Diffuse alveolar damage

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Diffuse alveolar damage
Hyaline membranes - very high mag.jpg
Micrograph showing hyaline membranes, the key histologic feature of diffuse alveolar damage. H&E stain.
Specialty Respirology

Diffuse alveolar damage (DAD) is a histologic term used to describe specific changes that occur to the structure of the lungs during injury or disease. Most often DAD is described in association with the early stages of acute respiratory distress syndrome (ARDS). [1] DAD can be seen in situations other than ARDS (such as acute interstitial pneumonia) and that ARDS can occur without DAD. [1]

Contents

Definitions

Berlin Criteria: as stated on UpToDate (2020)

The Berlin Criteria specifies: [4]

  1. Timing: onset of respiratory symptoms within one week of an injury/insult.
  2. Chest Imaging: either chest x-ray or CT scan, must show bilateral opacities that cannot be fully explained by other conditions such as effusion, lung/lobar collapse, or lung nodules.
  3. Origin of Edema: respiratory failure that cannot be fully explained by cardiac failure or fluid overload, this needs objective assessment such as an echocardiogram.
  4. Impaired Oxygenation: this can be determined by looking at the ratio of arterial oxygen tension to fraction of inspired oxygen (PaO2/FiO2) that can be obtained based on an arterial blood gas test. Note: all PaO2/FiO2 ratios used in the determination of the severity of ARDS require that the patient be on a ventilator at a setting that includes 5 cm H2O or more of positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP).
Level of ARDSPaO2/FiO2 RangePEEP/CPAP
Mild ARDS201–300≥5 cm H2O
Moderate ARDS101–200
Severe ARDS<100

Histology/Progression

The epithelial lining of alveoli are composed of two different types of cells. Alveolar type I epithelial cells comprise about 80% of the alveolar surface area and are primarily responsible for gas exchange. [5] Alveolar type II epithelial cells play the critical roles of producing surfactant, moving water out of the airspaces, and regenerating alveolar epithelium. [5] The alveolar type II epithelial cells are more resistant to damage, so after an insult to the alveoli, most of the damage will occur to the alveolar type I epithelial cells. [5]

Left side demonstrate the structure of a normal alveolus including the difference between type I and type II alveolar epithelial cells. Right side depicts what occurs after injury to the alveolus during the acute/exudative phase. The-normal-alveolus-Left-Hand-Side-and-the-injured-alveolus-in-the-acute.jpg
Left side demonstrate the structure of a normal alveolus including the difference between type I and type II alveolar epithelial cells. Right side depicts what occurs after injury to the alveolus during the acute/exudative phase.

Once the initial insult has damaged the alveoli and begun the process of DAD, the condition will typically progress in three phases: exudative, proliferative, and fibrotic. [6] Below are the description of the phases, paraphrased from Sweeney et al. (2016). [6]

Causes/Mechanism

DAD can occur in settings other than ARDS and that ARDS can occur with histology other than DAD. That being said, the histologic finding of DAD is often associated with the clinical syndrome ARDS but it can also be seen in conditions such as acute interstitial pneumonia (essentially ARDS but without a known inciting cause), acute exacerbation of idiopathic pulmonary fibrosis, and primary graft dysfunction after lung transplant. [1] The most common causes of ARDS are pneumonia, non-pulmonary sepsis, and aspiration. [7]

To reiterate, the hallmark of DAD is hyaline membrane formation. [1] There is a similar process which occurs in newborns called hyaline membrane disease, although the preferred term is surfactant-deficiency disorder, that also has the formation of hyaline membranes. [8] This disorder typically develops due to prematurity, especially when the infant is delivered prior to 36 weeks since surfactant doesn't start being produced until 35 weeks gestation. [8] The lack of surfactant causes alveolar collapse and subsequent damage to the epithelial lining of the alveoli, causing the same path of damage described in the above section.

Diagnosis

In order to make a diagnosis of DAD a biopsy of the lung must be obtained, processed, and examined microscopically. As described above, the hallmark of diagnosing DAD is the presence of hyaline membranes. [1] Most frequently DAD is associated with ARDS, but since there are clinical criteria (see Berlin criteria above) upon which we can diagnose ARDS, it is often unnecessary in all cases to obtain invasive biopsies of the lung. Additionally, there are limitations of the biopsy test since it is possible to sample a potentially normal area of lung even though there is DAD in the rest of the lung, resulting in a false negative. [1]

Treatment

The most important factor for treating DAD or ARDS is to treat the underlying cause of the injury to the lungs, [9] for example pneumonia or sepsis. These patients will have problems with oxygenation, meaning they will likely need a breathing tube, medications to keep them comfortable (sedative, paralytic, and/or analgesic), and a mechanical ventilator to breathe for them. [10] The mechanical ventilator will often be set to a setting of at least 5 cm H2O of positive end-expiratory pressure (PEEP) to keep the alveoli from collapsing during exhalation. [9] Other treatments to improve oxygenation may include prone positioning or extracorporeal membrane oxygenation (ECMO). [6]

