黃疸手作坊

編輯歷史

時間	作者	版本
2017-07-17 16:23	(unknown)	r2
顯示 diff （533 行未修改）
2017-07-12 07:09 – 07:09	(unknown)	r0 – r1
顯示 diff + 黃疸手作坊 + 影片連結：https://en.wikipedia.org/wiki/File:Jaundice-video-osmosis.webm + + 1 + 00:00:01,839 --> 00:00:11,130 + Jaundice, which doesn’t have the most intuitive + name, comes from the french jaunice, meaning + * + 2 + 00:00:11,130 --> 00:00:15,900 + yellowing. It’s also sometimes referred + to as icterus though, the origin of which + * + 3 + 00:00:15,900 --> 00:00:20,770 + is even less intuitive, coming from the thought + that jaundice could once be cured by looking + * + 4 + 00:00:20,770 --> 00:00:28,380 + at a yellow bird, the more you know! Anyways, + as you’ve probably gathered, jaundice involves + * + 5 + 00:00:28,380 --> 00:00:34,230 + someone taking on yellow pigments, specifically + in the skin and eyes. The yellowing pigment + * + 6 + 00:00:34,230 --> 00:00:39,300 + is caused by a compound called bilirubin, + a component of bile and the main cause of + * + 7 + 00:00:39,300 --> 00:00:45,079 + bruises being yellow, and after its metabolism, + the yellow-ness of urine and brown-ness of + * + 8 + 00:00:45,079 --> 00:00:51,540 + feces. So since bilirubin’s our main culprit + of yellow-ness, it’s super important to + * + 9 + 00:00:51,540 --> 00:00:56,410 + know where it comes from. As red blood cells + near the end of their lifespan—which is + * + 10 + 00:00:56,410 --> 00:01:03,110 + about 120 days—they’re eaten up or phagocytosed + by macrophages in the reticuloendothelial + * + 11 + 00:01:03,110 --> 00:01:09,200 + system, aka the macrophage system, where the + spleen plays the largest part, but it’s + * + 12 + 00:01:09,200 --> 00:01:15,170 + also made of parts of the lymph nodes. K so + first the macrophage eats up the blood cell, + * + 13 + 00:01:15,170 --> 00:01:21,179 + and hemoglobin is broken up into heme and + globin, the globin is further broken into + * + 14 + 00:01:21,179 --> 00:01:27,999 + amino acids. The heme on the other hand is + split into iron and protoporphyrin, protoporphyrin + * + 15 + 00:01:27,999 --> 00:01:34,799 + is then converted into unconjugated bilirubin, + or UCB. Unconjugated bilirubin is the form + * + 16 + 00:01:34,799 --> 00:01:39,359 + of bilirubin that’s lipid-soluble, meaning + it’s not water-soluble, sometimes it’s + * + 17 + 00:01:39,359 --> 00:01:44,560 + also known as indirect bilirubin. Albumin + in the blood then binds to UCB and gives it + * + 18 + 00:01:44,560 --> 00:01:49,179 + a lift over to the liver where it’s taken + up by hepatocytes, where it’s conjugated + * + 19 + 00:01:49,179 --> 00:01:57,119 + by an enzyme called uridine glucuronyl transferase + (UGT), making it now water soluble. At this + * + 20 + 00:01:57,119 --> 00:02:01,749 + point the conjugated bilrubin is secreted + out the bile canaliculi where it drains into + * + 21 + 00:02:01,749 --> 00:02:07,679 + the bile ducts and sent to the gallbladder + for storage as bile. Now when you eat a donut + * + 22 + 00:02:07,679 --> 00:02:14,510 + or something, your gallbladder secretes the + bile and CB, it moves through the common bile + * + 23 + 00:02:14,510 --> 00:02:20,890 + duct to the duodenum of the small intestine + and is converted to urobilinogen, or UBG, + * + 24 + 00:02:20,890 --> 00:02:26,379 + by intestinal microbes in the gut. Now it + undergoes spontaneous oxidation, turning it + * + 25 + 00:02:26,379 --> 00:02:32,730 + into urobilin, which is excreted and responsible + for the brown color of feces. About 