Hemolytic jaundice is a variant of the suprahepatic jaundice syndrome caused by hemolysis of red blood cells. It is manifested by jaundice and pallor of the skin and mucous membranes, splenomegaly, darkening of urine and feces, hemolytic crises. It is diagnosed using a blood test, determination of the concentration of indirect and total bilirubin, ultrasound of the abdominal organs. Corticosteroids, cytostatics, antibiotics, liver enzyme activators, infusion and phototherapy, transfusion of blood components are used for treatment. Splenectomy is performed according to the indications.
ICD 10
D59 P58
Meaning
Hemolytic (pleiocholic) jaundice develops when the level of free bilirubin is exceeded, which can freely conjugate in the liver. Under normal conditions, up to 100-200 million red blood cells per hour are destroyed in the human body, while the life span of red blood cell elements is on average 120 days. From 1 g of hemoglobin released during hemolysis, 35 mg of unconjugated pigment is formed (about 250-350 g / day).
The liver has a 3-4-fold functional reserve for binding excess bilirubin. With the shortening of the life span of red blood cells, their accelerated destruction, the pigment concentration exceeds the hepatic conjugation threshold, indirect bilirubin accumulates in the blood, is deposited in tissues, which is accompanied by the formation of a characteristic clinical picture.
Causes of hemolytic jaundice
The disease develops against the background of hemolysis with the formation of a large amount of indirect bilirubin, which does not have time to be conjugated by hepatocytes. The hemolytic form of jaundice is caused by the same etiological factors as pathological conditions with increased intravascular or extravascular destruction of red blood cells. Specialists in the field of modern gastroenterology and hematology identify the following causes of the disorder:
- Hereditary defects of erythrocytes and hemoglobin. Hemolysis can be caused by genetically determined enzymopathies (insufficiency of pyruvate kinase, glucose-6-phosphate dehydrogenase), failure of erythrocyte membranes (hereditary microspherocytosis, acanthocytosis, ovalocytosis, paroxysmal nocturnal hemoglobinuria). Jaundice of hemolytic type is also observed in hemoglobinopathies (thalassemia, sickle cell anemia, etc.).
- The effect of hemolytic plasma factors. The hemolysis reaction is caused by antibodies in hemolytic disease of newborns and transfusion of incompatible blood, hemolysins of pathogens of measles, rubella, sepsis, mumps, leptospirosis, malarial plasmodia, snake and other hemotoxic poisons (hydrogen sulfide, arsenic, lead, phosphorus, aniline, nitrobenzene), Erythrocytes are destroyed under the influence of a number of pharmaceuticals (sulfonamides, antipyretics, quinine).
- Extensive hemorrhages, heart attacks. Increased formation of free bilirubin is associated with massive disintegration of blood elements during resorption of large hematomas in soft tissues, parenchymal organs, body cavities. Hemolytic suprahepatic jaundice is complicated by massive gastrointestinal bleeding, delaminating aortic aneurysm, myocardial infarction, lung, hemorrhagic stroke, hemothorax. Usually this condition is associated with an existing disease, injury.
- Mechanical destruction of erythrocytes in blood vessels. Red blood cells undergo intravascular hemolysis when they are compressed in peripheral blood vessels adjacent to bone protrusions (marching hemoglobinuria), turbulence of blood flow during dysfunction of prosthetic heart valves. Hemolysis also occurs when erythrocytes pass through fibrin deposits in arterioles with DIC syndrome, hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura.
In some patients, the destruction of red blood cells with the development of hepatic jaundice is observed within the clinical picture of malignant tumors of different localization, leukemia, lymphoproliferative diseases, Addison-Biermer pernicious anemia, systemic connective tissue pathologies. The hemotoxic effect has powerful ionizing effects in radiation sickness, radiotherapy. Physiological jaundice occurs in newborns with increased hemolysis of fetal hemoglobin against the background of low activity of liver enzymes.
Pathogenesis
The mechanism of development of hemolytic jaundice is based on the relative functional insufficiency of liver cells that are unable to bind a large amount of free bilirubin formed during hemolysis of erythrocytes. An additional pathogenetic factor is a violation of intracellular pigment transport in hepatocytes at its high concentration. As a result, unconjugated bilirubin binds to albumins and circulates in the blood in the form of water-insoluble bilirubin-albumin complexes that cannot be excreted in the urine.
