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My Beloved Neutrophil Dr Boxer 2014 Neutropenia Family Conference
The Beloved Neutrophil: Its Function in Health and Disease Stem Cell Multipotent Progenitor Myeloid Lymphoid CMP IL-3, SCF, GM-CSF CLP Committed Progenitor MEP GMP GM-CSF, IL-3, SCF EPO TPO G-CSF M-CSF IL-5 IL-3 SCF RBC Platelet Neutrophil Monocyte/ Basophil B-cells Macrophage Eosinophil T-Cells Mast cell NK cells Mature Cell Dendritic cells PRODUCTION AND KINETICS OF NEUTROPHILS CELLS % CELLS TIME Bone Marrow: Myeloblast 1 7 - 9 Mitotic Promyelocyte 4 Days Myelocyte 16 Maturation/ Metamyelocyte 22 3 – 7 Storage Band 30 Days Seg 21 Vascular: Peripheral Blood Seg 2 6 – 12 hours 3 Marginating Pool Apoptosis and ? Tissue clearance by 0 – 3 macrophages days PHAGOCYTOSIS 1. Mobilization 2. Chemotaxis 3. Recognition (Opsonization) 4. Ingestion 5. Degranulation 6. Peroxidation 7. Killing and Digestion 8. Net formation Adhesion: β 2 Integrins ▪ Heterodimer of a and b chain ▪ Tight adhesion, migration, ingestion, co- stimulation of other PMN responses LFA-1 Mac-1 (CR3) p150,95 a2b2 a CD11a CD11b CD11c CD11d b CD18 CD18 CD18 CD18 Cells All PMN, Dendritic Mac, mono, leukocytes mono/mac, PMN, T cell LGL Ligands ICAMs ICAM-1 C3bi, ICAM-3, C3bi other other Fibrinogen other GRANULOCYTE CHEMOATTRACTANTS Chemoattractants Source Activators Lipids PAF Neutrophils C5a, LPS, FMLP Endothelium LTB4 Neutrophils FMLP, C5a, LPS Chemokines (a) IL-8 Monocytes, endothelium LPS, IL-1, TNF, IL-3 other cells Gro a, b, g Monocytes, endothelium IL-1, TNF other cells NAP-2 Activated platelets Platelet activation Others FMLP Bacteria C5a Activation of complement Other Important Receptors on PMNs ñ Pattern recognition receptors – Detect microbes - Toll receptor family - Mannose receptor - bGlucan receptor – fungal cell walls ñ Cytokine receptors – enhance PMN function - G-CSF, GM-CSF - TNF Receptor ñ Opsonin receptors – trigger phagocytosis - FcgRI, II, III - Complement receptors – ñ Mac1/CR3 (CD11b/CD18) – C3bi ñ CR-1 – C3b, C4b, C3bi, C1q, Mannose binding protein From JG Hirsch, J Exp Med 116:827, 1962, with permission. -
Leukemoid Reaction in a Patient with Acute Lymphoblastic Leukemia Following the Second Chemotherapy
262JCEI / Yokuş et al. Leukemoid reaction in ALL 2013; 4 (2): 262-263 Journal of Clinical and Experimental Investigations doi: 10.5799/ahinjs.01.2013.02.0280 LETTER TO EDITOR Leukemoid reaction in a patient with acute lymphoblastic leukemia following the second chemotherapy Akut lenfoblastik lösemili hastada ikinci kemoterapi sonrası gelişen lökomoid reaksiyon Osman Yokuş1, Murat Albayrak2, Aynur Albayrak3, Habip Gedik4 To the Editor, to 50.000 cells/µL. The examined peripheral blood smear appeared as similar to the chronic phase of The occurrence of persistent neutrophilic leukocy- CML (fig.2). A cytogenetic examination of Philadel- tosis above 50,000 cells/µL for reasons other than phia chromosome [t(9:22] was found to be nega- leukemia is defined as leukemoid reaction. Chronic tive, therefore, CML was excluded in the patient. myelogenous leukemia (CML) and chronic neutro- Hydroxurea was initiated once a day. Leukocytosis philic leukemia (CNL) should be excluded, and un- recovered to normal range after one week (fig.3) derlying diseases or causes should be examined, and bone marrow examination revealed remission. in differential diagnosis. The most commonly ob- Cytogenetic analysis was normal and this leukocy- served causes of leukemoid reactions are severe tosis was determined as reactive leukemoid reac- infections, intoxications, malignancies, severe hem- tion. We aimed to report this case owing to the fact orrhage, or acute hemolysis [1]. J Clin Exp Invest that leukocytosis associated with G-CSF, which is 2013; 4 (2): 262-263 used to increase the leukocyte count during neutro- Rarely, leukemoid reaction can be seen in pa- penia, has been reported previously but it occurred tients with acute leukemia subsequent to chemo- after second chemotherapy without G-CSF [4]. -
