Materiały źródłowe

• #1 Jaundice – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK544252/

  Jaundice, also known as hyperbilirubinemia, is defined as a yellow discoloration of the body tissue resulting from the accumulation of excess bilirubin. […] The pathophysiology of jaundice is best explained by dividing the metabolism of bilirubin into three phases: prehepatic, hepatic, and post-hepatic. […] Dysfunction in prehepatic phase results in elevated serum levels of unconjugated bilirubin while insult in post hepatic phase marks elevated conjugated bilirubin. Hepatic phase impairment can elevate both unconjugated and conjugated bilirubin. […] The basic mechanisms of jaundice include elevated production, decreased uptake, and faulty conjugation.

• #1 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Jaundice-Pathophysiology.aspx

  Jaundice is a symptom of an underlying condition that impairs the excretion of bilirubin from the body. […] The heme, on the other hand, undergoes an oxidation reaction catalyzed by the enzyme oxygenase, to give biliverdin, iron and carbon monoxide. The biliverdin is a green-colored pigment which then undergoes a reduction reaction to yield a yellow pigment called bilirubin. […] This insoluble bilirubin is referred to as free, indirect or unconjugated bilirubin and it moves towards the liver through the bloodstream, while bound to albumin. In the liver, the bilirubin is conjugated with glucuronic acid (catalyzed by UDP-glucuronyl transferase) to give bilirubin diglucuronide or conjugated bilirubin, which is the water soluble form of bilirubin that can be excreted. […] Jaundice is a yellowing of the skin, nail beds and whites of the eyes that is caused by a build-up of bilirubin in the bodys tissues.

• #1 Jaundice – Wikipedia

  https://en.wikipedia.org/wiki/Jaundice

  Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme metabolism, liver dysfunction, or biliary-tract obstruction. […] Causes of jaundice vary from relatively benign to potentially fatal. High unconjugated bilirubin may be due to excess red blood cell breakdown, large bruises, genetic conditions such as Gilbert’s syndrome, not eating for a prolonged period of time, newborn jaundice, or thyroid problems. High conjugated bilirubin may be due to liver diseases such as cirrhosis or hepatitis, infections, medications, or blockage of the bile duct, due to factors including gallstones, cancer, or pancreatitis. […] Jaundice is a sign indicating the presence of an underlying diseases involving abnormal bilirubin metabolism, liver dysfunction, or biliary-tract obstruction. In general, jaundice is present when blood levels of bilirubin exceed 3 mg/dl. Jaundice is classified into three categories, depending on which part of the physiological mechanism the pathology affects. The three categories are: Prehepatic/hemolytic, Hepatic/hepatocellular, and Posthepatic/cholestatic.

• #1 Jaundice – Pre, Intra, Post-hepatic – Management – TeachMeSurgery

  https://teachmesurgery.com/hpb/presentations/jaundice/

  Jaundice results from high levels of bilirubin in the blood. Bilirubin is the normal breakdown product from the catabolism of haem, and thus is formed from the destruction of red blood cells. […] Under normal circumstances, bilirubin undergoes conjugation within the liver, making it water-soluble. It is then excreted via the bile into the gastrointestinal tract to be metabolised into urobilinogen, the majority of which is then egested in the faeces as stercobilin (the metabolic breakdown product of urobilingoen). Around 10% of urobilinogen is reabsorbed into the bloodstream and excreted through the kidneys. Jaundice occurs when this pathway is disrupted. […] In pre-hepatic jaundice, there is excessive red cell breakdown which overwhelms the livers ability to conjugate bilirubin. This causes an unconjugated hyperbilirubinaemia.

• #1 Etiopathogenesis of jaundice | PPT

  https://www.slideshare.net/slideshow/etiopathogenesis-of-jaundice/250032915

  Like prehepatic AKI, prehepatic jaundice is the condition of jaundice raised before liver does its job. Thus results in increased unconjugated bilirubin mostly due to increased hemolysis. Conditions leading to prehepatic jaundice include: autoimmune hemolytic anemia, SLE, sickle cell anemia, thalassemia, malaria, hemolytic disease of newborn (neonatal jaundice). […] Improper functioning of liver causes jaundice results in increase of both unconjugated and conjugated bilirubin in blood. Lack of proper functioning of liver is due to various bacterial and viral infections (hepatitis A, B, C, D, E, EPSTEIN BARR virus), alcoholic hepatitis, cirrhosis etc. […] Jaundice resulting due to increased conjugated bilirubin. This is result of obstruction of flow of bilirubin from liver to gut which may be due to cholelithiasis (gall stones), pancreatitis etc.

• #1 Jaundice – Pre, Intra, Post-hepatic – Management – TeachMeSurgery

  https://teachmesurgery.com/hpb/presentations/jaundice/

  In hepatocellular (or intrahepatic) jaundice, there is dysfunction of the hepatic cells. The liver loses the ability to conjugate bilirubin, but in cases where it also may become cirrhotic, it compresses the intra-hepatic portions of the biliary tree to cause a degree of obstruction. This leads to both unconjugated and conjugated bilirubin in the blood, termed a mixed picture. […] Post-hepatic jaundice refers to obstruction of biliary drainage. The bilirubin that is not excreted will have been conjugated by the liver, hence the result is a conjugated hyperbilirubinaemia. […] Jaundice refers to the yellow discolouration of the sclera and skin that is due to hyperbilirubinaemia.

• #1 Jaundice – Hepatic and Biliary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/approach-to-the-patient-with-liver-disease/jaundice

  Most bilirubin is produced when hemoglobin (Hb) is broken down into unconjugated bilirubin (and other substances). Unconjugated bilirubin binds to albumin in the blood for transport to the liver, where it is taken up by hepatocytes and conjugated with glucuronic acid to make it water soluble. Conjugated bilirubin is excreted in bile into the duodenum. In the intestine, bacteria metabolize bilirubin to form urobilinogen. Some urobilinogen is eliminated in the feces, and some is reabsorbed, extracted by hepatocytes, reprocessed, and re-excreted in bile (enterohepatic circulationsee Overview of Bilirubin Metabolism). […] Hyperbilirubinemia may involve predominantly unconjugated or conjugated bilirubin. […] Unconjugated hyperbilirubinemia is most often caused by 1 of the following: Increased production, Decreased hepatic uptake, Decreased conjugation.

• #1 Diseases Associated with Hyperbilirubinemia

  https://library.med.utah.edu/NetBiochem/hi7d.htm

  Several diseases are associated with hyperbilirubinemia. […] Hyperbilirubinemia could be caused by increased bilirubin production […] decreased uptake into the liver cells […] impaired conjugation […] interference with the secretion of conjugated bilirubin. […] Hemolytic jaundice results in increased production of bilirubin. […] Here more bilirubin is conjugated and excreted than normally, but the conjugation mechanism is overwhelmed, and an abnormally large amount of unconjugated bilirubin is found in the blood. […] Gilbert’s disease may be caused by an inability of the hepatocytes to take up bilirubin from the blood. […] As a result, unconjugated bilirubin accumulates. […] Physiological jaundice and Crigler-Najjar syndrome are conditions in which conjugation is impaired.

• #1 Table: Mechanisms and Some Causes of Jaundice in Adults-MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/multimedia/table/mechanisms-and-some-causes-of-jaundice-in-adults

  Mechanisms and Some Causes of Jaundice in Adults […] Unconjugated hyperbilirubinemia […] Increased bilirubin production […] Common: Hemolysis […] Less common: Resorption of large hematomas, ineffective erythropoiesis […] Few or no clinical manifestations of hepatobiliary disease; sometimes anemia, ecchymoses […] Serum bilirubin level usually 3.5 mg/dL ( 59 micromol/L), no bilirubin in urine, normal aminotransferase levels […] Decreased hepatic bilirubin uptake […] Common: Heart failure […] Less common: Drugs, fasting, portosystemic shunts […] Decreased hepatic conjugation […] Common: Gilbert syndrome […] Less common: Ethinyl estradiol, Crigler-Najjar syndrome, hyperthyroidism […] Conjugated hyperbilirubinemia […] Hepatocellular dysfunction […] Common: Drugs, toxins, viral hepatitis

• #1 British Journal Of Midwifery – Bilirubin in the newborn: Physiology and pathophysiology

  https://www.britishjournalofmidwifery.com/content/clinical-practice/bilirubin-in-the-newborn-physiology-and-pathophysiology/

  Most bilirubin is produced during the breakdown of senescent red blood cells, with bilirubin being produced as a result of the breakdown of the haem component of haemoglobin. […] This occurs in phagocytic monocytes and macrophages in various tissues of the body (Mitra and Rennie, 2017), and first results in a form of bilirubin called unconjugated bilirubin. […] This is lipid-rather than water-soluble, so is transported to the liver for metabolism bound to albumin (Blackburn, 2017). […] In the liver it undergoes conjugation (it is combined with glucuronic acid by the enzyme glucuronyl transferase) to produce conjugated bilirubin, which is more water-soluble and can thus be excreted in urine and bile (Mitra and Rennie, 2017; Rankin, 2017). […] Mutations in this enzyme that reduce its function can result in Gilbert and Crigler-Najjar syndromes, which are characterised by hyperbilirubinaemia due to reduced functioning of the liver’s bilirubin-conjugating ability and the resulting build-up of unconjugated bilirubin (Wong and Stevenson, 2015; Chang et al, 2017). […] As the liver conjugating system also requires oxygen and glucose to function efficiently, hypoxia and hypoglycaemia may also slow down this process and increase the risk of hyperbilirubinaemia (Blackburn, 2017; Rankin, 2017).

