美国医学院讲师清晰讲解肝脏淤积基本知识。内容包括总胆红素;直接胆红素;间接胆红素;肝脏内管、肝脏外管堵塞的原理及相关疾病;间接胆红素转换为直接胆红素的原理及转换不正常的相关疾病;碱性磷酸酶检测和谷氨酰转肽酶检测等。

本文由‘中国推动’学者,英国爱丁堡大学医学院、浙江大学邵逸夫医院王珍女士翻译整理。

Welcome to another MedCram video. We’re going to talk about cholestasis here in liver function tests. So picking up on the theme that we were talking about before when we talked about AST, ALT, albumin, and PRO (prothrombin) time, we were talking about the actual liver parenchyma itself.

欢迎观看另一个MedCram视频。我们将在肝功能测试中讨论胆汁淤积。因此,当我们谈论AST,ALT,白蛋白和PRO(凝血酶原)时间时,我们所谈论的主题已经开始,我们谈论的是真正的肝器官的功能组织。

Next, we want to talk about cholestatic. What does that mean? Well, we talked about the liver, specifically, there is a gallbladder, and that is connected with a cystic duct. There is a then of common bile duct, and that dumps into the intestines. The purpose of this is two-fold: help with digestion of fats, but also to get rid of some products, specifically heme products, and that’s what we’re going to talk about next. We’re going to talk about things like the alkaline phosphatase, the gamma gluten transferase, serum bilirubin, bile acid, and things of that nature. 

接下来,我们要谈谈胆汁淤积。这意味着什么?好吧,我们谈到了肝脏。具体来说,有一个胆囊,它与胆囊管相连。然后有一条胆总管,并排入肠道。这有两个目的:帮助脂肪消化,还摆脱一些产品,特别是血红素产品,这就是我们接下来要讨论的内容。我们将谈论诸如碱性磷酸酶,γ-谷蛋白转移酶,血清胆红素,胆汁酸之类的事物。

So let’s go through that very carefully. Okay, so let’s draw a picture here of what’s going on schematically. Here is our liver. This is schematic, and we’ve got the red blood cell. So we’ve got blood over here, which lasts for about a hundred and twenty days. So here’s our red blood cell, and it gets broken down after a while, and spleen and the reticuloendothelial system, and what it gives up is something we call unconjugated, or another way of saying this is indirect (the way to measure it) bilirubin.

因此,让我们非常仔细地进行检查。好的,让我们在这里画一幅示意图。这是我们的肝脏。这是示意图,我们有红血球。所以我们这里有血迹,持续了一百二十天。因此,这是我们的红细胞,过一会儿就会分解,还有脾脏和网状内皮系统,而它所放弃的是我们所说的非结合的,或者说这是间接的(测量方法)胆红素。

And that goes to the liver, and it gets converted. So there is enzyme in there, and it gets converted and excreted as something different called conjugated, or direct bilirubin. And there are actually ducts in here. Those ducts that are inside the liver, just so you are aware, are intrahepatic, and the ducts outside are extrahepatic.

然后进入肝脏,并在那里转化, 并产生一些酶,然后继续转化并排出为另一种称为共轭或直接胆红素的物质。实际上,这里有管道。众所周知,那些位于肝内部的导管是肝内的,而那些外部的导管是肝外的。

Now the kidney also fits into this, in that the conjugated bilirubin, and not the unconjugated bilirubin, can be excreted through the kidney. So what do I mean by that? If for some reason there is a blockage here in the extrahepatic or in the intrahepatic ducts that are supposed to get rid of the bilirubin in the bile acids, what’s going to happen is the conjugated bilirubin is going to build up in the blood, and the unconjugated bilirubin is going to build up in the blood, and you’re going to be able to check it with a blood test.

现在肾脏也适合这个,因为结合的胆红素而不是未结合的胆红素可以通过肾脏排泄。那我是什么意思呢?如果由于某种原因在肝外或肝内导管中存在清除掉胆汁酸中的胆红素的阻塞,那么将发生的是结合的胆红素将在血液中积聚,并且未结合的胆红素会在血液中积聚,您将可以通过验血来检查它。

However, only one of these things, and that is specifically the conjugated bilirubin, because it’s conjugated, it is more water-soluble, is going to be able to make it through the blood and actually get excreted out through the kidney.

但是,只有其中之一,特别是结合胆红素,因为结合后胆红素的水溶性更高,因此能够通过血液制造并实际上通过肾脏排泄出去。

So if you see bilirubin urea, not amenia, but urea, that is the presence of conjugated bilirubin in the blood. You will not see unconjugated bilirubin being passed through the kidney. So if you see bilirubin in the urine, that means you must have conjugated bilirubin in the blood, and that means either intrahepatic or extrahepatic obstruction.

