发 绀发 绀

Cyanosis

原南京中大附属医院神内科主任、硕士生导师佛山大学医学院医学系孟红旗教授、主任医师Professor 、 Doctor director 、 Neurologist

Definition

Cyanosis refers to a bluish(带蓝色的；带青色

的 )color of the skin and mucous membranes resulting from an increased quantity of reduced hemoglobin(亚铁血红蛋白；

还原血红蛋白 ), or of hemoglobin derivatives, in the small blood vessels of those areas. It is usually most marked in the lips, nail beds, ears, and malar(颧骨的；颊

的 )eminences(隆起 ).

定义发绀是指血液中还原血红蛋白增多，或出现异常血红蛋白衍化物（高铁血红蛋白、硫化血红蛋白）时，皮肤粘膜呈青紫色现象。发绀在皮肤较薄、色素较少和毛细血管丰富的部位，如唇、舌、两颊、鼻尖、耳垂和甲床等处较明显易于观察。

发绀（紫绀）→血液中还原血红蛋白增多发绀（紫绀）→血液中还原血红蛋白增多→皮肤、粘膜呈青紫色→皮肤、粘膜呈青紫色

Mechanism of Cyanosis

Cyanosis, especially if developed recently, is more commonly detected by a family member than the patient. The florid(鲜红色的；气色好的 ) skin characteristic of polycythemia vera(真性红细胞增多症 ) must be distinguished from the true cyanosis discussed here. A cherry(樱桃 )-

colored flush(潮红 ), rather than cyanosis, is caused by COHb (Carboxyhemoglobin 碳氧血红蛋白 ).

The degree of cyanosis is modified by the color of the cutaneous(皮肤的 ) pigment and the thickness of the skin, as well as by the state of the cutaneous capillaries.The accurate clinical detection of the presence and degree of cyanosis is difficult, as proved by oximetric(血氧定量法

的 )studies

In some instances, central cyanosis can be detected reliably when the SaO2 has fallen to 85%; in others, particularly in dark-skinned persons, it may not be detected until it has declined to 75%. In the latter case, examination of the mucous membranes in the oral cavity and the conjunctivae(结膜 )rather than examination of the skin is more helpful in the detection of cyanosis.

The increase in the quantity of reduced hemoglobin in the mucocutaneous(皮肤粘膜

的 ) vessels that produces cyanosis may be brought about either by an increase in the quantity of venous blood as the result of dilatation of the venules(小静脉 ) and venous ends of the capillaries or by a reduction in the SaO2 in the capillary blood.

In general, cyanosis becomes apparent when the mean capillary concentration of reduced hemoglobin exceeds 50 g/L (5g/dL). It is the absolute rather than the relative quantity of reduced hemoglobin that is important in producing cyanosis

Thus, in a patient with severe anemia, the relative amount of reduced hemoglobin in the venous blood may be very large when considered in relation to the total amount of hemoglobin in the blood. However, since the concentration of the latter is markedly reduced, the absolute quantity of reduced hemoglobin may still be small, and therefore patients with severe anemia and even marked arterial desaturation(稀释 )do not display cyanosis.

Conversely, the higher the total hemoglobin content, the greater is the tendency toward cyanosis; thus, patients with marked polycythemia(红细胞增多症 )tend to be cyanotic at higher levels of SaO2 than patients with normal hematocrit(红细胞压积 ) values.

Likewise, local passive congestion, which causes an increase in the total amount of reduced hemoglobin in the vessels in a given area, may cause cyanosis.

HbO2

HHb2.6g/dl

正常

≥5g/dl

缺氧

发绀 (cyanosis)

15

5

20

5 5 5

0

5

10

15

20

Total HbR-Hb

Normal Polycythemia Anemia

g/dl

Mechanisms of Cyanosis Caused by absolute increase of amount of reducedHb in blood, usually > 5g/dl (capillary) The higher the hemoglobin concentration, The greater tendency toward cyanosis.