• #1 Jaundice – Hepatic and Biliary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/approach-to-the-patient-with-liver-disease/jaundice

  Conjugated hyperbilirubinemia is most often caused by 1 of the following: Dysfunction of hepatocytes (hepatocellular dysfunction), Slowing of bile egress from the liver (intrahepatic cholestasis), Obstruction of extrahepatic bile flow (extrahepatic cholestasis). […] Outcome is determined primarily by the cause of jaundice and the presence and severity of hepatic dysfunction. Hepatic dysfunction can result in coagulopathy, encephalopathy, and portal hypertension (which can lead to gastrointestinal bleeding).

• #1 Jaundice and cholestasis – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/jaundice-and-cholestasis/

  Posthepatic jaundice is caused by the accumulation of conjugated hyperbilirubinemia usually due to extrahepatic cholestasis from biliary obstruction. […] Hepatitis and cirrhosis can cause both conjugated and unconjugated hyperbilirubinemia. […] Cholestasis: impaired production, secretion, or outflow of bile. […] Varying degrees of jaundice and elevations of cholestatic enzymes (including ALP, GGT, and direct bilirubin) are seen in conditions that cause conjugated hyperbilirubinemia due to cholestasis.

• #1 Table: Mechanisms and Some Causes of Jaundice in Adults-MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/multimedia/table/mechanisms-and-some-causes-of-jaundice-in-adults

  Less common: Alcohol-related liver disease, hemochromatosis, primary biliary cholangitis, primary sclerosing cholangitis, steatohepatitis, Wilson disease […] Aminotransferase levels usually 500 U/L (8.35 microkat/L) […] Intrahepatic cholestasis […] Common: Alcohol-related liver disease, drugs, toxins, viral hepatitis […] Less common: Infiltrative disorders (eg, amyloidosis, lymphoma, sarcoidosis, tuberculosis), pregnancy, primary biliary cholangitis, steatohepatitis […] Gradual onset of jaundice, sometimes pruritus […] If severe, clay-colored stools, steatorrhea […] If long-standing, weight loss […] Alkaline phosphatase and GGT usually 3 times normal […] Aminotransferase levels 200 U/L (3.34 microkat/L) […] Extrahepatic cholestasis […] Common: Common bile duct stone, pancreatic cancer

• #1 Obstructive Jaundice

  https://jsms.sch.ac.kr/journal/view.php?number=620

  Jaundice is a medical condition in which the skin or sclera of the eyes becomes yellow, and elevation of bilirubin production or obstruction of bile excretion can cause jaundice while disrupting the balance between bilirubin production and bile excretion. […] Jaundice is always a pathological sign so that it should never be ignored. […] If jaundice occurs because of obstruction of bile flow after bile is produced, it is essentially obstructive jaundice. […] Obstruction at the level of the common bile duct causes backflow of bile into the liver, as well as into the blood stream, thereby causing jaundice. […] Jaundice itself warrants further investigation as it is always a pathological sign. […] Once jaundice occurs, it makes sclerae yellow first. After that, yellowish skin becomes noticeable. […] Jaundice is one of the most visual clinical signs that both patients and physicians can easily recognize. It warrants further investigation regarding the cause of jaundice. Especially for obstructive jaundice, there are common medical conditions that are responsible for it.

• #1 Neonatal Jaundice: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/974786-overview

  Jaundice is the most common condition that requires medical attention and hospital readmission in newborns. The yellow coloration of the skin and sclera in newborns with jaundice is the result of accumulation of unconjugated bilirubin. […] However, in some infants, serum bilirubin levels may rise excessively, which can be cause for concern because unconjugated bilirubin IX (Z,Z) is neurotoxic and can cause death in newborns and lifelong neurologic sequelae in infants who survive (kernicterus). […] Neonatal physiologic jaundice results from simultaneous occurrence of the following two phenomena: Bilirubin production is elevated because of increased breakdown of fetal erythrocytes. This is the result of the shortened lifespan of fetal erythrocytes and the higher erythrocyte mass in neonates. […] Hepatic excretory capacity is low, because of low concentrations of the binding protein ligandin in the hepatocytes and because of low activity of glucuronyl transferase, the enzyme responsible for binding bilirubin to glucuronic acid, thus making bilirubin water soluble (conjugation).

• #1 Breastfeeding Jaundice and Breast Milk Jaundice

  https://www.birthinjuryhelpcenter.org/birth-injuries/help-center/jaundice-breastfeeding/

  Infant jaundice is a condition that occurs when a baby has elevated bilirubin levels, causing their skin and eyes to have a yellowish tint. […] Jaundice is often still present when a mother first starts breastfeeding, and usually, the consistent supply of milk helps lower the baby’s bilirubin levels. […] We know why babies get breastfeeding jaundice. It is generally from sub-optimal milk intake which causes bilirubin levels to rise. […] Bilirubin is a substance made during the normal breakdown of red blood cells and is passed through the liver before being excreted from the body. Infant jaundice stems from excessive bilirubin in the blood. This happens when there’s too much bilirubin in the baby’s blood. […] A newborn (especially preterm newborns) has an underdeveloped liver with limited function, which leads to slower metabolism of bilirubin.

• #1 Neonatal hyperbilirubinemia – McMaster Pathophysiology Review

  https://www.pathophys.org/neonatal-hyperbilirubinemia/

  Breast milk jaundice: Distinct from breastfeeding jaundice, breast milk jaundice develops in the second week of life, lasts longer than physiologic jaundice, and has no other identifiable cause. Pathophysiology is not well understood, but it is thought that substances in breast milk, such as beta-glucuronidases and nonesterified fatty acids, may inhibit normal bilirubin metabolism (e.g. via unconjugation and reabsorption of conjugated bilirubin excreted in bile). […] Anatomical abnormalities or disease processes that prevent bilirubin from being normally excreted in bile can cause a conjugated hyperbilirubinemia, defined as 17 umol/L if total is 85.6umol/L or less, or a conjugated component 20% of total, if total is greater than 85.6umol/L. […] Biliary atresia is the most common cause of biliary obstruction in the newborn, accounting for 40-50% of cases.

• #1 Neonatal Jaundice: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/974786-overview

  Bilirubin is produced in the reticuloendothelial system as the end product of heme catabolism and is formed through oxidation-reduction reactions. Approximately 75% of bilirubin is derived from hemoglobin, but degradation of myoglobin, cytochromes, and catalase also contributes. […] The presence of endogenous and exogenous binding competitors (eg, certain drugs) also reduces the binding affinity of albumin for bilirubin. A minute fraction of unconjugated bilirubin in serum is not bound to albumin. This free bilirubin is able to cross lipid-containing membranes, including the blood-brain barrier, leading to neurotoxicity. […] Bilirubin conjugation is biologically critical because it transforms a water-insoluble bilirubin molecule into a water-soluble molecule. Water solubility allows conjugated bilirubin to be excreted into bile. […] Infants who have Gilbert syndrome or who are compound heterozygotes for the Gilbert promoter and structural mutations of the UDPGT1A1 coding region are at an increased risk of significant hyperbilirubinemia.