因此,如果您看到的是胆红素尿素,这不是贫血,而是尿素,那就是血液中存在结合胆红素。您不会看到未结合的胆红素通过肾脏。因此,如果您在尿液中看到胆红素,则意味着您的血液中必须含有结合的胆红素,这意味着肝内或肝外阻塞。

Okay, so with that, let’s start going through this methodically. The first test that I want to talk about is the presence of alkaline phosphatase (ALK Phos). You’ll see this on a regular, complete metabolic panel. It has a low specificity for cholestasis because there are three things that can increase the level of alkaline phosphatase.

好的,让我们开始有条不紊的学习。我要谈的第一个测试是碱性磷酸酶(ALK Phos)的存在。您会在常规,完整的新陈代谢面板上看到这一点。它对胆汁淤积的特异性低,因为有三件事可以增加碱性磷酸酶的水平。

The first thing is cholestasis, which is exactly what we’re talking about here: any kind of blockage along the intra-hepatic or extra-hepatic area is cholestasis, which can increase the alkaline phosphatase. Alkaline phosphatase is what we call an inducible enzyme, which means it takes a little while for it to happen. It’s not going to happen right away, but it will happen. The second thing that can cause an increase in alkaline phosphatase is pregnancy.

首先是胆汁淤积,这正是我们在这里所说的:肝内或肝外区域的任何类型的阻塞都是胆汁淤积,它可以增加碱性磷酸酶。碱性磷酸酶是我们所谓的诱导酶,这意味着它需要一些时间才能发生。它不会马上发生,但是会发生。可以导致碱性磷酸酶增加的第二件事是怀孕。

The third thing that can cause an increase in alkaline phosphatase is bone disease, specifically bone growth. So where would we see something like that? For instance, Paget’s disease, where you have increased bone turnover, also in blastic, not lytic, type of cancers. What are the blastic type of cancers? Prostate and breast can cause blastic lesions. So cholestasis is just one of those things. So if you have an elevated alkaline phosphatase, you’re not exactly sure what’s causing it. Is it cholestasis pregnancy or bone growth?

可能导致碱性磷酸酶增加的第三件事是骨骼疾病,特别是骨骼生长。那么我们在哪里可以看到这样的东西?例如,佩吉特氏病(Paget’s disease),在这种情况下,您的骨转换率增加,而且是成骨性的而不是溶解性的癌症。什么是原发性癌症?前列腺和乳房会引起弹状病变。因此,胆汁淤积只是其中之一。因此,如果碱性磷酸酶升高,则不能完全确定是什么原因引起的。是胆汁淤积怀孕还是骨骼生长?

But cholestasis is one of those things. If we see a blockage here, you will get an increase in alkaline phosphatase, but it’s got a low specificity for cholestasis. The biliary ductal cells is what increases it. You can see an increase in most types of liver damage as a result of that, and high levels are seen in cholestasis.

但胆汁淤积是其中之一。如果我们在此处看到堵塞,则碱性磷酸酶会增加,但对胆汁淤积的特异性较低。胆管细胞增加了它。因此,您可以看到大多数类型的肝损伤有所增加,并且胆汁淤积症的水平很高。

So because of that uncertainty, there’s another test called a GGT, or otherwise known as Gamma-glutamyltransferase. Now, this is pretty good because you do see an increase in GGT in cholestasis, but you don’t see it in bone disease.

因此,由于存在这种不确定性,因此存在另一项称为GGT的测试,也称为γ-谷氨酰转肽酶。现在,这非常好,因为您确实发现胆汁淤积症中的GGT升高了,但是在骨病中却没有看到。

So, I’ll put a big X there. You do not see it in bone disease, just cholestasis. So the way this is used as if you have a patient with a high alkaline phosphatase, and you want to see whether or not this is GI-related or liver-related, you can get a Gamma-glutamyltransferase, and if it is low, if the Gamma-glutamyltransferase is low, that means it’s not from the liver. If it’s high, then that means it probably is from the liver. Interestingly, alcohol (ETOH), can also make Gamma-glutamyltransferase elevated.

因此,我将在其中放一个X。您没有在骨病中看到它,只是胆汁淤积。因此,使用此方法的方式就好像您有一个碱性磷酸酶高的患者,并且想要查看这是与胃肠道相关还是与肝有关,您可以得到一个Gamma-谷氨酰转移酶,如果它低,如果γ-谷氨酰转移酶低,则说明它不是来自肝脏。如果很高,则意味着它可能来自肝脏。有趣的是,酒精(ETOH)也可以使Gamma-谷氨酰转移酶升高。

So let’s take a look at our chart again. You can see here that if we have a lot of breakdown of blood products, we’re going to get a lot of unconjugated bilirubin, so you can see that indirect bilirubin. The way you would check for that is by checking total bilirubin on the blood test and also checking for direct bilirubin, and the difference between these two is going to be your indirect bilirubin.

