A. Etiological pathogenesis classification
1, hemolytic jaundice;
2, hepatocellular jaundice;
3.Biliary depression jaundice;
4, congenital non-hemolytic jaundice.
Second, according to the nature of bilirubin classification
(A) non-conjugated bilirubin is the main jaundice
1, excessive bilirubin production
2, impaired bilirubin uptake
3, bilirubin binding disorder
(ii) Jaundice dominated by increased conjugated bilirubin. It can be caused by impaired transport and excretion of bilirubin in hepatocytes or by simultaneous impaired uptake, binding and excretion of bilirubin.
Regardless of the classification method, the occurrence of jaundice ultimately stems from a disorder of one or more metabolic links of bilirubin.
Mechanisms and clinical features of various types of jaundice
I. Hemolytic jaundice
When a large number of red blood cells are destroyed (hemolysis), an excess of unconjugated bilirubin is produced, which exceeds the uptake, binding, and excretion capacity of the liver cells, resulting in the retention of unconjugated bilirubin in the blood and jaundice.
Features.
(1) Mild jaundice of the sclera, with fever, low back pain and often marked pallor of the skin and mucous membranes during acute attacks (hemolytic crisis);
(2) No pruritus of the skin;
(3) There is splenomegaly;
(4) There are signs of vigorous bone marrow proliferation, such as an increase in peripheral blood reticulocytes, the presence of nucleated red blood cells, and active proliferation of the bone marrow red blood cell system;
(5) Increased total serum bilirubin, usually not exceeding 85 μmol/L, mainly unconjugated bilirubin;
(6) Increased urinary urobilinogen without bilirubin, hemoglobinuria in acute attacks, and increased urinary iron-containing hemoglobin in chronic hemolysis;
Hepatocellular jaundice
Due to hepatocellular lesions, the uptake, binding and excretion of bilirubin are impaired, resulting in a considerable amount of non-conjugated bilirubin retained in the blood, and at the same time, due to hepatocellular damage and/or structural destruction of the liver lobules, resulting in the inability of conjugated bilirubin to drain normally into the small bile ducts and backflow into the hepatic lymphatic fluid and blood, resulting in jaundice.
Features.
(1) The skin and sclera are light yellow to dark golden yellow, and the skin is sometimes itchy;
(2) Increased unconjugated and conjugated bilirubin in the blood;
(3) Positive bilirubin in the urine and often increased urobilinogen, but at the peak of the disease, urobilinogen is reduced or absent due to intrahepatic biliary stasis;
(4) Serum aminotransferases are significantly elevated;
(5) Hepatitis virus markers in the blood are often positive;
(6) Liver biopsy is important for the diagnosis of diffuse liver disease.
(3) Biliary depression jaundice
Intrahepatic biliary depression refers molecularly and cytologically to a decrease in bile production and secretion, as well as bile flow stagnation and concentration. Intrahepatic biliary depression either occurs alone or in conjunction with liver parenchymal damage, and its production mechanism is quite complex, with multiple factors involved.
(1) Structural and functional alterations of the hepatocyte plasma membrane: The hepatocyte plasma membrane is composed of a liquid bilayer of lipid-mosaic proteins (carriers, receptors, structural proteins and enzymes), with a certain ratio of phospholipid to cholesterol content on the plasma membrane to maintain normal membrane microviscosity and membrane fluidity, in relation to carrier movement and Na+-K+-ATPase (sodium pump) activity to be of paramount importance. The production and secretion of bile and the transport of bile solutes to and from the hepatocyte depend on the integrity of the hepatocyte plasma membrane structure and its function. Damage to hepatocytes caused by chlorpromazine, estradiol, stannous acid, endotoxin and hypoxia can increase the cholesterol content of the plasma membrane and reduce membrane fluidity and sodium pump activity, resulting in reduced bile secretion and bile flow;
(2) Microfilament and microtubule dysfunction: the transport of bile acids, the movement of sodium and water to the lumen of the capillary bile ducts and the coordinated peristalsis and contraction around the capillary bile ducts are weakened, resulting in reduced bile flow and forward mobility;
(3) Increased permeability of the capillary bile duct membrane and tight junctions, diffusion or reflux of solute molecules in bile to the surrounding area, resulting in a decrease in water in bile;
(4) abnormal bile acid metabolism: inadequate hydroxylation, formation of toxic monohydroxycholic acid or lithobiliary acid, causing necrosis of hepatocytes and fine bile duct epithelium.
Features.
(1) Dark yellow, yellow-green or greenish-brown complexion;
(2) Pruritus of the skin is prominent and often occurs before the onset of jaundice;
(3) Increased bilirubin in the blood, mainly conjugated bilirubin, with a direct response to qualitative bilirubin tests;
(4) Positive urinary bilirubin, but reduced or absent urinary bilirubinogen;
(5) Decreased or absent urinary bilirubin in the feces, feces appear light gray or clay color;
(6) Increased serum total cholesterol, alkaline phosphatase, γ-glutamyl transpeptidase, and positive lipoprotein-X.
IV. Congenital non-hemolytic jaundice
1.Gilbert syndrome
It is caused by impaired uptake of free bilirubin by hepatocytes and insufficient glucuronosyltransferase in particulate bodies. There is an increase in non-conjugated bilirubin in the serum, normal liver function test, normal erythrocyte fragility, good gallbladder formation, and no abnormal liver biopsy.
2.Dubin-Johnson syndrome
It is due to the impaired excretion of conjugated bilirubin and other organic anions (indocyanine green, X-ray contrast agent) from hepatocytes to capillary bile ducts, resulting in increased serum conjugated bilirubin, but normal uptake and binding of bilirubin. The gallbladder is often not visualized with oral cholangiocontrast. The liver has a greenish-black appearance (black liver), and liver biopsy reveals diffuse brown pigment particles (melanin or adrenaline metabolite multimers) in the hepatocytes.
3.Rotor syndrome
Due to congenital defects in the uptake of free bilirubin and excretion of conjugated bilirubin by hepatocytes, the increase in conjugated bilirubin in the blood is predominant, and there is a decrease in indocyanine green (ICG) excretion test. The cholangiogram was mostly good, but a few were unremarkable. Liver biopsy was normal, and there were no pigment particles in the hepatocytes.
4.Crigler-Najjar syndrome
It is due to the lack of glucuronosyltransferase in hepatocytes, resulting in the inability to form conjugated bilirubin, thus the concentration of unconjugated bilirubin in blood is very high, which can be complicated by nuclear jaundice; the prognosis is very poor.