Jaundice, NOS Classification and external resources
Yellowing of the skin and sclera caused by Hepatitis A. The skin is the outer covering of living tissue of an animal (or plant The sclera, called the white or white of the eye, is the opaque (usually white though certain animals such as horses and lizards can have black sclera fibrous Hepatitis (plural hepatitides) implies injury to the Liver characterized by the presence of Inflammatory cells in the tissue of
ICD-10	R17.
ICD-9	782.4
DiseasesDB	7038
MedlinePlus	003243
MeSH	D007565

Jaundice, also known as icterus (attributive adjective: "icteric"), is yellowish discoloration of the skin, sclerae (whites of the eyes) and mucous membranes caused by hyperbilirubinemia (increased levels of bilirubin in the blood). The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings R00-R69 - Symptoms and Signs (R00-R09 Circulatory and Respiratory systems ( Abnormalities of Heart beat The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. MedlinePlus, with the MedlinePlus Medical Encyclopedia, is a website network containing Health information from the world's largest medical Library Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books The skin is the outer covering of living tissue of an animal (or plant The sclera, called the white or white of the eye, is the opaque (usually white though certain animals such as horses and lizards can have black sclera fibrous The mucous membranes (or mucosae; singular mucosa) are linings of mostly endodermal origin covered in Epithelium, which are involved in Bilirubin (formerly referred to as hematoidin) is the yellow breakdown product of normal Heme Catabolism. This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluids. Bilirubin (formerly referred to as hematoidin) is the yellow breakdown product of normal Heme Catabolism. Typically, the concentration of bilirubin in the plasma must exceed 1. Blood plasma is the Liquid component of Blood, in which the Blood cells are suspended 5 mg/dL^[1], three times the usual value of approximately 0. For other uses of the words gram or gramme see Gram (disambiguation. The litre or liter (see spelling differences) is a unit of Volume. 5mg/dL^[1], for the coloration to be easily visible. For other uses of the words gram or gramme see Gram (disambiguation. The litre or liter (see spelling differences) is a unit of Volume. Jaundice comes from the French word jaune, meaning yellow. French ( français,) is a Romance language spoken around the world by 118 million people as a native language and by about 180 to 260 million people

Contents 1 Normal Physiology 1.1 Pre-Hepatic events 1.2 Hepatic events 1.3 Post Hepatic events 2 Causes 2.1 Pre-hepatic 2.2 Hepatic 2.3 Post-hepatic 3 Laboratory Results 3.1 Laboratory Tests 4 Neonatal jaundice 5 Jaundiced eye 6 Hyperbilirubinemia 7 External links 8 See also 9 Footnotes

Normal Physiology

In order to understand how jaundice results, it is important to understand where the pathological processes that cause jaundice take their effect. It is also important to further recognize that jaundice itself is not a disease, but rather a symptom of an underlying pathological process that occurs at some point along the normal physiological pathway of the metabolism of bilirubin.

Pre-Hepatic events

When red blood cells have completed their life span of approximately 120 days, their membranes become fragile and prone to rupture. Red blood cells are the most common type of Blood cell and the Vertebrate body's principal means of delivering Oxygen to the body tissues via the Blood As the cell traverses through the reticuloendothelial system, their cell membranes rupture and the contents of the red blood cell is released into the blood. The reticuloendothelial system ( RES) part of the Immune system, consists of the phagocytic cells located in Reticular connective tissue, primarily The component of the red blood cell that is involved in jaundice is hemoglobin. Hemoglobin ( also spelled haemoglobin and abbreviated Hb or Hgb) is the Iron -containing Oxygen -transport Metalloprotein The hemoglobin released into the blood is phagocytosed by macrophages, and split into its heme and globin portions. Macrophages ( Greek: "big eaters" from makros "large" + phagein "eat" ( Mø) are cells within the tissues that A heme ( American English) or haem ( British English) is a Prosthetic group that consists of an Iron atom contained in the center of Globular proteins, or spheroproteins are one of the two main Protein classes comprising "globe" -like proteins that are more or less soluble in The globin portion, being protein, is degraded into amino acids and plays no further role in jaundice. Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this Two reactions then take place to the heme molecule. The first reaction is the oxidation of heme to form biliverdin. Redox (shorthand for reduction-oxidation reaction describes all Chemical reactions in which atoms have their Oxidation number ( Oxidation state Biliverdin is a green Pigment formed as a byproduct of Heme breakdown This reaction is catalyzed by microsomal enzyme heme oxygenase and it results in biliverdin (green color pigment), iron and carbon monoxide. Next step is reduction of biliverdin to yellow color tetrapyrol pigment bilirubin by cytosolic enzyme biliverdin reductase. This bilirubin is known as "unconjugated", "free" or "indirect" bilirubin. Approximately 4 mg per kg of bilirubin is produced each day. ^[2] The majority of this bilirubin comes from the breakdown of heme from expired red blood cells in the process just described. However approximately 20 per cent comes from other heme sources, including ineffective erythropoiesis, breakdown of other heme protrins such as muscle myoglobin and cytochrome enzymes. ^[2]

