blood and clotting Flashcards
what are the components of blood
-erytrocytes (RBC)
-leukocytes (type of WBC)
-platelets (for clotting blood)
what’s plasma
-pale watery solution of electrolytes, plasma portend, carbohydrates and lipids
what can colour variation of blood tell us
-pink: Hb released by heamolysis (RBC)
-brown/green: high bilirubin (RBC breakdown), liver or gall bladder issue
-cloudy: cryoglobulins (immunoglobin) which is aboral increase in viscosity leading to vessel obstruction and local thrombosis
what are the principle proteins in blood
-albumin(largest protein component in blood): oncotic pressure, binds to steroids, T3, bilirubin, bile salts, FA
-fibrinogen (large role in clotting): precursor of fibrin
-immunoglobulins : humoral immunity from plasma/ B cells
what are erythrocytes
-most abundant cell
-non-nucleated biconcave discs ,maximising SA:Vol
-mainly composed of haemoglobin
-shape maintained by cytoskeleton anchored to plasma membrane
what are the 3 functions of erythrocytes
-O2 carriage from lungs to systemic system
-CO2 carriage from tissues to lungs
-buffering of acids/bases
what are the two different types of leukocytes
-granulocytes
-non-granular
examples of granulocytes
-neutrophils- phagocytose bacteria
-eosinophils- combat parasites and viruses
-basophils- release IL-4, histamine, heparin and peroxidase
examples of non-granular leukocytes
-lymphocytes- matures into T cells and B cells (plasma cells)
-monocytes - macrophages and dendritic cells
what is the feedback mechanism for platelets
-platelets also have receptors for TPO
-abundant platelets bind to TPO
-megakaryocytes not generated
-platelets not made
-receptors do not bind to TPO
-TPO stimulates megokaryocyte production
-platelets generated
what does haemostasis mean
-prevention of haemorrhage
how does haemostasis prevent haemorrhage
1) vasoconstriction
2)increased tissue pressure- decreases transmural pressure
3) platelet plug (primary haemostasis)- short lived to prevent further blood loss, small breaches in vascular endothelium
a: adhesion
b:activation
c: aggregation
4) clot formation (secondary haemostasis)- stabilisation of weak platelet plug with fibrin leading to semisolid mass of platelets and fibrin mesh with trapped cells and serum
what do platelets consist of
-nucleus free-fragments
-mitochondria
-lysosomes
-peroxisomes
-alpha granules (VWF, fibrinogen, clotting factor, platelet derived growth factor)
-dense- core granules (ATP, ADP Ca2+)
-external coat rich in platelet receptors
-tubulin microtubules maintains discoid shape leads to a dynamic shape change in activation
-cytoskeleton contains actin and myosin: dispersed at rest, dynamic shape change in activation and clot retraction
what happens during platelet plug formation: platelet adhesion
-rapid temporary seal to prevent further blood loss
-damage to endothelium exposes subendothelial collagen (most thrombogenic)
-plasma VWF binds to exposed collagen and platelet receptors
-platelets adhesion mediated by platelet receptors
-further endothelial cell VWF released leading to additional links
-binding of platelet receptors leads to cascade of IC events and therefore activation
what happens during platelet plug formation: platelet activation
-intracellular signalling cascade initiates:
= secretion/ exocytosis of dense and alpha granules: VWF increases platelet adherence and activation, as well as ADP with thromboxane further activation
=secretion platelet derived growth factor leads to cell proliferation/ wound healing
=thromboxane leads to vasoconstriction and inflammation
=cytoskeleton changes: lamellipodium/filopodia
=expression of fibrinogen receptors
what happens during platelet plug formation: platelet aggregation
-platelet fibrinogen receptors bind to plasma fibrinogen
-this forms molecular bridges between platelets leading to aggregation (forms a plug)
-plugs breach in endothelium
-eventually actin and myosin contract leading to a more compact platelet plug
what happens during blood clot formation
-slower, complex process involving cascade of clotting factors with a more permanent fibrin mesh
-blood clot= semisolid mass
-activation triggers chain reaction converting precursors leading to activated factors
-controlled proteolysis amplifies clotting signals
what are the 2 ways clotting can occur
-intrinsic pathways (slower, contact activation)
-extrinsic pathway (trauma/inflammation)
what’s the intrinsic pathway
-initiated by factors within blood in contact with the negatively charged membrane surface of the activated platelet
-cascade of protease reactions
-positive feedback acts at several upstream levels, ending in activated factor Xa
what’s the extrinsic pathway
-triggered by injury to endothelium which allows tissues factor (receptor) in sub endothelial cells to become activated when blood factor VII in contact
-results in activated factor Xa
what’s the common pathway for both intrinsic and extrinsic pathway
-factor Xa from both pathways enters common pathway to generate thrombin (enzyme) and produce stable fibrin
how do homeostatic mechanisms prevent haemostasis
-promotion of anti-thrombotic state
-promotion of pro-thrombotic state
what occurs in the promotion of anti-thrombotic state
-normal endothelial cells maintain normal blood fluidity through paracrine factors and anticoagulant factors (acting locally)
-paracrine factors- e.g. prostacyclin promotes vasodilation, nitric oxide inhibit platelet adhesion and aggregation
-many anti-coagulant factors (including thrombomodulin- complexes with thrombin)
what occurs in the promotion of pro-thrombotic state
-event of vascular damage
-hypoxia (lack of oxygen)- expression of procoagulants (if damage to blood vessels, no blood can be given to them)
what happens with normal blood flow
-in a cylindrical blood vessel, laminae of blood form concentric cylinders
-velocities increase from wall to centre (thin layer next to wall cannot move)
-laminar flow leads to parabolic profile with maximal velocity at centre
-abnormal blood flow leads to endothelial injury
-turbulent flow caused by local stenosis, large radius, high velocity
what’s thrombus in pathology
-thrombus- intravascular blood clot
-arterial thrombosis- following erosion or rupture of atherosclerotic plaque
what’s vichrow triad
-primary risk factors are
=abnormal blood flow
=endothelial injury leading to platelet activation
=hypercoagulability
