Jaundice pathophysiology: Difference between revisions
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==Pathophysiology== | ==Pathophysiology== | ||
= | ==== Bilirubin formation and metabolism ==== | ||
=== Bilirubin formation and metabolism=== | |||
*[[Bilirubin]] is the final [[catabolic]] product of the [[heme]]. The heme is a component of various biological molecules and [[enzymes]] but, it is mainly incorporated in the [[hemoglobin]] which is the primary component of the [[red blood cells]].<ref name="pmid5824077">{{cite journal| author=Berk PD, Howe RB, Bloomer JR, Berlin NI| title=Studies of bilirubin kinetics in normal adults. | journal=J Clin Invest | year= 1969 | volume= 48 | issue= 11 | pages= 2176-90 | pmid=5824077 | doi=10.1172/JCI106184 | pmc=297471 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5824077 }}</ref><ref name="pmid15422003">{{cite journal| author=LONDON IM, WEST R, SHEMIN D, RITTENBERG D| title=On the origin of bile pigment in normal man. | journal=J Biol Chem | year= 1950 | volume= 184 | issue= 1 | pages= 351-8 | pmid=15422003 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15422003 }}</ref> | *[[Bilirubin]] is the final [[catabolic]] product of the [[heme]]. The heme is a component of various biological molecules and [[enzymes]] but, it is mainly incorporated in the [[hemoglobin]] which is the primary component of the [[red blood cells]].<ref name="pmid5824077">{{cite journal| author=Berk PD, Howe RB, Bloomer JR, Berlin NI| title=Studies of bilirubin kinetics in normal adults. | journal=J Clin Invest | year= 1969 | volume= 48 | issue= 11 | pages= 2176-90 | pmid=5824077 | doi=10.1172/JCI106184 | pmc=297471 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5824077 }}</ref><ref name="pmid15422003">{{cite journal| author=LONDON IM, WEST R, SHEMIN D, RITTENBERG D| title=On the origin of bile pigment in normal man. | journal=J Biol Chem | year= 1950 | volume= 184 | issue= 1 | pages= 351-8 | pmid=15422003 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15422003 }}</ref> | ||
*[[Bilirubin]] is formed mainly in [[Liver|the liver]] and [[spleen]] through two steps which include:<ref name="pmid3700551">{{cite journal| author=Knobloch E, Hodr R, Herzmann J, Houdková V| title=Kinetics of the formation of biliverdin during the photochemical oxidation of bilirubin monitored by column liquid chromatography. | journal=J Chromatogr | year= 1986 | volume= 375 | issue= 2 | pages= 245-53 | pmid=3700551 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3700551 }}</ref><ref name="pmid5038868">{{cite journal| author=Bissell DM, Hammaker L, Schmid R| title=Liver sinusoidal cells. Identification of a subpopulation for erythrocyte catabolism. | journal=J Cell Biol | year= 1972 | volume= 54 | issue= 1 | pages= 107-19 | pmid=5038868 | doi= | pmc=2108858 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5038868 }}</ref> | *[[Bilirubin]] is formed mainly in [[Liver|the liver]] and [[spleen]] through two steps which include:<ref name="pmid3700551">{{cite journal| author=Knobloch E, Hodr R, Herzmann J, Houdková V| title=Kinetics of the formation of biliverdin during the photochemical oxidation of bilirubin monitored by column liquid chromatography. | journal=J Chromatogr | year= 1986 | volume= 375 | issue= 2 | pages= 245-53 | pmid=3700551 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3700551 }}</ref><ref name="pmid5038868">{{cite journal| author=Bissell DM, Hammaker L, Schmid R| title=Liver sinusoidal cells. Identification of a subpopulation for erythrocyte catabolism. | journal=J Cell Biol | year= 1972 | volume= 54 | issue= 1 | pages= 107-19 | pmid=5038868 | doi= | pmc=2108858 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5038868 }}</ref> | ||
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***The [[unconjugated bilirubin]] is reabsorbed back into [[Blood|the blood]] and to the liver through the [[enterohepatic circulation]] of [[bilirubin]]. | ***The [[unconjugated bilirubin]] is reabsorbed back into [[Blood|the blood]] and to the liver through the [[enterohepatic circulation]] of [[bilirubin]]. | ||
