Here’s another pulmonary physiology question that everyone who gives O 2 to patients ought to know: 以下是另一个所有给患者提供氧气的人都应该知道的肺生理学问题:
What is the primary mechanism by which supplemental oxygen can increase PaCO2 in someone with severe COPD? 补充氧气通过何种主要机制可以增加严重 COPD 患者的 PaCO2? 1//1 /
This is a hard question! You probably learned that “its bad to give someone with COPD ‘too much’ O2 because they might stop breathing” 这是一个难题!你可能学过“给患有 COPD 的人‘过多’的氧气是不好的,因为他们可能会停止呼吸”
Turns out hypoxic respiratory drive causing apnea is a MYTH…but there is an important truth here: 事实证明,低氧性呼吸驱动导致呼吸暂停是一个神话……但这里有一个重要的事实:
A ^("B "){ }^{\text {B }} on Oxygen induced hypercapnia! 2/ 关于氧气诱导的高碳酸血症的 ^("B "){ }^{\text {B }} !2/
Every myth has a little kernel of truth: 每个神话都有一点真实的内核:
In the 8os it was shown that giving people with severe COPD (GOLD stage IV) high flow oxygen ( 15 lpm ) made their minute ventilation (VE) drop then return (almost) to normal, but PaCO 2 rose significantly. 在 80 年代,有研究表明,给予重度 COPD(GOLD 阶段 IV)患者高流量氧气(15 lpm)会导致他们的每分钟通气量(VE)下降,然后(几乎)恢复正常,但 PaCO2 显著上升。
Initially it was theorized that this increase in PaCO 2 was due to loss of hypoxic respiratory drive. This is probably the story you were told in medical or nursing school. 最初,有理论认为这种 PaCO2 的增加是由于缺氧呼吸驱动的丧失。这可能是你在医学院或护理学校听到的说法。
The only problem is this isn’t true! 唯一的问题是这不是真的!
. If we look close there are a few problems with this theory… 如果我们仔细观察,这个理论存在一些问题……
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PaCO 2 should be inversely proportional to minute ventilation. If you double you VE you should (roughly) half your PaCO2. PaCO2 应与每分钟通气量成反比。如果你将每分钟通气量加倍,你的 PaCO2 应该(大致)减半。
But that’s NOT what happened! 但事实并非如此!
Ultimately VE fell by only ∼5%\sim 5 \% (from 10 to 9.5l//min9.5 \mathrm{l} / \mathrm{min} ) but PaCO2 increased by 35%35 \% (from 63 to 85 mmHg )! 最终,VE 仅下降了 ∼5%\sim 5 \% (从 10 到 9.5l//min9.5 \mathrm{l} / \mathrm{min} ),但 PaCO2 增加了 35%35 \% (从 63 到 85 mmHg)!
What did we miss? 我们错过了什么? 5//5 /
Clearly the 5%5 \% decrease in minute ventilation (VE) can’t possibly explain a 35%35 \% rise in PaCO2! 显然, 5%5 \% 的分钟通气量(VE)减少不可能解释 35%35 \% 的动脉二氧化碳分压(PaCO2)上升!
If we do the math, the change in minute ventilation can explain at most 4.8 mmHg of the ∼22mmHg\sim 22 \mathrm{mmHg} rise in PaCO 2 . 如果我们进行计算,分钟通气量的变化最多可以解释动脉血二氧化碳分压(PaCO2)上升的 4.8 mmHg。
MYTH busted! This must be more than just a change in ventilation! 神话破灭!这一定不仅仅是通风的改变! 6//6 /
It turns out that in addition to carrying oxygen, Hemoglobin also carries carbon dioxide. 事实证明,除了携带氧气外,血红蛋白还携带二氧化碳。
It does this 3 ways: 它通过三种方式做到这一点:
Dissolved as CO2\mathrm{CO2} (10%) 溶解为 CO2\mathrm{CO2} (10%)
Bound to hemoglobin as HbCO 2 (30%) 与血红蛋白结合为 HbCO₂(30%)
Buffered as bicarbonate ( 60%60 \% of CO 2 ) 以碳酸氢盐缓冲( 60%60 \% 的 CO 2) CO2+H_(2)O-- > H_(2)CO_(3)-- > H++HCO_(3)^(-)\mathrm{CO} 2+\mathrm{H}_{2} \mathrm{O}-->\mathrm{H}_{2} \mathrm{CO}_{3}-->\mathrm{H}++\mathrm{HCO}_{3}^{-} 7//7 /
Hemoglobin picks up CO 2 in the tissues (where it is unloading O 2 ), and unloads CO 2 in the lungs (where it is picking up O2). 血红蛋白在组织中吸收二氧化碳(在那里它正在卸载氧气),并在肺部卸载二氧化碳(在那里它正在吸收氧气)。
