Symptom complexes Hyperbilirubinemia – pathological conditions characterized by an imbalance between the formation and secretion of bilirubin , the main clinical sign of which is jaundice.
Bilirubin is one of the yellow-red bile pigments that is formed from blood hemoglobin in the reticuloendothelial system (in bone marrow cells, spleen cells, in Kupffer liver cells, etc.), as well as in histocytes of connective tissue of any organ.
Outside the liver , bilirubin is transported into plasma in serum albumin bound form ( free, unconjugated, indirect bilirubin ).
The next step in the exchange of bilirubin is the penetration of the bilirubin-albumin complex through the sinusoidal membrane of hepatocytes. Inside the liver cells, bilirubin combines with one or two glucuronic acid residues with the participation of the glucuronyl transferase enzyme ( conjugated, direct bilirubin ).
The binding of bilirubin to glucuronic acid is a natural process of detoxification by the liver of a number of substances. Then the bilirubin-glucuronide complex penetrates the hepatocyte biliary membrane and is excreted in the bile via the intrahepatic and extrahepatic biliary system.
Bilirubin bound (conjugated) through the bile duct system enters the intestine, where, under the influence of its microflora, it is restored to urobilinogen and sterkobilinogen. The first is resorbed in the upper part of the small intestine and with the blood of the portal vein enters the liver, where it undergoes oxidation. With liver disease, it cannot perform this function, the urobiligen passes into the bloodstream and is excreted in the urine in the form of urobilin.
Sterkobilinogen is mainly excreted in the feces, turning in the rectum and outside it into sterkobilin, which gives the stool its normal color. A small part of stercobilinogen along hemorrhoidal veins, bypassing the liver, enters the general circulation and is excreted by the kidneys. Therefore, normal urine always contains traces of stercobilinogen, which under the influence of light and air turns into stercobilin.
Although urobilin and sterkobilin differ from each other both in chemical structure and in physical properties, it is very difficult to separate them in urine. Therefore, in laboratory practice they are not separated and are designated as urobilinoids. Violations in individual links of bilirubin metabolism, and even more so combined disorders, can lead to hyperbilirubinemia. With an increase in the content of total bilirubin in blood serum above 34.2 μmol / L (the norm is 8.5 – 20.5 μmol / L), jaundice develops.
Hyperbilirubinemia occurs with increased formation of bilirubin, as well as in violation of its transport to liver cells and excretion by these cells or in violation of the binding processes of free bilirubin (glucuronidation, sulfurization, etc.).
Free (Unconjugated) Bilirubin is sparingly soluble and toxic; it is neutralized in the liver by the formation of soluble diglucuronide – a pair of compounds of bilirubin with glucuronic acid (conjugated, or direct bilirubin).
High bilirubin concentrations inhibit oxidative phosphorylation and reduce oxygen consumption, which leads to tissue damage. The toxic effect of high concentrations of bilirubin is manifested by damage to the central nervous system, the occurrence of foci of necrosis in the parenchymal organs, suppression of the cellular immune response, the development of anemia due to hemolysis of red blood cells, etc.
Hyperbilirubinemia due to increased formation of bilirubin is noted with excessive hemolysis (for example, with hemolytic anemia during the hemolytic crisis, extensive hemorrhages, heart attacks, lobar pneumonia). This form of hyperbilirubinemia is called suprahepatic. or hemolytic . If it causes jaundice, then the latter bears similar names.
There may be no hyperbilirubinemia in the initial stage of hemolysis, since the liver is able to metabolize and excrete bilirubin in bile in an amount exceeding 3–4 times its production under physiological conditions. Over hepatic (hemolytic) hyperbilirubinemia, or jaundice, develops when the liver’s reserve capabilities are exhausted.
With an average degree of hemolysis, hyperbilirubinemia is mainly caused by unconjugated bilirubin, and with massive hemolysis it is caused by unconjugated and conjugated bilirubin. The latter can cause hyperbilirubinuria. Unconjugated bilirubin does not penetrate a healthy kidney filter and does not appear in urine.
