Haematopoeisis Tutorial 1.

Haematopoiesis is the formation of blood cell components primarily in the bone marrow while coagulation is the process by which blood forms clots. a. Describe the three major branches of the myeloid pathways. Erythroid i!e rise to red blood cells Megakaryocytic Pro!ide blood "thrombocyte# $irst Maintain endothelium defence and against haemorrhage Phagocytic platelet Monocytic macrophage# ranulocytic bacterial repair eosinophilic& "neutrophilic& infection% allergy and "monocyte%

parasitic infection% basophilic& mast cell precursor#

b. 'hat are the functions of the mature granulocytes( )eutrophilic& bacterial infection Eosinophilic& allergy and parasitic infection *asophilic& mast cell precursor% ha!e histamine% generate !asoacti!e amines and )T c. 'hat are three important essential physiologic components go!erning haematopoiesis( +tem cell pool% hematopoietic cytokines% hematopoietic inducti!e microen!ironment ,. 'hat is meant by e-tramedullary haematopoiesis and when does the process occurred( E-tramedullary haematopoesis means haematopoesis that occurred outside the bone marrow% which is in the li!er and spleen% during malignancies of haematopoietic stem cell "impossible blood component production period# such as& . During haematopoietic stress . 'hen marrow is replaced by metastatic breast cancer or by fibrosis especially when it infiltrate the bone marrow /. 'hat are the roles of the haematopoietic stem cells( 'hat are some common surface markers on the early or undifferentiated H+0s( 'hat kinds of H+0 e-ist in the marrow( 1ole . 1eplenish blood cell& myeloid "platelet% 1*0% granulocyte% monocyte# and lymphoid "*. cell% T.cell#

+urface markers 2 0.3it "a.k.a 0D114% a type of receptor that binds to stem cell factor and acti!ates tyrosine kinase#% 0D/5 "an adhesion molecule for T.cell to enter lymph node# 6 H.,3 Types of H+0 e-ist in the marrow7 8ong.term H+0 2 for cell renewal +hort.term H+0 2 for cell proliferation in short time into myeloid and lymphoid cells 5. 'hat is meant by Haematopoietic 9nducti!e Microen!ironment( 'hat is the role of spindle. shaped ).cadherin.e-pressing :steoblasts "+):s# and multipotential progenitors "MPPs# in the bone marrow( +troma comprises endothelial cells% fibroblasts and macrophage . 1ich in haematopoietic cytokines "paracrine hormone# that act on stem cells and early committed progenitor cells . Pro!ide important sorting mechanism% which permits only most immature cells "stem cells% committed progenitor cells# and most mature cell "1*0% neutrophils% platelet# to e-it the marrow +pindle.shaped ).chaderin.e-ressing :steoblasts "+):s# maintain ;uiescence and pre!ent differentiation of attached haematopoietic stem cells . The ;uiescence endosteal niche would maintain dormant H+0s long.term . 9n response to injury% ;uiescent H+0s might be acti!ated and recruited to the !ascular niche "self.renewing niche would contain ;uiescent H+0s intermingled with di!iding H+0# Multipotetial progenitors "MPPs# gi!e rise to all haematopoietic lineages <. 'hat are some of the features which can differentiate bone marrow stromal cells and the H+0s( 'hen bone marrow dissociated and the mi-ture of cells it contains is plated at low density% the stromal cells adhere to the surface of the culture dish% but H+0 do not *one marrow stromal cells "in specific in vitro conditions# form colonies from a single cell called the colony forming unit.$ "0$=.$# that differentiate as adipocytes or myelosupporti!e stroma *one marrow stromal cells can proliferate up to /< population doublings in !itro >. 'hat are the commonly used cytokines in the therapy% its target treatments and the responding cells( ranulocyte.0olony +timulating $actor " .0+$# 1esponding cell7 )eutrophil Treatment7 )eutropenia

