The epidermal barrier
英文原文
A mature epidermis is an effective barrier which prevents dehydration from the loss of body water, poisoning from the absorption of noxious substances, and systemic infection from invading surface microorganisms. The epidermal barrier resides within the most superficial layer of the skin, the stratum corneum. In utero the fetus has no need for a skin barrier, so the stratum corneum does not start to develop until around 24 weeks’ gestation. After 24 weeks there is a steady increase in the number of epidermal cell layers and in epidermal thickness, although it is not until around 34 weeks’ gestation that a well-defined stratum corneum has completely developed. A weak epidermal barrier is, therefore, present is very preterm infants (<30 weeks’ gestation) during the first 2–3 weeks of life and if the skin is damaged by trauma or disease.
对应中文
成熟的表皮是一种有效的屏障，它可以防止因失去身体水分而脱水、因吸收有毒物质而中毒、以及因表面微生物入侵而全身感染。表皮屏障位于皮肤最浅的一层，即角质层。在子宫内，胎儿不需要皮肤屏障，所以直到怀孕24周左右角质层才开始发育。24周后，表皮细胞层数和厚度稳步增加，但直到孕34周左右，角质层才完全发育。因此，在出生后的前2-3周内，如果皮肤受到创伤或疾病的损害，早产儿（<30周妊娠）会表现出表皮屏障虚弱。
英文原文
The skin is a vital organ, often taken for granted. Its most important function is to act as a barrier, preventing systemic infection from invading surface microorganisms, poisoning as a result of the absorption of drugs and chemicals, and dehydration from the loss of body water. The major barrier resides within the most superficial layer of the epidermis, the stratum corneum (SC). The deeper layers of the epidermis and the dermis, although much thicker than the epidermis, offer little resistance to drugs and water.
对应中文
皮肤是一个重要的器官，通常被认为是理所当然的。它最重要的功能是充当屏障，防止全身感染侵入表面微生物、防止全身因吸收药物和化学品而中毒、防止因失去身体水分而脱水。最主要的屏障位于表皮最浅的一层，角质层(SC)。表皮和真皮的深层，虽然比表皮厚得多，但对药物和水的抵抗力较低。
Structure of the epidermal barrier
表皮屏障的结构
英文原文
The SC is generated in the basal layer of the epidermis. As cells move towards the surface they lose their nuclei and develop keratohyalin to form an inert layer of dead, flattened, interdigitating cells. During this migration, the lipid content also changes. In the stratum granulosum, lipid is contained within intracellular lamellar bodies. As the cell moves into the SC this lipid is extruded into the intercellular spaces to form lipid bilayers around and between the corneocytes. The whole process shares some of the features of pulmonary surfactant production by the type-2 pneumocyte. The main difference is in the lipid composition, which in the SC is a mixture of cholesterol, ceramides and free fatty acids. The organization of these intercellular lipids and the degree of cohesion between cells seems to be vital for the maintenance of an effective epidermal barrier. As the cells move toward the skin surface the intercellular lipid becomes fragmented, the cohesive forces lessen and desquamation occurs. It follows that the epidermal barrier lies mainly in the deeper layers of the SC.
对应中文
SC产生于表皮的基底层。当细胞向表面移动时，它们失去细胞核，形成透明角质层，形成一层死的、扁平、交叉的细胞。在迁移过程中，脂质含量也会发生变化。在颗粒层中，脂质包含在细胞内的板层体内。当细胞进入SC时，这种脂质被挤出细胞间空间，在角细胞周围和之间形成脂质双层。整个过程具有2型肺细胞产生肺表面活性物质的一些特征。主要区别在于脂质成分，SC中的脂质成分是胆固醇、神经酰胺和游离脂肪酸的混合物。这些细胞间脂质的组织和细胞间的粘合程度似乎对维持有效的表皮屏障至关重要。当细胞向皮肤表面移动时，细胞间脂质变得碎片化，内聚力减少，并发生脱皮。因此，表皮屏障主要位于SC的深层。
Physiology of the epidermal barrier
表皮屏障的生理学
英文原文
The epidermal barrier of mature and intact skin has the following functions:
①It limits the loss of body water
②It prevents the absorption of chemicals and drugs
③It protects the body from invasion of micro-organisms
④It makes a small contribution to total respiration.