For this reason, dexoygenated Hb is better at carrying CO 2 & oxygenated Hb is not good at carrying CO2. 因此,去氧化的血红蛋白更适合携带二氧化碳,而氧合的血红蛋白不适合携带二氧化碳。
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For this reason, administration of high concentrations of Oxygen can “push” CO 2 off of hemoglobin and into solution, increased PaCO2. 出于这个原因,给予高浓度的氧气可以将二氧化碳从血红蛋白上“推”入溶液中,导致动脉血二氧化碳分压(PaCO2)增加。
That’s he Haldane Effect - the phenomenon where binding of oxygen to hemoglobin promotes the release of carbon dioxide (raising PaCO2). 这就是 Haldane 效应——氧与血红蛋白结合促进二氧化碳释放的现象(提高 PaCO2)。
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Although the Haldane effect is very real it’s effect isn’t huge; it increases the PaCO 2 by about 10%10 \%. 尽管 Haldane 效应确实存在,但其影响并不大;它使 PaCO₂增加约 10%10 \% 。
This means Haldane can only explain about 6 mmHg of the 22 mmHg increase in PaCO2\mathrm{PaCO2} ! This is an important contributor but it isn’t explaining most of the rise in CO 2. 这意味着 Haldane 只能解释 PaCO2\mathrm{PaCO2} 中 22 mmHg 增加中的约 6 mmHg!这是一个重要的因素,但它并不能解释 CO2 大部分的上升。
10//10 /
Sidebar: this doesn’t mean the Haldane effect is inconsequential. 侧栏:这并不意味着哈尔登效应无关紧要。
If my PaCO 2 rose from 40 to 44 mmhg I probably wouldn’t notice. 如果我的 PaCO₂从 40 升高到 44 mmHg,我可能不会注意到。
But in someone who chronically retains CO 2 this could be a big issue. Going from a PaCO2 of 80 to 88 mmHg could be enough to cause CO 2 narcosis… 但是对于慢性滞留二氧化碳的人来说,这可能是一个大问题。从 80 mmHg 的 PaCO2 升高到 88 mmHg 可能足以引起二氧化碳麻醉……
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So what causes O2 induced hypercapnea then? 那么是什么导致了氧气诱导的高碳酸血症呢?
Recall that different lung areas get differential ventilation. (This is especially true in people with parenchymal disease like COPD) 请记住,不同的肺区域获得不同的通气。(这在患有实质性疾病如慢性阻塞性肺病的人中尤其如此)
Fortunately the lung regulates blood flow, decreasing perfusion (Q) to poorly ventilated areas. 幸运的是,肺部调节血流,减少对通气不良区域的灌注(Q)。 12//12 /
CO2 gets excreted by well CO2 通过井排出
ventilated/perfused alveoli 通气/灌注的肺泡
But what if we provide ‘too much’ supplemental oxygen? 但如果我们提供“过多”的补充氧气怎么办?
This can cause the loss of hypoxic vasoconstriction increasing perfusion to the poorly ventilated alveoli. 这可能导致缺氧性血管收缩的丧失,从而增加对通气不良肺泡的灌注。
(Maybe a better term would be HYPERoxic vasodilation! h/t @sargsyanz for suggesting this perfect term!) (也许一个更好的术语是高氧性血管扩张!感谢@sargsyanz 建议这个完美的术语!) 13//13 /
This - the loss of hypoxic vasoconstriction to poorly ventilated lung areas - turns out to be the primary reason for oxygen induced hypercapnea. 这种对通气不良的肺区域失去低氧性肺血管收缩,结果是氧气诱导的高碳酸血症的主要原因。 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682248
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The role of ventilation-perfusion mismatching 通气-灌注不匹配的作用
Go to: *\cdot 去: *\cdot
