MLAB 1415- Hematology Keri Brophy-Martinez
Chapter 19: Granulocyte and Monocyte Disorders Review: Neutrophil Function
The contents of primary, secondary and tertiary granules in neutrophils are enzymes which are involved in killing and digesting bacteria and fungi. Review: Neutrophil Function
Primary function is phagocytosis which occurs in three stages. Stage 1: Migration and diapedesis Chemotaxis is the process of directional migration which occurs under the guidance of chemoattractants which are produced by the site of injury. The neutrophil transforms from smooth and round to rough and flat. Diapedesis is the movement of the neutrophil through the vessel wall. Review: Neutrophil Function
Stage 2: Opsonization and recognition Opsonization is the mechanism which facilitates recognition and attachment to the organism to be ingested. After the bacteria is coated by immunoglobulin and complement, it is referred to as an opsonin. Review: Neutrophil Function
Stage 3: Phagocytosis: Ingestion, killing and digestion The cytoplasm of the neutrophil forms a pseudopod which surrounds and envelops the microorganism forming a vacuole called a phagosome. Cytoplasmic granules migrate to the vacuole and release their lytic contents which kill and digest the organism. Disorders Affects granulocytes and monocytes
Response to various nonmalignant disease states and toxic changes Changes can be qualitative or quantitative Terms Leukocytosis Leukopenia
Total leukocyte count is more than 11.0 x 109/L in adult Most commonly caused by increase in neutrophils Leukopenia Decrease in leukocytes below 4.5 X 109/L Most commonly caused by decrease in neutrophils Disorders of Neutrophils: Quantitative
Causes Malignant Neoplastic transformation of hematopoietic stem cell (discussed later) Benign Acquired Neutrophilia: increase in total circulating absolute neutrophil concentration Neutropenia Neutrophilia ANC > 7.0 x 109/L
Occurs as a result of a reaction to a pathologic or physiologic process (reactive neutrophilia) Immediate Increase lasts about minutes Redistribution of neutrophils from marginal pool to circulating pool Neutrophils are mature Seen in acute exercise, anxiety shift neutrophilia or pseudoneutrophilia Acute Occurs 4-5 hours post-pathologic stimulus (i.e bacterial infection) Increase in flow of neutrophils from the bone marrow pool to the blood Immature neutrophils numbers may increase Chronic Follows acute neutrophila, if the stimulus continues beyond a few days Storage pool in bone marrow depletes Bone Marrow show increased numbers of early neutrophil precursors shift to the left Conditions Associated with neutrophilia
Reactive Chronic neutrophilia Leukocytes< 50 x 10 9/L Shift to the left Presence of toxic granulation, Dhle bodies and cytoplasmic vacuolization Dohle bodies Toxic granulation Neutrophilic Conditions
Bacterial Infection Most common cause of neutrophilia Seen with staphylocci and streptococci infections Bone marrow increases output of storage neutrophils to peripheral blood, see shift to the left Physiologic leukocytosis No shift to the left Birth to the first days of life Childbirth Extreme temperatures Emotional stimuli Tissue destruction/Injury, Metaboloic disorders Neutrophil input is increased from the bone marrow to the tissue Examples include: Rheumatoid arthritis, burns, gout, uremia, trauma Neutrophilic Conditions
Leukoerythroblastic reaction Presence of nRBCs Shift to the left Poik, tear drops, aniso Associated with chronic neoplastic myeloproliferative conditions Neutrophilic Conditions
Leukemoid reaction Leukocytes> 50 x 10 9/L Advanced degree of leukocytes in the blood that is not a result of leukemia Transient; leaves when stimulus is removed Many circulating immature leukocyte precursors seen Seen in chronic infections, carcinoma of certain organ systems Blood picture similar to chronic myelocytic leukemia(CML) Leukocyte Alkaline Phosphatase, is used to differentiate leukemoid reaction from CML LAP increased in leukemoid reaction, decreased in CML Neutropenia ANC 0.8 x 109/L
Seen in inflammatory conditions and malignancies Monocytopenia AMC < 0.2 x 109/L Seen in stem cell disorders Qualitative LIPID (LYSOSOMAL)STORAGE DISEASES Inherited disorders
Accumulation of unmetabolized material in the lysosomes of various cells.They are caused by various enzyme defects (inborn errors) in lipid metabolism linked to an enzyme deficiency Three main disorders Disorder #1 Gauchers Disease Enzyme deficiency: -glucocerebrosidase
Prevalent in the Ashkenazi Jewish population (eastern European) Macrophage can not digest the stroma of ingested cells Results in an accumulation of glucocerebroside Gauchers Cell Large histiocyte (20-100 m)
Displaced nucleus which contains one or more round nucleoli Cytoplasm is faintly blue/white with characteristic crumpled tissue paper appearance which is probably the result of glycolipid deposition Disorder #2 Niemann-Pick Disease Enzyme deficiency: sphingomyelinase
Increased incidence in the Jewish population Causes an accumulation of unmetabolized sphingomyelin and cholesterol Classic form presents with jaundice at birth, hepatosplenomegaly, enlarged lymph nodes, neurological symptoms, retarded physical and mental development. Death occurs by age 3. Niemann-Pick Cell Lipid-laden giant foamy cell found in BM, tissues and other organs Disorder #3 Tay Sachs Disease Enzyme deficiency: hexosaminidase A
Higher incidence in Ashkenazi Jewish population Severity of the disease correlates with residual enzyme activity. The buildup of unmetabolized GM2 ganglioside in the tissues has devastating effects in the central nervous system and eye. Physical and mental deterioration occur along with seizures and paralysis.Death comes by age 4. Tay Sachs Disease Foamy lymphocytes are present but are not diagnostic
The blue cells seen here are abnormally enlarged neurons