Measuring these functions can assess the integrity of the epidermal barrier.
对应中文
成熟完整皮肤的表皮屏障具有以下功能：
①限制身体水分的流失
②防止化学物质和毒物的吸收
③保护身体免受微生物入侵
④对总呼吸量的贡献很小
测量这些功能可以评估表皮屏障的完整性。
Transepidermal water loss
经表皮失水
英文原文
The SC is not completely waterproof, but allows a continuous diffusion of water out of the body called transepidermal water loss (TEWL). This is a passive process and must be distinguished from active sweating which occurs in response to thermal stress or emotion. In practice, this does not cause confusion when measuring skin water loss in the preterm infant since sweating does not occur until around 35 weeks’ gestation.
对应中文
SC不是完全防水的，它允许水分持续向体外扩散，称为经表皮失水(TEWL)。这是一个被动的过程，必须区别于因热应激或情绪而产生的主动出汗。实际上，这在测量早产儿皮肤失水时不会引起混淆，因为在怀孕35周左右才会出现出汗。
Factors affecting TEWL
影响TEWL的因素
Gestation
妊娠
英文原文
Term infants have a low TEWL (6 to 8 g/m2/hr), equivalent to that seen in adults. Skin water loss rises exponentially with increasing prematurity, particularly below 30 weeks’ gestation, when during the first few days of life more than 80 ml/kg (body weight) of fluid may be lost each day. TEWL is also high in low-birthweight infants, but this is merely secondary to the effect of gestation; birthweight has no independent effect.
对应中文
足月儿的TEWL较低 (6-8g/m2/hr)，与成人相当。皮肤水分损失随着早产儿的增加呈指数增加，特别是在妊娠30周以下，在生命的最初几天，每天可能会损失超过80ml/kg(体重)的液体。低出生体重儿的TEWL也很高，但这仅仅是次要的妊娠效应；出生体重没有独立的影响。
Post****natal age
出生后年龄
英文原文
In term infants, birth has no effect on TEWL. This contrasts sharply with the situation in preterm infants where the rapid structural maturation of skin causes a marked fall in TEWL, so that by 2 to 3 weeks of age values are similar to those found in term infants. The small amount of water lost through the mature skin of full-term and ex-premature infants is of little clinical importance.
对应中文
在足月儿中，分娩对TEWL没有影响。这与早产儿的情况形成鲜明对比，早产儿皮肤结构的快速成熟会导致TEWL显著下降，因此到2到3周时，TEWL值与足月儿相似。足月儿和早产儿通过成熟皮肤流失的少量水分在临床上并不重要。
Body temperature
体温
英文原文
Skin permeability and surface evaporation is increased by heat. TEWL is thus greater from warm than from cold skin. Raising the ambient temperature also increases skin water loss, although some of this effect is probably secondary to a concomitant increase in body temperature and fall in ambient relative humidity.
对应中文
皮肤渗透性和表面蒸发因受热而增加。因此，与寒冷皮肤相比，温暖皮肤的TEWL更大。提高环境温度也会增加皮肤失水，尽管这种影响可能是由于体温的持续升高和环境相对湿度的下降而导致的。
Ambient relative humidity
环境相对湿度
英文原文
Increasing ambient humidity leads to a linear fall in skin water loss. This observation is indicative of the passive nature of TEWL.
对应中文
增加环境湿度会使皮肤水分损失呈线性下降。这一观察结果表明TEWL的被动性质。
Radiant Heat
辐射热
英文原文
TEWL is increased by over 50% when radiant heaters are used as a means of thermal control because of an increase in surface evaporation. Phototherapy devices also deliver radiant heat, so a similar but smaller increase in water loss occurs.
对应中文
当使用辐射加热器作为热控制手段时，由于表面蒸发量的增加，TEWL增加了50%以上。光疗设备也能提供辐射热，因此水分流失也会出现类似但幅度较小的增加。
Skin damage
皮肤损伤
英文原文
The SC is readily damaged when adhesive tape is removed. This weakens the epidermal barrier and leads to an increase in TEWL.
