00:01
All right. So now if that's Centrilobular,
let us now move into our second subtype.
00:06
This is pan Acinar.
00:08
What was the last time you heard of Pan.
00:10
Mitral regurgitation.
00:12
And you've heard of Pan.
00:13
Systolic. What does that mean?
Throat. Pan means throat in general.
00:19
Now this is pan acinar Panasonic emphysema.
00:22
The entire acinus and secondary lobule are
affected uniformly.
00:26
This pathology is primarily seen at the base
of the lungs, which is a direct contrast to
the apex involvement seen with central
acinar emphysema.
00:34
Now this is a big problem.
00:36
How important is this?
Quite why it take a look.
00:41
Most common homozygous.
00:43
What's that mean? Both genes have been
affected in Caucasians.
00:48
One of the most common homozygous genetic
mutations in Caucasians.
00:53
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
seven. How popular are those?
Unfortunately quite in the Caucasian
population.
01:05
So what is this that we're talking about?
Before you get into details, understand the
concept.
01:11
Let's start from the start real quick.
01:13
Remember those neutrophils that were
recruited when smoking.
01:16
What did they release that enzyme.
01:19
Good. It was a elastase wasn't it.
01:21
This elastase was then released.
01:23
And what is it that normally neutralizes the
elastase.
01:26
Good. That's your alpha one antitrypsin and
centrilobular.
01:30
There is no genetic mutation was there in
Centrilobular.
01:34
What about panacea?
Yes there is.
01:36
So there's absolutely nothing protecting the
lung from the elastase.
01:41
So it comes from neutrophil.
01:42
Now I'm going to first give you a nonsmoker
a nonsmoker who shows up with fev1 FVC ratio.
01:51
Decreased pulmonary function test.
01:54
Disney has taken place on chest x ray.
01:56
You find a barrel chest nonsmoker age there
or maybe about 4545.
02:01
So without any smoking your patient is now
gone into emphysema.
02:05
But this is the panacea type.
02:07
And with the panacea type, you know, well,
you're thinking a Caucasian patient most
likely alpha one antitrypsin deficiency
deficiency.
02:16
So what is this gene?
Well, look at the gene here.
02:20
Normally it's called py mm.
02:22
What's that Py stand for.
02:24
Protease inhibitor.
02:26
Hmm. What's a protease.
02:28
An enzyme. Which enzyme.
02:30
Oh the enzyme from the neutrophil.
02:32
Yep. That that enzyme from neutrophil.
02:34
What was that called. Elastase.
02:36
So now you have to know a few names don't
you.
02:38
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.
02:49
Okay. So what happens now.
02:51
Well you pick up mutations.
02:54
What's homozygous mean.
02:55
Both genes for every Z that you pick up you
have further deficiency of alpha one
antitrypsin. You have both mutations taking
place.
03:08
You have two z's.
03:10
What does that mean to you.
03:11
This is homozygous alpha one antitrypsin
deficiency.
03:14
Wow. That means not a single alpha one
antitrypsin is being produced properly.
03:21
Hmm. Why did I emphasize the term properly?
You'll see why.
03:25
Okay, so now you have no proper amount of or
properly formed alpha one antitrypsin.
03:32
So who wins this battle automatically?
Elastase? Or are we done?
No. What other organ is highly dependent on
this protective mechanism?
The liver. The liver is so.
03:43
Therefore in a patient pensioner 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 isn't it.
03:58
So that's hemoglobin S isn't it.
04:00
It's hemoglobin hemoglobin S anyhow.
04:03
So as there's no alpha one antitrypsin.
04:05
And so not only is the lung being damaged
from from apex to base but as, as is the
liver and with the liver, you're worried
about this patient going on to what.
04:14
Cirrhosis. Nothing protecting it.
04:16
Now I'm going to walk you through this
properly formed type of alpha one antitrypsin
and why that's important to you clinically.
04:23
Childhood hepatitis evolving into cirrhosis
in adulthood would reveal protein globulins.
04:30
Stop there. Okay.
04:31
From henceforth, when you think of the term
hepatitis, do not think viral.
04:37
Only think about all the different reasons
why you can have hepatitis, hepatitis,
alcohol, hepatitis, autoimmune hepatitis,
Nash, hepatitis, Wilson's disease, hepatitis
O, viral hepatitis here, alpha one
antitrypsin deficiency.
04:52
All that hepatitis means is inflammation.
04:54
That's it okay.
04:55
But many many many, many, many, many causes
of hepatitis.
04:58
So as a child you were never.
05:00
Ever born as a homozygous.
05:01
You were never born with enzyme, so your
liver is already damaged.
05:05
You called that hepatitis?
Whew. With all that damage taking place,
what's setting in fibrosis?
Fibrosis. Fibrosis. Fibrosis.
05:12
Eventually, what are you going to result in?
A type of micronodular.
05:15
Type of cirrhosis?
Cirrhosis is my point.
