Jaundice pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (Template)
m (Bot: Removing from Primary care)
 
(12 intermediate revisions by 2 users not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{Jaundice}}
{{Jaundice}}
{{CMG}}; {{AE}}
{{CMG}}; {{AE}}{{EG}}, {{AEL}}


==Overview==
==Overview==
[[Bilirubin]] is the [[catabolic]] product of the [[heme]] which is the main component of the [[red blood cells]]. Bilirubin is formed in [[Liver|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 [[Bile|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 of the newborn|hemolytic disease]], [[ABO incompatibility (patient information)|ABO incompatibility disease]], and hemolytic disease due to [[Glucose-6-phosphate dehydrogenase deficiency|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|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]].<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>
**[[Heme oxygenase|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|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:<ref name="pmid12359823">{{cite journal| author=Paludetto R, Mansi G, Raimondi F, Romano A, Crivaro V, Bussi M et al.| title=Moderate hyperbilirubinemia induces a transient alteration of neonatal behavior. | journal=Pediatrics | year= 2002 | volume= 110 | issue= 4 | pages= e50 | pmid=12359823 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12359823  }}</ref>
**'''[[Hepatic]] uptake'''<ref name="pmid6866015">{{cite journal| author=Weiss JS, Gautam A, Lauff JJ, Sundberg MW, Jatlow P, Boyer JL et al.| title=The clinical importance of a protein-bound fraction of serum bilirubin in patients with hyperbilirubinemia. | journal=N Engl J Med | year= 1983 | volume= 309 | issue= 3 | pages= 147-50 | pmid=6866015 | doi=10.1056/NEJM198307213090305 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6866015  }}</ref>
***After the formation of the bilirubin and its secretion into the [[bloodstream]], bilirubin becomes bound to the [[albumin]] to facilitate its transportation to [[Liver|the liver]].
***[[Hepatocytes|The hepatocytes]] then reuptake the [[bilirubin]] and prepare it for excretion.
**'''[[Conjugation]]'''<ref name="pmid6796486">{{cite journal| author=Chowdhury JR, Chowdhury NR, Wu G, Shouval R, Arias IM| title=Bilirubin mono- and diglucuronide formation by human liver in vitro: assay by high-pressure liquid chromatography. | journal=Hepatology | year= 1981 | volume= 1 | issue= 6 | pages= 622-7 | pmid=6796486 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6796486  }}</ref><ref name="pmid8027054">{{cite journal| author=Bosma PJ, Seppen J, Goldhoorn B, Bakker C, Oude Elferink RP, Chowdhury JR et al.| title=Bilirubin UDP-glucuronosyltransferase 1 is the only relevant bilirubin glucuronidating isoform in man. | journal=J Biol Chem | year= 1994 | volume= 269 | issue= 27 | pages= 17960-4 | pmid=8027054 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8027054  }}</ref>
***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]].
***[[Conjugation|The conjugation]] process occurs by the [[Glucuronosyltransferase|glucuronosyltransferase enzyme]] in the [[liver cells]].
**'''[[Clearance (medicine)|Clearance]] and [[excretion]]'''<ref name="pmid15664250">{{cite journal| author=Vítek L, Zelenka J, Zadinová M, Malina J| title=The impact of intestinal microflora on serum bilirubin levels. | journal=J Hepatol | year= 2005 | volume= 42 | issue= 2 | pages= 238-43 | pmid=15664250 | doi=10.1016/j.jhep.2004.10.012 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15664250  }}</ref>
***After [[conjugation]] of the [[bilirubin]] in [[Liver|the liver]], it is secreted into the [[bile]] then into the [[gastrointestinal tract]].
***In the GIT, [[Conjugated bilirubin|the conjugated bilirubin]] is metabolized by [[Gut|the gut]] [[enzymes]] into [[urobilinogen]] which is [[oxidized]] into [[urobilin]].
***[[Metabolism]] of the conjugated bilirubin occurs properly in the adults. However, [[Newborns|the newborns]] have [[Gastrointestinal tract|sterile gastrointestinal canal]] which impedes the catalyzation of the conjugated bilirubin.
***The sterile tract ends up with a small amount of [[Bile|excreted bile]].
***The remaining conjugated bilirubin is unconjugated by the [[Beta-glucuronidase|beta-glucuronidase enzyme]] in the [[neonatal]] [[intestine]].
***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]].
==== 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===
* Jaundice in adult patients classified into two major types:
** [[Unconjugated bilirubin|Unconjugated]] [[hyperbilirubinemia]]
** [[Conjugated bilirubin|Conjugated]] [[hyperbilirubinemia]]
=== Unconjugated hyperbilirubinemia ===