Prognosis

As expected, the mortality rates increase as the severity of the ARDS increases with mortality rates at approximately 35%, 40%, and 46% for mild, moderate, and severe, respectively. [11] It has been revealed that patients with ARDS that show DAD on histology are at a high mortality rate of 71.9% compared to 45.5% in patients with ARDS but without DAD. [12] Of the patients who succumb to ARDS, the most common cause of death is septic shock with multi organ dysfunction syndrome. [13]

Among survivors upon discharge, many will have impairments in their lung function. The majority (approximately 80%) of patient will have decrease diffusion capacity while fewer patients (approximately 20%) will have issues with airflow (either obstructive or restrictive). [14] These airflow issues will typically resolve within six months and the diffusion issues will resolve within five years. [14]

Related Research Articles

<span class="mw-page-title-main">Meconium aspiration syndrome</span> Medical condition affecting newborn infants

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<span class="mw-page-title-main">Lung</span> Primary organ of the respiratory system

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<span class="mw-page-title-main">Pulmonary alveolus</span> Hollow cavity found in the lungs

A pulmonary alveolus, also known as an air sac or air space, is one of millions of hollow, distensible cup-shaped cavities in the lungs where pulmonary gas exchange takes place. Oxygen is exchanged for carbon dioxide at the blood–air barrier between the alveolar air and the pulmonary capillary. Alveoli make up the functional tissue of the mammalian lungs known as the lung parenchyma, which takes up 90 percent of the total lung volume.

<span class="mw-page-title-main">Respiratory failure</span> Inadequate gas exchange by the respiratory system

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<span class="mw-page-title-main">Acute respiratory distress syndrome</span> Respiratory failure due to widespread inflammation in the lungs

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<span class="mw-page-title-main">Infant respiratory distress syndrome</span> Human disease affecting newborns

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<span class="mw-page-title-main">Atelectasis</span> Partial collapse of a lung causing reduced gas exchange

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<span class="mw-page-title-main">Interstitial lung disease</span> Diseases of the space or tissue between the alveoli of the lungs

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<span class="mw-page-title-main">Pulmonary surfactant</span> Complex of phospholipids and proteins

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<span class="mw-page-title-main">Acute interstitial pneumonitis</span> Medical condition

Acute interstitial pneumonitis is a rare, severe lung disease that usually affects otherwise healthy individuals. There is no known cause or cure.

<span class="mw-page-title-main">Alveolar lung disease</span> Medical condition

Alveolar lung diseases, are a group of diseases that mainly affect the alveoli of the lungs.

<span class="mw-page-title-main">Surfactant protein B</span> Protein-coding gene in the species Homo sapiens

Surfactant protein B is an essential lipid-associated protein found in pulmonary surfactant. Without it, the lung would not be able to inflate after a deep breath out. It rearranges lipid molecules in the fluid lining the lung so that tiny air sacs in the lung, called alveoli, can more easily inflate.

Ventilator-associated lung injury (VALI) is an acute lung injury that develops during mechanical ventilation and is termed ventilator-induced lung injury (VILI) if it can be proven that the mechanical ventilation caused the acute lung injury. In contrast, ventilator-associated lung injury (VALI) exists if the cause cannot be proven. VALI is the appropriate term in most situations because it is virtually impossible to prove what actually caused the lung injury in the hospital.

<span class="mw-page-title-main">Pulmonary contusion</span> Internal bruise of the lungs

A pulmonary contusion, also known as lung contusion, is a bruise of the lung, caused by chest trauma. As a result of damage to capillaries, blood and other fluids accumulate in the lung tissue. The excess fluid interferes with gas exchange, potentially leading to inadequate oxygen levels (hypoxia). Unlike pulmonary laceration, another type of lung injury, pulmonary contusion does not involve a cut or tear of the lung tissue.

Surfactant metabolism dysfunction is a condition where pulmonary surfactant is insufficient for adequate respiration. Surface tension at the liquid-air interphase in the alveoli makes the air sacs prone to collapsing post expiration. This is due to the fact that water molecules in the liquid-air surface of alveoli are more attracted to one another than they are to molecules in the air. For sphere-like structures like alveoli, water molecules line the inner walls of the air sacs and stick tightly together through hydrogen bonds. These intermolecular forces put great restraint on the inner walls of the air sac, tighten the surface all together, and unyielding to stretch for inhalation. Thus, without something to alleviate this surface tension, alveoli can collapse and cannot be filled up again. Surfactant is essential mixture that is released into the air-facing surface of inner walls of air sacs to lessen the strength of surface tension. This mixture inserts itself among water molecules and breaks up hydrogen bonds that hold the tension. Multiple lung diseases, like ISD or RDS, in newborns and late-onsets cases have been linked to dysfunction of surfactant metabolism.

