Haematology 1 PDF

Haematology & Haemopoiesis Gavin Knight  Learning Objectives On completion of this session you should be able to: 1. Recognise the key cellular components of the peripheral blood. 2. Identify and use the correct terminology to describe blood cell development.  Normal Blood smear...

Haematology & Haemopoiesis Gavin Knight  Learning Objectives On completion of this session you should be able to: 1. Recognise the key cellular components of the peripheral blood. 2. Identify and use the correct terminology to describe blood cell development.  Normal Blood smear phagocytic Neutrophils · bacteria debris > Engulgs , (granulocyte) gorm ture-band ma less · Produce Antihistamine (in contrast to histamine) Eosinophil · Usegul Worm in killing infections ogg blood based · Part of the primary (granulocytes) Loading… haemostatic > - process interaction between platelets I ~ and blood vessels in order prevent blood to extravasating · Involved in Allergy platelet · Both reactive to allergic reaction (thrombocyte) Lymphocyte M · B cells and T cells Adaptive response Basophil · immune · Produce vasoactive compounds that blood vessel (granulocytes) cause dilation to · Produces - ↑ blood > flow inflammatory histamine Response Romanowsky stain (puberty Stage pallor Haemoglobina not mature Area of central · > · leave bone marrow , enter peripheral blood · Circulate as monocytes before extravasate into tissues · CarryO around the body Become macrophages lungs Monocyte = Carry CO2 back to Red cells · · phagocytic cells > - Also presents antigens · Maintain Acid-base homeostasis Important terminology 1) Haemopoiesis: Can also be: ‘haima’ – blood Haematopoiesis (UK) ‘poiesis’ – to make but not: hemopoiesis/hematopoiesis (US) 2) Subdivided into: Erythropoiesis Granulopoiesis Myelopoiesis Monopoiesis Generation of myeloid cells Thrombopoiesis Lymphopoiesis Summary The term haemopoiesis describes the production of blood cells Haemopoiesis can be further subdivided to describe the process of specific blood cell populations The effector cells: erythrocytes, leukocytes and thrombocytes all Loading… play a vital role in a variety of physiological processes Haemopoiesis: sites and drivers Gavin Knight  Learning Objectives On completion of this session you should be able to: Explain the general processes of blood cell development. Outline the key growth factors involved in blood cell development. Discuss the sites of blood cell development. Outline the morphological characteristics of blast cells.  Haemopoietic sites Sites of haemopoiesis depend upon age. Stage of Gestation Site development Embryo 0 – 2 months Yolk sac Foetus 2 – 7 months 5 – 9 months Loading… Liver, spleen Bone marrow https://obimages.net/free-chapter-normal-abnormal-first- trimester-exam/ Infants N/A All bones – bone marrow Adults N/A Vertebrae, ribs, sternum, skull, sacrum, pelvis, Bone marrow cellularity (%) = 100 - Age proximal ends of G looks Red at Marrow different types = Haemopoietic of Jone marrow marrow we have produces blood cells As age ↑ ↓ femur = Yellow Marrow = Adipose tissue ↑  Bone marrow architecture trephine http://www.sysmex.nl/nl-en/media-centre/normal-bone-marrow-cytology-7595.html Couple ways to assess Jone marrow function and appearance : Bone liquid biopsy Aspirate take of bonearrow. · marrow - a Bone trephine · marrow Core - biopsy taken of bone marrow tissue / L trabecula (supporting Structure) · Erythod precursore eus is lost = become · E3-E4 = different stages of red cell development; Ly – lymphocyte; Mega – · precurso megakaryocyte; Promy – promyelocyte, my – myelocyte, meta – metamyelocyte, platelets Platelets will bud · off band - band form; SC – stromal cell, Seg – segmented neutrophil cell membrane and release into peripheral circulation  Where does blood cell development begin? Begins with pluripotent stem cells Involves the formation of ‘blasts’ Key morphological features of blasts include: Loading… 1. High nucleocytoplasmic ratio = usually Nucleus