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]]
* Reduced [[bilirubin]] uptake
* Impaired [[bilirubin]] [[conjugation]]
** The combination of progestational and estrogenic steroids may result in increased [[UDP glucuronosyltransferase 1 family, polypeptide A1|UDP-glucuronyl transferase]] activity
=== 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.
* [[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]]<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]]
** Adult ''[[Ascaris lumbricoides]]''
** Eggs of certain [[liver flukes]] (e.g., ''[[Clonorchis sinensis]]'', ''[[Fasciola hepatica]]'')
* [[AIDS]] cholangiopathy<ref name="pmid15010025">{{cite journal |vauthors=Yusuf TE, Baron TH |title=AIDS Cholangiopathy |journal=Curr Treat Options Gastroenterol |volume=7 |issue=2 |pages=111–117 |date=April 2004 |pmid=15010025 |doi= |url=}}</ref>
** ''[[Cryptosporidium]]'' species
** [[Cytomegalovirus]]
** [[HIV]]
*** [[Viral hepatitis]] ([[Hepatitis|hepatitis viruses]], [[herpes simplex virus]], [[Epstein-Barr virus]])
*** [[Mycobacterium tuberculosis|''Mycobacterium'' tuberculosis]] and [[atypical mycobacteria]] (especially [[Mycobacterium avium intracellulare|''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 [[Viral hepatitis X (non-A,-B,-C,-D,-E)|click here]]
* [[Alcoholic hepatitis]]: For more information about viral hepatitis [[Alcoholic hepatitis pathophysiology|click here]]
* [[Nonalcoholic steatohepatitis]]: For more information about viral hepatitis [[Non-alcoholic fatty liver disease|click here]]
* [[Primary biliary cholangitis]]: For more information about viral hepatitis [[Primary biliary cirrhosis pathophysiology|click here]]
* [[Toxicity]]<ref name="pmid171822">{{cite journal |vauthors=Schaffner F |title=Hepatic drug metabolism and adverse hepatic drug reactions |journal=Vet. Pathol. |volume=12 |issue=2 |pages=145–56 |date= 1975 |pmid=171822 |doi=10.1177/030098587501200206 |url=}}</ref>
** Dose-related fashion (e.g., alkylated steroids such as [[methyltestosterone]] and [[ethinyl estradiol]])
** [[Idiosyncratic reaction|Idiosyncratic]] or [[allergic reaction]] (e.g., [[chlorpromazine]], [[halothane]]).
** [[Pyrrolizidine alkaloid|Pyrrolizidine alkaloids]] which may cause [[veno-occlusive disease]] of the [[liver]] (e.g., Jamaican bush tea)
* [[Sepsis]] and low perfusion states<ref name="pmid12919846">{{cite journal |vauthors=Famularo G, De Simone C, Nicotra GC |title=Jaundice and the sepsis syndrome: a neglected link |journal=Eur. J. Intern. Med. |volume=14 |issue=4 |pages=269–271 |date=July 2003 |pmid=12919846 |doi= |url=}}</ref>
** [[Hypotension]]
** [[Drugs]]
** [[Bacterial endotoxins]]
* [[Paraneoplastic syndromes]]
** [[Renal cell carcinoma]]
** [[Lymphoproliferative disease|Malignant lymphoproliferative diseases]]
** [[Gynecologic cancer|Gynecologic malignancies]]
** [[Prostate cancer]]
* [[Infiltrative and Metabolic Diseases Affecting the Liver|Infiltrative diseases of the liver]]
** [[Amyloidosis]]
** [[Lymphoma]]
** [[Sarcoidosis]]
** [[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>
** At least two to three weeks of [[Total parenteral nutrition|TPN]] may lead to development of [[cholestasis]].
*** Intestinal [[endotoxins]] transfer into the [[portal system]]
*** Bacterial [[sepsis]]
*** Formation of secondary [[Bile acid|bile acids]] (e.g., lithocholic acid)
*** Biliary sludge after six weeks of [[Total parenteral nutrition|TPN]]
*** Hepatotoxic factors, such as [[tryptophan]] degradation metabolites and [[Aluminium|aluminum]] contaminants
*** [[Small bowel bacterial overgrowth syndrome|Bacterial overgrowth in the small intestine]]
* [[Sickle cell disease]]<ref name="pmid3186339">{{cite journal |vauthors=Mallouh AA, Asha MI |title=Acute cholestatic jaundice in children with sickle cell disease: hepatic crises or hepatitis? |journal=Pediatr. Infect. Dis. J. |volume=7 |issue=10 |pages=689–92 |date=October 1988 |pmid=3186339 |doi= |url=}}</ref>
** [[Hemolysis]]
** Mild [[hepatic dysfunction]]
** Both [[Unconjugated bilirubin|unconjugated]] and [[conjugated bilirubin]] accumulate in the [[plasma]]
* [[Intrahepatic cholestasis of pregnancy]]<ref name="pmid19418576">{{cite journal| author=Geenes V, Williamson C| title=Intrahepatic cholestasis of pregnancy. | journal=World J Gastroenterol | year= 2009 | volume= 15 | issue= 17 | pages= 2049-66 | pmid=19418576 | doi= | pmc=2678574 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19418576  }}</ref>
** 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]]


