INDIAN JOURNAL OF CARDIOVASCULAR DISEASES JOURNAL in women (IJCD) 2016 VOL 1 ISSUE 4 CLINICAL ROUNDS 1 WINCARS CYANOSIS – PART 1 Maddury Jyotsna, B. Srinivas, Nemani Lalita DEFINITION: Cyanosis has to be distinguished from florid skin Cyanosis refers to bluish discoloration of the skin and characteristic of Polycythemia Vera and a cherry-colored mucous membranes as a result of increased quantity of flush is caused by Carboxy Hb. reduced hemoglobin, or hemoglobin derivatives, in the The degree of cyanosis is dependent on: small blood vessels of those areas. The name cyanosis 1. The color of the cutaneous pigment literally means "the blue disease" or "the blue condition". 2. The thickness of the skin It is derived from the color cyan, which comes from 3. The state of the cutaneous capillaries. kyanós, the Greek word for "blue". Cyanosis is commonly noted in: It is the absolute, rather than the relative, quantity of 1. Lips reduced hemoglobin that is important in producing 2. Tongue cyanosis. Based on Lundsgaard and Van Slyke's work 3. Oral mucus membrane [1], it is classically described as occurring if 5.0 g/dl or 4. Nail beds more of deoxyhemoglobin is present [2]. This was based 5. Malar prominences. on an "estimate" of capillary saturation which depends 6. Ear lobes on a mean of arterial versus peripheral venous blood gas 7. Trunk measurements [3]. Since estimation of hypoxia is usually 8. Conjunctiva now based either on arterial blood gas measurement or 9. Circumoral pulse oximetry, this is probably an overestimate, with Lips are more specific for the detection of cyanosis. evidence that levels of 2.0 g/dl of deoxyhemoglobin may reliably produce cyanosis. Physiology of cyanosis: The normal color of flesh is thought to result from the combination of the pigments- Cyanosis is masked in a patient with severe anemia. oxyhemoglobin, deoxyhemoglobin, melanin, and Cyanosis becomes more apparent in: carotene, and from the optical effect of scattering. Blue skin coloration would result if the quantity of reflected 1. Polycythemia ( Patients with marked Polycythemia blue waves increased disproportionately or if the tend to be cyanotic at higher levels of SaO2 ), quantity of other reflected wavelengths decreased 2. Local passive congestion disproportionately. 3. Presence of nonfunctional hemoglobin ( However, blue skin color detected in individuals who methemoglobin or sulfhemoglobin) have increased amounts of deoxyhemoglobin cannot be explained on the basis of reflection of increased Cyanosis can be detected reliably when the SaO2 has quantities of high-frequency wavelengths from a "blue" fallen to 85%. However, in some, particularly in dark- pigment. Presumably, the deoxyhemoglobin is less red than oxyhemoglobin and therefore absorbs more red skinned persons, it may not be detected until it has spectrum. By subtraction of red wavelengths, the blue declined to 75%. spectrum is allowed to predominate in the reflected light Cyanosis may be brought about by (i.e., something that is less red is more blue). 1. An increase in the quantity of venous blood as a result of dilation of the venules and venous ends of the capillaries 2. A reduction in the SaO2 in the capillary blood Maddury Jyotsna 1, B. Srinivas 2, Nemani Lalita2, Cyanosis can be central or peripheral. All causes of 1 Professor & HOU-IV, Department of Cardiology, NIMS, India central cyanosis cause peripheral cyanosis but the vice- 2Associate Professor, Department of Cardiology, NIMS. Corresponding Author: Maddury Jyotsna versa is not true. Both central and peripheral cyanosis Email: [email protected] differ in etiology and mechanism and treatment. Central cyanosis can be due to cardiac or non-cardiac causes (See INDIAN JOURNAL OF CARDIOVASCULAR DISEASES JOURNAL in women (IJCD) 2016 VOL 1 ISSUE 4 CLINICAL ROUNDS 2 WINCARS Table 1). For a details list of cardiac causes for central. cyanosis, see Table 3 Table 1: Differences between peripheral and central cyanosis Parameter Peripheral cyanosis Central cyanosis Etiology Slowing of blood flow and abnormally great Sao2 is reduced or presence of abnormal extraction of SaO2. hemoglobin. Causes 1. Reduced cardiac output -heart failure, 1. Central nervous system shock. involvement (impairing normal 2. Peripheral arterial disease - Thrombosis, ventilation) - Intracranial hemorrhage, atheroma or embolism. Drug overdose like heroin, Tonic–clonic 3. Vasoconstriction: Cold exposure, seizure Raynaud's phenomenon, Acrocyanosis, 2. Respiratory system ( Impaired Erythrocyanosis and Beta-blocker drugs. pulmonary function)-Pneumonia, 4. Venous obstruction – lower limb deep Bronchiolitis, Bronchospasm , Pulmonary vein thrombosis hypertension, Pulmonary embolism (Painful blue leg -phlegmasia cerulea 3. Congenital heart diseases (E.g Tetralogy dolens), Superior vena cava obstruction of Fallot, right to left shunts in heart or (cyanosis, and oedema affecting the great vessels), face). 