黑色字体是原文献

红色字体是机翻

蓝色字体是人肉翻，校对，讲解，注释等等 

Deranged Physiology  Required Reading  Endocrinology, Metabolism and Nutrition

精神错乱的生理学必读《内分泌学、代谢与营养》

Physiological adaptation to prolonged starvation

对长期饥饿的生理适应

This is a summary of the physiological responses to the total or near-total absence of nutrition.

这是对完全或接近完全缺乏营养的生理反应的总结。

The metabolic response to starvation is characterised by a switch from carbohydrate metabolism to fat cmetabolism, in the context of a hypometabolic state, with minimised catabolism.

在低代谢状态下，对饥饿的代谢反应的特征是从碳水化合物代谢转变为脂肪代谢，分解代谢最小化。

说人话：对于饿了데代谢反应的特征是一个转变，就是说 你饿了，你的代谢特征会有一个转变，这个转变系虾米呢，是从碳水分解→脂肪分解，当然 这个有一个大背景，就是说是在低代谢低分解의情况下（这不废话嘛，人类低分解低代谢肯定要么是虚弱要么饿极了呗。。）

Initially, stores of carbohydrate precursors (eg. glycogen) are depleted.

最初，碳水化合物前体（如糖原）的储存被耗尽。

Then, in the first 24-48 hours there is increased gluconeogenesis from amino acids and glycerol.

然后，在最初的24-48小时内，氨基酸和甘油的糖异生增加。

Subsequently, ketogenesis takes over, and much of the body metabolic needs are met by ketone bodies and free fatty acids.

随后，酮体生成占据了主导地位，酮体和游离脂肪酸满足了大部分身体代谢需求。

This is the consequence of decreasing insulin levels, and relatively increased influence from catecholamines and cortisol.

这是胰岛素水平下降以及儿茶酚胺和皮质醇影响相对增加的结果。

说人话，上述转变，就是因为3个要素，1胰岛素降了 2儿茶酚胺增了3皮质醇增了

Over prolonged starvation, protein catabolism begins, resulting in degradation of structurally important proteins, and organ system dysfunction.

长期饥饿后，蛋白质分解代谢开始，导致结构重要的蛋白质降解，器官系统功能障碍。

这句话机翻有问题，实际上会导致의系，重要的蛋白会产生结构上의讲解

The physiological adaptation to starvation has been asked about in Question 27 from the second paper of 2013. Specifically, the college wanted to know about the metabolic changes of starvation and the stress response.

Composition and quantity of nutrients stored in the human body

George F Cahill is the guru of food deprivation physiology. His 1970 article "Starvation in Man" remains a masterpiece of scientific writing. Therein one may find a table entitled "Fuel Composition Of Normal Man" which I have uselessly interpreted into another weird cylinder diagram.

Whatever the value of that may be.

2013年第二篇论文的问题27中提出了对饥饿的生理适应。具体来说，学院想了解饥饿的代谢变化和压力反应。

人体内储存的营养成分和数量

乔治·F·卡希尔是食物匮乏生理学的大师。他1970年的文章《人的饥饿》仍然是科学写作的杰作。在那里可以找到一张题为“普通人的燃料成分”的表格，我把它无用地解释成了另一张奇怪的气缸图。

不管它的价值是什么。

这一大堆没啥干货，就不人肉矫正了。。

Anyway, each of us has about 20-25g of circulating fuel (of which the majority is glucose), worth about 113 calories. If we take this Homo vulgaris to be a 20 year old specimen measuring 70kg and 170cm, we can calculate that at their basal metabolic rate of 1800kcal/day they go through one blood volume worth of calories every 90 minutes.

