Blood PDF

The Blood Dr Pip Garner Clinical Sciences [email protected]  Learning Objectives Describe structure & function of the blood Describe the cells of the blood Explain the origins of blood cells Expla...

The Blood Dr Pip Garner Clinical Sciences [email protected]  Learning Objectives Describe structure & function of the blood Describe the cells of the blood Explain the origins of blood cells Explain the functions and production of RBCs Explain functions and production of platelets Explain haemostasis Explain blood typing Describe some blood related disorders Functions and properties Liquid connective tissue (supports, connects, separates different tissues) Extracellular matrix is called plasma 1. Transports: dissolved gasses, hormones, nutrients, heat & waste (lungs, liver, GI, kidneys, endocrine glands etc) 2. Regulation: pH- buffers, temperature (absorbing & blood flow) and osmosis (dissolved ions) 3. Protection: clot, WBC’s, antibodies, interferon's and other proteins Physical properties (thicker Denser and more viscous than water 38⁰C, slightly alkaline When saturated with oxygen is bright red, unsaturated is dark red 8% of body mass 4-6 litres depending on gender & size Blood volume and osmotic pressure is tightly regulated by hormones (aldosterone, ADH, anti natiuretic peptide) Sampled by venipuncture with a torniquet X Method of sampling blood by injecting needle into the vein Blood components Blood components Formed elements i. RBC’s ii. Platelets iii. WBC’s a. Granular Neutrophils Eosinophils Basophils a. Agranular leuckocytes T & B lymphocytes Monocytes leukocytes BEN Granular leukocytes Agranular leukocytes T & B cells Haematocrit Men = more testosterone = more erythropoietin = ↑ RBC production Volume taken up by RBC’s Females 38-46% Males 40-54% Testosterone caused erythropoietin, produces RBC Anaemia = less RBC & RBC mass Polycythemia = 65%. Increased viscosity increases resistance, heart works harder. Increase blood pressure and stroke risk. Causes include improper RBC production, tissue >- hypoxia, dehydration and blood doping Illegal way of RBC & - ↑ less 02 Production  The Blood I Describe structure & function of the blood Describe the cells of the blood Explain the origins of blood cells Explain the functions and production of RBCs Explain functions and production of platelets Explain haemostasis Explain blood typing Explain some blood related disorders Blood cell formation Some lymphocytes have a life time of years Most formed elements have hours, days, weeks so need replacement Negative feedback controls RBC & platelet number WBC number varies with infection infection ↑ WBC count = Haemopoiesis = formation of blood cells Occurs in red bone marrow Red vs Yellow Bone Marrow Red bone marrow In newborns all marrow is red, is converted to yellow over time Process can be reversed under trauma Home of pluripotent stem cells (can repopulate yellow ~ marrow) can differentiate into any cell Bone marrow exam To diagnose disorders such as leukaemia Morphology granularity Nuclear defects counts Blood cell formation Platelets Blood cell formation Pluripotent stem cells in RBM produce 2 subtypes of stem cells Myeloid stem cells & lymphoid stem cells Myeloid stem cells develop in the RBM and give rise to platelets, RBC, monocytes, neutrophils, eosinophils and basophils Lymphoid stem cells begin to develop in the RBM but end in lymphatic tissues, they give rise to the lymphocytes Lymphatic tissue lymphatic system is a network of small vessels which carry lymph. Lymph fluid: Carries waste products around your body Carries cells that are part of your immune system Your lymph vessels take the fluid to your lymph nodes(also called lymph glands). Haemopoiesis Some myeloid stem cells differentiate into progenitor cells, others & the lymphoid stem cells develop straight into precursor cells Progenitor cells cannot reproduce, they are committed to forming their designated cell type (CFU eg CFU-E) Precursor cells (blasts) over several divisions develop into the actual formed elements of blood Blood cell formation Cytokines CSFs IL’s Production Erythropoietin Thrombopoietin M (kidney) (liver) maturation RBC production of platelets Medical uses of Haemopoietic growth factors Recombinant growth factors Erythropoietin for kidney disease Granulocyte CSF for WBC formation after chemotherapy Thrombopoietin for chemotherapy Also used for clotting disorders & a range of neonatal disorders  The Blood Describe structure & function of the blood Describe the cells of the blood Explain the origins of blood cells Explain the functions and production of RBCs Explain functions and production of platelets Explain haemostasis Explain blood typing Explain some