Hepatic events

The unconjugated bilirubin then travels to the liver through the bloodstream. The liver is a vital organ in the human body and is present in Vertebrates and some other animals Because this bilirubin is not soluble, however, it is transported through the blood bound to serum albumin. Serum albumin, often referred to simply as albumin, is the most abundant Plasma protein in humans and other Mammals Albumin is essential for maintaining Once it arrives at the liver, it is conjugated with glucuronic acid (to form bilirubin diglucuronide, or just "conjugated bilirubin") to become more water soluble. Glucuronic acid (from Greek γλυκερός - "sweet" is a Carboxylic acid. The reaction is catalyzed by the enzyme UDP-glucuronide transferase.

Post Hepatic events

This conjugated bilirubin is excreted from the liver into the biliary and cystic ducts as part of bile. Bile or gall is a bitter yellow or green Alkaline fluid secreted by Hepatocytes from the Liver of most Vertebrates In many species Intestinal bacteria convert the bilirubin into urobilinogen. Urobilinogen is a colourless product of Bilirubin reduction It is formed in the intestines by Bacterial action From here the urobilinogen can take two pathways. It can either be further converted into stercobilinogen, which is then oxidized to stercobilin and passed out in the faeces, or it can be reabsorbed by the intestinal cells, transported in the blood to the kidneys, and passed out in the urine as the oxidised product urobilin. Stercobilinogen is a precursor of Stercobilin.Bilirubin is pigment which results from the breakdown of the heme moiety of hemoglobin Redox (shorthand for reduction-oxidation reaction describes all Chemical reactions in which atoms have their Oxidation number ( Oxidation state Stercobilin is a Tetrapyrrole chemical compound responsible for the typical brown color of human Feces. Feces, faeces, or fæces (see spelling differences) is a waste product from an animal's digestive tract expelled through the Anus The kidneys are complicated organs that have numerous biological roles Urine is a liquid waste product of the body secreted by the Kidneys by a process of filtration from Blood and Excreted through the Urethra. Urobilin is a yellow linear tetrapyrrole resulting from the breakdown of Haem, a cyclic tetrapyrrole Stercobilin and urobilin are the products responsible for the coloration of faeces and urine, respectively.

Causes

When a pathological process interferes with the normal functioning of the metabolism and excretion of bilirubin just described, jaundice may be the result. Jaundice is classified into three categories, depending on which part of the physiological mechanism the pathology affects. The three categories are:

• Pre-hepatic: The pathology is occurring prior the liver
• Hepatic: The pathology is located within the liver
• Post-Hepatic: The pathology is located after the conjugation of bilirubin in the liver

