Jaundice - causes, treatment & pathology

Summary

This script delves into jaundice, a condition characterized by the yellowing of skin and eyes due to bilirubin accumulation. It explains the process of bilirubin production from red blood cells, its metabolism in the liver, and excretion via bile and urine. The script also covers various causes of jaundice, including increased bilirubin production, liver dysfunction, and genetic disorders, and touches on treatments like phototherapy. It highlights the importance of understanding the bilirubin metabolism pathway for diagnosing and managing jaundice effectively.

Takeaways

• 📘 Jaundice, also known as icterus, is a condition characterized by yellowing of the skin and eyes due to the accumulation of bilirubin.
• 🩸 Bilirubin is a byproduct of hemoglobin breakdown from red blood cells, which have a lifespan of about 120 days.
• 🧬 The reticuloendothelial system, particularly the spleen, plays a key role in breaking down old red blood cells into heme and globin.
• 🧪 Heme is further broken down into iron and protoporphyrin, which is then converted into unconjugated bilirubin (UCB).
• 🚑 UCB is lipid-soluble and bound by albumin in the blood, transported to the liver, and converted into water-soluble conjugated bilirubin (CB) by the enzyme UGT.
• 🌱 CB is secreted into the bile and stored in the gallbladder, then released into the small intestine where it is converted to urobilinogen (UBG) by gut microbes.
• 💩 Stercobilin, derived from UBG, is responsible for the brown color of feces, while some UBG is recycled and contributes to the yellow color of urine.
• 🚨 Disruptions in bilirubin metabolism can lead to jaundice, with symptoms including yellowing of the skin and sclera of the eyes.
• 👶 Physiologic jaundice of newborns is common due to immature liver function and the breakdown of fetal red blood cells, which can be treated with phototherapy.
• 🧬 Genetic disorders such as Gilbert's syndrome and Crigler-Najjar syndrome can affect the liver's ability to process bilirubin, leading to jaundice.
• 🔍 Jaundice can be caused by various factors including increased red blood cell breakdown, liver disease, bile duct obstruction, and viral infections.

Q & A

What is the medical term for the yellowing of the skin and eyes due to a buildup of a certain pigment?

The medical term for the yellowing of the skin and eyes is jaundice, which is caused by a buildup of bilirubin.

What is the origin of the term 'jaundice'?

The term 'jaundice' comes from the French word 'jaunice,' meaning yellowing, and is also sometimes referred to as icterus.

What is bilirubin and why is it significant in the context of jaundice?

Bilirubin is a yellow pigment that is a component of bile. It is significant in jaundice because its buildup in the blood causes the yellowing of the skin and eyes.

Where does bilirubin come from in the body?

Bilirubin comes from the breakdown of hemoglobin in red blood cells by macrophages in the reticuloendothelial system, primarily in the spleen.

What is the role of the liver in the metabolism of bilirubin?

The liver plays a crucial role in the metabolism of bilirubin by taking up unconjugated bilirubin (UCB), conjugating it with an enzyme called uridine glucuronyl transferase (UGT), and making it water-soluble for excretion.

How is bilirubin transported from the liver to the gallbladder and eventually to the small intestine?

Conjugated bilirubin is secreted into the bile canaliculi, drains into the bile ducts, and is stored in the gallbladder. Upon eating, the gallbladder secretes bile containing conjugated bilirubin, which then moves to the duodenum of the small intestine.

What happens to bilirubin in the small intestine and what is urobilinogen?

In the small intestine, intestinal microbes convert conjugated bilirubin to urobilinogen (UBG), which is further reduced to stercobilin, contributing to the brown color of feces, and some of it is recycled back into the blood.

What causes the yellow color in the urine in the context of jaundice?

The yellow color in the urine during jaundice is due to the presence of urobilin, a product of the oxidation of urobilinogen, which is excreted by the kidneys.

What are some conditions that can lead to increased levels of unconjugated bilirubin in the blood?

Conditions that can lead to increased levels of unconjugated bilirubin in the blood include extravascular hemolytic anemias, where red blood cells are broken down prematurely, and ineffective hematopoiesis, where blood cells don't form correctly in the bone marrow.

What is the potential risk of high levels of unconjugated bilirubin in newborns?