Wikipedia: the Term Leukemoid Reaction Describes an Elevated White Blood
Correspondence: I. Potasman, MD Leukemoid Reaction: Spectrum and Prognosis of 173 Adult Patients Infectious Diseases, ABSTRACT No. Bnai Zion Med. Ctr. 47 Golomb St., Haifa 31048. 39147 Israel Potasman, MD and Moti Grupper, MD Tel. 972-48359055 Fax. 972-48359755 Bnai Zion Med. Ctr., Haifa, Israel Email: [email protected] LR- CLINICAL and LABORATORY FEATURES CHRONIC DISEASES & CONDITIONS CAUSING LR METHODS WikipediA: The term leukemoid reaction describes an elevated white blood cell count, or leukocytosis, that is a physiological response to stress or infection (as Table 1: Leukemoid Reaction: Demographics, Major Clinical, and Laboratory features, and Table 2: Chronic & possible Instigating diseases Causing Leukemoid Reaction (n=173) The BZMC is a 411 bed university hospital located in Haifa, Israel. Mortality (n=173) Disease/Drug Occurrences (%) opposed to a primary blood malignancy, such as leukemia). Contains all basic departments except for neurosurgery, cardiovascular surgery and solid-tumor oncology. The respi- Parameter N (%) Alive Dead n Age (years, mean ±S.D.) 69.4 ±19.6 63.3±21.2 79.4±11.2 Background ratory intensive care unit inhabits six patients; additional respirators are in use in the 3 departments of medicine. History of Cardiovascular 86 (49.7%) Minimal-Maximal 21-97 21-97 28-97 ABSTRACT During an average year there are 29,508 hospitalizations of adults (>18 years) with ~150,000 hospitalization-days, Median 75 69 81 disease Diabetes Mellitus 46 (26.6%) and an average occupancy of 92%. Patients were eligible throughout hospital stay, and wherever they were admit- Chronic Lung disease 29 (16.8%) ted. -
Practice Parameter for the Diagnosis and Management of Primary Immunodeficiency
Practice parameter Practice parameter for the diagnosis and management of primary immunodeficiency Francisco A. Bonilla, MD, PhD, David A. Khan, MD, Zuhair K. Ballas, MD, Javier Chinen, MD, PhD, Michael M. Frank, MD, Joyce T. Hsu, MD, Michael Keller, MD, Lisa J. Kobrynski, MD, Hirsh D. Komarow, MD, Bruce Mazer, MD, Robert P. Nelson, Jr, MD, Jordan S. Orange, MD, PhD, John M. Routes, MD, William T. Shearer, MD, PhD, Ricardo U. Sorensen, MD, James W. Verbsky, MD, PhD, David I. Bernstein, MD, Joann Blessing-Moore, MD, David Lang, MD, Richard A. Nicklas, MD, John Oppenheimer, MD, Jay M. Portnoy, MD, Christopher R. Randolph, MD, Diane Schuller, MD, Sheldon L. Spector, MD, Stephen Tilles, MD, Dana Wallace, MD Chief Editor: Francisco A. Bonilla, MD, PhD Co-Editor: David A. Khan, MD Members of the Joint Task Force on Practice Parameters: David I. Bernstein, MD, Joann Blessing-Moore, MD, David Khan, MD, David Lang, MD, Richard A. Nicklas, MD, John Oppenheimer, MD, Jay M. Portnoy, MD, Christopher R. Randolph, MD, Diane Schuller, MD, Sheldon L. Spector, MD, Stephen Tilles, MD, Dana Wallace, MD Primary Immunodeficiency Workgroup: Chairman: Francisco A. Bonilla, MD, PhD Members: Zuhair K. Ballas, MD, Javier Chinen, MD, PhD, Michael M. Frank, MD, Joyce T. Hsu, MD, Michael Keller, MD, Lisa J. Kobrynski, MD, Hirsh D. Komarow, MD, Bruce Mazer, MD, Robert P. Nelson, Jr, MD, Jordan S. Orange, MD, PhD, John M. Routes, MD, William T. Shearer, MD, PhD, Ricardo U. Sorensen, MD, James W. Verbsky, MD, PhD GlaxoSmithKline, Merck, and Aerocrine; has received payment for lectures from Genentech/ These parameters were developed by the Joint Task Force on Practice Parameters, representing Novartis, GlaxoSmithKline, and Merck; and has received research support from Genentech/ the American Academy of Allergy, Asthma & Immunology; the American College of Novartis and Merck. -
