Dyspnea or shortness of breath is a normal manifestation of heavy exertion, but it can also be caused by different underlying diseases, therefore understanding the etiology, pathophysiology and differential diagnosis of dyspnea is important in the diagnosis of serious underlying clinical conditions. In this article, etiology, pathophysiology and differential diagnosis of dyspnea will be discussed in detail.
layout presenting the pathophysiology of dyspnea

layout presenting the pathophysiology of dyspnea

Definition of Dyspnea

Dyspnea — the shortness of breath

Dyspnea is defined as the subjective sensation of chest tightness or shortness of the breath. It can be caused by pulmonary and extrapulmonary causes.

Etiology of Dyspnea

Causes of Dyspnea

Dyspnea is one of the most common manifestations affecting individuals with pulmonary diseases, although it can be caused by other varieties of causes, such as heart failure, ischemic heart disease (IHD), hypobaric hypoxia, extreme anemia, metabolic acidosis, panic attacks with hyperventilation and any restrictions to the lungs such as obesity or kyphoscoliosis.  Differential diagnosis of dyspnea can be broadly divided into pulmonary and extrapulmonary causes.

Clinical Anatomy of Pulmonary System

Respiratory system

Image: “the respiratory system consists of the airways, the lungs, and the respiratory muscles that mediate the movement of air into and out of the body” by LadyofHats. License: Public Domain

Anatomy of the Lung

Image: “The Anatomy of the Lung” by Phil Schatz License: CC-BY 4.0

To understand the pathophysiology and differential diagnosis of dyspnea, it is essential to understand the anatomy of different structures of the airways and the lungs. The human lungs are divided into lobes. The right lung has three lobes − upper, lower and middle lobes – while the left lung two lobes − upper and lower lobes. These lobes are demarcated by intervening visceral pleura.

Tracheobronchial tree is a term used in describing the branching structure of the respiratory airways and includes: trachea, bronchi, and bronchiolesFurther anatomical division of the tracheobronchial tree into conducting airways and terminal respiratory units or acini.

Conducting airways

These airways deliver the air from the upper respiratory passages into the lungs to the areas of gas exchange.

Terminal respiratory units or acini

These are the airways and the alveoli involved in the process of gas exchange.

Proximal conducting airways (bronchi) are lined by ciliated pseudostratified columnar epithelium with secretory glands and supported by cartilage. These cilia move unidirectionally and uniformly towards the pharynx to move the mucus layer continuously outside the lungs.

Any lung disease affects the function of the cilia or increases the mucous production, or both as in chronic bronchitis with smoker patients will result in accumulation of mucus in the respiratory passages. Circumferential airway smooth muscle is also present, constriction of these smooth muscles as in patients with asthma may result in narrowing the airways and shortness of breath.

The smallest conducting airways (non-respiratory bronchioles) are lined by cuboidal epithelium that may be ciliated, but they don’t have circumferential smooth muscles and cartilage support.

Bronchial anatomy detail of alveoli and lung circulation

Image: “Bronchial anatomy detail of alveoli and lung circulation” by Patrick J. Lynch. License: (CC BY 2.5) A – Alveoli, AS – Septum alveolare, BR – Bronchus respiratorius, BT – Bronchus terminalis, D – Mucous gland, DA – Ductus alveolaris, M – Musculus, N – Nervus, PA – Branch of Arteria pulm, PV – Branch of Vena pulm.


Image: “An alveolus is an anatomical structure that has the form of a hollow cavity” by LadyofHats. License: Public Domain

The lobes of the lungs are divided into lobules, which are a collection of terminal respiratory units. The thin epithelial walls of the alveoli provide the gas exchange with the alveolar capillary bed.

Conducting airways Trachea Cartilage, Bronchial glands
Bronchioles Nonrespiratory
Terminal Respiratory Units Respiratory
Alveolar ducts & alveoli

Pathophysiology of Dyspnea

Dyspnea occurs due to an imbalance between the required gas exchange and the workload on the muscles of breathing.

layout presenting the pathophysiology of dyspnea

Layout presenting the pathophysiology of dyspnea

The sensation of shortness of breath can be caused by different physiological changes:

  • Increased airway resistance due to any pulmonary disease will require greater muscular effort by the intercostals muscles and chest wall to overcome this resistance, resulting in dyspnea.
  • Obstructive airway diseases as emphysema may result in hyperinflation of the lungs with decreased lung compliance, thus the work of breathing increases and results in dyspnea.  
  • Marked airway obstruction may result in ventilation/perfusion mismatching producing arterial hypoxemia that will stimulate the central and peripheral chemoreceptors resulting in increased respiratory drive and dyspnea.

