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工作细胞(二)擦伤

2020-05-09 21:14 作者:濮天老师  | 我要投稿

Episode 2 - Scrape wound
第二集:擦伤



角色介绍
Platelet
血小板

血小板

When I started this, I had figured that the logical progression would be RBC > neutrophil > platelet, but it's pretty clear the platelet is the star of this episode (not to mention a fan favourite), and so merits next discussion.
刚开始时,我还以为这番应该按 红细胞 --> 中性粒细胞 -->血小板 的顺序来介绍。但这集的主角明显是血小板嘛 (人活着就是为了血小板),所以接下来介绍它们。


The platelet is the smallest cell in the human body--that is, if we were to even consider it a cell. Platelets are actually cellular fragments that mature and break off of the very large precursor, the megakaryocyte. They are extremely small--2 to 3 microns in diameters--and have a relatively simple structure. Like the RBC, they have no nucleus, which means they have no regenerative potential. Normal humans should have 150-450 thousand per microliter of blood, or around 0.5-2.5 trillion in total.
血小板是人体里最小的细胞,如果你还把它当细胞的话。血小板其实是细胞残余,它从它的前身,一个超级大的细胞“巨核细胞”中脱落下来。它们超级小,直径2-3微米,结构比较简单。像红血球一样,它们也没有细胞核,也就是无法再生。一微升的血液里有15-45万个血小板,也就是,人体里大概有5000亿~2.5万亿个血小板。


The platelet's primary (actually, sole) function is to trigger hemostasis, or clotting. Hemostasis is an extremely complex and highly regulated process with many different moving parts and players. To briefly summarize it, platelets circulate in the blood stream, happily rolling along until they encounter a damaged vessel. Instead of the normal smooth vascular endothelium, they come into contact with exposed subendothelial collagen and von Willebrand factor.
血小板的主要(唯一)作用是止血。止血过程非常复杂,需要好多玩意儿一起协调管理。简单来说,血小板在血液中流动,碰到破损的血管就会停下来。它们不接触平滑的血管内皮,而是与暴露出的 内皮下胶原 和'血管假性血友病因子'(von Willebrand factor)结合。


Platelets express receptors that help them bind to this substrate (glycoprotein 1b complex, or GP1b). Once bound, they become activated, secreting numerous chemical substances from either alpha granules or dense granules. These substances include proteins that bind more platelets and small molecules cause more activation (examples: calcium, thromboxane-A2, and ADP). Importantly, the use of an NSAID poisons platelets, stopping them from producing thromboxane-A2, and impairing their function. This is (one of many) reasons a patient at risk of cardiovascular disease may take a daily aspirin.
血小板产生受体,帮它们和底物GP1b结合(糖蛋白1b复合物)。一旦结合,血小板就会活化,从'α颗粒体'和'致密颗粒'中分泌出一系列化学物质。这些东西包括,可以粘上更多血小板的蛋白质,以及导致它更加活化的小分子(比如,钙离子,血栓素A2,ADP)。阿司匹林等抗炎药会毒害血小板,不让它们产生血栓素。这就是为什么心血管病病人,每天可能得吃片阿司匹林。


血小板的书包是GP1b,血小板和这种蛋白质结合之后,就会变得‘粘’起来


And recall that since the platelet has no regenerative potential, there is naught to do but wait for the platelet to be eliminated and replaced with unpoisoned platelets (their lifespan is around 7 days). You may have a relative whose surgery was deferred for a week for such a reason, as it increases the risk of bleeding. The activated platelets express another receptor, glycoprotein IIb/IIIa, which allows them to bind other platelets by linking through a molecule called fibrinogen, which is produced by the liver and floats in the circulating plasma. The platelets and fibrinogen constitute a "platelet plug"--this is the process of primary hemostasis.


还记得吧,血小板不可自我再生。所以,我们只能等着中毒的血小板被清理走,换成健康的血小板(血小板存活天数:大约7天)。手术就可能因此推迟一周,因为中毒的血小板会导致大出血。活化的血小板还有另一个受体,糖蛋白IIb/IIIa, 它让血小板通过‘纤维蛋白原’(从肝脏产生)和其他的血小板伙伴们结合。‘血小板’和‘纤维蛋白原’组成了‘血小板栓’ - 就是初期止血的过程。


A platelet plug is not very sturdy, however, and maturation of the plug requires the effect of coagulation factors, more soluble proteins usually made in the liver. This process is kind of complicated, so let's not get into it. What results is the enzymatic cleavage of fibrinogen into mature fibrin, which is much more sturdy. This is the process of secondary hemostasis.
但是,血小板栓不太结实。成熟的‘血小板栓’,需要一种更可溶的蛋白质,凝血因子(通常在肝脏产生)。这个过程比较复杂,就不细说了。结果就是,‘纤维蛋白原’分开,变成更结实的‘血纤蛋白’。这是第二期止血过程。


血纤蛋白,可以更有效地止血

A few other random thoughts about platelets: There are many diseases that involve platelets (and hemostasis more broadly), whether through inherited defect (Von Willebrand disease, Glanzmann's thrombasthenia, Bernard-Soulier disease) or acquired malfunction (DIC, TTP, ITP, PTP). Unclear if these will come up.. What you should take away is that the platelet initiates and largely controls clotting. I don't have anything insightful to say about their character design, however. The hat, boots, and oversized shirt are not immediately reminiscent of platelet cytomorphology. Their blue theme is probably also stylistic.


