Review Question - QID 104813

This patient is presenting with alpha-1 antitrypsin deficiency which results in chronic obstructive pulmonary disease and cirrhosis as seen in figure C.

Alpha-1 antitrypsin deficiency is a genetic disorder that causes defective production of the alpha 1-antitrypsin enzyme. In the lungs, severe deficiency of alpha 1-antitrypsin causes interalveolar septal destruction and destruction of alveolar walls. This ultimately leads to panacinar COPD. The classic presentation is COPD in a relatively young patient with no smoking history or other risk factors for COPD. In the liver, alpha 1-antitrypsin deficiency causes misfolded gene products to aggregate in the hepatocellular endoplasmic reticulum. This accumulation ultimately results in cirrhosis with PAS-positive globules in the liver (Illustration A). The current primary treatment modality is intravenous infusions of alpha-1 antitrypsin.

When approaching this question it is important to first understand that a decreased FEV1/FVC with the chest radiograph demonstrating hyperinflation of the lungs suggests an obstructive pattern of pulmonary disease. In such a young patient (even with a smoking history) alpha-1 antitrypsin deficiency should jump to mind over other chronic diseases like COPD and emphysema which you would expect to see in older smokers. It is key to know other findings in alpha-1 antitrypisin deficiency such as the cirrhosis that occurs from aggregates of misfolded alpha-1 antitrypisin. Knowing that there are aggregates of misfolded protein should guide you to the correct histology even if you have never seen a biopsy of this disease!

Figures A-E are described in the incorrect answer explanations below. Figure F is a chest radiograph demonstrating emphysema. Note the increased hyperlucent lungs of large volume and flattened hemidiaphragms. Illustration A demonstrates PAS-positive globules in the liver which is characteristic of alpha-1 antitrypsin deficiency.

Incorrect Answers:
Answer 1: Figure A demonstrates normal liver histology.
Answer 2: Figure B demonstrates hepatic steatosis. Note the macrovesicular steatosis and hepatocytes followed with fat droplets. This could be seen in alcoholic fatty liver disease (history of alcohol abuse) and non-alcoholic fatty liver disease (ALT > AST, both elevated in an obese, non-alcoholic).
Answer 4: Figure D demonstrates hepatocellular carcinoma. Note the multitude of irregular cells characteristic of hepatocellular carcinoma. Many processes can predispose to HCC such as smoking, aflatoxin exposure (aspergillus), hemochromatosis, Hep B and chronic alcohol abuse.
Answer 5: Figure E demonstrates Mallory bodies (intracytoplasmic eosinophilic inclusion) which are characteristic of alcoholic hepatitis or non-alcoholic fatty liver disease.

Patients without any smoking history or risk factors should be tested for alpha-1-antitrypsin deficiency. Arterial blood gas testing is recommended for patients presenting with signs of severe disease, right-sided heart failure, or significant hypoxemia (1).