无论如何，我们每个人都有大约20-25克的循环燃料（其中大部分是葡萄糖），价值大约113卡路里。如果我们把这个普通人作为一个20岁的标本，测量70公斤和170厘米，我们可以计算出，在他们1800kcal/天的基础代谢率下，他们每90分钟消耗一个血液体积的热量。

一个血液体积是什么鬼？然而貌似只能这么翻译야。。

The total metabolic fuel stores in a normal human body

正常人体内储存的总代谢燃料

正常人体内储存的总代谢燃料

Thus, the circulating nutrient volume is constantly being consumed and replenished.

因此，循环营养物质的体积不断被消耗和补充。

Then, we have a rapidly available glycogen storehouse, of which two thirds resides in the muscle. There is a total 900kcal of this stuff, and it is also constantly being consumed and replenished. It is replenished after meals (when insulin drives glucose into cells and promotes glyconeogenesis) and it is consumed between meals (when glucagon activated glycogenolysis, releasing glucose out of cells).

然后，我们有了一个快速可用的糖原库，其中三分之二存在于肌肉中。这种物质总共有900千卡，而且还在不断地消耗和补充。它在餐后补充（当胰岛素将葡萄糖驱动到细胞中并促进糖原生成时），并在餐间消耗（当胰高血糖素激活糖原分解，将葡萄糖释放出细胞时）。

糖原有两种，肝糖原and肌糖原，肌糖原多一些大概占了三分之二。

胰岛素能够把血糖中의葡萄弄到细胞里，并且把它们变成肝糖原

胰高血糖素则是让肝糖原分解，让他们총细胞里跑到血糖

Glycogen is a poor means of storing energy. It is a starch-like branching molecule, has a low calorie density, only about 4 kcal per gram. Cahill reminds us that this density is actually measured in dried glycogen - in reality, 2g of water is stored together with each 1g of glycogen (in order to maintain intracellular isotonicity) and this dilutes its energy density even further.

糖原是储存能量的不良手段。它是一种淀粉样支化分子，热量密度低，每克仅约4千卡。Cahill提醒我们，这种密度实际上是用干糖原来测量的——事实上，每1g糖原储存2g水（以保持细胞内的等渗性），这会进一步稀释其能量密度。

就是说 糖原储能其实也就那么回事而已，木有脂肪储能牛叉。糖原里面有结合水（我猜的应该是结合水바。。） 这结合水是为了维持细胞渗透压平衡，然后因为里面有水，所以糖原实际把水去掉后，储能就更不咋样了

Fat, on the other hand, is stored in blobs which are essentially free of water. It is a much more efficient energy storage system. And the vast majority of the fat in the body is available as a metabolic fuel, if push comes to shove. Those blobs are cushioning, they serve a purely cosmetic role and if you need to burn them to survive, so be it- they will not be missed. Not only that, but fat has a far higher energy density - something like 9.4 kcal per gram.

另一方面，脂肪储存在基本上不含水的团块中。这是一个效率高得多的储能系统。如果情况紧急，体内绝大多数脂肪都可以作为代谢燃料。这些斑点是缓冲的，它们纯粹起到美容的作用，如果你需要烧掉它们来生存，那就顺其自然吧——它们不会被错过。不仅如此，脂肪的能量密度也高得多——大约每克9.4千卡。

这些斑点系缓冲의特喵的神马鬼。。应该就是说脂肪是用来缓冲的物质，如果你要美容那就烧掉他们

Protein does not come in a fuel storage form. It is structurally important; all of your protein has some function, and to burn it as fuel would be a gesture of desperation. An organism which is consuming its own protein is truly struggling. That said, if your organism is struggling it has some 6kg or so of protein to get through before it dies.

蛋白质不是以燃料储存的形式出现的，它在结构上很重要；你所有的蛋白质都有一些功能，把它当作燃料燃烧是一种绝望的姿态。一个正在消耗自身蛋白质的有机体真的在挣扎。也就是说，如果你的生物体正在挣扎，它在死亡前有大约6公斤左右的蛋白质需要通过。

换言之 当糖原 脂肪都烧完了，那么离gg，还有6kg蛋白可以烧。

Metabolic adaptation to a brief period of fasting

The main change from the normal pattern is the refusal of the myocardium and skeletal muscle to use glucose. Instead, they switch over exclusively to free fatty acid and ketone metabolism.

