Alpha 1 antitrypsin deficiency causes, symptoms, diagnosis, treatment, pathology
Summary
TLDRAlpha-1 antitrypsin deficiency is a genetic disorder where the alpha-1 antitrypsin protein, a protease inhibitor, is defective or absent, leading to lung and liver diseases. The lack of this protein allows neutrophil elastase to damage lung tissue, causing emphysema and chronic bronchitis, which are types of COPD. Liver issues arise from misfolded alpha-1 antitrypsin accumulating in hepatocytes, potentially leading to cirrhosis. The condition is diagnosed through imaging, pulmonary function tests, and blood level measurements. Treatment includes augmentation therapy and managing COPD and liver complications, but it does not cure the disease.
Takeaways
- 🧬 Alpha-1 antitrypsin deficiency is a genetic disorder affecting the protein alpha-1 antitrypsin, which is crucial for preventing lung and liver diseases.
- 🛡️ Alpha-1 antitrypsin acts as a protease inhibitor, neutralizing proteases like neutrophil elastase that can break down proteins, including elastin in lung tissues.
- 🚨 In the absence of alpha-1 antitrypsin, neutrophil elastase can damage lung tissue, leading to a loss of elasticity and structural integrity of the alveoli, causing emphysema.
- 💨 Emphysema caused by alpha-1 antitrypsin deficiency is pan-acinar, affecting the entire acinus and predominantly impacting the lower lobes of the lungs.
- 🚭 Smoking exacerbates the effects of alpha-1 antitrypsin deficiency, leading to an earlier onset of chronic obstructive pulmonary disease (COPD).
- 🧬 The gene responsible for encoding alpha-1 antitrypsin is called SERPINA1, and mutations in this gene can lead to the production of misfolded proteins or no protein at all.
- 🧬 The most common mutation, PiZ, results in misfolded alpha-1 antitrypsin that can aggregate and cause liver damage due to accumulation in hepatocytes.
- 🌟 Alpha-1 antitrypsin deficiency is a recessive disease, requiring two mutant copies of the gene (ZZ) for the disease to manifest.
- 🏥 Diagnosis of alpha-1 antitrypsin deficiency can involve chest imaging, pulmonary function testing, and blood level measurements of the protein.
- 🛠️ Treatment options include augmentation therapy to replace alpha-1 antitrypsin in the blood and standard treatments for cirrhosis if liver problems are present.
Q & A
What is alpha-1 antitrypsin deficiency?
-Alpha-1 antitrypsin deficiency is a genetic disorder where the protein alpha-1 antitrypsin is defective or absent, leading to lung and liver diseases.
What is the role of alpha-1 antitrypsin in the body?
-Alpha-1 antitrypsin is a protease inhibitor that inactivates proteases like trypsin and neutrophil elastase, preventing the breakdown of proteins, especially elastin in the lungs.
How does alpha-1 antitrypsin deficiency affect the lungs?
-Without alpha-1 antitrypsin, neutrophil elastase breaks down elastin in the lungs, damaging the alveoli, leading to a loss of elasticity and structural integrity, and causing emphysema.
What type of emphysema is caused by alpha-1 antitrypsin deficiency?
-Alpha-1 antitrypsin deficiency causes panacinar emphysema, which affects the whole acinus and tends to impact the lower lobes of the lungs the most.
How can alpha-1 antitrypsin deficiency lead to chronic bronchitis?
-Unchecked inflammation due to alpha-1 antitrypsin deficiency can result in increased mucus production and narrowing of the airways, leading to chronic bronchitis.
How does smoking affect individuals with alpha-1 antitrypsin deficiency?
-If someone with alpha-1 antitrypsin deficiency smokes, they are likely to experience an earlier onset of COPD due to the combined effects of genetic and environmental factors.
What is the gene responsible for encoding alpha-1 antitrypsin protein?
-The gene that encodes the alpha-1 antitrypsin protein is called SERPINA1, which stands for serine peptidase inhibitor, clade A, member 1.
What is the most common mutation associated with alpha-1 antitrypsin deficiency?
-The most common mutation associated with alpha-1 antitrypsin deficiency is the PiZ mutation, which results in a misfolded alpha-1 antitrypsin protein.
How does alpha-1 antitrypsin deficiency affect the liver?
-Misfolded alpha-1 antitrypsin can aggregate and get stuck in the endoplasmic reticulum of liver hepatocytes, causing cell death and potentially leading to cirrhosis.
What are the typical symptoms of alpha-1 antitrypsin deficiency in the lungs and liver?
-Symptoms of alpha-1 antitrypsin deficiency in the lungs include shortness of breath, wheezing, mucus production, and chronic cough. In the liver, it can lead to cirrhosis, which has various complications such as difficulty in making coagulation factors, hepatic encephalopathy, and an increased risk of hepatocellular carcinoma.
