A 47-year-old man comes to the office due to worsening shortness of breath for several months. The patient has no fever, weight loss, or cough. He has no other medical conditions and takes no medications. The patient does not use tobacco, alcohol, or illicit drugs. Vital signs are normal. Pulmonary examination demonstrates wheezing and poor air movement. Laboratory results are as follows: A liver biopsy is subsequently performed. Light microscopy of the tissue specimen after treatment with diastase and periodic acid-Schiff staining is shown in the exhibit. Given these findings, which of the following is the most likely cause of this patient's shortness of breath?

Question

A 47-year-old man comes to the office due to worsening shortness of breath for several months.  The patient has no fever, weight loss, or cough.  He has no other medical conditions and takes no medications.  The patient does not use tobacco, alcohol, or illicit drugs.  Vital signs are normal.  Pulmonary examination demonstrates wheezing and poor air movement.  Laboratory results are as follows:  A liver biopsy is subsequently performed.  Light microscopy of the tissue specimen after treatment with diastase and periodic acid-Schiff staining is shown in the exhibit.  Given these findings, which of the following is the most likely cause of this patient's shortness of breath?

Quizplus · Accepted Answer

11ec160b_3b28_710a_9249_11ddf2fc81c5_MD0001_00 This patient has alpha-1 antitrypsin (AAT) deficiency, an autosomal codominant disorder that can affect the lungs and liver. Produced primarily in the liver, AAT is a serum protein that inhibits several different proteolytic enzymes (in particular, neutrophil elastase), thereby reducing tissue damage caused by inflammation. Most individuals with AAT deficiency are homozygous for the Z allele, which causes decreased secretion of AAT secondary to abnormal protein folding. The diagnosis of AAT deficiency is established by measurement of the serum AAT level, followed by confirmatory genetic testing. Most individuals with AAT deficiency eventually develop severe panacinar emphysema due to unchecked destruction of the interalveolar septa (which contain large amounts of elastin). Smoking plays a synergistic role in the disease process by inducing lung inflammation and permanently inactivating AAT through oxidation of a crucial methionine residue. Therefore, smokers with AAT deficiency tend to develop dyspnea at a median age of 36 versus a median age of 51 in nonsmokers. Some patients with AAT deficiency develop liver disease due to intrahepatocyte accumulation of polymerized AAT molecules; the liver disease can progress to cirrhosis (the second most common cause of death behind emphysema in this population) and hepatocellular carcinoma. Histologically, intracellular granules of unsecreted AAT are seen within the periportal hepatocytes. These globules resist digestion by diastase (an enzyme that breaks down glycogen) and appear reddish-pink with the periodic acid-Schiff stain. (Choice A) Bronchial hyperreactivity is a hallmark of chronic asthma. (Choice C) Interstitial infiltration is a finding in interstitial pneumonitis. (Choice D) Intraalveolar substance accumulation is a finding in alveolar proteinosis. (Choice E) Pulmonary congestion is a finding in congestive heart failure. (Choice F) Pulmonary vascular obstruction occurs in pulmonary embolism or vasculopathy. Educational objective: Alpha-1 antitrypsin (AAT) is a serum protein that, through the inhibition of neutrophil elastase, reduces tissue damage caused by inflammation. Histologically, AAT deficiency can demonstrate reddish-pink globules on periodic acid-Schiff stain; these globules represent unsecreted, polymerized AAT in the periportal hepatocytes. __________ References: Diagnosis and management of patients with a1-antitrypsin (A1AT) deficiency. (http://www.ncbi.nlm.nih.gov/pubmed/22200689)

A 47-Year-Old Man Comes to the Office Due to Worsening