Cyanosis: Causes

Pathogenesis (development of disease)

Cyanosis results from an increase in the amount of reduced hemoglobin in capillary blood. True cyanosis can be distinguished from pseudocyanosis. Pseudocyanosis is a bluish or grayish-bluish discoloration of the skin and/or mucous membranes that, unlike true cyanosis, is not due to hypoxemia (reduced oxygen content of the blood) or ischemia (reduced blood flow) but is usually due to pigment deposits. Causes include drug side effects (phenothiazines, amiodarone, and chloroquine can cause bluish to grayish skin discoloration) or ingestion of certain metals and metal compounds. Pseudocyanosis is also sometimes referred to as the dark reddish skin changes seen in polycythaemia vera (PV). The following forms of true cyanosis can be distinguished:

  • Hemoglobin cyanosis (nonoxygenated hemoglobin rises to more than 5 g/dL in capillary blood).
    • Central cyanosis results from decreased oxygenation (oxygenation) of the blood (that is, bluish discoloration of the skin and central mucous membranes). Two forms of central cyanosis can be distinguished:
      • Pulmonary cyanosis (originating in the lungs): impaired ventilation, diffusion or perfusion; this leads to inadequate oxygenation of the blood in the alveoli (pulmonary alveoli) and capillaries.
      • Cardiac cyanosis (originating from the heart): e.g., mixing of oxygenated blood in arteriovenous anastomoses, i.e., admixture of venous to arterial blood
    • Peripheral cyanosis (central O2 saturation is normal) – results from increased oxygen depletion in the body periphery; blue coloration of the lips and the acras (finger/toe extremities, nose, ears); in contrast, the central mucous membranes are rosy!
    • Combination of central and peripheral cyanosis.
  • Hemiglobin cyanosis (in which pathological hemoglobins are formed, which have a reduced ability of hemoblobin to bind oxygen; here iron is bound in trivalent form, which is not capable of oxygen binding); causes of hemiglobin cyanosis are the occurrence of:
    • Carboxyhemoglobin (due to CO intoxication) → carboxyhemoglobinemia.
    • Methemoglobin (e.g., due to methemoglobin-stimulating drugs, cyanogen poisoning) → methemoglobinemia
    • Sulfhemoglobin (by hemoglobin oxidation due todrug intake (see below) or hydrogen sulfide intoxication) → carboxyhemoglobinemia.

* If cyanosis affects the acra (fingers, toes, or nose), it is called acrocyanosis.

Etiology (causes)

Hemoglobin cyanosis

Central cyanosis

Disease-related causes

Respiratory System (J00-J99)

  • Acute and chronic respiratory insufficiency (respiratory failure).
  • ARDS (Acute Respiratory Distress Syndrome) – adult acute respiratory failure.
  • Bronchial asthma
  • Airway obstruction (e.g. sleep apnea, Pickwick’s syndrome).
  • Bronchiectasis (synonym: bronchiectasis) – persistent irreversible saccular or cylindrical dilatation of the bronchi (medium-sized airways) that may be congenital or acquired; symptoms: chronic cough with “mouthful expectoration” (large-volume triple-layered sputum: foam, mucus, and pus), fatigue, weight loss, and decreased exercise capacity
  • Chronic bronchitis (inflammation of the mucous membrane of the bronchi).
  • Chronic obstructive pulmonary disease (COPD)
  • Interstitial lung disease
  • Pulmonary emphysema (distension of the lungs)
  • Pulmonary edema – accumulation of water in the lungs.
  • Pneumonia (pneumonia)
  • Pneumothorax (collapsed lung)
  • Honeycomb lung (cyst lung)

Blood, blood-forming organs – immune system (D50-D90)

  • Cold agglutination disease – acquired disease caused by the formation of cold agglutinins.
  • Cryoglobulinemia – chronic recurrent immune complex vasculitides.
  • Methemoglobinemia – increased concentration of methemoglobin in erythrocytes (red blood cells).
  • Polyglobulia – increased red cell count (erythrocytosis) or hemoglobin concentration in the blood due to increased blood formation.

