From Big Medical Encyclopedia

TOXIC DYSTROPHY OF THE LIVER (Greek toxikos the employee for greasing of arrows, i.e. poisonous; Greek dys-+ trophe food; synonym: massive necrosis of a liver, toxic necrosis of a liver, autolysis of a liver, acute yellow hepatatrophia) — the syndrome which is characterized by development of an extensive necrosis of a liver, shown symptoms of hepatocerebral insufficiency.

The etiology

Etc. the item can develop at influence of various factors. The acute viral hepatitis is its most frequent reason (see. viral hepatitis ), is more rare — poisonings with plant and industrial hepatotoxic substances, alcohol, and also nek-ry pharmaceuticals. Emergence Etc. of the item can be promoted by the hypoxia (see) caused by acute anemia or the expressed disturbances of blood circulation.

A pathogeny

Massive necroses of a liver at a viral hepatitis can be a consequence of replication of a virus in hepatic cells (see Viruses, Replication) and autoimmune reaction of hepatic membranes to native antigens. The leading role in a pathogeny Etc. of the item belongs to strengthening of processes of peroxide oxidation of lipids of membranes of hepatocytes and decrease in the anti-radical protection of cells which is carried out by a complex system of antioxidants (see. Antioxidants ). As a result of impact on a liver of the majority of viruses and hepatotoxic substances in organic compounds, hl. obr. in unsaturated fatty acids of phospholipids of cellular membranes of hepatocytes, the excess number of the free radicals (see Radicals free) having high reactivity and initiating chain reaction with formation of peroxides and hydroperoxides is formed. Strengthening of processes of peroxide oxidation of lipids in membranes of hepatocytes and decrease in antiradi-kalny protection of cells is accompanied by the deep disturbances of structure and function of a phospholipidic layer of cellular membranes leading to increase in their permeability, accumulation of ions of Sa + and Na + in cells, to dissociation of oxidizing phosphorylation, activation of lysosomic enzymes, destruction of SH-group of enzymes, polymerization of proteins, swelling and destruction of membranes. These processes are followed by disintegration of cellular structures and the subsequent necrosis of hepatocytes therefore there is a disturbance of their main functions — oxidations, methylations, acetyl of an irovaniye, recovery, hydrolysis, conjugation, excretion, etc. Disturbance of metabolism of ammonia, increase in blood of content of amino acids and products of their oxidation — phenols, amines, indoles (especially V-feniletilamina, an oktopamina, acting as false neurotransmitters) — leads to defeat of c. N of page, cardiovascular, respiratory, digestive and other systems. Important pathogenetic value has accumulation in an organism pyroracemic, milk, low-molecular fatty acids, deficit of coenzyme A, disturbance electrolytic and acid-base equilibrium, decrease of the activity of Na — K-ATP-ases, increase in transmembrane permeability.

Pathological anatomy

Essence morfol. changes at Etc. item consists in the progressing necrosis of hepatocytes (see. Liver ). Depending on localization of necrotic changes in various departments of hepatic segments distinguish a zone and diffusion necrosis (see). The zone necrosis more often happens centrolobular or periportal, the diffusion necrosis occupies various departments of segments. Depending on prevalence of necrotic changes in a liver distinguish a massive and submassive necrosis. At a massive necrosis big sites of a parenchyma of a liver are involved in process. At a submassive necrosis, an example to-rogo is the bridge-like (connecting) necrosis, the lobular structure remains. At a massive necrosis the acute course of a disease is usually observed, at submassive — subacute.