• #1 Neonatal Hyperbilirubinemia – Pediatrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pediatrics/metabolic-electrolyte-and-toxic-disorders-in-neonates/neonatal-hyperbilirubinemia

  Hyperbilirubinemia is an elevated serum bilirubin concentration, causing jaundice (a yellow discoloration of the skin and eyes). […] Almost all hyperbilirubinemia in the immediate neonatal period is unconjugated, which is also termed indirect bilirubin; conjugated bilirubin is termed direct bilirubin. […] Neurotoxicity is the major negative consequence of neonatal hyperbilirubinemia. An acute encephalopathy can be followed by a variety of neurologic impairments, including cerebral palsy and sensorimotor deficits; cognition is usually spared. Chronic bilirubin encephalopathy (CBE), formerly known as kernicterus, is the most severe form of neurotoxicity. […] CBE is brain damage caused by unconjugated bilirubin deposition in basal ganglia and brain stem nuclei, caused by either acute or chronic hyperbilirubinemia.

• #1 Neonatal Hyperbilirubinemia – Pediatrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pediatrics/metabolic-electrolyte-and-toxic-disorders-in-neonates/neonatal-hyperbilirubinemia

  Normally, bilirubin bound to serum albumin stays in the intravascular space. However, unconjugated bilirubin can cross the blood-brain barrier and cause CBE in certain situations: When serum bilirubin concentration is markedly elevated, When serum albumin concentration is markedly low (eg, in preterm infants), When bilirubin is displaced from albumin by competitive binders. […] Hyperbilirubinemia can be caused by one or more of the following processes: Increased production, Decreased hepatic uptake, Decreased conjugation, Impaired excretion, Impaired bile flow (cholestasis), Increased enterohepatic circulation. […] The majority of bilirubin is produced from the breakdown of hemoglobin into unconjugated bilirubin (and other substances). Unconjugated bilirubin binds to albumin in the blood for transport to the liver, where it is taken up by hepatocytes and conjugated with glucuronic acid by the enzyme uridine diphosphogluconurate glucuronosyltransferase (UGT) to make it water-soluble. The conjugated bilirubin is excreted in bile into the duodenum.

• #1 Hyperbilirubinemia in the Term Newborn | AAFP

  https://www.aafp.org/pubs/afp/issues/2002/0215/p599.html

  Jaundice typically results from the deposition of unconjugated bilirubin pigment in the skin and mucus membranes. […] Unconjugated hyperbilirubinemia, the primary focus of this article, is the most common form of jaundice encountered by family physicians. […] The causes of neonatal hyperbilirubinemia can be classified into three groups based on mechanism of accumulation: bilirubin overproduction, decreased bilirubin conjugation, and impaired bilirubin excretion. […] Kernicterus refers to the neurologic consequences of the deposition of unconjugated bilirubin in brain tissue. Subsequent damage and scarring of the basal ganglia and brainstem nuclei may occur. […] The precise role of bilirubin in the development of kernicterus is not completely understood. If the serum unconjugated bilirubin level exceeds the binding capacity of albumin, unbound lipid-soluble bilirubin crosses the blood-brain barrier.

• #1 Mechanical Jaundice of Calculous Etiology: Pathogenesis, Complications and Therapeutic Tactics

  http://article.sapub.org/10.5923.j.ajmms.20241409.37.html

  The current rise in the incidence of cholelithiasis is accompanied by an increased frequency of its complicated forms. Mechanical jaundice is a common unfavourable complication of cholelithiasis and choledocholithiasis, its consequence. […] Much attention is given to its pathogenetic mechanisms. […] The anatomical and physiological unity of the liver and extrahepatic biliary tract leads to their friendly damage in prolonged and recurrent forms of mechanical jaundice. […] Cholestasis caused by mechanical obstruction quickly leads to cholestatic intoxication, cholangitis, progressive liver failure, expressed by complex symptoms of disorders, the leading cause of which is the suppression of detoxification and synthetic liver functions. […] Violation of bilirubin release into the biliary tract with the development of biliary hypertension has a toxic effect on hepatocytes with impaired function and leads to changes in the properties and structure of cellular membranes, due to changes in the composition of membrane lipids, cholesterol and fatty acids, impaired activity of membrane-bound enzymes involved in the processes of transport through the membrane.

• #1 Mechanical Jaundice of Calculous Etiology: Pathogenesis, Complications and Therapeutic Tactics

  http://article.sapub.org/10.5923.j.ajmms.20241409.37.html

  In the pathogenesis of liver dysfunction, damage to subcellular structures that are extremely sensitive to hypoxia occupies a leading place. […] Mechanical jaundice and liver failure are integral parts of a single process that develops independently of the etiology of biliary tract obstruction. […] The large role of endogenous intoxication in the pathogenesis of mechanical jaundice of non-tumor etiology determines the importance of timely intensive complex therapy that can prevent the development of irreversible disorders of the structure and function of many organs and systems and contribute to the processes of repair and adaptation.

• #1 Hyperbilirubinemia and Neonatal Infection

  https://jpp.mums.ac.ir/article_2026.html

  Hyperbilirubinemia is a common and in most cases benign problem in first mouth of life which is often physiologic and intervention is not usually necessary. Jaundice may develop serious complications like kernicterus and lifelong disability (1,2). […] One of these factors is infection which is a serious clinical problem among newborns (5,6). The incidence rate of hyperbilirubinemia due to infection is unknown (7,8). It is well known that clinical manifestations of neonatal infection pretends as a wide spectrum, ranging from nonspecific signs and symptoms to severe illness as well as poor feeding, fever, vomiting, renal failure and respiratory distress (9,10). Hyperbilirubinemia may be the only manifestation of infection, especially UTI within neonatal period (10-12). […] Bacterial infection has been well-documented as a cause of neonatal jaundice in previous studies (6) but the prevalence rate, jaundice presentation time and the differences between the jaundice associated with infection and other types of jaundice was unknown yet.

• #1 Hyperbilirubinemia and Neonatal Infection

  https://jpp.mums.ac.ir/article_2026.html

  The aim of this study was to determine the incidence rate, symptoms, and age at presentation, predisposing factors, characteristics, the severity of jaundice associated with infection and complications and the etiology of infection among neonates with hyperbilirubinemia in the first month- of life. […] Neonatal infection was found in approximately 10% of jaundiced newborns. The most common infection associated with neonatal jaundice was UTI (77.9%), Sepsis (16.8%) and pneumonia (5.3%), in order. […] The mechanism of jaundice in neonatal pneumonia is not well known. This partially may be related to the congestion of liver affected by pneumonia. Mean bilirubin value was significantly higher in sepsis subgroup as compared with noninfectious subjects (23.8 mg/dl versus 21.2 mg/dl). The mechanism of jaundice in neonatal sepsis maybe related to liver involvement by infection or hemolysis, although this mechanism is not well known. Conjugated hyperbilirubinemia can be associated with cholestasis secondary to bacterial infection. The mechanism in which infection causes cholestasis is not clear, but possible mechanisms include microcirculatory changes in the liver, direct effects from bacterial products, and/or from endotoxin-induced mediators (13,14). […] We concluded that bacterial infection was a significant cause of unexplained Hyperbilirubinemia among jaundice neonates. Our results indicate that urinary tract infections after and sepsis before the first week of life may be associated with jaundice.

• #1 Neonatal jaundice is associated with increased risks of congenital anomalies of the kidney and urinary tract and concomitant urinary tract infection | Scientific Reports

  https://www.nature.com/articles/s41598-024-59943-2

  The link between neonatal jaundice and urinary tract infection (UTI) remains debated, with congenital kidney and urinary tract anomalies (CAKUT) potentially playing a role. […] Infants with neonatal jaundice had a significantly higher risk of CAKUT (adjusted odds ratio [aOR] 1.24, 95% confidence interval [CI] 1.111.39) during early childhood. […] Among the subtypes of CAKUT, obstructive uropathy, vesicoureteral reflux and other CAKUT were associated with an increased risk of neonatal jaundice. […] Our findings indicate a notable association between neonatal jaundice and increased risks of UTIs in the context of CAKUT. […] The association between neonatal jaundice and UTI may be influenced by several potential mechanisms. One potential mechanism for the association between neonatal jaundice and UTI is hemolysis caused by E. coli and other gram-negative bacteria.