High levels of unconjugated bilirubin in newborns can lead to a condition called kernicterus, where bilirubin accumulates in the basal ganglia of the brain, potentially causing brain damage or death.

How is jaundice in newborns typically treated?

Jaundice in newborns is typically treated with phototherapy, which uses light to induce changes in the bilirubin molecule, making it more soluble and easier to excrete in the urine.

What is the difference between Gilbert's syndrome and Crigler-Najjar syndrome in terms of bilirubin metabolism?

Gilbert's syndrome is characterized by low UGT enzyme activity, which can lead to an accumulation of unconjugated bilirubin in the blood under certain conditions. Crigler-Najjar syndrome, on the other hand, is characterized by a near absence of UGT, leading to extremely high levels of unconjugated bilirubin and a high risk of kernicterus.

What is Dubin-Johnson syndrome and how does it relate to jaundice?

Dubin-Johnson syndrome is an autosomal recessive disorder characterized by a deficiency in the MRP2 protein, which helps move conjugated bilirubin from liver cells to bile ducts. This leads to an accumulation of conjugated bilirubin in the liver and its subsequent leakage into the blood, causing jaundice.

What is obstructive jaundice and what causes it?

Obstructive jaundice occurs when there is a blockage in the flow of bile, which can be caused by gallstones, pancreatic carcinomas, cholangiocarcinomas, or parasites like the liver fluke. This blockage leads to an increase in conjugated bilirubin in the blood and other symptoms.

How does viral hepatitis affect bilirubin levels in the blood?

Viral hepatitis can lead to both conjugated and unconjugated bilirubin in the blood. Infected and dying hepatocytes lose the ability to conjugate bilirubin, leading to excess unconjugated bilirubin, and also allow bile to leak into the blood, increasing conjugated bilirubin levels.

Outlines

00:00

🟡 Jaundice: Causes and Bilirubin Metabolism

This paragraph explains the concept of jaundice, a condition characterized by the yellowing of the skin and eyes due to the accumulation of bilirubin. Bilirubin is a byproduct of red blood cell breakdown, which is normally processed by the liver and excreted through bile. The process involves macrophages breaking down old red blood cells, converting heme into bilirubin, and the liver's role in making bilirubin water-soluble for excretion. Disruptions in this process, such as liver damage or increased red blood cell breakdown, can lead to jaundice. The paragraph also discusses how jaundice can be identified by the yellowing of the sclera before the skin and the different types of disorders that can cause jaundice, such as extravascular hemolytic anemias and ineffective hematopoiesis.

05:02

💼 Bilirubin Overload and Jaundice Variants

This paragraph delves into the consequences of bilirubin overload, focusing on the formation of pigmented gallstones and the darker urine due to the presence of urobilinogen. It discusses the challenges faced by hepatocytes in processing unconjugated bilirubin (UCB), particularly in conditions like physiologic jaundice of newborns, where the liver has a lower capacity to convert UCB. The paragraph also covers treatments like phototherapy and genetic conditions such as Gilbert's syndrome and Crigler-Najjar syndrome, which affect the liver's ability to process bilirubin. Additionally, it touches on Dubin-Johnson syndrome, obstructive jaundice, and the effects of viral hepatitis on bilirubin levels, highlighting the various ways in which jaundice can manifest and be treated.

10:07

📢 Conclusion and Call to Action

The final paragraph serves as a conclusion to the video script, summarizing the information on jaundice and its various causes. It also includes a call to action, encouraging viewers to support the channel through Patreon donations, subscribing to the channel, or sharing it on social media. This paragraph wraps up the discussion on jaundice by emphasizing the importance of understanding the condition and the various ways viewers can contribute to and engage with the content.

Keywords

💡Jaundice

Jaundice, derived from the French word 'jaunice' meaning yellowing, is a medical condition characterized by the yellowing of the skin and eyes due to the presence of bilirubin. It is central to the video's theme as it explains the process that leads to jaundice and its various causes. The script uses the term to describe the condition resulting from bilirubin accumulation in the blood.

💡Bilirubin

Bilirubin is a yellow compound that is a byproduct of red blood cell breakdown and is a key player in the development of jaundice. The script explains that bilirubin is produced when macrophages break down old red blood cells, and its accumulation in the blood leads to the yellowing of the skin and eyes, which is the main focus of the video.

