Cholestasis in Neonates and Young Infants

Overview

Definition

Cholestasis in neonates and young infants is conjugated hyperbilirubinemia Conjugated hyperbilirubinemia Hyperbilirubinemia of the Newborn in the 1st 3 months of life due to impaired bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy excretion.

Etiology

Biliary tract Biliary tract Bile is secreted by hepatocytes into thin channels called canaliculi. These canaliculi lead into slightly larger interlobular bile ductules, which are part of the portal triads at the “corners” of hepatic lobules. The bile leaves the liver via the right and left hepatic ducts, which join together to form the common hepatic duct. Gallbladder and Biliary Tract: Anatomy malformations involving the gallbladder Gallbladder The gallbladder is a pear-shaped sac, located directly beneath the liver, that sits on top of the superior part of the duodenum. The primary functions of the gallbladder include concentrating and storing up to 50 mL of bile. Gallbladder and Biliary Tract: Anatomy and bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct are grouped into cystic Cystic Fibrocystic Change and noncystic obliterative cholangiopathies, the most common of which is biliary atresia Atresia Hypoplastic Left Heart Syndrome (HLHS). Less common causes include the genetic Alagille syndrome Alagille Syndrome Hyperbilirubinemia of the Newborn, infectious causes, and metabolic disorders.

• Obstructive causes:
  • Biliary atresia Atresia Hypoplastic Left Heart Syndrome (HLHS)
  • Choledochal cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change
  • Other obstructive causes:
    • Stones
    • Tumors
    • Neonatal sclerosing cholangitis
• Infectious causes:
  • TORCH infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
    • Toxoplasmosis
    • Other ( syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis)
    • Rubella
    • Cytomegalovirus (CMV)
    • Herpes simplex virus Simplex Virus A genus of the family herpesviridae, subfamily alphaherpesvirinae, consisting of herpes simplex-like viruses. The type species is herpesvirus 1, human. Herpes Simplex Virus 1 and 2 ( HSV HSV Herpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals. Herpes Simplex Virus 1 and 2)
  • Viral infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
    • Echovirus Echovirus Echoviruses are single-stranded positive-sense RNA viruses belonging to the genus Enterovirus. Transmission is most commonly through the fecal-oral route. The majority of patients are asymptomatic. Patients who are symptomatic can exhibit a wide range of illnesses ranging from nonspecific URIs and exanthems to severe and life-threatening illnesses. Echovirus
    • Adenovirus Adenovirus Adenovirus (member of the family Adenoviridae) is a nonenveloped, double-stranded DNA virus. Adenovirus is transmitted in a variety of ways, and it can have various presentations based on the site of entry. Presentation can include febrile pharyngitis, conjunctivitis, acute respiratory disease, atypical pneumonia, and gastroenteritis. Adenovirus
    • Parvovirus B19 Parvovirus B19 Primate erythroparvovirus 1 (generally referred to as parvovirus B19, B19 virus, or sometimes erythrovirus B19) ranks among the smallest DNA viruses. Parvovirus B19 is of the family Parvoviridae and genus Erythrovirus. In immunocompetent humans, parvovirus B19 classically results in erythema infectiosum (5th disease) or “slapped cheek syndrome.” Parvovirus B19
  • Neonatal urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy infection
• Genetic causes:
  • Alagille syndrome Alagille Syndrome Hyperbilirubinemia of the Newborn (syndromic paucity of the interlobular bile ducts Interlobular bile ducts Gallbladder and Biliary Tract: Anatomy)
  • Alpha-1 antitrypsin Alpha-1 antitrypsin Plasma glycoprotein member of the serpin superfamily which inhibits trypsin; neutrophil elastase; and other proteolytic enzymes. Alpha-1 Antitrypsin (AAT) Deficiency deficiency
  • Progressive familial intrahepatic cholestasis
  • Cystic Cystic Fibrocystic Change fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans
• Metabolic disorders/inborn errors of metabolism:
  • Carbohydrate metabolism: galactosemia Galactosemia Galactosemia is a disorder caused by defects in galactose metabolism. Galactosemia is an inherited, autosomal-recessive condition, which results in inadequate galactose processing and high blood levels of monosaccharide. The rare disorder often presents in infants with symptoms of lethargy, nausea, vomiting, diarrhea, and jaundice. Galactosemia
  • Amino acids Amino acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Basics of Amino Acids: tyrosinemia Tyrosinemia A group of disorders which have in common elevations of tyrosine in the blood and urine secondary to an enzyme deficiency. Type I tyrosinemia features episodic weakness, self-mutilation, hepatic necrosis, renal tubular injury, and seizures and is caused by a deficiency of the enzyme fumarylacetoacetase. Type II tyrosinemia features intellectual disability, painful corneal ulcers, and keratosis of the palms and plantar surfaces and is caused by a deficiency of the enzyme tyrosine transaminase. Type III tyrosinemia features intellectual disability and is caused by a deficiency of the enzyme 4-hydroxyphenylpyruvate dioxygenase. Renal Tubular Acidosis
  • Lipids Lipids Lipids are a diverse group of hydrophobic organic molecules, which include fats, oils, sterols, and waxes. Fatty Acids and Lipids:
    • Niemann-Pick type C
    • Gaucher disease Gaucher disease Gaucher Disease (GD) is an autosomal recessive lysosomal storage disorder caused by a deficiency of glucocerebrosidase enzyme activity, resulting in accumulation of glucocerebroside in cells and certain organs. The disease is categorized into 3 types with variable clinical presentation. Gaucher Disease type 2 Type 2 Spinal Muscular Atrophy
  • Disorders of bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy acid metabolism
• Toxic
  • Intestinal failure–associated liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease ( parenteral nutrition Parenteral nutrition The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). Central Venous Catheter)
  • Drugs

