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Jaundice is the yellow coloration of the skin and mucous membranes, associated with the accumulation of bilirubin in them due to hyperbilirubinemia. The occurrence of jaundice is always associated with a violation of bilirubin metabolism.
Since the liver plays a primary role in the metabolism of bilirubin, jaundice traditionally refers to typical large hepatic syndromes, although in some cases it can occur without liver disease (for example, in massive hemolysis). The jaundice is caused by an increase in bilirubin in the blood (hyperbilirubinemia) of more than 34.2 μmol / L (2 mg / dl), when it accumulates in the skin, mucous membranes and sclera. Yellow staining of the skin - the main external manifestation of hyperbilirubinemia - can be caused by other factors - carotene (taking appropriate food, for example carrots, tomatoes), acrichine, picric acid salts, but in these cases there is no staining of the sclera.
From the clinical standpoint, it is important to bear in mind that the staining of different areas depends on the degree of hyperbilirubinemia: first of all appears icteric sclera, the mucous membrane of the lower surface of the tongue and the sky, then the face, palms, soles, and all skin turn yellow. Sometimes there may be a discrepancy between the level of bilirubin and the degree of jaundice: for example, jaundice is less noticeable with simultaneous presence of hypo-oncotic edema, with anemia, obesity; on the contrary, thin and muscular faces are more jaundiced. It is interesting that with a stagnant liver, if hyperbilirubinemia occurs, then the upper half of the trunk turns yellow.
With more prolonged hyperbilirubinemia, icteric staining becomes greenish (oxidation of bilirubin in the skin and the formation of biliverdin) and even bronze-black (melanogeltuccino).
Hyperbilirubinemia is a consequence of disorders in one or more units of bilirubin metabolism. The following bilirubin fractions are distinguished: free (indirect), or unbound (unconjugated), and bound (direct) or conjugated, which is divided into poorly studied bilirubin I (monoglucuronide) and bilirubin II (diglucuronide-bilirubin). Usually, the parameters of unconjugated bilirubin and conjugated bilirubin II (diglucuronide) are used to characterize bilirubin metabolism.
Causes of jaundice
Jaundice may be a result of increased formation of bilirubin or diseases of the hepatobiliary system (hepatobiliary jaundice). Hepatobiliary jaundice can be the result of hepatobiliary dysfunction or cholestasis. Isolate cholestasis intrahepatic and extrahepatic.
Increased formation of bilirubin and hepatocellular diseases lead to a disruption or decrease in the conjugation of bilirubin in the liver and cause hyperbilirubinemia due to unbound bilirubin. Violation of bile excretion leads to hyperbilirubinemia due to bound bilirubin. Although these mechanisms seem to be different, in clinical practice jaundice, especially caused by hepatobiliary diseases, almost always results from hyperbilirubinemia due to unrelated and bound bilirubin (mixed hyperbilirubinemia).
With some disorders, a certain fraction of bilirubin predominates. Unrelated hyperbilirubinemia due to increased formation of bilirubin can be a consequence of hemolytic disorders; a decrease in bilirubin conjugation is observed with Gilbert's syndrome (small bilirubinemia) and Kriegler-Nayyar syndrome (severe bilirubinemia).
Hyperbilirubinemia due to bound bilirubin due to impairment of excretion can be observed with Dabin-Johnson syndrome. Conjugated hyperbilirubinemia as a result of intrahepatic cholestasis can be a consequence of hepatitis, toxic effects of drugs and alcoholic liver disease. Less common causes include cirrhosis of the liver, namely, primary biliary cirrhosis, cholestasis in pregnancy, and metastatic cancer. Conjugated hyperbilirubinemia as a result of extrahepatic cholestasis can be a consequence of choledocholithiasis or pancreatic cancer. More rare causes can be strictures of the common bile duct (usually this is due to previous surgical intervention), ductal carcinoma, pancreatitis, pancreatic pseudocyst and sclerosing cholangitis.
