Alpha-1 Anti-Trypsin Deficiency
Really important for you to know.
Third most common
or really not even third
but it is
A third important genetic disease
in the Caucasian population.
Quickly walk me
through alpha-1 anti-trypsin
we did this in pulmonology,
when we did our
Remember that Alpha-1 Anti-Trypsin
is a protease inhibitor.
What protease am I referring to?
So, as long as the proper amount of Alpha-1 Anti-Trypsin
is being synthesize where?
Then, to be able to properly combat
and control the amount
of Elastase activity
Two major organs,
where it becomes crucial,
For proper amount of Alpha-1 Anti-Trypsin
include the lungs and the liver.
Of the two organs,
which pair of symptoms
or which set of symptoms
Is the patient going to first
come in with?
Is the patient truly going to come in
As being the prevalent symptom?
Our is it going to be more
of an obstructive type emphysema?
First and foremost, you're going to look
for a decrease FEV1/FVC ratio.
Severely decreased less than 80%
and maybe down to 25% Or 30%, Panecinar.
How old is your patient most likely
with Alpha-1 Anti-Trypsin
that presents with such emphysema?
Well, if they weren't smokers,
maybe about 40 to 45, hmm...
What if they are smoking
and have Alpha-1 Anti-Trypsin
How old is that patient?
A good decade younger.
Wow! At 30-35, really dangerous!
The deficiency of Alpha-1
with the accumulation of proteases
in the liver causing damage to it.
What is a gene for Alpha-1 Anti-Trypsin?
Stands for protease inhibitor
What a beautiful name for an enzyme
that does exactly
what you expected it to do.
To hold back your protease.
That's your PI.
For every Z that you pick up,
What do you mean every Z?
How do you pick up every Z?
You go to a local Walmart
or gas station to pick up a Z?
No, you pick up and Z unfortunately,
What I'm saying is,
for every Z that you pick up,
you become more deficient
of Alpha-1 Anti-Trypsin
You pick up one Z
that is heterozygous,
Yeah, might be losing a little bit of
your patient is going to survive.
The only issue really there
will be more so, the liver, right?
What if there were to Z’s?
That is homozygous.
So if you're missing both,
I'm saying, both alleles,
are making the patient deficient
of Alpha-1 Anti-Trypsin. Then, immediately
are making the patient deficient
of Alpha-1 Anti-Trypsin.
The entire lung,
In the liver gets damage
as well going into Cirrhosis.
What are you going to find on biopsy?
Are like the following, pay attention:
The very end of the sentence says PAS
Periodic Acid Shift, positive globules
within your liver biopsy.
Will show you within hepatocytes
Walk me through this.
is Alpha-1 Anti-Trypsin to your survival?
Crucial. Without it,
we’re pretty much dead. Ok?
So, if it is that crucial for existence,
this is a type of enzyme or protein.
All protein is produced
We're talking about translation,
transcription in the nucleus
And from the nucleus,
you've just produced a protein.
Or you just produced a messenger RNA.
Out comes the mRNA, where is it going?
Rough endoplasmic reticulum, good.
And you begin the process
of protein synthesis, right?
But now, you don't have
the proper genes for it.
The rough endoplasmic reticulum
is still producing protein.
It is abnormal.
You are going to use this
to your advantage as a clinician
upon biopsy within hepatocyte
to look for that globule
within the rough endoplasmic reticulum.
You see how important that statement is?
Because that's what's going to help you
get your question right.
That is what is going to help you,
properly manage your patient,
who has severe Alpha-1
All jokes aside, important.
What does that mean?
And liver transplant is curative
Alpha-1 Anti-Trypsin deficiency
If it gets strictly
thinking about the liver,
Your focus now, remember,
this is the way that they will
word it on your exams
is the fact that, what is the next step of management
in this patient with
Alpha-1 Anti-Trypsin deficiency?
And you'll have to organs
to choose from.
And that makes it difficult, hmm.
So am I going to address more
of the pulmonary issue?
Or am I going to address more
of the liver issue?
Look for the stem of the question.
Whether this patient
is giving you predominantly
Liver symptoms such as jaundice, fatigue,
may be things of that nature,
elevated liver function tests
Or the patient in the stem, remember
It has to be black and white
in a question.
It can't be controversial.
with the question has to be
Or they will give you a decrease
In which, at that point,
your management is going to be
occurring with the respiratory system.
If your dealing with the liver,