短暂禁食的代谢适应

与正常模式相比，主要的变化是心肌和骨骼肌拒绝使用葡萄糖。相反，它们完全转向游离脂肪酸和酮的代谢。

The glycogen reserves in humans never get completely depleted. There is at all times a hepatic reserve, waiting to mobilise and rescue the organism from some sort of horrible situation.

人类体内的糖原储备从未完全耗尽。在任何时候都有一个肝脏储备，等待着将生物体从某种可怕的情况下动员起来并拯救出来。

The diagram below is again a paraphrase of Cahill; the mass of nutrients given in it is the amount consumed in a 24 hour period.

下图再次是对卡希尔的转述；其中所含营养物质的质量是24小时内所消耗的量。

饥饿过程中大量营养物质代谢的变化

macronutrient metabolic changes during starvation

饥饿过程中大量营养物质代谢的变化

Furthermore, the Cori cycle plays a more important role. 36g of the daily glucose is converted into lactate, which shuttles back to the liver.

此外，科里循环发挥着更重要的作用。每天36克的葡萄糖被转化为乳酸，乳酸被送回肝脏。

介个循环我我没听过。。而且。。变回乳酸意义何在？

The liver uses free fatty acids to power the process of gluconeogenesis.

肝脏利用游离脂肪酸为糖异生过程提供动力。

介个好理解 糖异生分为脂肪 and 氨基酸两种

Thus, any lactate converted back to glucose is really free fatty acid energy converted to glucose. In essence, all these Cori-cycling anaerobic glycolysis tissues are running on free fatty acid energy, and glucose and lactate merely act as vessels which contain that energy.

因此，任何转化回葡萄糖的乳酸盐实际上都是转化为葡萄糖的游离脂肪酸能量。本质上，所有这些科里循环厌氧糖酵解组织都是依靠游离脂肪酸能量运行的，而葡萄糖和乳酸只是作为含有这种能量的血管。

这局话半懂不懂，血管翻译成容器更好吧。。

 

Hormones responsible for the metabolic adaptation to brief fasting

负责代谢适应短暂禁食的激素

说人话就是，你短期绝食，代谢肯定要适应这种变化对吧，那是什么激素让代谢产生了这种适应呢

Well, its all about increasing the rate of lipolysis, is it not. And the rate of lipolysis in fatty tissues is governed by the intracellular content of cAMP, which responds to both insulin and noradrenaline.

好吧，这一切都是为了提高脂解的速度，不是吗。脂肪组织中的脂解速率由细胞内cAMP的含量决定，cAMP对胰岛素和去甲肾上腺素都有反应。

说白了就系camp干的好事，介个camp能对胰岛素et去甲肾腺素有反应，camp系一种腺苷，环磷酸腺苷，这玩意也是一种信使。。这玩意系atp脱了2个磷脂缩合的。。主要作用就系营养心肌，换言之 这玩意越多，脂代谢越快

second messenger systems involved in activation of hormone-sensitive lipase

参与激素敏感脂肪酶激活的第二信使系统

激素-敏感 ？敏感性激素把？

The major hormonal player in this adaptation is insulin, or rather, its lack. With the absence of regular glucose peaks (given the lack of eating) insulin levels drop. Insulin is the primary inhibitor of lipolysis, because the tyrosine kinase activity of its intracellular domain activates a phosphodiesterase, which keeps intracellular cAMP levels low. As insulin levels drop, the background sympathetic activity becomes unopposed, and the hormone sensitive lipase begins to dismantle their triglyceride stores, releasing delicious fatty acids into the bloodstream.