发病机制当毛细血管中脱氧血红蛋白浓度增加到 5g/dl 时，可使皮肤与粘膜呈青紫色，称为发绀 (cyanosis) 。循环性缺氧时，因血液流经毛细血管时间延长，从单位容量血液弥散给组织的氧量增加，故静脉血氧含量明显降低。毛细血管中脱氧血红蛋白含量可超过 5g/dl ，所以可出现发绀。血液性缺氧无发绀，严重贫血的病人， Hb 数量减少，面色苍白，毛细血管中脱氧血红蛋白达不到 5g/dl ，不会出现发绀。在因 Hb 与 O2 亲和力增强引起的血液性缺氧时，动脉血氧容量和氧含量可不低，甚至还稍高于正常 , 毛细血管中脱氧血红蛋白含量不会超过 5g/dl ，所以不会引起发绀。

发病机制

碳氧血红蛋白血症(Carboxy hemoglobinemia) HbCO: 亲和力高 ; 抑制糖酵解 ; 樱桃红色CO 中毒，因 HbCO 呈樱桃红色，但重度中毒，严重缺氧，由于皮肤血管收缩，皮肤、粘膜可呈苍白色。

高铁血红蛋白使皮肤、粘膜呈现咖啡色或青石板色，但不是发绀。

高铁血红蛋白血症（ methemoglobinemia)

肠源性紫绀(enterogenous cyanosis)

Fe2+ Fe2+

Fe2+ Fe2+

Hb: 22

Hb-Fe2+ HbFe3+OH氧化还原 （咖啡色）

Clinical Classification & Etiology

True Cyanosis (increased amount of reduced Hb)

— Central Type — Peripheral Type — Mixed Type

Cyanosis due to abnormal Hb derivatives — Methemoglobinemia( 高铁血红蛋白血症 ) — Sulfhemoglobinemia( 硫化血红蛋白血症 )

病因与临床表现病因与临床表现

1.1. 血液中还原血红蛋白增多血液中还原血红蛋白增多：： (1) (1) 中心性发绀中心性发绀 (2) (2) 周围性发绀周围性发绀 (3) (3) 混合性发绀混合性发绀

22 ．．血液中存在异常血红蛋白衍化物血液中存在异常血红蛋白衍化物(1)(1) 先天性高铁血红蛋白血症先天性高铁血红蛋白血症(2)(2) 硫化血红蛋白血症硫化血红蛋白血症

Impaired pulmonary function1. Airway obstruction2. Pulmonary diseases3. Pleural( 胸膜的 )diseases

Right-to-left shunting of blood

Tetralogy of Fallot

Central Cyanosis

Central Cyanosis

Seriously impaired pulmonary function, through perfusion(灌注 ) of unventilated(通气不畅 ) or poorly ventilated areas of the lung or alveolar hypoventilation, is a common cause of central cyanosis.This condition may occur acutely, as in extensive pneumonia or pulmonary edema, or chronically with chronic pulmonary diseases .In the last situation, secondary polycythemia(红血球增多症 ) is generally present, and clubbing(杵状指 )of the fingers may occur.

clubbing

The selective bullous(大疱的 ,大泡的 ) enlargement of the distal segments of the fingers and toes due to proliferation of connective tissue, particularly on the dorsal surface, is termed clubbing; there is increased sponginess(海棉质 ) of the soft tissue at the base of the nail.

