Severe pulmonary disease 

Alpha-1 Antitrypsin Deficiency

Alpha 1-AT deficiency was first described in the late 1960s in patients with severe pulmonary disease. Shortly thereafter it was discovered to be a cause of neonatal liver disease, and now it is known to be a cause of liver disease in infancy, early childhood, adolescence, and in adults. The natural history of liver disease in alpha-1-antitrypsin deficiency is quite variable. Many individuals with the ZZ genotype never develop disease throughout their entire lives.
Alpha 1- AT deficiency becomes apparent in adults because of screening for liver disease in individuals who have liver function test abnormalities. The only hint to diagnosis may be coexistent lung disease at a relatively young age or a family history of liver and/or lung disease. Diagnosis is established by determining a reduced serum level of alAT as well as the performance of Alpha 1- AT genotyping.
Liver biopsy in Alpha 1- AT disease shows characteristic PAS-positive diastase-resistant globules in the periphery of the hepatic lobule.

Treatment

Treatment of Alpha 1- AT is nonspecific and supportive. Liver transplantation is curative. Recombinant AT administered IV has been used in patients with chronic lung disease due to 1-AT deficiency but is of no benefit in patients with Alpha 1- AT liver disease.

Alpha 1 antitrypsin deficiency:

• Due to protease inhibitor deficiency
• Increased neutrophil elastase
• Neonatal cholestasis may occur,
• Hepatocellular carcinoma may also develop
• Pulmonary disease may occur in form of emphysema
• Gene located on chromosome 14

Ans.C. Wegeners granulamatosis
Alfa 1 antitrypsin is an inhibitor of proteinase 3. Antiproteinase antibodies are seen in Wegener’s granulomatosis. 

Ans. is ‘b’ i.e., Pulmonary emphysema; ‘c’ i.e., Diastase resistant hepatic cells

o a₁-anti-trypsin deficiency, is an autosomal recessive disease marked by abnormally low levels of (serum) of this major protease inhibitor (Pi)

• Deficiency of the enzyme leads to pulmonary emphysema (panacinar)
• Liver is characterised by :

           Presence of round to oval cytoplasmic globular inclusions in hepatocytes which on H and E stains acidophilic and indistinctly demarcated from surrounding cytoplasm.

           They are PAS positive and diastase resistant

           In most part, only distinctive feature is globules infrequently-fatty change, mallory bodies.

           Neonatal hepatitis with cholestasis

           Fatty change (steatosis)

           Cirrhosis may develop which can transform into hepatocellular carcinoma.

Following information has been added in 8thie of Robbins

o In addition, cutaneous panniculitis, arterial aneurysm, bronchiectasis and wegener’s granulomatosis can occur in odi antitrypsin deficiency.

Ans. is ‘a’ i.e., PAS positive and diastase resistant globules are seen; ‘b’ i.e., Cirrhosis of liver; `c’ i.e., Mallory hyaline

• Adults: cirrhosis, chronic hepatitis, portal hypertension, jaundice, hepatocellular carcinoma, liver failure
• Liver, random, ultrasound guided needle core biopsy:

Hepatocytes with cytoplasmic PAS diastase positive globules compatible with alpha-1 antitrypsin deficiency

• Seen mallory hyaline

Ans. is ‘a’ i.e., Autosomal recessive
Alpha-1-antitrypsin deficiency is an autosomal recessive disorder. The most common manifestation is emphysema, which becomes evident by the third to fourth decade

Ans. is ‘a^‘ i.e., Panacinar-emphysema

Emphysema

• Emphysema is a condition of the lung characterized by abnormal permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of their walls and without obvious fibrosis. “Destruction of walls” is necessary to define emphysema. Enlargement of airspaces without destruction of their walls is termed overinflation, for example, the distention of airspaces that occurs in the remaining lung after unilateral pneumonectomy.

Types of emphysema

• Emphysema is classified according to its anatomic distribution within the lobule. There are four major types of emphysema ‑

1. Centriacinar (centrilobular) emphysema

• Centriacinar emphysema is the most common type of emphysema seen clinically. It is characterized by involvement of respiratory bronchioles, i.e. central (proximal) part of the acinus. So, both emphysematous and normal airspaces exist within the same acinus and lobule.
• The lesions are more common and more severe in the upper lobe, particularly in the apical segments.
• This is the type of emphysema that occurs predominantly in heavy smokers and usually coexists with chronic bronchitis.

2. Panacinar (Panlobular) emphysema

• The acini are uniformly enlarged from the level of the respiratory bronchiole to the terminal blind alveoli.
• This type of emphysema tends to occur more commonly in the lower zones and in the anterior margins of the lung, and it is usually most severe at the base.
• This type of emphysema is associated with al-antitrypsin deficiency.

3. Distal acinar (Paraseptal) emphysema

• This type of emphysema involves distal part of the acinus, while proximal part is normal. It is localized adjacent to the pleura, along perilobular septa.
• The involvement is seen adjacent to areas of fibrosis, scarring, or atelectasis and is usually more severe in the upper half of lungs.
• This type of emphysema is a common cause of spontaneous pneumothorax in young adults.

4. Irregular emphysema (Para-cicatricial emphysema)

• The acinus is involved irregularly and is almost invariably associated with scarring. It is the most common type of emphysema histologically.
• Most common type of emphysema is irregular emphysema, but it is not clinically significant as most patients are asymptomatic and it is only an autopsy finding. Most common type of emphysema seen clinically is centracinar emphysema.