Page 57 of 73
DISTURBANCES OF THE METABOLISM
12.84. INSUFFICIENCY and, - ANTITRYPSIN
a1-Antitripsin — inhibitor of trypsin and other proteolichesky enzymes. This glycoprotein is synthesized in a liver and makes about 80% of a1-globulinovy fraction of serum. In serum a1-antitrypsin is present at 24 fenotichesky forms. A normal phenotype of system of an ingibition of proteases — M; type Z, and also the intermediate MS, MZ and SZ types is associated with diseases of a liver. The phenotype of Z meets frequency of 1:2000 — 1:4000, is inherited on autosomal codominant type.
Clinical and datas of laboratory. The main signs at children to 3-month age — cholestatic jaundice and increase in a liver. Along with nonspecific increase a game -
centrations in serum of bilirubin, aminotransferases and an alkaline phosphatase decrease of the activity of a1-antitrypsin to 10 — 20% and disappearance of peak of a1-globulin on elektroforegramma is noted. The defining diagnostic character — detection of a phenotype of Pi by means of an immunoelectrophoresis.
Patomorfologiya. Periportal fibrosis and a cholestasia are constantly noted. Granules, PAS positive, resistant to a diastase (at the beginning of a disease they are found in periportal gepatsita, and further — in an average zone) (see fig. 12-23) are characteristic. These granules consist of abnormal sya-antitrypsin and collect in a liver owing to their small solubility. Other histologic signs are variable and include a hypoplasia of bilious channels, a periportal inflammation, existence of colossal cells and formation of pseudo-channels.
Treatment. Carry out a maintenance therapy.
Forecast. At most of children cirrhosis develops. At adults who since the childhood suffer from insufficiency of a1-antitrypsin and secondary damage of a liver the risk of development of a carcinoma of a liver considerably increases.
On autopsy damage of a liver is noted in 20 — 40% of cases; usually it is the centers of the biliary cirrhosis which developed owing to obstruction of bilious channels slime clots. Sometimes the mucoviscidosis is shown at newborns by cholestatic jaundice, a hepatomegalia and not specific rejections of functional tests. The first symptom of a disease — jaundice which spontaneously disappears in several weeks after the birth.
Cholestasia at babies do not treat. Further complications of polyfocal biliary cirrhosis and portal hypertensia, especially gastrointestinal bleedings, can demand creation of a porto-caval anastomosis.
This frustration inherited on autosomal recessively type is caused by deficit galaktozo-1-fosfaturidiltransferazy. Damage of a liver, a cataract and a delay of intellectual development are typical for it. Toxic manifestations are caused by galaktozo-1-phosphate accumulation.
Clinical and datas of laboratory. The disturbances connected with this defect arise during the pre-natal period and amplify after the birth when the child begins to receive the food rich with lactose (milk). Vomiting, a diarrhea, an arrest of development precede developing of cholestatic jaundice, a hepatomegalia, ascites, a hypoglycemia and spasms. If not to stop receipt of a galactose with food, then the child within several weeks will die from a liver failure. The presumable diagnosis is based on positive test of Benedict or detection of a galactose in the child's urine with cholestatic jaundice. The final diagnosis is made by means of a contents assessment in erythrocytes galaktozo-1-fosfaturidiltransferazy.
Patomorfologiya. The pseudo-acinar arrangement of hepatocytes is often observed at a galactosemia, but maybe at other metabolic frustration. The cholestasia and a steatosis is noted; besides, the cicatricial fabric destroying very tectonics of segments violently develops.
Treatment. The besgalaktozny diet rich with casein or proteins of soy is shown. Further the high security of food excluding a galactose and lactose is necessary. In case of development of a cataract surgical Treatment can be required.
Forecast. The galactose exception of food of the newborn gives surprising effect — within several days signs of damage of a liver disappear even if there were manifestations of its wrinkling or ascites. Further development of a cataract stops or it resolves. Treatment has no significant effect on the mental status of the patient.
HEREDITARY INTOLERANCE OF FRUCTOSE
This autosomal and recessive disease is caused by deficit fruktozo-1-fosfataldolazy (often) or fruktozo-1,6-diphosphatases (seldom). A toxic metabolite is fruktozo-1-phosphate. Symptoms of toxicosis (vomiting, diarrhea, a hypoglycemia, faints) and cholestatic jaundice appear after the beginning of consumption with food of fructose or sucrose. The liver increases, ascites develops; if not to exclude fructose from food, then there are cirrhosis and a liver failure. After loading fructose (intravenously) there are a proteinuria, a fruktozuriya, a hypoglycemia, a hypophosphatemia, excretion of uric acid increases.
The morphological picture of damage of a liver is characterized by a steatosis, parenchyma hypostasis, formation of pseudo-segments, a cholestasia and extensive periportal fibrosis. The diagnosis is confirmed by a histochemical method (lack of zymohexase and diphosphatase in liver tissue).
Purpose of the diet which is not containing fructose at all conducts to involution of changes in a liver; the patient can lead a normal life. It has a strong disgust for sweet.
This disease with an autosomal and recessive mode of inheritance affects a liver, kidneys and a pancreas. It is endemic in Northern Quebec (Canada). At the heart of a disease
deficit of an oxidase, parahydroxyphenyl-pyruvic acid, the enzyme turning this acid into homogentistic acid lies.