***A small amount of [[bilirubin]] is cleared into the [[urine]] as [[urobilinogen]]. | ***A small amount of [[bilirubin]] is cleared into the [[urine]] as [[urobilinogen]]. | ||
==== For more information about viral hepatitis pathophysiology [[Viral hepatitis|click here]] ==== | |||
==== For more information about cirrhosis pathophysiology [[Cirrhosis pathophysiology|click here]] ==== | |||
==== For more information about neonatal jaundice pathophysiology [[Neonatal jaundice pathophysiology|click here]] ==== | |||
===Pathogenesis of Adult jaundice=== | ===Pathogenesis of Adult jaundice=== | ||
* Jaundice in adult patients classified into two major types: | * Jaundice in adult patients classified into two major types: | ||
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** [[Conjugated bilirubin|Conjugated]] [[hyperbilirubinemia]] | ** [[Conjugated bilirubin|Conjugated]] [[hyperbilirubinemia]] | ||
=== Unconjugated hyperbilirubinemia === | === Unconjugated hyperbilirubinemia === | ||
The | The primary [[pathophysiology]] of unconjugated hyperbilirubinemia include:<ref name="pmid16512459">{{cite journal |vauthors=Duseja A, Das A, Das R, Dhiman RK, Chawla Y, Bhansali A |title=Unconjugated hyperbilirubinemia in nonalcoholic steatohepatitis--is it Gilbert's syndrome? |journal=Trop Gastroenterol |volume=26 |issue=3 |pages=123–5 |date= 2005 |pmid=16512459 |doi= |url=}}</ref> | ||
* Overproduction of [[bilirubin]] | * Overproduction of [[bilirubin]] | ||
* Reduced [[bilirubin]] uptake | * Reduced [[bilirubin]] uptake | ||
* Impaired [[bilirubin]] [[conjugation]] | * Impaired [[bilirubin]] [[conjugation]] | ||
** The combination of progestational and estrogenic steroids | ** The combination of progestational and estrogenic steroids may result in increased [[UDP glucuronosyltransferase 1 family, polypeptide A1|UDP-glucuronyl transferase]] activity | ||
=== Conjugated hyperbilirubinemia === | === Conjugated hyperbilirubinemia === | ||
==== | ==== Biliary tract obstruction<ref name="pmid18345288">{{cite journal| author=Abdallah AA, Krige JE, Bornman PC| title=Biliary tract obstruction in chronic pancreatitis. | journal=HPB (Oxford) | year= 2007 | volume= 9 | issue= 6 | pages= 421-8 | pmid=18345288 | doi=10.1080/13651820701774883 | pmc=2215354 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18345288 }}</ref> ==== | ||
* [[Biliary obstruction|Biliary tract obstruction]] leads to both conjugated and unconjugated bilirubinemia | * [[Biliary obstruction|Biliary tract obstruction]] leads to both conjugated and unconjugated bilirubinemia. | ||
* [[Bilirubin]] is transported back to the plasma by ATP-consuming pumps | * [[Bilirubin]] is transported back to the plasma by ATP-consuming pumps. | ||
* The markers are serum concentrations of [[bilirubin]] and [[alkaline phosphatase]] | * The markers are serum concentrations of [[bilirubin]] and [[alkaline phosphatase]]. | ||
* Biliary retention secondary to obstruction may reverse the glucuronidation | * Biliary retention secondary to obstruction may reverse the glucuronidation. | ||
* Produced unconjugated [[bilirubin]] will diffuse or be transported back into the [[plasma]] | * Produced unconjugated [[bilirubin]] will diffuse or be transported back into the [[plasma]]. | ||
* [[Mirizzi syndrome]]<ref name="pmid23002333">{{cite journal| author=Beltrán MA| title=Mirizzi syndrome: history, current knowledge and proposal of a simplified classification. | journal=World J Gastroenterol | year= 2012 | volume= 18 | issue= 34 | pages= 4639-50 | pmid=23002333 | doi=10.3748/wjg.v18.i34.4639 | pmc=3442202 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23002333 }}</ref> | |||
** [[Extrahepatic bile ducts]] compression by a distended [[gallbladder]] due to [[cholelithiasis]]. | |||
* | * [[Primary sclerosing cholangitis]] and cholangiocarcinoma | ||
** [[Intrahepatic bile ducts|Intrahepatic]] and [[Extrahepatic bile ducts|extrahepatic]] portions of the bile ducts are affected. | |||
* [[Parasites]] | * [[Parasites]] | ||