Liver diseases and biliary obstruction usually cause various disorders, accompanied by an increase in bound and unbound bilirubin.
Overview of bilirubin metabolism
The destruction of the heme leads to the formation of bilirubin (an insoluble product of metabolism) and other bile pigments. Before distinguishing itself in the composition of bile, bilirubin must be transformed into a water-soluble form. This transformation occurs in five stages: formation, transportation by plasma of blood, capture by the liver, conjugation and excretion by bile.
Education. About 250-350 mg of unconjugated (unbound) bilirubin is formed daily; 70-80% is formed when erythrocytes are destroyed and 20-30% - in the bone marrow and liver from other heme proteins. Hemoglobin is split into iron and biliverdin, which is converted to bilirubin.
Transportation. Unconjugated (indirect) bilirubin does not dissolve in water and is transported in albumin-bound form. He can not pass through the glomerular membrane of the kidney and get into the urine. Under certain conditions (for example, acidosis), the bond with albumin is weakened, and some substances (for example, salicylates, some antibiotics) compete for bond sites.
Grabbing the liver. The liver quickly seizes the bilirubin.
Conjugation. In the liver, unbound bilirubin is conjugated, forming mainly diglucuronide bilirubin or conjugated (direct) bilirubin. This reaction, catalyzed by the microsomal enzyme glucoronyl transferase, leads to the formation of water-soluble bilirubin.
Excretion of bile. Small tubules, located between the hepatocytes, gradually join the ducts, interlobular biliary tracts and large hepatic ducts. Outside the portal vein, the hepatic duct itself merges with the duct of the gallbladder with the formation of a common bile duct, which flows into the duodenum through the nipple tapers.
Associated bilirubin is secreted into the biliary tract along with other components of the bile. In the intestine, the bacteria metabolize bilirubin into urobilinogen, most of which is further converted into sterbilin, which gives the stool a brown color. With complete biliary obstruction, the stool loses its normal color and becomes light gray (clay-like stools). Immediately urobilinogen is reabsorbed, captured by hepatocytes and re-enters bile (enterohepatic circulation). A small amount of bilirubin is excreted in the urine.
Because the bound bilirubin enters the urine, and the unbound does not, bilirubinuria is caused only by a bound bilirubin fraction (eg, hepatocellular or cholestatic jaundice).
Diagnosis of jaundice
In the presence of jaundice, the examination should begin with the diagnosis of hepatobiliary diseases. Hepatobiliary jaundice can be a consequence of cholestasis or hepatocellular dysfunction. Cholestasis can be intrahepatic or extrahepatic. The diagnosis (for example, hemolysis or Gilbert's syndrome, if there is no other hepatobiliary pathology, viruses, toxins, hepatic manifestations of systemic diseases or primary liver damage with hepatocellular dysfunction, gallstones with extrahepatic cholestasis) is the determining factor for determining the cause of jaundice. Although laboratory and instrumental studies are of great importance in diagnosis, most errors result from underestimation of clinical data and incorrect evaluation of the results.
Nausea or vomiting, preceding jaundice, often indicates acute hepatitis or obstruction of the common bile duct by concrement; pain in the abdomen or chills appear later. The gradual development of anorexia and malaise is usually characteristic of alcoholic liver damage, chronic hepatitis and cancer.
Since with hyperbilirubinemia urine darkens before the appearance of visible jaundice, this indicates hyperbilirubinemia more reliably than the appearance of jaundice.
Minor jaundice is best visualized when examining a sclera in natural light; it is usually seen if serum bilirubin reaches 2-2.5 mg / dL (34-43 mmol / l). Minor jaundice in the absence of dark urine suggests unconjugated hyperbilirubinemia (most often caused by hemolysis or Gilbert's syndrome); more pronounced jaundice or jaundice, accompanied by a darkening of the urine, suggests hepatobiliary disease. Symptoms of portal hypertension or portosystemic encephalopathy, skin or endocrine changes suggest chronic liver disease.