Clinical and datas of laboratory. The hereditary galactosemia meets in 2 forms. The acute form quickly conducts to a liver failure; the lethality among children of chest age is very high. At a chronic form modular cirrhosis, vitamin - D-resistant rickets, Fankoni's syndrome gradually develop, development of the child is late. At the second option of a current often there is a gepatoma. Level of tyrosine and methionine in plasma is increased, excretion of tyrosine and its metabolites with urine is increased. However these an izmenepiya are not specific; it is possible to suspect a tirozinemiya if the condition of the child who is treated concerning a galactosemia or hereditary intolerance of fructose does not improve against the corresponding diet.
Treatment. The diet with the low content of phenylalanine and tyrosine is shown. It improves a condition of kidneys, but has no effect on a liver.
NEONATAL HEPATITIS WITH INSUFFICIENCY OF ADRENAL GLANDS
This state strikes children with a hypopituitarism or an inborn hypoplasia of adrenal glands. The first signs appear aged till 3 months; they remind a cryptogenic cholestasia of newborns. The pathogeny, apparently, is connected with deficit of cortisol.
The clinical picture is characterized by a hypoglycemia and cholestatic jaundice, and also symptoms of an associated disease. The diagnosis is established on the basis of the low level of a serumal cortisone and reduction of products of a growth hormone at the patient with a hypopituitarism. Histologically damage of a liver is shown by the extensive giant-cell transformation which is minimum expressed by inflammatory reaction and absence of fibrosis. Replacement therapy by cortisol leads to clinical improvement and a complete recovery of functions of a liver.
The main infectious agents affecting a liver of newborns and babies are the hepatitis B virus, a cytomegalovirus, a virus of a herpes simplex, a rubella, a koksaka In; echoviruses 14 and 19; spirochetes (inborn syphilis) and toxoplasma (toxoplasmosis). Some specific characters of the infections caused by these activators are given in this section, however properties of activators are described in chapter 9.
Infection with a virus of hepatitis B can occur in utera, at the time of delivery and in the post-natal period. Usually the illness is transmitted from mother who is the asymptomatic carrier of a viral antigen "е" or at whom the acute viral hepatitis In in 2 months prior to childbirth or within 2 months after the delivery develops. Perinatal hepatitis B generally does not give clinical symptomatology. In typical cases the child within 2 months becomes the HBsAg carrier and remains to them for many years. At some patients the level of aminotransferases increases, and in bioptata of a liver the easy inflammatory phenomena in portal zones are found. In rare instances hepatitis flows immediately, is followed by heavy jaundice, in several days the child fells into a coma; 60 — 80% of patients perish. At adults, being since the childhood hepatitis B virus carriers, afterwards: the hepatocellular carcinoma can develop.
As effective protection against vertical transfer of a virus of hepatitis B serves administration of immunoglobulin against this virus in the first 48 h after the birth (in the subsequent terms efficiency of drug sharply falls) and then through certain intervals within 6 months.
The cytomegalovirus affecting a liver can get into an organism of the child of in utera, and also after the birth with milk or mother's saliva. Clinical and laboratory signs of tsitomegalovirusny hepatitis same, as cryptogenic cholestasia. The diagnosis is confirmed by detection of a virus in urine and increase of a caption of specific IgG-and IgM-antibodies. Occasionally in bioptata of a liver it is possible to observe characteristic cytoplasmic inclusions in hepatocytes and bilious channels (see fig. 12-24). The cytomegalovirus causes heavy inflammatory reaction after which extensive fibrosis and destruction of very tectonics of segments develop in a liver. A usual outcome are cirrhosis and portal hypertensia.
The transplacental infection a virus of a herpes simplex, Koksaki, echoviruses 14 and 19 leading to damage of a liver is usually deadly to the child. The extensive necrosis of tissue of liver and the progressing liver failure are characteristic of these morbid conditions. There is no specific treatment. The inborn rubella can cause hepatitis which clinical displays are typical for a cryptogenic cholestasia. Histologically this illness is characterized by a cholestasia, slight periportaljny fibrosis and the centers of a necrosis. Usually function of a liver is completely recovered, however cases of transition to the chronic hepatitis which is combined with a krasnushny syndrome (damage of heart, a cataract, a delay of intellectual development) are described.
Jaundice can be the only symptom of the sepsis caused E. coli (section 7.59). At such children blood coagulation disturbance therefore the biopsy of a liver is contraindicated is often observed. If bioptata nevertheless are taken, then in them it is possible to observe the necrosis centers on all segment, a periportal infiltration polymorphonuclear leukocytes and small abscesses. The current and the forecast are defined by a basic disease and its treatment.
Inborn syphilitic hepatitis meets seldom (section 9.55). The earliest symptom is jaundice; the diagnosis is established by means of reaction of VDRL. In bioptata of a liver reveal fibrosis of segments with a pericentral infiltration mononuclear leukocytes. Recovery of function of a liver can achieve by means of a penicillin therapy.
Damage of a liver at an inborn toxoplasmosis clinically reminds sepsis. Jaundice is changeable and unsharply expressed. The diagnosis is confirmed by positive test with Seybin's dye — Feldman. At histologic research of a liver find a nonspecific periportal inflammation; sometimes it is possible to reveal the histiocytes filled with toksoplazma.