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.