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High direct bilirubin: causes


Bilirubin is among hemoglobin breakdown products. It is constantly being generated in the body in the course of red blood cells renewal. Initially just indirect bilirubin is formed. Its transformation (or conjugation) into direct bilirubin takes place in the liver. After conjugation direct bilirubin is excreted with bile into the intestine.


Mechanism of hepatic elevation of direct bilirubin
Mechanism of hepatic elevation of direct bilirubin: a transport of direct bilirubin from hepatocites to bile is affected and/or a flow of bile in intrahepatic bile ducts is obsructed

There are a variety of liver diseases that influence bilirubin metabolism in either one way or another. Some of them hinder conjugation of indirect bilirubin contributing to high level of indirect bilirubin in blood. But such conditions form a small set. Diseases that increase direct bilirubin make up the majority. They affect a transport of direct bilirubin from hepatocites to bile and/or obstruct a flow of bile in intrahepatic bile ducts:

  1. Hepatitis, or inflamatory damage of hepatic cells. It is responsible for elevated direct biliribin level. In hepatitis indirect bilirubin is increased too, but not as much as direct bilirubin ([link]: how to identify, which of bilirubin forms is increased). There are also excess transaminase enzymes (AST and ALT).
    • Viral hepatitis is the most common type of hepatitis. Depending on virus type they are identified by the letters 'A', 'B', 'C', 'D', 'E'. Hepatitis A and E are transmitted through the fecal-oral route and never lead to chronic hepatitis. Hepatitis B, C, D are transmitted by blood and often progress to chronic form, especially hepatitis C. Hepatitis D is not self-sufficient, it only comes with hepatitis B.
    • Parasitic hepatitis might be induced by:
      • protozoans, such as malaria parasite Plasmodium, Entamoeba histolytica (the causative agent of amoebic diarrhea)
      • parasitic flukes, which may be carried by infected fish and molluscs. Most often they parasitize in intrahepatic bile ducts.
    • Bacterial hepatitis can be acute or chronic. Acute bacteril hepatitis are characterized by high severity and tendency to develop intrahepatic abscesses. Among the causes of acute bacteril hepatitis are septicemia, severe pneumonia, leptospirosis or Weil's disease, intestinal infections. Chronic bacteril hepatitis can be caused by mycobacteria (the causative agent of tuberculosis), Treponema pallidum (the causative agent of syphilis) etc.
    • Toxic hepatitis, among which are:
      • alcoholic hepatitis ranks equally with viral hepatitis in terms of incidence. '2 beers per day' is a sure recipe for this condition. Alcoholic hepatitis tends to run a chronic course and is often complicated with cirrhosis.
      • hepatitis induced by drugs, such as:
        • tetracycline antibiotics
        • antituberculosis drugs, such as isoniazid
        • antidepressants
        • drugs that contain anabolic steroids
        • paracetamol
      • hepatitis induced by industrial toxins such as organic solvents, insecticides
      • hepatitis induced by herbal toxins, poisonous mushrooms
    • Autoimmune hepatitis are chronic. They might coexist with other autoimmune diseases such as thyroiditis (inflammation of thyroid), arthritis (inflammation of joints), ulcerative colitis (inflammation of colon), nephritis (inflammation of kidneys), hemolytic anemia etc. Blood tests detect specific antibodies to hepatic cells.
    • Hepatitis induced by inherited disorders of metabolism:
      • hemochromatosis (disorder of iron metabolism)
      • Wilson disease (disorder of copper metabolism)
      Their marked characteristics are chronic course and buildup of iron and copper accordingly in hepatic tissue. For more accurate diagnostics liver biopsy is required.
  2. Cirrhosis: chronic disease, in which normal hepatic tissue is being replaced by scar tissue. Cirrhosis can be a primary autoimmune disease (primary biliary cirrhosis) or be preceded by other chronic liver diseases that are chronic hepatitis B, C and alcoholic hepatitis in most cases. Diagnostics of cirrosis also requires liver biopsy.
  3. Tumors of liver
  4. Rare hereditary diseases:
    • Dubin-Johnson syndrome
    • Rotor syndrome
    Transport of direct bilirubin from liver cell to bile does not function properly due to defects in genetic code for transport enzymes.


Mechanism of post-hepatic elevation of direct bilirubin
Mechanism of post-hepatic elevation of direct bilirubin: obstruction of common bile duct

Only direct bilirubin enters the bile and travels with it from liver to duodenum through only available channel that is common bile duct. The final portion of common bile duct is normally embedded in pancreas and opens into duodenum along with pancreatic duct. This circumstance makes a process of bile outflow vulnerable to any sort of pathologies of the duct, pancreas and duodenum.

Blockage of common bile duct from inside or outside results in complete or partial blockage of bile outflow and return of direct bilirubin to blood. It may induce so-called "obstructive" or "post-hepatic" jaundice. Long-lasting obstructive jaundice damages liver function.

In obstructive jaundice blood test shows normal or slightly elevated levels of transaminase (ALT, AST) and highly elevated level of alkaline phosphatase.

Blockage of extrahepatic bile ducts may be due to:

  • Choledocholithiasis: gallstone migrates from gallbladder to common bile duct and blocks it up.
  • Cholangitis: inflammation in the inner lining of bile ducts, may be acute or chronic and involve both common bile duct and smaller conduits. The most common causes of cholangitis are:
    • bacteria occupying the ducts, which may have spread from duodenum or gallbladder
    • protozoans and parazites, which may have taken up residence in bile ducts.
  • Fibrous stricture of common bile duct: a result of long-lasting cholangitis or surgery.
  • Tumors of pancreas head, duodenum, bile ducts.
  • Cysts within the head of pancreas.
  • Duodenal diverticulum: a pouch attached to the wall of duodenum, accomponied with its chronic inflammation. In case the diverticulum is near the common bile duct orifice (Ampulla of Vater), there is a chance of its blockage due to swelling or corrosive stricture.
  • Aneurysm of hepatic artery: this large blood vessel is located in a close proximity to the bile ducts and may become a cause of their compression.

To identify the cause of blockage of extrahepatic bile ducts, instrumental diagnostics methods, such as ultrasound, ERC (Endoscopic Retrograde Cholangiography), CT scans (Computered Tomography), MRI (Magnetic Resonance Imaging), should be used.


hepatic direct bilirubin buildup post-hepatic direct bilirubin buildup
main causes hepatitis, cirrhosis cholelithiasis, tumors
mechanism of buildup disorder of direct bilirubin transport from hepatic cells to bile, stoppage of bile flow in intrahepatic bile ducts obstruction of extrahepatic bile ducts by gallstones, tumors, strictures
feces discoloration possible (total or partial) yes
indirect bilirubin normal or slighly elevated normal
direct bilirubin high high
transaminase (ALT, AST) high normal
alkaline phosphatase (ALP) normal or moderately elevated extraelevated
bilirubin in urine yes yes
urobilinogen in urine high or absent absent