Complete Blood Count in Primary Care
Complete Blood Count in Primary Care bpac nz better medicine Editorial Team bpacnz Tony Fraser 10 George Street Professor Murray Tilyard PO Box 6032, Dunedin Clinical Advisory Group phone 03 477 5418 Dr Dave Colquhoun Michele Cray free fax 0800 bpac nz Dr Rosemary Ikram www.bpac.org.nz Dr Peter Jensen Dr Cam Kyle Dr Chris Leathart Dr Lynn McBain Associate Professor Jim Reid Dr David Reith Professor Murray Tilyard Programme Development Team Noni Allison Rachael Clarke Rebecca Didham Terry Ehau Peter Ellison Dr Malcolm Kendall-Smith Dr Anne Marie Tangney Dr Trevor Walker Dr Sharyn Willis Dave Woods Report Development Team Justine Broadley Todd Gillies Lana Johnson Web Gordon Smith Design Michael Crawford Management and Administration Kaye Baldwin Tony Fraser Kyla Letman Professor Murray Tilyard Distribution Zane Lindon Lyn Thomlinson Colleen Witchall All information is intended for use by competent health care professionals and should be utilised in conjunction with © May 2008 pertinent clinical data. Contents Key points/purpose 2 Introduction 2 Background ▪ Haematopoiesis - Cell development 3 ▪ Limitations of reference ranges for the CBC 4 ▪ Borderline abnormal results must be interpreted in clinical context 4 ▪ History and clinical examination 4 White Cells ▪ Neutrophils 5 ▪ Lymphocytes 9 ▪ Monocytes 11 ▪ Basophils 12 ▪ Eosinophils 12 ▪ Platelets 13 Haemoglobin and red cell indices ▪ Low haemoglobin 15 ▪ Microcytic anaemia 15 ▪ Normocytic anaemia 16 ▪ Macrocytic anaemia 17 ▪ High haemoglobin 17 ▪ Other red cell indices 18 Summary Table 19 Glossary 20 This resource is a consensus document, developed with haematology and general practice input. We would like to thank: Dr Liam Fernyhough, Haematologist, Canterbury Health Laboratories Dr Chris Leathart, GP, Christchurch Dr Edward Theakston, Haematologist, Diagnostic Medlab Ltd We would like to acknowledge their advice, expertise and valuable feedback on this document. -
Management of Hepatic Burkitt Lymphoma in Children
Gastroenterology & Hepatology International Journal ISSN: 2574-8009 Management of Hepatic Burkitt Lymphoma in Children Elhoudzi J* and Harif M Case Report Pediatric Hematology & Oncology Department, University Hospital Center, Morocco Volume 3 Issue 1 Medical school of Marrakesh, Cady Ayad University, Morocco Received Date: June 02, 2018 Published Date: June 15, 2018 *Corresponding author: Jamila Elhoudzi, Pediatric Hematology & Oncology Department, University Hospital Center, Morocco, Ibn Sina street, Ammerchich, 40000, Morocco, Tel: 00212661544256; Email: [email protected] . Abstract Hepatic Burkitt lymphoma is extremely rare in childhood and can be overlooked in differential diagnosis of liver masses. Patient: A8-year-old girl presented with a 1 month history of abdominal pain and weight loss and jaundice. Results: Physical examination revealed hepatomegaly and no palpable lymph node. Laboratory finding showed mild anemia (hemoglobin, 10,8 g/dL), elevated transaminase (ALT, 305 IU/L; ASAT,755 IU/L), elevated bilitubin (Bilirubin total, 179mg/L, Bilirubin direct, 143mg/l). Abdominal ultrasound shouwed a multiple hepatic lesions. Liver biopsy examination confirmed Burkitt's lymphoma. No metastasis was detected in the thoracic cavity, bone marrow, and spinal fluid. The patient was treated with the combination regimen of cyclophosphamide, doxorubicin, vincristine, prednisone and high dose methotrexate. Cytosine arabinoside and methotrexate were added for CNS prophylaxis by intrathecal installation. Serial follow-up ultrasound showed a marked decrease in the size of hepatic lesions but residual hilar lymph nodes at 2cm and the control showed stable size of lymph node after 28 months of chemotherapy. Conclusion: The clinical feature of primary hepaticlymphoma varies from no symptom to fulminant hepatic failure. There are no specific imaging criteria for diagnosing primary hepatic Burkitt’s lymphoma. -
