Harrison's Practice: Cyanosis and Clubbing

Harrison's Practice

Cyanosis and Clubbing

Definition

Cyanosis
- A bluish color of the skin and mucous membranes resulting from an increased quantity of reduced hemoglobin (deoxyhemoglobin), or of hemoglobin derivatives, in the small blood vessels of those areas
- Becomes apparent when the mean capillary concentration of reduced hemoglobin exceeds approximately 50 g/L (5 g/dL)
- 2 types of cyanosis
  - Central
    - Oxygen saturation of arterial blood (Sa_O₂) is reduced or an abnormal hemoglobin derivative is present.
    - Mucous membranes and skin are both affected.
  - Peripheral
    - Due to a slowing of blood flow and abnormally great extraction of oxygen from normally saturated arterial blood
    - Mucous membranes of oral cavity or those beneath the tongue may be spared.
Clubbing
- Selective bullous enlargement of the distal segments of the fingers and toes, particularly on the dorsal surface
- Increased sponginess of the soft tissue at the base of the nail is characteristic.
- Clubbing can occur with chronic central cyanosis, in isolation, or in association with hypertrophic osteoarthropathy, a systemic disorder affecting bone and joints.

Epidemiology

Cyanosis
- Uncommon in the general population
- More common in hospitalized patients
Clubbing
- Primary or idiopathic clubbing is rare.
- Secondary clubbing (due to lung, cardiac, GI, hepatic, or other disorders) is more common.
  - 33% of patients with lung cancer
  - 38% of patients with Crohn’s disease
  - 15% of patients with ulcerative colitis

Mechanism

Cyanosis
- May be brought about by either:
  - Reduction in the Sa_O₂ in the capillary blood
  - Increase in the quantity of venous blood as the result of dilatation of the venules and venous ends of the capillaries
- In general, cyanosis becomes apparent when the mean capillary concentration of reduced hemoglobin exceeds 50 g/L (5 g/dL).
- It is the absolute rather than the relative quantity of reduced hemoglobin that is important in producing cyanosis.
Central cyanosis
- Results from arterial desaturation
  - Usually evident when arterial saturation is < 85%
  - May not be detected until saturation is 75% in dark-skinned persons
Peripheral cyanosis
- Occurs with normal SaO₂ with increased extraction of oxygen from capillary blood caused by decreased localized blood flow
Clubbing
- May be hereditary, idiopathic, or acquired
- The mechanism is unclear.
  - Proliferation of connective tissue, particularly on the dorsal surface of distal segments of the fingers and toes
  - Appears to be secondary to a humoral substance that causes dilation of the vessels of the tip of the digits

Symptoms & Signs

Cyanosis
- Bluish color of the skin and mucous membranes
  - Usually most marked in the lips, nail beds, ears, and malar eminences
  - May also be detected in mucous membranes in the oral cavity and conjunctivae in central but not in peripheral cyanosis
- Modified by the color of the cutaneous pigment, thickness of the skin, and state of the cutaneous capillaries
- Examine the chest for evidence of pulmonary disease, pulmonary edema, or murmurs associated with congenital heart disease.
- If cyanosis is localized to an extremity, evaluate for peripheral vascular obstruction.
Clubbing
- Bullous enlargement of the distal segments of the extremities, particularly on the dorsal surface
- Usually painless, unless associated with hypertrophic osteoarthropathy
- Nail-fold angle
  - Normal: Nail projects from the nail bed at an angle of ~160°.
  - Clubbing: Angle approaches or exceeds a straight line (180°).
- Schamroth sign
  - Normal fingers: Opposition of the index fingers nail-to-nail creates a diamond-shaped window.
  - Clubbed fingers: obliteration of this space due to increase in nail bed tissue
- Palpation
  - Increased sponginess of the soft tissue at the base of the nail
- Hypertrophic osteoarthropathy
  - Periarticular pain and swelling, most often in the wrists, ankles, knees, and elbows

Differential Diagnosis

Central cyanosis

Decreased SaO₂
- Decreased atmospheric pressure—high altitude
- Impaired pulmonary function
  - Alveolar hypoventilation
  - Uneven relationships between pulmonary ventilation and perfusion
  - Impaired oxygen diffusion
  - Pneumonia
  - Pulmonary edema
  - Chronic obstructive pulmonary disease
- Anatomic shunts
  - Cyanotic congenital heart disease
  - Pulmonary arteriovenous fistulas
  - Multiple small intrapulmonary shunts
- Hemoglobin with low affinity for oxygen
  - Hb Kansas
Hemoglobin abnormalities
- Methemoglobinemia—hereditary, acquired
- Sulfhemoglobinemia—acquired
- Carboxyhemoglobinemia (cherry red color, not true cyanosis)

Peripheral cyanosis

Cold exposure
Reduced cardiac output
- Shock of any cause
- Heart failure of any cause
Redistribution of blood flow from extremities
Arterial obstruction
- Peripheral vascular disease
- Systemic embolus
- Raynaud’s phenomenon
Venous obstruction
- Thrombophlebitis