因此,让我们再次看看图表。您可以在这里看到,如果我们的血液制品分解很多,我们将得到很多未结合的胆红素,因此您可以看到间接胆红素。您检查血液的方法是检查血液中的总胆红素,并检查直接胆红素,两者之间的差异将是您的间接胆红素。

If you see that that is high, it can either mean that you have a lot of breakdown of blood products. So where would we see that? We’d see that in DIC (Disseminated intravascular coagulation) intravascular hemolysis, that type of thing, or it could be the inability to convert unconjugated bilirubin to direct conjugated bilirubin. What are one of these diseases? Well, the most common disease is this thing called Gilbert’s disease, it looks like Gilbert.

如果您发现该数字很高,则可能意味着您有很多血液制品分解。那么我们在哪里看到呢?我们将看到,在DIC(弥散性血管内凝血)中,血管内溶血是这种类型的事情,或者可能是无法将未结合的胆红素转化为直接的结合胆红素。这些疾病是什么之一?好吧,最常见的疾病就是这种叫做吉尔伯特氏病的东西,看起来像吉尔伯特氏病。。全称是胆红素尿苷二磷酸葡萄糖苷酸基转移酶——BUGT。爱丁堡大学医学院JANE提供。】

But it’s pronounced G-Bears disease. Believe it or not, this condition is present in up to 5% of the general population, and you would see an increase in the total bilirubin up to about 3.0 milligrams per deciliter. And this is a result of decreased expression of this enzyme glucuronyltransferase, which is the important step in the conversion of indirect bilirubin to direct bilirubin.

但这是明显的G-熊疾病。信不信由你,这种情况在总人口中所占比例高达5%,您会发现胆红素的总增加量高达每分升3.0毫克。这是该酶葡糖醛酸转移酶表达降低的结果,这是间接胆红素转化为直接胆红素的重要步骤。

Now, if you get a problem anywhere along here, so liver damage, drug damage, inability to excrete the direct conjugated bilirubin after it’s been processed back into the biliary ducts. This is the intrahepatic ducts or in the extrahepatic portion. Let’s say you’ve got a tumor of the pancreas, or you’ve got a stone blocking the common bile duct, you will get an increase in this conjugated direct bilirubin, and it will back up into the blood.

现在,如果您在这里的任何地方都遇到问题,那么肝脏损伤,药物损伤以及直接结合的胆红素在被处理回到胆管后都无法排泄。这是肝内导管或肝外部分。假设您患有胰腺肿瘤,或者您的结石阻塞了胆总管,那么这种结合的直接胆红素就会增加,并会回到血液中。

Not only that, you’ll also see an increase in unconjugated or indirect bilirubin. So how do you tell if that’s what’s going on? Well in this situation, because the blockage is here, you’re going to see at least 50% of the bilirubin in the blood being of the direct type. So if you check total bilirubin and direct bilirubin, you’ll see that the direct bilirubin is more than 50 percent of the total bilirubin. That led you to believe that there is some either intrahepatic or extrahepatic obstruction causing this cholestatic jaundice.

不仅如此,您还会看到未结合的或间接的胆红素增加。那么,如何判断这是怎么回事?很好,在这种情况下,由于存在阻塞,您将看到血液中至少50%的胆红素为直接型。因此,如果您检查总胆红素和直接胆红素,您会发现直接胆红素占总胆红素的50%以上。这使您相信,肝内或肝外都有一些阻塞会导致胆汁淤积性黄疸。

Now because direct bilirubin is building up in the blood, and because it is more water-soluble, it’s going to pass from the blood into the kidney, and you’re going to pick up hyper bilirubin urea, and that’s another sign that you’ve got direct conjugated bilirubin in the blood.

现在,由于直接胆红素在血液中累积,并且由于它更易溶于水,因此它将从血液传递到肾脏,您将摄取高胆红素尿素,这是您“血液中直接结合了胆红素。

Okay. So with this background in the next lecture, what we’re going to talk about is the type of patterns that you would see in actual diseases. We’re going to talk about acute hepatitis, chronic hepatitis, and cholestatic liver disease. So join us for the next lecture. Thanks very much!

好的。因此,在下一堂课的背景下,我们要讨论的是您在实际疾病中会看到的模式类型。我们将讨论急性肝炎,慢性肝炎和胆汁淤积性肝病。因此,请加入我们的下一堂课。非常感谢!

 

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