1. Physical Diagnosis
Cyanosis

2. 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(甲床), ears, and malar(颧骨的；颊的)eminences(隆起).

3. Definition of cyanosis
A bluish color of skin and mucous
membranes, especially in lips, nail beds, and malar
eminences, caused by increased amount
of reduced hemoglobin(Hb) or abnormal
Hb derivatives in small blood vessels.

4. Mechanism of Cyanosis

5. 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.

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

7. 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.

8. The accurate clinical detection of the presence and degree of cyanosis is difficult, as proved by oximetric(血氧定量法的)studies.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. Cyanosis also is observed when nonfunctional hemoglobin such as methemoglobin(正铁血红蛋白，高铁血红蛋白)or sulfhemoglobin(硫化血红蛋白) is present in blood.

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

17. 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)

18. Cyanosis may be subdivided into central and peripheral types
  Cyanosis may be subdivided into central and peripheral types. In the central type, the SaO2 is reduced or an abnormal hemoglobin derivative is present, and the mucous membranes and skin are both affected.

19. Peripheral cyanosis is due to a slowing of blood flow and abnormally great extraction of O2 from normally saturated arterial blood. It results from vasoconstriction and diminished peripheral blood flow, such as occurs in cold exposure, shock, congestive failure, and peripheral vascular disease.

20. Often in these conditions the mucous membranes of the oral cavity or those beneath the tongue may be spared. Clinical differentiation between central and peripheral cyanosis may not always be simple, and in conditions such as cardiogenic shock (心源性休克)with pulmonary edema(肺水肿)there may be a mixture of both types.

21. Central Cyanosis Impaired pulmonary function Right-to-left shunting
1. Airway obstruction
2. Pulmonary diseases
3. Pleural(胸膜的)diseases
Right-to-left shunting
of blood
Tetralogy of Fallot

22. Peripheral Cyanosis
Caused by increased oxygen consumption in peripheral tissue.
Vasoconstriction
Low cardiac output
Exposure to cold air or water
Slowing of blood flow
Right heart failure

23. Mixed Cyanosis (Central + Peripheral) Cardiogenic Edema Shock
Pulmonary
Edema
Cardiogenic
Shock

24. Central Cyanosis Decreased SaO2 results from a marked reduction in the PaO2. This reduction may be brought about by a decline in the FIO2(fraction of inspired oxygen 吸人氧气分数)without sufficient compensatory alveolar(肺泡的) hyperventilation(通气过度,换气过度)to maintain alveolar PO2.

25. Cyanosis does not occur to a significant degree in an ascent to an altitude of 2500 m (8000 ft) but is marked in a further ascent to 5000 m (16,000 ft). The reason for this difference becomes clear on studying the S shape of the Hb-O2 dissociation curve.

26. At 2500 m (8000 ft) the FIO2 is about 120 mmHg, the alveolar PO2 is approximately 80 mmHg, and the SaO2 is nearly normal.

27. However, at 5000 m (16,000 ft) the FIO2 and alveolar PO2 are about 85 and 50 mmHg, respectively, and the SaO2 is only about 75%. This leaves 25% of the hemoglobin in the arterial blood in the reduced form, an amount likely to be associated with cyanosis in the absence of anemia.

28. Similarly, a mutant hemoglobin with a low affinity for O2 (e. g
Similarly, a mutant hemoglobin with a low affinity for O2 (e.g., Hb Kansas) causes lowered SaO2 and resultant central cyanosis.

29.   Seriously impaired pulmonary function, through perfusion(灌注) of unventilated or poorly ventilated areas of the lung or alveolar hypoventilation, is a common cause of central cyanosis.

30. This condition may occur acutely, as in extensive pneumonia or pulmonary edema, or chronically with chronic pulmonary diseases (e.g., emphysema 肺气肿). 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.

31. However, in many types of chronic pulmonary disease with fibrosis and obliteration(闭塞)of the capillary vascular bed, cyanosis does not occur because there is relatively little perfusion of underventilated areas.

32.   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.

33. 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.

34. 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).

35. The more severe the obstruction, the greater the degree of right-to-left shunting and resultant cyanosis. In patients with patent ductus arteriosus, pulmonary hypertension, and right-to-left shunt, differential cyanosis results; that is, cyanosis occurs in the lower but not in the upper extremities.

36.   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.

37. They occur with some frequency in hereditary hemorrhagic telangiectasia (毛细管扩张). SaO2 reduction and cyanosis may also occur in some patients with cirrhosis, presumably as a consequence of pulmonary arteriovenous fistulas or portal vein-pulmonary vein anastomose(吻合术).