Clubbing

Cardiovascular disease
- Cyanotic congenital heart disease
- Infective endocarditis
Pulmonary conditions
- Primary lung cancer
- Metastatic lung cancer
- Bronchiectasis
- Lung abscess
- Cystic fibrosis
- Mesothelioma
- Idiopathic pulmonary fibrosis
GI diseases
- Inflammatory bowel disease
- Hepatic cirrhosis
Occupational
- Jackhammer operator

Diagnostic Approach

Cyanosis

History
- Duration
  - Cyanosis since birth suggests congenital heart disease.
- Exposures
  - Drugs or chemicals that result in abnormal hemoglobins
  - Methemoglobins: nitrate or nitrites
Physical examination
- Differentiate central from peripheral cyanosis by examining nail beds, lips, and mucous membranes.
  - Peripheral cyanosis is most intense in nail beds and may resolve with gentle warming of extremities.
- Check for clubbing of fingers and toes.
  - Combination of clubbing and cyanosis is frequent in congenital heart disease.
  - Combination occurs occasionally with pulmonary disease (lung abscess, bronchiectasis, and pulmonary arteriovenous shunts) but uncommonly with uncomplicated obstructive lung disease.
- Examine chest for:
  - Evidence of pulmonary disease
  - Pulmonary edema
  - Murmurs associated with congenital heart disease
Laboratory and imaging studies
- Obtain arterial blood gas to measure systemic oxygen saturation.
- Evaluate abnormal hemoglobins.

Clubbing

History
- Signs and symptoms of disorders in which clubbing occurs
  - May occasionally occur in healthy persons
  - May be occupational (e.g., in jackhammer operators)
Physical examination
- Cyanosis
  - Combination of clubbing and cyanosis is frequent in congenital heart disease and occasionally with pulmonary disease (see above).
  - Clubbing without cyanosis is frequent in patients with infective endocarditis and inflammatory bowel disease, and occurs occasionally in hepatic cirrhosis.
- Hypertrophic osteoarthropathy
  - Causes pain and symmetric arthritis-like changes in the shoulders, knees, ankles, wrists, and elbows
  - Associated with clubbing in patients with primary and metastatic lung cancer, mesothelioma, bronchiectasis, and hepatic cirrhosis
Laboratory and imaging studies
- Bone radiography, to confirm diagnosis of hypertrophic osteoarthropathy

Laboratory Tests

Cyanosis
- Arterial blood gas measurement
  - Measures systemic oxygen saturation
  - Repeat while patient inhales 100% oxygen.
    - If saturation fails to increase to > 95%, intravascular shunting of blood bypassing alveoli is likely (e.g., right-to-left intracardiac shunts, pulmonary arteriovenous fistulae).
- Tests for abnormal types of hemoglobin
  - Hemoglobin electrophoresis
  - Spectroscopy
  - Methemoglobin level
Clubbing
- No specific tests
- Laboratory testing is guided by clinical presentation and suspected cause of clubbing.

Imaging

Cyanosis
- Chest radiography and other imaging of the chest, to aid in evaluation of central cyanosis
- When cyanosis is localized to an extremity, evaluate for peripheral vascular obstruction.
Clubbing
- Bone radiography
  - To confirm diagnosis of hypertrophic osteoarthropathy
- Chest radiography and other chest imaging
  - To evaluate for presence of lung disease, heart disease, or cancer

Diagnostic Procedures

As indicated by any discovered underlying disease

Treatment Approach

Cyanosis
- Supplemental oxygen for cyanotic patients who are proved to be hypoxemic
- Treatment of the underlying disorder
Clubbing
- No specific therapy for clubbing itself
- Treatment of the underlying disorder

Specific Treatments

Cyanosis

Supplemental oxygen for cyanotic patients who are proved to be hypoxemic
Specific treatment depends on the underlying cause.
See specific disorders.
- Central cyanosis
  - Hypoventilation
  - Pneumonia
  - Pulmonary edema
  - Pulmonary thromboembolism
  - Chronic obstructive pulmonary disease
  - Congenital heart disease
- Peripheral cyanosis
  - Shock
  - Heart failure
  - Constrictive pericarditis
  - Peripheral vascular disease
  - Deep venous thrombosis
  - Raynaud’s phenomenon

Clubbing

Specific treatment depends on the underlying cause.
See specific disorders.
- Cyanotic congenital heart disease
- Infective endocarditis
- Primary lung cancer
- Metastatic lung cancer
- Bronchiectasis
- Lung abscess
- Cystic fibrosis
- Mesothelioma
- Idiopathic pulmonary fibrosis
- Inflammatory bowel disease
- Hepatic cirrhosis

Monitoring

Patient monitoring depends on the underlying cause of the cyanosis and/or clubbing.

Complications

Complications are not due to the cyanosis and/or clubbing, but rather the underlying disorder leading to these physical signs.
Associated complications depend on the underlying cause of the cyanosis and/or clubbing.

Prognosis

Prognosis depends on the underlying cause of the cyanosis and/or clubbing.

Prevention

General cyanosis
- No specific means of prevention
- Prevent or treat the underlying disorder.
Peripheral cyanosis due to cold exposure
- Avoid cold exposure.
General clubbing
- No specific means of prevention
- Prevent or treat the underlying disorder.
Clubbing due to occupational exposure
- Minimize harmful activity.

ICD-9-CM

782.5 Cyanosis