这种适应的主要荷尔蒙因素是胰岛素，或者更确切地说，它的缺乏。由于缺乏正常的葡萄糖峰值（考虑到缺乏进食），胰岛素水平下降。胰岛素是脂解的主要抑制剂，因为其细胞内结构域的酪氨酸激酶活性激活磷酸二酯酶，使细胞内cAMP水平保持在较低水平。随着胰岛素水平的下降，背景交感神经活性变得没有对抗，激素敏感的脂肪酶开始分解其甘油三酯储存，向血液中释放美味的脂肪酸。

因为挨饿，自然血糖低，自然胰岛素下降。胰岛素高→脂肪消耗慢。胰岛素高→脂肪解就快。camp低→脂肪酶就活跃了，甘油三酯就开始变成脂肪酸了。这些脂肪酸开始参与三羧酸循环

(Yes, there are three lipases in the pathway, because there are three fatty acid molecules attached to the glycerol. Only the first lipase is hormone-sensitive.)

（是的，该途径中有三种脂肪酶，因为甘油上有三个脂肪酸分子。只有第一种脂肪酶对激素敏感。）

介个有中学化学or生物基础的应该偶知道吧。。甘油三酯三个键，第一个键和后面两个键连接的官能团并不一样，很合理。。

So, noradrenaline increases the rate of lipolysis (by affecting the bored and lonely beta-3 receptor, which doesn't seem to have much of a function outside of lipolysis), and insulin decreases the rate of lipolysis. Which effect is dominant in ICU patients who are frequently marinading in infusions of both noradrenaline and insulin? Hard to say. The catecholamine excess associated with critical illness definitely causes lipolysis, even in absence of exogenous catecholamines.

因此，去甲肾上腺素增加了脂解速率（通过影响无聊而孤独的β-3受体，它似乎在脂解之外没有太多功能），而胰岛素降低了脂解的速率。在经常浸泡在去甲肾上腺素和胰岛素输注中的ICU患者中，哪种影响占主导地位？很难说。与危重症相关的儿茶酚胺过量肯定会导致脂解，即使在没有外源性儿茶酚胺的情况下也是如此。

换言之β-3受体只会影响脂肪解，木有其他功能的样子。。去甲肾上腺素这玩意是收camp影响的，camp低了，导致去甲肾上腺素高了，然后就增加了脂肪解

儿茶酚胺高了→脂肪gg快，胰岛素高了→脂肪gg慢，去甲肾上腺素高了→脂肪gg快

Proteolysis in fasting is not studied as well as lipolysis, but it is clear that an insulin deficit also activates proteolytic pathways (because the administration of small amounts of intravenous dextrose seems to inhibit proteolysis)

禁食时的蛋白水解和脂解没有得到研究，但很明显，胰岛素缺乏也会激活蛋白水解途径（因为静脉注射少量葡萄糖似乎会抑制蛋白水解）

这其实很好理解，胰岛素少了→蛋白分解快。葡萄糖多了→蛋白水解慢 很合理的说poi

Which brings up an interesting question. Nobody ever just lies there and starves quietly for their first few days in the ICU. What happens to these patients?

这就引出了一个有趣的问题。没有人会躺在那里，在重症监护室的头几天安静地挨饿。这些病人怎么了？

这个其实好解释吧。。病人都快gg了。。体内各种信号系统 通道系统都乱了呗。。

They still starve.

But, if 150g (600kcal) or so of simple carbohydrate is delivered every day (which is 3 litres of 5% dextrose, or around 600ml of Jevity), the proteolytic pathway is switched off. Lipolysis continues, but the exogenous glucose results in enough insulin release to abort the ketogenesis.

他们仍然挨饿。

但是，如果每天输送150克（600千卡）左右的简单碳水化合物（即3升5%葡萄糖，或约600毫升Jevity），蛋白水解途径就会被切断。脂解仍在继续，但外源性葡萄糖会导致足够的胰岛素释放，从而中止生酮。

换言之，血糖对于蛋白水解 et 脂肪水解虽然都有抑制作用。然而一个是直接的，一个是间接的。前者直接影响，然而原理我我还没研究。后者则是间接影响，通过血糖→胰岛素→脂肪水解

In short, feeding your patient even a tiny amount of carbohydrate will prevent ketosis and protein catabolism.

