Central cyanosis, chest pain, and clubbing

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2]

Abbreviations: ABG= Arterial blood gas, ANP= Atrial natriuretic peptide, BNP= Brain natriuretic peptide, CBC= Complete blood count, COPD= Chronic obstructive pulmonary disease, CRP= C-reactive protein, CT= Computed tomography, CXR= Chest X-ray, DVT= Deep vein thrombosis, ESR= Erythrocyte sedimentation rate, HRCT= High Resolution CT, IgE= Immunoglobulin E, LDH= Lactate dehydrogenase, PCWP= Pulmonary capillary wedge pressure.

Diseases			Cyanosis		Clinical manifestations						Para-clinical findings							Gold standard	Additional findings
					Symptoms			Physical examination
											Lab Findings				Imaging
			Peripheral	Central	Dyspnea	Fever	Chest pain	Clubbing	Peripheral edema	Auscultation	CBC	ABG	Electrolytes	Other	X-ray	CT scan	Other
Pulmonary diseases	Airway disorder	Chronic bronchitis	-	+	+	+/-	+/-	+	-	Rales, crackles, Wheeze	Leukocytosis	↓O2, ↑CO2, Respiratory acidosis	Hypokalemia, Hypernatremia	Gram stain of sputum	Elongated heart, Flattened diaphragms, Prominent hilar vasculature	Bronchial wall thickening with increased bronchovascular markings	-	HRCT	Productive cough, Chest tightness
	Parenchymal disorder	Alveolitis	+/-	+	+	+	+	+/-	-	Wheeze, Crackles	Leukocytosis, Eosinophilia	↓O2, ↑CO2	Normal	↑ESR, ↑CRP	Scattered opacities, Fine reticulation	Homogeneous ground-glass opacity	-	HRCT PLUS Clinical findings	Malaise, Chills, Headache
		Pneumonia	-	+	+	+	+	+/-	-	Rales, Crackles, Wheeze, Pleural friction rub	Leukocytosis with neutrophilia	Normal	Hyponatremia	-	Entire lobe consolidated, Air bronchograms	Focal ground-glass opacity	-	HRCT	Tachycardia, Bradycardia (Legionella)
		Asthma (Late)	-	+	+	-	+/-	+/-	-	End expiratory wheeze	Eosinophilia	↓O2, ↑CO2	Normal	↑ IgE	Atelectasis	Allergic bronchopulmonary aspergillosis, Bronchiectasis	-	Spirometry before and after bronchodilator	Triad of asthma, nasal polyps, and rash is indicative of aspirin sensitivity.
		Tuberculosis	-	+	+	+	+	+/-	-	Reduced breath sounds, Wheeze, Inspiratory crackles	Leukocytosis, ↑Lymphocyte	↓O2, ↑CO2	Hyponatremia, Hyperkalemia, Hypochloremia	PPD, interferon-gamma release assay (IGRA)	Dense, homogeneous parenchymal consolidation	Nodules with low-density centers and rim enhancement	Fluorodeoxyglucose positron emission tomography/CT (FDG PET/CT)	Sputum culture, QuantiFERON-TB Gold (QFT)	Loss of appetite, Night sweats
		Pulmonary fibrosis	-	+	+	-	+	+	-	Inspiratory crackles	Anemia	↓O2, ↑CO2	Normal	Matrix metalloproteinases (MMPs)	Honeycombing	Traction bronchiectasis, Interlobular septal thickening	HRCT	HRCT	Fatigue, Weight loss
		Pneumoconiosis	-	+	+	-	+/-	+/-	-	End expiratory wheeze	Leukocytosis, Anemia	↓O2, ↑CO2, Respiratory acidosis	Hyper/Hypocalcemia, Hypermagnesemia	-	Small to large round nodular opacities	Diffuse distribution of small nodules	MRI and PET-CT scan	CT/HRCT scan	Tightness in the chest
		Lung cancer	-	+	+	-	+/-	+	-	Absence of breath sounds, Stridor, Wheezing	Leukocytosis, Anemia	↓O2, ↑CO2	Hyponatremia	↑CRP, ↑ESR	Pulmonary nodule or mass, Mediastinal widening Hilar lymphadenopathy	Massive lymphadenopathy, Direct mediastinal invasion	MRI, PET-CT scan, Bronchoscopy	Low dose computed tomography scan (LDCT)	Weight loss, Loss of appetite
	Pulmonary vascular disorders	Pulmonary arterio-venous malformation	-	+	+	-	+	+	-	Pulmonary bruit	Normal	↓O2, ↑CO2, Respiratory acidosis	Normal	-	One or more rounded or multilobular opacities	Connecting vessel in hilum	Magnetic resonance angiography, Echocardiography	Contrast enhanced magnetic resonance angiography	Cerebral arteriovenous malformation