Depending on character morfol. changes in a liver distinguish two stages Etc. of the item; stage of yellow and red dystrophy. Necrotic changes develop in stages of yellow dystrophy (1 — 2 week of a disease) in a liver. At the same time the liver decreases (weight makes it 500 — 400 g), the capsule becomes wrinkled, sites of retraction of various size and a form are defined. The liver is flabby, on a section of yellow or gray-brown color with a greenish shade at cholestasia (see). Microscopically in various departments of segments the centers of a necrosis of hepatocytes in the form of nuclear-free weight are visible, in a cut accumulations of macrophages, star-shaped retikuloendoteliotsit, segmentoyaderny leukocytes, lymphoid cells are defined. In a stage of red dystrophy there is a lysis and a resorption of necrotic masses, the reticular stroma is bared. The liver becomes even less, has a flabby consistence, red color on a section. At a necrosis of the whole hepatic lobe on its place there is only an empty wrinkled a little reinforced capsule. At the subacute course of a disease macroscopically find the liver reduced in sizes with a set of the fine-grained sites formed by growth of granulyatsionny fabric on site of the centers of a necrosis. In sites of the remained parenchyma eminating nodes regenerates of various sizes are visible. At microscopic examination the remains of a detritis, sharply expanded sinusoids, hemorrhages are defined. In the remained sites of a parenchyma along with dystrophic changes it is possible to see manifestations of regeneration in the form of the increased hepatocytes, two-nuclear cells. In the outcome Etc. and. at a subacute current makronodulyarny (macronodular) cirrhosis often forms (see). If necrotic changes develop within only one share, in the outcome of a disease on its place the hem which is located near not changed part of body is formed.

Depending on an etiology Etc. the item morfol. changes of a liver have a number of features. So, at a viral hepatitis the liver is sharply reduced in sizes, covered with the wrinkled capsule with funneled retractions of red color on site of the centers of a necrosis. Microscopic changes of a liver are characterized by emergence of the multiple centers of a kollikvatsionny and coagulative necrosis in all departments of segments, however the largest centers find in their central departments. The centers of a necrosis merge among themselves with formation of submassive or massive necroses. Kaunsilmen's little bodies occur among necrotic masses (see the Liver), proliferation of star-shaped retikuloendoteliotsit is expressed, accumulations of lymphocytes, macrophages, single segmentoyaderny leukocytes are visible, the cholestasia is noted (see). The hepatocytes remaining more often in peripheral departments of segments are in a state proteinaceous (gidropichesky, balloon) dystrophies (cm. Proteinaceous dystrophy). Regeneration is characterized by polymorphism of hepatocytes, their kernels, existence of two-nuclear cells. Portal paths, as a rule, plentifully of an infiltrirovana lymphocytes, plasmocytes, histiocytes, meet segmentoyaderny leukocytes.

At poisoning with hepatotoxic substances (perchloromethane and its compounds, a dichloroethane, tetrachlorethane, trinitrotoluene, drugs of selenium, DDT and other insecticides, phosphorus, poisonous mushrooms) the liver is a little increased owing to development of fatty dystrophy in the beginning (see), then decreases, flabby, from a surface and on a section — bright yellow color (at a cholestasia with a greenish shade) with the centers of hemorrhages, under the capsule on site of the centers of a necrosis sites of retraction are visible. Against the background of fatty dystrophy of hepatocytes the centers of a necrosis which are localized preferential in centrolobular departments develop various size. Among necrotic masses accumulations of macrophages, star-shaped retikuloendoteliotsit, segmentoyaderny leukocytes are visible, hemorrhages often meet, in portal paths inflammatory infiltration is expressed poorly. In the remained hepatocytes fatty dystrophy is noted. At poisoning with phosphorus the centers of a necrosis develop often periportalno, the cholestasia meets here. At poisoning with mushrooms massive centrolobular necroses with slight inflammatory reaction, with multiple hemorrhages, the phenomena of an endophlebitis of hepatic veins often develop; similar changes develop at poisoning with alkaloid of a heliotrope (see. Heliotropic toxicosis ).

All hepatotoxic substances are protoplasmatic poisons therefore at electronic microscopic examination of a liver in hepatocytes note destruction of membranes of organellas, formation near them of lipids, frequent accumulation of calcium in mitochondrions that demonstrates disturbance of processes of breath and oxidizing phosphorylation.

