Biliary atresia — Transcript

Full transcript

1. 0:02With biliary atresia, biliary refers to
2. 0:06the extrahepatic bile ducts, while
3. 0:09atresia means an abnormal closure or
4. 0:11absence of a normal opening. So, in
5. 0:14biliary atresia, there's partial or
6. 0:16complete obstruction of the extrahepatic
7. 0:19bile ducts, which prevents normal flow
8. 0:21of the bile out of the liver. As a
9. 0:23result, the bile builds up in the liver,
10. 0:25which triggers inflammation, progressive
11. 0:28fibrosis, and eventually cirrhosis.
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18. 0:51>> But before we proceed, first, let's
19. 0:53focus on the bile ducts. Everything
20. 0:56starts with hepatocytes, which carefully
21. 0:58mix several ingredients to create bile.
22. 1:02These include bile salts, phospholipids,
23. 1:05cholesterol, and conjugated bilirubin.
24. 1:08Once they produce bile, hepatocytes
25. 1:10drain it into tiny intrahepatic channels
26. 1:13called bile canaliculi. These canaliculi
27. 1:17merge to form progressively larger
28. 1:19intrahepatic bile ducts, which combine
29. 1:21to create the right and left hepatic
30. 1:24ducts. Eventually, these two join to
31. 1:26create the common hepatic duct, marking
32. 1:29the beginning of the extrahepatic
33. 1:30biliary system.
34. 1:32The common hepatic duct then meets the
35. 1:35cystic duct from the gallbladder to form
36. 1:37the common bile duct, which empties into
37. 1:40the duodenum.
38. 1:44But what hepatocytes produce is not the
39. 1:47final product that reaches the
40. 1:48intestine. That's because intrahepatic
41. 1:51and extrahepatic bile ducts are lined
42. 1:54with cholangiocytes that fine-tune the
43. 1:57composition of bile as it flows toward
44. 1:59the intestine.
45. 2:00The ultimate bile product in the
46. 2:02intestine helps digest fats and absorb
47. 2:05fat-soluble vitamins A, D, E, and K.
48. 2:09Also, conjugated bilirubin gives the
49. 2:12stool its specific color.
50. 2:16Now, in biliary atresia, something
51. 2:19triggers a partial or complete
52. 2:21obstruction of the bile ducts, blocking
53. 2:23the normal flow of bile out of the
54. 2:25liver. This buildup is known as
55. 2:27cholestasis.
56. 2:29Based on the timing of this obstruction,
57. 2:31we can subdivide biliary atresia into
58. 2:33two main types, fetal type and perinatal
59. 2:37type.
60. 2:40The fetal type is less common and occurs
61. 2:42when the bile ducts don't develop
62. 2:44properly before birth. So, basically,
63. 2:47when a baby is born, the biliary system
64. 2:49cannot pass bile to the intestines.
65. 2:52The exact cause remains unclear, but
66. 2:55it's often associated with other
67. 2:56congenital anomalies, such as intestinal
68. 2:59malrotation, heart defects, interrupted
69. 3:02inferior vena cava, and polysplenia,
70. 3:05which refers to the presence of multiple
71. 3:08small accessory spleens.
72. 3:12Because ducts never form properly, bile
73. 3:14has nowhere to go. As a result, it
74. 3:17starts backing up in the liver.
75. 3:19This stretches the tiny intrahepatic
76. 3:22ducts, causing them to proliferate in an
77. 3:24attempt to find new drainage routes.
78. 3:27This attempt to reroute bile drainage is
79. 3:30called a ductular reaction.
80. 3:34Meanwhile, hepatocytes can't get rid of
81. 3:37their bile salts, which act like tiny
82. 3:39detergents, damaging cell membranes and
83. 3:42letting water in.
84. 3:43Ultimately, this results in hepatocyte
85. 3:46swelling and destruction of the internal
86. 3:48components, creating a pale, streaky
87. 3:51appearance called feathery degeneration.
88. 3:56As hepatocytes die, the liver tries to
89. 3:59repair itself by laying down collagen,
90. 4:03which leads to progressive periportal
91. 4:05fibrosis.
92. 4:07Over time, this fibrosis spreads
93. 4:09outwards, creating bridging fibrosis
94. 4:11that links adjacent portal tracts. If
95. 4:14left untreated within 3 to 6 months,
96. 4:17fibrosis progresses to biliary
97. 4:19cirrhosis.
98. 4:23The second type is the perinatal type,
99. 4:25which is far more common.
100. 4:27Here, the bile ducts develop normally
101. 4:29before birth, but become damaged several
102. 4:32weeks after birth.
103. 4:34The exact trigger remains unknown, but
104. 4:36it's thought to involve a viral
105. 4:38infection or a toxin exposure that sets
106. 4:41off an abnormal immune response.
