黃疸手作坊

最後編輯：2016-03-18 建立：2016-03-18 歷史紀錄

慈濟英美系翻譯教育合作慈濟英美系翻譯教育合作

黃瑞霖影片連結：https://en.wikipedia.org/wiki/File:Jaundice-video-osmosis.webm

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Jaundice, which doesn’t have the most intuitive
name, comes from the french jaunice, meaning
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yellowing. It’s also sometimes referred
to as icterus though, the origin of which
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is even less intuitive, coming from the thought
that jaundice could once be cured by looking
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at a yellow bird, the more you know! Anyways,
as you’ve probably gathered, jaundice involves
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someone taking on yellow pigments, specifically
in the skin and eyes. The yellowing pigment
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is caused by a compound called bilirubin,
a component of bile and the main cause of
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bruises being yellow, and after its metabolism,
the yellow-ness of urine and brown-ness of
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feces. So since bilirubin’s our main culprit
of yellow-ness, it’s super important to
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know where it comes from. As red blood cells
near the end of their lifespan—which is
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about 120 days—they’re eaten up or phagocytosed
by macrophages in the reticuloendothelial
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system, aka the macrophage system, where the
spleen plays the largest part, but it’s
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also made of parts of the lymph nodes. K so
first the macrophage eats up the blood cell,
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and hemoglobin is broken up into heme and
globin, the globin is further broken into
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amino acids. The heme on the other hand is
split into iron and protoporphyrin, protoporphyrin
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is then converted into unconjugated bilirubin,
or UCB. Unconjugated bilirubin is the form
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of bilirubin that’s lipid-soluble, meaning
it’s not water-soluble, sometimes it’s
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also known as indirect bilirubin. Albumin
in the blood then binds to UCB and gives it
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a lift over to the liver where it’s taken
up by hepatocytes, where it’s conjugated
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by an enzyme called uridine glucuronyl transferase
(UGT), making it now water soluble. At this
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point the conjugated bilrubin is secreted
out the bile canaliculi where it drains into
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the bile ducts and sent to the gallbladder
for storage as bile. Now when you eat a donut
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or something, your gallbladder secretes the
bile and CB, it moves through the common bile
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duct to the duodenum of the small intestine
and is converted to urobilinogen, or UBG,
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by intestinal microbes in the gut. Now it
undergoes spontaneous oxidation, turning it
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into urobilin, which is excreted and responsible
for the brown color of feces. About 20% of
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that UBG is actually recycled, though, in
other words it doesn’t get oxidized and
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instead gets reabsorbed into the blood and
gets sent to the liver and kidneys, about
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90% going to the liver and 10% going to the
kidneys. The 10% that goes to the kidneys
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and is excreted causes the yellow-ness of
urine! And there you have it, bilirubin metabolism
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in a nutshell.
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Now if some point in this process is disrupted,
for example if your liver cells are damaged
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and can’t conjugate bilirubin anymore, or
if they die and release their bilirubin, you
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can end up with increased bilirubin in the
blood, which can be conjugated or unconjugated,
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or both! This is what accounts for the yellow
color in the skin and eyes. Usually it takes
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about 2.5 mg/dL or greater of serum bilirubin
to give the skin that Simpsons-esque yellow
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skin tone. The earliest sign of jaundice and
increased bilirubin in the blood is by looking
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at the sclera of the eyes. Scleral tissue
is high in elastin, which has a particular
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fondness for bilirubin and binds it with a
high affinity, giving the scleral tissue a
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yellow color often before the skin. Now as
you might imagine after looking at this process,
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there’re quite a few potential pitfalls
along the way that can lead to jaundice, and
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they’re lumped together depending on whether
they have more UCB in the blood, more CB in
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the blood, or more of both in the blood.
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Two types of disorders that have increased
UCB and similar presentation of jaundice are
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extravascular hemolytic anemias, where red
blood cells are broken down earlier than they
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normally would, and ineffective hematopoesis,
where your blood cells don’t form quite
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right in your bone marrow, causing macrophages
to break them down. In both cases, the red
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blood cells are broken down, causing high
levels of UCB. Since your hepatocytes can
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only work so hard converting UCB to CB, they
can get overwhelmed. As an imaginary example,
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say that this liver cell can conjugate 10
molecules of UCB a minute, max, but normally
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they only see 5, so that’s easy. If all
the sudden your body starts breaking down
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more blood cells and the UCB molecules on
this cell’s docket jumps to 15/min, this
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liver cell can’t keep up, and that excess
of 5 molecules of UCB stays in the blood,
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that’s the first issue. In addition, as
