Haematology: Leukocytes

Question	Answer
Two lineages from pluripotent stem cells:	Two lineages from pluripotent stem cells: Myeloid series which arises from myeloid stem cells; Erythrocytes, megakaryocytes, monocytes and granulocytes. Lymphoid series which arises from lymphoid stem cells; T lymphocytes, Natural killer lymphocytes and B lymphocytes
Assessment of blood: Quantitative assessment: Qualitative assessment:	Assessment of blood: Highly automated using haematology analyzer giving high accuracy leukocyte differentials. Qualitative assessment is obtained from blood films and bone marrow biopsy. Bone marrow biopsy involves the use of a trephine needle inserted into the posterior superior iliac crest (PSIC) with the patient lying in the recovery position.
Pancytopenia: Causes:	Pancytopenia: Anaemia, thrombocytopenia and neutropenia. Due to reduced marrow production. Causes: 1. Infiltration of the bone marrow: Metastatic cancer Leukemia Lymphoma 2. Aplasia-hypoplasia of bone marrow: High dose chemotherapy, radiation Aplastic anaemia (rare, autoimmune condition) 3. Drugs: Chemotherapy 4. Myelofibrosis: 5. Ineffective hematopoiesis: Myelodysplastic syndrome Megaloblastic anaemia
Leukoerythroblastic blood film:	Leukoerythroblastic blood film: A sign of a full bone marrow. Often primary myelofibrosis or metastatic cancer. Usually associated with pancytopenia. See immature WBCs (myelocytes) and RBCs (nucleated or tear-drop shaped).
Neutrophils: Maturation sequence: Immature neutrophil count: Mature neutrophil count: Function: Neutrophil adhesion, migration and invagination:	Neutrophils: Maturation sequence: Myeloblast, promyelocyte, myelocyte, metamyelocyte, band neutrophil and segmented neutrophil. Immature neutrophil count: Promyelocytes, myelocytes and metamyelocytes. Mature neutrophil count: Band and segmented neutrophils. Function: Search, ingest and destroy bacteria. Neutrophil adhesion, migration and invagination: Firstly, the neutrophils adhere to the endothelium via expression of selectins and integrins. They then migrate along the endothelium following chemokines. Finally, they migrate between epithelial cells into the area in a process called diapedesis (Rolling, slow rolling, arrest, crawling, interstitial migration).
Neutrophils can die via two ways: NETosis (Neutrophil extracellular traps): Roles for NETosis in disease:	Neutrophils can die via two ways: Apoptosis (anti-inflammatory effects) and NETosis (pro-inflammatory effects). NETosis (Neutrophil extracellular traps):Neutrophils release their genomic DNA which is rich in histones and proteases, in which bacteria are held captive and killed. Roles for NETosis in disease: NETosis is quite common in SLE: Low density granulocytes (a subset of abnormal neutrophils with high expression of TNF and IFN 1) have been identified in SLE and undergo spontaneous NETosis. In gout, aggregated neutrophil extracellular traps limit inflammation by degrading chemokines and cytokines
Isolated neutropenia causes:	Isolated neutropenia causes: Usually chemotherapy. Drug induced (affects the bone marrow or causes immunologic destruction). Genetic variants e.g ethnic. Acute viruses such as EBV. Acute severe bacterial infection- transient due to increased utilization (rare but important)
Neutropenia: Critical cutoff: If febrile: If afebrile:	Neutropenia: Critical cutoff; 0.4x109/L (0.3-0.5). If febrile, admit for IV antibiotics. If afebrile, then establish a diagnosis, withdraw drugs as needed and possibly admit.
Neutrophilia: Elevated neutrophils: Causes:	Neutrophilia: Elevated neutrophils; >7.5x109/L Causes: Bacterial infection such as in pneumonia, tonsillitis where there is left shift to immature cells. In the presence of inflammation as occurs with myocardial infarction. Steroids can cause softening of the neutrophil cytoskeleton and reduced selectin binding resulting in reduced margination resulting in increased circulating neutrophils. Paraneoplastic syndromes such as lung cancer (non small cell types). Leukemia of the myeloid cell lineage e.g chronic myeloid leukemia.
