Leukocyte Disorders. Dr Alauldeen Mudhafar Zubair
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1 Leukocyte Disorders Dr Alauldeen Mudhafar Zubair
2 Composition of blood Specialized connective tissue Blood cells (formed elements) suspended in plasma Blood volume: 5-6 liters (approx 1.5 gal) in males and 4-5 liters in females Dr. Alauldeen Mudhafar Zubair 2
3 Blood Centrifuged (spun) to separate Clinically important hematocrit % of blood volume consisting of erythrocytes (red blood cells) Male average 47; female average 42 Plasma at top: water with many ions, molecules, and 3 types of important proteins: Albumin Globulins Fibrinogen Dr. Alauldeen Mudhafar Zubair 3
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5 Serum Blood that is allowed to stand clots Clot is a tangle of the formed elements (some are not truly cells) RBCs lack nuclei and organelles Platelets are fragments Most cannot divide Clear fluid serum is left = plasma without the clotting factors When spun in centrifuge, buffy coat lies between RBCs and plasma: of leukocytes (white blood cells) and platelets Dr. Alauldeen Mudhafar Zubair 5
6 Scanning EM Blood is examined in a smear Smears are stained Light microscope Dr. Alauldeen Mudhafar Zubair 6
7 Formation of blood cells Hematopoiesis Occurs mostly in red bone marrow All cells arise from same blood stem cell (pluripotent hematopoietic stem cells) Recently some have been found in adults which are mesenchymal stem cells, which can also form fat cells, osteoblasts, chondrocytes, fibroblasts and muscle cells Dr. Alauldeen Mudhafar Zubair 7
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9 Blood stem cells divide into: 1.myeloid stem cells or 2.lymphoid stem cells All except for lymphocyte s arise from myeloid stem cells All originate in the bone marrow Dr. Alauldeen Mudhafar Zubair 9
10 As the cells divide they become committed, that is, they can only become one kind of cell Also called CFU s (colony-forming units) Structural differentiation occurs Dr. Alauldeen Mudhafar Zubair 10
11 CBC is probably commonest test done ( complete blood count -how much of each type of cell) Hemoglobin (gm/dl) usually 15 Hematocrit (%) RBC count WBC in thousands/cumm Differential if ordered: broken down to amount of each type WBC Platelet count in thousands/cumm Dr. Alauldeen Mudhafar Zubair 11
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18 Leukocytes AKA WBCs: white blood cells Dr. Alauldeen Mudhafar Zubair 18
19 RBC Leukocytes neutrophil basophil eosinophil AKA WBCs: white blood cells Are complete cells Function outside the blood small lymphocyte monocyte Note the size difference compared to erythrocytes Dr. Alauldeen Mudhafar Zubair 19
20 Granulolcytes, which include three types of cells: neutrophils, eosinophils & basophils; together with monocyte comprise the phagocytes. Normally only mature phagocytic cells and lymphocytes are found in the peripheral blood. Lymphocyte, their precursor cells and plasma cells make up the immunocytes. Dr. Alauldeen Mudhafar Zubair 20
21 Leukocyte types Artificial division into granulocytes and agranulocytes Granulocytes: neutrophils, eosinophils, basophils (according to how stain) Granules Lobed nuclei All are phagocytic Agranulocytes: lymphocytes, monocytes Dr. Alauldeen Mudhafar Zubair 21
22 All arise from stem cells All originate in the bone marrow Not shown are mast cells, osteoclasts, dendritic cells Dr. Alauldeen Mudhafar Zubair 22
23 60% of all WBCs Nuclei of 2-6 lobes Other names: Neutrophils Polymorphonuclear cells (PMNs, polys, segs) Granules have enzymes Can damage tissue if severe or prolonged Pus Dr. Alauldeen Mudhafar Zubair 23
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25 Eosinophils 1-4 % of leukocytes Bilobed Granules have digestive enzymes Role in ending allergic reactions and in fighting parasitic infections Dr. Alauldeen Mudhafar Zubair 25