blood related disorders Red Blood cells (erythrocytes) Contain oxygen carrying haemoglobin Produce 2 million RBCs per sec Blood contains 5 million per μl No nucleus or mitochondria- anaerobic respiration only, flexible, bi-concave Red Blood cells (erythrocytes) 5-8% of CO2 in the body is bound physically to haemoglobin Bind & carry NO for vasodilation and thrombotic L X blood clot widening of blood vessels regulation control & of formation = ↓ bp ↑ blood flow Carbonic anhydrase, creates carbonic acid which dissociates into bicarbonate ions (HCO3-), is important for buffer control and plasma to carry CO2 Red Blood cell life cycle RBCs are rapidly damaged in transit They contain no nucleus or other organelles so cannot synthesise proteins for repair As the PM become fragile they may burst Ruptured RBC are removed by fixed macrophages Their contents are re-cycled Red Blood cell lifecycle endocytosis storage Iron overload and tissue damage Fe2+ + Fe3+ bind to and damage cells Plasma doesn't contain free iron Iron carrying proteins can be overloaded Iron-dependent microbes Erythropoiesis RBC production starts in RBM with the precursor cell type pro-erythroblast They divide several times, producing cells which make haemoglobin Eventually they differentiate into reticulocytes, which eject their nuclei They pass into the blood and differentiate into RBC Erythropoiesis Erythropoiesis sometimes doesn't keep up with red cell demand Can lead to hypoxia Can be due to anaemia or dietary deficiencies Can be caused by circulatory problems Blood doping Injection of epoetin alfa (used to treat anemia) Caused 15 deaths in competitive cyclists in the 1980s Hard to measure Kenya for natural blood doping  The Blood Describe structure & function of the blood Describe the cells of the blood Explain the origins of blood cells Explain the functions and production of RBCs Explain functions and production of platelets Explain haemostasis Explain blood typing Explain some blood related disorders Platelets Thrombopoietin causes haemopoietic stem cells to differentiate into megakaryoblasts, which produce megakarocytes Small anucleate cells required for haemostasis 150000 – 400000/ml Life span 5-9 days Platelets Haemostasis Upon injury the following occur 1. Vascular spasm: arteries/ arterioles constrict to reduce blood flow 2. Platelet plug formation 3. Blood clotting Platelet plug formation Platelet plug formation Requires exposure of extracellular matrix proteins o vWF o Fibrinogen Converts to fibrin for blood clotting) o Collagen Requires several steps o Adhesion o Outside-in signalling- integrin activation o Secretion o Aggregation o Thrombin production Platelets Blood clotting: coagulation Extrinsic has fewer steps and is rapid. Is initiated by TF leaking into the blood from cells outside the blood stream Intrinsic is more complex and is slower. Outside tissue damage is not needed e.g. caused by endothelial cell damage Blood clotting: coagulation Blood clotting: coagulation Intrinsic is more complex and is slower. Outside tissue damage is not needed e.g. caused by endothelial cell damage 1. Surface contact activates FXII 2. FXIIa activates FXI and releases bradykinin (a vasodilator) from HMWK 3. Ca2+ & FXIa activate FIX, a serine protease 4. FIXa hydrolyses FX (along with Ca2+, and phosphatidylserine on activated platelets, and FVIIIa- the tenase complex) 5. FVIII is a co factor activated by thrombin from platelets 6. FX is activated leading to the common pathway Blood clotting: coagulation Extrinsic has fewer steps and is rapid. Is initiated by TF leaking into the blood from cells outside the blood stream FVII is activated by thrombin and FXa (from the intrinsic pathway) FVIIa and its cofactor TF (FIII) activate FX Common pathway FXa cleaves prothrombin (FII) on the surface of activated platelets (creates a prothrombinase complex with Ca2+ , phospholipids, prothrombin, FXa and FVa) FV is activated by small amounts of thrombin Fibrinogen is converted to fibrin by thrombin Thrombin also activates FXIII which cross-links the fibrin clot Fibrinolysis for clot localisation The clot plugs the ruptured area Clot retraction is the tightening of the fibrin clot The fibrin threads attached to the damaged surfaces of the blood vessel contract as platelets pull on them This pulls the edges of the wound together Fibrinolysis dissolves small inappropriate clots and dissolved clots as sites of repair Inactive plasminogen is incorporated into the clot Is activated to plasmin by substances in the body tissue (thrombin and t-PA) Plasmin digests fibrin threads and inactivates fibrinogen, prothrombin and FV and FXII Fibrinolysis for clot localisation Thrombin Activatable Fibrinolysis