Acute inhalation injury may result from frequent and widespread use of household cleaning agents and industrial gases. The airways and lungs receive continuous first-pass exposure to non-toxic and irritant or toxic gases via inhalation. Irritant gases are those that, on inhalation, dissolve in the water of the respiratory tract mucosa and provoke an inflammatory response, usually from the release of acidic or alkaline radicals. Smoke, chlorine, phosgene, sulfur dioxide, hydrogen chloride, hydrogen sulfide, nitrogen dioxide, ozone, and ammonia are common irritants.

<span class="mw-page-title-main">Pathophysiology of acute respiratory distress syndrome</span>

The pathophysiology of acute respiratory distress syndrome involves fluid accumulation in the lungs not explained by heart failure. It is typically provoked by an acute injury to the lungs that results in flooding of the lungs' microscopic air sacs responsible for the exchange of gases such as oxygen and carbon dioxide with capillaries in the lungs. Additional common findings in ARDS include partial collapse of the lungs (atelectasis) and low levels of oxygen in the blood (hypoxemia). The clinical syndrome is associated with pathological findings including pneumonia, eosinophilic pneumonia, cryptogenic organizing pneumonia, acute fibrinous organizing pneumonia, and diffuse alveolar damage (DAD). Of these, the pathology most commonly associated with ARDS is DAD, which is characterized by a diffuse inflammation of lung tissue. The triggering insult to the tissue usually results in an initial release of chemical signals and other inflammatory mediators secreted by local epithelial and endothelial cells.

Whole lung lavage (WLL), also called lung washing, is a medical procedure in which the patient's lungs are washed with saline by filling and draining repeatedly. It is used to treat pulmonary alveolar proteinosis, in which excess lung surfactant proteins prevent the patient from breathing. Some sources consider it a variation of bronchoalveolar lavage.

References

  1. 1 2 3 4 5 6 7 Cardinal-Fernández, Pablo; Lorente, José A.; Ballén-Barragán, Aída; Matute-Bello, Gustavo (June 2017). "Acute Respiratory Distress Syndrome and Diffuse Alveolar Damage. New Insights on a Complex Relationship". Annals of the American Thoracic Society. 14 (6): 844–850. doi:10.1513/AnnalsATS.201609-728PS. ISSN   2329-6933. PMID   28570160.
  2. ↑ Berry, Gerald J; Rouse, Robert V (November 20, 2010). "Acute Interstitial Pneumonia - Diffuse Alveolar Damage". surgpathcriteria.stanford.edu. Archived from the original on 2014-11-23. Retrieved 2020-04-03.
  3. ↑ "Acute Respiratory Distress Syndrome (ARDS) | American Lung Association | American Lung Association". www.lung.org. Retrieved 2020-04-03.
  4. ↑ Siegel, Mark D (March 2020). "Acute Respiratory Distress Syndrome: Clinical Features, Diagnosis, and Complications in Adults". UpToDate. Archived from the original on 2020-04-11. Retrieved 2020-04-03.
  5. 1 2 3 Manicone, Anne M (2009-01-01). "Role of the pulmonary epithelium and inflammatory signals in acute lung injury". Expert Review of Clinical Immunology. 5 (1): 63–75. doi:10.1586/1744666X.5.1.63. ISSN   1744-666X. PMC   2745180 . PMID   19885383.
  6. 1 2 3 Sweeney, Rob Mac; McAuley, Daniel F. (2016-11-12). "Acute respiratory distress syndrome". The Lancet. 388 (10058): 2416–2430. doi:10.1016/S0140-6736(16)00578-X. ISSN   0140-6736. PMC   7138018 . PMID   27133972.
  7. ↑ Rezoagli, Emanuele; Fumagalli, Roberto; Bellani, Giacomo (July 2017). "Definition and epidemiology of acute respiratory distress syndrome". Annals of Translational Medicine. 5 (14): 282. doi: 10.21037/atm.2017.06.62 . ISSN   2305-5839. PMC   5537110 . PMID   28828357.
  8. 1 2 Agrawal, Rishi. "Respiratory distress syndrome | Radiology Reference Article | Radiopaedia.org". Radiopaedia. Retrieved 2020-04-09.
  9. 1 2 Yoshikawa, A.; Fukuoka, J. "Acute respiratory distress syndrome (ARDS) / diffuse alveolar damage (DAD)". www.pathologyoutlines.com. Archived from the original on 2012-05-05. Retrieved 2020-04-09.
  10. ↑ Siegel, