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An Approach to Dyspnea: from atmosphere to hemoglobin

September 26, 2019

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Authors: Jeff Redinger, Tyler Albert

Definition: a subjective sensation of abnormal or uncomfortable breathing
Pathophysiologic Mechanisms of Dyspnea:
  • Decreased arterial O2 levels
  • Increased CO2 levels
  • Low blood pH
  • Neuromechanical dissociation
    • a mismatch between respiratory effort and ventilation
      • elicits dyspnea in cases of abnormal chest wall compliance or airway resistance
Etiologies: follow O2 as we breathe
1) Drive to breathe
  • The impulse to breathe is generated in the brainstem (medulla and pons) via mechanical and chemical stimuli
  • Together with pulmonary and skeletal muscle stretch receptors, O2 and CO2 are the major contributors to the complex feedback control system of basic breathing
    • O2 is sensed by peripheral chemoreceptors in the carotid and aortic bodies
    • CO2 and pH are sensed primarily in the brain by medullary chemoreceptors
    • Muted or absent responses can lead to a decreased “drive” to breathe, as in obesity hypoventilation
2) Generating negative pressure
  • We generate negative pressure to move oxygen from the atmosphere into the lungs
  • Abnormal neuromuscular function and/or poor respiratory system compliance can lead to neuromechanical dissociation and cause CO2 retention
  • Abnormal neuromuscular function:
    • Diaphragmatic paralysis
    • Myasthenia gravis
    • Guillain-Barré
  • Poor respiratory system compliance
    • Pulmonary fibrosis
    • Pleural effusions
    • Obesity
    • Ascites
    • Pregnancy
3) Airways
  • Large airway disorders:
    • COPD
    • Asthma
    • Bronchospasm
    • Obstructing tumor
    • Foreign body
  • Small airway diseases (i.e. bronchiolitis, appearing as “tree-in-bud” opacities on CT imaging):
    • Infectious: viral, bacterial, mycobacterial
    • Inflammatory: RA, SLE, vasculitis
    • Fibro-proliferative: post lung transplantation
    • Inhalational: exposure to tobacco, toxic fumes, mineral dusts
4) Alveolar filling processes
  • Cause dyspnea by impairing gas exchange due to shunt
  • Common etiologies:
    • Blood (alveolar hemorrhage)
    • Pus (pneumonia)
    • Water (pulmonary edema)
    • Atelectasis can cause shunt due to complete collapse of alveoli
5) Alveolar-capillary membrane
  • Gas exchange depends on a thin alveolar-capillary membrane and a large surface area
  • Diseases that destroy (emphysema) or thicken (pulmonary fibrosis) the alveolar-capillary membrane decrease the total membrane surface area and slow the rate of diffusion
  • Membrane abnormalities are rarely a cause of dyspnea. Rather, these disorders have other features as a source of dyspnea, as in COPD (hyperinflation, air trapping) or fibrosis (decreased compliance, increased work of breathing)
  • One exception: alveolar-capillary membrane diseases can result in dyspnea during exercise due to shortened capillary transit time
6) O2 transport in the blood
  • The majority of O2 is bound to hemoglobin, with some dissolved in blood as well
  • Low O2 content can result from decreased total hemoglobin or functional alterations of hemoglobin leading to impaired O2 binding
  • Two main etiologies:
    • Anemia
    • Dyshemoglobinemias (CO poisoning or methemoglobinemia)
7) Inefficient blood flow
  • Cardiac disorders: systolic or diastolic heart failure, MI, arrhythmia, tamponade
  • Pulmonary vascular diseases: pulmonary hypertension, PE
  1. Dyspnea is not always from a pulmonary disorder
  2. An easy way to build a differential diagnosis is to follow the oxygen molecule from atmosphere to hemoglobin
  3. Blood, pus, or water are the main causes of alveolar shunt
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  • Manning HL, Schwartzstein RM. Pathophysiology of dyspnea. N Engl J Med 1995; 333:1547.
  • Parshall MB, et al. An Official American Thoracic Society Statement: Update on the Mechanisms, Assessment, and Management of Dyspnea. Am J Respir Crit Care Med. Vol 185, 4, 435-452. Feb 2012.
  • Schwartzstein RM and Adams L. Dyspnea. In Broaddus VC, Murray JF, Nadel JA, eds. Murray and Nadel’s Textbook of Respiratory Medicine. Philadelphia, Elsevier Saunders, 6th edition, 2016: 485-496.