Introduction
Arterial liver dysplasia syndrome-Arteriohepatic dysplasia syndrome, also known as cholestasis syndrome, Alagille syndrome. The condition is a hereditary disease, which is autosomal dominant and has a family-like tendency.
Cause
(1) Causes of the disease
This disease is autosomal dominant.
(two) pathogenesis
1. The bile excreted in the bile contains bile acid, which increases bile secretion and promotes the excretion of bilirubin, cholesterol, phospholipids and other fat-soluble organisms (including certain drugs) from the bile. When bile acid enters the duodenum, it emulsifies fat and forms water-soluble micelle with the fat breakdown product so that the fat is absorbed by the intestinal mucosa. Cholic acid is produced by the metabolism of cholesterol in the blood through the liver cells. After being combined with glycine and taurine in the cells, it is discharged into the capillary tube and enters the intestinal tract. After assisting the absorption of fat, most of it is absorbed in the distal part of the ileum. Entry into the portal and intestinal-hepatic circulation can be reused. Hepatocytes convert cholesterol into bile acid, which is regulated by blood bile acid concentration. When bile acid is increased, this reaction can be inhibited, and when it is lowered, the reaction is promoted.
2. Pathophysiology and clinical features of cholestasis can cause the following pathophysiological changes and clinical consequences (Figure 1).
(1) Substances that are normally excreted through the bile are detained or refluxed to the body, causing their blood levels to rise and produce corresponding clinical manifestations. Such as high binding bilirubinemia, causing jaundice; hypercholesterolemia, can cause skin itching; hypercholesterolemia, can cause yellow tumor in severe cases. Serum phospholipids and lipoprotein X were both increased. Excretion of certain drugs, contrast agents, such as sodium sulfonium bromide (BSP), 131I rose red, etc., also occurs.
(2) When the intestinal bile is reduced or absent, and the combined bilirubin is reduced, the fecal color is pale or grayish white; the bile acid is reduced, resulting in fat and fat-soluble vitamin absorption disorder, and the child may develop steatorrhea, malnutrition, and growth. Stable development and fat-soluble vitamin deficiency. Vitamin A deficiency can occur in the spot, skin and mucous membrane keratosis; D deficiency causes rickets, hand and foot sputum; E deficiency can cause neuromuscular degeneration, proximal muscle atrophy; K deficiency can cause intracranial, gastrointestinal, etc. Bleeding, prolonged blood prothrombin time.
(3) Hepatocyte damage and/or intra-biliary cholestasis caused by primary disease can often cause focal necrosis of the liver, giant liver cell deformation, hepatosplenomegaly and abnormal liver function, such as ALT, AST, Alkaline phosphatase, 5-nucleotidase and alpha-fetoprotein are elevated, and albumin and coagulation factors are impaired. Progression of the lesion can progress to biliary cirrhosis, eventually leading to portal hypertension and/or liver failure. However, most of the sick children can recover smoothly.
symptom
Sustained jaundice begins after birth, and itching occurs throughout the body about 3 months. Chronic intrahepatic cholestasis of tendons or subcutaneous skin with pigmentation such as yellow tumor; characteristic appearance (forehead protrusion, eyeball depression, eye distance increase) , saddle nose, small sacral tip, forward extension); spinal deformity; delayed development; mental retardation; hypogonadism; cardiovascular malformation: more than 80% with congenital cardiovascular abnormalities, peripheral pulmonary artery Stenosis is the most common. The rest were arterial catheter closure, atrial or ventricular septal defect, tetralogy of Fallot, permanent arterial trunk, aortic coarctation, renal artery, coronary artery and left subclavian artery stenosis.
diagnosis
According to chronic intrahepatic cholestasis, peripheral pulmonary stenosis, specific facial and butterfly-shaped spine, cardiovascular malformations and other characteristics can be diagnosed.
Identification
1. Hepatic cholestasis must carefully distinguish between intrahepatic infectious cholestasis and hereditary and metabolic causes (congenital abnormalities) because their clinical manifestations are very similar. Examinations for galactosemia, congenital fructose intolerance and tyrosinemia should be performed promptly, as special dietary therapies can be implemented. Alpha 1-antitrypsin deficiency, cystic fibrosis, and neonatal iron storage disorders should also be considered. When considering Alagille or Zellweger syndrome, special physical characteristics are helpful for diagnosis. Unless the bile duct is spontaneously perforated, the child with extrahepatic cholestasis generally performs well; the stool is usually completely white and the liver is enlarged and hard. Premature infants and children below the gestational age are considered to be infant hepatitis.