再随便聊聊血小板。血小板和很多疾病有关,有的原因是基因缺陷(血友病,血小板无力症,巨大血小板综合症),有的是后天缺陷(DIC, TTP, ITP, PTP)。不知道以后会不会提到这些……现在记得血小板启动、并且控制止血就好。对于血小板的角色设计,我没什么好说的。帽子,鞋,还有大T-shirt和血小板细胞本身的造型没什么关系。它们身上的蓝色也估计是为了造型。


血小板是最小的细胞

Episode 2 - Scrape wound
第二集 - 擦伤


Intro: A scrape wound, or "abrasion" in typical doctor-speak, is a superficial injury sustained to the epidermis. These injuries can bleed and be painful, but usually do not require special intervention or treatment beyond being kept clean and can resolve by themselves, as we shall see.
擦伤,是表皮上产生的表面伤害。伤口可能会流血,疼痛,但除了保持伤口清洁之外,并不需要特别处理。如之后所见,它会自愈。


Our protagonist RBC, AE-3806 is on a delivery trip to drop off some nutrients. Capillary 34?! Try 3.4 billion! No wonder she's always getting lost. 

AE-3806在搞快递,输送营养。毛细管34?!应该是34亿才对!怪不得她总迷路。

毛细血管34号?应该是34亿号才是


A note on the nutrients that came up last time: Red blood cells do not generally carry nutrients. They do contain some amount of sugar and amino acids, and their lipid membranes do constitute some usable energy, but by and large "food" is dissolved in plasma. Glucose (the most readily usable energy source for any organ, and especially preferred by nervous tissue and RBCs) is directly dissolved. Amino acids too, if I recall correctly. Lipids tend to be transported in small protein-bound particles (lipoproteins), as their nonpolar nature precludes direct dissolution in plasma, which is aqueous. See?


上回说过,红细胞一般不输送营养。它们的确含糖以及氨基酸,它们的磷脂双分子层(细胞膜上的)里也有可用的能量,但大部分情况下,“食物”溶解在血浆里。葡萄糖(最容易被利用的能源,神经组织和红细胞的最爱)会直接溶解到血里。印象里氨基酸也可以溶解。磷脂会由脂蛋白运送,因为它们非极性(不溶于水),不会直接溶解在水性的血浆里。


A bunch of platelets are transporting...something. We'll learn what later. They have some trouble getting down some stairs--this does not represent any physiologic process to me, probably it's just them being cute. Hopefully a gaggle of platelets moving in a group does not represent a thrombus (clot), that would not be something you'd want floating around...
一群血小板在运送个……啥?后面我们就知道了。他们下台阶不太顺利,这和生理过程没啥关系,就是为了卖萌吧。血小板这么聚集在一起,希望这并不代表血栓,谁都不想让那玩意动来动去啊!

血小板下台阶,就是为了卖萌吧

Oh, the big package is fibrin. Well, it's probably fibrinogen, as used fibrin cannot be "recycled" but is instead digested by a series of fibrinolytic enzymes expressed by endothelial cells. These enzymes have been reverse-engineered by us to be used as "clot busters" in stroke and heart attack patients.
哦呀,大箱子里是“血纤蛋白”。其实应该是“纤维蛋白原”吧,因为用过的“血纤蛋白”不能回收,而是会被内皮上分泌的一系列“ 纤维蛋白溶解酶”消化掉。我们也可以反过来利用这些酶,‘捅开’中风或心脏病人的血栓。

网状物是纤维蛋白原

AE3803 and her senpai travel to a superficial vessel in the skin. To briefly summarize, the skin is one large, continuous epithelial lining which functions in thermoregulation, in sensation, but most importantly as a barrier to the external environment. If you were to lose your skin (say, suffer a severe burn), you will find that it becomes difficult to impossible to regulate your internal environment, not to mention inviting a bunch of foreign invaders, as we shall see...
AE3803和红血球前辈在皮肤表层的血管走动。简单来说,皮肤是一大片连续的上皮层,它控制温度、感知,但最重要的是,它隔离了外界。如果你没了皮肤(比如严重烧伤),就会发现很难、或者不可能调节身体内部环境,而且还会让外敌入侵,我们待会就看到了……