107. 4:47When this happens, T cells and
108. 4:48macrophages infiltrate the extrahepatic
109. 4:51bile ducts and the gallbladder, causing
110. 4:54inflammation that destroys the
111. 4:56cholangiocytes.
112. 4:57Next, the body tries to repair the
113. 4:59injury by activating fibroblasts to lay
114. 5:02down collagen.
115. 5:04This leads to fibrosis and eventual
116. 5:06obliteration of the ducts, but the
117. 5:08damage doesn't stop there.
118. 5:12The inflammation spreads upstream to the
119. 5:14liver.
120. 5:15Without proper drainage, bile backs up
121. 5:18in the intrahepatic ducts,
122. 5:20triggering ductular reaction and
123. 5:22feathery degeneration of hepatocytes.
124. 5:25Similarly, the ongoing inflammation
125. 5:27leads to progressive fibrosis and
126. 5:29eventually biliary cirrhosis.
127. 5:33Now, moving on to clinical
128. 5:35manifestations.
129. 5:36In the fetal type, the bile ducts are
130. 5:38already abnormal at birth, meaning the
131. 5:40signs of biliary obstruction appear soon
132. 5:43after birth.
133. 5:44On the flip side, in the perinatal type,
134. 5:47babies initially appear healthy. They're
135. 5:49feeding well and gaining weight.
136. 5:51However, as the bile ducts gradually get
137. 5:53blocked, the first signs usually appear
138. 5:56between two and six weeks of age.
139. 5:59Despite the difference in timing,
140. 6:01clinical manifestations are similar.
141. 6:04Because bile cannot reach the intestine,
142. 6:06conjugated bilirubin enters the
143. 6:08bloodstream causing progressive
144. 6:10jaundice. Next, the kidneys attempt to
145. 6:14excrete excess of bilirubin, which leads
146. 6:16to dark tea-colored urine, while the
147. 6:19absence of bilirubin in the intestines
148. 6:21results in pale, clay-colored, or white
149. 6:24stools. This is known as acholic stools.
150. 6:27In addition, bile salts from the
151. 6:29bloodstream accumulate in the skin
152. 6:31causing pruritus.
153. 6:33On top of that, no bile in the
154. 6:35intestines impairs fat absorption and
155. 6:38results in failure to thrive.
156. 6:40As liver damage and fibrosis progress,
157. 6:43cirrhosis develops along with signs of
158. 6:45portal hypertension such as
159. 6:48splenomegaly, hepatomegaly, and ascites.
160. 6:53When it comes to diagnosis, labs are
161. 6:55usually the first clue.
162. 6:57In biliary atresia, conjugated bilirubin
163. 6:59is high. This is important because it
164. 7:02sets it apart from other causes of
165. 7:04newborn jaundice where unconjugated
166. 7:06bilirubin dominates. Next, gamma
167. 7:09glutamyl transferase and alkaline
168. 7:12phosphatase are also high reflecting
169. 7:15bile duct injury.
170. 7:17Imaging comes next. Abdominal ultrasound
171. 7:20often shows the triangular cord sign,
172. 7:23which is a fibrotic remnant of the
173. 7:25obliterated extrahepatic bile ducts at
174. 7:27the porta hepatis. Additionally, the
175. 7:30gallbladder will be absent or abnormal.
176. 7:33Another imaging tool is the HIDA scan,
177. 7:35which uses a radioactive tracer to track
178. 7:38bile excretion. In biliary atresia, the
179. 7:41tracer enters the liver, but it never
180. 7:44appears in the intestine, confirming
181. 7:46biliary obstruction. And to tie
182. 7:48everything together, the definitive
183. 7:50diagnosis comes from a liver biopsy.
184. 7:54Once biliary atresia is diagnosed, the
185. 7:57main treatment is surgery. If the
186. 7:59obstruction affects only the
187. 8:01extrahepatic ducts, the go-to method is
188. 8:04the Kasai procedure or
189. 8:06hepatoportoenterostomy.
190. 8:09On the flip side, in later stages, when
191. 8:11inflammation and obstruction spread to
192. 8:13the intrahepatic ducts, the management
193. 8:16requires liver transplantation.
194. 8:19All right, as a quick recap,
195. 8:22in biliary atresia, something triggers a
196. 8:24partial or complete obstruction of the
197. 8:26bile ducts. In the fetal type, the bile
198. 8:29ducts don't develop properly, so
199. 8:31obstruction is present at birth. In the
200. 8:34perinatal type, the bile ducts develop
201. 8:36normally, but become damaged due to
202. 8:39infections or a toxic exposure. In both,
203. 8:42the outcome is the same. Bile
204. 8:45accumulates in the liver, causing
205. 8:46inflammation and fibrosis, which
206. 8:48eventually progresses to biliary
207. 8:51cirrhosis.
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