biliary atresia
recently, i had a professorial tutorial during which a case was discussed. this is the rough background:
- 7 months old girl
- jaundiced at birth
- initially treated with phototherapy a few days after birth
- diagnosed with physiological jaundice
- jaundice failed to resolve after photoTx
- acholic stools and tea colored urine a few days later
- steatorrhea
- now presenting with jaundice, hepatosplenomegay with malaema. developmentally delayed in all aspects but otherwise well.
O/E:
- generalized jaundice with scleral icterus but absent bitot's spots. no other significant skin findings (e.g. purpura/ecchymosis)
- distended abdomen with prominent veins. umbilicus flushed, no Kaput Medusae
- hepatosplenomegaly
- no scratch marks suggestive of pruritus (obviously, in view of the child's age)
- acholic stools, tea colored urine
- no spider naevi
Problems list:
1. jaundice with hepatosplenomegaly
2. malaena
How bad is the jaundice, you may ask. There is a general rule of thumb:
1. Jaundice limited to the face: Tbil = 5mg/dL
2. jaundice to midabdomen: Tbil = 15mg/dL
3. Jaundice to soles: Tbil = 20mg/dL
Approach:
1. physiological jaundice? breastfeeding jaundce? breastmilk jaundice?
2. conjugated/unconjugated hyperbilirubinaemia? how can you tell?
3. what investigations are appropriate?
Okay. So this obviously isnt a case of physiological jaundice because anything that lasts beyond 2-3 weeks is abnormal plus physiological jaundice usually appears only AFTER 24 hours due to suboptimal caloric intake.
Should hemolytic anemia be considered? of course! a series of blood test (e.g. FBC) will r/o anemia. If there is indeed anemia, further investigations like reticulocyte count and PBFs will yield major clues.
We've established that this isn't physiological/BF/BM jaundice. so what we could do next is to carry out some investigations:
1. FBC
2. LFT
3. CMV-IgM (r/o congenital infection CMV)
4. HBS U/S
FBC: as mentioned above, FBC will r/o any anemia
LFT: this is vital in the assessment of whether it is a direct/indirect hyperbilirubinaemia.
components of the LFT include: bilirubin, 5 enzymes, albumin/PT/PTT
(i) total bilirubin (Tbil)
(ii) direct bilirubin and direct/Tbil ratio
(iii) AST/ALT: aspartate transaminase/alanine transaminase. ALT is more specific in liver, but may be raised in muscular pathologies. AST is also found in RBC and blood (GOT1) while those in liver are of GOT2 isoenzyme type.
(iv) LDH: lactate dehydrogenase: like AST, may be elevated in lysis of RBC
(v) Albumin, PT/PTT: assess the productive function of the liver
(vi) ALP: raised in children (bone growth, maybe even rickets), usually N at 300
(vii) GGT: raised in children up to 2 months (biliary remodelling)
Some tips at reading LFT:
(i) a. 1mg% or 20mmol of direct Bil or b. 10-15% directbil/Tbil = conjugated hyperbilirubinaemia
(ii) GGT >350
(iii) GGT/ALT > 4
(iv) GGT/AST > 4
for factors (ii) (iii) and (iv) --> biliary atresia until proven otherwise
(v) PT>>PTT with normal albumin levels = acute hepatic insult. One should give Vitamin K to r/o cholestatic jaundice. (i.e. injection of phytomenadione) will correct the PT in the event of cholestatic jaundice whereas in hepatic disease, PT will still be elevated.
anyway our child was found to have conjugated hyperbilirubinaemia (DirectBil/Tbil > 20%) and GGT > 350, GGT/ALT and GGT/AST > 4
So the child was suspected to have biliary atresia unless proven otherwise
Other causes of jaundice should be considered:
Unconjugated jaundice:
1. Breast milk jaundice: unlikely, jaundice in her case was too prolonged
2. infection: an CMV-IgM was done and shown to be negative. A septic workup was done as jaundice in children may be a non-specific symptom. However, FBC did not suggest an infective picture, neither did the child show
3. Haemolytic anemia: unlikely
4. CNS: Criggler Najjar syndrome (CNS1: AR, no UGT1A1, CNS2: AD, reduced UGT1A1)
Conjugated jaundice: our main consideration
1. Anatomical causes: BA, choledochal cyst
2. Congenital infections
3. Inborn errors of metabolism: 5 main: a1 antitrypsin deficiency, tyrosinaemia (type 1), galactossemia, fructose intolerance
4. cystic fibrosis: erh. in singapore? if you love death, u may mention this to your prof.