中心性发绀呼吸系统疾病：呼吸系统是使血红蛋白能够和氧结合，成为氧合血红蛋白的地方，凡能阻碍血红蛋白和空气接触的任何支气管和肺的疾病，都可使全身动脉血的氧合血红蛋白减少，还原血红蛋白增多，产生紫绀。这些疾病包括喉部或气管阻塞 ( 如痰液阻塞、气管异物 ) 、支气管哮喘、重的慢性支气管炎和重的肺部疾病 ( 如肺结核、肺炎、尘肺、肺气肿、肺水肿等 ) 等。空气里氧含量不够，如在高空里，即使呼吸系统是健康的，也会因为血红蛋白不能充分氧合而产生紫绀。

Central Cyanosis

Another cause of reduced SaO2 is shunting of systemic venous blood into the arterial circuit. Certain forms of congenital heart disease are associated with cyanosis.Since blood flows from a higher-pressure to a lower-pressure region, for a cardiac defect to result in a right-to-left shunt, it must ordinarily be combined with an obstructive lesion distal to the defect or with elevated pulmonary vascular resistance.

Central Cyanosis

The most common congenital cardiac lesion associated with cyanosis in the adult is the combination of ventricular septal defect and pulmonary outflow tract obstruction (tetralogy of Fallot).Pulmonary arteriovenous fistulae may be congenital or acquired, solitary or multiple, microscopic or massive. The severity of cyanosis produced by these fistulae depends on their size and number.

中心性发绀紫绀型先天性心脏血管病：有些先天性心脏病在心脏内或大血管之间有不正常的通路，使右半边心脏里未经氧合的血，不经过肺而直接流到左半边心脏和主动脉里去，因而动脉血里混进了许多还原血红蛋白，产生紫绀。常见的有先天性紫绀四联症、肺动脉高压性右至左分流综合症和肺动静脉瘘等。

特点：发绀呈全身性（包括颜面、四肢、舌、口腔黏膜与躯干皮肤），发绀部位皮肤温暖。严重者常伴呼吸困难。

Peripheral Type

Probably the most common cause of peripheral cyanosis is the normal vasoconstriction resulting from exposure to cold air or water.When cardiac output is low, as in severe congestive heart failure or shock, cutaneous vasoconstriction occurs.

Peripheral Type

Arterial obstruction to an extremity, as with an embolus, or arteriolar(小动脉的 ) constriction, as in cold-induced vasospasm (Raynaud’s phenomenon), generally results in pallor(苍白 ) and coldness, but there may be associated with cyanosis. Venous obstruction, as in thrombophlebitis(血栓性静脉炎 ), dilates the subpapillary venous plexuses(丛 ) and thereby intensifies cyanosis.

周围性紫绀 特点是紫绀常出现于肢体下垂部分及周围部位（如肢端、耳垂及颜面），皮肤是冰冷的，若经按摩或加温紫绀可消失，此点有助与中心性紫绀鉴别。常见于：（ 1 ）周围组织耗氧量增加；瘀血性周围性紫绀，见于右心衰竭、缩窄性心包炎等。（ 2 ）动脉缺血；见于严重休克时，心输出量明显减少，周围循环缺血缺氧，皮肤和粘膜呈青灰色。亦可见于小动脉收缩（寒冷时）、闭塞性脉管炎、雷诺病等。

Cyanosis due to abnormal Hb derivatives

Methemoglobinemia — Hereditary: very rare — Acquired: >3g/dl in blood - intake or exposure to some

drugs or chemicals, such as sulfa drugs,

nitrite salt. “ enterogenic cyanosis ”

Sulfhemoglobinemia — Caused by some drugs or

chemicals, — Sulfhemoglobin > 0.5g/dl in blood

血液中存在异常血红蛋白衍化物血液中存在异常血红蛋白衍化物

(1)(1) 先天性高铁血红蛋白血症先天性高铁血红蛋白血症(2)(2) 硫化血红蛋白血症硫化血红蛋白血症

（ 1 ）高铁血红蛋白血症：伯氨喹啉、亚硝酸盐等中毒导致 Fe++ 被 Fe+++ 取代。特点：急骤出现，病情危重，静脉血呈深棕色暴露于空气中不转鲜红。抢救措施：静脉注射亚甲蓝溶液或大剂量Vc肠源性青紫症：进食大量含亚硝酸盐的变质蔬菜引起的发绀。

