Alpha-1 Antitrypsin Deficiency: Diagnosis

00:01 Alpha-1 Anti-Trypsin Deficiency Really important for you to know.

00:06 Third most common or really not even third but it is A third important genetic disease in the Caucasian population.

00:15 Quickly walk me through alpha-1 anti-trypsin we did this in pulmonology, when we did our Panacinar Emphysema.

00:20 Remember that Alpha-1 Anti-Trypsin is a protease inhibitor.

00:24 What protease am I referring to? Elastase.

00:29 So, as long as the proper amount of Alpha-1 Anti-Trypsin is being synthesize where? Liver.

00:35 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.

00:49 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 with jaundice? As being the prevalent symptom? Our is it going to be more of an obstructive type emphysema? Obstructive.

01:08 First and foremost, you're going to look for a decrease FEV1/FVC ratio.

01:13 Severely decreased less than 80% and maybe down to 25% Or 30%, Panecinar.

01:20 How old is your patient most likely with Alpha-1 Anti-Trypsin that presents with such emphysema? Well, if they weren't smokers, still young, maybe about 40 to 45, hmm...

01:31 What if they are smoking and have Alpha-1 Anti-Trypsin deficiency? How old is that patient? A good decade younger.

01:38 Wow! At 30-35, really dangerous! Let's continue.

01:43 The deficiency of Alpha-1 Anti-Trypsin enzyme with the accumulation of proteases in the liver causing damage to it.

01:50 What is a gene for Alpha-1 Anti-Trypsin? PI. Remember? PI Stands for protease inhibitor What a beautiful name for an enzyme that does exactly what you expected it to do.

02:04 To hold back your protease.

02:06 That's your PI.

02:07 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, genetically.

02:19 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 Alpha-1 Anti-Trypsin But luckily, your patient is going to survive.

02:38 The only issue really there with heterozygous will be more so, the liver, right? What if there were to Z’s? That is homozygous.

02:46 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. Then, immediately The entire lung, Panecinar emphysema In the liver gets damage as well going into Cirrhosis.

03:05 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.

03:22 Will show you within hepatocytes these globules.

03:26 Walk me through this.

03:28 How important 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, hepatocyte remember this is a type of enzyme or protein.

03:41 All protein is produced from your...good.

03:46 We're talking about translation, transcription in the nucleus And from the nucleus, you've just produced a protein.

03:52 Or you just produced a messenger RNA.

03:55 Out comes the mRNA, where is it going? Rough endoplasmic reticulum, good.

04:00 And you begin the process of protein synthesis, right? Translation.

04:05 But now, you don't have the proper genes for it.

04:08 But yet, The rough endoplasmic reticulum is still producing protein.

04:12 It is abnormal.

04:14 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.

04:24 You see how important that statement is? Because that's what's going to help you get your question right.

04:30 That is what is going to help you, properly manage your patient, who has severe Alpha-1 Anti-Trypsin deficiency.

04:36 And this is also very important for you to know.