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27 Rarest WBC Bilobed nucleus Dark purple granules Basophils Later stages of reaction to allergies and parasitic infections Dr. Alauldeen Mudhafar Zubair 27
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29 * Lymphocytes* Most important WBC 20-45% Most are enmeshed in lymphoid connective tissue, e.g. lymph nodes, tonsils, spleen Dr. Alauldeen Mudhafar Zubair 29
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31 Lymphocytes: Nucleus occupies most of the cell volume Response to antigens (foreign proteins or parts of cells) is specific. Two main types attack antigens in different ways: T cells B cells plus natural killer cells Dr. Alauldeen Mudhafar Zubair 31
32 T cells attack foreign cells directly Killer cells ( cytotoxic ), or CD8+ is a main type Dr. Alauldeen Mudhafar Zubair 32
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34 B cells Differentiate into plasma cells Plasma cells secrete antibodies Antibodies flag cells for destruction by macrophages (see stem cell chart) Dr. Alauldeen Mudhafar Zubair 34
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36 Monocytes * 4-8% of WBCs In connective tissue they transform into macrophages (phagocytic cells with pseudopods) Dr. Alauldeen Mudhafar Zubair 36
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40 Normal Values: for adult Caucasian Total leukocytes X 10 9 /l Neutrophils X 10 9 /l Eosinophils X 10 9 /l Monocytes X 10 9 /l Basophils X 10 9 /l Lymphocytes X 10 9 /l Normal black and Middle Eastern subjects may have lower counts due to margination. Dr. Alauldeen Mudhafar Zubair 40
41 Development in the bone marrow (14 days) Myeloblast Promyelocyte Myelocyte Metamyelocyte Band Neutrophils. These stages are seen only in the bone marrow in healthy people. However, they appear in peripheral blood in pathological conditions. Dr. Alauldeen Mudhafar Zubair 41
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44 Granulopoiesis The blood granulocytes and monocytes are formed in the bone marrow from a common precursor cell. Large numbers of band and segmented neutrophils are held in the marrow as a reserve pool or storage compartment. Dr. Alauldeen Mudhafar Zubair 44
45 The bone marrow normally contains more myeloid cells than erythroid cells. In the stable or normal state, the bone marrow storage compartment contains times the number of granulocytes found in the peripheral blood. Dr. Alauldeen Mudhafar Zubair 45
46 In the bloodstream there are two pools usually of about equal size: the circulating pool (included in the blood count) and the marginating pool (not included in the blood count). Dr. Alauldeen Mudhafar Zubair 46
47 Following their release from the bone marrow, granulocytes spend only 6 10 hours in the circulation before moving into the tissues where they perform their phagocytic function. They spend on average 4 5 days in the tissues before they are destroyed during defensive action or as the result of senescence. Dr. Alauldeen Mudhafar Zubair 47
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51 Classification of Leukocyte Disorders: Benign or Malignant Hereditary or Acquired Functional or Numerical Morphological Dr. Alauldeen Mudhafar Zubair 51
52 Congenital Variations in Morphology Barr bodies: Drumstick appendage in females, it represents inactive X chromosome. Dr. Alauldeen Mudhafar Zubair 52
53 Pelger Huet anomaly: bilobed neutrophil Dr. Alauldeen Mudhafar Zubair 53
54 Neutrophil Hypersegmentation: Autosomal Dominant Dr. Alauldeen Mudhafar Zubair 54
55 Chediak-Higashi syndrome: is a rare autosomal recessive disorder characterized by oculocutaneous albinism, recurrent and severe bacterial infections, giant blue-grey granules in the cytoplasm of granulocytes, monocytes & lymphocytes, a mild bleeding diathesis, progressive peripheral neuropathy and cranial nerve abnormalities. Dr. Alauldeen Mudhafar Zubair 55