对应中文
当胶带试验中拆下胶带时，SC很容易损坏，这会削弱表皮屏障，导致TEWL增加。
英文原文
In summary, the effect of gestation, postnatal age, and skin damage on epidermal function (measured by TEWL) and epidermal structure are closely correlated. A weak epidermal barrier is associated with a thin or damaged SC. TEWL is also seen to be a passive process with the rate determined by the diffusion gradient between the relative humidity of skin (fully saturated) and the surface environment (variable). In the clinical setting advantage can be taken of this; TEWL can be reduced by increasing ambient relative humidity or waterproofing the skin with, for instance, soft paraffin.
对应中文
总之，妊娠、出生后年龄和皮肤损伤对表皮功能(TEWL测量)和表皮结构的影响是密切相关的。脆弱的表皮屏障与薄的或受损的SC有关。TEWL也被认为是一个被动的过程，其速率由皮肤的相对湿度(完全饱和)和表面环境(变量)之间的扩散梯度决定。在临床环境中，可以利用这一点；TEWL可以通过增加环境相对湿度或使用例如软石蜡对皮肤进行防水来减少。
Percutaneous absorption of drugs and chemicals
药物和化学品的经皮吸收
英文原文
The poisoning of newborn infants by percutaneous absorbtion of aniline dye (causing methaemoglobinaemia) used as a laundry marker on nappies during the 19th century was first reported in 1886. More recently, the culprits have been antiseptics: hexachlorophene causing a spongioform myelinopathy, iodine causing hypothyroidism and goitre, and alcohol causing haemorrhagic skin necrosis and systemic intoxication. Techniques have now been devised that quantify percutaneous drug absorption and allow the integrity of the epidermal barrier to be assessed.
对应中文
1886年首次报道了19世纪时新生儿因经皮吸收苯胺染料导致高铁血红蛋白血症（该染料用来作尿布上的洗衣标记物)。最近，罪魁祸首是防腐剂：导致海绵状髓鞘病的六氯酚，导致甲状腺功能减退和甲状腺肿的碘，以及导致出血性皮肤坏死和全身中毒的酒精。现在已经对量化经皮药物吸收并评估表皮屏障完整性的技术进行了改进。
Factors affecting percutaneous absorption
影响经皮吸收的因素
Gestation
妊娠
英文原文
Poisoning as a result of percutaneous chemical and drug absorption is more common in preterm infants. Evidence that this is because of the poor epidermal barrier came from studies which showed that the blanching response to topical phenylephrine grew with increasing prematurity. Using cadaver skin in a perfusion cell, it has been shown that preterm skin is up to 50 times more permeable to alcohol, and more than 100 times more permeable to salicylate than term infant’s skin. Percutaneous absorption of buprenor- phine and diamorphine is also known to be greater in the most preterm infants.
对应中文
由于经皮化学和药物吸收导致的中毒在早产儿中更为常见。有证据表明这是因为表皮屏障差，研究表明，局部使用去氧肾上腺素的反应随着早产的增加而增加。使用尸体皮肤做灌注细胞试验，研究表明早产儿皮肤对酒精的渗透性是足月婴儿皮肤的50倍，对水杨酸的渗透性是足月婴儿皮肤的100倍以上。丁丙诺啡和二氢吗啡的经皮吸收在大多数早产儿中也被认为是更大的。
英文原文
The increased permeability of the preterm infant’s skin has also been demonstrated in studies aimed at developing transdermal therapy in babies. Theophylline and caffeine can be delivered percutaneously in preterm infants and therapeutic concentrations maintained for up to 3 days. These studies found that the highest levels were achieved in the most preterm infants.
对应中文
早产儿皮肤渗透性的增加在旨在开发婴儿透皮疗法的研究中也得到了证实。茶碱和咖啡因可经皮给早产儿使用，治疗浓度可维持3天。这些研究发现，大多数早产儿达到了最高的水平。
Postnatal age
出生后年龄
英文原文
The permeability of preterm infants’ skin to drugs and chemicals is transient. By 2 to 3 weeks of age, poisoning as a result of the percutaneous absorption of noxious agents is unlikely, and transdermal therapy with theophylline and caffeine delivers small and sub-therapeutic amounts of drug.