Pre-hepatic

Pre-hepatic jaundice is caused by anything which causes an increased rate of hemolysis (breakdown of red blood cells). Hemolysis (or haemolysis)—from the Greek Hemo-, Greek meaning blood - Lysis, meaning to break open—is the breaking Red blood cells are the most common type of Blood cell and the Vertebrate body's principal means of delivering Oxygen to the body tissues via the Blood In tropical countries, malaria can cause jaundice in this manner. Malaria is a vector -borne Infectious disease caused by Protozoan Parasites It is widespread in tropical and subtropical regions including Certain genetic diseases, such as sickle cell anemia, spherocytosis and glucose 6-phosphate dehydrogenase deficiency can lead to increased red cell lysis and therefore hemolytic jaundice. A genetic disorder is a condition caused by abnormalities in Genes or Chromosomes While some diseases such as Cancer, are due to genetic abnormalities acquired Sickle-cell disease or sickle-cell anaemia (or anemia) is a Blood disorder characterized by Red blood cells that assume an abnormal rigid Spherocytosis is an auto- hemolytic Anemia (a disease of the blood) characterized by the production of Red blood cells (RBCs or erythrocytes Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive Hereditary disease characterised by abnormally low levels of Glucose-6-phosphate Commonly, diseases of the kidney, such as hemolytic uremic syndrome, can also lead to coloration. In Medicine, hemolytic-uremic syndrome (or haemolytic-uraemic syndrome, abbreviated HUS is a disease characterized by Microangiopathic hemolytic anemia Defects in bilirubin metabolism also present as jaundice. Bilirubin (formerly referred to as hematoidin) is the yellow breakdown product of normal Heme Catabolism. Jaundice usually comes with high fevers.

Laboratory findings include:

• Urine: no bilirubin present, urobilirubin > 2 units (except in infants where gut flora has not developed). The gut flora are the Microorganisms that normally live in the Digestive tract and can perform a number of useful functions for their hosts
• Serum: increased unconjugated bilirubin.

Hepatic

Hepatic jaundice causes include acute hepatitis, hepatotoxicity and alcoholic liver disease, whereby cell necrosis reduces the liver's ability to metabolise and excrete bilirubin leading to a buildup in the blood. Hepatitis (plural hepatitides) implies injury to the Liver characterized by the presence of Inflammatory cells in the tissue of Drug metabolism in liver The human body identifies almost all drugs as foreign substances (i Alcoholic liver disease is the major cause of Liver disease in Western countries (in Asian countries viral Hepatitis is the major cause Bilirubin (formerly referred to as hematoidin) is the yellow breakdown product of normal Heme Catabolism. Less common causes include primary biliary cirrhosis, Gilbert's syndrome (a genetic disorder of bilirubin metabolism which can result in mild jaundice, which is found in about 5% of the population), Crigler-Najjar syndrome and metastatic carcinoma. Primary biliary cirrhosis is an Autoimmune disease of the Liver marked by the slow progressive destruction of the small bile ducts ( Bile canaliculi) within Gilbert's syndrome, often shortened to the acronym GS, is the most common Hereditary cause of increased Bilirubin, and is found in up to 5% of the population Crigler-Najjar Syndrome or CNS is a rare disorder affecting the Metabolism of Bilirubin, a chemical formed from the breakdown of blood. Metastasis ( Greek: displacement μετά=next + στάσις=placement, plural metastases) sometimes abbreviated mets, A carcinoma is any Malignant Cancer that arises from epithelial cells. Jaundice seen in the newborn, known as neonatal jaundice, is common, occurring in almost every newborn as hepatic machinery for the conjugation and excretion of bilirubin does not fully mature until approximately two weeks of age. The liver is a vital organ in the human body and is present in Vertebrates and some other animals

Laboratory Findings include:

• Urine: Conjugated bilirubin present, Urobilirubin > 2 units but variable (Except in children)

Post-hepatic

Post-hepatic jaundice, also called obstructive jaundice, is caused by an interruption to the drainage of bile in the biliary system. Bile or gall is a bitter yellow or green Alkaline fluid secreted by Hepatocytes from the Liver of most Vertebrates In many species The most common causes are gallstones in the common bile duct, and pancreatic cancer in the head of the pancreas. In Medicine, gallstones (choleliths are Crystalline bodies formed within the body by accretion or concretion of normal or abnormal Bile component Bile, which is synthesized in the liver is carried to the right and left hepatic ducts which converge along with the Cystic duct to form the Common hepatic duct. Pancreatic cancer is a malignant tumor of the Pancreas. Each year about 37680 individuals in the United States are diagnosed with this condition and 34290 The pancreas is a Gland organ in the digestive and Endocrine system of Vertebrates. Also, a group of parasites known as "liver flukes" live in the common bile duct, causing obstructive jaundice. Liver flukes are a Polyphyletic group of Trematodes (phylum Platyhelminthes) Other causes include strictures of the common bile duct, biliary atresia, ductal carcinoma, pancreatitis and pancreatic pseudocysts. Biliary atresia is a rare condition in newborn infants in which the common Bile duct between the Liver and the Small intestine is Pancreatitis is the Inflammation of the Pancreas. See also Acute pancreatitis and Chronic pancreatitis for more details A pancreatic pseudocyst is a circumscribed collection of fluid rich in Pancreatic enzymes Blood, and Necrotic tissue, typically located in the A rare cause of obstructive jaundice is Mirizzi's syndrome. Mirizzi's syndrome is a rare cause of acquired Jaundice. It is caused by chronic Cholecystitis and large Gallstones resulting in stenosis of the