** Adult ''[[Ascaris lumbricoides]]'' | ** Adult ''[[Ascaris lumbricoides]]'' | ||
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*** Drug-induced liver disease | *** Drug-induced liver disease | ||
==== | ==== Liver infrastructure damage ==== | ||
* [[Viral hepatitis]]: For more information about viral hepatitis [[Viral hepatitis X (non-A,-B,-C,-D,-E)|click here]] | * [[Viral hepatitis]]: For more information about viral hepatitis [[Viral hepatitis X (non-A,-B,-C,-D,-E)|click here]] | ||
* [[Alcoholic hepatitis]]: For more information about viral hepatitis [[Alcoholic hepatitis pathophysiology|click here]] | * [[Alcoholic hepatitis]]: For more information about viral hepatitis [[Alcoholic hepatitis pathophysiology|click here]] | ||
| Line 95: | Line 94: | ||
** [[Tuberculosis]] | ** [[Tuberculosis]] | ||
* [[Total parenteral nutrition|Total parenteral nutrition (TPN)]]<ref name="pmid8468653">{{cite journal |vauthors=Moss RL, Das JB, Ansari G, Raffensperger JG |title=Hepatobiliary dysfunction during total parenteral nutrition is caused by infusate, not the route of administration |journal=J. Pediatr. Surg. |volume=28 |issue=3 |pages=391–6; discussion 396–7 |date=March 1993 |pmid=8468653 |doi= |url=}}</ref> | * [[Total parenteral nutrition|Total parenteral nutrition (TPN)]]<ref name="pmid8468653">{{cite journal |vauthors=Moss RL, Das JB, Ansari G, Raffensperger JG |title=Hepatobiliary dysfunction during total parenteral nutrition is caused by infusate, not the route of administration |journal=J. Pediatr. Surg. |volume=28 |issue=3 |pages=391–6; discussion 396–7 |date=March 1993 |pmid=8468653 |doi= |url=}}</ref> | ||
** At least two to three weeks of [[Total parenteral nutrition|TPN]] may lead to development of [[cholestasis]] | ** At least two to three weeks of [[Total parenteral nutrition|TPN]] may lead to development of [[cholestasis]]. | ||
*** Intestinal [[endotoxins]] transfer into the [[portal system]] | *** Intestinal [[endotoxins]] transfer into the [[portal system]] | ||
*** Bacterial [[sepsis]] | *** Bacterial [[sepsis]] | ||
| Line 113: | Line 112: | ||
==== [[Hepatocellular Disease|Hepatocellular injury]]<ref name="pmid21532726">{{cite journal| author=Gowda S, Desai PB, Hull VV, Math AA, Vernekar SN, Kulkarni SS| title=A review on laboratory liver function tests. | journal=Pan Afr Med J | year= 2009 | volume= 3 | issue= | pages= 17 | pmid=21532726 | doi= | pmc=2984286 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21532726 }}</ref> ==== | ==== [[Hepatocellular Disease|Hepatocellular injury]]<ref name="pmid21532726">{{cite journal| author=Gowda S, Desai PB, Hull VV, Math AA, Vernekar SN, Kulkarni SS| title=A review on laboratory liver function tests. | journal=Pan Afr Med J | year= 2009 | volume= 3 | issue= | pages= 17 | pmid=21532726 | doi= | pmc=2984286 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21532726 }}</ref> ==== | ||
* Different presentations simulate [[Cholestatic liver diseases|cholestatic syndromes]] | * Different presentations simulate [[Cholestatic liver diseases|cholestatic syndromes]]. | ||
* Intracellular [[proteins]] and small molecules are released into the [[plasma]] | * Intracellular [[proteins]] and small molecules are released into the [[plasma]]. | ||
* Increased [[transaminases]], such as [[Aspartate aminotransferase|aspartate aminotransferase (AST)]] and [[Alanine aminotransferase|alanine aminotransferase (ALT)]] | * Increased [[transaminases]], such as [[Aspartate aminotransferase|aspartate aminotransferase (AST)]] and [[Alanine aminotransferase|alanine aminotransferase (ALT)]]. | ||
<br> | <br> | ||
<small> | <small> | ||
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==References== | ==References== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
{{WH}} | |||
{{WS}} | |||
[[Category:Needs content]] | [[Category:Needs content]] | ||
[[Category:Disease]] | [[Category:Disease]] | ||
[[Category:Gastroenterology]] | [[Category:Gastroenterology]] | ||
[[Category:Hepatology]] | [[Category:Hepatology]] | ||
Latest revision as of 22:27, 29 July 2020
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2], Ahmed Elsaiey, MBBCH [3]