• #1 Phototherapy for Jaundice: Background, Indications, Contraindications

  https://emedicine.medscape.com/article/1894477-overview

  Jaundice refers to the yellow appearance of the skin that occurs with the deposition of bilirubin in the dermal and subcutaneous tissue. Normally in the body, bilirubin is processed through the liver, where it is conjugated to glucuronic acid by the enzyme uridine diphosphate glucuronyl transferase (UGT) 1A1. This conjugated form of bilirubin is then excreted into the bile and removed from the body via the gut. When this excretion process is low following birth, does not work efficiently, or is overwhelmed by the amount of endogenously produced bilirubin, the amount of bilirubin in the body increases, resulting in hyperbilirubinemia and jaundice. […] At its most basic, phototherapy refers to the use of light to convert bilirubin molecules in the body into water soluble isomers that can be excreted by the body. The absorption of light by normal bilirubin (4Z,15Z-bilirubin) results in the creation of 2 isomeric forms of bilirubin: structural isomers and configurational isomers. The main structural isomer of bilirubin is Z-lumirubin. The main configurational isomer of bilirubin is 4Z,15 E -bilirubin. Configurational isomerization is reversible, and structural isomerization is irreversible. Both the configurational and structural isomers of bilirubin are less lipophilic than normal bilirubin and can be excreted into bile without undergoing glucuronidation in the liver. Some of the configurational isomers of bilirubin, however, revert back to the native form after excretion into bile and can be reabsorbed via enterohepatic circulation in the gut. Structural bilirubin isomers, like Z-lumirubin, can also be excreted in the urine.

• #1 Phototherapy for Jaundice: Background, Indications, Contraindications

  https://emedicine.medscape.com/article/1894477-overview

  The absorptions of light by bilirubin also results in the generation of excited-state bilirubin molecules that react with oxygen to produce colorless oxidation products, or photooxidation products. This process occurs more slowly than configurational or structural isomerization. Photooxidation products are primarily excreted in the urine. […] Mechanism of phototherapy: Blue-green light in the range of 460-490 nm is most effective for phototherapy. The absorption of light by the normal bilirubin (4Z,15Z-bilirubin) generates configuration isomers, structural isomers, and photooxidation products. The 2 principal photoisomers formed in humans are shown. Configurational isomerization is reversible and much faster than structural isomerization. Structural isomerization is slow and irreversible. Photooxidation occurs more slowly than both configurational and structural isomerization. Photooxidation products are excreted mainly in urine.

• #1 Phototherapy for neonatal jaundice

  https://www.rch.org.au/rchcpg/hospital_clinical_guideline_index/phototherapy_for_neonatal_jaundice/

  Unconjugated bilirubin can cross the blood-brain barrier and cause neurotoxic effects. […] Kernicterus: the pathogenic diagnosis characterised by bilirubin staining of the brain stem and cerebellum. Also the term used to refer to chronic bilirubin encephalopathy. Clinical findings include cerebral palsy, developmental and intellectual delay, hearing deficit, dental dysplasia and oculomotor disturbances. […] Commence phototherapy once SBR is greater than the appropriate reference range for neonates gestation/weight and presence of risk factors. […] Ensure that phototherapy unit is turned off during collection of blood for SBR levels, as both conjugated and unconjugated bilirubin are photo-oxidized when exposed to white or ultraviolet light.

• #1 Mechanism of bilirubin elimination in urine: insights and prospects for neonatal jaundice

  https://www.degruyterbrill.com/document/doi/10.1515/cclm-2020-1759/html?lang=en&srsltid=AfmBOopZqj7NR-iysdFZK00RmwpP93S6yk2IYqgZ-Div19tPQTx5yfJU

  Despite a century of research, bilirubin metabolism and the transport mechanisms responsible for homeostasis of bilirubin in serum remain controversial. […] Emerging evidence on the hepatic membrane transporters and inherited disorders of bilirubin metabolism have contributed to a greater understanding of the various steps involved in bilirubin homeostasis and its associated excretory pathways. […] New insights gained speculate that a proportion of conjugated bilirubin is excreted via the renal system, as an alternative to the intestinal excretion, even in normal physiological jaundice with no associated pathological concerns. […] Finally, this paper discusses the clinical relevance of targeting the altered renal excretory pathway, as bilirubin in urine may hold diagnostic importance in screening for neonatal jaundice.

• #1 Jaundice – Etiology, pathogenesis, Clinical features, Investigation, Treatment and Outcome | PPT

  https://www.slideshare.net/slideshow/jaundice-etiology-pathogenesis-clinical-features-investigation-treatment-and-outcome/241071760

  Jaundice, or icterus, is caused by increased levels of bilirubin in the blood which deposits in tissues. […] Defects in bilirubin production, uptake, conjugation or excretion by the liver can lead to jaundice. […] Jaundice is caused by a buildup of bilirubin in the bloodstream. Bilirubin is produced from the breakdown of red blood cells and normally processed by the liver. Jaundice can be caused by liver disease or inflammation, bile duct obstruction, or conditions that increase the breakdown of red blood cells like hepatitis or hemolytic anemia. […] Jaundice can be pre-hepatic from excessive bilirubin production, hepatic from impaired conjugation or transport, or post-hepatic from bile duct obstruction. […] Jaundice occurs when there is excessive bilirubin production or impaired clearance. […] Jaundice is usually present clinically when the plasma bilirubin concentration reaches 2 to 3 mg/dl. […] Jaundice can be detected when serum bilirubin is above 2-2.5 mg/dL. […] Jaundice is classified based on bilirubin type, etiology, and site of disease.

• #1 Jaundice: types, etiology, pathogenesis & treatment | FirstHope

  https://www.firsthope.co.in/jaundice-symptoms-types-etiology-pathogenesis-of-jaundice-treatment

  Jaundice is characterized by yellowing of the skin and eyes due to elevated bilirubin levels. […] Increased bilirubin production, as seen in hemolysis, leads to elevated levels exceeding the liver’s ability to conjugate and excrete it. […] Liver diseases such as hepatitis or cirrhosis impair bilirubin conjugation and excretion. Damage to hepatocytes reduces their ability to process bilirubin. […] Obstruction of bile flow, due to gallstones or tumors, prevents bilirubin excretion into the intestines, leading to its accumulation in the blood.

• #2 Jaundice – Pre, Intra, Post-hepatic – Management – TeachMeSurgery

  https://teachmesurgery.com/hpb/presentations/jaundice/

  Jaundice results from high levels of bilirubin in the blood. Bilirubin is the normal breakdown product from the catabolism of haem, and thus is formed from the destruction of red blood cells. […] Under normal circumstances, bilirubin undergoes conjugation within the liver, making it water-soluble. It is then excreted via the bile into the gastrointestinal tract to be metabolised into urobilinogen, the majority of which is then egested in the faeces as stercobilin (the metabolic breakdown product of urobilingoen). Around 10% of urobilinogen is reabsorbed into the bloodstream and excreted through the kidneys. Jaundice occurs when this pathway is disrupted. […] In pre-hepatic jaundice, there is excessive red cell breakdown which overwhelms the livers ability to conjugate bilirubin. This causes an unconjugated hyperbilirubinaemia.

• #2 Jaundice – Hepatic and Biliary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/approach-to-the-patient-with-liver-disease/jaundice

  Most bilirubin is produced when hemoglobin (Hb) is broken down into unconjugated bilirubin (and other substances). Unconjugated bilirubin binds to albumin in the blood for transport to the liver, where it is taken up by hepatocytes and conjugated with glucuronic acid to make it water soluble. Conjugated bilirubin is excreted in bile into the duodenum. In the intestine, bacteria metabolize bilirubin to form urobilinogen. Some urobilinogen is eliminated in the feces, and some is reabsorbed, extracted by hepatocytes, reprocessed, and re-excreted in bile (enterohepatic circulationsee Overview of Bilirubin Metabolism). […] Hyperbilirubinemia may involve predominantly unconjugated or conjugated bilirubin. […] Unconjugated hyperbilirubinemia is most often caused by 1 of the following: Increased production, Decreased hepatic uptake, Decreased conjugation.

