Hepatosplenomegaly: Causes, complications, and treatment
Everything You Need To Know About Jaundice
Adults and children with jaundice may notice a yellowish tinge to their skin, mucous membranes, and the whites of the eyes. It can happen with various health conditions and usually indicates a problem with the liver or bile ducts.
When the liver is not working properly, it can cause a waste material called bilirubin to build up in the blood.
With moderate bilirubin levels, a person's skin, eyes, and mucous membranes can turn yellow. As it progresses, the color can also change from yellow to green. The green color occurs due to biliverdin, the green pigment present in bile.
Jaundice can develop in people of all ages and is normally the result of an underlying condition. Newborns and older adults have the highest likelihood of developing jaundice.
This article discusses what causes jaundice, how healthcare professionals diagnose and treat the condition, and how a person can help to prevent it from occurring. It also explores the symptoms a person can expect.
According to the American Family Physician (AAFP), jaundice is the yellowing of the skin, mucous membranes, and the whites of the eyes that occurs when the body does not process bilirubin as it should.
Bilirubin levels increase as the red blood cells naturally break down. Typically, the liver filters this waste material out of the bloodstream and turns it into a new form called conjugated bilirubin. The new form then exits the body in a person's stool.
If there is too much bilirubin for the liver to process, it can build up in the body. This is known as hyperbilirubinemia, and it causes the yellow color in the skin and eyes.
Jaundice typically occurs due to an underlying disorder that either causes the production of too much bilirubin or prevents the liver from eliminating it.
Some possible underlying conditions and causes of jaundice include:
Treatment will depend on the underlying cause of jaundice.
Jaundice can lead to itching, or pruritis. A 2021 article notes that a person can have warm baths containing oatmeal and take antihistamines for mild pruritis.
A healthcare professional may prescribe medications for those experiencing moderate to severe pruritis, such as cholestyramine or colestipol.
As jaundice may sometimes indicate damage to the liver, a liver transplant may be necessary in some cases, depending on the severity of the injury.
Jaundice is related to liver function.
People can help take care of their liver with several lifestyle changes, such as:
A 2021 article also suggests:
Common symptoms of jaundice include:
In infants, the yellowish tinge can start at the head and spread down the body to the toes.
The United Kingdom's National Health Service (NHS) notes that jaundice may be less apparent on Black and Brown skin. It is more obvious in the whites of the eyes.
Accompanying symptoms of jaundice may include:
High levels of bilirubin can be toxic and lead to a rare type of brain damage called kernicterus in infants.
The underlying conditions causing jaundice can also lead to their own complications.
Three main types of jaundice include:
Jaundice is a common health issue in newborn children.
The Centers for Disease Control and Prevention (CDC) note that approximately 60% of newborns develop jaundice, and signs appear within 48 hours of birth. A doctor or nurse should examine the baby when they are between 3–5 days old. This is because the bilirubin levels are usually at their highest during this time.
Red blood cells in the body of an infant are frequently broken down and replaced. This causes the production of more bilirubin. In addition, the livers of infants are less developed and are therefore less effective at filtering bilirubin from the body.
Symptoms will usually resolve without treatment in mild cases. However, infants with extremely high bilirubin levels will require treatment with either a blood transfusion or phototherapy.
In these cases, jaundice treatment in newborns is vital to help prevent kernicterus.
Causes of jaundice in newbornsAlthough jaundice in babies is common and often resolves without treatment, some underlying medical conditions can cause jaundice. These include:
Breastfeeding or chestfeeding can also increase the chance of jaundice in newborns. However, there is no need for a person to stop feeding the baby this way. In these cases, the symptoms of jaundice resolve in a few weeks.
According to a 2021 article, normal bilirubin levels are less than 1 milligram per deciliter (mg/dl).
A person has jaundice if these levels reach approximately 3 mg/dl.
A 2021 article notes that doctors may diagnose jaundice in infants if the bilirubin levels increase to 5 mg/dl per day or more than 0.2 mg/dl per hour.
These ranges may differ between laboratories. How far above the normal range a person's levels will help a doctor determine the best course of treatment.
Doctors will most likely start with the person's history and a physical exam to diagnose jaundice. They may later also order lab tests.
During an examination, they will pay close attention to the abdomen, liver, and skin.
