blood, part 3
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Blood, part 3. Thrombocytes, Hemostasis, Hemostatic Disorders, Blood Typing and Transfusions. Thrombocytes (platelets). Not true cells Cytoplasmic fragments w/purple granules that contain chemicals for blood clotting Enzymes Serotonin Ca 2+ ions ADP PDGF (Platelet-derived Growth Factor ) - PowerPoint PPT PresentationTRANSCRIPT
Blood, part 3Thrombocytes, Hemostasis, Hemostatic
Disorders, Blood Typing and Transfusions
Thrombocytes (platelets)• Not true cells• Cytoplasmic fragments w/purple granules that contain chemicals
for blood clotting– Enzymes– Serotonin– Ca2+ ions– ADP– PDGF (Platelet-derived Growth Factor)
• Normally kept in “inactive” state by molecules secreted by endothelial cells of blood vessels
• When activated, form temporary plug that helps to seal breaks in blood vessels
Activated platelet amorphous w/extensions that help them stick to vessels and each other
Thrombopoiesis (Platelet formation)• Cytoplasmic fragments derived from megakaryocytes
– Mega = large– Karyo = nuclei– Cyte = mature cell
• Thrombopoietin promotes formation of megakaryocyte, created by multiple mitosis w/o cytokinesis
• Megakaryocyte presses against sinusoid (capillary) of bone marrow and pinches off to make fragments
Hemostasis
• Series of reactions to stop a bleed
• Phases:1. Vascular spasm 2. Platelet plug3. Coagulation (clotting)4. Clot Retraction 5. Fibrinolysis (Clot
Eradication)
1. Vascular Spasm1. Vascular Spasm• Constriction of damaged vessel,
triggered by:- Endothelium- platelets- Pain receptors
• Slows the bleed
2. Platelet Plug Formation• Damaged endothelium activate platelets by
releasing– VWF (von Willebrand Factor)
• Platelets become amorphous:– Stick to exposed collagen fibers of endothelium– Release
• serotonin ( spasms)• ADP (attract more platelets)• Thromboxane ( both )• Prostacyclin (inhibits aggregation elsewhere)
3. Coagulation (Blood Clotting)• Blood transformed from liquid to gel • 3 Critical Steps:
1. Prothrombin Activator Forms (complex series of biochemical rxns!) - require Ca2+ ion and procoagulants to promote sequence of rxns- Two pathways:
a. Intrinsic Pathways (slower) – within damaged vesselb. Extrinsic Pathway (faster) – outer tissue around vessel
2. Prothrombin converted to Thrombin3. Thrombin catalyzes joining of fibrinogen into fibrin mesh
- Glue platelets together
4. Clot Retraction• Clot Retraction
– Platelets contract (like a muscle) to stabilize clot• Contractions pulls on fibrin
squeeze out serum from clotCompact the clotRuptured ends of blood vessel drawn closer together
– PDGF and VEGF released from platelets• (PDGF) Stimulates fibroblast and smooth muscle
mitosis to rebuild wall • (VEGF) Promotes endothelial restoration
5. Fibrinolysis
• tPA (Tissue Plasminogen Activator)– Released by endothelium around clot– Activates plasminogen– Plasminogen plasmin
• Plasmin– Digestive “clot busting” enzyme
• Remnants of clot phagocytized by WBCs– Macrophages– eosinophils
How are clots prevented from becoming TOO large?
1. Fast moving blood– Washes away excess Thrombin
2. Inhibition of clotting factors– Anti-thrombin III (ATIII): plasma protein inactivates
thrombin– Protein C: inhibits clotting factors– Heparin: enhances ATIII
Hemostatic Disorders:Undesirable Clotting
• Thrombus: a clot that develops in an unbroken vessel– blocks circulation
tissue death– Coronary thrombosis
Heart attackDeath of cardiac muscle
Hemostatic Disorders:Undesirable Clotting
• Embolus: freely floating thrombus in bloodstream– Pulmonary Embolism
• Impairs O2 delivery• Death of lung tissue
– Cerebral Embolism• Stroke, • Death of brain tissue
Hemostatic Disorders:Undesirable Bleeding
Thrombocytopenia• reduced platelet count < 50,000/mm3
– Bone marrow disease or destruction• petechiae on skin due to widespread hemorrhage• Treatment: blood transfusions
Hemostatic Disorders:Undesirable Bleeding
Hemophilia:• Hereditary• Lack of clotting factors
– hp A - defective Factor VIII (83%)– hp B - defective Factor IX (10%)
• Genentech. Inc. - now engineers tPA and Factor VIII less transfusions needed
• glycoprotein antigens exist on external surfaces of RBCs
• Antigens are:– Unique to the individual – “foreign” to other individuals– promotes agglutination
• Presence or absence of these antigens is used to classify blood groups
Human Blood Groups
Blood Typing
• anti-A or anti-B antibody serums are added to blood
• agglutination occurs between the antibody and the corresponding antigens
Blood Donors and Recipients
BloodType
Antigen SerumAntibody
DonateTo
Receive From
A A Anti-B A and AB A and O
B B Anti-A B and AB B and O
AB A and B NoneAB
onlyAll Types
O None Anti-A Anti-B All Types O only
• Rh antigens:– 8 types– Most common: types C, D, and E
• Anti-Rh antibodies do not exist in Rh- individuals until they are exposed to Rh+ blood (1st pregnancy)
• Leads to complications during 2nd pregnancies, if Rh- mother is carrying Rh+ child
Rh Blood Groups
Transfusions
• Blood bank:– Mix donor blood with anticoagulants that bind to Ca2+ – Tested for viruses, ABO, and Rh factor– 35 day shelf life at 40 C– Blood separated into component parts
• Whole blood: (rare)– Only for rapid and substantial blood loss
• Packed red cells (plasma removed)– To restore O2 carrying capacity
• Occur when mismatched blood is infused• Donor’s blood cells are attacked by the recipient’s
plasma antibodies causing:– Ruptured RBCs– Diminished O2 carrying capacity– Clumped cells (agglutination)– Blood clots– “Free” hemoglobin due to lysis of RBC
• Hemoglobin solidifies in kidneys – Kidney fails
Transfusion Reactions