WBCs production(leucopoiesis): Note: this sheet contain only extra notes.j - leucopoiesis is the most complicated process in body because many reasons which are : 1- the production of many cells(monocyte, lymphocyte, neutrophil, etc.) 2- the process effected by many factors or hormones or cytokines or chemical substances ( more than 10 factors are affect WBCs production ). factors that affect WBCs also affect RBCs + platelet production. 3- these chemical factors produced from many sources. - the duration of leucopoiesis similar to duration of erythropoiesis which its about 3-7 days. - need 6 days to release to circulation (mature ) but in RBCs =2-3 days, and this the only different in WBCs +RBCs production process. - more than 6 factors affect mother stem cells, then these factors produce 2 types of cells : committed stem cell and bone marrow lymphocyte precursor. - some books say that bone marrow lymphocyte precursor originate from committed stem cell.
- cells that produce RBCs, platelet, WBCs,monocyte and lymphocyte affected by specific factors called colony stimulated factors. these factors distribute to make colony cells from committed stem cell. - why called colony stimulated factors? Because they make appropriate single cell to proliferate and make colony in culture medium so make many cells from one cell. - basophil need 2 cytokines IL- 3 and IL- 4.AND eosinophil need 2 cytokines IL- 5 and GM.CSF. - RBCs, platelet and cells which produce monocyte and neutrophil need G.CFS and M.CSF. - ALL FACTORS have overlap action on each others, so affect production of RBCs+ platelet as well as WBCs. TABLE 27-2 : THE Dr. read the table and focus on erythropoietin,scf,g.csf, M.CSF - Sources range from many cell types endothelium, fibroblast, macrophage, mast cell and plasma cell. - chemotaxis : attraction of WBCs by inflamed tissue and leave contacted tissue by chemical substances.. - almost all WBCs have enzymes (ex : peroxidase ) To engulf, kill and digest pathogens. - some abnormal conditions in count of WBCs :
1- when increase Number of WBCs : usually in infection(bacteria or viral ) all blood cells increase count put there is specific point for each type of them to reach to do their function normally this called leukocytosis but when cause is eliminate count return to normal level TABLE 19-2 : the Dr. read all the table (I think it's important ) - In these cases the account of them increase or decrease by specific causes but MORE IMPORTANT HIGH ACCOUNT conditions. - There is certain level which WBCs count become high and no return to normal this is called = leukemia, here number is greatly increase and uncontrolled production of WBCs. - causes of leukemia still unknown, but there are some factors that almost contribute in this disease : - 1- radiation ( like what happened in Nagasaki and Hiroshima) 2- environment : some areas make leukemia like in JORDAN ( south or north has more cases of leukemia) 3- certain chemical 4- genetic factors
5- Some acute viral infection, in certain people may become infected by leukemia after the infection which it has two forms acute and chronic infection. - symptoms of leukemia :paleness, pain, tendency to bleeding(coz deficiency of platelet ), bone pain and frequent infection ( similar to flu ). - 2 types of leukemia according to the origin of disease; lymphocytic and myelocytic. Also can divide to acute and chronic forms. - Acute leukemia usually appear in children and may in adult after chronic form (chronic but on an acute form ). - Chronic form is the most common type of leukemia in adult after age of 45 and symptoms like in acute form. - lymphocytic leukemia more curable than myelocytic if the diagnose happen early. - some patient may has a disease for 20 years and he don t know then May discovered by Routine check. - Leukemic patient has frequent infection due to leukemic cells are usually undifferentiated cells. -also leukemic cells make metastasis to surrounding areas. Platelet (thrombocyte) - develop from megakaryocyte in bone marrow
- single megakaryocyte produce 4000 platelet s, in some books 10,000 or 20,000 platelets. I'm sorry I can't hear the record at 26:00 - need 10 days to differentiate of platelet from stem cell remember in WBCs AND RBCs need 6 days. - production is regulated by thrombopoietin which produced by kidney more than liver. - no different in count between male and female. - Survival time 7-14 days. - Usually no change in its count by different conditions like WBCs (different count during day- night ). - contain substances in granules or in cytoplasm which important in blood clotting and hemostasis. - 2 types of granules in platelet 1- electron dense granules 2- specific Alpha granules. - there is another type called cytoplasmic granules : substances inside cytoplasm not in granules. - examples of these granules : Alpha granules Acid hydrolysis Fibrinogen fibronectin electron dense granules nucleotide ADP serotonin Cytoplasmic granules K+ Mg++ histamine
heparin Ca++ Adrenalin Factor 8 Catecholamine Albumin, plasmin thromboglobulin Prostaglandin Thromboxian A 2 25%of bone marrow RBCs and along with these there - are megakaryocyte and platelet )but bone marrow contain 1 days reserve of platelet therefore human suspected to produce thrombocytopenia faster than leukcytopenia or erythrocytopenia - platelet contain substances responsible for normal integrity of blood vessel, in sever platelet deficiency RBCs migrate from blood vessel to tissue. - platelet play essential role hemostasis and blood clotting. - in hemostasis (stop blood loss from injured blood vessel by 3 process : A- vasoconstriction of injured blood vessel (very fast action). B- form platelet plug. C- form blood clotting. A- How vasoconstriction Is produced? 1- mild** contraction; because of injury ( I'm not sure What he said )
2- substances produced by injured endothelial cells or plasma or platelet, and these are : Endothelin 1>> from injured endothelium cell Adrenalin >> by either plasma or rupture platelet. Serotonin >> from platelet The result is reducing blood flow Thromboxane A2 >> platelet B- Formation of platelet plug: 1- platelet adhesion ;when blood vessel injured collagen released and they are good surface for platelet adhesion 2- release the action (stimulate and rupture platelet either from cytoplasm or granules ) 3- aggregation of platelet and accumulate platelet above each others. 4- coagulation action ; by production of phospholipid medium. 5- Injury infused and platelet fusion. - for platelet adhesion 2 factors are needed : first Factor is glucoprotein- 1 in platelet membrane if it deficient no adhesion property ) and factor 8 : its protein that produced by endothelial cell or by platelet. - Platelet has several function parts Factor 8 von Willebrand for adhesion Factor 8- Related Antigen for aggregation Factor 8 C: for clotting
3- Platelet release : when Platelet exposed to collagen- ADP- fibrinogen- serotonin cytokine- thrombin all are released during aggregation. - thromboxane A2 is produced very potent vasoconstriction of blood vessel and essential for aggregation. - people use aspirin as preventive medicine in specific doses to prevent dangerous platelet aggregation. - 2 substances are produce to inhibit farther aggregation and these are vasodilator they are produce from platelet, endothelium and injured cells, they are nitric oxide(no) and prostacyclin => to prevent spread of aggregation to surrounding area. 3- coagulation production : "formation of phospholipid" when thromboxane A2 work probably then platelet will aggregate, after that phospholipid and factor 8 von Willebrand are produced,platelet now available for coagulation process.(this surface is ideal template for orientation of protein for normal coagulation cascade reaction ).
5- platelet fusion : high concentration of ADP=> enzyme release during reaction, thromboxane function as irreversible function at platelet aggregation. Also Thrombin => for fusion of platelet at site of injury. Fibrin => reinforce stability of platelet clot. Sorry for any mistake ووما تددرريي بما فعلل االددعاء قالل االامامم االشافعي : ااتهھززا أ بالددعاء ووتززددرريیهھ لهھا اامدد ووللامدد اانقضاء سهھامم االليیلل لا تخططا وولكنن