Alpha-1 Antitrypsin Deficiency – causes, symptoms, diagnosis, treatment, pathology

learning medicine is hard work osmosis makes it easy it takes our lectures and notes to create a personalized study plan with exclusive videos practice questions and flashcards and so much more try it free today alpha-1 antitrypsin deficiency is a genetic disorder where a protein called alpha 1-antitrypsin is defective or absent the name alpha 1-antitrypsin is a holdover from when the protein was discovered a name given before its function was actually known as it turns out alpha 1-antitrypsin is a protease inhibitor that inactivates elastase which is a type of protease an enzyme that breaks down other proteins since alpha 1-antitrypsin inactivates elastase elastase can’t break down elastin so alpha 1-antitrypsin deficiency leads to the opposite case elastin breakdown which particularly affects the lungs in addition defective alpha 1-antitrypsin can cause damage to the liver now in the lungs let’s zoom in on a tiny alveolus which is where gas exchange happens if there’s some sort of infection or other cause of inflammation inflammatory cells like neutrophils arrive on the scene neutrophils make an enzyme called neutrophil elastase a protease capable of breaking down elastin which is an extracellular matrix protein that gives elasticity and strength to the lung tissues so while these little guys can help fight off infection by breaking down proteins of the bacteria they can also go on to break down that precious elastin fortunately the liver makes alpha 1-antitrypsin which gets released into the blood and sent to the lungs where it inhibits neutrophil elastase in activating it before it can break down the protein elastin without alpha 1-antitrypsin the opposite happens neutrophil elastase goes unchecked and it damages the walls of the alveoli and without that elastin the alveoli lose their elasticity and structural integrity zooming out a bit and looking at the acid s which is a bunch of alveoli it just turns into one big cavity this destruction and enlargement of the air spaces is called emphysema it turns out that emphysema can develop in a couple different ways and alpha 1-antitrypsin deficiency causes pan acinar emphysema meaning the whole acid s is affected and it also tends to affect the lungs lower lobes the most another effect of unchecked inflammation in Elfa one antitrypsin deficiency is chronic bronchitis in bronchiectasis two conditions resulting from chronic airway inflammation so alpha 1-antitrypsin deficiency can lead to emphysema bronchiectasis and chronic bronchitis all types of chronic obstructive pulmonary disease or COPD another more common cause of COPD is smoking and if someone with alpha 1-antitrypsin deficiency also smokes they tend to get an earlier onset of COPD than they would have otherwise an example of a gene environment interaction the gene that encodes alpha one antitrypsin protein is called sir panel one which stands for serine protease inhibitor clade a member one which is found on the long arm of chromosome 14 while some mutations in sir Pinot one completely about the genes message meaning no protein gets made others like the most common mutation called Piz results in a miss folded alpha one antitrypsin protein being made miss folded alpha one antitrypsin can aggregate and get stuck in the endoplasmic reticulum of the liver hepatocyte swear it’s made causing some of those cells to die now each wild-type or normal copy of alpha one antitrypsin protein termed P I M contributes 50% of normal alpha 1-antitrypsin or a 180 activity meaning two normal copies gets you 100% which just means that there’s a normal amount of alpha 1-antitrypsin in the blood if instead they had one normal copy in one mutant copy or z abbreviated PMZ the mutated gene only contributes about 10% of normal amounts so these individuals only have about 60% the normal levels which is usually enough to protect the lungs in non-smokers if both copies of the gene were mutant Z copies then typically there’s only 15 to 20 percent of normal levels which results in alpha 1-antitrypsin deficiency while there is some increased risk of lung and liver injury in P imz individuals severe deficiency with these two mutant genes gives these individuals a much higher risk of lung and liver disease having said that though some people with Piz Z deficiency can live their entire lives with no longer liver disease if their environmental exposures are minimal symptoms of alpha 1-antitrypsin deficiency typically involve the lungs and liver the changes in the lungs that cause chronic obstructive pulmonary disease can result in shortness of breath as well as wheezing mucus production in a chronic cough the death of liver cells can ultimately lead to cirrhosis a process in which normal liver tissues replaced with scar tissue cirrhosis can ultimately lead to a number of complications including an inability to make coagulation factors difficulty with detoxification leading to a buildup of waste products that can cause hepatic encephalopathy portal hypertension that can lead to esophageal varices and an increase in the risk of a type of liver cancer called hepatocellular carcinoma although cirrhosis usually affects adults even newborns can have complications like jaundice which is a buildup of bilirubin in the blood because of poor excretion by the liver a very small minority of infants who are born with 2z genes can develop liver failure during their first years of life and require a liver transplant if though somebody has a mutant syrup you know one that results in no alpha 1-antitrypsin as opposed to the misfolded ones that gets stuck then they typically don’t have liver disease diagnosis of alpha 1-antitrypsin deficiency often starts with a chest x-ray or chest CT scan to look for hyper-inflated lungs or evidence of damaged lung tissue in addition pulmonary function testing can be used to measure how quickly air exits the lungs which can be slower than normal the level of alpha 1-antitrypsin in the blood can also be measured cirrhosis caused by alpha 1-antitrypsin can be diagnosed with liver ultrasound or a liver biopsy when evaluating a biopsy microscopic sections of liver tissue are stained with a combination of two reagents called periodic acid Schiff or pas this test stains glycoproteins like alpha-1 antitrypsin a pink color the tissue is also exposed to dye a space what is an enzyme that normally destroys a lot of glycoproteins but since alpha 1-antitrypsin is stuck and hidden away in the endoplasmic reticulum the eye states can’t get to it and so it’s diastasis resistant so we say that they be periodic acid shift+ or pas positive as well as diastasis resistant in terms of treatment augmentation therapy is where you give intravenous infusions of normal alpha 1-antitrypsin protein purified from the blood of healthy plasma donors this doesn’t cure the lung disease but it does slow or halt its progression so other therapies for chronic obstructive pulmonary disease like inhalers and supplemental oxygen are often needed as well supplementing the deficient protein in the blood doesn’t fix the liver problems since they’re caused by defective alpha 1-antitrypsin building up in the hepatocytes so standard treatments for cirrhosis are usually needed like lactulose to prevent hepatic encephalopathy all right as a quick recap in alpha 1-antitrypsin deficiency the alveoli in the lungs are damaged by neutrophil elastase since there’s insufficient alpha 1-antitrypsin to counter it causing chronic obstructive pulmonary disease and in the liver misfolded alpha 1-antitrypsin builds up killing hepatocyte sin leading to cirrhosis you