Cardiovascular system (I00-I99)

  • Valvular heart defects such as tetralogy of Fallot, pulmonary atresia with ventricular septal defect, transposition with great arteries
  • Pulmonary embolism
  • Myocarditis (inflammation of the heart muscle)
  • Vitia (heart defect) with right-to-left shunt (in this disorder, deoxygenated venous blood enters the systemic circulation directly, bypassing the pulmonary circulation)
    • Double outlet right ventricle (DORV) – group of congenital (congenital) malformations of the heart in which the aorta (large artery of the body) and arteria pulmonalis (pulmonary artery) arise exclusively from the right ventricle (heart chamber)
    • Fallot́s tri- and tetralogy – congenital malformation of the heart and vessels near the heart.
    • Single ventricle (one-chamber heart)
    • Transposition of the great vessels – congenital malformation of the heart in which the aorta is connected to the right ventricle and the pulmonary artery is connected to the left ventricle (heart chamber).
    • Truncus arteriosus communis (TAC) – congenital malformation of the heart in which the aorta and truncus pulmonalis (pulmonary artery) were not completely separated during fetal (early childhood) development.

Symptoms and abnormal clinical and laboratory findings not classified elsewhere (R00-R99)

  • Cardiogenic shock – form of shock caused by weakened pumping action of the heart.

Medication

Environmental pollution – intoxications (poisonings).

  • Carbon dioxide poisoning
  • Pesticide poisoning
  • Hypobaric hypoxia (exposure to high altitude).

Peripheral generalized cyanosis

Disease-related causes

Cardiovascular (I00-I99).

  • Heart failure (cardiac insufficiency), in:
    • Arrthythmias (cardiac arrhythmias).
    • Ischemic or dilated cardiomyopathy (DCM, heart muscle disease).
    • Valvular vitiation (valvular heart disease)
    • Pericardial tamponade (pericardial tamponade)

Peripheral localized cyanosis

Disease-related causes

Cardiovascular (I00-I99).

Environmental pollution – intoxications (poisonings)

  • Cold

Combination of central and peripheral cyanosis

Disease-related causes

Cardiovascular (I00-I99).

Hemiglobin cyanosis

Carboxyhemoglobinemia

Environmental exposures – intoxications (poisonings).

  • CO intoxication (CO poisoning).

Methemoglobinemia

Disease-related causes

Endocrine, nutritional and metabolic diseases (E00-E90).

  • Congenital methemoglobinemia – increased methemoglobin concentration in erythrocytes (red blood cells).
  • Methemoglobin reductase deficiency – leads to methemoglobinemia.

Medications

  • Chloroquine (antimalarial drug)
  • Benzocaine – “teething aids” and other OTC preparations containing benzocaine.
  • Dapsone (anti-inflammatory with antibiotic effect, belonging to the group of sulfones).
  • Lidocaine (local anesthetic)
  • Metoclopramide (antiemetic)
  • Nitrofuran (antibiotic)
  • Nitroprusside (antihypertensive)
  • Phenacetin (analgesic)
  • Phenytoin (antiepileptic)
  • Prilocaine (local anesthetic)
  • Primaquine (antimalarial)
  • Sulfonamides (antibiotic)

Environmental pollution – intoxications (poisoning).

  • Acetanilide
  • Aniline/aniline dyes
  • Amino compounds
  • Arsenic
  • Benzene derivatives
  • Chlorates
  • Cyanic compounds
  • Dinitrophenol
  • Insecticides
  • Methylene blue
  • Sodium thiocyanate
  • Nitrates
  • Nitrites
  • Nitrobenzene
  • Nitrobenzene
  • Nitroglycerin
  • Nitro compounds
  • Nitrous gases
  • Paraquat (contact herbicide)
  • Phenol
  • Smoke inhalation
  • Trinitrotoluene

Sulfhemoglobinemia

Causes related to disease

Medication

  • Intoxication with phenacetin (pain reliever).
  • Intoxication with sulfonamides – poisoning with agents that act against bacterial infections.

Environmental pollution – intoxications (poisonings).

  • Hydrogen sulfide