The fat-soluble free pigment easily penetrates through cellular and mitochondrial membranes, turns the skin and mucous membranes yellow, disrupts the processes of oxidative phosphorylation, protein synthesis, and the transmembrane potential of cells. Damage to the nuclei of the brain, particularly sensitive to the toxic effect of indirect bilirubin, leads to the development of encephalopathy (nuclear jaundice) with pronounced neurological symptoms. The binding capacity of albumins is insufficient in indirect hyperbilirubinemia of more than 260-550 mmol/l.
Active conjugation of the pigment in the liver is accompanied by its increased excretion into the intestinal lumen with the formation of urobilinogen in the small intestine and then sterkobilinogen in the colon. An excessive amount of urobilinogen absorbed into the blood, which cannot be completely eliminated by hepatocytes, continues to circulate in the blood. The high level of sterkobilinogen excreted in urine, absorbed in hemorrhoidal veins, and sterkobilin in feces gives the excrement a characteristic brown color. After the exhaustion of the ability of hepatocytes to secrete direct (conjugated) bilirubin into the bile, the reverse diffusion of the bound form of the pigment into the blood occurs.
Classification
The systematization of forms of hemolytic jaundice takes into account the etiological factors under the influence of which hemolysis occurred. This approach allows you to choose the optimal therapeutic tactics that maximally compensates for the effect of the root cause of the disease. Gastroenterologists and hematologists distinguish the following types of hemolytic suprahepatic jaundice:
- Hemolytic corpuscular jaundice. They are associated with various types of erythrocyte insolvency — deficiency or insufficient activity of enzyme systems, defects in hemoglobin, membrane structures. Usually corpuscular pleiocholic jaundice is caused by genetic abnormalities, their treatment is mainly symptomatic.
- Hemolytic extracorpuscular jaundice. The destruction of erythrocytes is caused by the action of various external factors — antibodies, microbial toxins, hemolytic poisons, mechanical loads. Along with the elimination of individual symptoms, this allows the use of methods aimed at eliminating the etiopathogen and individual links in the pathogenesis of hemolysis.
- Hemolytic posthemorrhagic jaundice. They occur against the background of massive disintegration of red blood cells in the areas of hemorrhages. Usually complicate the course of severe injuries and other urgent conditions. Predicting the development of suprahepatic jaundice makes it possible to prescribe preventive therapy to prevent further complications.
Symptoms of hemolytic jaundice
A characteristic sign of the disease is a combination of pallor of the skin with lemon—yellow coloring of the skin, conjunctiva of the eyes in the absence of itching. In most patients with suprahepatic jaundice, darkening of the urine is observed. There may be moderate abdominal pain, dyspeptic disorders – nausea, belching, diarrhea. Exacerbation of the disease (hemolytic crisis) is clinically manifested by febrile fever, headache, myalgia, intense pain in the left hypochondrium due to enlargement of the spleen. If the disease is caused by acute poisoning with chemical compounds or drugs, intoxication symptoms are added in the form of depression of consciousness up to coma, pronounced tachycardia, falling blood pressure, respiratory disorders and urinary excretion.
Complications
The presence of suprahepatic jaundice in the patient increases the risk of stagnation in the gallbladder, which leads to the formation of pigment stones and obstruction of the bile ducts. A complication of hemolytic jaundice can be toxic nephropathy with acute renal failure, which develops with pronounced violations of the biochemical composition of the blood and the accumulation of toxic compounds. With a prolonged course of the disease, liver failure may occur, in which there is a sharp suppression of all organ functions, which is clinically manifested by cachexia, dystrophic changes, persistent metabolic disorders. Pleiocholic jaundice is sometimes complicated by bilirubin encephalopathy due to brain intoxication.
Diagnostics
Diagnosis is not difficult in the presence of a typical clinical picture of the disease. A distinctive sign of hemolytic jaundice is jaundice staining of the skin without itching and enlargement of the liver. Diagnostic search is aimed at identifying the root cause of the disease. The examination plan includes the following instrumental and laboratory methods:
- Blood test. During the study, a sharp decrease in the amount of hemoglobin and erythrocytes is determined with a simultaneous increase in the content of reticulocytes over 1%. Morphological evaluation may reveal specific cells indicating a certain type of hemolytic anemia: spherocytes, target-shaped, sickle-shaped erythrocytes. In the acute period and in autoimmune processes, leukocytosis is observed with a shift of the formula to the left.