==Pathophysiology==
==== [[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]].
* 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)]].
<br>
<small>
 
{{family tree/start}}
{{family tree| | A01 | | A02 | | A03 | | A04 | | A05 | | A06 | | A07 | | A08 | | A09 | | A10 | | | | | | | | | |A01=[[Sepsis]]|A02=[[Paraneoplastic syndrome]]|A03=[[Infiltrative and Metabolic Diseases Affecting the Liver|Infiltrative hepatic diseases]]|A04=[[Total parenteral nutrition]]|A05=[[Sickle cell disease]]|A06=[[Pregnancy]]|A07=[[hemolysis|Extravascular hemolysis]]|A08=[[hemolysis|Intravascular hemolysis]]|A09=[[Extravasation]]|A10=[[Dyserythropoiesis]]}}
{{family tree| | |`|-|-|-|^|-|-|-|^|-|-|v|^|-|-|-|^|-|-|-|'| | | |`|-|-|-|+|-|-|-|^|-|-|-|'| | | | | | | | | | |}}
{{family tree| | | | | | | | | | | | | |!| | | | | | | | | | | | | | | | |!| | | | | | | | | | | | | | | | |}}
{{family tree|boxstyle=text-align: left; | | B01 | | B02 | | B03 | |!| | B04 | | B05 | | B06 | | B07 |!| B08 | | B09 | | B10 | | B11 | |B01=• [[Cholelithiasis]]<br>• [[Tumor]]<br>• [[Primary biliary cholangitis]]<br>• [[Parasites]]<br>• [[Pancreatitis]]<br>• [[Stricture]]|B02=• [[Choledochal cyst]]<br>• [[Cholelithiasis]]<br>• [[Tumor]]|B03=• [[Biliary atresia]]<br>• [[Choledochal cyst]]|B04=• Decreased [[hepatic]] [[blood flow]]<br>• Decreased delivery of [[bilirubin]]|B05=• Capillarization of the sinusoidal [[endothelial cells]] (loss of [[fenestrae]])|B06=• Impaired [[bilirubin]] uptake at the [[sinusoidal]] surface of [[hepatocytes]]|B07=• [[Rifamycin]] [[antibiotics]]<br>• [[Probenecid]]<br>• Flavaspidic acid<br>• Bunamiodyl (a cholecystographic agent)|B08=• [[Crigler-Najjar syndrome|Type I and II Crigler Najjar syndrome]]|B09=• [[Hyperthyroidism]]<br>• [[Ethinyl estradiol]]|B10=• [[Novobiocin]]<br>• [[Gentamicin]]|B11=• [[Chronic hepatitis|Chronic persistent hepatitis]]<br>• Advanced [[cirrhosis]]<br>• [[Wilson's disease]]}}
{{family tree| | |!| | | |!| | | |!| | |!| | |!| | | |!| | | |!| | | |!| |!| |!| | | |`|-|-|-|+|-|-|-|'| | |}}
{{family tree| | B01 | | B02 | | B03 | |!| | B04 | | B05 | | B06 | | B07 |!| B08 | | | | | | B09 | | | | | |B01=Adult|B02=Children|B03=Neonates and infants|B04=[[Heart failure]]<br>[[Portocaval anastomoses|Portosystemic shunt]]|B05=[[Cirrhosis]]|B06=[[Gilbert's Syndrome]]|B07=[[Drug-induced]] defect|B08=↓ or No[[UDP-glucuronosyltransferase|UGT]] activity|B09=Inhibit [[UDP-glucuronosyltransferase|UGT]]}}
{{family tree| | |`|-|-|-|+|-|-|-|'| | |!| | |`|-|-|-|^|-|v|-|^|-|-|-|'| |!| |`|-|-|-|-|-|v|-|'| | | | | | |}}
{{family tree| | | | | | |!| | | | | | |!| | | | | | | | |!| | | | | | | |!| | | | | | | |!| | | | | | | | |}}
{{family tree| | C01 | | C02 | | | | | C03 | | | | | | | C04 | | | | | | C05 | | | | | | C06 | | | | | | | |C01=[[Hepatocellular Disease]]|C02=[[Biliary obstruction]]|C03=[[Intrahepatic cholestasis]]|C04=Reduced [[bilirubin]] uptake|C05=Overproduction of [[bilirubin]]|C06=Impaired [[conjugation|bilirubin conjugation]]}}
{{family tree| | |`|-|-|-|^|-|v|-|-|-|-|'| | | | | | | | |`|-|-|-|-|-|-|-|+|-|-|-|-|-|-|-|'| | | | | | | | |}}
{{family tree| | | | | | | | D01 | | | | | | | | | | | | | | | | | | | | D02 | | | | | | | | | | | | | | | |D01='''''Conjugated hyperbilirubinemia'''''|D02='''''Unconjugated hyperbilirubinemia'''''}}
{{family tree| | | | | | | | |`|-|-|-|-|-|-|-|-|-|-|v|-|-|-|-|-|-|-|-|-|-|'| | | | | | | | | | | | | | | | |}}
{{family tree| | | | | | | | | | | | | | | | | | | E01 | | | | | | | | | | | | | | | | | | | | | | | | | | |E01='''Jaundice'''}}
{{family tree/end}}
</small>