4. Heart failure 5. Abnormal Blood -Methemoglobinemia Polycythemia, Congenital cyanosis and 6. Others (High altitude, Hypothermia, Obstructive sleep apnea, cyanide toxicity). Oral cavity mucus Normal Blue discoloration membrane Massage or gentle Cyanosis is abolished Cyanosis persists warming of a cyanotic extremity Associated with No Yes clubbing Congenital cyanosis: May be due to HbM Boston which Low-affinity hemoglobin should be considered in is due to a mutation in the α-codon resulting in a patients with cyanosis and a low hematocrit when no change of primary sequence (H → Y). Tyrosine stabilizes other reason is apparent after thorough evaluation. The the Fe (III) form that is oxyhemoglobin creating a P50 test confirms the diagnosis. Cyanosis can be caused permanent T-state of Hb. HbM is inherited in an by small quantities of circulating methemoglobin and by autosomal dominant pattern. It has 5 variants. even smaller quantities of sulfhemoglobin. Oxidation of Individuals in whom an alpha chain substitution has deoxyhemoglobin to form methemoglobin can be caused occurred are noted to be cyanotic beginning at birth. by many drugs and toxins including nitrites, Those in whom beta chain substitution has occurred sulfonamides, and aniline derivatives. These abnormal often do not become cyanotic until three to six months of oxyhemoglobin derivatives should be sought by age because of the normal changeover from gamma to spectroscopy and digital clubbing does not occur with them. beta chain synthesis during that time. INDIAN JOURNAL OF CARDIOVASCULAR DISEASES JOURNAL in women (IJCD) 2016 VOL 1 ISSUE 4 CLINICAL ROUNDS 3 WINCARS Approach to assessing the etiology of cyanosis: Table 2: Approach to assessing etiology of cyanosis Obtain a heparinized arterial blood specimen If specimen obtained is A bright red arterial brown and does not If the sample is dark red specimen obtained in a change color on shaking and becomes bright red patient with generalized in air, the plasma should on shaking in air, blue skin color s be allowed to separate If the plasma is clear, one Perform blood gas If the plasma is brown, should suspect the Suspect deposition of analysis on another methemalbumin is likely presence of nonheme pigment in the specimen to confirm to be present. methemoglobin or skin arterial hypoxemia. sulfhemoglobin Drug and substance induced: Ingestion of substances cyanosis, polycythemia, paradoxical embolism and even containing gold or silver can produce bluish skin stroke. Examples are: coloration that is most prominent in sun-exposed 1. The drainage of the SVC to LA portions of the body. The bluish skin color associated 2. Persistent SVC with unroofed coronary sinus with hemosiderin deposition is more apparent in parts (Raghib syndrome) of the body with less melatonin pigment. A more bronze 3. Partial or complete drainage of the IVC into the LA color is seen in the presence of melanin. Polymers of the 4. Total anomalous systemic venous drainage (TASVC) oxidation products of chlorpromazine, when deposited including the hepatic veins and the coronary sinus in the skin and other organs, can result in a blue to draining into the Pulmonary venous atresia also purple color. The antiarrhythmic agent, amiodarone, can presents as TAPVC with severe pulmonary venous cause lipofuscin deposition in the skin. In sun-exposed obstruction usually has intense cyanosis as areas, a blue skin color is seen in a small percentage of obstructed TAPVC. patients on long-term therapy. Cyanotic congenital heart defects: Mainly these are Pulmonary arteriovenous fistula (PAVF): classified as VSD+PS physiology, Transposition physiology, Admixture physiology, Eisenmenger If right to left shunt is greater than 20 percent of physiology and miscellaneous. List of the disease under systemic CO or size > 2 cm, then the patient may have this heading are mentioned in Table 3. Duct dependent obvious cyanosis. The tendency for shunting and pulmonary circulation like pulmonary atresia and duct cyanosis increases with age. In some cases of HHT dependent systemic circulation like HLHS are always (Hereditary hemorrhagic telangiectasia) even though the produces cyanosis. right to left shunt is > 20% of CO, cyanosis may be The abnormalities of position and connection of the hidden by anemia or when systemic arteries rather than major systemic venous channels draining to the heart are pulmonary arteries feed the fistulas. PAVF with mostly rare incidental findings with not much of cyanosis, who anticipate pregnancy need treatment. hemodynamic significance. In some cases it can cause INDIAN JOURNAL OF CARDIOVASCULAR DISEASES JOURNAL in women (IJCD) 2016 VOL 1 ISSUE 4 CLINICAL ROUNDS 4 WINCARS Table 3 : Cyanotic congenital heart defects The time of onset of cyanosis gives a clue to aetiology of the congenital heart disease: 1. VSD+PS physiology. a. Tetralogy of Fallot (TOF). Table 2: Clue to CHD based on time of onset of cyanosis b. D-TGA+VSD+PS c. Doutlet right ventricle (DORV)+VSD+PS. Onset of cyanosis Diagnosis d. Tricuspid atresia+ VSD+PS. Cyanosis on day 1 d-TGA or other complex e. Single ventricle +PS. situations (see Cyanosis part-2 ). 2. Transposition physiology. Few weeks after birth TOF (as the severity of Fallot a. D-transposition of great arteries (d- increases, the cyanosis can TGA)+VSD+PS.