Overview
Bilirubin is the catabolic product of the heme which is the main component of the red blood cells. Bilirubin is formed in the liver and spleen then it passes through several process in order to be metabolized. Metabolism processes include hepatic uptake, conjugation, clearance and excretion of the bilirubin in the bile. Jaundice develops due to increase the level of bilirubin and deposition under the skin and cause the yellow discoloration of the skin. Pathogenesis of neonatal jaundice includes physiologic process of bilirubin accumulation or pathological mechanism. The pathological jaundice may be acquired or inherited. Acquired neonatal jaundice include Rh hemolytic disease, ABO incompatibility disease, and hemolytic disease due to G6PD enzyme deficiency. Inherited neonatal jaundice is due to defect of one of the processes of bilirubin metabolism and it concludes some inherited syndromes. Inherited neonatal jaundice include Gilbert's syndrome, Crigler-Najjar syndrome type I and II, Lucey-Driscoll syndrome, Dubin-Johnson syndrome, and Rotor syndrome.
Pathophysiology
Bilirubin formation and metabolism
- Bilirubin is the final catabolic product of the heme. The heme is a component of various biological molecules and enzymes but, it is mainly incorporated in the hemoglobin which is the primary component of the red blood cells.[1][2]
- Bilirubin is formed mainly in the liver and spleen through two steps which include:[3][4]
- Heme oxygenase enzyme degrades the porphyrin ring of the heme and breaks it down. A green compound called biliverdin is then formed as a result of the previous reaction. Carbon monoxide is released as a result of the reaction.
- Biliverdin reductase enzyme catalyzes the formation of bilirubin from biliverdin.
- Bilirubin is a toxic metabolite so, the body has physiologic processes to eliminate the bilirubin. Bilirubin elimination process includes:[5]
- Hepatic uptake[6]
- After the formation of the bilirubin and its secretion into the bloodstream, bilirubin becomes bound to the albumin to facilitate its transportation to the liver.
- The hepatocytes then reuptake the bilirubin and prepare it for excretion.
- Conjugation[7][8]
- Bilirubin is then conjugated with glucuronic acid producing bilirubin diglucuronide which is water soluble.
- Being water soluble, hence, the conjugated bilirubin can be excreted into bile.
- The conjugation process occurs by the glucuronosyltransferase enzyme in the liver cells.
- Clearance and excretion[9]
- After conjugation of the bilirubin in the liver, it is secreted into the bile then into the gastrointestinal tract.
- In the GIT, the conjugated bilirubin is metabolized by the gut enzymes into urobilinogen which is oxidized into urobilin.
- Metabolism of the conjugated bilirubin occurs properly in the adults. However, the newborns have sterile gastrointestinal canal which impedes the catalyzation of the conjugated bilirubin.
- The sterile tract ends up with a small amount of excreted bile.
- The remaining conjugated bilirubin is unconjugated by the beta-glucuronidase enzyme in the neonatal intestine.
- The unconjugated bilirubin is reabsorbed back into the blood and to the liver through the enterohepatic circulation of bilirubin.
- A small amount of bilirubin is cleared into the urine as urobilinogen.
- Hepatic uptake[6]
For more information about viral hepatitis pathophysiology click here
For more information about cirrhosis pathophysiology click here
For more information about neonatal jaundice pathophysiology click here
Pathogenesis of Adult jaundice
- Jaundice in adult patients classified into two major types:
Unconjugated hyperbilirubinemia
The primary pathophysiology of unconjugated hyperbilirubinemia include:[10]
- Overproduction of bilirubin
- Reduced bilirubin uptake
- Impaired bilirubin conjugation
- The combination of progestational and estrogenic steroids may result in increased UDP-glucuronyl transferase activity
Conjugated hyperbilirubinemia
Biliary tract obstruction[11]
- Biliary tract obstruction leads to both conjugated and unconjugated bilirubinemia.