56 Chediak-Higashi Syndrome Oculocutaneous albinism Photophobia Sun sensitivity Neuropathy Infections, esp Staph aureus W. B. Saunders Adv Neonatal Care TX: BMT Dr. Alauldeen Mudhafar Zubair 56
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60 Acquired Toxic Granulation: Infection Hypersegmented Neutrophils: megaloblastic anemia, cytotoxic drugs Pseudo- Pelger Huet(acquired): in myelodysplasia Dr. Alauldeen Mudhafar Zubair 60
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62 Shift to the left: increase in the number of band forms and the occasional presence of more primitive cells in the peripheral blood. Leukoerythroblastic picture: a presence of a shift to left plus nucleated RBC in the peripheral blood. Dr. Alauldeen Mudhafar Zubair 62
63 Causes of leucoerythroblastic blood film Metastatic neoplasm in the marrow Primary myelofi brosis Acute and chronic myeloid leukaemia Myeloma, lymphoma Miliary tuberculosis Severe megaloblastic anaemia Severe hemolysis Osteopetrosis Dr. Alauldeen Mudhafar Zubair 63
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66 The Leukomoid Reaction: a reactive excessive leukocytosis with the presence of immature cells (myeloblasts, promyelocytes and myelocyte) in the peripheral blood. In other words (leukocytosis + left shift). Usually it is a neutrophil leukocytosis. It can be lymphoid Causes : 1. Severe infection 2. Severe haemolysis 3. Metastatic cancer Dr. Alauldeen Mudhafar Zubair 66
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68 Variations in Number: Neutrophilia Causes are: 1. Infection (bacterial) 2. Inflammatory conditions 3. Neoplasia 4. Metabolic conditions 5. Hemorrhage, Hemolysis 6. MPD Dr. Alauldeen Mudhafar Zubair 68
69 7. Drugs (e.g. corticosteroid therapy (inhibits margination): lithium, tetracycline) 8. Treatment with myeloid growth factors (e.g. G - CSF) 9. Rare inherited disorders 10. Asplenia Dr. Alauldeen Mudhafar Zubair 69
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71 Neutropenia The lower limit of the normal neutrophil count is 2.5 *10 9 /L except in black people and in the Middle East where 1.5 *10 9 /L is normal. When the absolute neutrophil level falls below 0.5 *10 9 /L the patient is likely to have recurrent infections Dr. Alauldeen Mudhafar Zubair 71
72 Neutropenia Causes are: 1. Congenital (Kostmann s syndrome) 2. Cyclical neutropenia 3. Marrow aplasia 4. Megaloblastic anemia 5. Infections (typhoid, miliary TB, viral hepatitis) 6. Drugs 7. Irradiation 8. Immune disorders 9. Hypersplenism Dr. Alauldeen Mudhafar Zubair 72
73 Eosinophilia Causes are: 1. Parasitic infection 2. Skin disorders 3. Allergic conditions 4. Neoplasia 5. Myeloproliferative disorders 6. Hypereosinophilic syndrome Dr. Alauldeen Mudhafar Zubair 73
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75 Basophilia: An increase in blood basophils above 0.1 *10 9 /L is uncommon. The usual cause is a myeloproliferative disorder such as chronic myeloid leukemia or polycythaemia vera. Reactive basophil increases are sometimes seen in myxoedema, during smallpox or chickenpox infection and in ulcerative colitis. Dr. Alauldeen Mudhafar Zubair 75
76 Monocytosis: A rise in blood monocyte count above 0.8 *10 9 /L is infrequent. Causes are: Chronic bacterial infections: tuberculosis, brucellosis, bacterial endocarditis, typhoid Connective tissue diseases SLE, temporal arteritis, rheumatoid arthritis Protozoan infections Chronic neutropenia Hodgkin lymphoma, AML and other malignancies Chronic myelomonocytic leukemia Dr. Alauldeen Mudhafar Zubair 76
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78 Lymphocytosis Causes are: 1. Viral infections (infectious mononeuclosis, infectious lymphocytosis, CMV etc). 2. Bacterial infections: (Pertussis, occasionally healing TB, Brucellosis, Secondary and Congenital Syphilis, Typhoid fever, Diphtheria) 3. Protozoal infections: Toxoplasmosis 4. Lymphoproliferative Disorders: CLL, Lymphoma Dr. Alauldeen Mudhafar Zubair 78
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