5. TPN cholestasis: come on, TPN in this case? brains boy, brains
6. Alagille's syndrome: intrahepatic biliary hypoplasia, characteristic facies (broad forehead, hypertelorism, deep set eyes, small pointed chin, triangular face), pulmonary stenosis, tetrallogy of Fallot.
Anyway, with BA (biliary atresia) being at the top on our list, we shall investigate as such:
1. HBS U/S
2. HIDA scan
3. Liver biopsy
4. exploratory laparotomy with intraoperative cholangiogram + KIV Kasai hepatoportoenterostomy
HBS U/S:
Good test! Unlike what most books say, Prof Kua stated during the tutorial that the pick up rate for BA using HBSUS is actually good at 90% (assuming it being done by an experienced operator). This is usually done when the child is fasted. This allows time for GB to collect bile which can then be visualized. Then, the baby is fed and the GB should empty. if it does not, suspect BA. Also, triangular cord sign (95% accurate) may be picked up at the porta hepatis.
HIDA scan: hydroxyiminodiacetic acid scan
Normal uptake of isotope w/o excretion
- Very high false positives (i.e. poor positive predictive value): liver so bad, does not take up isotope or liver so swollen, does not excrete isotope
- very low false negatives (i.e. good negative predictive value)
Liver Biopsy:
Liver biopsy will pick up fibrous bands with dilated and proliferating bile ducts
Working diagnosis:
Biliary atresia
Issues:
1. what is biliary atresia
2. complications
3. should we do a KASAI now?
4. how do we know if KASAI is successful? what advice do we give to the parents
Biliary atresia:
Biliary atresia is a progressive disease where there is destruction or absence of extrahepatic biliary trees and intrahepatic biliary ducts. the jaundice is of conjugated form and does not cause kernicterus. Anatomically divided into 3 types by Kasai classification.
Complications of chronic liver disease + cholestasis: HEPATIC + ADEK and fats
(i) Hepatic encephalopathy, hepatorenal sydnrome (renal failure)
(ii) Esophageal varices and bleeding
(iii) Portal hypertension, hepatopulmonary syndrome (platypnea, orthodeoxia)
(iv) Ascites
(v) Thrombosis of portal vein, thrombotic dysfunction (lack of factor synthesis)
(vi) Infection (SBP)
(vii) Carcinoma (HCC)
cholestasis: ADEK:
Vitamin A: Bitot's spots, night blindness
Vitamin D: rickets (in children), osteopenia (in adutls)
Vitamin E: a whole host of neurological signs
Vitamin K: reduced clotting factors
Steatorrhea
KASAI hepatoportoenterostomy should ube done before 100 days old and not beyond 4 months because
(i) liver already very cirrhotic
How is KASAI judged to be successful?
(i) ascending cholangitis
(ii) normalized bilirubin 1 month after op
--> many still need liver transplant 20-30 years down the road
Partially successful?
(i) improvement of jaundice, but still jaundiced
--> transplant within 1st decade
Failure!
(i) bilirubin levels not nromalzied after 1 month, but keep in mind that it may take up to 6 months before normalizing. LOOK AT TREND!
(ii) stools still acholic, jaundice persistent
==> DIE within 1-2 years if without transplant
Advice to parents:3 points of Kasai
1. optimum do before 100 days
2. hmm
(i) 30% Kasai FAILS
(ii) 30% Kasai partially successful
(iii) 30% successful
3. chances of success
(i) experience of surgeon
(ii) age of child, the older the child, the lower the chance of success
ANYWAY ADDITIONAL STUFF
treatment of portal hypertension:
TIPS: transjugular intrahepatic portosystemic shunt
- it should be discussed with the parents with regards to TIPS for it may serve to contradict a liver transplant in the future
Note to self:
1. breastfeeding jaundice and breastmilk jaundice are obviously different. Breast feeding jaundice is occurs early after birth (usually within the 1st week) and is due to insufficient feeding or breast milk production. Breastmilk jaundice, however, is due to ingredients within the breast milk that hinders conjugation and excretion of breast milk and thus resulting in unconjugated jaundice (indirect jaundice) appears later (after 1st week):
A. progesterone metabolite inhibits UDPGA(uridine diphosphoglucuronic acid) glucuronyl transferase
B. increased concentration of non-esterified fatty acids inhibit hepatic glucuronyl transferase
C. increased beta glucuronidase activity in breast milk, delayed establishment of enteric flora in breastfed infants ==> increased hepatoenteric cycling
- 7 months old girl
- jaundiced at birth
- initially treated with phototherapy a few days after birth
- diagnosed with physiological jaundice
- jaundice failed to resolve after photoTx
- acholic stools and tea colored urine a few days later
- steatorrhea
- now presenting with jaundice, hepatosplenomegay with malaema. developmentally delayed in all aspects but otherwise well.