红细胞在皮肤表层的血管里流动

Oops, giant scrape wound. We better get used to AE3803 being helpless and saved a lot, as erythrocytes truly do not have any sort of defense mechanisms. In typical fashion, U-1146 is one of the first responders.
呀哈,好大的伤口。我们也该习惯AE3803弱小可怜又无助了,因为红细胞真的没有任何的防御机制。按套路,U-1146又是第一个回应的。

巨大的伤口坑

Invasion! We get a glimpse of some new bacteria. I can't begin to identify all of them without some additional cues, but we will get to look at a couple in depth here.
入侵警告!我们看到了一些新细菌。我不能一一辨认,但会仔细说下其中几个细菌。

各类病菌从伤口入侵


Staphylococcus Aureus

金黄色葡萄球菌

金黄色葡萄球菌,没有伤口的话,她的危害并不大

Staphylococcus Aureus is one of the most common human pathogens. It, like most staph and strep species, is a skin commensal--that is, it normally lives on the surface of your skin, not causing any problems unless it is introduced into a wound. The design of this character gives it away immediately; staph aureus is known for producing a pigment that gives it a bright golden color, staphyloxanthin (Staph aureus, from the latin "aurum" meaning gold). Also notice the clusters of, uhh, balls on her. This is an allusion to its tendency to form "clusters" in culture. It also causes a huge number of diseases and expresses a wide variety of virulence factors. It can cause skin infections (cellulitis), pneumonia, endocarditis, really it can **** with any organ it gets into. And alarmingly, it is resistant to a number of antibiotics, a number that is steadily growing.
金黄色葡萄球菌是最常见的一种人类病原体。像大部分的葡萄球菌和链球菌一样,它一般活在皮肤表面。一般来说,它不会造成任何问题,除非——你有了伤口。它的人设非常有特点,让人一眼就知道是它。‘金黄色葡萄球菌’会产生一种染料,让它变成金黄色(金黄色葡萄球菌的英文是Staph aureus, aureus就是拉丁语的‘金子’,所以化学符号Au也代表‘金’)。还有注意它那一串串的……嗯……球球。这代表它在培养液里容易形成“菌落”。它也会造成许许多多的疾病。它能导致皮肤炎(蜂窝组织炎),肺炎,心内膜炎,基本上能搞坏任何它接触的器官。更可怕的是,它对一些消炎药有抗药性,并且抗药的种类越来越多。


培养液和显微镜下的金色葡萄球菌

Streptococcus Pyogenes
酿脓链球菌

酿脓链球菌,可以引起‘链球菌性喉炎’

Streptococcus Pyogenes is another common skin commensal related to our friend pneumococcus. It too is gram-positive, though this guy is not blue. Maybe my old theory should be tossed. Like staph aureus, it can cause all manner of infection, though the one you are probably most familiar with is strep throat. We have some visual cues again; the "balls" are arranged in chains this time, reflecting its tendency to form chains in culture.

酿脓链球菌是另一种常见的皮肤上的细菌,它和之前的肺炎球菌也有关系。它也是革兰氏阳性,虽然这家伙并不是蓝色的。也许我之前的理论不对。和金黄色葡萄球菌一样,它也可以引起各种感染,但你们最熟悉的应该是它引起的咽喉炎。他的人设也是有道理的;他身上的“球”排成一串,是因为它容易在培养液里形成‘串’。

显微镜下的酿脓链球菌,会排成一串串的

Pseudomonas Aeruginosa
绿脓杆菌

绿脓杆菌

Pseudomonas Aeruginosa is another very common bug. This one is, to my knowledge, not a typical skin commensal, but it is ubiquitous in the environment, in soil, etc. Unlike all of the other bugs so far, it is a gram-negative rod, and this guy's green color is due to a pigment involved in binding iron (pyocyanins, pyoverdin). It too can cause a huge variety of infections, and can be notoriously resistant to antibiotics. It also has a distinctive, uh, "grapey" odor.

绿脓杆菌也是个常见的细菌。不过据我所知,它在皮肤上不常见,但是它在外界环境里到处都有,比如土壤里就有。和其他的几位不一样,它是革兰氏阴性。这家伙是绿色的,因为它和铁结合就绿了(绿脓青素)。它也可以引起一大堆感染,也对消炎药有抗药性。它还有很特别的“葡萄味”。


培养液和显微镜下的绿脓杆菌


The vessels are constricting. This is a normal reflexive process with any sort of vascular damage to minimize blood loss, and its driven by both neural impulse (though someone may wanna check me on that) and chemicals like endothelin.

血管在收缩。这是正常条件反射,血管受损时,这样可以减少流血量。收缩由神经信号以及化学物质(如内皮素)引起。

血管收缩,这是对擦伤的正常反应

Damn valve. We've already been over them (Ep. 1).
又是静脉瓣。第一集里说过了。

静脉瓣只能单向通行

Lmao neutrophils back on the scene. I wanted to point this out last episode, but if the neuts seem single-minded in their pursuit of bacteria, it's because they are. They are actually quite "dumb" and just move towards any foreign antigen and try to eat or kill it.