05:18
And when you have cirrhosis taking place, I
told you properly, you don't have properly
formed alpha one antitrypsin.
05:25
What is an enzyme?
A protein a protein is formed.
05:29
In what organelle? In your cell.
05:31
Good. Rough endoplasmic reticulum.
05:33
Okay, now my point is this.
05:34
So now you can't form an alpha one
antitrypsin because of the deficiency enzyme
deficiency genetic mutation.
05:41
But is the liver desperate enough to produce
alpha one antitrypsin?
It is desperate.
05:46
It needs it so that it can protect the liver
and maintain homeostasis.
05:51
So it tries.
05:53
But when it tries, it produces what, a
protein globule in the.
05:58
Read the full statement here.
05:59
Hepatocyte endoplasmic reticulum upon liver
biopsy.
06:05
Is that clear?
Why is our protein globule being formed.
06:09
Because you're trying to form who is.
06:10
The liver is trying to form your alpha one
antitrypsin, but it doesn't produce properly.
06:14
So within your hepatocyte and endoplasmic
reticulum, you end up finding a protein
globule. That is the full picture of panacea
and how it's strictly associated with your
genetic mutation being homozygous.
06:27
Now, your patient here, I told you, was a
nonsmoker at the age of 45.
06:32
Well, could you have a patient with panacea
and this type of alpha one antitrypsin
deficiency was a smoker?
Sure. So if they're a smoker and they have
alpha one antitrypsin deficiency homozygous
type, how old do you think he or she is when
they then present with penicillin or
emphysema? 35.
06:50
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.
07:00
It's a pair receptors where we are.
07:01
This is distal acinar emphysema.
07:03
What does it do? Results in destruction of
the alveolar duct.
07:06
It may occur alone in combination with any
of the above two types.
07:10
Referring to your well centrilobular or
Penicillium.
07:14
When your patients are infected with
parasitic emphysema alone, it usually results
in spontaneous pneumothorax.
07:21
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.
07:29
Are we clear. Go back and take a look at the
definition proximal.
07:33
With this you can have a centrilobular type
of pattern without alpha one antitrypsin
deficiency. But if there is alpha one
antitrypsin deficiency that is panacea.
07:41
We just talked about all of this.
07:44
If the distal portion is affected now you're
distal from the respiratory bronchiole.
07:48
Where are you? You're one step closer to the
alveolar alveoli.
07:52
So affecting the alveolar duct and maybe
even the alveoli.
07:55
Hmm. If that happens then you're weakening
and weakening and weakening the parenchyma.
07:59
What may then happen.
08:00
Uh oh. Rupture.
08:02
Mm. We now rupture taking place along.
08:04
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?
Uh, when's your birthday?
Well, during the birthday, maybe you got
balloons.
08:21
If you didn't, then I'm sorry.
08:23
I don't know what to tell you, but anyhow.
08:24
So you know what a balloon is.
08:25
You're blowing it up. You're blowing it up.
08:27
You're blowing it up. That's your lung.
08:28
Okay. How do you keep it open?
Well, as long as you have, uh, negative
intrapleural pressure, you keep it expanded.
08:34
Are we clear? Then you take a pin.
08:36
You ever have this? Once.
08:37
You one of those maybe, uh, mischievous, uh,
little, uh, little dudes or dudettes.
08:43
And what are you doing? You're going around
popping balloons.
08:45
Bop bop bop bop.
08:47
All right, so this is what you're doing in
spontaneous pneumothorax?
That needle, you pop the balloon, what
happens?
A balloon, which is your lung collapses.
08:56
That's spontaneous pneumothorax.
08:57
That is the best method of explaining in
simple terms as to what spontaneous
pneumothorax is.
09:03
So when you have distal, your alveolar duct,
which is undergoing massive destruction,
please understand that you might then
introduce spontaneous pneumothorax.
09:14
You then tell me as to what you can expect
upon percussion of your chest.
09:19
Will it be tympanic or will it be dull?
Your lung just collapsed, for Pete's sakes.
09:25
This is all empty.
09:26
So upon percussion it'll be thing.
09:29
Obviously I'm exaggerating, but it'll be
tympanic.
09:32
Is that clear?
The lecture Emphysema: Pathogenesis B by Carlo Raj, MD is from the course Obstructive Lung Disease.
Which of the following gene mutations leads to the development of panacinar emphysema?
In addition to lungs, which of the following organs is affected in alpha-1 antitrypsin deficiency?
Which of the following organelles accumulates protein globules in childhood hepatitis that progresses to cirrhosis in adulthood?
What is the composition of alpha-1 antitrypsin molecules?
Which of the following is a common complication of distal acinar emphysema?
Which of the following statements is not true regarding emphysema?
Which of the following cell organelles produces alpha-1 antitrypsin?
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Very easy to understand Lectures. Well Explained. Liked it very much.
I would never get it without you, Dr. Raj! Thank you soooooooooooooo much!!!!!!