the liver cells max out, now there’s all
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this CB that goes to the bile, which increases
the risk for pigmented bilirubin gallstones.
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Not only that, once all that CB is sent to
the duodenum, it’s converted to urobilinogen.
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Remember 20% of that urobilinogen is recycled
back into the blood and some of it is excreted
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in the urine, giving it a much darker color.
The UCB is not excreted because it’s not
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water soluble!
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In the previous two cases, too much UCB was
created, but you can also have hepatocytes
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that just can’t work hard enough and keep
up. Physiologic jaundice of newborn is one
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of these cases; newborn livers having a lower
amount of UGT in the liver to convert UCB,
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and after birth, UCB levels can be high due
to the natural process of macrophages destroying
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fetal red blood cells. Typically this is normal,
but can cause complications if UCB rises a
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LOT; since it’s fat soluble, it can collect
in the basal ganglia of the brain, which is
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called kernicterus, and cause damage to the
brain or death. Treatment of this condition
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is usually phototherapy, which uses light
to induce structural and configurational changes
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in the bilirubin molecule, basically it absorbs
the energy from the light and changes shape.
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These new shapes are more soluble, and can
be excreted in the urine. This can be a super
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effective and non-invasive way to get excess
UCB out of the blood.
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Another potential case where not enough UCB
can be conjugated is through hereditary defects.
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One case is called Gilbert’s syndrome, where
their UGT enzyme activity is low and has a
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hard time cranking up when needed, so maybe
this liver cell can only pump through a max
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of 6 molecules/minute. Unfortunately, if something
comes along that increases hemolysis, like
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infection, stress, or starvation, the unconjugated
bilirubin load will increase which can easily
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overwhelm these hepatocytes, cause buildup
of unconjugated bilirubin in the blood and
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lead to jaundice.
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Another genetic example is called Crigler
Najjar syndrome, where gilbert’s syndrome
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was a low amount of UGT, Crigler Najjar is
where there’s pretty much no UGT and therefore
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no ability to conjugate UCB, this will lead
to SUPER high levels of UCB, and likely UCB
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deposits in the brain and kernicterus; Crigler
Najjar syndrome is usually fatal.
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The previous couple examples focused on high
levels of unconjugated bilirubin in the blood,
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but there are also examples of jaundice with
high levels of conjugated bilirubin in the
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blood.
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Dubin-Johnson syndrome is an autosomal recessive
disorder where there’s a deficiency in the
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protein that helps move CB from the liver
cell to the bile ducts, called MRP2, so CB
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builds up in the hepatocyte. It’s thought
that when the MRP2 transporter is defected,
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another transporter, MRP3 is upregulated,
though this transporter moves it into the
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interstitial space and blood flow, as opposed
to the bile canaliculus, so in this case you’ll
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have increased CB in the blood, which also
gets excreted into the urine, giving it a
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darker color, this leakage also causes the
liver itself to get super dark.
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Another high-CB category of jaundice is called
obstructive jaundice, and this is basically
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where something blocks the flow of bile, these
blockages could be anything from gallstones,
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pancreatic carcinomas and cholangiocarcinomas,
to parasites like the liver fluke. Remember
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that bile’s made up of conjugated bilirubin
and this blockage basically causes pressure
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to rise in the bile duct, which literally
causes bile to leak through the tight junctions
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between hepatocytes, but that’s not the
only thing that leaks out though; bile salts,
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bile acids, and cholesterol all can can get
into the blood. If they deposit in the skin,
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it could lead to itchiness or pruritus, but
also lead to things like hypercholesterolemia
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and xanthomas. The excess CB is excreted in
the urine, leading again to dark urine. Also,
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since you’re losing bile, you won’t be
able to absorb fat as well, which (1) causes
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you to excrete a ton of fat, a condition called
steatorrhea, and (2) causes you to not be
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able to absorb as many fat-soluble vitamins
as you need.
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Finally, viral hepatitis leads to both conjugated
and unconjugated bilirubin in the blood. When
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hepatocytes get infected and start to die
off, they both lose the ability to conjugate
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bilirubin, leading to excess UCB in the blood,
AND since they also line the bile ducts, when
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they die they let bile leak out into the blood,
causing an increase in blood CB as well. Again,
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since CB is up, patients will have more CB
excreted and darker urine.