Kinin and Coagulation Factors – Protein Effector Cascades

by Richard Mitchell, MD, PhD

My Notes
  • Required.
Save Cancel
    Learning Material 2
    • PDF
      Slides Acute and Chronic Inflammation Effector cascades.pdf
    • PDF
      Download Lecture Overview
    Report mistake

    00:01 Let's look at kinins and coagulation factors which are very intimately linked.

    00:05 And we're starting with a simple dot at the beginning.

    00:09 It gets to be a fairly complex series.

    00:12 So hang in there.

    00:13 Again, feel the force, kind of get a feeling for this without getting too bogged down in all the details.

    00:21 So factor XII is technically part of the coagulation cascade, it's called hageman factor.

    00:26 So factor XII can be by a variety of molecules activated.

    00:31 In factor XII interacts with collagen, or basement membrane, or activated platelets in the presence of a cofactor, called high molecular weight kininogen we will activate it, we will turn it into an active protease.

    00:47 So this is beginning of a cascade and activated protease.

    00:51 And whenever we activate coagulation factors, as we'll talk about in a subsequent set of topic discussions, we label it A.

    01:00 So this is factor XIIa, meaning that it's activated.

    01:04 Factor XIIa will do a variety of things.

    01:07 On the right hand side, it will feed into the clotting cascade.

    01:12 And we'll show more of that in just a second.

    01:15 It will also feed into the kinin cascade.

    01:18 So that proteolytic activity of activated XIIa will act on a variety of other proteins that are present, either in the circulation or in tissues.

    01:29 Let's look specifically at clotting. So this is the coagulation cascade.

    01:34 So downstream from XIIa You see XIIa at the very beginning, and it will act on factor XI to XIa there are a whole bunch of things.

    01:43 We'll come back to this because we'll spend more time in a subsequent topic discussion.

    01:48 But the main goal here is to activate prothrombin, which is factor II, to an activated form IIa, that will cleave fibrinogen to fibrin and we get a clot.

    01:59 Great.

    02:00 So we're getting down that cascade because we activated factor XIIa at the very beginning.

    02:08 Interestingly, thrombin does more than just cleave fibrinogen to fibrin to make a clot.

    02:15 It also is very pro inflammatory.

    02:17 And we will in the clotting cascade talk later about this pro inflammation aspect of thrombin.

    02:26 So thrombin activates inflammatory pathways.

    02:28 And that's all we really care about right now.

    02:30 So we've gotten XII, XIIa coagulation and we're also getting pro inflammatory effects.

    02:38 Just hang on to that.

    02:39 The details not important. Concept really cool.

    02:42 Okay, back over.

    02:44 The other thing that XIIa can do is activate the kinin cascade.

    02:47 So it's going to proteolytically cleaved prekallikrein to kallikrein Bunch of words.

    02:53 But in fact, now kallikrein is going to do one other element that we haven't really talked about yet, in all this inflammatory stuff.

    03:01 And that's pain.

    03:03 Kallikrein choose on high molecular weight kininogen, HMWK to make bradykinin.

    03:10 And bradykinin is a major pain mediator.

    03:13 It also mediates permeability.

    03:16 But kallikrein is going to get us into the pain pathway, which is part of the cardinal features of inflammation.

    03:24 Cool.

    03:25 Kallikrein will also start to counter regulate the clotting cascade.

    03:31 So, again, that truism for every pro, there's an anti.

    03:35 Well, we have procoagulant on the right hand side, and we have anticoagulation being driven on the left hand side, all through the same concurrent activation to XIIa.

    03:47 So we will activate plasminogen, cleave it to plasmin.

    03:51 And that will break down fibrin.

    03:54 So that we can limit the amount of clot.

    03:57 This becomes very important because we don't limit it, you can potentially clot the entire vasculature with just the initial activation of XII to XIIa.

    04:08 So kallikrein also activates a fibrinolytic system, in addition to mediating pain through bradykinin.

    04:15 And plasmin, which got activated through kallikrein is now going to drive the complement cascade.

    04:21 Whoa, all this stuff is interrelated.

    04:25 And it's all part of a cascade.

    04:28 So take this picture, just see the colored boxes and the bold font.

    04:35 The details not too important, but the concepts here of the interrelationship of these cascades really important.

    About the Lecture

    The lecture Kinin and Coagulation Factors – Protein Effector Cascades by Richard Mitchell, MD, PhD is from the course Acute and Chronic Inflammation.

    Included Quiz Questions

    1. Endothelial collagen
    2. Macrophages
    3. Complements
    4. Kinin
    5. Prothrombin
    1. Kinin cascade
    2. Coagulation cascade
    3. Complement cascade
    4. 5-lipoxygenase cascade
    5. Leukocyte adhesion cascade
    1. ...activated Factor X (Xa).
    2. ...activated Factor XIII (XIIIa).
    3. ...activated fibrin.
    4. ...activated protein C.
    5. ...activated protein S.

    Author of lecture Kinin and Coagulation Factors – Protein Effector Cascades

     Richard Mitchell, MD, PhD

    Richard Mitchell, MD, PhD

    Customer reviews

    5,0 of 5 stars
    5 Stars
    4 Stars
    3 Stars
    2 Stars
    1  Star