  1. hola saludos desde argerntina!!! impecable como siempre!! you inspired me to start my own channel on youtube!! thannks !!

  2. Every video made by u is extraodinary i note each and every word spoken in ur video its really helpful to grab entire concept on a specific topic….

  3. I'm getting tested for this atm. I'm 35 with all of a sudden severe emphysema. They are worried because my dad died at 40 from liver cancer. And here I am so tired and sick just since Nov… I also have the alpha 1 skin issue which I've had since age 3. Maybe I can wear my first real bathing suit without shorts.. If I dont die first.

  4. Omg thank you for existing! I've been trying to understand this for days reading in text book and I have been so confused! You clarified EVERYTHING in 8 minutes! Wow! Thank you!!!

  5. I just want to say there’s 2 ways you can have this “alpha-1” can be a carrier or have it. My aunt died at age 42 bc the alpha one was effecting her after having a Brian angerizium-don’t quote me on how to spell that- and also my baby cousin just died at 3 months old due to fluid build up in her lungs “another act of this rare genetic disease” So my daughter was born today and since I’m a carrier and could easily pass it down to her… I’m making her get tested the doctors thinks it’s best to do a family tree but I don’t think that’s 110% accurate!! And I know the blood test are I just don’t think I need to waste time and see what my family trees gonna turn out to be. I wish everyone here with this rare disease good luck and wish everyone the best..!!!

Leave a Reply

(*) Required, Your email will not be published