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blood disorders Flashcards

1
Q

keeping blood fluid, with the ability to coagulate when necessary is essential. What is required for this process?

A

a balance between coagulants and anticoagulants

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2
Q

what is an anticoagulant? what is it needed for? what does it involve?

A
  • molecule that prevents/reduces clot formation
  • needed for thrombosis
  • anticoagulant factors, fibrinolytic factors and healed endothelium
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3
Q

what is a coagulant? what does it involve?

A
  • molecule that promotes wound healing/the prevention of blood loss
  • endothelial damage, platelet activation, coagulation activation
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4
Q

what are two key elements of homeostasis?

A

(1) blood

(2) vascular endothelium

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5
Q

what is blood comprised of? (2)

A

(1) plasma = liquid component that plays a role in the transport of proteins, hormones, electrolytes, etc.
(2) cellular components = platelets, erythrocytes, leukocytes

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6
Q

when there is no injury to vasculature platelets are in what state?

A

the quiescent state

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7
Q

what is vascular endothelium?

A

-a mono-layer of endothelial cells that (under resting conditions) produce factors tht prevent inapropriate initiation of homeostasis

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8
Q

what separates blood and procoagulant factors found in the subendothelial layer? why is this important for homeostasis?

A
  • vascular endothelium
  • when there’s an injury to the vascular endothelium, blood is exposed to these procoagulant factors and platelet plug formation begins
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9
Q

what are the three stages of homeostasis? explain what happens (generally) in each.

A

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

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10
Q

explain vasocontriction for 1° homeostasis. what is the goal of this process? how is it triggered further?

A
  • 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)
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11
Q

what does vWF do?

A

binds collagen in the exposed subendothelium

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12
Q

explain the process of platelet plug formation

A
  • 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
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13
Q

is the platelet plug stable?

A

nah, only temporary seal (requires reinforcement)

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14
Q

give a general explanation of the coagulation cascade and what is the main goal?

A
  • a sequence of reactions resulting in the formation of fibrin and thus the homeostatic plug
  • to prevent blood loss while the vessel repairs
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15
Q

what is the primary component of the homeostatic plug? how does this element act?

A
  • fibrin

- forms a cross-linked mesh which acts to stabilize platelet plug and trap erythrocytes & leukocytes in the process

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16
Q

is the homeostatic plug stable

A

yes very

17
Q

what are coagulation factors?

A

-often enzymes, in the inactive (zymogen), form that circulate the blood and help with blood clot formation

18
Q

how are zymogens activated? where can this activation occur?

A
  • 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)
19
Q

explain how the coagulation cascade is initiated

A
  • injury exposes the SM layer of vasculature which contains tissue factors (TF)
  • interaction between TF and FVII initiates the coagulation cascade
20
Q

explain what happens once the coagulation cascade has been initiated

A

-clotting factors (which are circulating plasma zymogens) undergo a series of proteolytic activations resulting in fibrin

21
Q

what are the pathways of the coagulation cascade?

A

the intrinsic, extrinsic and common pathways

22
Q

what is FXa, how is it activated, and what does it do?

A
  • 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
23
Q

does fibrin circulate in the blood?

A

nope

24
Q

what propogates the coagulation cascade?

A

positive feedback
(from thrombin to FXI, FVIIIa and FXIIIa)
(8,11,13)

25
Q

what are the characteristics of the extrinsic pathway?

A
  • sparks the pathway in repsonse to injury

- produces some fibrin

26
Q

what are the characteristics of the intrinsic pathway?

A
  • 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
27
Q

what is fibrinolysis?

A

enzymatic process of breaking down cross-linked fibrin into its degradation products

28
Q

why is fibrinolysis important?

A
  • controls the size and spread of fibrin clot

- removes clot completely once damage is repaired

29
Q

explain the fibrinolysis pathway

A
  • 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
30
Q

how is fibrinolysis controlled?

A

-once the clots been broken down plasminogen activator inhibitors (PAI) inhibit uPA and tPA
(which are responisble for converting plasminogen to plasmin)

31
Q

explain the role of nitric oxide in negative regualtion of 1° homeostasis

A

healthy endo secretes NO to prevent platelet adhesion and aggregation

32
Q

explain the role of prostacyclin in negative regualtion of 1° homeostasis

A

healthy endo secretes prostacyclin (lipid molecule) to prevent platelet adhesion and aggregation

33
Q

explain the role of CD39 in negative regualtion of 1° homeostasis

A
  • healthy endo expressess CD39 (a transmembrane ATPase) that catalyzes the dephosphorylation of ATP
  • this prevents platelet activation
34
Q

explain the role of tissue factor pathway inhibitor (TFPI) in negative regualtion of the coagulation cascade.
what produces TFPI?

A
  • TFPI inhibits the extrinsic pathway to prevent further input from the intrinsic pathway
  • TFPI is produced by endo cells and megakaryocytes
35
Q

explain the role of antithrombin in negative regualtion of the coagulation cascade.
what produces antithrombin?
is it found in circulating plasma?

A
  • 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
36
Q

explain the role of protein C in negative regualtion of the coagulation cascade.
what is protein C activated by?

A
  • activated by thrombin bound to thrombomodulin

- protein C needs protein S as a cofactor to mediate proteolytic inactivation of FVIIIa and FVa

37
Q

how do we diagnose blood disorders?

A
  • measuring levels of protein in a plasma sample

- need to centrifuge sample to separate cellular components from the plasma

38
Q

what is crucial when taking blood samples and why?

A
  • tubes must be coated with anticoagulant (e.g. EDTA)

- prevents blood from clotting

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