• #2 Mechanism Of Jaundice – Personal Use – Armando Hasudunganbookprintchevron-leftchevron-rightfacebookfilteruser-mdangle-downyoutubeinstagramlong-arrow-upline-chartx-twittermagnifiercrossyoutubedownloadmore-verticaluser

  https://armandoh.org/shop/mechanism-of-jaundice/?srsltid=AfmBOooHoWmwjWMhmrXe4bifiW1PW9ZP8xCTRuKUcJieD8UqdOc75EAK

  Jaundice is a condition that is characterized by the yellowing of the skin and whites of the eyes due to an accumulation of bilirubin, a yellowish pigment that is produced by the breakdown of red blood cells. Jaundice can occur in individuals of all ages, and it is typically classified into three main types based on the underlying cause: […] Prehepatic jaundice: This type of jaundice is caused by an increase in the production of bilirubin, such as in cases of hemolytic anemia (a condition in which red blood cells are destroyed faster than they can be replaced). […] Hepatic jaundice: This type of jaundice is caused by a problem in the liver, such as liver disease or damage, which prevents the liver from properly processing and excreting bilirubin. […] Posthepatic jaundice: This type of jaundice is caused by a blockage in the bile ducts, which prevents bilirubin from being properly excreted from the body. This can be caused by a variety of factors, including gallstones, pancreatic cancer, and inflammatory bowel disease.

• #2 Jaundice – Wikipedia

  https://en.wikipedia.org/wiki/Jaundice

  Prehepatic jaundice results from a pathological increase in bilirubin production: an increased rate of erythrocyte hemolysis causes increased bilirubin production, leading to increased deposition of bilirubin in mucosal tissues and the appearance of a yellow hue. […] Hepatic jaundice (hepatocellular jaundice) is due to significant disruption of liver function, leading to hepatic cell death and necrosis and impaired bilirubin transport across hepatocytes. Bilirubin transport across hepatocytes may be impaired at any point between hepatocellular uptake of unconjugated bilirubin and hepatocellular transport of conjugated bilirubin into the gallbladder. […] Posthepatic jaundice, also called obstructive jaundice, is due to the blockage of bile excretion from the biliary tract, which leads to increased conjugated bilirubin and bile salts there. In complete obstruction of the bile duct, conjugated bilirubin cannot access the intestinal tract, disrupting further bilirubin conversion to urobilinogen and, therefore, no stercobilin or urobilin is produced.

• #2 Jaundice – Wikipedia

  https://en.wikipedia.org/wiki/Jaundice

  Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme metabolism, liver dysfunction, or biliary-tract obstruction. […] Causes of jaundice vary from relatively benign to potentially fatal. High unconjugated bilirubin may be due to excess red blood cell breakdown, large bruises, genetic conditions such as Gilbert’s syndrome, not eating for a prolonged period of time, newborn jaundice, or thyroid problems. High conjugated bilirubin may be due to liver diseases such as cirrhosis or hepatitis, infections, medications, or blockage of the bile duct, due to factors including gallstones, cancer, or pancreatitis. […] Jaundice is a sign indicating the presence of an underlying diseases involving abnormal bilirubin metabolism, liver dysfunction, or biliary-tract obstruction. In general, jaundice is present when blood levels of bilirubin exceed 3 mg/dl. Jaundice is classified into three categories, depending on which part of the physiological mechanism the pathology affects. The three categories are: Prehepatic/hemolytic, Hepatic/hepatocellular, and Posthepatic/cholestatic.

• #2 Table: Mechanisms and Some Causes of Jaundice in Adults-MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/multimedia/table/mechanisms-and-some-causes-of-jaundice-in-adults

  Mechanisms and Some Causes of Jaundice in Adults […] Unconjugated hyperbilirubinemia […] Increased bilirubin production […] Common: Hemolysis […] Less common: Resorption of large hematomas, ineffective erythropoiesis […] Few or no clinical manifestations of hepatobiliary disease; sometimes anemia, ecchymoses […] Serum bilirubin level usually 3.5 mg/dL ( 59 micromol/L), no bilirubin in urine, normal aminotransferase levels […] Decreased hepatic bilirubin uptake […] Common: Heart failure […] Less common: Drugs, fasting, portosystemic shunts […] Decreased hepatic conjugation […] Common: Gilbert syndrome […] Less common: Ethinyl estradiol, Crigler-Najjar syndrome, hyperthyroidism […] Conjugated hyperbilirubinemia […] Hepatocellular dysfunction […] Common: Drugs, toxins, viral hepatitis

• #2 Obstructive Jaundice | Center for Advanced Digestive Care – NewYork-Presbyterian/Weill Cornell Medical Center

  https://www.nyp.org/cadc/liver-diseases-and-transplantation/obstructive-jaundice

  Jaundice is a yellow color of the skin, mucus membranes, or eyes. The yellow coloring comes from bilirubin, a byproduct of old red blood cells. Obstructive jaundice is a specific type of jaundice, where symptoms develop due to a narrowed or blocked bile duct or pancreatic duct, preventing the normal drainage of bile from the bloodstream into the intestines. […] Obstructive jaundice may be due to a number of causes, all of which narrow or block the bile ducts in some way: Gallstones, Pancreatic cancer, when it occurs near the tube connecting the pancreas to the intestines, Swelling of lymph glands near the bile duct, Pancreatic cysts, Other pancreatic duct obstructions such as scarring. […] The treatment of obstructive jaundice depends on its cause. Clogged or narrowed bile or pancreatic ducts may be relieved by inserting a stent using ERCP.

• #2 Jaundice and cholestasis – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/jaundice-and-cholestasis/

  Jaundice is due to an elevated level of serum bilirubin, which may be caused by prehepatic, intrahepatic, or posthepatic defects. […] Serum bilirubin concentration depends on the rate of formation and hepatobiliary elimination of bilirubin. […] Any pathology that impairs the process could increase serum bilirubin level: See Unconjugated hyperbilirubinemia and Conjugated hyperbilirubinemia for details. […] Jaundice can be divided into prehepatic, intrahepatic, and posthepatic etiologies. […] Prehepatic jaundice is caused by the accumulation of unconjugated bilirubin, which is due to either increased hemoglobin breakdown or impaired hepatic uptake. […] Intrahepatic jaundice may be caused by intrahepatic cholestasis, impaired bilirubin conjugation, or impaired excretion of bilirubin by the liver.

• #2 Neonatal jaundice – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/neonatal-jaundice/

  Neonatal jaundice is one of the most common conditions occurring in newborn infants and is characterized by elevated levels of bilirubin in the blood (total serum bilirubin concentration 5 mg/dL or 85.5 mol/L). […] The most common cause of neonatal jaundice is a physiological rise in unconjugated bilirubin, which results from hemolysis of fetal hemoglobin and an immature hepatic metabolism of bilirubin. […] Pathologic neonatal jaundice can be conjugated or unconjugated and is typically a symptom of an underlying disease. […] Hyperbilirubinemia can cause drowsiness and poor feeding in the newborn, and in severe cases, unconjugated bilirubin can cross the blood-brain barrier and cause permanent neurological damage (kernicterus). […] Pathological neonatal jaundice can be caused by multiple mechanisms: increased production of bilirubin (e.g., conditions with increased hemolysis), decreased hepatic uptake (e.g., due to liver immaturity), decreased conjugation (e.g., Crigler-Najjar syndrome), impaired excretion (e.g., conditions with cholestasis, gastrourinary malformations), and increased enterohepatic circulation (e.g., conditions with decreased intestinal motility, breastfeeding jaundice).

• #2 Inborn Metabolic Disorders Causing Hyperbilirubinemia – Hepatic and Biliary Disorders – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/hepatic-and-biliary-disorders/approach-to-the-patient-with-liver-disease/inborn-metabolic-disorders-causing-hyperbilirubinemia

  Hereditary or inborn metabolic disorders may cause unconjugated or conjugated hyperbilirubinemia (see Overview of bilirubin metabolism). […] This rare inherited liver disorder is caused by deficiency of the enzyme glucuronyl transferase (UGT1A1), which catalyzes the conjugation of bilirubin (mainly to bilirubin diglucuronide) to render bilirubin water soluble. […] Pathogenesis may involve complex defects in the livers uptake of bilirubin. Glucuronyl transferase activity is low, though not as low as in Crigler-Najjar syndrome type II. […] This rare, familial, benign condition is characterized by overproduction of early-labeled bilirubin (bilirubin derived from ineffective erythropoiesis and nonhemoglobin heme rather than from normal red blood cell turnover).