Biliary Atresia

Biliary atresia Atresia Hypoplastic Left Heart Syndrome (HLHS) is an idiopathic Idiopathic Dermatomyositis, progressive, fibrotic obliteration of the extrahepatic biliary tree Biliary tree The bile ducts and the gallbladder. Gallbladder and Biliary Tract: Anatomy that presents with biliary obstruction within the 1st 3 months of life.

• Classification:
  • Neonatal form (80%–90% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship):
    • Isolated biliary atresia Atresia Hypoplastic Left Heart Syndrome (HLHS)
    • Neonate Neonate An infant during the first 28 days after birth. Physical Examination of the Newborn is normal at birth; progressive obliteration of extrahepatic bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy ducts develops within weeks.
  • Embryonic or fetal form:
    • Present at birth
    • Associated with other congenital Congenital Chorioretinitis anomalies (situs inversus, polysplenia, intestinal malrotation Malrotation Pediatric Gastrointestinal Abnormalities, heart disease)
  • Severity of obstruction:
    • Noncorrectable: obliteration of the entire extrahepatic biliary tree Biliary tree The bile ducts and the gallbladder. Gallbladder and Biliary Tract: Anatomy is seen in approximately 85% of cases
    • Surgically correctable form (less common): distal segmental bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct obliteration with patent extrahepatic ducts 
• Epidemiology:
  • 1 in 10,000–15,000 live births
  • More common in the East Asian population
  • Unlikely to occur within the same family
• Etiology: pathogenesis is unknown, but several mechanisms have been implicated:
  • Viral
  • Toxin-mediated inflammatory response
  • Genetic factors
  • Immune etiologies
• Pathophysiology:
  • Perinatal insult (possible viral infection) causes bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct injury.
  • Immunologic response → inflammatory infiltration and obstruction
  • Epithelial proliferation → progressive sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor → obliteration of extrahepatic biliary ducts and atresia Atresia Hypoplastic Left Heart Syndrome (HLHS) in the 1st few months of life
  • Cholestasis → hepatocellular injury with secondary cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
• Clinical presentation:
  • May not be present at birth and may appear over the 1st 2 weeks
  • May show normal appetite and growth during early weeks
  • Variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables degrees of:
    • Jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice, scleral icterus Scleral Icterus Jaundice
    • Dark urine (bilirubinuria)
    • Acholic (pale) stools 
    • Hepatomegaly 
    • Splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly may gradually develop owing to portal hypertension Portal hypertension Portal hypertension is increased pressure in the portal venous system. This increased pressure can lead to splanchnic vasodilation, collateral blood flow through portosystemic anastomoses, and increased hydrostatic pressure. There are a number of etiologies, including cirrhosis, right-sided congestive heart failure, schistosomiasis, portal vein thrombosis, hepatitis, and Budd-Chiari syndrome. Portal Hypertension.
  • Physiologic jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice ( indirect hyperbilirubinemia Indirect Hyperbilirubinemia Hyperbilirubinemia of the Newborn; resolves within 2 weeks) returns after 8 weeks ( direct hyperbilirubinemia Direct Hyperbilirubinemia Hyperbilirubinemia of the Newborn, pathologic)