Reactive neutrophil changes in severe inflammation:	Reactive neutrophil changes in severe inflammation: Toxic granulation: Increased numbers and sizes of lysosomal granules. Vacuolation: Phagosomes/phagolysosomes. Dohle body: Patch of blue (immature) cytoplasm.
Monocytes: Function: Mature from ________in the bone marrow. They become ______ in tissues. They constitute ____ of all cells in every organ	Monocytes: Function: Phagocytose. Sometimes show fine granules. Mature from monoblasts in the bone marrow. They become macrophages in tissues. They constitute 10-15% of all cells in every orga
Monocytosis: Causes: To distinguish between the two:	Monocytosis: Monocytes >1.0x109/L Causes: Reactive chronic inflammatory states: Prolonged or chronic bacterial infection such as after several days of pneumonia or tuberculosis Myelodysplastic syndrome, especially the subtypes chronic myelomonocytic leukemia (CMML). To distinguish between the two, do a CRP, which is normal in MDS.
Eosinophilia: Causes:	Eosinophilia: >0.4x109/L. Causes: Parasitic infection. Allergic reactions. Involved in multiple immunological networks but their role is far from clear. IL-5 from T cells, mast cells and macrophages stimulates eosinophil production.
Basophils: Function: Clinical utility:	Basophils: <0.3% of all leukocytes. Involved in allergic reactions and defence against parasitic infections (worms and ticks). In the lab, an elevated basophil count makes us suspicious of CML, but otherwise no clinical utility.
Leukocytes: 3 main cell types in blood:	Leukocytes: 3 main cell types in blood: T lymphocytes 60-80% B lymphocytes 15-30% NK cells 5-10%
Lymphocytosis: Causes in children: Causes in adults:	Lymphocytosis: Causes in children: Viral infections (CMV, EBV) Pertussis (whooping cough). Acute lymphoblastic leukemia (usually B cell). Causes in adults: EBV, CMV (CD8 T cells). HIV (CD8 T cells). Leukemia (T or B cells). Post splenectomy. Smoking.
Counting and identifying lymphocytes: Techniques: CD19 is expressed 0n__, CD3 on ___ and CD16/CD56 expressed on____.	Counting and identifying lymphocytes: Blood film. Flow cytometry used to characterize lymphocytosis > 40 years of age. CD19 is expressed on B cells, CD3 on T cells and CD16/CD56 expressed on NK cells.
Lymphopenia: Not very useful clinically since we usually know the cause:	Lymphopenia: Not very useful clinically since we usually know the cause: Lymphoma. Drugs: Immunosuppressive or cytotoxic agents: Prolonged steroid use. Methotrexate for connective tissue disorder; MTX therapy is associated with pneumocystis carinii pneumonia. HIV (low CD4 count). Stress (high endogenous steroid-cortisol).
Natural killer cells/large granular lymphocytes: Function:	Natural killer cells/large granular lymphocytes: Function: role in the innate immune system to protect against cancer and autoimmune diseases. Chronic low grade proliferations common in the elderly; associated with neutropenia but not problematic.
Glandular fever-acute EBV infection: Epstein Barr virus infects: The large atypical lymphocytes in blood: Infectious mononucleosis is a crazy name since: Any age can be affected: Symptoms: Acute CMV: Symptoms: Seroprevalence and clinical concern:	Glandular fever-acute EBV infection: Epstein Barr virus infects B cells. The large atypical lymphocytes in blood are reactive T cells. Infectious mononucleosis is a crazy name since monocytes are not involved. Any age can be affected; usually 0-40 years. Symptoms: Fever, bilateral enlargement of lymph nodes, sore throat and tonsillitis, enlarged spleen (rarely ruptured). Mild hepatitis, transient neutropenia and thrombocytopenia. Acute CMV: Virtually identical to EBV; lymphadenopathy, lymphocytosis with reactive lymphocytes, fatigue and mild hepatitis. Seroprevalence is similar to EBV but we notice it less often; probably not as important clinically,

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	Created by Ashutosh Kumar about 7 years ago