• #2 Neonatal Hyperbilirubinemia – Pediatrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pediatrics/metabolic-electrolyte-and-toxic-disorders-in-neonates/neonatal-hyperbilirubinemia

  Normally, bilirubin bound to serum albumin stays in the intravascular space. However, unconjugated bilirubin can cross the blood-brain barrier and cause CBE in certain situations: When serum bilirubin concentration is markedly elevated, When serum albumin concentration is markedly low (eg, in preterm infants), When bilirubin is displaced from albumin by competitive binders. […] Hyperbilirubinemia can be caused by one or more of the following processes: Increased production, Decreased hepatic uptake, Decreased conjugation, Impaired excretion, Impaired bile flow (cholestasis), Increased enterohepatic circulation. […] The majority of bilirubin is produced from the breakdown of hemoglobin into unconjugated bilirubin (and other substances). Unconjugated bilirubin binds to albumin in the blood for transport to the liver, where it is taken up by hepatocytes and conjugated with glucuronic acid by the enzyme uridine diphosphogluconurate glucuronosyltransferase (UGT) to make it water-soluble. The conjugated bilirubin is excreted in bile into the duodenum.

• #2 Jaundice and cholestasis – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/jaundice-and-cholestasis/

  Posthepatic jaundice is caused by the accumulation of conjugated hyperbilirubinemia usually due to extrahepatic cholestasis from biliary obstruction. […] Hepatitis and cirrhosis can cause both conjugated and unconjugated hyperbilirubinemia. […] Cholestasis: impaired production, secretion, or outflow of bile. […] Varying degrees of jaundice and elevations of cholestatic enzymes (including ALP, GGT, and direct bilirubin) are seen in conditions that cause conjugated hyperbilirubinemia due to cholestasis.

• #2 Table: Mechanisms and Some Causes of Jaundice in Adults-MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/multimedia/table/mechanisms-and-some-causes-of-jaundice-in-adults

  Less common: Alcohol-related liver disease, hemochromatosis, primary biliary cholangitis, primary sclerosing cholangitis, steatohepatitis, Wilson disease […] Aminotransferase levels usually 500 U/L (8.35 microkat/L) […] Intrahepatic cholestasis […] Common: Alcohol-related liver disease, drugs, toxins, viral hepatitis […] Less common: Infiltrative disorders (eg, amyloidosis, lymphoma, sarcoidosis, tuberculosis), pregnancy, primary biliary cholangitis, steatohepatitis […] Gradual onset of jaundice, sometimes pruritus […] If severe, clay-colored stools, steatorrhea […] If long-standing, weight loss […] Alkaline phosphatase and GGT usually 3 times normal […] Aminotransferase levels 200 U/L (3.34 microkat/L) […] Extrahepatic cholestasis […] Common: Common bile duct stone, pancreatic cancer

• #2 Obstructive Jaundice

  https://jsms.sch.ac.kr/journal/view.php?doi=10.15746/sms.22.018

  Jaundice is a medical condition in which the skin or sclera of the eyes becomes yellow, and elevation of bilirubin production or obstruction of bile excretion can cause jaundice while disrupting the balance between bilirubin production and bile excretion. […] Jaundice is always a pathological sign so that it should never be ignored. […] If jaundice occurs because of obstruction of bile flow after bile is produced, it is essentially obstructive jaundice. […] In other words, obstruction at the level of the common bile duct causes backflow of bile into the liver, as well as into the blood stream, thereby causing jaundice. […] Jaundice itself warrants further investigation as it is always a pathological sign. […] By being aware of this simple yet important clinical sign, a numerous hepatobiliary and pancreatic diseases can be diagnosed early for benefiting patients through appropriate and prompt treatment.

• #2 Table: Mechanisms and Some Causes of Jaundice in Adults-MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/multimedia/table/mechanisms-and-some-causes-of-jaundice-in-adults

  Less common: Acute cholangitis, pancreatic pseudocyst, primary sclerosing cholangitis, common duct strictures caused by previous surgery, other tumors […] Depending on cause, manifestations possibly similar to those of intrahepatic cholestasis or a more acute disorder (eg, abdominal pain or vomiting due to a common bile duct stone or acute pancreatitis) […] Alkaline phosphatase and GGT usually 3 times normal […] Aminotransferase levels 200 U/L (3.34 microkat/L) […] Other, less common mechanisms […] Hereditary disorders (mainly Dubin-Johnson syndrome and Rotor syndrome) […] Normal liver enzymes […] Bilirubin is present in urine.

• #2 British Journal Of Midwifery – Bilirubin in the newborn: Physiology and pathophysiology

  https://www.britishjournalofmidwifery.com/content/clinical-practice/bilirubin-in-the-newborn-physiology-and-pathophysiology/

  Physiological jaundice is common in the first week of life, occurring in around 60% of term and 80% of preterm infants (Ng and How, 2015; Mitra and Rennie, 2017). […] It is the result of rising levels of bilirubin, which eventually binds to tissues such as the skin and sclera, producing clinically recognisable jaundice around day 3 or 4 (Mitra and Rennie, 2017; Rankin, 2017). […] Bilirubin is produced during the breakdown of red blood cells, and in newborn infants there is a transitional imbalance between its production and elimination, resulting in an excess of bilirubin. […] This normal imbalance that produces physiological jaundice can, however, be exacerbated by factors that result in pathological jaundice, which can result in neurological damage, dysfunction, and death (Ng and How, 2015).

• #2 CASE STUDY INVESTIGATION | The Effect of Neonatal Jaundice on Infants’ Auditory Mechanism in Nigeria – American Academy of Audiology

  https://www.audiology.org/news-and-publications/audiology-today/articles/case-study-investigation-the-effect-of-neonatal-jaundice-on-infants-auditory-mechanism-in-nigeria/

  Jaundice in infants is caused by the accumulation of unconjugated bilirubin. This normally reflects as the yellow coloration of the skin and sclera in newborns. Unconjugated bilirubin is neurotoxic and can lead to death in newborns or lifelong neurologic sequelae. […] Hepatic excretory capacity is low both because of low concentrations of the binding protein ligandin in the hepatocytes and because of low activity of glucuronyl transferase, the enzyme responsible for binding bilirubin to glucuronic acid, thus making bilirubin water soluble (conjugation).

• #2 Breastfeeding Jaundice and Breast Milk Jaundice

  https://www.birthinjuryhelpcenter.org/birth-injuries/help-center/jaundice-breastfeeding/

  Breastfeeding jaundice usually occurs in the first week of life while the baby and mother are in the early stages of learning how to breastfeed. […] Breast milk jaundice occurs when certain substances in the mother’s milk may slow down the breakdown of bilirubin in the baby’s body. […] The cause of breast milk jaundice is currently unknown, but doctors believe it is linked to some type of substance in the breast milk that inhibits the liver’s ability to break down and process bilirubin. […] Breast milk by itself actually does not cause jaundice. Infant jaundice is caused by elevated bilirubin levels in the blood which is the result of various factors after birth. […] However, breast milk can potentially make infant jaundice worse or last longer. […] If jaundice develops into kernicterus it can seriously and permanently damage a baby’s brain.

• #2 Jaundice and Breastfeeding | Breastfeeding special circumstances | CDC

  https://www.cdc.gov/breastfeeding-special-circumstances/hcp/illnesses-conditions/jaundice.html

  Jaundice (yellow discoloration of a baby’s skin and eyes) is a sign of elevated bilirubin levels. […] Bilirubin is a product from the normal breakdown of red blood cells. It is elevated in newborns because they: […] Have immature liver function, leading to a slower metabolism of bilirubin. […] In most newborns, jaundice is termed „physiologic jaundice” and is considered harmless. […] The exact mechanism leading to breast milk jaundice is unknown. Some believe that substances in the mother’s milk may inhibit the ability of the infant’s liver to process bilirubin. […] More frequent breastfeeding can improve the mother’s milk supply. This can also improve the infant’s caloric intake and hydration, thus reducing elevated bilirubin. […] Ongoing clinical assessment, including repeat bilirubin level measurements, will help determine when breastfeeding can resume. […] Jaundice is a possible reason to supplement healthy, term infants with additional feedings.

• #2 Neonatal Jaundice: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/974786-overview

  Thus, some interindividual variations in the course and severity of neonatal jaundice may be explained genetically. […] Once excreted into bile and transferred to the intestines, bilirubin is eventually reduced to colorless tetrapyrroles by microbes in the colon. However, some deconjugation occurs in the proximal small intestine through the action of B-glucuronidases located in the brush border. […] Neonatal jaundice, although a normal transitional phenomenon in most infants, can occasionally become more pronounced. Blood group incompatibilities (eg, Rh, ABO) may increase bilirubin production through increased hemolysis. […] Nonimmune hemolytic disorders (spherocytosis, G-6-PD deficiency) may also cause increased jaundice, and increased hemolysis appears to have been present in some of the infants reported to have developed kernicterus in the United States in the past 15-20 years. […] These discoveries also highlight the challenges involved in the common use of the terms „physiologic jaundice” and „pathologic jaundice.” […] Although physiologic jaundice is a helpful concept from a didactic perspective, applying it to an actual neonate with jaundice is more difficult.