University of Birmingham the Primary Immunodeficiency Disorders
University of Birmingham The primary immunodeficiency disorders Shields, Adrian; Patel, Smita Y DOI: 10.1016/j.mpmed.2017.07.011 License: Creative Commons: Attribution-NonCommercial-NoDerivs (CC BY-NC-ND) Document Version Peer reviewed version Citation for published version (Harvard): Shields, A & Patel, SY 2017, 'The primary immunodeficiency disorders', Medicine, vol. 45, no. 10, pp. 597-604. https://doi.org/10.1016/j.mpmed.2017.07.011 Link to publication on Research at Birmingham portal Publisher Rights Statement: Shields, A. Patel, S. (2017) The primary immunodeficiency disorders, Medicine, volume 45, issue 10, pages 597-604, https://doi.org/10.1016/j.mpmed.2017.07.011 General rights Unless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or the copyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposes permitted by law. •Users may freely distribute the URL that is used to identify this publication. •Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research. •User may use extracts from the document in line with the concept of ‘fair dealing’ under the Copyright, Designs and Patents Act 1988 (?) •Users may not further distribute the material nor use it for the purposes of commercial gain. Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document. When citing, please reference the published version. -
BHS Leucocytosis and Leucopenia Dr Caers
Leucocytoses & leucopenia Jo Caers Dept of Clinical Hematology [email protected] Bone marrow Blood Granulopoiesis Proliferation & 5 days maturation Storage 1 day Marginisation& Circulation 1 day Tissues 1-2 days Granulopoiesis Proliferation & 5 days maturation Storage 1 day Marginisation& Circulation 1 day Tissues 1-2 days Granulopoiesis Proliferation & 5 days maturation Storage 1 day Marginisation& Circulation 1 day Tissues 1-2 days Lymphocytes Monocytes NORMAL BLOOD CELL COUNT Hemoglobin 12.0 – 15.0 g/dl (F) 13.0 – 17.0 g/dl (M) Red Blood Cells 3.9 – 5.6 x 10 6/µl (F) 4.5 – 6.5 x 10 6/µl (M) Hematocrit 36 – 48% (F) 40 – 52% (M) Mean Corpuscular Volume 80 – 95µ³ Mean Hb Concentration 27 – 34 pg Conc corp mean Hb 30 – 35 g/dl Reticulocytes 0.5 – 20 % Leucocytes 4.0 – 10.0 x 10 3/µl ¨ Neutophils 1.8 – 7.5 Lymphocytes 1.5 – 3.5 Monocytes 0.2 – 0.8 Eosinophils 0.04 – 0.45 Basophils 0.01 – 0.1 Platelets 100 – 400 x 10 3/dl Hyperleucocytosis > 10.000 WBC/mm³ Normal Cells Abnormal cells or blastic cells Infections ? Neutrophilia (> 7.500/mm³) Acute Leukemias Lymphocytosis (> 4.500/mm³) Chronic Myelomonocytic Leukemias Chronic Lymhocytic leukemia Chronic Myeloid Leukemia Non Hodgkin Lymphoma Chronic Monocytosis (> 800/mm³) … Inflammations? Eosinophilia (> 400/mm³) Basophilia (> 100/mm³) Leukoerythroblastic reaction Cytopenia with immature RBCs (normoblasts) immature WBCs (agranular neutrophils, myelocytes, metamyelocytes ) Causes BM infiltration • Solid tumor or hematological malignancy • Myelofibrosis Strong BM stimulation • Infection, -
ESID Registry – Working Definitions for Clinical Diagnosis of PID
