Comparison chart between chronic granulomatous disease and
myeloperoxidase. We'll take a look at two different enzymes.
And what may then happen when there is a deficiency to begin
with. Chronic granulomatous disease, what enzyme are you missing
please? NADPH oxidase only. The only cell to be then damaged or
injured would be the functioning of a neutrophil.
Your patient is now catalase positive susceptible. You know
why already. Because now with NADPH oxidase deficiency.
In CGD you do not have deficiency of myeloperoxidase. So if you
have a catalase negative organism such as Strep, it's feeding us.
Let's say that I have CGD, it would be feeding me the hydrogen
peroxide and myeloperoxidase will kill the Strep.
But a Staph which is catalase positive, even if it's feeding me
to hydrogen peroxide, because the bacteria contains catalase
it won't get killed. X-linked recessive for CGD. Myeloperoxidase,
autosomal recessive. And CGD, absence of your NADPH oxidase,
in myeloperoxidase deficiency, only deficiency of myeloperoxidase.
Let me ask you something here. Which one of these conditions
is more dangerous. NADPH oxidase deficiency or myeloperoxidase
deficiency. You must know, clinically significant, NADPH oxidase
deficiency, CGD, much more dangerous clinically than this
myeloperoxidase deficiency. Respiratory burst, remember.
NADPH oxidase is the first enzyme that will take the oxygen and
turn into what? Superoxide. This is called a respiratory burst.
This is not happening in CGD. What about hydrogen peroxide? It is
absent in CGD but it's present in myeloperoxidase deficiency.
And in which one of this condition would there be loss of bleach
or hypochlorous acid? In both. Meaning to say that if NADPH oxidase
is not present, that means that you would not be then properly, you
can't form hydrogen peroxide. And so therefore you can't have bleach.
If there is myeloperoxidase deficiency, yes there is going to be
hydrogen peroxide, but then once again you don't have the enzyme
to then form your hypochlorous acid, HOCL, bleach. We'll go through
integrated arachidonic acid pathway here. And the reason that I
bring this to you attention, our focus with inflammation is going
to be only with those mediators dealing with arachidonic acid.
I'm not going to walk you through every single arachidonic acid
issue but in red what you are seing here are important
clinical points from pharmacology that you want to be
very comfortable with. So let's identify here,
in arachidonic acid pathway, which mediators that we will be
paying attention to. These include LTB4, Leukotriene B4 primarily.
Others would include well what you are seing here. There are
two pathways from arachidonic acid if you remember your
phospholipase A2. Quickly, phospholipase A2 is inhibited by
corticosteroids. Stimulated by calcium. And you knew that already
because of irreversible injury. We have the COX pathway,
cyclo-oxygenase. Here it's inhibited irreversibly by
aspirin, NSAIDs. And then we'll go down to our PGH2 and prostacyclin.
Here you are thinking about the following. Endothelium in green
and you have prostacyclin. It is important for you to know that.
Prostacyclin is going to be responsible for quite a bit of
vasodilation. Keep that in mind. That is important. Remember in
inflammation what is the state of your blood vessel? Inflammed.
You want that to be dilated. Make sure you have that in mind. Now
you have others here that you should know about, PGE2
responsible for fever and PGE2 when it comes to inflammation
is going to be also dolor, which is what? Pain.
So two major factors responsible for pain is going to be
bradykinin and we also have our PGE2.
Next, let's move on to LOX pathway please. Our LOX pathway is
then going to form our most important chemotactic factor,
leukotriene B4. The rest of this C,D,E 4 are then called what's
known as your slow reacting substances when a anaphylaxis.
In other words, CDE4 will be responsible for bronchoconstriction.
Keep that separate from B4 please. B4 should be important for us
in inflammation in this section because of chemotaxis. When it
comes to inhibiting the LOX pathway, then you should be
thinking about silutin. What if you want to block the receptor.
It's called montelukast or zafirlukast. In the meantime,
at some point, when you have gotten into hemodynamics you will
be dealing with thromboxane quite a bit which is not our topic
today or in this section. Our topic in this section is strictly
neutrophil, but if you're dealing with hemodynamics,
and you're dealing with platelets then thromboxane will be
responsible for, good, platelet aggregation. Okay.
Hence, aspirin and NSAIDs by inhibiting COX pathway, inhibits
thromboxane and therefore called a 'blood thinner'.
A nicer overview of arachidonic acid. All the different things
that you need to make sure that you know from pharmacology.
And those substances that I have extracted here specifically
for inflammation including leukotriene B4 and prostacyclin.
Bradykinin, pain. And if you have a patient who has high blood
pressure, hypertension, and you're administering ACE inhibitor
there is every possibility that the patient now increases
levels of bradykinin resulting in dry cough.