💡Unconjugated Bilirubin (UCB)

Unconjugated Bilirubin, also known as indirect bilirubin, is a lipid-soluble form of bilirubin that is not water-soluble. The script discusses how UCB is produced from the breakdown of heme and is transported to the liver where it is processed. An increase in UCB levels in the blood can lead to jaundice, as seen in conditions like hemolytic anemia or Gilbert's syndrome.

💡Conjugated Bilirubin (CB)

Conjugated Bilirubin, or direct bilirubin, is the water-soluble form of bilirubin that the liver produces by adding glucuronic acid to UCB. The script explains that this process is crucial for the excretion of bilirubin in bile. Disruptions in this process can lead to jaundice, as seen in conditions like Dubin-Johnson syndrome or when there is an obstruction in the bile ducts.

💡Macrophages

Macrophages are a type of white blood cell that play a significant role in the body's immune response by engulfing and digesting cellular debris and pathogens. In the context of the video, macrophages are responsible for breaking down old red blood cells, leading to the production of bilirubin, which is a key step in the development of jaundice.

💡Hemoglobin

Hemoglobin is the iron-containing protein in red blood cells that carries oxygen from the lungs to the rest of the body. The script describes how hemoglobin is broken down into its components, heme and globin, by macrophages during the red blood cell recycling process, which contributes to the formation of bilirubin.

💡Uridine Glucuronyl Transferase (UGT)

Uridine Glucuronyl Transferase is an enzyme found in liver cells that is responsible for the conjugation of bilirubin, making it water-soluble for excretion. The script highlights the importance of UGT in the liver's processing of bilirubin and how deficiencies or defects in this enzyme can lead to jaundice.

💡Urobilinogen (UBG)

Urobilinogen is a compound produced in the intestine when bilirubin is broken down by bacteria. The script explains that some of the UBG is converted to stercobilin, which gives feces their brown color, while the rest is reabsorbed into the blood and contributes to the yellow color of urine.

💡Sclera

The sclera is the white, outer layer of the eye that covers the entire surface except for the cornea. The script notes that the sclera is one of the first areas to show signs of jaundice due to its high elastin content, which binds bilirubin, causing a yellow discoloration.

💡Kernicterus

Kernicterus is a serious condition that occurs when unconjugated bilirubin accumulates in the brain, potentially causing brain damage or death. The script mentions this condition in the context of severe jaundice in newborns, where high levels of UCB can cross the blood-brain barrier and lead to kernicterus.

💡Phototherapy

Phototherapy is a treatment method used for jaundice in newborns, where light is used to change the structure of bilirubin, making it more soluble and easier to excrete. The script describes phototherapy as a non-invasive way to reduce bilirubin levels and prevent kernicterus.

Highlights

Jaundice, also known as icterus, is characterized by yellowing of the skin and eyes due to the presence of bilirubin.

Bilirubin is a component of bile and is responsible for the yellow color of bruises, urine, and brown color of feces.

Bilirubin originates from the breakdown of hemoglobin by macrophages in the reticuloendothelial system, primarily in the spleen.

Unconjugated bilirubin (UCB) is lipid-soluble and requires transport to the liver for conjugation.

In the liver, hepatocytes convert UCB into water-soluble conjugated bilirubin (CB) with the help of the UGT enzyme.

CB is secreted into bile and stored in the gallbladder, then released into the small intestine for further metabolism.

Urobilinogen and stercobilin, produced in the intestine, contribute to the color of urine and feces, respectively.

Disruption in bilirubin metabolism can lead to jaundice, with increased levels of either UCB or CB in the blood.

Jaundice can be identified by the yellowing of the sclera, which binds bilirubin with high affinity.

Extravascular hemolytic anemias and ineffective hematopoiesis can cause increased UCB levels and jaundice.

Physiologic jaundice of newborns is due to immature liver function and rapid breakdown of fetal red blood cells.

Phototherapy is an effective treatment for neonatal jaundice, inducing changes in bilirubin to facilitate excretion.

Gilbert's syndrome is a hereditary condition with reduced UGT activity, leading to increased UCB levels and potential jaundice.

Crigler-Najjar syndrome is a severe genetic disorder with little to no UGT activity, resulting in dangerously high UCB levels.

