Central cyanosis

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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 Sleep apnea[1] - + + - - - - Normal Polycythemia O2, ↑CO2 Normal - Normal Normal Polysomnography Polysomnography Nightmares, Snoring
Chronic bronchitis[2] - + + +/- +/- + - 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
Atelectasis[3] - + + - + - - Localized diminished breath sounds, Wheeze Leukocytosis O2, ↑CO2, Respiratory acidosis Normal - Localized increased opacity, Deviation toward the atelectasis Local crowding of pulmonary vessels and bronchi MRI for distinguishing obstructive from non-obstructive HRCT Cough, Shallow breathing
Parenchymal disorder Alveolitis[4] +/- + + + + +/- - 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[5] - + + + + +/- - 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)[6] - + + - +/- +/- - 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[7] - + + + + +/- - 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[8] - + + - + + - Inspiratory crackles Anemia O2, ↑CO2 Normal Matrix metalloproteinases (MMPs) Honeycombing Traction bronchiectasis,

Interlobular septal thickening

HRCT HRCT Fatigue, Weight loss
Pneumoconiosis[9] - + + - +/- +/- - End expiratory wheeze Leukocytosis, Anemia O2, ↑CO2, Respiratory acidosis Hyper/Hypocalcemia,


- 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[10] - + + - +/- + - 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
Acute respiratory distress syndrome[11] - + + +/- + - - Inspiratory crackles Leukopenia/Leukocytosis O2, ↓CO2, Respiratory alkalosis Hyponatremia, Hyperkalemia BNP, ↑Von Willebrand factor (VWF) Bilateral pulmonary infiltrates (patchy to diffuse) Emphysema, Pneumothorax and pneumomediastinum, Mediastinal lymphadenopathy Invasive Hemodynamic Monitoring (PCWP), Bronchoscopy Chest CT scan Tachypnea, Muscle weakness
Pulmonary vascular disorders Pulmonary arterio-venous malformation[12][13][14] - + + - + + - 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[15] - + + - +/- +/- - 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[16] +/- + + - +/- +/- - 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
Ebstein anomaly[17] - + +/- - +/- - - Loud S1 Normal Normal Normal Pulse oximetry Cardiomegaly, "Box shape" heart Apical displacement of the septal and posterior leaflets of the tricuspid valve "Atrialisation" of the right ventricle in MRI, Tricuspid regurgitation in echocardiography Echocardiography Fatigue, Palpitations
Tetralogy of Fallot[18] - + +/- - +/- - - Harsh systolic murmur Normal Normal Normal Pulse oximetry "Boot-shaped" heart with an upturned cardiac apex Aortopulmonary collateral vessels Peripheral pulmonary stenosis and atresia in echocardiography Echocardiography Fainting, Palpitation
Pulmonic stenosis[19] - + + - + +/- - 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[20] - + + - +/- +/- - 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[21] - + + - +/- +/- - 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[22] - + +/- - +/- +/- - Holosystolic or ejection type murmur Normal O2 Normal Pulse oximetry Moderate cardiomegalypulmonary plethoraWidened mediastinum Single cardiac trunk Anomalous anatomy in MRI Echocardiography Fatigue, Sweating, Pale or cool skin
Patent ductus arteriosus[23] - + +/- - +/- +/- - 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 Myocardial infarction[24] - + + +/- + - - S3 and S4 Normal Normal Hyponatremia, Hypokalemia Elevated troponin I and CKMB Rolling out other causes Coronary luminal narrowing in CT perfusion scan Wall motion abnormality in echocardiography Cardiac troponin I Dizziness, Fatigue, Lightheadedness, Cold sweat
Cardiogenic shock[25] +/- + + - - - + Muffled heart sound Anemia O2, ↑CO2 Hyperkalemia PaO2 in pulse oximetry Normal Normal Echocardiography  Clinical findings Tachypnea, Palpitation, Hypotension, Weak pulse
Cardiomyopathy[26] - + + - + + + 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[27] - + + - +/- +/- +/- 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[28] - + + - +/- +/- +/- 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
Disease Peripheral Central Dyspnea Fever Chest pain Clubbing Peripheral edema Auscultation CBC ABG Electrolytes Other X-ray CT scan Other Gold standard Additional findings
Hematologic diseases Methemoglobinemia[29] - + + +/- + - - Wheezing Anemia, Methemoglobinemia Normal PaO2, ↑SaO2, "Saturation gap" Normal SaO2 in pulse oximetry Normal Normal Echocardiography for ruling out other causes Co-oximetry, ABG paired with pulse oximetry. Serum methemoglobin levels Headache, Altered mental status, Delirium, Seizure, Coma
Polycythemia[30] + + + +/- +/- + - 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
Neurological disease Breath-holding spells[31] - + + - +/- - - Wheezing Hypochromic microcytic anemia O2 Hypocalcemia, Hypokalemia Iron deficiency Ruling out foreign body aspiration Normal EEG monitoring Clinical findings Fainting, Twitching muscles, Seizure
Seizure[32] - + + +/- - - - Normal Normal O2, ↑CO2 Hyponatremia, Hypo/Hypercalcemia CPK, ↑LDH, Normal Normal EEG EEG Fainting, Tonic-clonic movements
Coma[33] - + - - - - +/- Wheezing Normal O2, ↑CO2 Normal - Underlying disease Underlying disease - Glasgow Coma Scale (GCS) Depressed brainstem reflexes, Agonal breathing
Head trauma[34] - + + - - - - Normal Normal O2, ↑CO2 Normal - Skull fracture Intracranial hemorrhage MRI CT scan Nausea, Hypertension, Bradycardia,Tachypnea
Miscellaneous High altitude exposure[35] +/- + + - +/- + - Wheezing Polycythemia O2, ↓CO2, Respiratory alkalosis Hyperphosphatemia, Hypercalcemia, Hyponatremia, Hypokalemia, Hypomagnesemia Decreased bicarbonate Central interstitial edema Pulmonary consolidation - Hypoxic challenge test Dizziness, Coma, Death
Smoke inhalation[36] +/- + + - + - - Wheezing Anemia, Carboxyhemoglobin O2, ↑CO2, Respiratory acidosis Normal CO-oximetry Diffuse opacities Pulmonary infiltration Pulmonary function testing Bronchoscopy Cough, Hoarseness, Hemoptysis, Headache, Fainting


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