Biliary atresia

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Introduction0:00–0:23

With biliary atresia, biliary refers to the extra hepatic bile ducts, while atresia means an abnormal closure or absence of a normal opening.
So in biliary atresia, there's partial or complete obstruction of the extra hepatic bile ducts, which prevents normal flow of the bile out of the liver.
As a result, the bile builds up in the liver which triggers inflammation, progressive fibrosis, and eventually cirrhosis.

Pathology0:23–1:08

But before we proceed, first, let's focus on the bile ducts. Everything starts with hepatocytes which carefully mix several ingredients to create bile.
These include bile salts, phospholipids, cholesterol, and conjugated bilirubin. Once they produce bile, hepatocytes drain it into tiny intrahepatic channels called bile canaliculi.
These canaliculi merge to form progressively larger intrahepatic bile ducts which combine to create the right and left hepatic ducts.
Eventually these two join to create the common hepatic duct, marking the beginning of the extrahepatic biliary system. The common hepatic duct then meets the cystic duct from the gallbladder to form the common bile duct which empties into the duodenum.

Symptoms1:08–1:51

But what hepatocytes produce is not the final product that reaches the intestine. That's because intrahepatic and extrahepatic bile ducts are lined with cholangiocytes that fine tune the composition of bile as it flows toward the intestine.
The ultimate bile product in the intestine helps digest fats and absorb fat soluble vitamins A, D, E, and K. Also, conjugated bilirubin gives the stool its specific color.

Treatment1:51–8:32

Now in biliary atresia, something triggers a partial or complete obstruction of the bile ducts blocking the normal flow of bile out of the liver.
This buildup is known as cholestasis. Based on the timing of this obstruction, we can subdivide biliary atresia into two main types fetal type and perinatal type.
The fetal type is less common and occurs when the bile ducts don't develop properly before birth, so basically when a baby is born, the biliary system cannot pass bile to the intestines.
The exact cause remains unclear, but it's often associated with other congenital anomalies such as intestinal malrotation, heart defects, interrupted inferior vena cava, and polysplenia, which refers to the presence of multiple small accessory spleens.
Because ducts never form properly, bile has nowhere to go. As a result, it starts backing up in the liver.
This stretches the tiny intrahepatic ducts, causing them to proliferate in an attempt to find new drainage routes. This attempt to reroute bile drainage is called a ductular reaction.
Meanwhile, hepatocytes can't get rid of their bile salts, which act like tiny detergents, damaging cell membranes and letting water in.
Ultimately, this results in hepatocyte swelling and destruction of the internal components, creating a pale, streaky appearance called feathery degeneration.
As hepatocytes die, the liver tries to repair itself by laying down collagen. Which leads to progressive perioral fibrosis.
Over time, this fibrosis spreads outwards, creating bridging fibrosis that links adjacent portal tracts. If left untreated within 3 to 6 months, fibrosis progresses to biliary cirrhosis.
The second type is the perinatal type, which is far more common here. The bile ducts develop normally before birth but become damaged several weeks after birth.
The exact trigger remains unknown, but it's thought to involve a viral infection or a toxin exposure that sets off an abnormal immune response.
When this happens, T cells and macrophages infiltrate the extra hepatic bile ducts and the gallbladder, causing inflammation that destroys the cholangiocytes.
Next, the body tries to repair the injury by activating fibroblasts to lay down collagen. This leads to fibrosis and eventual obliteration of the ducts, but the damage doesn't stop there.
The inflammation spreads upstream to the liver without proper drainage. B Ble backs up in the intrahepatic ducts, triggering ductular reaction and feathery degeneration of hepatocytes.
Similarly, the ongoing inflammation leads to progressive fibrosis and eventually biliary cirrhosis. Now moving on to clinical manifestations in the fetal type, the bile ducts are already abnormal at birth, meaning the signs of biliary obstruction appear soon after birth.
On the flip side, in the perinatal type, babies initially appear healthy. They are feeding well and gaining weight.
However, as the bile ducts gradually get blocked, the first signs usually appear between 2 and 6 weeks of age. Despite the difference in timing, clinical manifestations are similar because bile cannot reach the intestine.
Conjugated bilirubin enters the bloodstream, causing progressive jaundice. Next, the kidneys attempt to excrete excessive bilirubin, which leads to dark tea-colored urine, while the absence of bilirubin in the intestines results in pale, clay-colored or white stools.
This is known as echolic stools. In addition, bile salts from the bloodstream accumulate in the skin, causing pruritis.
On top of that, no bile in the intestines impairs fat absorption and results in failure to thrive. As liver damage and fibrosis progress, cirrhosis develops along with signs of portal hypertension, such as splenomegaly, hepatomegaly, and ascites.
When it comes to diagnosis, labs are usually the first clue. In biliary atresia, conjugated bilirubin is high.
This is important because it sets it apart from other causes of newborn jaundice, where unconjugated bilirubin dominates.
Next, gamma glutamyl transferase and alkaline phosphatase are also high, reflecting bile duct injury. Imaging comes next.
Abdominal ultrasound often shows the triangular cord sign, which is a fibrotic remnant of the obliterated extrahepatic bile ducts at the porta hepatis.
Additionally, the gallbladder will be absent or abnormal. Another imaging tool is the HIA scan, which uses a radioactive tracer to track bile excretion.
In biliary atresia, the tracer enters the liver, but it never appears in the intestine. Confirming biliary obstruction and to tie everything together, the definitive diagnosis comes from a liver biopsy.
Once biliary atresia is diagnosed, the main treatment is surgery. If the obstruction affects only the extra hepatic ducts, the go to method is the CASSI procedure or hepatoportoenterostomy.
On the flip side, in later stages, when inflammation and obstruction spread to the intrahepatic ducts, the management requires liver transplantation.
All right, as a quick recap. In biliary atresia, something triggers a partial or complete obstruction of the bile ducts.
In the fetal type, the bile ducts don't develop properly, so obstruction is present at birth. In the perinatal type, the bile ducts develop normally but become damaged due to infections or a toxic exposure.
In both, the outcome is the same. Bile accumulates in the liver, causing inflammation and fibrosis, which eventually progresses to biliary cirrhosis.