How is alpha-1 antitrypsin deficiency diagnosed?
-Diagnosis of alpha-1 antitrypsin deficiency often starts with a chest X-ray or CT scan to look for hyper-inflated lungs or damaged lung tissue. Pulmonary function testing and measuring the level of alpha-1 antitrypsin in the blood can also be used. For liver issues, a liver biopsy can be performed, and the tissue can be tested for PAS positivity and diastasis resistance.
What is the treatment for alpha-1 antitrypsin deficiency?
-Augmentation therapy, which involves replacing alpha-1 antitrypsin in the blood, is one treatment option. However, it does not cure the disease, and other therapies for COPD, such as supplemental oxygen, may also be needed. Liver problems due to alpha-1 antitrypsin buildup require standard treatments for cirrhosis, like using lactulose to prevent hepatic encephalopathy.
Outlines
😷 Alpha-1 Antitrypsin Deficiency and Its Effects
Alpha-1 antitrypsin deficiency is a genetic disorder where the alpha-1 antitrypsin protein, a protease inhibitor, is defective or absent, leading to lung and liver diseases. This protein normally prevents proteases like neutrophil elastase from breaking down elastin, a protein important for lung elasticity. When absent, proteases damage lung tissue, causing emphysema characterized by enlarged air spaces. The condition affects the lower lung lobes predominantly and can lead to chronic bronchitis, contributing to chronic obstructive pulmonary disease (COPD). The genetic aspect involves mutations in the SERPINA1 gene, which may either delete the gene's message or result in misfolded proteins that cause liver damage. The disease is recessive, and symptoms include shortness of breath, wheezing, and chronic cough due to COPD, and liver cirrhosis due to cell death in the liver.
🧬 Diagnosis and Treatment of Alpha-1 Antitrypsin Deficiency
Diagnosing alpha-1 antitrypsin deficiency involves chest X-rays or CT scans to identify lung damage, pulmonary function tests to measure airflow, and blood tests to measure the protein's levels. Liver cirrhosis due to the buildup of misfolded alpha-1 antitrypsin can be confirmed with a liver biopsy, where the liver cells are stained with periodic acid and Schiff reagents, revealing diastasis-resistant alpha-1 antitrypsin. Treatment options include augmentation therapy, which replaces the deficient protein in the blood, and supplemental therapies for COPD such as supplemental oxygen. Liver issues are treated with standard cirrhosis therapies, like lactulose to prevent hepatic encephalopathy. The video concludes with a recap of the disease's impact on lung function and liver health, and a reference to Osmosis.org for further educational resources.
Mindmap
Keywords
💡alpha-1 antitrypsin deficiency
💡protease
💡neutrophil elastase
💡emphysema
💡chronic bronchitis
💡COPD
💡SERPINA1
💡misfolded protein
💡cirrhosis
💡augmentation therapy
💡lactulose
Highlights
Alpha-1 antitrypsin deficiency is a genetic disorder affecting the protein alpha 1-antitrypsin, leading to lung and liver disease.
Alpha 1-antitrypsin is a protease inhibitor that prevents the breakdown of proteins by proteases.
Neutrophil elastase, an enzyme from immune cells, breaks down elastin in the lungs, affecting their elasticity and strength.
The liver produces alpha 1-antitrypsin to inhibit neutrophil elastase, protecting lung tissues.
Without alpha 1-antitrypsin, neutrophil elastase damages the alveoli, causing emphysema.
Alpha-1 antitrypsin deficiency leads to pan acinar emphysema, affecting the entire lung and predominantly the lower lobes.
Unchecked inflammation from the deficiency can also result in chronic bronchitis.
Alpha-1 antitrypsin deficiency can cause both emphysema and chronic bronchitis, which are types of COPD.
Smoking can exacerbate COPD in individuals with alpha 1-antitrypsin deficiency, leading to earlier onset.
The gene responsible for alpha 1-antitrypsin is called SERPINA1, with mutations impacting the protein's function.
The most common mutation, PiZ, results in misfolded alpha 1-antitrypsin that can aggregate in the liver.
Having one normal and one mutant gene (PiMZ) results in about 60% of normal alpha 1-antitrypsin levels.
Two mutant Z copies lead to alpha 1-antitrypsin deficiency, with only 15-20% of normal levels.
Symptoms of alpha 1-antitrypsin deficiency include shortness of breath, wheezing, and chronic cough.
Liver complications can lead to cirrhosis, which has several severe health implications.
Diagnosis of alpha 1-antitrypsin deficiency involves chest imaging, pulmonary function testing, and blood level measurements.
Liver cirrhosis caused by misfolded alpha 1-antitrypsin can be diagnosed with a liver biopsy and specific staining tests.