The doctor may often include lab tests to help determine the underlying cause of jaundice. These include:
The doctor will also examine the structure of the liver if they suspect an obstruction. In these cases, they will use imaging tests, including MRI, CT, and ultrasound scans.
In addition, they may carry out an endoscopic retrograde cholangiopancreatography (ERCP). This is a procedure combining endoscopy and X-ray imaging.
The AAFP states that a healthcare professional may perform a liver biopsy. A liver biopsy can check for inflammation, cirrhosis, cancer, and fatty liver. This test involves inserting a needle into the liver to obtain a tissue sample. A healthcare professional will then examine the sample under the microscope.
Jaundice is the yellowing of the skin, mucous membranes, and whites of the eyes. It is a symptom of an underlying condition or health concern that involves the liver.
It occurs when the liver cannot keep up with the demand to process waste in the blood or when the liver becomes damaged. Several conditions can cause liver issues and result in jaundice.
Treatment for jaundice typically involves treating the underlying condition.
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Gotta Go? We've Finally Found Out What Makes Urine Yellow
Enlarge Science Photo Library reader comments 132There are many mysteries in life that we end up shrugging off. Why is urine yellow? It just is, right? Rather than flush that 125-year-old question down the toilet, scientists sought out the answer, discovering a previously unknown microbial enzyme was to blame.
The enzyme that has eluded us for so long is now known as bilirubin reductase. It was identified by researcher and assistant professor Brantley Hall of the University of Maryland, who was part of a team based at the university and the National Institutes of Health.
Bilirubin is an orange pigment released by red blood cells after they die. Gut microbes then use bilirubin reductase to break down bilirubin into colorless urobilinogen, which degrades into yellowish urobilin, giving urine that infamous hue. While urobilin previously had an association with the color of urine, the enzyme that starts the process by producing urobilinogen was unknown until now.
"Though it was previously thought that multiple enzymes were involved in the reduction of bilirubin, our results support the finding that a single enzyme performs the reduction of bilirubin to urobilinogen," the research team said in a study recently published in Nature Microbiology.
Gut feelingBecause some gut bacteria had been known to reduce bilirubin, Hall and his team knew where to start but wanted to fill in the unknowns by finding out which particular species actually do this—and how. This meant they had to find the gene responsible for encoding bilirubin reductase.
Previous studies had found that the species Clostridiodes difficile was capable of reducing bilirubin (though the mechanism it used was unknown). Using C. Difficile as a basis for comparison, the team cultured different species of gut bacteria and exposed them to bilirubin to see whether that bacteria could produce urobilinogen, detecting its presence using a fluorescence assay.
AdvertisementThe fluorescence assay told Hall and his colleagues that there were nine strains within the tested species that they thought were capable of reducing bilirubin, although how these bacteria were breaking it down was still unclear. After the fluorescence assay, the genomes of the most closely related strains were analyzed, and several turned out to share a gene that encoded an enzyme that could reduce bilirubin—bilirubin reductase.
Bacterial strains that metabolized bilirubin using bilirubin reductase all came from species that were found to belong to a single clade (the researchers informally referred to it as the bilirubin reductase clade). Within that clade, most of these species are from the class Clostridia in the phylum Firmicutes, a phylum of bacteria important to gut health.
More than… you knowThe discovery of bilirubin reductase goes beyond the origin of urine color. After identifying the enzyme, the researchers found out that, while bilirubin reductase is present in healthy adults, there is a deficit in newborns and adults with inflammatory bowel disease, which could eventually influence future treatments
By sequencing infant gut genomes, Hall and his team saw that bilirubin reductase was often missing during the first few months of life. Too much bilirubin building up in the blood turns the skin and the whites of the eyes yellow, a symptom known as jaundice. Most infants have some level of jaundice, but it usually goes away on its own.
The absence of bilirubin reductase is also associated with pigmented gallstones in adults with inflammatory bowel disease (inflammatory bowel disease, or IBD, is a general term that can refer to several different diagnoses). Sequencing adult gut genomes showed that there was a deficit of this enzyme in most patients with Crohn's disease or ulcerative colitis whose gut genomes were sequenced.
"With the knowledge of the species, genes, and enzymes involved in bilirubin reduction, future research can now focus on the extent to which gut microbial bilirubin metabolism affects… the role of bilirubin reduction in health and disease," the researchers said in the same study.