Grades of Dyspnea

Classification of dyspnea

The Medical Research Council (MRC) has classified the dyspnea due to lung diseases into four degrees depending on its severity. It is also known as MRC breathlessness scale.

Grade 0 Dyspnea occurs only during strenuous exercise.
Grade I Dyspnea is only caused by brisk walking.
Grade II Brisk walking is not possible because of the shortness of breath.
Grade III Stopping is needed due to dyspnea after 100 m of walking.
Grade IV One does not leave the house due to shortness of breath.

Differential Diagnosis of Dyspnea

Pulmonary causes of dyspnea

Obstructive lung diseases

Obstructive pulmonary diseases are characterized by increased resistance to airflow during inspiration and expiration.


  • Cigarette smoking for years suggests strongly diagnosis of COPD
  • Atopy (allergy) with episodes of wheezes suggests asthma
  • Instrumentation (e.g. prolonged endotracheal tube) suggests upper airway stenosis
  • Dyspnea is exaggerated by exercise, not by changing body position

Examination: Auscultation reveals wheezes all over the lungs, in contrast to restrictive lung diseases where normal lung auscultation is observed.

Pulmonary function tests: FEV1, FVC is stable, FEV1/FVC

Restrictive lung diseases They are characterized by decreased lung compliance as a result of:

  1. Inflammation: Pneumonia
  2. Fibrosis: Pulmonary fibrosis
  3. Occupational: Pneumoconiosis
  4. Neoplastic infiltration: Lung tumor


  • History of occupational exposure to harmful dust
  • Risk factors for lung tumors

Examination: Auscultation: Normal lungs fields, pulmonary function tests are used to differentiate restrictive from obstructive pulmonary diseases.

Pulmonary function tests: FEV1, FVC more than FEV1, FEV1/FVC

Vascular lung diseases Most common disorder affecting pulmonary vessels is pulmonary emboli.


  • Sudden onset of shortness of breath and clear lungs in patients with risk factors, such as bed rode patients with DVT.

Examination: No specific clinical findings for pulmonary embolism; clear lung fields

Standard investigation: CT angiogram

Exrapulmonary causes of dyspnea

Cardiac dyspnea Occurs mainly due to left-sided heart failure, caused by:

  • Impended blood flow to left-sided heart blood accumulated in pulmonary vascular bed transudation of fluid resulting in interstitial and alveolar edema


  • Orthopnea: Dyspnea increases in supine position due to the aggravation of pulmonary congestion.
  • Paroxysmal nocturnal dyspnea awakens patients from sleep

ExaminationLung auscultation reveals bilateral basal rales.

Anemia Acute loss of blood leads to hypovolemic shock and dyspnea due to impaired tissue oxygenation. Chronic anemia is well tolerated and produces dyspnea only with strenuous exercise.
Metabolic acidosis Stimulates the brain stem resulting in alveolar hyperventilation and deep breathing to compensate acidosis by washing out the CO2; Most common causes:

  1. Ketoacidosis in diabetes
  2. Acidosis in renal insufficiency
  3. Intoxication: overdose of salicylate
Anxiety Panic attacks commonly occur in young females in different situations, often presents with shortness of breath, chest pain and dizziness with a feeling of inability to take enough deep breaths. Hyperventilation associated with anxiety may lead to acute respiratory alkalosis manifested as:

  1. Paresthesia at the fingertips and around the mouth
  2. Tetanic cramps in severe cases
Extrapulmonary  restrictions Can be caused by:

  1. Pleural effusions
  2. Pleural thickening
  3. Tumors (e. g., mesothelioma)
  4. Deformities of the thorax
  5. Weakness of the diaphragm

Review Questions

The correct answers can be found below the references.

1. You are examining a 30-year-old male patient, who is suffering from a cough and dyspnea for more than three months. He is working as a laborer in a very dense and non-hygienic working place for more than three years. While studying the X-ray report of lungs, you observed pleural effusion in the left lung. How many lobes are in the left lung in humans?

  1. One
  2. Two
  3. Three
  4. Four
  5. Five

2. A 57-year-old male reported that he is observing dyspnea only during strenuous exercise. Which of the following grades of the dyspnea is this patient suffering from?

  1. Grade 0
  2. Grade I
  3. Grade II
  4. Grade III
  5. Grade IV

3. Which of the following is not an extrapulmonary cause of dyspnea?

  1. Anxiety
  2. Anemia
  3. Metabolic acidosis
  4. Cardiac dyspnea
  5. COPD
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