The presence of pale stools and dark urine suggests an obstructive or post-hepatic cause as normal feces get their color from bile pigments. Bilins or bilanes are biological pigments formed in many organisms as a metabolic product of certain Porphyrins Bilin (also called bilichrome was named as a

Patients also can present with elevated serum cholesterol, and often complain of severe itching or "pruritus".

Laboratory Results

Laboratory Tests

	Pre-hepatic Jaundice	Hepatic Jaundice	Post-hepatic Jaundice
Total bilirubin	Normal / Increased	Increased	Increased
Conjugated bilirubin	Normal	Normal / Decreased	Increased
Unconjugated bilirubin	Increased	Normal / Increased	Normal
Urobilinogen	Increased	Normal / Increased	Decreased / Negative
Urine Colour	Normal	Dark	Dark
Stool colour	Normal	Normal	Pale

Neonatal jaundice

Main article: Neonatal jaundice

Neonatal jaundice is usually harmless: this condition is often seen in infants around the second day after birth, lasting until day 8 in normal births, or to around day 14 in premature births. Neonatal jaundice is a yellowing of the Skin and other tissues of a newborn Infant. Premature birth (also known as preterm birth) is the Birth of a Baby before the standard period of Pregnancy is completed Serum bilirubin normally drops to a low level without any intervention required: the jaundice is presumably a consequence of metabolic and physiological adjustments after birth. Bilirubin (formerly referred to as hematoidin) is the yellow breakdown product of normal Heme Catabolism. In extreme cases, a brain-damaging condition known as kernicterus can occur; there are concerns that this condition has been rising in recent years due to inadequate detection and treatment of neonatal hyperbilirubinemia. Kernicterus is damage to the brain centers of infants caused by increased levels of unconjugated-indirect Bilirubin which is free (not bound to albumin Neonatal jaundice is a risk factor for hearing loss. ^[3]

Jaundiced eye

It was once believed persons suffering from the medical condition jaundice saw everything as yellow. By extension, the jaundiced eye came to mean a prejudiced view, usually rather negative or critical. Alexander Pope, in 'An Essay on Criticism' (1711), wrote: "All seems infected that the infected spy, As all looks yellow to the jaundiced eye. Alexander Pope (21 May 1688 – 30 May 1744 is generally regarded as the greatest English Poet of the eighteenth century best known for his Satirical "^[4] Similarly in the mid 19th century the English poet Lord Alfred Tennyson wrote in the poem 'Locksley Hall': "So I triumphe'd ere my passion sweeping thro' me left me dry, left me with the palsied heart, and left me with a jaundiced eye. Alfred Tennyson 1st Baron Tennyson (6 August 1809 – 6 October 1892 was Poet Laureate of the United Kingdom and remains one of the most popular English poets "

Hyperbilirubinemia

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What is hyperbilirubinemia? Hyperbilirubinemia is a condition in which there is too much bilirubin in the blood. When red blood cells break down, a substance called bilirubin is formed. Babies are not easily able to get rid of the bilirubin and it can build up in the blood and other tissues and fluids of the baby's body. This is called hyperbilirubinemia. Because bilirubin has a pigment or coloring, it causes a yellowing of the baby's skin and tissues. This is called jaundice.

Depending on the cause of the hyperbilirubinemia, jaundice may appear at birth or at any time afterward.

What causes hyperbilirubinemia? During pregnancy, the placenta excretes bilirubin. When the baby is born, the baby's liver must take over this function. There are several causes of hyperbilirubinemia and jaundice, including the following:

Physiologic jaundice Physiologic jaundice occurs as a "normal" response to the baby's limited ability to excrete bilirubin in the first days of life.