2 ）硫化血红蛋白血症：有致高铁血红蛋白血症的药物或化学物质存在，同时有便秘或服用硫化物，在肠内形成大量的硫化氢，可产生硫化血红蛋白血症（不可逆）。特点：发绀持续时间长，可达数月或更长，患者血液呈蓝褐色。

病例一个 19岁女性患者，由家长护送，匆忙到内科急症室，唇、指甲及面色紫绀、心跳快。头晕、头痛、乏力、气短、恶心、呕吐，有呼吸困难、心律不齐、血压下降等症状明显。主任经过检查立即诊断为“亚硝酸盐中毒”，给予亚甲基蓝解毒，及其他措施，效果很好， 30 分钟后，患者症状缓解，打算继续入院观察。

但是其中毒原因却不明了，反复追问病史：患者为小饭店服务员，于1 小时之前与其弟弟一起吃了前一天晚上煮的面条，她就中毒了，弟弟安然无事。

经过再反复追问了半个小时，排除了她们小饭店有亚硝酸毒盐的可能性，到底毒源哪里来的呢？如果不排除，可能家中会继续中毒，大家都束手无策。突然，我想起以前报纸上面看到的一个报道，开始追问情况，如下：

问：面条是不是比较淡？答：是的 ，你怎么知道？问；你是否加了酱油，你弟弟没有加，对不？答：是的问；加了还淡，又加了很多，是不是？答：是的，我加了很多，还是不咸，将就着吃了

旁边的人莫名其妙，摸不着头脑，我接着说：你回家看看，那个酱油不是酱油，可能是“老水”（注：老水是我们那里卤菜最为常用的一种传统添加剂，其中含有亚硝酸盐，其样子酷似酱油，几乎所有卤菜店都有）。

几位高年资医师均不以为然，认为我是瞎猜。其母若有所思，立刻回家检查，果然是刚刚买的“老水”，放错位置了，其女错拿老水当酱油，幸亏我指出，否则如果用在第二天的早点制作上，可能会造成大面积食客的中毒。其家人千恩万谢。看起来我在后面追问病史不着边际，其实我是想起了很久以前一个不起眼报道以及浅显推理，也是一个餐馆由于错拿老水当酱油，造成大面积的食客亚硝酸盐中毒。其弟弟由于不觉得面条咸，就没有加“酱油”，躲过一场灾难。我于是利用倒问的方法，果然差不多。感想：当医生需要广博的知识，注意平时细心积累，同时可能还需要些侦探小说中的推理吧；）。

Approach to Patients with CyanosisDifferentiation of central as opposed to peripheral

Cyanosis Skin temp. Massage(按摩 )or warming Central Warm No change Peripheral Cool Cyanosis fades

Associated symptoms AND INQUIRY

Certain features are important in arriving at the cause of cyanosis:1. The history, particularly the onset (cyanosis present since birth is usually due to congenital heart disease), and possible exposure to drugs or chemicals that may produce abnormal types of hemoglobin.

病例2000年夏天曾经处理过一起两家人六口集体中毒，印象有点模糊了，当时情况是这两家人中午在一起吃饭，其中有人买了一份凉拌海白菜，事后证明就是这份海白菜为罪魁祸首，饭后不久即先后有人出现心慌胸闷憋气嘴唇发紫，最重者一例意识无，相继入我院，考虑食物中毒，请主任急来后确诊为亚硝酸盐中毒，给予大剂量 vc紧急购来亚甲蓝溶液，最后均康复出院，此事上报了卫生局，经食检所检验所食海白菜亚硝酸盐含量严重超标，原因是新腌制的海白菜容易产生大量亚硝酸盐，安全吃法应当是即食即腌或者两周后再吃。据说卖此海白菜者最后赔款 2 万。

2. Clinical differentiation of central as opposed to peripheral cyanosis. Objective evidence by physical or radiographic examination of disorders of the respiratory or cardiovascular systems. Massage or gentle warming of a cyanotic extremity will increase peripheral blood flow and abolish peripheral but not central cyanosis

3. The presence or absence of clubbing of the digits. Clubbing without cyanosis is frequent in patients with infective endocarditis and ulcerative colitis; it may occasionally occur in healthy persons, and in some instances it may be occupational, e.g., in jackhammer(手提钻 )operators.