妈妈咪呀,中性粒细胞又回来了。这些中性粒细胞追细菌时非常一根筋,这是因为他们就是头脑简单。它们蛮傻的,只会冲向外来抗原,要么吃掉它们,要么杀掉它们。

中性粒细胞碰到细菌,就是会这么一根筋地干干干

Oh, I forgot to describe the process of neutrophil diapedesis earlier. A detailed explanation can wait until I do the neutrophil character highlight, but briefly: In order to reach their target tissues, neutrophils have adhesion molecules that allow them to cling to vascular endothelium and squeeze between them (transmigration). L-selectin is a protein that allows them to bind...I'm not actually sure what specifically ("sulfatides and sulfated polysaccharides", apparently).

忘了说“中性粒细胞渗出”了。详细的等‘中性粒细胞’做主角时再讲,简单来说就是,为了贴近目标,中性粒细胞身上有粘合性的分子,把它们粘在血管内皮上,然后再从内皮之间挤过去。蛋白质‘L-选择素’就可以让中性粒细胞和‘硫脂类’和‘硫酸多糖类’结合。
这个渗出过程后面有表现,我先贴这儿了。

中性粒细胞渗出,为了接近目标,他会‘挤’过血管

I don't agree with Staph Aureus's assessment that by overcoming local neutrophil response that she'll be able to sneak right on through. A localized infection takes hold, but you can bet that as long as there are still foreign peptides and inflammatory cytokines, the immune system will keep sending soldiers.
我不同意金葡菌的分析,啥?冲破了中性粒细胞的防线就能入侵进去?感染目前只在一小片区域,但只要有外界物质和感染的‘细胞因子’,免疫系统就会不断输送士兵过来。


Platelets inbound! Aha, see? GP1b. And I guess the metal things are coagulation factors (reminder that these are normally dissolved in plasma, and generally not directly carried by platelets).
血小板入场!看吧,GP1b。我估计金属的东西是“凝血因子”。提醒下,这些因子一般溶于血浆,不由血小板输送。

血小板的书包是GP1b,拿的圆东西是凝血因子

Aaaand boom, secondary hemostasis. Oh yeah, although fibrin is the chief protein required for forming a mature clot, any cells in the vicinity will get stuck and incorporated into the clot. The ultimate fate of all of these cells (platelets, entrapped RBCs and anything else) will be to ultimately die and degenerate as the clot matures, until it is either broken up by fibrinolytic enzymes, eaten up by macrophages, or (as scabs do) falls away. Late in the healing process, the normal tissues will regenerate.

当当当。第二次止血过程。哦,没错,尽管止血主要需要‘血纤蛋白’,但是它也会把周边的细胞吸过来。这些细胞的最终命运(血小板,被吸的红血球等等),就是在血凝块形成好时死去,降解。它们可能被“溶解纤维蛋白酶”分解,被“巨噬细胞”吃掉,或者随着血痂脱落。之后的愈合期里,会再生出正常组织。


被拉走的红细胞、白细胞,还有血小板本该都死掉

Summary

总结
Another fairly humdrum infectious incursion resulting from an abrasion. Again, this probably required no treatment and resolved naturally. I think we can get comfortable with our heroes sticking around for a long time, because they really should have died by now.


总结,这是擦伤引起的临时性感染。它也不需要特别处理,会自己痊愈。主角们都自带光环,因为它们现在本该死掉。


生物类单词

platelet  血小板

precusor  前身

megakaryocyte  巨核细胞

nucleus  细胞核

hemostasis  止血

vessel  血管

vascular endothelium  血管内皮

collagen 胶原

receptor 受体

substrate  底物

glycoprotein  糖蛋白

fibrinogen  纤维蛋白原

platelet plug  血小板栓

coagulation factor  凝血因子

fibrin  血纤蛋白

fibrinogen  纤维蛋白原

inherited defect  先天缺陷

acquired malfunction  后天缺陷

cytomorphology  细胞形态

epidermis  表皮

amino acid  氨基酸

plasma  血浆

lipid  磷脂

glucose 葡萄糖

nonpolar  非极性

thrombus  血栓

endothelial  内皮的

endothelium 内皮

epithelial  上皮的

Staphylococcus Aureus  金黄色葡萄球菌

culture  培养液

pneumonia  肺炎

endocarditis   心内膜炎

Streptococcus Pyogenes  酿脓链球菌

strep throat  链球菌性喉炎

Pseudomonas Aeruginosa  绿脓杆菌

antibiotics  抗生素

diapedesis   血细胞渗出

cytokine    细胞因子




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