  • Cardiac murmurs may suggest associated anomalies.
• Diagnosis:
  • Screening Screening Preoperative Care in high-risk populations: stool color cards
  • Labs:
    • Total and direct (conjugated) bilirubin Bilirubin A bile pigment that is a degradation product of heme. Heme Metabolism: both elevated
    • Obstructive pattern of liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes: significant elevation of alkaline phosphatase Alkaline Phosphatase An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. Osteosarcoma, mild elevation of ALT ALT An enzyme that catalyzes the conversion of l-alanine and 2-oxoglutarate to pyruvate and l-glutamate. Liver Function Tests and AST AST Enzymes of the transferase class that catalyze the conversion of l-aspartate and 2-ketoglutarate to oxaloacetate and l-glutamate. Liver Function Tests
  • Abdominal ultrasonography may identify:
    • Other causes of neonatal cholestasis
    • Associated anomalies such as polysplenia
    • Hypoplastic or absent gallbladder Gallbladder The gallbladder is a pear-shaped sac, located directly beneath the liver, that sits on top of the superior part of the duodenum. The primary functions of the gallbladder include concentrating and storing up to 50 mL of bile. Gallbladder and Biliary Tract: Anatomy
    • Triangular cord sign: represents the fibrous Fibrous Fibrocystic Change ductal remnant of the extrahepatic bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct in biliary atresia Atresia Hypoplastic Left Heart Syndrome (HLHS)
  • MRCP MRCP Non-invasive diagnostic technique for visualizing the pancreatic ducts and bile ducts without the use of injected contrast media or x-ray. Mri scans provide excellent sensitivity for duct dilatation, biliary stricture, and intraductal abnormalities. Primary Sclerosing Cholangitis may be indicated for preoperative evaluation. 
  • Percutaneous liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma:
    • Most valuable test
    • Shows proliferation and plugging of bile ductules Bile ductules Gallbladder and Biliary Tract: Anatomy with relatively intact lobular structure
• Management:
  • Exploratory laparotomy Exploratory Laparotomy Laparotomy and Laparoscopy + direct cholangiography (preferably before 8 weeks of life)
  • Surgically correctable lesions are corrected.
  • Noncorrectable lesions: treated in the short term with a portoenterostomy (Kasai procedure)
    • The liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy is anastomosed to a piece of intestine, allowing multiple small bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct remnants to empty into the intestine. 
    • This procedure delays the onset of cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis and allows for normal growth. 
    • Most individuals with noncorrectable lesions eventually develop portal hypertension Portal hypertension Portal hypertension is increased pressure in the portal venous system. This increased pressure can lead to splanchnic vasodilation, collateral blood flow through portosystemic anastomoses, and increased hydrostatic pressure. There are a number of etiologies, including cirrhosis, right-sided congestive heart failure, schistosomiasis, portal vein thrombosis, hepatitis, and Budd-Chiari syndrome. Portal Hypertension and recurrent hepatic dysfunction. 
    • Liver transplantation Liver transplantation The transference of a part of or an entire liver from one human or animal to another. Hepatocellular Carcinoma (HCC) and Liver Metastases done later is curative.

