Alpha 1 antitrypsin deficiency causes, symptoms, diagnosis, treatment, pathology

Summary

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. 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.