At poisoning with pharmaceuticals the massive necrosis (can develop at poisoning with chloroform, a halothane, acetaminophen, drugs of gold, an isoniazid, Sulfasalazinum, a methotrexate) and a submassive necrosis (at poisoning with Butadionum, isoniazid, Methyldopa, tetracycline, erythromycin, Oxacillinum, streptomycin, etc.). At a massive necrosis the liver is reduced, flabby, bright yellow color on a section; necrotic changes develop against the background of fatty dystrophy of hepatocytes, begin in the central departments of segments and gradually extend to the periphery, among necrotic masses segmentoyaderny leukocytes prevail; inflammatory changes in portal paths are insignificant. At a submassive necrosis the liver is reduced slightly, flabby, on a section on a bright yellow background multiple small sites of red color are visible; in a liver against the background of fatty dystrophy there are bridge-like necroses, among necrotic masses accumulations of macrophages, lymphocytes, segmentoyaderny leukocytes, often eosinophils are visible; portal paths of an infiltrirovana limfogistio-cytic elements with impurity of segmentoyaderny leukocytes. At Etc. item, developed at treatment by antibiotics, along with fatty dystrophy it is possible to see the centers of gpdropichesky dystrophy of hepatocytes, a cholestasia, the expressed proliferation of star-shaped retikuloendoteliotsit, in cytoplasm to-rykh accumulations of a pigment of brown color meet, puffiness, infiltration by lymphocytes, plasmocytes, eosinophilic and neytrofilnymp leukocytes of portal paths, proliferation of bilious channels is noted.

The clinical picture

At Etc. item is observed the hepatocerebral insufficiency which is characterized by psychological frustration, in particular strengthening of tendon jerks, increase in a muscle tone, muscular twitchings, motor excitement, expansion of pupils, hallucinations, nonsense and other symptoms up to development of a hepatic coma (it is detailed see. Hepatargy ), and also dysfunction of digestive organs (constant pains in right the hypochondrium, a stomach, is more rare — in a waist, dispeptic frustration). A sign developing Etc. the item are reduction of the sizes of a liver and jaundice (see), intensity a cut, as a rule, increases. At the same time the level of bilirubin in blood exceeds norm by 5 times and more.

The hemorrhagic syndrome which is characterized by emergence of skin hemorrhages, nasal bleedings, metrorrhagias, a hematemesis is very characteristic of Etc. item. Etc. the item quite often is followed by hypostases (see. Swelled ), ascites.

A hepatic coma (see. Coma ) can develop slowly and sharply, sometimes at total absence of jaundice and rather low bilirubinemia; speed of its approach depends on rate of dystrophic disturbances in a liver. At slow development of coma 3 periods are noted: prodromal (1 — 2 week), prekomatozny (from several hours to 1 — 2 days) and the period of a deep coma. At acute development of a coma the prodromal stage is shortened up to 1 — 4 days and quickly passes into a deep coma, edges comes to an end letalno in 1 — 3 day. The prodromal stage is characterized by short-term unconscious conditions, attacks of suffocation, dizziness, perspiration, a hiccups, yawning, a loss of appetite, nausea, vomiting, a sleep disorder. In the prekomatozny period the sharp headache, sleeplessness is noted. Against the background of the accruing devocalization (see) at a part of patients motive excitement with incoherence of speech, disorientation in surrounding, attacks of melancholy, fear of death sharply accrues; at other patients the prekomatozny state is characterized by block, the drowsiness turning into hibernation. Patients stiffen in an inconvenient pose or make the uniform movements, repeat the heard words. The speech becomes chanted. In a prekomatozny state epileptiform attacks are possible. Further devocalization passes into a sopor and a coma, after a cut most often there comes death.