- Bilirubin is transported back to the plasma by ATP-consuming pumps.
- The markers are serum concentrations of bilirubin and alkaline phosphatase.
- Biliary retention secondary to obstruction may reverse the glucuronidation.
- Produced unconjugated bilirubin will diffuse or be transported back into the plasma.
- Mirizzi syndrome[12]
- Extrahepatic bile ducts compression by a distended gallbladder due to cholelithiasis.
- Primary sclerosing cholangitis and cholangiocarcinoma
- Intrahepatic and extrahepatic portions of the bile ducts are affected.
- Parasites
- Adult Ascaris lumbricoides
- Eggs of certain liver flukes (e.g., Clonorchis sinensis, Fasciola hepatica)
- AIDS cholangiopathy[13]
- Cryptosporidium species
- Cytomegalovirus
- HIV
- Viral hepatitis (hepatitis viruses, herpes simplex virus, Epstein-Barr virus)
- Mycobacterium tuberculosis and atypical mycobacteria (especially Mycobacterium avium intracellulare)
- Fungal infections (Cryptococcus neoformans, Histoplasma capsulatum, Candida albicans, Coccidioides immitis)
- Parasites (Pneumocystis carinii)
- Tumor infiltration (lymphoma, Kaposi sarcoma)
- Drug-induced liver disease
Liver infrastructure damage
- Viral hepatitis: For more information about viral hepatitis click here
- Alcoholic hepatitis: For more information about viral hepatitis click here
- Nonalcoholic steatohepatitis: For more information about viral hepatitis click here
- Primary biliary cholangitis: For more information about viral hepatitis click here
- Toxicity[14]
- Dose-related fashion (e.g., alkylated steroids such as methyltestosterone and ethinyl estradiol)
- Idiosyncratic or allergic reaction (e.g., chlorpromazine, halothane).
- Pyrrolizidine alkaloids which may cause veno-occlusive disease of the liver (e.g., Jamaican bush tea)
- Sepsis and low perfusion states[15]
- Paraneoplastic syndromes
- Infiltrative diseases of the liver
- Total parenteral nutrition (TPN)[16]
- At least two to three weeks of TPN may lead to development of cholestasis.
- Intestinal endotoxins transfer into the portal system
- Bacterial sepsis
- Formation of secondary bile acids (e.g., lithocholic acid)
- Biliary sludge after six weeks of TPN
- Hepatotoxic factors, such as tryptophan degradation metabolites and aluminum contaminants
- Bacterial overgrowth in the small intestine
- At least two to three weeks of TPN may lead to development of cholestasis.
- Sickle cell disease[17]
- Hemolysis
- Mild hepatic dysfunction
- Both unconjugated and conjugated bilirubin accumulate in the plasma
- Intrahepatic cholestasis of pregnancy[18]
- Usually in the third trimester but sometimes earlier
- Heralds cholestasis and then frank jaundice
- May be associated with increased stillbirths and prematurity
- All the pathologic changes would disappear after delivery
Hepatocellular injury[19]
- Different presentations simulate cholestatic syndromes.
- Intracellular proteins and small molecules are released into the plasma.
- Increased transaminases, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT).
References
- ↑ Berk PD, Howe RB, Bloomer JR, Berlin NI (1969). "Studies of bilirubin kinetics in normal adults". J Clin Invest. 48 (11): 2176–90. doi:10.1172/JCI106184. PMC 297471. PMID 5824077.
- ↑ LONDON IM, WEST R, SHEMIN D, RITTENBERG D (1950). "On the origin of bile pigment in normal man". J Biol Chem. 184 (1): 351–8. PMID 15422003.
- ↑ Knobloch E, Hodr R, Herzmann J, Houdková V (1986). "Kinetics of the formation of biliverdin during the photochemical oxidation of bilirubin monitored by column liquid chromatography". J Chromatogr. 375 (2): 245–53. PMID 3700551.