The combination of cyanosis and clubbing is frequent in patients with congenital heart disease and right-to-left shunting and is seen occasionally in persons with pulmonary disease such as lung abscess or pulmonary arteriovenous fistulae.In contrast, peripheral cyanosis or acutely developing central cyanosis is not associated with clubbed digits.

4. Determination of PaO2 tension and SaO2 and spectroscopic and other examinations of the blood for abnormal types of hemoglobin (critical in the differential diagnosis of cyanosis).

Cyanosis + Dyspnea( 呼吸困难 ) Disorders of respiratory or cardiovascular

systemCyanosis with mild or no dyspnea

Methemoglobinemia Sulfhemoglobinemia: Spectroscopy

helpfulCyanosis + clubbing

Severe, long durationDetermination of arterial oxygen saturation

问诊要点及伴随症状

　问诊时要注意紫绀出现的年龄，有无服用特殊药物及食物，心肺疾病史及伴随症状。如伴有高度呼吸困难的紫绀常见于重症心、肺疾病；紫绀明显而无呼吸困难者见于高铁血红蛋白血症；紫绀并杵状指（趾），说明紫绀严重、病程较长、主要见于紫绀型先天性心脏病或先天性高铁血经蛋白症；急性紫绀伴衰竭状态或意识障碍，常见于某些药物或化学物品急性中毒、休克、急性肺部感染或急性心功能不全；肢端紫绀常由于局部循环障碍所致、如血栓闭塞性脉管炎、雷诺病及雷诺现象等。

病例３我在急诊科碰到这样一个病例：一个 70岁的老太婆，一年多时间内反复出现全身发绀、恶心呕吐、意识淡漠七次，到医院里经治疗，都恢复正常。，她的老伴于 3 个月前出现与她同样的临床表现，但病情严重，经抢救无效死亡。很明显，这是一个典型的“肠源性紫绀”病例，经用美兰后 20 分钟恢复正常。但以前接诊的医生没有查问中毒的原因，病人及家属也不知道“肠源性紫绀”是什么东西，我只问病人家里有没有亚硝酸盐一类的东西或经常吃腌菜，病人家属马上想起在地窑里放着一缸亚硝酸钠，老太婆误认是食盐，长期在使用！我想，医生与病人交流时，不要太注重专业术语了，应该使用病人能够理解的话，如果此病人早发现中毒的原因，她的老伴也不会死了，这是一个血的教训！

病例３我刚刚进入临床工作时，有一次白班，这时急诊来了三个青年男子，吵吵闹闹说中午吃火锅后呕吐，我看了其中一个，他没有呕吐，自诉饭后有心慌。我做了常规检查包括 EKG没有什么特殊，生命体征平稳。看样子就是想诈钱，本人看不顺眼，本想随便照开点补液，拿点胃药就叫他回家。后来想想三个人是一起来的，看看其他人怎么处理。来到另一诊舍，主任指着患者的口唇 和手指给我看，紫绀。这是一起食物中毒！马上给与留观，洗胃，大量补液，利尿，通知疾病控制中心。疾病控制中心抽血报告：血液检测到高浓度亚硝酸盐。马上予与1 ％亚甲蓝 60mg 静推，口唇甲端立刻变红润。主任说起上个月一个女孩也是亚硝酸盐中毒，当时还以为是女孩有先天性心脏病，口唇甲端都紫绀。教训： 1 对于集体进食后出现不适的，要留观，警惕食物中毒。2 查体要全面，除了生命体征外，要全面，做到观颜察色。