Platelets And RBCs Flashcards
Describe the structure of a resting platelet
Small 3-5nm biconvex disc
No nucleus
Contain open canalicular system
Organelles including granules and mitochondria
Has surface glycocalyx
Has an actin, tubulin and spectrin cytoskeleton- actin supports edges, tubulin supports middle and spectrin lays under the PM and chord the actin cytoskeleton
How do platelets change upon activation?
Change shape- relaxation of membrane skeleton➡️ turnover of the resting actin cytoskeleton➡️ changes in the microtubule cytoskeleton➡️ polymerisation of actin and MTs
Secrete granules- mediated by t-SNAREs and v-SNAREs
-Alpha granules contain integral proteins, coagulants, adhesion proteins (fibrinogen vWB), chemokines, growth factors, angiogenic factors, immune mediators
-Dense granules contain cations, polyphosphates, bio active amines (serotonin and histamine) nucleotides (ADP, ATP)
Become sticky- adhesion is mediated by integrines, ligand binding activated membrane bound integrines which are joined by fibrinogen
List done common platelet receptors and their ligands
GP1b-9-5 complex- vWF
GP6/FcRy complex- collagen (laminin, convulixin)
TxA2- thromboxane
P2Y1, P2Y12- ADP
PAR1, PAR4- thrombin
Alpha2beta1 integrin- collagen (laminin)
Alpha2b-beta3 integrin- fibrinogen (vWB, thrombospondin, fibronectin, vitronectin)
What happens to platelets if the vessel wall is damaged?
Usually the platelets receive inhibitory signals from the intact vessel wall
Damage cause the release of PGI and the exposure of collagen and vWB
Platelets roll across surface become adhered and start to spread, secrete TX(A2) and ADP to recruit more platelets which aggregate by fibrinogen becoming fibrin and forming a mesh around the plates forming as thrombus on the site of damage
Describe proplatelet formation from megakaryocytes
Pseudopodia formation using microtubules
Elongation of pseudopodia into proplatelet extensions
Bifurcation of proplatelet processes
Delivery of platelet material to tips
Retraction and release of proplatelets
The microtubules slide past each other using dynein motors to provide the force of proplatelet extension
Platelets are uniform in shape and composition- precision delivery via kinesin motors
The proplatelets need to cross the blood vessel wall in vivo- actin-rich podosomes and matrix metalloproteinases are required to protrude through the vessel wall
What are the steps of haemostasis?
- Blood vessel response- vasoconstriction
- Activation of platelets and formation of platelet plug
- Blood coagulation- intrinsic and extrinsic pathways
- Clot retraction and fibrinolysis
Steps 2-4 mediated by key molecule, thrombin
Describe the extrinsic pathway
Initiation stage of coagulation
Exposure of tissue factor (F3)➡️ TF binds to circulating F7➡️ activation into F7a➡️ F10 activation by F6a and Ca2+➡️ F10a, phosphatidyl serine, Ca2+, F5a activates prothrombin➡️ thrombin
Describe the intrinsic pathway
Amplification stage of coagulation
Tissue damage activates F7➡️ F7a + F11➡️ F11a + F9➡️ F9a + F8a, Ca2+, phosphatidylserine activates F10➡️ F10a and F5a, Ca2+, phosphatidyl serine activate prothrombin to thrombin
What does thrombin do?
Thrombin helps drives its own generation by activating F11, F8, F5, F7
Thrombin directly activates fibrinogen to fibrin and activates F3 which helps cross linking into a fibrin mesh
It activates platelets which provide a pro-coagulation surface by flipping phosphatidyl serine which forms a Ca2+, F10a, F5a complex that supports thrombin
What is Virchows triad?
Stasis of blood flow- most prominent
Hypercoagulability- abnormalities in coagulation cascade or platelet activation
Endothelial injury
Name some disorders involving platelets
Low platelet count-thrombocytopenia
High platelet count- thrombocytosis
Platelets can also be macro or micro in each case
What can cause changes in platelet count?
Low count could be due to low production (B12 deficiency, viral infection, toxic chemicals, alcohol, leukaemia or inherited thrombocytopenia) or high destruction (some medications, autoimmune, pregnancy, bacterial infection, inherited thrombocytopenia or autoimmune disorders)
Increased count- mutations in progenitors, chronic inflammation, cancer or inherited mutations in progenitors
How would you test platelet function?
Light transmission aggregometry- as platelets clump together more light is let through (less cloudy) after initial activation and change shape
Common agonist include- collagen and collage related peptide on GP5, thrombin on PAR1,4, ADP on P2Y1 and P2Y12
TxA2 analogue U46619 on the TxA2 receptor
Aspirin blocks COX activity and stops arachadonic acid causing aggregation via the TxA2 pathway
U46619 can overcome this
Von willebrand factor alone does not cause aggregation, add Riscocetin leads to agglutination which does not activate alpha2b-beta3 integrin
Can block secretion
Describe erythroblast development
Early stages of differentiation can only be identified by cell markers Multipotent stem cell, BFU-E, CFU-E➡️ Late differentiation- pro erythroblasts Early erythroblasts Late erythroblasts Reticulocytes ➡️RBCs Erythroblastic islands- blood cells form in groups around macrophages for cytokine signalling and nuclear phagocytosis
Describe RBC structure
Biconcave
Normoblasts extrude nucleus
Autophagy in reticulocytes- no mitochondria
Sensitive to oxidative damage
V flexible due analytic and spectrin proteins attached to the membrane