Dubin-Johnson syndrome involves a deficiency in the MRP2 protein, leading to increased CB levels and dark liver.

Obstructive jaundice occurs when bile flow is blocked, causing increased CB levels in the blood and urine.

Viral hepatitis can cause both increased UCB and CB levels due to liver cell damage and bile duct obstruction.

Bile duct obstruction can lead to various symptoms, including pruritus, hypercholesterolemia, and steatorrhea.

Transcripts

Jaundice, which doesn’t have the most intuitive name, comes from the french jaunice, meaning

yellowing.

It’s also sometimes referred to as icterus though, the origin of which is even less intuitive,

coming from the thought that jaundice could once be cured by looking at a yellow bird,

the more you know!

Anyways, as you’ve probably gathered, jaundice involves someone taking on yellow pigments,

specifically in the skin and eyes.

The yellowing pigment is caused by a compound called bilirubin, a component of bile and

the main cause of bruises being yellow, and after its metabolism, the yellow-ness of urine

and brown-ness of feces.

So since bilirubin’s our main culprit of yellow-ness, it’s super important to know

where it comes from.

As red blood cells near the end of their lifespan—which is about 120 days—they’re eaten up or

phagocytosed by macrophages in the reticuloendothelial system, aka the macrophage system, where the

spleen plays the largest part, but it’s also made of parts of the lymph nodes.

K so first the macrophage eats up the blood cell, and hemoglobin is broken up into heme

and globin, the globin is further broken into amino acids.

The heme on the other hand is split into iron and protoporphyrin, protoporphyrin is then

converted into unconjugated bilirubin, or UCB.

Unconjugated bilirubin is the form of bilirubin that’s lipid-soluble, meaning it’s not

water-soluble, sometimes it’s also known as indirect bilirubin.

Albumin in the blood then binds to UCB and gives it a lift over to the liver where it’s

taken up by hepatocytes, where it’s conjugated by an enzyme called uridine glucuronyl transferase

(UGT), making it now water soluble.

At this point the conjugated bilirubin is secreted out the bile canaliculi where it

drains into the bile ducts and sent to the gallbladder for storage as bile.

Now when you eat a donut or something, your gallbladder secretes the bile and CB, it moves

through the common bile duct to the duodenum of the small intestine and is converted to

urobilinogen, or UBG, by intestinal microbes in the gut.

Now some of that urobilinogen is reduced to stercobilin which is excreted and responsible

for the brown color of feces.

Some of that UBG is actually recycled, though, and it gets reabsorbed into the blood and

spontaneously oxidizes into urobilin, most of which is sent to the liver to the liver

and some of which goes to the kidneys.

It’s then excreted and is responsible for the yellow-ness of urine!

And there you have it, bilirubin metabolism in a nutshell.

Now if some point in this process is disrupted, for example if your liver cells are damaged

and can’t conjugate bilirubin anymore, or if they die and release their bilirubin, you

can end up with increased bilirubin in the blood, which can be conjugated or unconjugated,

or both!

This is what accounts for the yellow color in the skin and eyes.

Usually it takes about 2.5 mg/dL or greater of serum bilirubin to give the skin that Simpsons-esque

yellow skin tone.

The earliest sign of jaundice and increased bilirubin in the blood is by looking at the

sclera of the eyes.

Scleral tissue is high in elastin, which has a particular fondness for bilirubin and binds

it with a high affinity, giving the scleral tissue a yellow color often before the skin.

Now as you might imagine after looking at this process, there’re quite a few potential

pitfalls along the way that can lead to jaundice, and they’re lumped together depending on

whether they have more UCB in the blood, more CB in the blood, or more of both in the blood.

Two types of disorders that have increased UCB and similar presentation of jaundice are

extravascular hemolytic anemias, where red blood cells are broken down earlier than they

normally would, and ineffective hematopoesis, where your blood cells don’t form quite

right in your bone marrow, causing macrophages to break them down.

In both cases, the red blood cells are broken down, causing high levels of UCB.

Since your hepatocytes can only work so hard converting UCB to CB, they can get overwhelmed.

As an imaginary example, say that this liver cell can conjugate 10 molecules of UCB a minute,

max, but normally they only see 5, so that’s easy.