Features a wedge, pictures depend from etiol. the factor which caused development Etc. by the item. The heaviest current is observed at Etc. item, caused by reception of toxicant inside since at the same time the hepatocerebral syndrome develops, as a rule, and gepatorenalny syndrome (see). Sometimes it is possible to reveal the signs specific to effect of this or that poison, medicine. Poisoning with a death angel causes an acute picture of a hepatargy (see), jaundice, defeat of c. N of page. At poisoning with alkaloids of a heliotrope there is a toxic damage of a liver which is followed by ascites (see. Heliotropic toxicosis). Etc. the item, developing at an acute drunkenness (see. Alcoholic intoxication ), it is quite often shown by the expressed pain and dispeptic syndrome, fever, hemolysis, a giperfermentemiya with significant increase in blood gamma glutamiltranspeptidazy. Etc. the item at poisoning with pharmaceuticals often is followed by the allergic phenomena (skin rashes like small tortoiseshell, an arthralgia, fever, an eosinophilia). At less intensive, but longer or repeated influence of disturbing factors at patients with Etc. item postnecrotic can develop cirrhosis (see).

The diagnosis is made on the basis of the anamnesis, by a wedge, pictures, data a lab. researches. In blood at dynamic observation along with increase in level of bilirubin, ammonia decrease in maintenance of a prothrombin, cholesterol, urea, crude protein and its albuminous fraction, decrease of the activity of aminotransferases, gamma glutamiltranspeptidazy is noted.


Treatment of patients with Etc. item more often symptomatic that also enough clear ideas of the mechanism of development and the chemical nature of the leading syndrome — hepatocerebral insufficiency are connected with lack of etiotropic means. Difficulties of treatment are connected as well with the fact that Etc. the item is followed by disturbance of functions of many systems of an organism. Lech. actions are directed to elimination etiol. a factor, stabilization of cellular membranes, strengthening of process of regeneration, fight against ischemia, normalization of a lymphokinesis, and also correction of the broken metabolism and a homeostasis. Patients with symptoms Etc. with the item shall be immediately hospitalized. For the purpose of the prevention of an intestinal endointoxication limit protein content in a daily diet (no more than 50 g a day), in the period of harbingers of a coma of squirrels completely exclude. The regular enteroclysis by means of siphon enemas (see), continuous suction of duodenal contents via the probe, peroral introduction of high doses of antibiotics of a broad spectrum of activity is recommended (ampicillin, Kanamycinum, Neomycinum, etc.). Intravenously enter 1000 — 1500 ml in days of 5% of solution of glucose thanks to what reserves of a glycogen in a liver are supplemented, disintegration of proteins of own fabrics is a little limited, and also there are reactions of binding of ammonia glutaminic to - that. Before glucose the fructose having big affinity to hepatocytes has Nek-ry advantages; she assimilates quicker and does not demand administration of insulin. Along with glucose intravenously enter potassium chloride, insulin (10 — 12 PIECES), ascorbic to - that (to 10 ml of 5% of solution), Haemodesum (400 — 500 ml a day), Ringer's solution (800 — 1000 ml a day), and also 200 — 600 ml of 2,5 — 4% of solution of hydrosodium carbonate and 200 — 300 mg of co-carboxylase for the purpose of correction of the developing acidosis. The B1, B2, B6, B12, C, PP vitamins exerting impact on metabolic processes in an organism and also intravenous administration of 10 — 12 ml in days of the drug Essentiale containing a complex of vitamins and essential phospholipids are shown. Daily intramusculary enter 4 — 6 ml of 0,5% of solution lipoic to - you. For prevention of bleedings appoint Σ-aminocaproic to - that to - that to - that, Vikasolum, Dicynonum, a gluconate of calcium, etc. Binding of ammonia in blood and transformation it in nontoxic connections is reached by intravenous administration of an ornitsetil (5 — 10 g a day), glutaminic to - you (25 — 100 ml of 1% of solution). Often apply hormonal means to treatment of hepatocerebral insufficiency. Besides, use plasma exchange (see), hemosorption (see), and also hyperbaric oxygenation (see).

Forecast and Prevention

Forecast, as a rule, adverse.

Prevention consists in timely diagnosis and full treatment of a viral hepatitis, and also in strict observance of rules of use of chemical means on production and in life, preparations and implementations of mushrooms, in the careful treatment of medicines.

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P. Ya. Grigoriev; T. H. Thrush (stalemate. An.), M. A. Tsivilno (psikhiat.).