2. Bile Concentration Syndrome This condition is due to the fact that some hemolytic diseases (Rh, ABO) newborns and some infants who receive total venous nutrition have their bile accumulated in the bile duct or medium-sized bile duct. The same mechanism can cause an inherent blockage of the common bile duct. Hypoxia-reperfusion injury in the absence of Rh blood group can also cause cholestasis. In severe hemolysis, cholestasis can be complete with white stools. The level of bilirubin can be as high as 40 mg/dl (684 μmol/L), which is mainly a direct reaction. If bile concentration occurs in the extrahepatic bile duct, it is more difficult to distinguish from bile duct atresia. Feasible choleretic agentPhenobarbital, ursolic acid deoxycholic acid) test treatment. Once the bowel color changes to normal or the 99mTc-DIDA scan sees bile excretion into the duodenum, it can be determined that the extrahepatic bile duct is open. During the transition of stool color to normal, parents sometimes complained of small bile-colored emboli in the stool of the child. Although most cases require a slow recovery within 2 to 6 months, further examination (ultrasound, DIDA scan, liver biopsy) is required for complete cholestasis lasting more than 2 weeks. Where possible, laparotomy for extrahepatic bile ducts . If necessary, the common bile duct is flushed to remove the obstructed concentrated bile material.
When suspected to be idiopathic (uninfected, metabolic, and toxic), a "surgical" disease of the bile duct should be confirmed rather than extrahepatic. DIDA scans and ultrasound examinations in this area may be helpful in diagnosis. Some people used a gut test during DIDA scan to prove that the biliary tract is not blocked. Liver biopsy often has diagnostic significance, especially for infants older than 6-8 weeks. However, biopsy may be misleading for infants under 4 weeks of age. If you fail to check the opening of the biliary tree, the liver biopsy does not diagnose the typical case of the disease, or the persistent complete cholestasis (white stool), it prompts the need for experienced surgeons to do small laparotomy And cholangiography during surgery. Occasionally, a small but unclosed extrahepatic bile duct tree (hypopy) is likely to be the result of a reduction in bile flow, rather than a cause, without having to rebuild the hypoplastic bile duct.
3. Extrahepatic bile duct atresia with multiple malformations, early liver enlargement, subsequent progressive increase, blood alkaline phosphatase, 5-nucleotidase and low-density lipoprotein (lipoprotein X, LP-X) The increase is significant, although there is a small overlap between the two. Abnormal gallbladder or dysplasia was found during B-ultrasound examination. If the gallbladder is present, cholangiography is also required. There is yellow bile in the gallbladder, indicating that there is no atresia in the proximal end of the extrahepatic bile duct system. Radiography shows a contrast agent in the duodenum, which can rule out obstruction of the distal extrahepatic bile duct.
complication
Delayed growth and development, mental retardation; yellow tumor; hypogonadism; often accompanied by congenital cardiovascular abnormalities.
treatment
Western medicine treatment
CholestyramineCholestyramineWith a low-fat diet, a variety of fat-soluble vitamins can alleviate jaundice and help the absorption of yellow tumors and the growth and development of children. Peripheral pulmonary stenosis does not require special treatment, other cardiovascular malformations are surgically treated according to the condition.
prevention
The disease is autosomal dominant, and precautions should be taken from pre-pregnancy to prenatal:
Pre-marital medical examination plays an active role in preventing birth defects. The size of the effect depends on the examination items and contents, including serological examination (such as hepatitis B virus, treponema pallidum, HIV), reproductive system examination (such as screening for cervical inflammation), Ordinary medical examinations (such as blood pressure, electrocardiogram) and asking about the family history of the disease, personal medical history, etc., do a good job in genetic disease counseling.
Pregnant women should avoid harmful factors as much as possible, including away from smoke, alcohol, drugs, radiation, pesticides, noise, volatile harmful gases, and toxic and harmful heavy metals. Systemic birth defect screening is required during antenatal care during pregnancy, including regular ultrasound, serological screening, and, if necessary, chromosomal examination.
Once an abnormal result occurs, it is necessary to determine whether to terminate the pregnancy; the safety of the fetus in the uterus; whether there is sequelae after birth, whether it can be treated, and how the prognosis is. Take practical and feasible treatment measures.
The prenatal diagnostic techniques used are: 1 amniocentesis cell culture and related biochemical tests (amniotic puncture time is appropriate for 16 to 20 weeks of pregnancy); 2 maternal blood and amniotic fluid alpha-fetoprotein determination; 3 ultrasound imaging (applicable in about 4 months of pregnancy) 4X line examination (after 5 months of pregnancy) is beneficial for the diagnosis of fetal skeletal malformation; 5 chromatin determination of villus cells (40 to 70 days of conception), predicting fetal sex to help diagnose X-linked genetic diseases; 6 application gene linkage analysis; 7 fetal microscopy.
Through the application of the above technology, the birth of a fetus with severe genetic diseases and congenital malformations is prevented.
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