made up of chromatin opened closed configuration Prominent nucleoli important 2. ribosome > - Can have or C = in 3. Open chromatin configuration · Actively transcribinga Translate 4. Basophilic cytoplasm · polypeptide present = mRNA Sequence (colour) Blasts then mature in a lineage specific manner in response to growth factors End result = effector cells Overview of Haemopoiesis: Myelopoiesis Pluripotent stem cell terleukins GIL-3 · Communication molecules · WBCs SCF CFU BFU GEMM CFU EMEG GMEo TPO GM-CSF BFUE -thrombopoietin Granulocyte macrophage colony stimulating factor CFU CFU GM CFUEo CFUBaso EPO ↳ MEG Erythropoietin M- G- IL-5 CSF CSF Colony ↳ CFUE CFUM CFUG Basophils Red cells Platelets Monocytes Neutrophils Eosinophils Basophils - Overview of Haemopoiesis: Lymphopoiesis IL-3 IL-1 IL-6 Pluripotent stem cell - CFU-L CFU-GEMM Pre B-cell Thymocyte ↓ IL-4 B-cell IL-2 T-cell IL-7 Summary Sites of haemopoiesis becoming restricted during ageing The bone marrow is the principal site of haemopoiesis in the adult Examination of the bone marrow are useful when trying to identify diagnosing cancers of the blood Haemopoiesis is a dynamic, linear process and understanding the morphological changes of cells through their development can help us understand haematological diseases Growth factors are important drivers of haemopoiesis and allow the bone marrow to respond to environmental demands Erythropoiesis Gavin Knight  Learning Objectives On completion of this session you should be able to: Explain the process of red cell development. Identify the principal hormone involved in the production of red cells. Recognise the different erythroid intermediates. Explain the consequences of a failure of erythropoiesis.  Erythropoiesis erythroid cells ↳ Begins with CFU-GEMM maturing into BFUEMEG then BFUE - Burst BFUE differentiate into CFU-E Unit forming > Colony - forming unit Late BFUE and CFUE express EPO receptors (EPOR) BFU Kine se · = Cluster together ↳Foundin · CFU = More sporadically CFUE form proerythroblasts ↑O ↓ erythropoietina Spread the plate Loading… = hormone that drives red cell production , across deals transfersunibody iron ↑ > Capture Expression of the Transferrin receptor ensures iron availability Proerythroblasts mature into early, intermediate and then late erythroblasts > - > - configiration nucleus Cytoplasm Changes changes Late erythroblasts form reticulocytes following removal of nucleus ↳ no nucleus Mature red blood cells develop Failure of erythropoiesis results in anaemia  Pluripotent stem cell EPO signalling and Erythropoiesis SCF CFU GEMM BFU- GM- EMEG CSF BFU-E CFU-Meg CFU-GMEo CFU-Baso EPO TPO CFU-Eo CFU- GM CFU-E CFU-G CFU-M G-CSF M-CSF IL-5 IL-3 Bhoopalan SV, Huang LJ, Weiss MJ. Erythropoietin regulation of red blood cell production: from bench to bedside and back. F1000Res. 2020 Red cells Platelets Neutrophils Monocytes Eosinophils Basophils Erythropoiesis Loading… maturation BFUE Proerythroblast intermediate late Polychromatic red cell CFUE (Reticulocyte) Erythroblasts  Summary Erythropoiesis describes the production of red cells Dynamic process involving erythropoietin, synthesis of haemoglobin, the loss of organelles and removal of the cell nucleus Erythropoietin, synthesised in relatively hypoxic conditions in the kidney, promotes the survival, proliferation and maturation of red cell precursors Failure to produce sufficient red cells to meet the needs of the body results in anaemia Granulopoiesis and Monopoiesis Gavin Knight  Learning Objectives On completion of this session you should be able to: Explain the processes of granulopoiesis and monopoiesis. Describe the morphological characteristics of granulocyte progenitors. Outline the key growth factors involved in granulocyte and monocyte development. Explain the consequences of a failure in granulopoiesis and monopoiesis.  