Physiologically, alveolar ventilation and perfusion are well matched. Two extremes of ventilationperfusion ( Va//Q\mathrm{Va} / \mathrm{Q} ) mismatch may occur: (a) no ventilation of an alveolus but adequate perfusion, resulting in shunting, and (b) adequate ventilation but no perfusion, resulting in dead space ventilation. The body has protective mechanisms to optimize the Va/Q ratio. When alveolar oxygen tension decreases (for example, in bronchoconstriction), local mediators induce vasoconstriction of pulmonary capillaries supporting this particular alveolus, counteracting possible shunting, a mechanism called hypoxic pulmonary vasoconstriction (Figure 2). The strongest mediator for hypoxic pulmonary vasoconstriction is alveolar pO_(2)\mathrm{pO}_{2} (partial pressure of oxygen). Therefore, a high fraction of inspired O_(2)(FiO_(2))\mathrm{O}_{2}\left(\mathrm{FiO}_{2}\right) will increase O_(2)\mathrm{O}_{2} tension in alveoli with a low level of ventilation, inhibiting hypoxic pulmonary vasoconstriction. As a result, alveoli with relatively impaired ventilation are well perfused, leading to an increase in Va/Q mismatch. Indeed, the study by Aubier and colleagues [4] revealed that high FiO_(2)\mathrm{FiO}_{2} impaired Va/Q matching and increased dead space ventilation from 77%77 \% to 82%82 \%. Robinson and colleagues [5] also studied the Va/Q mismatch during oxygen therapy. The Va/Q mismatch increased in both the retainer and non-retainer groups of patients. The authors also concluded that this was due to less hypoxic pulmonary vasoconstriction in both groups. Although overall ventilation decreased in the retainer group, ventilation to lung units with higher Va/Q mismatch increased, leading to increased alveolar dead space ventilation in the retainer group. An earlier report using a computer model to simulate pulmonary circulation found that the increased physiologic dead space through worsened Va/Q was sufficient to account for the oxygen-induced hypercapnia [Z]. 生理上,肺泡通气和灌注是良好匹配的。可能出现两种极端的通气灌注( Va//Q\mathrm{Va} / \mathrm{Q} )不匹配情况:(a)肺泡无通气但灌注充足,导致分流;(b)通气充足但无灌注,导致无效腔通气。身体有保护机制来优化 Va/Q 比。当肺泡氧张力下降时(例如,在支气管收缩中),局部介质诱导支持该特定肺泡的肺毛细血管收缩,以抵消可能的分流,这一机制称为缺氧性肺血管收缩(图 2)。缺氧性肺血管收缩的最强介质是肺泡 pO_(2)\mathrm{pO}_{2} (氧的分压)。因此,高比例的吸入 O_(2)(FiO_(2))\mathrm{O}_{2}\left(\mathrm{FiO}_{2}\right) 会增加通气水平低的肺泡中的 O_(2)\mathrm{O}_{2} 张力,抑制缺氧性肺血管收缩。结果是,通气相对受损的肺泡灌注良好,导致 Va/Q 不匹配增加。实际上,Aubier 及其同事的研究[4]表明,高 FiO_(2)\mathrm{FiO}_{2} 损害了 Va/Q 匹配,并将无效腔通气从 77%77 \% 增加到 82%82 \% 。 Robinson 及其同事[5]也研究了氧疗期间的通气/血流(Va/Q)失调。在保留者和非保留者患者组中,Va/Q 失调均增加。作者还得出结论,这在两个组中都是由于缺氧性肺血管收缩减少所致。尽管在保留者组中总体通气减少,但通向具有较高 Va/Q 失调的肺单位的通气增加,导致保留者组的肺泡无效腔通气增加。早期的一份使用计算机模型模拟肺循环的报告发现,通过恶化的 Va/Q 导致的生理无效腔增加足以解释氧诱导的高碳酸血症[Z]。
Figure 2 图 2
Hypoxic pulmonary vasoconstriction. The left frame shows normal alveolar ventilation and perfusion. In the right frame, reduced ventilation (thus O_(2)\mathrm{O}_{2} tension) in the alveolus (green) leads to a reduced perfusion because of the hypoxic pulmonary vasoconstriction mechanism. Reprinted with permission from BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health [13]. 低氧性肺血管收缩。左图显示正常的肺泡通气和灌注。在右图中,肺泡(绿色)中的通气减少(因此 O_(2)\mathrm{O}_{2} 张力)导致灌注减少,这是由于低氧性肺血管收缩机制。经 BMJ 出版集团有限公司和皇家儿科与儿童健康学院许可转载[13]。
Bottom line: 底线:
Giving supplemental O 2 to someone w/ severe COPD really can cause oxygen induced hypercapnea. 给患有严重 COPD 的人补充氧气确实可能导致氧气诱导的高碳酸血症。
It occurs for three reasons: 发生这种情况有三个原因:
Loss of hypoxic vasoconstriction --> worse V/Q matching (major reason) 缺氧性血管收缩丧失 --> 更差的通气/灌注匹配(主要原因)