L9-Hameostasis Flashcards
(31 cards)
4 stages of Haemostasis
Stage I - Vasoconstriction
Stage II - Activation of platelets and formation of platelet plug.
Stage III - Coagulation(complex cascade of reactions that convert fibrinogen (a soluble protein) into fibrin, forming a mesh-like structure that traps blood cells and platelets to create a stable clot), fibrin formation & clot retraction.
Stage IV - Fibrinolysis
Define Haemostasis
stopping bleeding from damaged blood vessels.
Define thrombosis
formation of blot clot inside a blood vessel.
What does pathological thrombosis can give rise to ?
To chronic thrombosis which can occlude(BLOCK OR CLOSE UP) blood vessel and cause downstream tissue ischaemia(blood flow is restricted beyond a blockage or narrowing in a blood vessel, leading to a shortage of oxygen and nutrients in the affected tissue.)
what are the key players in haemostasis
1.Vessel wall
2.Platelets - Primary Haemostatic plug
3. Thrombin & Plasma - Secondary
Haemostatic plug
4. Plasmin
Explain stage I
- Vasoconstriction reduces blood flow to injured vessels.
- Reduction of blood flow to injured areas – reduce blood loss
- Increases likelihood of contact activation of platelets and coagulation factors.
ie- 1. Direct injury to vascular smooth
muscle cells.
2. Molecules released from injured endothelial cells
3. Molecules released from activated
platelets.
4. Neuronal signals from local pain receptors.
Part 1 of stage III :-
How the 1o haemostatic plug is formed.
- In a normal blood vessel NO & PGI are being produced from the endothelial cells. and blood flow and platelets are going through.
- When the blood vessel is damaged, -ve signals are gone
- Underlying collagen and matrix are exposed.
- Won Willebrand factor sticks with collagen to provide a surface which is highly reactive to platelets.
- platelets then stick on to this, tether and roll along it. and start to spread out, binding it and plug in the gap(damage).
- Because of their granules. the release TXA2 and ADP to the local environment which bathed other platelets. to activate and change their shape.
- Through the binding of fibrinogen which forms the 1o haemostatic plug.
Part 2 of stage III :-How the 2o haemostatic plug.
- Platelet aggregate primary plug activated fibrinogen(insoluble protein) linking them together.
- Convert fibrinogen to a protein called fibrin.
- These can cross-link themselves giving the ability to transform the initial platelet aggregation into a thrombus.
- Thrombin is an enzyme produced during coagulation.
(i) Thrombin is the protease that cleaves fibrinogen into fibrin.
(ii) Thrombin also activates other factors which cause cross-linking of fibrin. - Finally thrombin generation is what drives the formation of insoluble cross-linked fibrin mesh which sits around the aggregates to hold it so its a lot more stable blood clot.
Where is thrombin generated? and what is used?
-Through Coagulation cascade
-Factors from the coagulation is used in the conversion of the prothrombin to its active form.
How is thrombin generated?
- A proteolysis cascade converting precursor factors into active factors.
- Each step in the pathway provides an amplification of the signal.
- End result is the generation of thrombin.
- The cascade also has negative feedback loop s to ensure local and limited
thrombin generation.
Explain stage IV - Fibrinolysis
- Stopping the blood clot forming forever.
-During blood vessel damage, factors are released that bind to fibrin and recruit plasminogen to the clot. - Constant balance of generation and turnover of blood clot.
- Fibrin bound protease is activated and acts on plasminogen to release plasmin.
- Plasmin then degrades the fibrin.
- Fibrinolysis is localised to fibrin in the clot to limit fibrinolysis to the site of the injury.
- It dissolves and break down the clot by preventing the excessive thrombus growth.
Write the summary of Haematopoiesis part I
- HSCs are self renewing, multipotent stem cell that can differentiate into all the blood cells in the body but limited.
- Massive potential for cell production – produce ~ 4.2 x 1011 cells per day.
-Balance between self renewal and differentiation allows for maintenance of
the HSC population and production of sufficient blood cells.
-HSCs are defined by cell surface markers.
- Primitive haematopoiesis is the very early embryonic formation of blood cells
occurs in the yolk sac.
-Definitive haematopoiesis occurs when AGM & foetal liver derived HSCs begin
production of blood cells. This transfers to the bone marrow at late gestation
and throughout adult life. Then both bone marrow and the placenta is populated by the HSCs cells.