- ↑ Bissell DM, Hammaker L, Schmid R (1972). "Liver sinusoidal cells. Identification of a subpopulation for erythrocyte catabolism". J Cell Biol. 54 (1): 107–19. PMC 2108858. PMID 5038868.
- ↑ Paludetto R, Mansi G, Raimondi F, Romano A, Crivaro V, Bussi M; et al. (2002). "Moderate hyperbilirubinemia induces a transient alteration of neonatal behavior". Pediatrics. 110 (4): e50. PMID 12359823.
- ↑ Weiss JS, Gautam A, Lauff JJ, Sundberg MW, Jatlow P, Boyer JL; et al. (1983). "The clinical importance of a protein-bound fraction of serum bilirubin in patients with hyperbilirubinemia". N Engl J Med. 309 (3): 147–50. doi:10.1056/NEJM198307213090305. PMID 6866015.
- ↑ Chowdhury JR, Chowdhury NR, Wu G, Shouval R, Arias IM (1981). "Bilirubin mono- and diglucuronide formation by human liver in vitro: assay by high-pressure liquid chromatography". Hepatology. 1 (6): 622–7. PMID 6796486.
- ↑ Bosma PJ, Seppen J, Goldhoorn B, Bakker C, Oude Elferink RP, Chowdhury JR; et al. (1994). "Bilirubin UDP-glucuronosyltransferase 1 is the only relevant bilirubin glucuronidating isoform in man". J Biol Chem. 269 (27): 17960–4. PMID 8027054.
- ↑ Vítek L, Zelenka J, Zadinová M, Malina J (2005). "The impact of intestinal microflora on serum bilirubin levels". J Hepatol. 42 (2): 238–43. doi:10.1016/j.jhep.2004.10.012. PMID 15664250.
- ↑ Duseja A, Das A, Das R, Dhiman RK, Chawla Y, Bhansali A (2005). "Unconjugated hyperbilirubinemia in nonalcoholic steatohepatitis--is it Gilbert's syndrome?". Trop Gastroenterol. 26 (3): 123–5. PMID 16512459.
- ↑ Abdallah AA, Krige JE, Bornman PC (2007). "Biliary tract obstruction in chronic pancreatitis". HPB (Oxford). 9 (6): 421–8. doi:10.1080/13651820701774883. PMC 2215354. PMID 18345288.
- ↑ Beltrán MA (2012). "Mirizzi syndrome: history, current knowledge and proposal of a simplified classification". World J Gastroenterol. 18 (34): 4639–50. doi:10.3748/wjg.v18.i34.4639. PMC 3442202. PMID 23002333.
- ↑ Yusuf TE, Baron TH (April 2004). "AIDS Cholangiopathy". Curr Treat Options Gastroenterol. 7 (2): 111–117. PMID 15010025.
- ↑ Schaffner F (1975). "Hepatic drug metabolism and adverse hepatic drug reactions". Vet. Pathol. 12 (2): 145–56. doi:10.1177/030098587501200206. PMID 171822.
- ↑ Famularo G, De Simone C, Nicotra GC (July 2003). "Jaundice and the sepsis syndrome: a neglected link". Eur. J. Intern. Med. 14 (4): 269–271. PMID 12919846.
- ↑ Moss RL, Das JB, Ansari G, Raffensperger JG (March 1993). "Hepatobiliary dysfunction during total parenteral nutrition is caused by infusate, not the route of administration". J. Pediatr. Surg. 28 (3): 391–6, discussion 396–7. PMID 8468653.
- ↑ Mallouh AA, Asha MI (October 1988). "Acute cholestatic jaundice in children with sickle cell disease: hepatic crises or hepatitis?". Pediatr. Infect. Dis. J. 7 (10): 689–92. PMID 3186339.
- ↑ Geenes V, Williamson C (2009). "Intrahepatic cholestasis of pregnancy". World J Gastroenterol. 15 (17): 2049–66. PMC 2678574. PMID 19418576.
- ↑ Gowda S, Desai PB, Hull VV, Math AA, Vernekar SN, Kulkarni SS (2009). "A review on laboratory liver function tests". Pan Afr Med J. 3: 17. PMC 2984286. PMID 21532726.