In patients with hepatomegaly and ascites, swollen jugular veins indicate the possibility of a heart attack or a squeezing pericarditis. Cachexia and unusually dense or tuberous liver are more likely to indicate liver cancer than cirrhosis. Diffuse lymphadenopathy suggests infectious mononucleosis with acute jaundice, lymphoma or leukemia in chronic jaundice. Hepatosplenomegaly in the absence of other symptoms of chronic liver disease can be caused by infiltrative lesions (eg, lymphoma, amyloidosis or endemic areas of schistosomiasis or malaria), although jaundice is usually not expressed or absent in such diseases.
Aminotransferase and alkaline phosphatase levels should be determined. Small hyperbilirubinemia [eg, bilirubin <3 mg / dl (<51 μmol / l)] with a normal level of aminotransferases and alkaline phosphatase is often characteristic of unconjugated bilirubin (eg hemolysis or Gilbert's syndrome, not hepatobiliary disease). Moderate or severe hyperbilirubinemia, bilirubinuria, high levels of alkaline phosphatase or aminotransferases suggest hepatobiliary disease. Hyperbilirubinemia due to unbound bilirubin is usually confirmed by the study of bilirubin fractions.
Other blood tests should be performed according to the indications. For example, serological tests should be performed in case of suspected acute or chronic hepatitis, PV or MHO in case of suspected liver failure, determination of albumin and globulin levels in case of suspected chronic liver disease and determination of the level of antimitochondrial antibodies in case of suspected primary biliary cirrhosis. In cases of an isolated increase in the level of alkaline phosphatase, the level of gamma-glutamyltranspeptidase (GGT) should be investigated; these enzymes increase with hepatobiliary disease, but a high level of alkaline phosphatase can also be a consequence of bone pathology.
In the hepatobiliary pathology, neither the determination of bilirubin fractions nor the degree of bilirubin increase help in the differential diagnosis of hepatocellular pathology and cholestatic jaundice. An increase in the level of aminotransferases of more than 500 units suggests a hepatocellular pathology (hepatitis or acute liver hypoxia), a disproportionate increase in the level of alkaline phosphatase (eg, alkaline phosphatase greater than 3 VGN and aminotransferase less than 200 units) suggests cholestasis. Infiltration of the liver can also lead to a disproportionate increase in the level of alkaline phosphatase relative to aminotransferases, but the level of bilirubin usually does not increase or increases slightly.
Because isolated hepatobiliary disease rarely causes an increase in the level of bilirubin greater than 30 mg / dL (> 513 μmol / L), higher bilirubin levels usually reflect a combination of severe hepatobiliary pathology and hemolysis or renal dysfunction. A low level of albumin and a high level of globulin suggest chronic rather than acute liver pathology. Increases in PV or MHO, which decrease after taking vitamin K (5-10 mg intramuscularly for 2-3 days), indicate a greater degree of cholestasis than hepatocellular pathology, but this is not determinative.
Instrumental examination makes it possible to better diagnose infiltrative changes in the liver and the causes of cholestatic jaundice. Ultrasonography of the abdominal cavity, CT or MRI is usually performed immediately. These studies can detect changes in the biliary tree and focal liver lesions, but they are less informative in the diagnosis of diffuse hepatocellular changes (eg, hepatitis, cirrhosis). With extrahepatic cholestasis, endoscopic or magnetic resonance cholangiopancreatography (ERCPG, MRCPG) provides a more accurate assessment of the biliary tract; ERCP also provides treatment for obstruction (eg, removal of calculus, stenting of stricture).
Liver biopsy is rarely used to diagnose jaundice directly, but may be useful for intrahepatic cholestasis and certain types of hepatitis. Laparoscopy (peritoneoscopy) allows you to examine the liver and gall bladder without traumatic laparotomy. Unexplained cholestatic jaundice justifies laparoscopy, and sometimes diagnostic laparotomy.