If all the sudden your body starts breaking down more blood cells and the UCB molecules

on this cell’s docket jumps to 15/min, this liver cell can’t keep up, and that excess

of 5 molecules of UCB stays in the blood, that’s the first issue.

In addition, as the liver cells max out, now there’s all this CB that goes to the bile,

which increases the risk for pigmented bilirubin gallstones.

Not only that, once all that CB is sent to the duodenum, it’s converted to urobilinogen.

Remember some of that urobilinogen is recycled back into the blood, oxidized to urobilin,and

excreted in the urine, giving it a much darker color.

The UCB is not excreted because it’s not water soluble!

In the previous two cases, too much UCB was created, but you can also have hepatocytes

that just can’t work hard enough and keep up.

Physiologic jaundice of newborn is one of these cases; newborn livers having a lower

amount of UGT in the liver to convert UCB, and after birth, UCB levels can be high due

to the natural process of macrophages destroying fetal red blood cells.

Typically this is normal, but can cause complications if UCB rises a LOT; since it’s fat soluble,

it can collect in the basal ganglia of the brain, which is called kernicterus, and cause

damage to the brain or death.

Treatment of this condition is usually phototherapy, which uses light to induce structural and

configurational changes in the bilirubin molecule, basically it absorbs the energy from the light

and changes shape.

These new shapes are more soluble, and can be excreted in the urine.

This can be a super effective and non-invasive way to get excess UCB out of the blood.

Another potential case where not enough UCB can be conjugated is through hereditary defects.

One case is called Gilbert’s syndrome, where their UGT enzyme activity is low and has a

hard time cranking up when needed, so maybe this liver cell can only pump through a max

of 6 molecules/minute.

Unfortunately, if something comes along that increases hemolysis, like infection, stress,

or starvation, the unconjugated bilirubin load will increase which can easily overwhelm

these hepatocytes, cause buildup of unconjugated bilirubin in the blood and lead to jaundice.

Another genetic example is called Crigler Najjar syndrome, where gilbert’s syndrome

was a low amount of UGT, Crigler Najjar is where there’s pretty much no UGT and therefore

no ability to conjugate UCB, this will lead to SUPER high levels of UCB, and likely UCB

deposits in the brain and kernicterus; Crigler Najjar syndrome is usually fatal.

The previous couple examples focused on high levels of unconjugated bilirubin in the blood,

but there are also examples of jaundice with high levels of conjugated bilirubin in the

blood.

Dubin-Johnson syndrome is an autosomal recessive disorder where there’s a deficiency in the

protein that helps move CB from the liver cell to the bile ducts, called MRP2, so CB

builds up in the hepatocyte.

It’s thought that when the MRP2 transporter is defected, another transporter, MRP3 is

upregulated, though this transporter moves it into the interstitial space and blood flow,

as opposed to the bile canaliculus, so in this case you’ll have increased CB in the

blood, which also gets excreted into the urine, giving it a darker color, this leakage also

causes the liver itself to get super dark.

Another high-CB category of jaundice is called obstructive jaundice, and this is basically

where something blocks the flow of bile, these blockages could be anything from gallstones,

pancreatic carcinomas and cholangiocarcinomas, to parasites like the liver fluke.

Remember that bile’s made up of conjugated bilirubin and this blockage basically causes

pressure to rise in the bile duct, which literally causes bile to leak through the tight junctions

between hepatocytes, but that’s not the only thing that leaks out though; bile salts,

bile acids, and cholesterol all can can get into the blood.

If they deposit in the skin, it could lead to itchiness or pruritus, but also lead to

things like hypercholesterolemia and xanthomas.

The excess CB is excreted in the urine, leading again to dark urine.

Also, since you’re losing bile, you won’t be able to absorb fat as well, which (1) causes

you to excrete a ton of fat, a condition called steatorrhea, and (2) causes you to not be

able to absorb as many fat-soluble vitamins as you need.

Finally, viral hepatitis leads to both conjugated and unconjugated bilirubin in the blood.

When hepatocytes get infected and start to die off, they both lose the ability to conjugate

bilirubin, leading to excess UCB in the blood, AND since they also line the bile ducts, when

they die they let bile leak out into the blood, causing an increase in blood CB as well.

Again, since CB is up, patients will have more CB excreted and darker urine.

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