38.   In patients with cardiac or pulmonary right-to-left shunts, the presence and severity of cyanosis depend on the size of the shunt relative to the systemic flow as well as on the Hb-O2 saturation of the venous blood.

39. With increased extraction of O2 from the blood by the exercising muscles, the venous blood returning to the right side of the heart is more unsaturated than at rest, and shunting of this blood or its passage through lungs incapable of normal oxygenation intensifies the cyanosis.

40. Also, since the systemic vascular resistance falls with exercise, the right-to-left shunt is augmented by exercise in patients with congenital heart disease and communications between the two sides of the heart. Secondary polycythemia occurs frequently in patients with arterial O2 unsaturation and contributes to the cyanosis.

41.   Cyanosis can be caused by small amounts of circulating methemoglobin and by even smaller amounts of sulfhemoglobin. Although they are uncommon causes of cyanosis, these abnormal hemoglobin pigments should be sought by spectroscopy(分光镜检查)when cyanosis is not readily explained by malfunction of the circulatory or respiratory systems.

42. Generally, digital clubbing does not occur with them
Generally, digital clubbing does not occur with them. The diagnosis of methemoglobinemia can be suspected if the patient's blood remains brown after being mixed in a test tube and exposed to air.

43. 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

44. Approach to Patients with Cyanosis
Differentiation of central as opposed to peripheral
Cyanosis Skin temp Massage(按摩)or warming
Central Warm No change
Peripheral Cool Cyanosis fades

45. Peripheral Cyanosis

46. Probably the most common cause of peripheral cyanosis is the normal vasoconstriction resulting from exposure to cold air or water.

47. When cardiac output is low, as in severe congestive heart failure or shock, cutaneous vasoconstriction occurs as a compensatory mechanism so that blood is diverted from the skin to more vital areas such as the central nervous system and heart, and intense cyanosis associated with cool extremities may result.

48. Even though the arterial blood is normally saturated, the reduced volume flow through the skin and the reduced PO2 at the venous end of the capillary result in cyanosis.

49.   Arterial obstruction to an extremity, as with an embolus, or arteriolar(小动脉的) constriction, as in cold-induced vasospasm血管痉挛 (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.

50. Approach to the Patient

51. Certain features are important in arriving at the cause of cyanosis:

52.   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.

53.   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.

54. 3. The presence or absence of clubbing of the digits.

55. 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.

56. 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.

57. In contrast, peripheral cyanosis or acutely developing central cyanosis is not associated with clubbed digits.  

58. 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).  

59. Cyanosis + Dyspnea(呼吸困难)
Disorders of respiratory or cardiovascular system
Cyanosis with mild or no dyspnea
Methemoglobinemia
Sulfhemoglobinemia: Spectroscopy helpful
Cyanosis + clubbing
Severe, long duration
Determination of arterial oxygen saturation

60. CLUBBING

61.   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.

62. Clubbing may be hereditary, idiopathic, or acquired and associated with a variety of disorders, including cyanotic congenital heart disease, infective endocarditis, and a variety of pulmonary conditions (among them primary and metastatic lung cancer, bronchiectasis(支气管扩张), lung abscess, cystic fibrosis(囊肿性纤维化), and mesothelioma间皮瘤), as well as with some gastrointestinal diseases (including regional enteritis, chronic ulcerative colitis, and hepatic cirrhosis).

63. Bleeding in Skin & Mucous Membranes

64. Introduction of BSMM BSMM is caused by the abnormalities of hemostasis(止血) and /or coagulation mechanisms, and characterized by local or extensive mucocutaneous hemorrhage spontaneously or following slight trauma.

65. According to its extent, there are several types of BSMM
According to its extent, there are several types of BSMM. Pinpoint hemorrhage, equal or less than 2mm in diameter is called petechiae; 3 -5mm hemorrhagic lesion called purpura; more than 5mm, ecchymosis; local elevation and fluctuation, hematoma.

66. Small pinpoint hemorrhages into the dermis due to the leakage of red cells through capillaries are called petechiae and are characteristic of platelet disorders ¾ in particular, severe thrombocytopenia (血小板减少 症).

67. Larger subcutaneous collections of blood due to leakage of blood from small arterioles and venules are called ecchymoses (common bruises) or, if somewhat deeper and palpable, hematomas.

68. They are also common in patients with platelet defects and result from minor trauma. Dilated capillaries, or telangiectasia, may cause bleeding without any hemostatic defect.

69. In addition, the loss of connective tissue support for capillaries and small veins that accompanies aging increases the fragility of superficial vessels, such as those on the dorsum(背部) of the hand, leading to extravasation(外渗) of blood into subcutaneous tissue¾senile(老年的) purpura.

