Alright, so, now, if that’s centrilobular,
let us now move into our 2nd sub-type. This
is Panacinar. When was the last time you’ve
heard of Pan? Mitral regurgitation and you’ve
heard of pansystolic. What does that mean?
Throughout, pan means throughout in general.
Now, this is panacinar and what that basically
represents is the fact that the entire acinus
has now become damaged. Now this is a big problem.
How important is this? Quite, why? Take a
look, most common homozygous, what does
that mean? Both genes have been affected.
In Caucasians, one of the most common homozygous
genetic mutations in Caucasians.
What are some of the other ones that you know
of? You definitely know about Down, trisomy
21 and you know about cystic fibrosis chromosome
7, how popular are those? Unfortunately,
quite in the Caucasian population. So, what
is this that we’re talking about? Now, before
you get into details understand the concept.
Let’s start from the start real quick. Remember
those neutrophils that were recruited when
smoking, what did they release? That enzyme?
Good, it was a elastase, wasn’t it? This
elastase was then released and what is it
that normally neutralizes elastase? Good,
that’s your alpha-1 antitrypsin. In centrilobular,
there is no genetic mutation, was there? In
centrilobular. What about panacinar? Yes there is.
So, there is absolutely nothing protecting
the lung from elastase. So here comes some neutrophils.
Now, I’m going to first give you a non-smoker.
A non-smoker who shows up with FEV1/FVC ratio,
decreased pulmonary function test, dyspnoea
is taking place, on chest X-rays we find a
barrel chest. Non-smoker, age there? Maybe
about 45. So without any smoking your
patient has now gone into emphysema but this
is the panacinar type and with the panacinar
type you know, well you’re thinking, Caucasian
patient? Mostly likely alpha-1 antitrypsin
deficiency. So, what is this gene?
Well, look at the gene here. Normally it’s
called PI. What does PI stand for? Protease
inhibitor. What's a protease? An enzyme.
Which enzyme? The enzyme from the neutrophil?
Yup, that enzyme from the neutrophil. What was
that called? Elastase. So, now you have to
know a few names don’t you? So, that neutrophil
releasing that proteolytic enzyme, protease
known as elastase and PI stands for protease
inhibitor. I think that’s a beautiful
name, appropriately done.
Okay, so what happens now? Well, you pick
up mutations. What’s homozygous mean?
Both genes. For every “z” that you pick
up, you have further deficiency of alpha-1
antitrypsin. You have both mutations taking place,
you have two "z’s" what does that mean to
you? This is homozygous, alpha-1 antitrypsin
deficiency. That means not a single alpha-1
antitrypsin is being produced properly. Why
did I emphasize the term “properly”? You’ll
see why, okay? So, now, you have no proper
amount of, or properly formed alpha-1 antitrypsin.
So who wins this battle automatically? Elastase,
and kills off the entire lung. Are we done?
No. What other organ is highly dependent on
this protective mechanism? The liver. The
liver is. So therefore, in a patient, panacinar,
this is a big deal with homozygous. You know
about homozygous for example, there’s a
difference between sickle cell trait and sickle
cell disease. What is sickle cell disease?
That’s homozygous, is'nt it? That’s haemoglobin
S, is'nt it? That’s haemoglobin S. Anyhow,
so PIZZ, there’s no alpha-1 antitrypsin
and so, not only is the lung being damaged
from apex to base, but as is the liver, and
with the liver you’re worried about this
patient going on to what? Cirrhosis, nothing
Now, I’m going to walk you through this
properly formed type of alpha-1 antitrypsin
and why that’s important to you clinically.
Childhood hepatitis evolving into cirrhosis
in adulthood will reveal protein globules,
stop there. Okay, from henceforth, when you
think of the term “hepatitis”, do not
think viral only. Think about all the different
reasons why you can have hepatitis. Hepatitis
alcohol, hepatitis autoimmune, hepatitis nash,
hepatitis Wilson’s disease, hepatitis
viral? Hepatitis here, alpha-1 antitrypsin
deficiency. All that hepatitis means is inflammation
that’s it, okay. But many
causes of hepatitis.