ESID Registry – Working Definitions for Clinical Diagnosis of PID These criteria are only for patients with no genetic diagnosis*. *Exceptions: Atypical SCID, DiGeorge syndrome – a known genetic defect and confirmation of criteria is mandatory Available entries (Please click on an entry to see the criteria.) Page Acquired angioedema .................................................................................................................................................................. 4 Agammaglobulinaemia ................................................................................................................................................................ 4 Asplenia syndrome (Ivemark syndrome) ................................................................................................................................... 4 Ataxia telangiectasia (ATM) ......................................................................................................................................................... 4 Atypical Severe Combined Immunodeficiency (Atypical SCID) ............................................................................................... 5 Autoimmune lymphoproliferative syndrome (ALPS) ................................................................................................................ 5 APECED / APS1 with CMC - Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) .................. 5 Barth syndrome ........................................................................................................................................................................... -
Reactive Splenomegaly and Variation of Lymphoid-Plasma Cell Population Associated with a Mouse Pituitary Thyrotropic Tumor*
Reactive Splenomegaly and Variation of Lymphoid-Plasma Cell Population Associated with a Mouse Pituitary Thyrotropic Tumor* EDITH E. SPROULANDRAUL GRINBERG (Rosiceli Park Memorial Institute and New York Slate Department of Health, Buffalo, New York) SUMMARY A transplantable thyrotropic pituitary tumor, subline L24a, which grew after 13 months of dormancy in an intact mouse was associated in its early passage with a variety of lymphoid tumors. On subsequent passage, slow growth over a 6- to 12- month period was regularly accompanied by striking splenomegaly without lymphoid or thymic neoplasia. The enlargement was due to a great increase in cells of the lymphoid series in the red pulp without loss of splenic architecture. In thyroidec- tomized mice plasma cells with many Russell bodies were especially numerous, and these cells were found hi hypertrophied lymphoid follicles within other organs. It is suggested that the splenomegaly and, hi earlier passage the lymphoid tumors, may represent an exaggerated antibody response to a tumor's having unusual or abnormal hormonal activity. The transplanted pituitary tumors, in turn, showed severe hemor- rhagic degeneration with peripheral small lymphocyte stasis in the lymphatics. Initial observations concerning pleomorphic reticulum through the courtesy of Dr. Jacob Furth, was studied cell- and lymphosarcomas or lymphoid hyperplasias through repeated passage for purposes of comparison. regularly accompanying a thyrotropic mouse pituitary This tumor has maintained uniform behavior with rapid neoplasm, subline L24a, have been reported (22). The autonomous growth, active secretion of TSH, and a sex original L24 pituitary tumor was developed by Dr. Jacob dependence which was lacking in the L24 line. A mam- Furth by I131thyroid ablation. -
Leukemias Leukemia - Tumor Disease of the Blood System Is Characterized by Three Main Features: 1