Sneakily, one can achieve the same effect by administering insulin as a part of an insulin-dextrose infusion. At protocol rate (80ml/hr) one ends up giving only 1920ml of 5% dextrose in 24 hours, which is just short of 100g (or 400kCal); but the exogenous insulin switches off the ketogenesis and proteolysis anyway.

简而言之，给患者喂食哪怕是少量的碳水化合物也可以防止酮症和蛋白质分解代谢。

偷偷地，通过将胰岛素作为胰岛素-葡萄糖输注的一部分来给药，可以达到同样的效果。按照方案速率（80ml/小时），24小时内只能产生1920ml的5%葡萄糖，这还差100克（或400千卡）；但外源性胰岛素无论如何都会切断生酮和蛋白水解。

这个很好理解啦，血糖 et 胰岛素是线性正相关，那你往患者体内注入哪个其实意思都差不多的说喵。。 

Weight loss due to fasting

Rate of weight loss with starvationWith total acaloric fasting, a certain healthy 41 yr old member of a cloistered religious community lost 0.9kg per day for the first few days of the fast, a rate which decreased to a stable 0.3kg/day towards the third week of fasting.

禁食减肥

禁食减肥率在完全非传统禁食的情况下，一位41岁的健康的与世隔绝的宗教团体成员在禁食的头几天每天减重0.9公斤，在禁食的第三周，这一比率降至稳定的0.3公斤/天。

基本数据跟我差不多 ，一般前3天掉1-3kg，后面每天0.7 0.5 0.6之类浮动 约到后面越少

This rate seems consistent among various experimentally fasted subjects. Most seem to lose about 20% of their body weight during a 30 day fast.

这一比率在各种实验禁食的受试者中似乎是一致的。大多数人似乎在30天的禁食中减掉了大约20%的体重。

没试过30days+，不发言了。。

The total amount of weight lost in the course of a fasting experiment is not representative of the critical care population. Our patients are infrequently monastic ovolactovegetarians with a normal BMI. Additionally, in a critical care setting the metabochanges in the rate of urinary electrolyte loss during starvationlic demands are greatly increased. One can only estimate that the ICU patient loses weight at a much faster rate, especially if burns, trauma or sepsis are involved.

禁食实验过程中体重减轻的总量不能代表重症监护人群。我们的患者很少是体重指数正常的素食主义者。此外，在重症监护环境中，饥饿需求期间尿电解质损失率的代谢变化大大增加。人们只能估计重症监护室患者的体重减轻速度要快得多，尤其是在涉及烧伤、创伤或败血症的情况下。

这个肯定 毕竟患者的身体比起健康人肯定有问题，尤其创伤烧伤类，本身还需要额外蛋白修复以及各种能量供应，这个说得通，傻子都懂。但是患者尿电解质损失率增加这个暂时理解不了，按理说病人体内基础代谢会更低，理论上每日代谢产物也会低。。怎么电解质流逝还多呢

Electrolyte changes during prolonged starvation

The 41 yr old monk lost 0.9kg per day for the first few days of the fast. This initial rapid weight loss is not totally due to the loss of dry nutrient mass. Think about it: the burning of 0.9kg of fat protein and carbohydrate in one day day would yield 3150 kcal in total, which is insane (given that a basal metabolic rate we agreed on is 1800 kcal/day).

The extra weight loss is actually due to diuresis and natriuresis. The urinary loss of the sodium cation is obligatory loss. As ketone anions are lost in the urine, they require a cation to accompany them; initially this is sodium, and later in the fast it is ammonium.

