antitrypsin deficiency
Introduction
Introduction to antitrypsin deficiency Since 1963, Laurell and Eriksson have found that 1-antitypsin (1-antitypsin, abbreviated as 1-AT) is closely related to emphysema, and that 1-AT deficiency is the main cause of familial emphysema. The lack of 1-AT is closely related to the cirrhosis of infants and the onset of liver cancer. basic knowledge The proportion of illness: 0.001% - 0.003% Susceptible people: no specific population Mode of infection: non-infectious Complications: respiratory failure
Cause
Antitrypsin deficiency etiology
(1) Causes of the disease
The content of 1-AT is determined by the different types of a set of autosomal alleles. The locus is named Pi. In the genetic process, the homozygous PiMM consisting of two M-type alleles is normal. Type, PiMM is the most common normal functional genotype, PiZZ is a severely deleted allele of 1-AT, homozygous for ZZ, serum 1-AT content is 15% to 20% of normal people, this person often occurs Obstructive emphysema and juvenile cirrhosis, the homozygous SS of the PiS allele has a lack of 1-AT in the serum of 60% of normal people, and this person also has a tendency to emphysema; Heterozygos such as MZ and SZ also have 1-AT deficiency, in which emphysema and cirrhosis occur.
(two) pathogenesis
1. Normal metabolism of 1-AT
1-AT is a glycoprotein secreted by hepatocytes, with a molecular weight of 45,000 to 560 million (52 Kda). The release of 1-AT into plasma constitutes the main component of 1-AT globulin, and 1-AT in normal human (PiMM type) plasma. The concentration was 1.3 mg/ml, and the concentration of different Pi-type individuals was different.
1-AT is the most important protease inhibitor (PI) in human plasma, which can form complexes with various serine proteases, including elastase, trypsin, chymotrypsin, thrombin and bacterial protease. Its important role is to inhibit the elastase of neutrophils. Elastase can act on the structural proteins of elastin and its tissues in the alveolar wall to cause tissue damage. Therefore, the main physiological function of 1-AT is to protect the lower respiratory tract and others. The tissue is protected from elastase damage.
2. Genetics
The content of 1-AT is determined by the different types of a set of autosomal alleles. The locus is named Pi. Using the band electrophoresis technique, there are more than 70 kinds of 1-AT with different swimming speeds in the serum. The bands and alleles are arranged in English alphabet according to the speed of electrophoretic migration: B, E, F, G, I, L, M, N, P, O, R, S, V, W, X, Z, The international conference named PiM, PiS, Piz and other 1-AT variants and subtypes, constitute a protease inhibitor genetic phenotype system, in the genetic process, the homozygous PiMM consisting of two M-type alleles is normal The phenotype, PiMM is the most common normal functional genotype, PiZZ is a severely deleted allele of 1-AT, homozygous for ZZ, serum 1-AT content is 15% to 20% of normal people, such a person Obstructive emphysema and juvenile cirrhosis often occur. The homozygous SS of the PiS allele has a lack of 1-AT in the serum of 60% of normal people. This person also has a tendency to emphysema; Other phenotypes such as MZ, SZ and other heterozygotes also have 1-AT deficiency, some of which have emphysema and cirrhosis, currently considered PiZZ Mainly found in the Caucasian population, PiSZ, PiSS and other types are mainly found in the southern European population. China's research has not found PiZZ type, only a few heterozygous phenotypes, so it is considered that the hereditary 1-AT deficiency caused by emphysema is not in China. As important as Europeans, the clinical significance of heterozygous phenotypes needs further study.
3. Pathophysiological mechanisms
Under normal circumstances, the protease in the body is in equilibrium with the anti-protease. In the 1-AT deficiency, the elastase and anti-protease are imbalanced. When the protease activity exceeds the protease inhibition process, elastase causes continuous damage to the alveolar structure, lung tissue erosion, and alveolar septal damage. The persistence of the air cavity is extended, and the clinical manifestation is emphysema. Due to the disappearance of the alveolar wall, the small airway loses the stent and collapses during exhalation, causing damage to the lung function, which is mainly caused by damage to the alveolar connective tissue. Elastic fibers cause emphysema.
The 1-AT deficiency is caused by the fact that 1-AT synthesized in hepatocytes cannot be secreted into plasma, but accumulates to form inclusion bodies, and the cause of non-secretion is related to the accumulation of Z-type protease, and some of them have the risk of developing cirrhosis. By analyzing the inclusion bodies in hepatocytes, it is found that the structure of carbohydrates is abnormal, lacking the terminal N-acetyl sialic acid residue, and the core containing multiple mannose is a glycoprotein with incomplete processing.
Prevention
Antitrypsin deficiency prevention
Smoking has a great influence on the age and course of onset. 98% of women who do not smoke, 65% of men can live to 55 years old, and only 30% of women who smoke, 18% of men can live to the same age. Therefore, you should quit smoking.
Complication
Antitrypsin deficiency complications Complications, respiratory failure
Concurrent with hypercapnia and respiratory failure.
Symptom
Antitrypsin deficiency symptoms Common symptoms Hepatomegaly upper gastrointestinal bleeding Hepatic coma portal hypertension Huangqi
In the Caucasian population, about 1% to 2% of patients with emphysema are associated with 1-AT deficiency, and 80% to 90% of PiZZ individuals have total lobular emphysema. The clinical features are: early onset, respiratory symptoms Appeared in 30 to 40 years old, early symptoms are dyspnea after activity, cough and repeated respiratory infections, physical examination showed that patients have excessive weight loss, low breath sounds; chest radiograph showed horizontal sputum low level, lung hyperinflation, peripheral blood vessels decreased, In particular, the pulmonary lobule is obvious, the lung function indicates severe emphysema, the total amount of lung is limited, and the amount of diffusion is reduced. The blood gas analysis indicates that there is mild to moderate hypoxemia in the early stage without hypercapnia; Hypoxemia is associated with hypercapnia, and electrocardiogram shows right ventricular hypertrophy, which may be associated with right bundle branch block.
Examine
Antitrypsin deficiency test
Serum protein electrophoresis, acetate fiber electrophoresis, radioimmunoassay and electrophoretic immunoassay can also be used to measure serum trypsin inhibitory activity.
The ratio of lung residual capacity/lung volume increased, expiration was limited, diffusion decreased, and lung compliance increased.
Diagnosis
Diagnosis and identification of antitrypsin deficiency
diagnosis
Clinical manifestations combined with medical history can make a diagnosis of emphysema. In the Caucasian population, all patients with emphysema should be excluded from the possibility of 1-AT deficiency, and can be immunized by serum protein electrophoresis, acetate fiber electrophoresis, radioimmunoassay and electrophoresis. Analysis and other immunoassays can also measure serum trypsin inhibitory activity, and further stereotypes can help diagnose 1-AT deficiency.
Differential diagnosis
Should be differentiated from chronic obstructive emphysema and pulmonary heart disease.
