Platelets & Homeostasis (2) Flashcards
Where do platelets come from?
Platelets are cell fragments shed from megakaryotcytes
Do platelets have any organelles or nucleus?
No nucleus but a few organelles = mitochondria and ER fragments
What are megakaryocytes, and where are they found?
Extraordinarily large bone marrow-bound cells
Up to 60mm in diameter
What is haemostasis and its function?
Haemostasis stops blood loss from damaged small vessels
Stops haemorrhage
What are the steps to the formation of a platelet plug?
- Circulating platelets adhere to and are activated by exposed collagen at the site of vessel injury
- Activated platelets release ADP and Thromboxane A2
3.These chemical messengers work together to activate other platelets passing by
- Newly activated platelets aggregate onto the growing platelet plug and release even more platelet-attracting chemicals
- The uninjured endothelium releases prostacyclin and nitric oxide, which inhibits platelet aggregation = so platelet plug is confined to the site of injury
How do platelets adhere to collagen?
Injured blood vessels have exposed collagen
Von Willibrand Factor binds the collagent
Platelets have receptors that bind this factor
What do activated platelets release?
ADP = promotes platelet aggregation by activating other platelets.
Thromboxane A2 = induces vasoconstriction and platelet aggregation
What molecules inhibit platelet aggregation?
Prostacyclin
Nitric oxide
What is aspirin used for?
Blood thinner = inhibits COX1 pathway
COX1 needed to produce thromboxane A2
Also, anti-inflammatory because prevents prostaglandin production
What is the immediate response of an injured blood vessel?
Vascular spasm = vasoconstriction to physically reduce the flow of blood leaving the vessel
Overview of clot conversion
Prothrombin is converted into thrombin when blood clotting is needed
Thrombin then converts fibrinogen into fibrin
What is the role of fibrin?
Stabilizing the platelet plug
How is the fibrin mesh formed?
Fibrin monomers crosslink to each order facilitated by factor XIII (13) aka fibrin stabilizing factor
What activates factor 13?
Thrombin
What is the difference between the intrinsic and extrinsic clotting pathways?
Intrinsic pathway precipitates clotting within damaged vessels AND clotting of blood samples in test tubes
Extrinsic pathway initiates clotting of blood that as escaped into the tissues
What is the role of clot retraction?
Platelets trapped within the clot contract and shrink the fibrin mesh = pulling the edges of the damaged vessel closer together
Necessary for haemostasis and wound healing and to restore flow past obstructive thrombi
Describe the extrinsic clotting pathway
Describe the intrinsic clotting pathway
What initiates the extrinsic clotting pathway?
Tissue thromboplastin (factor 3) released from damaged tissue
Where are the clotting factors made and which need Vit K?
Liver
2, 7, 9 + 10
What dissolves clots?
Fibrinolytic plasmin becomes trapped in the clot and later dissolves it by slowly breaking down the fibrin meshwork
Why is plasmin important?
To prevent inappropriate clot formation
What happens when a vessel is being repaired?
Fibroblasts form a scar at the vessel defect
What is the precursor of plasmin and what converts it to plasmin?
Plasminogen converts to plasmin by plasminogen activators
Tissue plasminogen activator (tPA)
Urokinase, streptokinase, staphylokinase
Vampire bat plasminogen activator
What is the role of PAI-1?
Inhibits tissue plasminogen activator (tPA)
leading to no conversion of plasminogen to active plasmin
Where and in what concentrations is PAI-1 found?
Present in the blood in small concentrations
What does α2-antiplasmin do?
Physiological inhibitor of plasmin = prevents fibrin being converted into fibrin degradation products
No degradation of fibrin clots (core of thrombus = prolongs clots
What concentraiton is α2-antiplasmin found?
Present in blood in concentrations 6-8X exceeding therapeutic dose of plasmin
The therapeutic amount of plasmin used must be sufficient to overcome the natural inhibitory effect of α2-antiplasmin in the bloodstream.
What can inappropriate clotting produce?
Thromboembolism
What is a thromboembolism?
Obstruction of a blood vessel by a blood clot that has become dislodged from another site in the circulation.
What is a thrombus/
Thrombus = abnormal intravascular clot attached to a vessel wall
What is an emboli?
Emboli = freely floating clots
What causes haemophilia?
Deficiency of one of the clotting cascade factors
What effect can liver disease have on blood clotting?
Inability to synthesize procoagulants
Inability to produce bile and to absorb fat and VitK
What is our source of Vit K?
Half Vit K comes from gut bacteria other flat from diet
What can cause Vit K defieciency?
Long-term antibiotic use results in Vit K deficiency and bleeding disorders
What is thrombocytopenia?
Condition in which number of circulating platelets is too low (less than 50million/m)
Normal range = 200-500million/mL
What does thrombocytopenia cause?
Spontaneous, widespread haemorrhage
Visible by small purple spots on the skin
What causes thrombocytopenia?
Damage or destruction of bone marrow either due to cancer or chemotherapy
What is the treatment for thrombocytopenia?
Fresh whole blood transfusions or platelet transfusion
What causes thrombosis?
Inappropriate clotting due to roughened surface of a vessel, endothelial cell injury or disturbed blood flow (stasis)
Define thrombus
Clot that develops and persists in an unbroken blood vessel
Thrombi can block circulation, resulting in tissue death
How does blood pressure induce clots?
Affects endothelial cells and induces damage, which causes platelet activation
What is atherosclerosis, and how does it induce clots?
Build up of oxidized LDL, fatty plaques in vessels
Narrows the blood vessels, causing less elasticity and higher blood pressure
How is blood type determined?
Antigens are present on our RBCs
If RBC has antigen A then the antibody found in plasma will be B because otherwise our antigens would attack the RBCs
What is Rh?
Rhesus factor found on RBCs
What happens when Type B donates blood to Type A recipient?
The recipient has Type B antibodies which will bind to the Type B antigens on RBCs causing agglutination of the blood.
Clumping blocks blood flow in capillaries = oxygen and nutrient flow to cells and tissues is reduced
The immune system targets the type B RBCs and causes hemolysis
What causes the haemolytic disease of the newborn?
This disease occurs during second or later pregnancies of an Rh- mother and Rh+ baby. During pregnancy, you don’t share blood with the fetus you’re carrying. However, a small amount of blood from the fetus can mix with your blood during labour and delivery.
The Rh- mother becomes sensitized when Rh+ blood caused her body to synthesize anti-Rh antibodies.
This means the mother has anti-Rh antibodies which cross the placenta and cause agglutination and haemolysis of fetal RBCs
How is haemolytic disease of the newborn prevented?
Injected anti-RH antibodies eliminate Rh+ cells before they can stimulate the mother to produce her own anti-Rh antibodies
The injected anti-Rh antibodies get ‘washed out’ within weeks