Potassium decreases initially, and remains stable at around 3.0 mmol/L. There is a constant rate of urinary potassium loss, which is thought to be the result of lean tissue dissolving. It seems to parallel the rate of proteolysis, and it seems related to lean body mass.

Magnesium remains surprisingly stable.

Calcium remains stable

Phosphate remains stable

Uric acid levels increase, perhaps as a product of protein catabolism; not only that but urate seems to compete with ketoacids for renal tubular transport sites.

长期饥饿期间电解质的变化

这位41岁的僧人在斋戒的头几天每天减重0.9公斤。这种最初的快速减肥并不完全是由于干燥营养物质的损失。想想看：一天内燃烧0.9公斤的脂肪蛋白和碳水化合物总共会产生3150千卡的热量，这太疯狂了（考虑到我们商定的基础代谢率是1800千卡/天）。

额外的体重减轻实际上是由于利尿和利尿。尿中钠离子的损失是必然的损失。由于酮阴离子在尿液中丢失，它们需要一种阳离子伴随；一开始是钠，后来禁食是铵。

很合理，tongniao必然带走一部分阳离子。而且3150大卡几乎是正常人2天的基础代谢量，算算就会发现不对劲

钾最初减少，并在3.0mmol/L左右保持稳定。尿钾的流失率是恒定的，这被认为是瘦组织溶解的结果。它似乎与蛋白水解的速率相似，而且似乎与瘦体重有关。

受组织什么鬼，，应该是瘦肉肌把。。这个也合理，当瘦肉开始水解后，体内蛋白分解会有一个拐点，之后曲线开始走平。。这个有空回头把另个文献讲解下届时会有图表格的说。。

镁保持惊人的稳定。

钙保持稳定

磷酸盐保持稳定

尿酸水平升高，可能是蛋白质分解代谢的产物；不仅如此，尿酸盐似乎与酮酸竞争肾小管转运位点。

盲猜这是因为肾小管转运位点，这尿酸盐 et 酮酸 ，准确说是尿酸根 and 酮酸根 ，使用的系同一种同向转运体？

Cardiovascular effects of prolonged starvation

Heart rate decreases, and healthy fasted volunteers may get as bradycardic as 35 BPM.

The heart rate increases again (slightly ) after the 4th week.

Blood pressure decreases, and in the 1982 study by Kerndt et al the subject terminated his fast because the postural hypotension was interfering with his monastic duties.

ECG changes occur: most commonly, a right axis deviation and a decrease in T wave and QRS amplitude. Extreme starvation and malnutrition (eg. in long term prisoners of war) also results in QT interval prolongation, T wave inversion and ST depression.

长期饥饿对心血管的影响

心率下降，健康禁食的志愿者可能会出现35 BPM的心动过缓。

心率在第4周后再次（轻微）增加。

血压下降，在1982年Kerndt等人的研究中，受试者终止了禁食，因为体位性低血压干扰了他的修道职责。

心电图发生变化：最常见的是右轴偏移以及T波和QRS波振幅下降。极度饥饿和营养不良（如长期战俘）也会导致QT间期延长、T波倒置和ST段压低。

这些其实是能理解的，但是然而。。为啥木有rmr数值？我我个人感觉这玩意其实对rmr影响更大。。心率四周后开始增加，是线性增加的嘛？

血压down能理解，合情合理 没啥好说。

t波右偏，一般两种，一种先天性的 一般都是女的雌激素少，或者紊乱。后天性的 一般是冠心病or心肌缺血。。估计这和心肌缺血有干吧。。

qts波振幅下降一般是有心脏因素，肺部因素，然后就是营养不良 or 皮肤干燥了。。讲到这里懂的都懂了呗。。

QT间期延长也分获得性and先天性。获得性主要就是电解质紊乱 比如血k低，或者药物作用。。介个肯定系血k浓度造成得啦。。

T波倒置。。一样。。口服k盐即可。。没啥好说的。。

ST段压低一般意味着心肌缺血。。