20% of + * + 26 + 00:02:32,730 --> 00:02:37,480 + that UBG is actually recycled, though, in + other words it doesn’t get oxidized and + * + 27 + 00:02:37,480 --> 00:02:42,810 + instead gets reabsorbed into the blood and + gets sent to the liver and kidneys, about + * + 28 + 00:02:42,810 --> 00:02:48,810 + 90% going to the liver and 10% going to the + kidneys. The 10% that goes to the kidneys + * + 29 + 00:02:48,810 --> 00:02:54,790 + and is excreted causes the yellow-ness of + urine! And there you have it, bilirubin metabolism + * + 30 + 00:02:54,790 --> 00:02:57,209 + in a nutshell. + + 31 + 00:02:57,209 --> 00:03:02,219 + Now if some point in this process is disrupted, + for example if your liver cells are damaged + * + 32 + 00:03:02,219 --> 00:03:07,469 + and can’t conjugate bilirubin anymore, or + if they die and release their bilirubin, you + * + 33 + 00:03:07,469 --> 00:03:12,549 + can end up with increased bilirubin in the + blood, which can be conjugated or unconjugated, + * + 34 + 00:03:12,549 --> 00:03:18,349 + or both! This is what accounts for the yellow + color in the skin and eyes. Usually it takes + * + 35 + 00:03:18,349 --> 00:03:25,170 + about 2.5 mg/dL or greater of serum bilirubin + to give the skin that Simpsons-esque yellow + * + 36 + 00:03:25,170 --> 00:03:30,959 + skin tone. The earliest sign of jaundice and + increased bilirubin in the blood is by looking + * + 37 + 00:03:30,959 --> 00:03:36,999 + at the sclera of the eyes. Scleral tissue + is high in elastin, which has a particular + * + 38 + 00:03:36,999 --> 00:03:43,590 + fondness for bilirubin and binds it with a + high affinity, giving the scleral tissue a + * + 39 + 00:03:43,590 --> 00:03:49,069 + yellow color often before the skin. Now as + you might imagine after looking at this process, + * + 40 + 00:03:49,069 --> 00:03:53,799 + there’re quite a few potential pitfalls + along the way that can lead to jaundice, and + * + 41 + 00:03:53,799 --> 00:03:59,579 + they’re lumped together depending on whether + they have more UCB in the blood, more CB in + * + 42 + 00:03:59,579 --> 00:04:02,439 + the blood, or more of both in the blood. + + 43 + 00:04:02,439 --> 00:04:07,870 + Two types of disorders that have increased + UCB and similar presentation of jaundice are + * + 44 + 00:04:07,870 --> 00:04:12,889 + extravascular hemolytic anemias, where red + blood cells are broken down earlier than they + * + 45 + 00:04:12,889 --> 00:04:18,620 + normally would, and ineffective hematopoesis, + where your blood cells don’t form quite + * + 46 + 00:04:18,620 --> 00:04:24,699 + right in your bone marrow, causing macrophages + to break them down. In both cases, the red + * + 47 + 00:04:24,699 --> 00:04:31,550 + blood cells are broken down, causing high + levels of UCB. Since your hepatocytes can + * + 48 + 00:04:31,550 --> 00:04:39,830 + only work so hard converting UCB to CB, they + can get overwhelmed. As an imaginary example, + * + 49 + 00:04:39,830 --> 00:04:46,729 + say that this liver cell can conjugate 10 + molecules of UCB a minute, max, but normally + * + 50 + 00:04:46,729 --> 00:04:51,479 + they only see 5, so that’s easy. If all + the sudden your body starts breaking down + * + 51 + 00:04:51,479 --> 00:04:58,940 + more blood cells and the UCB molecules on + this cell’s docket jumps to 15/min, this + * + 52 + 00:04:58,940 --> 00:05:06,129 + liver cell can’t keep up, and that excess + of 5 molecules of UCB stays in the blood, + * + 53 + 00:05:06,129 --> 00:05:11,979 + that’s the first issue. In addition, as + the liver cells max out, now there’s all + * + 54 + 00:05:11,979 --> 00:05:19,440 + this CB that goes to the bile, which increases + the risk for pigmented bilirubin gallstones. + * + 55 + 00:05:19,440 --> 00:05:25,650 + Not only that, once all that CB is sent to + the duodenum, it’s converted to urobilinogen. + * + 56 + 00:05:25,650 --> 00:05:30,990 + Remember 20% of that urobilinogen is recycled + back into the blood and some of it is excreted + * + 57 + 00:05:30,990 --> 00:05:38,300 + in the urine, giving it a much darker color. + The UCB is not excreted because it’s not + * + 58 + 00:05:38,300 --> 00:05:39,539 + water soluble! + + 59 + 00:05:39,539 --> 00:05:46,020 + In the previous two cases, too much UCB was + created, but you can also have hepatocytes + * + 60 + 00:05:46,020 --> 00:05:52,599 + that just can’t work hard enough and keep + up. Physiologic jaundice of newborn is one + * + 61 + 00:05:52,599 --> 00:06:00,949 + of these cases; newborn livers having a lower + amount of UGT in the liver to convert UCB, + * + 62 + 00:06:00,949 --> 00:06:07,460 + and after birth, UCB levels can be high due + to the natural process of macrophages destroying + * + 63 + 00:06:07,460 --> 00:06:14,650 + fetal red blood cells. Typically this is normal, + but can cause complications if UCB rises a + * + 64 + 00:06:14,650 --> 00:06:20,500 + LOT; since it’s fat soluble, it can collect + in the basal ganglia of the brain, which is + * + 65 + 00:06:20,500 --> 00:06:26,139 + called kernicterus, and cause damage to the + brain or death. Treatment of this condition + * + 66 + 00:06:26,139 --> 00:06:31,319 + is usually phototherapy, which uses light + to induce structural and configurational changes + * + 67 + 00:06:31,319 --> 00:06:37,169 + in the bilirubin molecule, basically it absorbs + the energy from the light and changes shape. + * + 68 + 00:06:37,169 --> 00:06:41,860 + These new shapes are more soluble, and can + be excreted in the urine. This can be a super + * + 69 + 00:06:41,860 --> 00:06:47,319 + effective and non-invasive way to get excess + UCB out of the blood. + * + 70 + 00:06:47,319 --> 00:06:54,020 + Another potential case where not enough UCB + can be conjugated is through hereditary defects. + * + 71 + 00:06:54,020 --> 00:06:58,370 + One case is called Gilbert’s syndrome, where + their UGT enzyme activity is low and has a + * + 72 + 00:06:58,370 --> 00:07:03,030 + hard time cranking up when needed, so maybe + this liver cell can only pump through a max + * + 73 + 00:07:03,030 --> 00:07:09,340 + of 6 molecules/minute. Unfortunately, if something + comes along that increases hemolysis, like + * + 74 + 00:07:09,340 --> 00:07:14,900 + infection, stress, or starvation, the unconjugated + bilirubin load will increase which can easily + * + 75 + 00:07:14,900 --> 00:07:19,229 + overwhelm these hepatocytes, cause buildup + of unconjugated bilirubin in the blood and + * + 76 + 00:07:19,229 --> 00:07:22,250 + lead to jaundice. + + 77 + 00:07:22,250 --> 00:07:26,139 + Another genetic example is called Crigler + Najjar syndrome, where gilbert’s syndrome + * + 78 + 00:07:26,139 --> 00:07:32,889 + was a low amount of UGT, Crigler Najjar is + where there’s pretty much no UGT and therefore + * + 79 + 00:07:32,889 --> 00:07:41,379 + no ability to conjugate UCB, this will lead + to SUPER high levels of UCB, and likely UCB + * + 80 + 00:07:41,379 --> 00:07:49,439 + deposits in the brain and kernicterus; Crigler + Najjar