Alagille Syndrome

Alagille syndrome Alagille Syndrome Hyperbilirubinemia of the Newborn is a genetic disorder characterized by a paucity of bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy ducts in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, leading to cholestasis. This syndrome also affects other organs.

• Etiology:
  • Autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance mutations in the JAG1 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics in > 90% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • Others have mutations in the NOTCH2 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics.
• Clinical presentation:
  • Hepatic manifestations:
    • Paucity of interlobular bile ducts Interlobular bile ducts Gallbladder and Biliary Tract: Anatomy
    • Chronic cholestasis (in 90%)
    • Jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice
    • Cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
    • Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema) (80%)
    • Xanthomas Xanthomas Lipid Disorders
  • Cardiac murmur or anomalies in 85%–91%, most commonly pulmonic stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS)
  • Renal dysplasia Renal Dysplasia Congenital Renal Abnormalities
  • Butterfly vertebrae
  • Typical facial features:
    • “Triangular” facies with prominent forehead Forehead The part of the face above the eyes. Melasma, broad nasal bridge, and pointed chin Chin The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. Melasma 
    • Deep-set eyes
  • Other minor abnormalities in growth and intellectual disability Disability Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for social security and workman’s compensation benefits. ABCDE Assessment
• Diagnosis:
  • Lab findings:
    • Conjugated hyperbilirubinemia Conjugated hyperbilirubinemia Hyperbilirubinemia of the Newborn
    • Elevated liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes (aminotransferases) and disproportionately increased gamma-glutamyl transpeptidase Gamma-glutamyl transpeptidase An enzyme, sometimes called ggt, with a key role in the synthesis and degradation of glutathione; (GSH, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid. Liver Function Tests ( GGTP GGTP An enzyme, sometimes called ggt, with a key role in the synthesis and degradation of glutathione; (GSH, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid. Liver Function Tests)
  • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma: reduced number of interlobular bile ducts Interlobular bile ducts Gallbladder and Biliary Tract: Anatomy
  • Genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies to confirm gene mutation Gene Mutation Myotonic Dystrophies
• Management:
  • Cholestatic liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease is of variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables severity; may stabilize by school age.
  • Medical management of pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema) to improve quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of life:
    • Ursodeoxycholic acid Ursodeoxycholic acid An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic. Primary Biliary Cholangitis
    • Bile acid sequestrants Bile Acid Sequestrants Antidiarrheal Drugs ( cholestyramine Cholestyramine A strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium cl(-) anion. Lipid Control Drugs, colesevelam Colesevelam An allylamine derivative that binds bile acids in the intestine and is used as an anticholesteremic agent in the treatment of hypercholesterolemia and hyperlipidemias. Lipid Control Drugs)
    • Refractory to medical treatment in approximately 40% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship; surgery with biliary diversion or liver transplantation Liver transplantation The transference of a part of or an entire liver from one human or animal to another. Hepatocellular Carcinoma (HCC) and Liver Metastases may be indicated.
  • Complication: portal hypertension Portal hypertension Portal hypertension is increased pressure in the portal venous system. This increased pressure can lead to splanchnic vasodilation, collateral blood flow through portosystemic anastomoses, and increased hydrostatic pressure. There are a number of etiologies, including cirrhosis, right-sided congestive heart failure, schistosomiasis, portal vein thrombosis, hepatitis, and Budd-Chiari syndrome. Portal Hypertension later in childhood
  • Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas: In a study of 293 individuals, transplant-free survival was 24% up to age 18.

Choledochal Cysts

Choledochal cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change are congenital Congenital Chorioretinitis bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct anomalies that cause abnormal enlargement and obstruction of the intrahepatic and/or extrahepatic bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy ducts.