Hepatic jaundice (hepatocellular or parenchymal) is hyperbilirubinemia resulting from Inflammatory ( hepatitis, cirrhosis ) or Toxic ( poisoning with chemicals, drug intolerance, etc.) liver damage.
Damaged hepatocytes are not able to fully capture bilirubin from the blood, bind to glucuronic acid and excrete it into the bile ducts.
As a result, the content of unconjugated (indirect) bilirubin in the blood serum increases. In addition, with dystrophy of the liver cells, back diffusion of conjugated (direct) bilirubin from the bile canaliculi to the blood capillaries is observed. This pathological mechanism causes an increase in serum levels of conjugated (direct) bilirubin, as well as hyperbilirubinuria and a decrease in the excretion of stercobilin with feces.
In total, in case of damage to the liver parenchyma cells in the blood serum, the content of unconjugated and conjugated bilirubin can increase by 4-10 times or more. With parenchymal lesions of the liver, the ability of liver cells to capture bile acids from the blood decreases sharply, as a result of which they accumulate in the blood and are excreted in the urine.
Mandatory studies for patients with jaundice.
- Biochemical blood analysis:
Bilirubin, AsAT, GGTP, ALP (Alkaline phosphatase), Albumin, Hemaglobin, Reticulocytes, Prothrombin time, HBsAg, HBeAg and others based on the type of jaundice.
- Chest x-ray to rule out bronchial cancer and lung metastases.
TREATMENT is carried out depending on the cause of jaundice.
PIGMENT steatosis OR FUNCTIONALITY syndromes hyperbilirubinemia
This is a very rare syndrome, it happens only in men.
This is a hereditary pathology, which is a violation of the bilirubin metabolism at the conjugation level due to a lack of the transglucuronyltransferase enzyme. This enzyme binds bilirubin in the liver, turning it into conjugated, bound. Due to the lack of the enzyme, there is an excess of free bilirubin, goes into the bloodstream, jaundice begins. This process is most manifested during physical, emotional stress. The rest of the time this is a healthy person. Even all samples are normal, only bilirubin is elevated.
Gilbert called this syndrome simple family cholemia, these people are more icteric than sick. Although this is a hereditary pathology, it begins after 17 years, at 20-30 years, in children does not happen. This Gilbert syndrome is very similar to residual posthepatitis syndrome, which is not hereditary. This syndrome often occurs after acute viral hepatitis , when all liver functions are restored, only bilirubin does not bind to glucuronic acid, goes into the bloodstream, and jaundice appears.
DABIN’S SYNDROME – JOHNSON.
FUNCTIONAL HYPERBILIRUBINEMIA BUT CONJUGATED (RELATED). It occurs in both men and women. Here, conjugation is not impaired, but the transport of conjugated bilirubin into the blood is impaired , accumulates in the cells and during overload, overvoltage immediately enters the bloodstream in large quantities, yellowness appears. This is also a hereditary disease. This syndrome is a more serious pathology than Gilbert’s syndrome, but it still does not go into hepatitis, into cirrhosis.
Liver amyloidosis is detected in 50% of patients with systemic amyloidosis.
Amyloid does not accumulate in the cells, but in the intercellular region, in the connective tissue around the vessels , but not in hepatocytes. It very rarely goes into cirrhosis, since it takes a very long time for so much amyloid to accumulate. The liver can be enlarged, painless, unlike fatty hepatosis , a significant increase in alkaline phosphatase, liver tests within normal limits. The treatment is symptomatic.
Krigler Syndrome – Najara (Nayyara).
This is congenital non-hemolytic unconjugated bilirubinemia, (nuclear jaundice) . If manifested after 5 years, then the prognosis is favorable, if from birth, the prognosis is unfavorable. The brain is affected.
SYMPTOM OF A ROTOR.
Associated bilirubin increases , but without deposition of melanin. There is no cure. The forecast is favorable.