对应中文
早产儿皮肤对药物和化学品的渗透性是短暂的：到2到3周大时，不太可能因经皮吸收有毒物质而中毒，而茶碱和咖啡因的透皮疗法会透过少量和亚治疗剂量的药物。吸收。用软膏或防水敷料封闭皮肤会增加SC的水合，削弱表皮屏障。
Skin damage and disease
皮肤损伤和疾病
英文原文
Skin damage from trauma or disease weakens the SC and renders the epidermis more permeable to drugs. This was illustrated most tragically in France, where an industrial incident led to the contamination of talcum powder with a higher than intended concentration of hexachlorophene. Percutaneous hexachlorophene poisoning occurred on a large scale, but the most severely affected babies had a nappy rash. Under more controlled conditions, the blanching response to topical phenylephrine is markedly increased when the SC is stripped by the removal of adhesive tape. Similarly, isopropyl alcohol, used as a local antiseptic wipe, is only likely to cause haemorrhagic skin necrosis if applied to damaged preterm skin since it evaporates too quickly to be absorbed through intact preterm skin. Occluding the skin with an ointment or waterproof dressing increases the hydration of the SC and weakens the epidermal barrier.
对应中文
创伤或疾病造成的皮肤损伤会削弱SC，并使表皮对药物更具渗透性。这一点在法国表现得最为悲惨：一次工业事故导致滑石粉受到污染，滑石粉中的六氯苯浓度高于预期浓度，结果发生了大规模的自发性六氯苯中毒，受影响最严重的婴儿出现了尿布疹。在更受控制的条件下，当胶带试验中胶带剥离SC时，SC对局部去氧肾上腺素的反应显著增加。同样，异丙醇作为局部消毒擦拭，如果应用于受损的早产皮肤，只可能导致出血性皮肤坏死，因为它蒸发得太快，无法通过完整的早产皮肤吸收。用软膏或防水敷料封闭皮肤会增加SC的水合，削弱表皮屏障。
Chemical characteristics
化学特性
英文原文
A further insight into the nature of the epidermal barrier can be gained by studying the characteristics of chemicals that penetrate the skin. Chemicals (and drugs) diffuse from an area of high concen- tration to an area of low concentration, with the rate of movement governed by the diffusion gradient. Molecular weight also affects the rate of diffusion, with small molecules diffusing most rapidly. These features indicate that chemical diffusion is passive, and that in this respect the SC is acting as a semipermeable membrane. For agents with a molecular weight below 800 daltons, chemical solubility becomes more important than molecular size. A high degree of solubility in water and lipid allows rapid diffusion through the cell membrane, which is composed mainly of lipoprotein, as well as through the aqueous-based cell contents.
对应中文
通过研究渗入皮肤的化学物质的特性，可以进一步了解表皮载体的性质。化学品（和药物）从高浓度区域扩散到低浓度区域，其移动速度由扩散半径决定。分子量也影响扩散速率，小分子扩散最快。这些特征表明，化学扩散是被动的，在这方面，SC起着半透膜的作用。对于分子量低于800道尔顿的试剂，化学溶解性变得比分子大小更重要。在水和脂质中的高度溶解度允许主要由脂蛋白组成的细胞膜和水基细胞内容物快速扩散。
英文原文
In summary, chemical and drug absorption through skin follows similar rules to those established for water loss, a passive process governed mainly by the integrity of the SC. In addition, the effect of lipid solubility on absorption indicates the importance of intercellular lipids to the epidermal barrier.
对应中文
总而言之，通过皮肤吸收化学物质和药物的规则与水分流失的规则相似，这是一个被动的过程，主要由SC的完整性控制。此外，脂溶性对吸收的影响表明细胞间脂质对表皮屏障的重要性。
Percutaneous gas diffusion
经皮气体扩散
英文原文
In healthy infants percutaneous respiration makes only a small contribution to total respiration, although this can be enhanced in the very preterm. Of more importance is the knowledge that studies of percutaneous oxygen and carbon-dioxide diffusion make to the nature of the epidermal barrier.
对应中文
在健康的婴儿中，经皮呼吸只占总呼吸的一小部分，尽管这在早产期可以增强。更重要的是研究经皮氧和二氧化碳扩散对表皮载体性质的影响。
Factors affecting percutaneous respiration
影响经皮呼吸的因素
Gestation
妊娠
英文原文
In full-term infants (and adults) the skin is relatively impermeable to oxygen and carbon dioxide, with only 1–2% of total respiration occurring percutaneously. By contrast, in infants of less than 30 weeks gestation the rate of oxygen absorption and carbon-dioxide excretion during the first 4 days of life is 6–11 times greater than at term, with infants of 30–36 weeks’ gestation having intermediate values.