70. Type and Clinical Manifestation
Petechia(出血点;瘀点): pinpoint hemorrhage
Purpura(紫癜): > 5mm in diameter
Ecchymosis(瘀斑): common bruise, >10mm
Hematoma(血肿): local elevation and fluctuation
bleeding in skin, mucous membrane, joint cavity and viscera.

71. Petechiae
Purpura

72. Ecchymosis
(Bruise)
Hematoma

73. Etiology & Pathogenesis
Defects on the capillary wall
Abnormalities of blood platelets
— Quantitative platelets defects
— Qualitative platelets defects
Disturbance of coagulation
— Deficiency of coagulation factors
— Increase of anti-coagulation substances

74. There are a lot of factors participating in the process of the hemostasis and coagulation. Defects in one of following factors may lead to BSMM.

75. First, extravascular factor: Lack of tissue support to the vessel due to tissue degeneration and atrophy may facilitate BSMM. It is a rare cause of BSMM, and is responsible for senile purpura and purpura in Cushing syndrome. In this situation both bleeding time and coagulation time are normal.

76. Second, the vascular factor The constriction of a small vessel plays a role in hemostasis and the pliability of a vessel keeps it intact. If a small vessel becomes fragile and fails to constrict after its damage, BSMM may occur. For example, in allergic purpura, Non-thrombocytopenic purpura due to infection or vitamine C deficiency and hereditary telangiectasis, vascular factor is the contributory cause of BSMM. In this situation, BT and CT are normal, but capillary fragility test is positive.

77. Defects on Capillary Wall
Fragile, or failure to constriction after damage
Allergic purpura;
Hereditary telangioectasia;
Non- thrombocytopenic purpura
— Severe infection
— Vitamin C deficiency
— Uremia(尿毒症)

78. The Third factor is the platelet defects
The Third factor is the platelet defects. Blood platelets play an important role in hemostasis. Platelet defects can be divided into two types, the quantitative type and qualitative type. In the former one, the blood platelet count (or BPC) is lower than normal, that is, thrombocytopenia(血小板减少症). In the latter one, BPC is normal, but its function is abnormal, as in thrombasthenia(血小板无力).

79. In platelet defects, BPC is often lower, occasionally it is normal
In platelet defects, BPC is often lower, occasionally it is normal. Bleeding time is prolonged and clot retraction is poor.

80. Abnormalities of Blood Platelets
Quantitative platelets defects
— BPC is low, as thrombocytopenia with various causes
Qualitative platelets defects
— Platelets dysfunction, as thrombasthenia(血 小板无力)

81. The final cause is the deficiency of coagulation factors.

82. The mechanism of coagulation is complex
The mechanism of coagulation is complex.There are at least twelve coagulation factors that participate in coagulation.This process can be roughly divided into three stages.

83. The First stage is applied to the formation of activated thrombokinase
The First stage is applied to the formation of activated thrombokinase. In the second stage, thrombokinase converts prothrombin into thrombin. In the final stage, thrombin in turn converts fibrinogen into fibrin.

84. Any failure in this process may result in coagulopathy凝血病
Any failure in this process may result in coagulopathy凝血病. Most of the coagulation disorders are congenital,such as hemophilia. In classic hemophilia, there is the deficiency of coagulation factor .

85. A few of coagulation disorders are acquired, such as liver diseases, as we know most of coagulation factors are made by liver. In this situation, coagulation time is prolonged.

86. Disturbance of Coagulation
I. Formation of activated thrombokinase
II. Prothrombin Thrombin
III Fibrinogen Fibrin
Deficiency of coagulation factors
— Congenital : Hemophilia
— Acquired : Severe liver disease
Increase of anti-coagulation substances
— During anti-coagulation therapy

87. Approach to patients with BSMM is a complex problem, here we only discuss a few key points.

88. In history-taking, we should ask whether bleeding is spontaneous or following trauma, ask about past history of bleeding tendency, such as bleeding after tooth extraction, and ask whether there is liver disease.

89. In physical examination, bleeding should be traced over whole body, sometimes including urine and stool. In addition, the jaundice and the size of liver and spleen should be noted. Capillary fragility test is helpful if some vascular factor is suspected.

90. Laboratory routine tests, including blood routine, blood platelet count, bleeding time, and coagulation time, should be done. If necessary, bone marrow study and coagulation factors determination should be added.

91. Approach to Patients with BSMM
History
— Bleeding whether spontaneously or after trauma
— Past history of bleeding tendency
— Liver disease
Physical Examination
— Jaundice,
— Size of liver and spleen,
— Joints
Laboratory Tests
— Blood routine, blood platelet count, bleeding time,
— Coagulation time, bone marrow study
— Coagulation factors determination