KONOVALOV’S DISEASE – WILSON.
It is a consequence of a genetic defect in copper metabolism . Copper accumulates in the liver and brain (Hepatolenticular Degeneration or Dystrophy) , the cause of which is unknown. Copper also accumulates in the kidneys and cornea (Kaiser-Fleischer rings) . A very rare disease. The forecast is unfavorable. Diagnostic signs: Neuropsychiatric disorders (decreased intelligence, difficulty in monotonous speech, “fluttering” tremor of fingers of outstretched arms, rigidity, etc.). Most often, these symptoms begin in childhood, less often in adolescence. Symptoms of chronic active hepatitis with jaundice or cirrhosis with ascites, liver failure can occur unexpectedly, increased ALT, AST, hypergammaglobulin. An important diagnostic value is the brownish-green pigmentation that appears on the periphery of the cornea. It can be detected only by examination with a slit lamp, and sometimes it is absent. Laboratory tests show a decrease in serum cerruloplasmin and copper levels, an increase in copper excretion in the urine, and an excessive accumulation of copper in the liver, as determined by biopsy.
Diet – an increase in nutritional proteins. Limit lamb, poultry, nuts, prunes, chocolate, cocoa, honey, peppers, and legumes. BAL – British anti-myositis IM up to 2.5 mg / kg 2 times a day, from 10-20 days. Unitiol 20% 5-10 ml im up to 1 month. Penicillamine is prescribed for life with a constant intake of the drug from 300 to 600 mg / day. You can not suddenly stop the medicine. Family members should be examined.
HEMOCHROMATOSIS (Idiopathic Siderophilia, “Bronze Diabetes”, Pigment Cirrhosis).
This is a genetically caused disease caused by increased absorption of iron in the small intestine. Iron accumulates in the liver, pancreas, heart, in all endocrine glands, skin, and mucous membrane. Sick men from 40 to 60 years. Morphologically accumulates hemosiderin.
Fatigue, weight loss, signs of cirrhosis. The skin has a bronze or smoky hue, which is more noticeable on the face, hands, other parts of the body, the liver is enlarged, usually dense, the surface is smooth, the edge is pointed, ascites may appear. Often there is thirst, hunger, polyuria, glucosuria, hyperglycemia, and other symptoms of diabetes. Endocrine disorders – the pituitary gland, adrenal glands, hypo and hyperthyroidism, osteoporosis, osteomalacia, mental disorders. The forecast is unfavorable.
Diet – Do not eat foods containing iron. Desferol 10.0 iv from 20-40 days. Bloodletting.
POSTHEPATITAL RESIDUAL SYNDROMES (RESIDUAL DEFECT).
Residual hepatomegaly is when the patient has recovered, all instrumental and laboratory data are normal, only there may be an enlargement of the liver and fibro-altered areas. This happens when hepatitis proceeds with necrosis and after recovery foci of fibrosis remain in separate areas.
Hepatic coma is the most severe manifestation of decompensated hepatic cell failure (PCN). PCN can be acute and chronic. Hepatic coma can develop as a result of chronic liver diseases: hepatitis , cirrhosis.
3 stages of hepatic cell failure (PNA) (both acute and chronic): 1. Stage compensated. 2. Stage subcompensated. 3. Stage decompensated.
- In the 1st stage , the following manifestations begin: poor tolerance to alcohol, hepatomegaly, positive exercise tests.
- In the 2nd stage: general weakness, poor nutrition syndrome, hepatomegaly, jaundice, endocrine and skin signs, edema, small ascites, moderate increase in AL, AST, thymol and sublimate activity are moderately positive, decrease in albumin.
- In the 3rd stage, everything is the same, only there is sharp weakness and jaundice, severe ascites and edematous syndrome, for the first time hemorrhagic syndrome, diathesis, low-grade fever. Laboratory data are pronounced. Hepatic coma is characterized by severe brain damage with cerebro-toxic substances (ammonia, phenol). There are pathological reflexes.