Granulopoiesis & Monopoiesis As with all myeloid lineages, begins at the CFU-GEMM stage Granulocyte-Macrophage Colony-Stimulating Factor GM-CSF and IL-3 induce production of CFU-GMEo and CFU-Baso CFU-GMEo differentiate further to CFU-GM and CFU-Eo Growth factors: Granulocyte colony Loading… Stimulating factor ~ G-CSF – neutrophils (on CFU-GM) - M-CSF – monocytes (on CFU-GM) Macrophage Colony-stimulating Factor IL-5 – eosinophils (on CFU-Eo) IL-3 – basophils (on CFU-Baso) Failure of granulopoiesis and monopoiesis results in neutropenia and monocytopenia - > Reduction thing in Granulocyte Progenitors · Cytoplasm of promyelocytes. Also, contain secondary granules contains primary granules. = Cell-specific granules > - Neutrophil = Fine violet granules Mayappear see Type , te myeloblast ↑ Eosinophil-Orange infection > - = no granules > Basophil = Dark purple + black cytoplasm Blast Promyelocyte myelocyte metamyelocyte with in Type II myeloblast = band neutrophi ,i eosinophil , basophi = few granules Scattered within = Effector Cytoplasm cells Loading… Mature All mitotic Maturation Monopoiesis form macrophages ↳ polymorphonuclear Cell E Development  Summary ⑧ Granulopoiesis and monopoiesis are dynamic processes that result in the development of neutrophils, eosinophils, basophils and monocytes ⑧ General and specific growth factors are responsible for terminal differentiation into terminally differentiated effector cells · Failure of granulopoiesis and monopoiesis results in a deficiency of effector cells, primarily neutrophils and monocytes, which will compromise the primary immune response Thrombopoiesis Gavin Knight · Production of Platelets  Learning Objectives On completion of this session you should be able to: Explain the process of platelet development. Discuss the roles of growth factors involved in thrombopoiesis. Explain the consequences of a failure in thrombopoiesis.  Thrombopoiesis Megakaryoblasts form from CFU MEG Nucleus undergoea ell · Undergo endomitotic replication division Megakaryocytes form Loading… Cells are polyploid Proplatelets form > platelets Platelets are released into venous sinuses IL-3, IL-6, GM-CSF and TPO critical https://imagebank.hematology.org/image/1164/megakaryocytic-maturation--2?type=upload Failure of thrombopoiesis leads to thrombocytopenia TPO signalling Peripheral blood (TPO circulating) Myeloproliferative Leukaemia · Protein Platelet membrane (TPO and MPL/TPOR binding) Cytoplasm (signal transduction and ironelst Pateletis · translation of mRNA into protein) , Modified from: https://www.researchgate.net/figure/Acti vated-c-Mpl-dimer-leads-to-activation- of-multiple-signaling-pathways-which- Nucleus (Transcription of mRNA) promote_fig1_343121005  Pluripotent stem cell SCF CFU GEMM CFU-L BFUEM GM- EG CSF BFU-E CFU-Meg Loading… CFU-GMEo CFU- Baso EP TP CFU-Eo CFU- GM O CFU-E O CFU-G CFU-M G- M- IL-5 IL- CSF CSF 3 Red cells platelets neutrophils monocytes eosinophils basophils Thrombopoiesis · multiple nuclei · Matelets start to shed Megakaryoblast Megakaryocyte Platelet budding Platelets (4-32n) (8-64n) Bone marrow Peripheral blood https://imagebank.hematology.org/image/1186/platel https://www.clevelandclinicmeded.com/medicalpubs/diseasemanage et-forming-megakaryocyte--1?type=upload ment/hematology-oncology/chronic-myeloproliferative-disorders/ https://www.bloodline.net/imageatlas/bone-marrow/  Summary Thrombopoiesis is the process of producing platelets Platelets are critically important in the process of primary haemostasis Platelet production is dependent upon TPO binding to TPO-R Signalling is also augmented by IL-3 and IL-6, the latter producing platelets during inflammation Failure to produce sufficient platelets causes thrombocytopenia which can lead to easy bruising and bleeding  LECTURE NOTES Erythrocytosis = RBCs unknown Cause , Polycythaemia = n RBCs , Clonal disease , one progenitor Tugor test-test for dehydration S -monolayer f => Cells should beapart overlapping Carboxy H : -> Prevents formation of OxyH > - Supresses O2 > - tissues - > Acute exposure Often gatal > - Chronic exposure = hypoxia = Compensatory erythrocytosis