		Pulmonary hypertension	-	+	+	-	+/-	+/-	-	Tricuspid regurgitation murmur, Pulmonic insufficiency murmur	Mild anemia	↓O2, ↑CO2	Hypernatremia	↑BNP, ↑ANP	Right deviated cardiac apex, Prominent pulmonary artery	Ill-defined nodules, Interlobular septal thickening	CT pulmonary angiography (CTPA), MRA	Cardiac catheterization (PCWP)	Fatigue, Inability to exercise
Disease			Peripheral	Central	Dyspnea	Fever	Chest pain	Clubbing	Peripheral edema	Auscultation	CBC	ABG	Electrolytes	Other	X-ray	CT scan	Other	Gold standard	Additional findings
Cardiac diseases	Congenital disorders	Atrioventricular canal defect	+/-	+	+	-	+/-	+/-	-	Wheezing,Holosystolic or systolic ejection murmur	Normal	Normal	Normal	Pulse oximetry	Cardiomegaly, Increased pulmonary vascular markings	Normal	Echocardiography, MRI	Echocardiography	Tachypnea, Lack of appetite, Pale skin color, Excessive sweating
		Pulmonic stenosis	-	+	+	-	+	+/-	-	Crescendo-decrescendo ejection murmur	Schistocyte	↓O2	Normal	Pulse oximetry	Right ventricular hypertrophy, Dilated main pulmonary artery	Stenotic segment, Post stenotic dilatation	Severity of the stenosis by velocity encoded phase contrast (VEC) cine sequences	Echocardiography	Fainting, Palpitation
		Total anomalous pulmonary venous connection	-	+	+	-	+/-	+/-	-	Systolic murmur over the pulmonary area	Normal	↓O2	Normal	Pulse oximetry	Snowman sign	Anomalous venous return	Blind ended left atrium with no connecting veins in echocardiography	Echocardiography	Pounding heart, Weak pulse, Extreme sleepiness
		Transposition of the great vessels	-	+	+	-	+/-	+/-	-	Diastolic and Systolic murmur	Normal	↓O2	Normal	Pulse oximetry	Cardiomegaly with narrow superior mediastinum (egg on a string sign)	Abnormal great vessel anatomy	Flow dynamics on Steady-state free precession (SSFP) MRI	Echocardiography	Lack of appetite, Poor weight gain
		Truncus arteriosus	-	+	+/-	-	+/-	+/-	-	Holosystolic or ejection type murmur	Normal	↓O2	Normal	Pulse oximetry	Moderate cardiomegaly, pulmonary plethora, Widened mediastinum	Single cardiac trunk	Anomalous anatomy in MRI	Echocardiography	Fatigue, Sweating, Pale or cool skin
		Patent ductus arteriosus	-	+	+/-	-	+/-	+/-	-	Continuous machinery murmur	Normal	↓O2, ↑CO2	Normal	Pulse oximetry	Cardiomegaly, Aortopulmonary window obsecuration	Tortuous morphology of ductus (Krichenko classification)	Spiral CT pulmonary angiogram	Echocardiography	Failure to thrive, Respiratory distress
	Acquired disorders	Cardiomyopathy	-	+	+	-	+	+	+	S3 and S4	Lymphocytosis	↓O2, ↑CO2	Normal	↓PaO2 in pulse oximetry	Enlarged left ventricle and atria, Pulmonary edema	Normal	MRI	Endomyocardial biopsy	Arrhythmia, Bloating
		Heart tumors	-	+	+	-	+/-	+/-	+/-	Early diastolic tumor plop	Normal	Normal	Normal	Mild ↓PaO2 in pulse oximetry	Calcification in lateral view	Intracardiac mass	Echocardiography	Histologic diagnosis (biopsy)	Syncope, Weight loss
		Mitral Stenosis	-	+	+	-	+/-	+/-	+/-	Diastolic murmur	Normal	Normal	Normal	Mild ↓PaO2 in pulse oximetry	Left atrial enlargement, Mitral annular calcification	Secondary pulmonary hemosiderosis	Velocity-encoded cine-magnetic resonance imaging (VEC-MRI)	Echocardiography	Dizziness, Hemoptysis
Hematologic diseases		Polycythemia	+	+	+	+/-	+/-	+	-	Normal	↑RBC, ↑WBC, ↑HGB, ↑Plt	↓O2	Hyperkalemia	↑Leukocyte alkaline phosphatase, ↑Ferritin, ↑Erythropoietin	AVM, COPD, pulmonary hypertension	Normal	Abdominal ultrasound or renal vascular studies for ruling out renal artery stenosis	RBC mass (RCM) and plasma volume measurement	Itchiness, Headache. Dizziness. Blurred vision
Miscellaneous		High altitude exposure	+/-	+	+	-	+/-	+	-	Wheezing	Polycythemia	↓O2, ↓CO2, Respiratory alkalosis	Hyperphosphatemia, Hypercalcemia, Hyponatremia, Hypokalemia, Hypomagnesemia	Decreased bicarbonate	Central interstitial edema	Pulmonary consolidation	-	Hypoxic challenge test	Dizziness, Coma, Death