• #2 Phototherapy for neonatal jaundice

  https://www.rch.org.au/rchcpg/hospital_clinical_guideline_index/phototherapy_for_neonatal_jaundice/

  Unconjugated bilirubin can cross the blood-brain barrier and cause neurotoxic effects. […] Kernicterus: the pathogenic diagnosis characterised by bilirubin staining of the brain stem and cerebellum. Also the term used to refer to chronic bilirubin encephalopathy. Clinical findings include cerebral palsy, developmental and intellectual delay, hearing deficit, dental dysplasia and oculomotor disturbances. […] Commence phototherapy once SBR is greater than the appropriate reference range for neonates gestation/weight and presence of risk factors. […] Ensure that phototherapy unit is turned off during collection of blood for SBR levels, as both conjugated and unconjugated bilirubin are photo-oxidized when exposed to white or ultraviolet light.

• #2 Hyperbilirubinemia in the Term Newborn | AAFP

  https://www.aafp.org/pubs/afp/issues/2002/0215/p599.html

  Jaundice typically results from the deposition of unconjugated bilirubin pigment in the skin and mucus membranes. […] Unconjugated hyperbilirubinemia, the primary focus of this article, is the most common form of jaundice encountered by family physicians. […] The causes of neonatal hyperbilirubinemia can be classified into three groups based on mechanism of accumulation: bilirubin overproduction, decreased bilirubin conjugation, and impaired bilirubin excretion. […] Kernicterus refers to the neurologic consequences of the deposition of unconjugated bilirubin in brain tissue. Subsequent damage and scarring of the basal ganglia and brainstem nuclei may occur. […] The precise role of bilirubin in the development of kernicterus is not completely understood. If the serum unconjugated bilirubin level exceeds the binding capacity of albumin, unbound lipid-soluble bilirubin crosses the blood-brain barrier.

• #2 Infant jaundice – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/infant-jaundice/symptoms-causes/syc-20373865

  Infant jaundice occurs because the baby’s blood contains an excess of bilirubin (bil-ih-ROO-bin), a yellow pigment of red blood cells. […] Excess bilirubin (hyperbilirubinemia) is the main cause of jaundice. Bilirubin, which is responsible for the yellow color of jaundice, is a normal part of the pigment released from the breakdown of „used” red blood cells. […] A newborn’s immature liver often can’t remove bilirubin quickly enough, causing an excess of bilirubin. Jaundice due to these normal newborn conditions is called physiologic jaundice, and it typically appears on the second or third day of life. […] An underlying disorder may cause infant jaundice. In these cases, jaundice often appears much earlier or much later than does the more common form of infant jaundice. […] High levels of bilirubin that cause severe jaundice can result in serious complications if not treated. […] If a baby has severe jaundice, there’s a risk of bilirubin passing into the brain, a condition called acute bilirubin encephalopathy.

• #2 Mechanical Jaundice of Calculous Etiology: Pathogenesis, Complications and Therapeutic Tactics

  http://article.sapub.org/10.5923.j.ajmms.20241409.37.html

  In the pathogenesis of liver dysfunction, damage to subcellular structures that are extremely sensitive to hypoxia occupies a leading place. […] Mechanical jaundice and liver failure are integral parts of a single process that develops independently of the etiology of biliary tract obstruction. […] The large role of endogenous intoxication in the pathogenesis of mechanical jaundice of non-tumor etiology determines the importance of timely intensive complex therapy that can prevent the development of irreversible disorders of the structure and function of many organs and systems and contribute to the processes of repair and adaptation.

• #2 Hyperbilirubinemia and Neonatal Infection

  https://jpp.mums.ac.ir/article_2026.html

  The aim of this study was to determine the incidence rate, symptoms, and age at presentation, predisposing factors, characteristics, the severity of jaundice associated with infection and complications and the etiology of infection among neonates with hyperbilirubinemia in the first month- of life. […] Neonatal infection was found in approximately 10% of jaundiced newborns. The most common infection associated with neonatal jaundice was UTI (77.9%), Sepsis (16.8%) and pneumonia (5.3%), in order. […] The mechanism of jaundice in neonatal pneumonia is not well known. This partially may be related to the congestion of liver affected by pneumonia. Mean bilirubin value was significantly higher in sepsis subgroup as compared with noninfectious subjects (23.8 mg/dl versus 21.2 mg/dl). The mechanism of jaundice in neonatal sepsis maybe related to liver involvement by infection or hemolysis, although this mechanism is not well known. Conjugated hyperbilirubinemia can be associated with cholestasis secondary to bacterial infection. The mechanism in which infection causes cholestasis is not clear, but possible mechanisms include microcirculatory changes in the liver, direct effects from bacterial products, and/or from endotoxin-induced mediators (13,14). […] We concluded that bacterial infection was a significant cause of unexplained Hyperbilirubinemia among jaundice neonates. Our results indicate that urinary tract infections after and sepsis before the first week of life may be associated with jaundice.

• #2 Neonatal jaundice is associated with increased risks of congenital anomalies of the kidney and urinary tract and concomitant urinary tract infection | Scientific Reports

  https://www.nature.com/articles/s41598-024-59943-2

  This suggests that dehydration or hypohydration, potentially secondary to jaundice, could be a risk factor for UTIs in neonates. […] Our study demonstrated an increased risk of CAKUT, an important predisposing factor of UTI, in jaundiced infants in comparison to non-jaundiced infants and may provide indirect evidence that contributes to elucidating the potential correlation between neonatal jaundice and UTI. […] While our study identifies a significant association between neonatal jaundice and increased risks of UTI in the context of CAKUT, it is important to emphasize that not all cases of CAKUT lead to UTIs. […] The implications of these findings may provide essential insights for clinicians to identify potential cases of UTI among infants with neonatal jaundice. […] Infants with neonatal jaundice were associated with elevated risks of concomitant UTI during hospitalization and CAKUT in early childhood.

• #2 Phototherapy for Jaundice: Background, Indications, Contraindications

  https://emedicine.medscape.com/article/1894477-overview

  Jaundice refers to the yellow appearance of the skin that occurs with the deposition of bilirubin in the dermal and subcutaneous tissue. Normally in the body, bilirubin is processed through the liver, where it is conjugated to glucuronic acid by the enzyme uridine diphosphate glucuronyl transferase (UGT) 1A1. This conjugated form of bilirubin is then excreted into the bile and removed from the body via the gut. When this excretion process is low following birth, does not work efficiently, or is overwhelmed by the amount of endogenously produced bilirubin, the amount of bilirubin in the body increases, resulting in hyperbilirubinemia and jaundice. […] At its most basic, phototherapy refers to the use of light to convert bilirubin molecules in the body into water soluble isomers that can be excreted by the body. The absorption of light by normal bilirubin (4Z,15Z-bilirubin) results in the creation of 2 isomeric forms of bilirubin: structural isomers and configurational isomers. The main structural isomer of bilirubin is Z-lumirubin. The main configurational isomer of bilirubin is 4Z,15 E -bilirubin. Configurational isomerization is reversible, and structural isomerization is irreversible. Both the configurational and structural isomers of bilirubin are less lipophilic than normal bilirubin and can be excreted into bile without undergoing glucuronidation in the liver. Some of the configurational isomers of bilirubin, however, revert back to the native form after excretion into bile and can be reabsorbed via enterohepatic circulation in the gut. Structural bilirubin isomers, like Z-lumirubin, can also be excreted in the urine.

• #2 Phototherapy for Jaundice: Background, Indications, Contraindications

  https://emedicine.medscape.com/article/1894477-overview

  The absorptions of light by bilirubin also results in the generation of excited-state bilirubin molecules that react with oxygen to produce colorless oxidation products, or photooxidation products. This process occurs more slowly than configurational or structural isomerization. Photooxidation products are primarily excreted in the urine. […] Mechanism of phototherapy: Blue-green light in the range of 460-490 nm is most effective for phototherapy. The absorption of light by the normal bilirubin (4Z,15Z-bilirubin) generates configuration isomers, structural isomers, and photooxidation products. The 2 principal photoisomers formed in humans are shown. Configurational isomerization is reversible and much faster than structural isomerization. Structural isomerization is slow and irreversible. Photooxidation occurs more slowly than both configurational and structural isomerization. Photooxidation products are excreted mainly in urine.