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
{{WH}}
{{WS}}


[[Category:Needs content]]
[[Category:Needs content]]
[[Category:Primary care]]
[[Category:Disease]]
[[Category:Disease]]
[[Category:Gastroenterology]]
[[Category:Gastroenterology]]
[[Category:Hepatology]]
[[Category:Hepatology]]
{{WH}}
{{WS}}

Latest revision as of 22:27, 29 July 2020

Jaundice Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Jaundice from other Conditions

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Chest X Ray

Electrocardiogram

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Jaundice pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Jaundice pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Jaundice pathophysiology

CDC on Jaundice pathophysiology

Jaundice pathophysiology in the news

Blogs on Jaundice pathophysiology

Directions to Hospitals Treating Jaundice

Risk calculators and risk factors for Jaundice pathophysiology

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

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

Unconjugated hyperbilirubinemia

The primary pathophysiology of unconjugated hyperbilirubinemia include:[10]

Conjugated hyperbilirubinemia

Biliary tract obstruction[11]

Liver infrastructure damage

Hepatocellular injury[19]


 
Sepsis
 
Paraneoplastic syndrome
 
Infiltrative hepatic diseases
 
Total parenteral nutrition
 
Sickle cell disease
 
Pregnancy
 
Extravascular hemolysis
 
Intravascular hemolysis
 
Extravasation
 
Dyserythropoiesis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• Cholelithiasis
• Tumor
• Primary biliary cholangitis
• Parasites
• Pancreatitis
• Stricture
 
• Choledochal cyst
• Cholelithiasis
• Tumor
 
• Biliary atresia
• Choledochal cyst
 
 
 
 
• Decreased hepatic blood flow
• Decreased delivery of bilirubin
 
• Capillarization of the sinusoidal endothelial cells (loss of fenestrae)
 
• Impaired bilirubin uptake at the sinusoidal surface of hepatocytes
 
• Rifamycin antibiotics
• Probenecid
• Flavaspidic acid
• Bunamiodyl (a cholecystographic agent)
 
 
• Type I and II Crigler Najjar syndrome
 
• Hyperthyroidism
• Ethinyl estradiol
 
• Novobiocin
• Gentamicin
 
• Chronic persistent hepatitis
• Advanced cirrhosis
• Wilson's disease
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adult
 
Children
 
Neonates and infants
 
 
 
 
Heart failure
Portosystemic shunt
 
Cirrhosis
 
Gilbert's Syndrome
 
Drug-induced defect
 
 
↓ or NoUGT activity
 
 
 
 
 
Inhibit UGT
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatocellular Disease
 
Biliary obstruction
 
 
 
 
Intrahepatic cholestasis
 
 
 
 
 
 
Reduced bilirubin uptake
 
 
 
 
 
Overproduction of bilirubin
 
 
 
 
 
Impaired bilirubin conjugation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Conjugated hyperbilirubinemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unconjugated hyperbilirubinemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Jaundice
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ Yusuf TE, Baron TH (April 2004). "AIDS Cholangiopathy". Curr Treat Options Gastroenterol. 7 (2): 111–117. PMID 15010025.
  14. ↑ Schaffner F (1975). "Hepatic drug metabolism and adverse hepatic drug reactions". Vet. Pathol. 12 (2): 145–56. doi:10.1177/030098587501200206. PMID 171822.
  15. ↑ 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.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ Geenes V, Williamson C (2009). "Intrahepatic cholestasis of pregnancy". World J Gastroenterol. 15 (17): 2049–66. PMC 2678574. PMID 19418576.
  19. ↑ 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.

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Jaundice_pathophysiology&oldid=1640012"