There is still more research to be done on bilirubin reductase and the health implications it could have. The team thinks there may be a link between the amount of urobilin produced in the body and insulin resistance, obesity, heart disease, and even heart failure. Next to that, we finally know why urine is yellow.
Nature Microbiology, 2023. DOI: 10.1038/s41564-023-01549-x
What Makes Urine Yellow? UMD Scientists Discover The Enzyme Responsible
Researchers at the University of Maryland and National Institutes of Health have identified the microbial enzyme responsible for giving urine its yellow hue, according to a new study published in the journal Nature Microbiology on January 3, 2024.
The discovery of this enzyme, called bilirubin reductase, paves the way for further research into the gut microbiome's role in ailments like jaundice and inflammatory bowel disease.
"This enzyme discovery finally unravels the mystery behind urine's yellow color," said the study's lead author Brantley Hall, an assistant professor in the University of Maryland's Department of Cell Biology and Molecular Genetics. "It's remarkable that an everyday biological phenomenon went unexplained for so long, and our team is excited to be able to explain it."
When red blood cells degrade after their six-month lifespan, a bright orange pigment called bilirubin is produced as a byproduct. Bilirubin is typically secreted into the gut, where it is destined for excretion but can also be partially reabsorbed. Excess reabsorption can lead to a buildup of bilirubin in the blood and can cause jaundice—a condition that leads to the yellowing of the skin and eyes. Once in the gut, the resident flora can convert bilirubin into other molecules.
"Gut microbes encode the enzyme bilirubin reductase that converts bilirubin into a colorless byproduct called urobilinogen," explained Hall, who has a joint appointment in the University of Maryland Institute for Advanced Computer Studies. "Urobilinogen then spontaneously degrades into a molecule called urobilin, which is responsible for the yellow color we are all familiar with."
Urobilin has long been linked to urine's yellow hue, but the research team's discovery of the enzyme responsible answers a question that has eluded scientists for over a century.
Aside from solving a scientific mystery, these findings could have important health implications. The research team found that bilirubin reductase is present in almost all healthy adults but is often missing from newborns and individuals with inflammatory bowel disease. They hypothesize that the absence of bilirubin reductase may contribute to infant jaundice and the formation of pigmented gallstones.
"Now that we've identified this enzyme, we can start investigating how the bacteria in our gut impact circulating bilirubin levels and related health conditions like jaundice," said study co-author and NIH Investigator Xiaofang Jiang. "This discovery lays the foundation for understanding the gut-liver axis."
In addition to jaundice and inflammatory bowel disease, the gut microbiome has been linked to various diseases and conditions, from allergies to arthritis to psoriasis. This latest discovery brings researchers closer to achieving a holistic understanding of the gut microbiome's role in human health.
"The multidisciplinary approach we were able to implement—thanks to the collaboration between our labs—was key to solving the physiological puzzle of why our urine appears yellow," Hall said. "It's the culmination of many years of work by our team and highlights yet another reason why our gut microbiome is so vital to human health."
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This article was adapted from text provided by Brantley Hall and Sophia Levy.
In addition to Hall, UMD-affiliated co-authors included Stephenie Abeysinghe (B.S. '23, public health science); Domenick Braccia (Ph.D. '22, biological sciences); biological sciences major Maggie Grant; biochemistry Ph.D. Student Conor Jenkins; biological sciences Ph.D. Students Gabriela Arp (B.S. '19, public health science; B.A. '19, Spanish language), Madison Jermain, Sophia Levy (B.S. '19, chemical engineering; B.S. '19, biological sciences) and Chih Hao Wu (B.S. '21, biological sciences); Glory Minabou Ndjite (B.S. '22, public health science); and Ashley Weiss (B.S. '22, biological sciences).
Their paper, "Discovery of a gut microbial enzyme that reduces bilirubin to urobilinogen," was published in the journal Nature Microbiology on January 3, 2024.
This research was supported by the NIH's Intramural Research Program, the National Library of Medicine and startup funding from UMD. This article does not necessarily reflect the views of these organizations.
JournalNature Microbiology
Article TitleBilR is a gut microbial enzyme that reduces bilirubin to urobilinogen
Article Publication Date3-Jan-2024
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