Inhibitor Fibrinolysis for clot localisation Haemophilia A (X linked leading to FVIII deficiency)  Extrinsic pathway (assessed by prothrombin time (PT) by addition of TF to plasma) is fine  Intrinsic pathway does not work (assessed by activated partial thrombosplastin time- APTT)- phospholipids are added to mimic contact factor  Affects 1:5000 males Haemophilia B (Christmas disease, X linked disorder leading to FIX deficiency)  Has a normal PT time but abnormal APTT time. Affects 1:30 000 males  The Blood Describe structure & function of the blood Describe the cells of the blood Explain the origins of blood cells Explain the functions and production of RBCs Explain functions and production of platelets Explain haemostasis Explain blood typing Explain some blood related disorders Blood groups Surface of RBCs contains range of glycoproteins and glycolipids which act as antigens Blood groups: Tranfusions Blood groups: Rhesus Don't normally have Rh antibodies Can develop them after blood transfusion, causes problem for later transfusions Haemolytic disease of the new born At child birth  The Blood Describe structure & function of the blood Describe the cells of the blood Explain the origins of blood cells Explain the functions and production of RBCs Explain functions and production of platelets Explain haemostasis Explain blood typing Explain some blood related disorders  This part of the session will run more as a workshop, please make sure you have access to a device in the session to do some research/answer questions Thrombosis (blood clotting within a vessel) and atherosclerosis Anticoagulants, aspirin and thrombolytic agents Warfarin: vitamin K antagonist to prevent Vitamin K is needed for production of many clotting factor activation clotting factors so blocking Its warfarin reducing blood clotting action, EDTA: to chelate calcium in donated blood removing it calcium clotting is essential for cascade, prevents clotting Aspirin: inhibits TxA2 synthesis Involved in platelet aggregation By reducing this , aspirin ↓ the likelihood. of clot formation Streptokinase: activates t-PA This down activates fibrin Plasmin clots ,. Plasmin breaks effectively dissolving and existing ↑ clots preventing new ones forming How do each of these treatments specifically stop blood clotting? Anaemia File:Symptoms of anemia.png Reduced oxygen carrying capacity 1. Iron- deficiency 2. Megaloblastic 3. Pernicious 4. Haemorrhagic 5. Haemolytic 6. Thalassemias How specifically do each of these kinds of anaemia cause problems? Sickle-cell disease Haemophilia Haemophilia A (X linked leading to FVIII deficiency) Haemophilia B (Christmas disease, X linked disorder leading to FIX deficiency) How do these deficiencies lead to excessive bleeding? Blood clotting: coagulation Fibrinolysis for clot localisation breaking down blood clots Haemophilia A (X linked leading to FVIII deficiency)  Extrinsic pathway (assessed by prothrombin time (PT) by addition of TF to plasma) is fine  Intrinsic pathway does not work (assessed by activated partial thrombosplastin time- APTT)- phospholipids are added to mimic contact factor  Affects 1:5000 males Haemophilia B (Christmas disease, X linked disorder leading to FIX deficiency)  Affects 1:30 000 males oncogenesis Leukaemias: production of malignant WBC cells, supress production of all normal cells in RBM Oncogenes: cause malignancy when mutated leading to their activation (growth factors, receptors, DNA binding proteins) Tumour suppressor genes: cause malignancy when mutated leading to their suppress growth) Why can leukaemia cause bleeding problems and anaemia? leukaemia leukaemia Acute lymphoblastic leukaemia: short onset, derived from lymphoid stem cells. Most common in children Acute myelogenous leukaemia. Affects all ages Chronic lymphoblastic leukaemia. Most common in adults (55+) Chronic myelogenous leukaemia: prolonged onset, derived from myeloid stem cells. Mostly in adults Causes often unknown but can be radiation or chemotherapy, genetics (down syndrome), environmental factors, viral e.g. Epstein-Barr virus Bone Marrow Transplant Replacement of cancerous or abnormal red bone marrow with healthy RBM Patient RBM is destroyed by chemotherapy and whole body radiation Healthy RBM can be from a donor or patient if in remission Marrow migrates to red bone marrow cavities and multiplies Can create graft vs. host disease Need to stay on immunosuppressant's  The Blood Describe structure & function of the blood Describe the cells of the blood Explain the origins of blood cells Explain the functions and production of RBCs Explain functions and production of platelets Explain haemostasis Explain blood typing Explain some blood related disorders