- In transition from p.h to d.h the environment of the AGM is important for the formation of the Long term HSCs.
-The bone marrow niche which is vital for the proper regulation, function of HSC and self renewal has 2 components.
-C.c and M.c
What are bone marrows made from?
basement membrane, extracellular matrix, collagen.
Features and properties of platelet
-Resting platelets are small, 3 – 5 m biconvex
discs
-Have an average lifespan of approx. 8 – 10 days
- Have no nucleus
Explain stage II, activated by what and what happens after activation?
platelets can be activated by multiple surface receptors. By:_
soluble activatory signals - TxA2, thrombin, ADP.
vessel wall acivatory signals - collagen, adhesion, GPVI / FcRgamma,
Upon the activation of the platelets they can:-
1.change shape to plug the damage to the wall and make platelets more likely to stick together.
2. Secrete dense and alpha granules to Reinforce platelet activation, Activate coagulation cascade, Drive vessel wall and tissue repair.
3.Become sticky and aggregate - Active integrins bind to fi
These changes are important for haemostatic plug formation
Summary of Haemostasis
-Haemostasis is a complex, multistage process by which the body prevents
blood loss following tissue and blood vessel damage
-Vasoconstriction helps to reduce blood flow to a damaged vessel
-Platelet activation and aggregation allows the development of the primary
haemostatic plug.
-Activation of thrombin via the coagulation cascade converts fibrinogen to fibrin and helps to stabilise the clot.
-Proteases act up on blood clots to prevent over growth and to remove them once bleeding stopped and the vessel is repaired.
-Platelets, the coagulation cascade and fibrinolysis can all be targeted clinically
to help reduce pathological thrombus formation in cardiovascular disease
features and properties of RESTING platelets.
- Internal membrane network - when activated, they become bigger.
- Lots of granules - darker regions- have a lot of content, drives this process.
- Plasma membrane packed with activation and adhesion receptors - recognise damaged signals.
- Highly organised cytoskeleton - maintain resting size.
What do platelets secrete?
-dense granules - LESS
-alpha granules - MORE
- 0-2 lysosomes which can secrete hydrolases.
Name the Stages of red blood cell formation
1.Erythrocytes
2. Proerythroblasts > 👆 se in heam synthesis. condensation of chromatin and 👇 se in nuclei size.
3. intermediate erythroblast - 👆 se in anerobic glycolitic pathway- as no Mitochondria to provide energy. developmetn of specrtin memebrane skeleton.
4. late erythroblast - enucleation. chromatin denses and nuclei 👇es in size.
5. reticulocyte
6. erythrocyte - cells leave bone marrow and enter the blood lumen.
Name the Stages of platelet formation
- megakaryocytes - large nucleated cell. its differentiation drive the formation of cells adapted to carry out haemostasis. polyploidization. 👆 se in cell size.
- megakaryoblast - 👆 se in internal membrane system. formation of granules. 👆 sed expression of platelet surface receptors. fromation of granules.
- megakaryocyte - 👆 se in size to form manu platelets.
- proplatelet forming megakaryocyte - reorganisation of cytoskeleton.
- platelets are formed.
Features of red blood cells
-42-6.1 million per uL blood
-flattened biconcave disc, no nucleus
- lifespan of ~120 days
-transport of O2 ( some CO2) between tissues and lungs
Features of platelets
150,000-400,000 per uL blood
-these are cellular fragments surrounded by plasma membrane.
-contains granules and cytoskeleton.
- lifespan of ~7 days
- haemostasis and release of growth factors for tissue repair.
Write the summary for Haematopoiesis part II
- A specific combination of cytokines, transcription factors, cell signalling molecules drive multipotent progenitor cells down specific lineage pathways.
- ie:- the cytokine TPO acts via its receptor cMpl to rive the differentiation of progenitors down the megakaryocytic lineage.
- A combination of general and lineage specific transcription factors, enhance or repress gene expression of cell specific genes( platelet specific genes).
- Megakaryocyte maturation involves preparing cells to make platelets.
- Erythrocytes maturation involves synthesis of haemoglobin and enucleation.
- Platelet release from megakaryocytes occurs via proplatelet formation.
Define TPR
systematic vascular resistance = Resistance provided by the body to the blood that’s being pumped out of the heart.