• #2 Mechanism of bilirubin elimination in urine: insights and prospects for neonatal jaundice

  https://www.degruyterbrill.com/document/doi/10.1515/cclm-2020-1759/html?lang=en&srsltid=AfmBOopZqj7NR-iysdFZK00RmwpP93S6yk2IYqgZ-Div19tPQTx5yfJU

  Despite a century of research, bilirubin metabolism and the transport mechanisms responsible for homeostasis of bilirubin in serum remain controversial. […] Emerging evidence on the hepatic membrane transporters and inherited disorders of bilirubin metabolism have contributed to a greater understanding of the various steps involved in bilirubin homeostasis and its associated excretory pathways. […] New insights gained speculate that a proportion of conjugated bilirubin is excreted via the renal system, as an alternative to the intestinal excretion, even in normal physiological jaundice with no associated pathological concerns. […] Finally, this paper discusses the clinical relevance of targeting the altered renal excretory pathway, as bilirubin in urine may hold diagnostic importance in screening for neonatal jaundice.

• #2 Jaundice – Signs and Symptoms – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.I.1.41.

  Jaundice (icterus) is yellow or yellowish coloration of the sclera, mucous membranes, and skin caused by the accumulation of bilirubin in tissues. […] Excess heme degradation, disruption to bile flow, or disruption of any step in the bile metabolism may result in hyperbilirubinemia (predominantly unconjugated or conjugated hyperbilirubinemia, depending on etiology) and clinically manifest as jaundice. […] Predominately unconjugated (indirect) hyperbilirubinemia is usually due to excess hemoglobin destruction or its compromised stability and survival. […] Predominately conjugated (direct) hyperbilirubinemia or mixed hyperbilirubinemia is usually due to cholestasis (obstructive jaundice), destruction of hepatocytes, or both.

• #2 Etiopathogenesis of jaundice | PPT

  https://www.slideshare.net/slideshow/etiopathogenesis-of-jaundice/250032915

  Jaundice is a condition of high bilirubin in the blood and is not a disease itself. It is divided into three types based on cause: pre-hepatic, hepatic, and post-hepatic jaundice. Pre-hepatic jaundice results from hemolysis and leads to increased unconjugated bilirubin. […] Hepatic jaundice is caused by liver dysfunction from infections, alcohol, or cirrhosis, increasing both conjugated and unconjugated bilirubin. Post-hepatic jaundice occurs when bile cannot flow from the liver to gut, such as from gallstones or pancreatitis, raising conjugated bilirubin levels. […] Jaundice is not a disease but a condition of hyperbilirubinemia (increased bilirubin in blood) due to varied pathologies. […] Based on the cause, jaundice is divided into three types: 1) Pre-hepatic jaundice 2) Hepatic jaundice 3) Post-hepatic jaundice.

• #3 Jaundice – Hepatic and Biliary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/approach-to-the-patient-with-liver-disease/jaundice

  Most bilirubin is produced when hemoglobin (Hb) is broken down into unconjugated bilirubin (and other substances). Unconjugated bilirubin binds to albumin in the blood for transport to the liver, where it is taken up by hepatocytes and conjugated with glucuronic acid to make it water soluble. Conjugated bilirubin is excreted in bile into the duodenum. In the intestine, bacteria metabolize bilirubin to form urobilinogen. Some urobilinogen is eliminated in the feces, and some is reabsorbed, extracted by hepatocytes, reprocessed, and re-excreted in bile (enterohepatic circulationsee Overview of Bilirubin Metabolism). […] Hyperbilirubinemia may involve predominantly unconjugated or conjugated bilirubin. […] Unconjugated hyperbilirubinemia is most often caused by 1 of the following: Increased production, Decreased hepatic uptake, Decreased conjugation.

• #3 Table: Mechanisms and Some Causes of Jaundice in Adults-MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/multimedia/table/mechanisms-and-some-causes-of-jaundice-in-adults

  Less common: Alcohol-related liver disease, hemochromatosis, primary biliary cholangitis, primary sclerosing cholangitis, steatohepatitis, Wilson disease […] Aminotransferase levels usually 500 U/L (8.35 microkat/L) […] Intrahepatic cholestasis […] Common: Alcohol-related liver disease, drugs, toxins, viral hepatitis […] Less common: Infiltrative disorders (eg, amyloidosis, lymphoma, sarcoidosis, tuberculosis), pregnancy, primary biliary cholangitis, steatohepatitis […] Gradual onset of jaundice, sometimes pruritus […] If severe, clay-colored stools, steatorrhea […] If long-standing, weight loss […] Alkaline phosphatase and GGT usually 3 times normal […] Aminotransferase levels 200 U/L (3.34 microkat/L) […] Extrahepatic cholestasis […] Common: Common bile duct stone, pancreatic cancer

• #3 Hyperbilirubinemia and Neonatal Infection

  https://jpp.mums.ac.ir/article_2026.html

  The aim of this study was to determine the incidence rate, symptoms, and age at presentation, predisposing factors, characteristics, the severity of jaundice associated with infection and complications and the etiology of infection among neonates with hyperbilirubinemia in the first month- of life. […] Neonatal infection was found in approximately 10% of jaundiced newborns. The most common infection associated with neonatal jaundice was UTI (77.9%), Sepsis (16.8%) and pneumonia (5.3%), in order. […] The mechanism of jaundice in neonatal pneumonia is not well known. This partially may be related to the congestion of liver affected by pneumonia. Mean bilirubin value was significantly higher in sepsis subgroup as compared with noninfectious subjects (23.8 mg/dl versus 21.2 mg/dl). The mechanism of jaundice in neonatal sepsis maybe related to liver involvement by infection or hemolysis, although this mechanism is not well known. Conjugated hyperbilirubinemia can be associated with cholestasis secondary to bacterial infection. The mechanism in which infection causes cholestasis is not clear, but possible mechanisms include microcirculatory changes in the liver, direct effects from bacterial products, and/or from endotoxin-induced mediators (13,14). […] We concluded that bacterial infection was a significant cause of unexplained Hyperbilirubinemia among jaundice neonates. Our results indicate that urinary tract infections after and sepsis before the first week of life may be associated with jaundice.

• #3 Mechanism of bilirubin elimination in urine: insights and prospects for neonatal jaundice

  https://www.degruyterbrill.com/document/doi/10.1515/cclm-2020-1759/html?lang=en&srsltid=AfmBOopZqj7NR-iysdFZK00RmwpP93S6yk2IYqgZ-Div19tPQTx5yfJU

  Despite a century of research, bilirubin metabolism and the transport mechanisms responsible for homeostasis of bilirubin in serum remain controversial. […] Emerging evidence on the hepatic membrane transporters and inherited disorders of bilirubin metabolism have contributed to a greater understanding of the various steps involved in bilirubin homeostasis and its associated excretory pathways. […] New insights gained speculate that a proportion of conjugated bilirubin is excreted via the renal system, as an alternative to the intestinal excretion, even in normal physiological jaundice with no associated pathological concerns. […] Finally, this paper discusses the clinical relevance of targeting the altered renal excretory pathway, as bilirubin in urine may hold diagnostic importance in screening for neonatal jaundice.

• #4 Mechanism of bilirubin elimination in urine: insights and prospects for neonatal jaundice

  https://www.degruyterbrill.com/document/doi/10.1515/cclm-2020-1759/html?lang=en&srsltid=AfmBOopZqj7NR-iysdFZK00RmwpP93S6yk2IYqgZ-Div19tPQTx5yfJU

  Despite a century of research, bilirubin metabolism and the transport mechanisms responsible for homeostasis of bilirubin in serum remain controversial. […] Emerging evidence on the hepatic membrane transporters and inherited disorders of bilirubin metabolism have contributed to a greater understanding of the various steps involved in bilirubin homeostasis and its associated excretory pathways. […] New insights gained speculate that a proportion of conjugated bilirubin is excreted via the renal system, as an alternative to the intestinal excretion, even in normal physiological jaundice with no associated pathological concerns. […] Finally, this paper discusses the clinical relevance of targeting the altered renal excretory pathway, as bilirubin in urine may hold diagnostic importance in screening for neonatal jaundice.

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