Treatment options include augmentation therapy to replace alpha 1-antitrypsin in the blood and standard treatments for cirrhosis.
Transcripts
alpha-1 antitrypsin deficiency is a
genetic disorder in which a protein
called alpha 1-antitrypsin is defective
or absent and this causes lung and liver
disease trips ins are a type of protease
which is an enzyme that can break down
other proteins
so this antitrypsin protein is a
protease inhibitor and inactivate strip
sins thereby preventing protein
breakdown the alpha one is just a letter
and number combination given before its
role was known
now in the lungs if we zoom in on a tiny
alveolus which is where gas exchange
happens when there's some sort of
infection or other cause of inflammation
immune 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 lung tissues
so while these little guys can help
fight off infection by breaking down
proteins of the bacteria it 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 just like
it inhibits trypsin in activating it
before it can break down the elastin
without alpha 1-antitrypsin the opposite
happens neutrophil elastase goes
unchecked and it damages the walls of
the alveolus and without that elastin
the alveolus loses its elasticity and
structural integrity
zooming out a bit and looking at the
hacen 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 Asness is affected and
it also tends to affect the lungs lower
lobes the most another effect of
unchecked inflammation in alpha-1
antitrypsin deficiency is chronic
bronchitis resulting from increased
mucus production in narrowing of the
Airways so alpha-1 antitrypsin
deficiency can lead to both emphysema
and chronic bronchitis which are the two
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
now the gene that encodes alpha
1-antitrypsin protein is called sir Pina
one which stands for serpent peptidase
inhibitor clade a member one while some
mutations in Serafina one completely
delete the genes message meaning there's
no alpha one antitrypsin protein 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
hepatocytes where it's made causing some
of those cells to die
now each wild-type or normal copy of the
alpha 1-antitrypsin gene termed M
contributes 50% of normal alpha
1-antitrypsin activity meaning its
codominant and two normal copies gets
you a hundred percent normal activity
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 z abbreviated
PMZ
the mutated gene only contributes about
10% of normal amounts so these
individuals only have about sixty
percent the normal levels in their blood
which is actually usually enough to
protect the lungs in non-smokers
if both copies of the gene were mutant Z
copies though then typically there's
only about fifteen to twenty percent of
normal levels which results in alpha
1-antitrypsin deficiency since you need
both mutant copies for the disease this
makes alpha 1-antitrypsin deficiency a
recessive disease symptoms of alpha
1-antitrypsin deficiency typically
involved the lungs in the liver the
changes in the lungs that cause chronic
obstructive pulmonary disease result in
shortness of breath as well as wheezing
mucus production and 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 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 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 or buildup
of bilirubin in the blood because of
poor excretion by the liver if though
somebody has the mutant subpoena one
gene that results in no alpha
1-antitrypsin protein as opposed to the
miss folded ones that gets stuck then
they typically don't have any liver
disease diagnosis of alpha 1-antitrypsin
deficiency often starts at the 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 misfolded alpha 1-antitrypsin
can be diagnosed with a liver biopsy
liver cells are treated with
accommodation of two reagents called
periodic acid and Schiff or pas this
test stains glycoproteins like alpha
1-antitrypsin a pink color the tissue is
also exposed to dye a space which is an
enzyme that normally destroys alpha
1-antitrypsin but since alpha
1-antitrypsin stuck and hidden away in
the endoplasmic reticulum dye states
can't get to it and destroy it and so we
say that it's diastasis resistant so we
say that they be periodic acid in shift+
or pas positive as well as diastasis
resistant
in terms of treatment augmentation
therapy is where you replace
alpha-1 antitrypsin in the blood
although this doesn't cure the disease
so other therapies for chronic
obstructive pulmonary disease like
supplemental oxygen are often needed as
well giving someone the deficient
protein in the blood doesn't fix the
liver problems since these are caused by
defective alpha-1 antitrypsin building
up in the hepatocytes so standard
treatments for cirrhosis are often
needed like using lactulose to prevent
hepatic encephalopathy all right as a
quick recap an alpha 1-antitrypsin
deficiency the alveoli the lungs are
damaged by neutrophil elastase since
there's no alpha 1-antitrypsin to
counter it and this causes chronic
obstructive pulmonary disease also in
the liver misfolded alpha 1-antitrypsin
builds up which kills the hepatocyte sin
leads to cirrhosis
what's up everyone thanks for watching
that video on alpha 1-antitrypsin
deficiency if you want to learn a little
bit more about that topic you should
head over to osmosis org we've got a
bunch of flashcards quiz questions
scheduling tools basically anything in a
med student or student in the medical
field you see that fly alright see you
guys
you
5.0 / 5 (0 votes)