对应中文
足月婴儿（和成人）的皮肤相对不易受到氧气和二氧化碳的影响，只有1-2%的总呼吸是经皮进行的。相比之下，妊娠不足30周的婴儿在出生后的头4天内的吸氧率和二氧化碳排泄率是足月婴儿的6-11倍，而妊娠30-36周的婴儿处于中间值。
Postnatal age
出生后年龄
英文原文
The high levels of percutaneous oxygen and carbon dioxide diffusion found in preterm infants shortly after birth are only transient. As the skin matures during the first 2–3 weeks of life, diffusion slows to the levels seen in term infants and adults.
对应中文
早产儿出生后不久发现的经皮氧和二氧化碳扩散的高水平只是暂时的。随着皮肤在生命的头2-3周内成熟，扩散速度减慢到足月婴儿和成人的水平。
Gas diffusion gradient
气体扩散梯度
英文原文
Increasing the ambient oxygen concentration increases the diffusion gradient across the skin and leads to a higher rate of oxygen absorption. Also, cutaneous vasoconstriction increases percutaneous respiration, presumably because tissue hypoxia and hypercarbia increase the oxygen and carbon-dioxide diffusion gradients. Although these findings indicate that gas diffusion is passive, it is notable that the relationship between the rate of oxygen absorption and ambient oxygen concentration is not quite linear. This suggests that percutaneous oxygen absorption is also limited by skin blood flow because only a proportion of cardiac output passes through the skin, whereas the whole cardiac output passes through the lungs.
对应中文
增加周围的氧气浓度会增加皮肤上的扩散梯度，并导致更高的氧气吸收速率。此外，皮肤血管收缩增加了经皮呼吸，可能是因为缺氧和高碳酸血症增加了氧气和二氧化碳的扩散梯度。尽管这些结果表明气体扩散是被动的，但值得注意的是，吸氧率与环境氧浓度之间的关系并不完全是线性的。这表明经皮吸氧也受到皮肤血流的限制，因为只有一部分心输出量通过皮肤，而整个心输出量通过肺。
Barrier to infection
屏障感染
英文原文
The nature of the epidermal barrier to microorganisms is uncertain, although some deductions can be made from common observations. Removal of the superficial part of the SC seems to be well tolerated. This situation is similar to that witnessed in the moderately preterm infant with intact skin, where even a thin SC resists infection. In contrast, extremely preterm infants are much more likely to suffer from cutaneous infection because the SC is barely developed. In these infants the situation is more akin to the sepsis seen when mature epidermis is destroyed by an abrasion or burn.
对应中文
表皮对微生物的屏障性质是不确定的，尽管可以从常见的观察结果中做出一些推论。移除SC的表面部分似乎是可以接受的。这种情况类似于皮肤完整的中度早产儿，即使是薄的SC也能抵抗感染。相比之下，极早产儿更容易遭受皮肤感染，因为SC几乎没有发育。在这些婴儿中，这种情况更类似于因磨损或烧伤而破坏成熟表皮的脓毒症。
Conclusion
结论
英文原文
The diffusion of substances through the skin is a passive process, with the SC acting as a semipermeable membrane. The rate of diffusion is controlled by the concentration gradient across the skin surface and the integrity of the epidermal barrier. Alterations in epidermal structure related to infant maturity, postnatal age, and skin damage are reflected in changes in TEWL, chemical absorption and percutaneous gas diffusion, which in turn are closely interrelated.
对应中文
物质通过皮肤的扩散是一个渐进的过程，SC起着半透膜的作用。扩散速率由穿过皮肤表面的浓度梯度和表皮载体的完整性控制。与婴儿成熟、出生后年龄和皮肤损伤相关的表皮结构的改变反映在TEWL、化学吸收和经皮气体扩散的变化中，这反过来又是密切相关的。
REFERENCES
1.THE EPIDERMAL BARRIER. The Lancet. 1987;329(8547):1414.