So, as a child, you were never born, as
a homozygous, you were never born with the
enzyme. So, your liver is already damaged
you call that hepatitis. With all
that damage taking place, what’s that again?
Eventually, what are you going to result in?
A type of micronodule type of cirrhosis.
Cirrhosis is my point. And when you have cirrhosis
taking place, I told you "properly", you don’t
have properly formed alpha-1 antitrypsin.
What is an enzyme? A protein. A protein is
formed in what organelle in your cell? Good,
rough endoplasmic reticulum. Okay, now, my
point is this. So now, you can’t form an
alpha-1 antitrypsin because of the deficiency,
enzyme deficiency, genetic mutation. But is
the liver desperate enough to produce alpha-1
antitrypsin? It is desperate, it needs it
so that it can protect the liver and maintain
homoeostasis. So, it tries but when it tries
it produces what? A protein globule in the,
read the full statement here, hepatocyte
endoplasmic reticulum upon liver biopsy. Is
that clear? Why is there protein globule
being formed? Because you are trying to form,
who is? The liver is trying to form your alpha-1
antitrypsin, but doesn’t produce properly
so within your hepatocyte and endoplasmic
reticulum you end up finding a protein globule.
That is the full picture of panacinar and
how it’s strictly associated with your genetic
mutation being homozygous.
Now, your patient here I told you was a non-smoker
at the age of 45. Well, could you have a
patient with panacinar and this type of alpha-1
antitrypsin deficiency as a smoker? Sure.
So, if they're smoker and they have alpha-1
antitrypsin deficiency homozygous type, how
old do you think he or she is when they then
present with panacinar emphysema? 35? That’s
crazy. That’s ridiculously young to be developing
such an issue with your lung and such.
Okay. Now, a couple other things here. So paraseptal
is where we are. This is distal acinar emphysema.
What does it do? Results in destruction of
the alveolar duct, it may occur alone, in
combination with any of the above 2 types
referring to your, well, centrilobular or
panacinar. When your patients are affected
with paraseptal emphysema alone, it usually
results in spontaneous pneumothorax. What
does that mean? Okay. So, the type that we
just looked at earlier was the proximal type
and with the proximal type you’re in the
respiratory bronchiole, are we clear? Go back
and take a look at the definition, proximal.
With this you can have a centrilobular type
of pattern without alpha-1 antitrypsin deficiency,
but if there is alpha-1 antitrypsin deficiency
that is panacinar, we just talked about
all of these. If the distal portion is affected
now you’re distal from the respiratory bronchiole.
Where are you? You’re one step closer to
the alveoli so affecting the alveolar
duct and maybe even the alveoli. If that happens
then you’re weakening
the parenchyma. What may then
happen? Rupture. When you have rupture
taking place in your lungs, what happens?
You’ve lost your negative pressure, right?
Because anything outside of the lung, what
happens to your pressure? It automatically
becomes positive, are we clear?
What’s your best analogy? When was your
birthday? Well, during your birthday, maybe
you got balloons. If you didn’t, then I’m
sorry, I don’t know what to tell you. But
anyhow, so you know what a balloon is. You’re
blowing it up
That’s your lung, okay?
How do you keep it open? Well, as long as
you have negative intrapleural pressure, you
keep it expanded. Are we clear? Then you take
a pin, you ever have this? Aren’t you one
of those maybe mischievous little dudes or
dudettes, and what were you doing? You're going
around popping balloons.
Alright. So this is what you’re doing in
spontaneous pneumothorax. That needle, you
pop the balloon, what happens to balloon which
is your lung? Collapses. That’s spontaneous
pneumothorax, that is the best method of explaining
in simple terms as to what spontaneous pneumothorax
is. So, when you have distal, your alveolar
duct which is undergoing massive destruction,
please understand that you might then introduce
spontaneous pneumothorax, you then tell me
as to what you can expect upon percussion
of your chest. Will it be tympanic or will
be dull? Your lung just collapsed for Pete’s
sake, this is all empty, so upon percussion
it will be tympanoc. Obviously, I’m exaggerating
but it will be tympanic, is that clear?