissues. They have anti-inflammatory and immunosuppressive functions, and thus they can both enhance and suppress features of the immune response. Agranulocytes/Mononuclear Cells Monocytes Monocytes Monocyte/Macrophage Kinetics Under normal circumstances, promonocytes undergo two mitotic divisions in 60 hours to produce a total of four (4) monocytes. Increased demands for monocytes will cause a production of 16 monocytes in 60 hours. (there is no storage pool for monocytes in blood and BM) Recent evidence, however, suggest that a relatively large reservoir of immature monocytes reside in the subcapsular red pulp of the spleen and appear to respond to tissue injury such as myocardial infarction and participates in wound healing. Monocyte/Macrophage Kinetics Monocytes remain in the circulation for approximately 3 days. Once in the tissues, monocytes differentiates into macrophages and can be as large as 40 – 50um in diameter. Life span of macrophages depends on whether they are responding to inflammation or infection, or are “resident” macrophages such as Kupffer cells or alveolar macrophages. Monocyte/Macrophage Functions Innate immunity Adaptive Immunity Housekeeping functions Monocyte/Macrophage Functions Innate immunity Can recognize wide range of bacterial pathogens that can stimulate inflammatory cytokine production and phagocytosis. They can synthesize nitric oxide which is cytotoxic against viruses, bacteria, fungi, protozoa, helminths and tumor cells. They have Fc receptors to phagocytize foreign materials coated with Ab or complement. Monocyte/Macrophage Functions Adaptive Immunity Both macrophages and dendritic cells degrade antigen and antigen fragments on their surfaces (APCs). Because of this they can interact with and activate both T lymphocytes and B lymphocytes to initiate adaptive immune response. Dendritic cells are the most efficient and potent of the APCs. Monocyte/Macrophage Functions Housekeeping functions These include removal of debris and dead cells at sites of infection or tissue damage, destruction of senescent RBCs and maintenance of a storage pool of iron for erythropoiesis, and synthesis of a wide variety of proteins including coagulation factors, complement components, IL, growth factors and enzymes. Lymphocytes Lymphocytes  Lymphocytes They are divided into three (3) major groups: T cell B cell NK cell  Lymphocytes T and B cell are major players in adaptive immunity. NK cells make up a small percentage of lymphocytes and are part of innate immunity. Self-antigens are “ignored” by the adaptive immunity under normal circumstances. (referred to as tolerance).  Lymphocytes Lymphocytes are different from the other leukocytes in several ways, including the following; 1. Lymphocytes are not end cells. They are resting cells and when stimulated they undergo mitosis to produce both memory and effector cells. 2. Unlike other leukocytes, lymphocytes recirculate from the blood to the tissues and back to the blood. 3. B and T lymphocytes are capable of rearranging antigen receptor gene segments to produce a wide variety of antibodies and surface receptors.  Lymphocytes Lymphocytes are different from the other leukocytes in several ways, including the following; 4. Although early lymphocytes progenitors such as the common lymphoid progenitor originate in the BM, T and NK lymphocytes develop and mature outside the BM. 5. More of lymphocyte functions and kinetics are part of immunology. WBC anomalies and Leukemia  Morphological abnormalities Normal morphology Morphologic Alterations of Neutrophil Nuclei Morphologic Alterations of Neutrophil Cytoplasm Morphologic Alterations of Lymphocytes and Monocytes Normal Morphology Normal Morphology Normal Morphology Morphologic Alterations of Neutrophil Nuclei Pelger-Huet Anomaly Hyper-segmented neutrophil Drumsticks Morphologic Alterations of Nuclear Cytoplasm Alder-Reilly Anomaly Chediak-Higashi Syndrome May-Hegglin Anomaly Dohle-Amato Bodies Toxic Granulation  Morphologic Alterations of Lymphocytes and Monocytes Reed-Sternberg Cells Hand-Mirror Cells Sezary Cells Smudge Cells Atypical lymphocyte Activated Monocytes Pelger-Huet Anomaly (PHA) A neutrophil with a hypolobulated, rounded nuclei and condensed chromatin. A thin strand of chromatin may connect the lobes, creating a “pince-nez” (spectacle) shape, or a larger bridge can give the nucleus a peanut appearance. Genetic disorder. (Heterozygotes are asymptomatic though can be mistaken as an immature cell and cause a misjudgment on clinical decisions) Pelger-Huet Anomaly Hyper-segmented neutrophil Neutrophils with abnormally increased number of nuclear lobes. >5% of PMN with 5 lobes or any appearance of 6-loop PMN. Very common in cases of megaloblastic anemia (Vit. B12 or folate deficiency). Hyper-segmented neutrophil Drumsticks Inactive X chromosome in females. Not seen in males (XY) and patients with Turners syndrome (XO) or other abnormalities with only one X chromosome. Drumsticks Alder-Reilly Anomaly Recessive disorder. Deposition of mucopolysaccharides (lipids) in cytoplasm. Appear as metachromatic granules. Alder-Reilly Anomaly Chediak-Higashi Syndrome Rare autosomal recessive trait. Abnormally large Peroxidase-Positive lysosome are seen in the PMN (and most cell of the body) results in Albinism. Chediak-Higashi Syndrome Chediak-Higashi Syndrome May-Hegglin Anomaly Rare autosomal dominant condition. Presence of Large Dohle-body like formation (combination of rods and granules that are ribosomal in origin.) May-Hegglin Anomaly Dohle bodies Small blue-gray (single or multiple) inclusions in the cytoplasm of neutrophils, often at the margins (eccentric). Composed of rough endoplasmic reticulum and glycogen granules. Associated with inflammatory disorders and burns. Dohle bodies Toxic Granulation Neutrophils that are characterized by an increased numbers of granules that are larger and more basophilic than normal. May appear in severe bacterial infections, burns, malignancies, and drug reaction. Toxic Granulation Reed-Sternberg cells (the mirror nuclei) Reed-Sternberg cells (the mirror nuclei) Hand-mirror cells Characteristics “hand-mirror” shape of T cells in a patient with T-cell acute lymphocytic leukemia. Hand-mirror cells Sezary cells Lymphocytes with frequently convoluted nuclei (sezary cells) in a patient with advanced mycosis fungoides. Sezary cells Smudge Cells Fragile lymphocytes rupture (during film preparation) Nucleus appears spread out with hazy borders and cytoplasm. Smudge Cells Atypical Lymphocyte Common in viral infections (e.g., Herpes infection ad HIV). Large lymph with prominent foamy/vaculated cytoplasm and irregular nucleus (kidney shaped or lobulated). Basophilic cytoplasm and coarse chromatin. Atypical Lymphocyte Activated monocytes Associated with inflammatory reaction to bacteremia Macrophages with increase granulation. Activated monocytes Auer Rods Are red, needle-like structures thought to be accumulation of primary granules. Characteristic of acute myeloid leukemia. Auer Rods