• Classification:
  • Type I (90%–95% of cases): a saccular or fusiform cystic Cystic Fibrocystic Change dilation of the extrahepatic biliary duct
  • Type II: a diverticulum Diverticulum A pouch or sac opening from the colon. Diverticular Disease of the common bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct 
  • Type III (choledochocele): a cyst in the common bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct in the duodenal wall
  • Type IV: involves dilation of both intrahepatic and extrahepatic ducts 
  • Type V (least common): multiple cystic Cystic Fibrocystic Change dilations of intrahepatic ducts
• Etiology:
  • Unknown, likely > 1 mechanism
  • May be congenital Congenital Chorioretinitis (most common) or acquired (rare) after cholecystectomy Cholecystectomy Cholecystectomy is a surgical procedure performed with the goal of resecting and extracting the gallbladder. It is one of the most common abdominal surgeries performed in the Western world. Cholecystectomy is performed for symptomatic cholelithiasis, cholecystitis, gallbladder polyps > 0.5 cm, porcelain gallbladder, choledocholithiasis and gallstone pancreatitis, and rarely, for gallbladder cancer. Cholecystectomy
  • Associated with a variety of other anatomic abnormalities:
    • Abnormal pancreatobiliary junction
    • Biliary, duodenal, or colonic atresia Atresia Hypoplastic Left Heart Syndrome (HLHS)
    • Double common bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct
    • Imperforate anus
    • Ventricular septal defect Ventricular Septal Defect Tetralogy of Fallot
    • Aortic hypoplasia Hypoplasia Hypoplastic Left Heart Syndrome (HLHS)
• Epidemiology:
  • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in Western countries: 1 in 100,000–150,000
  • Higher incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in Japan: about 1 in 1000
  • Female to male ratio is 3–4:1
  • Most often diagnosed in infancy or childhood, but sometimes in adulthood
• Clinical presentation:
  • Infants:
    • Obstructive jaundice Obstructive jaundice Hepatocellular Carcinoma (HCC) and Liver Metastases
    • Palpable mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast
    • Acholic stools
    • Hepatomegaly
    • Cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change may be an incidental finding on prenatal ultrasonography
  • Children (majority present at < 10 years):
    • Abdominal pain Abdominal Pain Acute Abdomen
    • Jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice 
    • Palpable mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast
    • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
    • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
    • Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema)
    • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
    • Bouts of acute pancreatitis Pancreatitis Inflammation of the pancreas. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of chronic pancreatitis. The two most common forms of acute pancreatitis are alcoholic pancreatitis and gallstone pancreatitis. Acute Pancreatitis; occasionally acute cholangitis Acute Cholangitis Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. Acute Cholangitis
• Diagnosis:
  • Laboratory studies:
    • Direct (conjugated) hyperbilirubinemia Hyperbilirubinemia A condition characterized by an abnormal increase of bilirubin in the blood, which may result in jaundice. Bilirubin, a breakdown product of heme, is normally excreted in the bile or further catabolized before excretion in the urine. Jaundice 
    • Obstructive pattern of liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes: significant elevation of alkaline phosphatase Alkaline Phosphatase An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. Osteosarcoma, mild elevation of ALT ALT An enzyme that catalyzes the conversion of l-alanine and 2-oxoglutarate to pyruvate and l-glutamate. Liver Function Tests and AST AST Enzymes of the transferase class that catalyze the conversion of l-aspartate and 2-ketoglutarate to oxaloacetate and l-glutamate. Liver Function Tests
  • Ultrasonography 
  • MRCP MRCP Non-invasive diagnostic technique for visualizing the pancreatic ducts and bile ducts without the use of injected contrast media or x-ray. Mri scans provide excellent sensitivity for duct dilatation, biliary stricture, and intraductal abnormalities. Primary Sclerosing Cholangitis for preoperative assessment 
• Treatment: primary cyst excision + biliary enteric (Roux-en-Y) anastomosis
• Complications:
  • If the obstruction is not relieved (especially in infancy), severe liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy dysfunction and coagulopathy may rapidly ensue.
  • Higher risk of cholangiocarcinoma Cholangiocarcinoma A malignant tumor arising from the epithelium of the bile ducts. Rare Malignant Liver Tumors if proper resection is not performed