- Ultrasound of the abdominal cavity. In pleiocholic jaundice, a significant increase in the spleen is determined during abdominal ultrasound with usually normal liver size and the structure of the hepatic parenchyma. Also, sonographically it is possible to identify diseases of the hepatobiliary system that can be combined with hemolytic pathology: cholelithiasis, cholecystitis, fibrous liver lesions, changes in hepatic vessels.
The concentration of ALT, AST, and alkaline phosphatase is usually within the normal range. In the general analysis of urine, a high content of sterkobilinogen and urobilin is detected, there is no bilirubinuria. The coprogram shows an increased level of sterkobilin. CT, MRI, cholangiopancreatography can be performed for a comprehensive assessment of the liver condition in jaundice. Additionally, the osmotic resistance of erythrocytes is being investigated, which increases with thalassemia and decreases with hemolytic spherocytic anemia. The Coombs test may detect anti-erythrocyte antibodies.
Differential diagnosis is carried out with Gilbert’s syndrome, parenchymal and mechanical jaundice, as well as with diseases that can cause these types of hyperbilirubinemia — hepatitis, leptospirosis, jaundice form of infectious mononucleosis, pseudotuberculosis, yersiniosis, amoebiasis, cholelithiasis, liver tumors and Fater’s nipple. In the direction of a gastroenterologist, if there are indications, the patient is advised by a hematologist, abdominal surgeon and other specialists.
Treatment for hemolytic jaundice
Complex therapy is recommended, which allows, if possible, to eliminate the cause of hemolysis, to influence pathogenetic links, to stop life-threatening symptoms. Treatment of the hemolytic form of suprahepatic jaundice is usually conservative and combined with diet therapy aimed at maintaining normal liver function. A significant restriction or complete exclusion of fatty, fried, spicy dishes, products containing a lot of carotene and coarse fiber is shown. Taking into account the possible cause of hemolytic anemia and jaundice, the treatment plan includes:
- Corticosteroids. The appointment of immunosuppressive hormone therapy is justified in the diagnosis of autoimmune disorders that provoke the development of acquired hemolytic anemia. In some patients with jaundice, taking cytostatic drugs is more effective.
- Antibiotics. They are used for hemolysis caused by the action of bacterial toxins. Means that do not enter into competitive displacement of bilirubin from compounds with glucuronic acid are recommended. Preparations from the groups of amphenicols, cephalosporins, sulfonamides are used with caution.
- Infusion therapy. It is carried out with hemolytic processes of toxic origin. The introduction of colloidal and crystalloid solutions, if necessary, is supplemented with forced diuresis, enterosorbents, antidotes for binding toxic substances, hemosorption, plasmapheresis, hemodialysis.
- Inducers of liver enzymes. Activate the microsomal enzyme system, which is associated with cytochrome P450. As a result of increased hepatocyte metabolism, the binding of bilirubin circulating in the blood improves. Stimulation of enzymes is effective in the presence of a functional reserve of the liver.
- Phototherapy. It is aimed at reducing hyperbilirubinemia. It is used to increase the level of bilirubin to subtoxic and toxic concentrations. Promotes the transfer of unconjugated pigment into a water-soluble isomeric form, which is excreted by the kidneys and liver without the formation of albumin complexes.
- Exchange blood transfusion. It is usually performed in immune hemolytic conditions with a critical content of free bilirubin for the nervous system. Up to 70% of the BCC can be replaced in one procedure, which reduces bilirubinemia, replenishes the deficiency of red blood cells, and stops hypoxia.
- Removal of the spleen. Surgical treatment is indicated for severe hemolytic corpuscular jaundice in patients with hereditary erythrocyte fermentopathies and membranopathies. Splenectomy makes it possible to exclude the destruction of erythrocytes in the sinuses of the organ and their utilization by macrophages.
Prognosis and prevention
Since the hemolytic variant of suprahepatic jaundice often manifests itself against the background of hereditary anemia, which are difficult to treat, the prognosis of the disease is considered serious. Complete recovery is observed in patients without severe intercurrent pathologies in the absence of irreversible liver dysfunction. Specific prevention of hemolytic jaundice has not been developed. To prevent the disease, it is necessary to carry out timely diagnosis and complex therapy of hemolytic anemia, severe infectious diseases, observe the rules of blood compatibility during blood transfusions, avoid polypragmasia and prescribing potentially hemotoxic medications.