Changes

This 68-year-old white female was afflicted with severe emphysema due to alpha 1α1-antitrypsin deficiency. She had a 10 pack-year history of cigarette smoking but she had quit smoking 30 years ago. She elected to undergo lung volume reduction surgery to reduce complications of her emphysema. Post-operatively, she was ventilator dependent and her liver function declined. Further studies revealed hepatic cirrhosis. Her pulmonary function continued to decline and she died 26 days after her initial surgery.

File:IPLab5Antitrypsin12.jpg|This is a high-power photomicrograph of liver stained with periodic-acid Schiff's (PAS) stain. This demonstrates the PAS-positive granules of defective alpha 1α1-antitrypsin that accumulate in the Golgi of hepatocytes (arrows).

* <spoiler text="What is the genetic defect and pattern of inheritance in alpha1α1-antitrypsin deficiency?">Alpha 1α1-antitrypsin deficiency is an autosomal recessive disorder caused by mutations in the protease inhibitor locus of chromosome 14. In the mutations that lead to a deficiency of the enzyme, the protein is transcribed but there is abnormal folding of the protein, thus it cannot be processed by the endoplasmic reticulum of hepatocytes. The protein, therefore, accumulates in the endoplasmic reticulum forming PAS-positive granules.</spoiler>* <spoiler text="What is the pathogenesis of emphysema in patients with alpha 1α1-antitrypsin deficiency?">Alpha 1α1-antitrypsin is the major antiprotease and is responsible for inhibiting neutrophil elastase that can cause destruction of the alveolar wall. With alpha1α1-antitrypsin deficiency, neutrophil elastase goes unchecked and tissue damage ensues.</spoiler>* <spoiler text="What role does smoking play in the development of emphysema in patients with alpha 1α1-antitrypsin deficiency?">Smoking increases the numbers of neutrophils in the lung and accentuates the release of elastase from these neutrophils. With a deficiency of alpha 1α1-antitrypsin there is marked tissue damage.</spoiler>* <spoiler text="Is hepatic cirrhosis common in patients with alpha1α1-antitrypsin deficiency and what is the pathogenesis of the cirrhosis?">The abnormal alpha 1α1-antitrypsin protein accumulates in hepatocytes of all patients with this abnormality but only 8 to 20% develop cirrhosis. The exact mechanism for hepatic cirrhosis in patients with alpha1α1-antitrypsin deficiency is not well understood.</spoiler>