Erythropoietin 1esponding cell7 *lood cell Treatment7 ?naemia disease Mechanism "additional#7 produced primarily by cells in the kidney. 'hen : , le!el drops "hypo-ia#% it binds to erythroid precursor cell% proliferate and mature% forming mature 1*0 Thrombopoietin 1esponding cell7 Megakaryocyte Treatment7 Thrombocytopenia "low platelet count# M.0+$ 1esponding cell7 Myeloid cells Treatment7 0ause proliferation and differentiation of myeloid cells% stimulate stem cell to produce granulocyte and de!elop monocyte into macrophage 4. Describe the mobili@ation% homing and lodging of the H+0s. Mobili@ation ?fter e-tra!asation from the bone marrow into the micro!asculature% H+0s are mobili@ed into the circulation "in response to .0+$# and are distributed to peripheral tissues such as the spleen or li!er Homing H+0s home to the bone marrow through the circulation% controlled by a number of adhesion molecules such as A8?5 and A8?< 8odging ?fter entering the bone marrow% H+0s specifically lodge in the niche. 9t re;uires membrane. bound stem cell factor "+0$# and osteopontin ":P)# and corresponding receptors 0B015 and E.selectin C. 8ist out the factorsDagents that can affect haematopoiesis process. 'hat is aplastic anemia( 9nfections 2 !iral hepatitis% par!o!irus% +tar!ation Hereditary 2 $anconiEs anaemia syndrome ?plastic anaemia is a result of failed or damage of any haematopoiesis component "haematopoietic stem cells% cytokines% bone marrow microen!ironment#. *lood cell production in marrow ceased entirely or fell to a le!el that is insufficient to meet bodyEs need. 1esult is pancytopenia7 anaemia% leukopenia and thrombocytopenia

Etiology "causation 6 origin#7 e-posure to to-ic chemicals or ionising irradiation 0lassification7 Primary "idiophatic#% +econdary Treatment7 9mmunosuppressi!e theraphy "e.g. with antithymocyte globulin#% allogeneic bone marrow transplantation *lood clotting cascade 1. Describe the fibrinolytic pathway. $ibrinolytic pathway F $ibrinolysis "breaking down of fibrin# $ibrinogen is con!erted into fibrin.clot by clotting cascade "thrombin# $ibrin.clot is then con!erted into crosslinked fibrin meshwork by plasmin "acti!e form of plasminogen# Plasmin is acti!ated by tissue plasminogen acti!ator "T.P?# ,. Describe the blood clotting pathway cascade in the intrinsic pathway. 9n!ol!e acti!ation of factor 1,% 11% G% 1H and thrombin ?ffected by antithrombine 999DHeparin 3ininogen kallikrein acti!ate $actor 1, into $actor 1,a $actor 1,a "with 0a,I# acti!ate $actor 11 into $actor 11a $actor 11a acti!ate $actor G into $actor Ga $actor Ga "with 0a,I 6 cofactor Ca# acti!ate $actor 1H into $actor 1Ha $actor 1Ha "with 0a,I 6 cofactor <a# change prothrombin into thrombin $rom here% refer to answer for J1 /. Describe the common pathway between the e-trinsic and intrinsic pathways in the blood clotting cascade. $actor 1Ha "with 0a,I 6 cofactor <a# change prothrombin into thrombin $rom here% refer to answer for J1 5. Describe the blood clotting pathway cascade in the e-trinsic pathway and gi!e a laboratory test which is commonly used to e-amine the pathway. Defect tissue "with 0a,I# acti!ate $actor 4 into $actor 4a $actor 4 "with 0a,I 6 cofactor /# acti!ate $actor 1H into $actor 1Ha $actor 1Ha "with 0a,I 6 cofactor <a# change prothrombin into thrombin $rom here% refer to answer for J1

8ab test to test& e-trinsic pathway7 Juick"PT#. test intrinsic pathway7 acti!ated partial thromboplastin time K"a#PTT.testL <. 'hat are the purposes to in!estigate thrombin time "TT# and acti!ated partial thromboplastin time "?PTT#( Thrombin time "TT# Measure the time taken for clot to form 9n this test% more thrombin is added . . Hence clotting is e-pected to be faster than normal 9f TT is prolonged "slower#% it must be because of ;ualitati!e or ;uantitati!e fibrinogen defect& Defect 1eason Jualitati!e .$ibrinogen dysfunction "8ess% slower clot# Juantitati!e .8ess amount of fibrinogen .Thrombosis in blood !essel elsewhere "use D.Dimer test to check for thrombosis# acti!ated partial thromboplastin time "?PTT# To test for $actor 1,% 11% G% C% 1H% <% prothrombin and fibrinogen Prolonged ?PTT means . . Deficiency of any one of these factors or Heparin contamination