- Endogenous PC or true, or hepatocellular or decay (perhaps with cirrhosis and hepatitis) .If this deep coma in hepatic dystrophy, necrosis, broken funktsii.I ammonia, phenols and poorly inaktiruyutsya and enter the brain.
- Exogenous or portocaval or shunt PC . Only in patients with cirrhosis proceeds with portal hypertension and the presence of portocaval anastomoses.
- Mixed PC. There is a liver moment. Endogenous and still anastomoses – discharge of blood, shunt option.
- Hypokalemic PC (not officially accepted).
Coma– this is practically a brain poisoning with cerebro-toxic substances. A major major role is given to ammonia and phenol. And also pyruvic acid, lactic acid, triptophan, methionine, tyrosine are important. In healthy people, ammonia is completely neutralized in the liver, and ammonia and phenol are formed. Phenols in the liver cell combine with glucuronic acid, i.e. they are neutralized, non-toxic. To start precoma and coma, it is necessary that 80-85% of the liver cells fail (massive liver necrosis, etc.). Ammonia and phenol penetrate through the brain membrane, making it permeable, then they penetrate into the cell H and Na, and K leaves, leads to intracellular potassium and pyruvic acid also penetrates inside, acidosis begins, then respiratory alkalosis. The penetration of Na and H leads to the penetration of water, cerebral edema begins, acidosis. Redox processes are inhibited, the brain gradually falls asleep. Cerebral edema is one of the leading causes of death. On the 2nd plan is pulmonary edema, renal failure, hypovolemic shock.
Hypokalemic version of coma.
If the patient has edema-acetic syndrome, diuretics are given uncontrollably, a lot of Potassium is lost and hypokalemia of the cells, edema, etc. Assigning hydrochlorothiazide , etc., it is necessary to designate drugs Potassium or veroshpiron (one To -sberegayuschy). With diuretics should be given veroshpiron . And you can already not give potassium preparations . Clinic. Hepatic manifestations also enter the coma clinic : jaundice intensifies or appears, hemorrhagic syndrome, ascites increase, dyspeptic manifestations intensify. In a state of hepatic coma, sharply positive laboratory tests.
There are 3 stages of coma.
- Threatening coma (the same precoma).
1) In the state of Precoma , euphoria, then melancholy, crying (emotional lability), sleep disturbance causelessly. At this stage, patients can commit unmotivated acts, there may be a slowdown in mental reaction, a decrease in intelligence, a slight confusion from several hours to several days or months and goes into stage 2. 2) Threatening Coma. Either deep depression, then hallucinations, delirium, the patient is unsafe – complete disorientation in space, in time, in personality. Very characteristic: bursting tremor of hands. A sharp slowdown in mental reactions, decreased intelligence. Encephalogram shows well. Usually stage 2 lasts from several hours to 2-3 days, sometimes 10 days. 3) Coma. Complete loss of consciousness, noisy deep breathing, masky face, strong ammonia smell, pathological reflexes, stiff neck, coma lasts from several minutes to several days.
TREATMENT OF HEPATIC COMA.
- Provide food: In / in a cap. 1-2 l of 10% Glucose, 100-150 mg Cocarboxylase , 100 mg B6, 3-6 g Vit. C, 10-20 mg Panangina, 500 mg B12.
- Broad-spectrum antibiotics ,
- Laxatives (via probe)
- L-arginine, glutamine – iv 25-50 g, per os.
- To reduce acidosis / injected Soda 150-200 ml 4-5% solution.
- Lactulose, 150 ml – laxative, stool oxidizing agent, promotes the withdrawal of ammonia (administered through a probe).
- Prednisolone , in the presence of a necrotic process.
- Essential 60-80-100 ml iv
- Plasmapheresis, Hemodialysis, Hemadsorption – blood purification.
- Enema with sodium sulfate (15-20 g per 100 ml of water), if there are constipation.