O/E:
- generalized jaundice with scleral icterus but absent bitot's spots. no other significant skin findings (e.g. purpura/ecchymosis)
- distended abdomen with prominent veins. umbilicus flushed, no Kaput Medusae
- hepatosplenomegaly
- no scratch marks suggestive of pruritus (obviously, in view of the child's age)
- acholic stools, tea colored urine
- no spider naevi
Problems list:
1. jaundice with hepatosplenomegaly
2. malaena
How bad is the jaundice, you may ask. There is a general rule of thumb:
1. Jaundice limited to the face: Tbil = 5mg/dL
2. jaundice to midabdomen: Tbil = 15mg/dL
3. Jaundice to soles: Tbil = 20mg/dL
Approach:
1. physiological jaundice? breastfeeding jaundce? breastmilk jaundice?
2. conjugated/unconjugated hyperbilirubinaemia? how can you tell?
3. what investigations are appropriate?
Okay. So this obviously isnt a case of physiological jaundice because anything that lasts beyond 2-3 weeks is abnormal plus physiological jaundice usually appears only AFTER 24 hours due to suboptimal caloric intake.
Should hemolytic anemia be considered? of course! a series of blood test (e.g. FBC) will r/o anemia. If there is indeed anemia, further investigations like reticulocyte count and PBFs will yield major clues.
We've established that this isn't physiological/BF/BM jaundice. so what we could do next is to carry out some investigations:
1. FBC
2. LFT
3. CMV-IgM (r/o congenital infection CMV)
4. HBS U/S
FBC: as mentioned above, FBC will r/o any anemia
LFT: this is vital in the assessment of whether it is a direct/indirect hyperbilirubinaemia.
components of the LFT include: bilirubin, 5 enzymes, albumin/PT/PTT
(i) total bilirubin (Tbil)
(ii) direct bilirubin and direct/Tbil ratio
(iii) AST/ALT: aspartate transaminase/alanine transaminase. ALT is more specific in liver, but may be raised in muscular pathologies. AST is also found in RBC and blood (GOT1) while those in liver are of GOT2 isoenzyme type.
(iv) LDH: lactate dehydrogenase: like AST, may be elevated in lysis of RBC
(v) Albumin, PT/PTT: assess the productive function of the liver
(vi) ALP: raised in children (bone growth, maybe even rickets), usually N at 300
(vii) GGT: raised in children up to 2 months (biliary remodelling)
Some tips at reading LFT:
(i) a. 1mg% or 20mmol of direct Bil or b. 10-15% directbil/Tbil = conjugated hyperbilirubinaemia
(ii) GGT >350
(iii) GGT/ALT > 4
(iv) GGT/AST > 4
for factors (ii) (iii) and (iv) --> biliary atresia until proven otherwise
(v) PT>>PTT with normal albumin levels = acute hepatic insult. One should give Vitamin K to r/o cholestatic jaundice. (i.e. injection of phytomenadione) will correct the PT in the event of cholestatic jaundice whereas in hepatic disease, PT will still be elevated.
anyway our child was found to have conjugated hyperbilirubinaemia (DirectBil/Tbil > 20%) and GGT > 350, GGT/ALT and GGT/AST > 4
So the child was suspected to have biliary atresia unless proven otherwise
Other causes of jaundice should be considered:
Unconjugated jaundice:
1. Breast milk jaundice: unlikely, jaundice in her case was too prolonged
2. infection: an CMV-IgM was done and shown to be negative. A septic workup was done as jaundice in children may be a non-specific symptom. However, FBC did not suggest an infective picture, neither did the child show
3. Haemolytic anemia: unlikely
4. CNS: Criggler Najjar syndrome (CNS1: AR, no UGT1A1, CNS2: AD, reduced UGT1A1)
Conjugated jaundice: our main consideration
1. Anatomical causes: BA, choledochal cyst
2. Congenital infections
3. Inborn errors of metabolism: 5 main: a1 antitrypsin deficiency, tyrosinaemia (type 1), galactossemia, fructose intolerance
4. cystic fibrosis: erh. in singapore? if you love death, u may mention this to your prof.