Leukemias Leukemia - tumor disease of the blood system is characterized by three main features: 1. Hyperplasia - proliferation of tumor, or a germ hematopoiesis in places where it should be in a normal state (in the bone marrow); 2. Anaplasia - is when the processes of proliferation (cell proliferation) prevails over the differentiation process; 3. Metaplasia - tumor proliferation, of any germ hematopoiesis in places where it should not be (inside the body, the brain, etc.), with an expanding germ hematopoiesis displaces local tissue elements, replacing them with a. Currently, this process is called metastasis. Unlike leucocytosis, leukemoid reactions and other reactive hematopoietic tissue growths at the base of leukemia is uncontrolled (unlimited) cell proliferation in violation of their ability to differentiation and maturation. Loss of ability to mature leukemia cells can take place much more than normal blood cells, the number of cycles of division, and that creates a huge cell production that characterizes leukemia. The etiology of leukemia to date is not certain. On the tumor nature of leukemia indicated by the presence of the general laws that unite leukemias and tumors: a violation of the cell's ability to differentiate; morphological and metabolic anaplasia cells; common etiological factors contributing to the development of leukemia and tumors, and others. The possible etiologic factors causing the development of leukemia, include ionizing radiation, a number of chemicals, viruses. Some importance in the development of leukemia is attached to genetic factors, hereditary and acquired immune deficiency action blastomogenic metabolite of tryptophan and tyrosine. Theories of the origin of leukemia. Radiation theory. The role of ionizing radiation in causing leukemia was proved experimentally. -
Vesiculopustular Eruption in a Neonate with Trisomy 21 Syndrome As a Clue of Transient Myeloproliferative Disorders
PEDIATRIC DERMATOLOGY Series Editor: Camila K. Janniger, MD Vesiculopustular Eruption in a Neonate With Trisomy 21 Syndrome as a Clue of Transient Myeloproliferative Disorders Fiammetta Piersigilli, MD; Andrea Diociaiuti, MD; Renata Boldrini, MD; Cinzia Auriti, MD; Marco Curci, MD; Maya El Hachem, MD; Giulio Seganti, MD We report the case of a vesiculopustular erup- some reports describe it in neonates who, despite tion associated with a transient myeloprolifera- being phenotypically normal, are mosaic for tri- tive disorder (TMD) in a neonate with trisomy 21 somy 21 syndrome.2-4 Between 20% and 30% of infants syndrome. Examination of a skin biopsy showed with TMD eventually have a leukemia relapse, usu- a dermal mixed inflammatory infiltrate including ally within a few years after resolution of TMD and atypical megakaryoblasts. As the white blood cell most frequently acute megakaryoblastic leukemia.5 count spontaneously normalized, the eruption Leukemia cutis is found in approximately 25% to disappeared. This case report and review of the 30% of all neonates with congenital leukemia.6 The literature demonstrates thatCUTIS a vesiculopustular typical skin lesions are blue or violaceous nodules eruption could be an important clue to identify measuring approximately 1 to 2 cm in diameter, TMD in a neonate. sometimes accompanied by ecchymoses. Histologic Cutis. 2010;85:286-288. examination reveals a dermal infiltrate of leukemic cells. Leukemoid reactions and TMDs also can be associated with various cutaneous manifestations eonates with trisomy 21 syndrome are at such as vesiculopustular eruptions7 that spontane- Doincreased risk for the developmentNot of leuke- ously resolveCopy without treatment. The development of N moid reactions, transient myeloproliferative pustules in a neonate requires a differential diagnosis disorders (TMDs), and congenital leukemia.