Breast milk jaundice About 2 percent of breastfed babies develop jaundice after the first week. Some develop breast milk jaundice in the first week due to low calorie intake or dehydration.

Jaundice from hemolysis Jaundice may occur with the breakdown of red blood cells due to hemolytic disease of the newborn (Rh disease), having too many red blood cells, or bleeding.

Jaundice related to inadequate liver function Jaundice may be related to inadequate liver function due to infection or other factors. Who is affected by hyperbilirubinemia? About 60 percent of term newborns and 80 percent of premature babies develop jaundice. Infants of diabetic mothers and of mothers with Rh disease are more likely to develop hyperbilirubinemia and jaundice.

Why is hyperbilirubinemia a concern? Although low levels of bilirubin are not usually a concern, large amounts can circulate to tissues in the brain and may cause seizures and brain damage. This is a condition called kernicterus.

What are the symptoms of hyperbilirubinemia? The following are the most common symptoms of hyperbilirubinemia. However, each baby may experience symptoms differently. Symptoms may include:

yellow coloring of the baby's skin (usually beginning on the face and moving down the body)

poor feeding or lethargy The symptoms of hyperbilirubinemia may resemble other conditions or medical problems. Always consult your baby's physician for a diagnosis.

How is hyperbilirubinemia diagnosed? The timing of the appearance of jaundice helps with the diagnosis. Jaundice appearing in the first 24 hours is quite serious and usually requires immediate treatment. When jaundice appears on the second or third day, it is usually "physiologic. " However, it can be a more serious type of jaundice. When jaundice appears on the third day to the first week, it may be due to an infection. Later appearance of jaundice, in the second week, is often related to breast milk feedings, but may have other causes.

Diagnostic procedures for hyperbilirubinemia may include:

direct and indirect bilirubin levels These reflect whether the bilirubin is bound with other substances by the liver so that it can be excreted (direct), or is circulating in the blood circulation (indirect).

red blood cell counts

blood type and testing for Rh incompatibility (Coomb's test) Treatment for hyperbilirubinemia: Specific treatment for hyperbilirubinemia will be determined by your baby's physician based on:

your baby's gestational age, overall health, and medical history extent of the disease your baby's tolerance for specific medications, procedures, or therapies expectations for the course of the disease your opinion or preference Treatment depends on many factors, including the cause of the hyperbilirubinemia and the level of bilirubin. The goal is to keep the level of bilirubin from increasing to dangerous levels. Treatment may include:

phototherapy Since bilirubin absorbs light, jaundice and increased bilirubin levels usually decrease when the baby is exposed to special blue spectrum lights. Phototherapy may take several hours to begin working and it is used throughout the day and night. The baby's position is changed to allow all of the skin to be exposed to the light. The baby's eyes must be protected and the temperature monitored during phototherapy. Blood levels of bilirubin are checked to monitor if the phototherapy is working.

fiberoptic blanket Another form of phototherapy is a fiberoptic blanket placed under the baby. This may be used alone or in combination with regular phototherapy.

exchange transfusion to replace the baby's damaged blood with fresh blood Exchange transfusion helps increase the red blood cell count and lower the levels of bilirubin. An exchange transfusion is done by alternating giving and withdrawing blood in small amounts through a vein or artery. Exchange transfusions may need to be repeated if the bilirubin levels remain high.

ceasing breastfeeding for one or two days Treatment of breast milk jaundice often requires stopping the breastfeeding for one to two days and giving the baby formula often helps lower the bilirubin levels. Breastfeeding can then be resumed.

treating any underlying cause of hyperbilirubinemia, such as infection Prevention of hyperbilirubinemia: While hyperbilirubinemia cannot be totally prevented, early recognition and treatment are important in preventing bilirubin levels from rising to dangerous levels.

Online source http://www.healthsystem.virginia.edu/uvahealth/peds_hrnewborn/hyperb.cfm List of sources: http://www.healthsystem.virginia.edu/uvahealth/peds_hrnewborn/online.cfm

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External links

• Children's Liver Disease Foundation: information on jaundice in infants

See also

• Cholestasis
• Neonatal jaundice

Footnotes

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