5. TPN cholestasis: come on, TPN in this case? brains boy, brains
6. Alagille's syndrome: intrahepatic biliary hypoplasia, characteristic facies (broad forehead, hypertelorism, deep set eyes, small pointed chin, triangular face), pulmonary stenosis, tetrallogy of Fallot.
Anyway, with BA (biliary atresia) being at the top on our list, we shall investigate as such:
1. HBS U/S
2. HIDA scan
3. Liver biopsy
4. exploratory laparotomy with intraoperative cholangiogram + KIV Kasai hepatoportoenterostomy
HBS U/S:
Good test! Unlike what most books say, Prof Kua stated during the tutorial that the pick up rate for BA using HBSUS is actually good at 90% (assuming it being done by an experienced operator). This is usually done when the child is fasted. This allows time for GB to collect bile which can then be visualized. Then, the baby is fed and the GB should empty. if it does not, suspect BA. Also, triangular cord sign (95% accurate) may be picked up at the porta hepatis.
HIDA scan: hydroxyiminodiacetic acid scan
Normal uptake of isotope w/o excretion
- Very high false positives (i.e. poor positive predictive value): liver so bad, does not take up isotope or liver so swollen, does not excrete isotope
- very low false negatives (i.e. good negative predictive value)
Liver Biopsy:
Liver biopsy will pick up fibrous bands with dilated and proliferating bile ducts
Working diagnosis:
Biliary atresia
Issues:
1. what is biliary atresia
2. complications
3. should we do a KASAI now?
4. how do we know if KASAI is successful? what advice do we give to the parents
Biliary atresia:
Biliary atresia is a progressive disease where there is destruction or absence of extrahepatic biliary trees and intrahepatic biliary ducts. the jaundice is of conjugated form and does not cause kernicterus. Anatomically divided into 3 types by Kasai classification.
Complications of chronic liver disease + cholestasis: HEPATIC + ADEK and fats
(i) Hepatic encephalopathy, hepatorenal sydnrome (renal failure)
(ii) Esophageal varices and bleeding
(iii) Portal hypertension, hepatopulmonary syndrome (platypnea, orthodeoxia)
(iv) Ascites
(v) Thrombosis of portal vein, thrombotic dysfunction (lack of factor synthesis)
(vi) Infection (SBP)
(vii) Carcinoma (HCC)
cholestasis: ADEK:
Vitamin A: Bitot's spots, night blindness
Vitamin D: rickets (in children), osteopenia (in adutls)
Vitamin E: a whole host of neurological signs
Vitamin K: reduced clotting factors
Steatorrhea
KASAI hepatoportoenterostomy should ube done before 100 days old and not beyond 4 months because
(i) liver already very cirrhotic
How is KASAI judged to be successful?
(i) ascending cholangitis
(ii) normalized bilirubin 1 month after op
--> many still need liver transplant 20-30 years down the road
Partially successful?
(i) improvement of jaundice, but still jaundiced
--> transplant within 1st decade
Failure!
(i) bilirubin levels not nromalzied after 1 month, but keep in mind that it may take up to 6 months before normalizing. LOOK AT TREND!
(ii) stools still acholic, jaundice persistent
==> DIE within 1-2 years if without transplant
Advice to parents:3 points of Kasai
1. optimum do before 100 days
2. hmm
(i) 30% Kasai FAILS
(ii) 30% Kasai partially successful
(iii) 30% successful
3. chances of success
(i) experience of surgeon
(ii) age of child, the older the child, the lower the chance of success
ANYWAY ADDITIONAL STUFF
treatment of portal hypertension:
TIPS: transjugular intrahepatic portosystemic shunt
- it should be discussed with the parents with regards to TIPS for it may serve to contradict a liver transplant in the future
Note to self:
1. breastfeeding jaundice and breastmilk jaundice are obviously different. Breast feeding jaundice is occurs early after birth (usually within the 1st week) and is due to insufficient feeding or breast milk production. Breastmilk jaundice, however, is due to ingredients within the breast milk that hinders conjugation and excretion of breast milk and thus resulting in unconjugated jaundice (indirect jaundice) appears later (after 1st week):
A. progesterone metabolite inhibits UDPGA(uridine diphosphoglucuronic acid) glucuronyl transferase
B. increased concentration of non-esterified fatty acids inhibit hepatic glucuronyl transferase
C. increased beta glucuronidase activity in breast milk, delayed establishment of enteric flora in breastfed infants ==> increased hepatoenteric cycling
posted by scientia at
6:35 AM
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