What is cyanosis and what are its causes?

Definition and Causes of Cyanosis

Cyanosis is defined as a bluish discoloration of the skin and/or mucous membranes resulting from inadequate oxygenation of the blood, generally requiring at least 5 g/L of unsaturated hemoglobin in tissue to be visible. 1

Definition and Pathophysiology

Cyanosis occurs when there is an increased amount of reduced (deoxygenated) hemoglobin or abnormal hemoglobin in the blood. For cyanosis to be clinically apparent:

• At least 5 g/L of unsaturated hemoglobin must be present in tissue 1
• This typically corresponds to oxygen unsaturation of approximately 6-7 volumes percent in the capillaries 2
• Anemia may result in hypoxemia that does not manifest as cyanosis due to insufficient total hemoglobin 1

Types of Cyanosis

Cyanosis can be classified into two main categories:

1. Central Cyanosis

Results from arterial desaturation due to:

• Cardiac causes (right-to-left shunting):

  • Congenital heart defects with right-to-left shunting 1
  • Eisenmenger syndrome 1
  • Complex congenital heart disease 1

• Pulmonary causes:

  • Severe lung diseases affecting gas exchange
  • Ventilation-perfusion mismatch
  • Alveolar hypoventilation
  • High altitude exposure (decreased alveolar oxygen tension) 2

• Abnormal hemoglobin:

  • Methemoglobinemia (congenital or acquired) 1, 3
    • Type I: CYB5R3 enzyme deficiency (20-30% MetHb levels) 1
    • Type II: Severe form with neurological manifestations 1
  • Hemoglobin M variants (substitution of tyrosine for histidine) 1
  • Sulfhemoglobinemia

2. Peripheral Cyanosis

Results from increased extraction of oxygen from normally saturated arterial blood:

• Decreased cardiac output:

  • Heart failure
  • Shock
  • Severe dehydration

• Peripheral vasoconstriction:

  • Cold exposure
  • Acrocyanosis 4
  • Raynaud's phenomenon
  • Peripheral vascular disease

• Venous stasis:

  • Deep vein thrombosis
  • Venous insufficiency

Secondary Complications of Chronic Cyanosis

Patients with chronic cyanosis develop several adaptive mechanisms and complications:

1. Hematologic adaptations:

   • Secondary erythrocytosis (increased red cell mass) 1
   • Rightward shift of the oxyhemoglobin dissociation curve 1
   • Increased cardiac output 1

2. Hematologic complications:

   • Hyperviscosity syndrome (headache, dizziness, fatigue, blurred vision) 1
   • Bleeding diathesis (thrombocytopenia and platelet dysfunction) 1
   • Iron deficiency 1

3. Systemic complications:

   • Renal dysfunction (abnormal glomeruli, reduced filtration) 1
   • Hyperuricemia and gout 1
   • Gallstones (calcium bilirubinate) 1
   • Orthopedic issues (hypertrophic osteoarthropathy, scoliosis) 1
   • Neurological complications (stroke risk, brain abscess) 1

Diagnostic Approach

When evaluating a cyanotic patient:

1. Differentiate central from peripheral cyanosis:

   • Central cyanosis affects mucous membranes and warm areas
   • Peripheral cyanosis typically spares mucous membranes

2. For suspected methemoglobinemia:

   • Measure methemoglobin levels using co-oximetry 1
   • Assess CYB5R enzyme activity
   • Consider genetic testing for congenital forms 1

3. For suspected cardiac causes:

   • Evaluate oxygen saturation with pulse oximetry
   • Consider arterial blood gas analysis
   • Echocardiography to identify structural heart defects

4. For chronic cyanosis monitoring:

   • Complete blood count with MCV
   • Iron studies (serum ferritin, transferrin saturation)
   • Renal function tests
   • Uric acid levels 1

Management Considerations

Management depends on the underlying cause, but important principles include:

• For hyperviscosity symptoms:

  • Therapeutic phlebotomy only if hemoglobin >20 g/dL and hematocrit >65% with symptoms 1
  • Avoid routine phlebotomies due to risk of iron depletion 1

• For iron deficiency:

  • Cautious iron supplementation with monitoring 1

• For methemoglobinemia:

  • Specific treatment based on type and severity

• General measures for chronic cyanosis:

  • Maintain hydration, especially during travel 1
  • Consider supplemental oxygen for long flights 1
  • Avoid high altitudes 1

Understanding the pathophysiology and causes of cyanosis is essential for proper diagnosis and management of this important clinical sign.