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Transcript
Physiology and histology of white blood cells and platelets 1. Outline the physiological role of white blood cells White blood cells (leukocytes) divided into: Granulocytes (contain lobed nucleus) o Neutrophils o Eosinophils o Basophils Agranulocytes (contain unlobed, rounded nucleus) o Monocytes o Lymphocytes Lymphocytes and monocytes circulate in the blood and are also contained in lymph nodes, thumus, spleen, tonsils, adenoids and Peyer patches. Lymphoid cells are also contained in the bone marrow, lungs, GIT and other tissue (not as much as in the lymphoid organs) WBC respond to foreign bodies presented to the cell and work to discard them Reactive proliferations of WBC occur during inflammatory responses. This is termed leukocytosis. During acute inflammation there is a release of cytokines (IL-1 and TNF) and this stimulates bone marrow stem cells and T cells to produce increased amounts of colony-stimulating factors that enhance differentiation and proliferation of granulocyte progenitor cells therefore increases production of neutrophils. Other growth factors stimulate other WBC. IL-5 enhances differentiation and proliferation of eosinophils. IL-7 enhances differentiation and proliferation of lymphocytes. Causes of leukocytosis Mechanism Endotoxemia Increased release from bone marrow Acute infection hypoxia Exercise Epinephrine Decreased margination Glucocorticoids Decreased extravasation into tissues Chronic infection or inflammation Increased numbers of marrow precursors. Tumours Myeloproliferative disorders Reference: Kumar et al, 2005 p. 664 2. Describe the role of platelets, endothelium and coagulation factors in the maintenance of the integrity of the vascular compartment Platelets circulate in blood plasma and are membrane bound smooth discs expressing a number of glycoprotein receptors of the inegrin family on their surfaces. They contain 2 types of granules: Alpha granules o Express P-selectin on their membranes o Contain fibrinogen, fibronectin, factors V and VIII, platelet factor 4, platelet derived growth factor and transforming growth factor β Dense bodies (δ granules) o Contain ADP and ATP, ionised calcium, histamine, serotonin and epinephrine After a vascular injury, platelets encounter collagen, proteoglycans, fibronectin and other adhesive glycoproteins all found in the extracellular matrix (ECM), beneath the endothelium. Once they encounter the ECM, platelets undergo 3 reactions: Adhesion and shape change o Mediated largely via interactions with von Willebrand factor (vWF). This acts as a bridge between platelet surface receptors (glycoprotein Ib and factors V and IX) and exposed collagen Secretion (release reaction) o Secretion of the contents of both granule types occurs soon after adhesion. o This process is initiated by binding of agonists to platelet surface receptors Aggregation o ADP mediates platelet aggregation, causes further ADP release from other platelets which leads to surface expression of phospholipid complexes which provide binding sites for Ca and coagulation factors in the intrinsic clotting pathway. o As well as ADP release, there is release of thromboxane (TxA₂) which promotes platelet aggregation. o The actions of both ADP and thromboxane causes platelet aggregation and forms the first haemostatic plug. This process is reversible however in the coagulation cascade, thrombin is activated which further causes platelet aggregation by binding to platelet surface receptor (PAR’s). o This is followed by platelet contraction that creates an irreversible fusion of a mass of platelets. This is the secondary haemostatic plug. o While this is happening, thrombin converts fibrinogen to fibrin within and around the platelet plug essentially cementing it in place. In summary platelets are freely circulating in the blood, however when they receive chemical signals from ADP and thromboxane, it causes platelets to bind to the epithelial cells with the help of vWF that is present in the subepithelial layer of the blood vessel. As the platelets adhere, they change shape, release more ADP which recruits more platelets to the area and thereby forming the first haemostatic plug. Once this plug forms, it triggers off the coagulation pathway which ultimately results in thrombin converting fibrinogen to fibrin. This fibrin forms within and around the platelet plug, cementing it in place and this is how platelets help to maintain the integrity of the vascular compartment. Endothelium Smooth surface lining blood vessels Antithrombotic effect: o Releases PGI2 (prostacyclin), NO and ADPase that inhibits platelet aggregation in normal healthy tissue. Prothrombotic effect: o Injury or activation of endothelial cells results in prothrombotic activities o Endothelial cells’ production of vWF is an essential co-factor for platelet binding to collagen o Synthesises tissue factor and activates extrinsic clotting cascade. Also binds activated FIXa and Xa which assists in the catalytic activities of the coagulation factors o Secretes inhibitors of plasminogen activator (PAI’s) which depress fibrinolysis Coagulation Factors p.128 Kumar enqymatic conversions turning inactive proenzymes into activated enzymes and eventually results in the formation of thrombin. Different factors play roles in moving the cascade forward (see diagram) Thrombin converts fibrinogen (soluble) to fibrin (insoluble) to form a plug. 3. Discuss the underlying physiology of bruising A bruise is an injury that does not disrupt the integrity of the skin, caused by a blow to the body, characterised by swelling, discolouration and pain. It is blood escaping from the blood vessels and clotting beneath the skin. Bruising can be caused by: Trauma which damages blood vessels Decrease platelet numbers due to increase destruction, decrease production (toxins, viruses, thrombocytopaenia, leukaemia) Decreased platelet functioning – acquired or genetic (decrease in vWF) Abnormalities of coagulation pathway – Vit K deficiency; haemophilia Changing colours of bruises: Red/Blue – local haemorrhage Blue/Green – local formation of biliverdin Red Bile – bilirubin Golden Yellow – haemosiderin Haemoglobin transformed to haemosiderin by macrophages phagocytosing red cell debris then lysosomal enzymes eventually convert haemoglobin to haemosiderin. 4. Identify the major cell types in a histological blood smear. Major cell types in a normal blood smear: erythrocytes (RBC) most abundant 5. neutrophils (lobed nucleus) lymphocytes (unlobed, rounded nucleus) monocytes (unlobed, rounded nucleus) Identify major cell types in a bone marrow expirate erythroblast Megakaryocyte Should see an equal ratio of fat cells and haematopoietic cells Fat cells Megakaryocytes (bone marrow cell, large lobed nucleus, normally not present in circulating blood) Erythroblasts Myeloblasts Lymphoblasts It is usually difficult to differentiate the different blast cells.