blood disorders Flashcards
keeping blood fluid, with the ability to coagulate when necessary is essential. What is required for this process?
a balance between coagulants and anticoagulants
what is an anticoagulant? what is it needed for? what does it involve?
- molecule that prevents/reduces clot formation
- needed for thrombosis
- anticoagulant factors, fibrinolytic factors and healed endothelium
what is a coagulant? what does it involve?
- molecule that promotes wound healing/the prevention of blood loss
- endothelial damage, platelet activation, coagulation activation
what are two key elements of homeostasis?
(1) blood
(2) vascular endothelium
what is blood comprised of? (2)
(1) plasma = liquid component that plays a role in the transport of proteins, hormones, electrolytes, etc.
(2) cellular components = platelets, erythrocytes, leukocytes
when there is no injury to vasculature platelets are in what state?
the quiescent state
what is vascular endothelium?
-a mono-layer of endothelial cells that (under resting conditions) produce factors tht prevent inapropriate initiation of homeostasis
what separates blood and procoagulant factors found in the subendothelial layer? why is this important for homeostasis?
- vascular endothelium
- when there’s an injury to the vascular endothelium, blood is exposed to these procoagulant factors and platelet plug formation begins
what are the three stages of homeostasis? explain what happens (generally) in each.
1° homeostasis = vasoconstriction and formation of the platelet plug
2° homeostasis = coagulation cascade (resulting in production of the homeostatic plug)
3° homeostasis = fibrinolysis (break down of homeostatic plug) and regulatory mechanisms
explain vasocontriction for 1° homeostasis. what is the goal of this process? how is it triggered further?
- relflex initiated at the site of injury
- to impede the amount of blood loss early on
- damaged endo cells trigger this further by releasing factors like endothelin & von Willerbrand factor (vWF)
what does vWF do?
binds collagen in the exposed subendothelium
explain the process of platelet plug formation
- injured endo cells release vWF
- circulating platelets have receptors for vWF
- results in platelet adhesion to the site of injury
- bound platelets activate, change in shape, releasing their granules/other contents which helps recruit additional platelets
- results in aggregation of platelets, forming the platelet plug
is the platelet plug stable?
nah, only temporary seal (requires reinforcement)
give a general explanation of the coagulation cascade and what is the main goal?
- a sequence of reactions resulting in the formation of fibrin and thus the homeostatic plug
- to prevent blood loss while the vessel repairs
what is the primary component of the homeostatic plug? how does this element act?
- fibrin
- forms a cross-linked mesh which acts to stabilize platelet plug and trap erythrocytes & leukocytes in the process
is the homeostatic plug stable
yes very
what are coagulation factors?
-often enzymes, in the inactive (zymogen), form that circulate the blood and help with blood clot formation
how are zymogens activated? where can this activation occur?
- by a procoagulant complex (which needs an active enzyme, a scaffolding cofactor (for position) and an inactive zymogen)
- the zymogen becomes an active enzyme and they cycle continues (snip aa which changes protein confirmaiton)
- can only occur on a procoagulant surface
- FIX –> FIXa (activated)
explain how the coagulation cascade is initiated
- injury exposes the SM layer of vasculature which contains tissue factors (TF)
- interaction between TF and FVII initiates the coagulation cascade
explain what happens once the coagulation cascade has been initiated
-clotting factors (which are circulating plasma zymogens) undergo a series of proteolytic activations resulting in fibrin
what are the pathways of the coagulation cascade?
the intrinsic, extrinsic and common pathways
what is FXa, how is it activated, and what does it do?
- can activated by the intrinsic and extrinsic pathway tenase complexes (which consist of an enzyme, a cofactor and a zymogen substrate)
- first clotting factor of the common pathway
- converts prothrombin to thrombin, which converts fibrinogen to fibrin
does fibrin circulate in the blood?
nope
what propogates the coagulation cascade?
positive feedback
(from thrombin to FXI, FVIIIa and FXIIIa)
(8,11,13)
what are the characteristics of the extrinsic pathway?
- sparks the pathway in repsonse to injury
- produces some fibrin
what are the characteristics of the intrinsic pathway?
- amplification (“work horse”)
- where most of coagulation occurs & most fibrin produced
- important - without this pathway extrinsic pathway could not produce enough fibrin to create a stable homeostatic plug
what is fibrinolysis?
enzymatic process of breaking down cross-linked fibrin into its degradation products
why is fibrinolysis important?
- controls the size and spread of fibrin clot
- removes clot completely once damage is repaired
explain the fibrinolysis pathway
- involves plasminogen activators that convert plasminogen to plasin
- plasmin breaks down the clot into its degradation products
- these products inhibit thrombin (inhibiting production of fibrin)
- this prevents the homeostatic plug from reforming
how is fibrinolysis controlled?
-once the clots been broken down plasminogen activator inhibitors (PAI) inhibit uPA and tPA
(which are responisble for converting plasminogen to plasmin)
explain the role of nitric oxide in negative regualtion of 1° homeostasis
healthy endo secretes NO to prevent platelet adhesion and aggregation
explain the role of prostacyclin in negative regualtion of 1° homeostasis
healthy endo secretes prostacyclin (lipid molecule) to prevent platelet adhesion and aggregation
explain the role of CD39 in negative regualtion of 1° homeostasis
- healthy endo expressess CD39 (a transmembrane ATPase) that catalyzes the dephosphorylation of ATP
- this prevents platelet activation
explain the role of tissue factor pathway inhibitor (TFPI) in negative regualtion of the coagulation cascade.
what produces TFPI?
- TFPI inhibits the extrinsic pathway to prevent further input from the intrinsic pathway
- TFPI is produced by endo cells and megakaryocytes
explain the role of antithrombin in negative regualtion of the coagulation cascade.
what produces antithrombin?
is it found in circulating plasma?
- interacts w heparin/heparin-like molecules found on the surface of endo cells to inactivate various coagulation factors (including FVII, FIX, X, XI, FIIa (thrombin))
- produced by hepatocytes in the liver
- found in circulating plasma
explain the role of protein C in negative regualtion of the coagulation cascade.
what is protein C activated by?
- activated by thrombin bound to thrombomodulin
- protein C needs protein S as a cofactor to mediate proteolytic inactivation of FVIIIa and FVa
how do we diagnose blood disorders?
- measuring levels of protein in a plasma sample
- need to centrifuge sample to separate cellular components from the plasma
what is crucial when taking blood samples and why?
- tubes must be coated with anticoagulant (e.g. EDTA)
- prevents blood from clotting