syndrome is usually fatal. + * + 81 + 00:07:49,439 --> 00:07:54,300 + The previous couple examples focused on high + levels of unconjugated bilirubin in the blood, + * + 82 + 00:07:54,300 --> 00:07:58,090 + but there are also examples of jaundice with + high levels of conjugated bilirubin in the + * + 83 + 00:07:58,090 --> 00:07:59,199 + blood. + + 84 + 00:07:59,199 --> 00:08:03,469 + Dubin-Johnson syndrome is an autosomal recessive + disorder where there’s a deficiency in the + * + 85 + 00:08:03,469 --> 00:08:13,289 + protein that helps move CB from the liver + cell to the bile ducts, called MRP2, so CB + * + 86 + 00:08:13,289 --> 00:08:20,569 + builds up in the hepatocyte. It’s thought + that when the MRP2 transporter is defected, + * + 87 + 00:08:20,569 --> 00:08:27,300 + another transporter, MRP3 is upregulated, + though this transporter moves it into the + * + 88 + 00:08:27,300 --> 00:08:33,599 + interstitial space and blood flow, as opposed + to the bile canaliculus, so in this case you’ll + * + 89 + 00:08:33,599 --> 00:08:38,380 + have increased CB in the blood, which also + gets excreted into the urine, giving it a + * + 90 + 00:08:38,380 --> 00:08:44,560 + darker color, this leakage also causes the + liver itself to get super dark. + * + 91 + 00:08:44,560 --> 00:08:50,470 + Another high-CB category of jaundice is called + obstructive jaundice, and this is basically + * + 92 + 00:08:50,470 --> 00:08:56,150 + where something blocks the flow of bile, these + blockages could be anything from gallstones, + * + 93 + 00:08:56,150 --> 00:09:02,350 + pancreatic carcinomas and cholangiocarcinomas, + to parasites like the liver fluke. Remember + * + 94 + 00:09:02,350 --> 00:09:07,200 + that bile’s made up of conjugated bilirubin + and this blockage basically causes pressure + * + 95 + 00:09:07,200 --> 00:09:11,940 + to rise in the bile duct, which literally + causes bile to leak through the tight junctions + * + 96 + 00:09:11,940 --> 00:09:19,570 + between hepatocytes, but that’s not the + only thing that leaks out though; bile salts, + * + 97 + 00:09:19,570 --> 00:09:24,510 + bile acids, and cholesterol all can can get + into the blood. If they deposit in the skin, + * + 98 + 00:09:24,510 --> 00:09:30,080 + it could lead to itchiness or pruritus, but + also lead to things like hypercholesterolemia + * + 99 + 00:09:30,080 --> 00:09:39,460 + and xanthomas. The excess CB is excreted in + the urine, leading again to dark urine. Also, + * + 100 + 00:09:39,460 --> 00:09:44,100 + since you’re losing bile, you won’t be + able to absorb fat as well, which (1) causes + * + 101 + 00:09:44,100 --> 00:09:50,190 + you to excrete a ton of fat, a condition called + steatorrhea, and (2) causes you to not be + * + 102 + 00:09:50,190 --> 00:09:54,280 + able to absorb as many fat-soluble vitamins + as you need. + * + 103 + 00:09:54,280 --> 00:10:01,060 + Finally, viral hepatitis leads to both conjugated + and unconjugated bilirubin in the blood. When + * + 104 + 00:10:01,060 --> 00:10:05,220 + hepatocytes get infected and start to die + off, they both lose the ability to conjugate + * + 105 + 00:10:05,220 --> 00:10:12,320 + bilirubin, leading to excess UCB in the blood, + AND since they also line the bile ducts, when + * + 106 + 00:10:12,320 --> 00:10:19,130 + they die they let bile leak out into the blood, + causing an increase in blood CB as well. Again, + * + 107 + 00:10:19,130 --> 00:10:29,820 + since CB is up, patients will have more CB + excreted and darker urine.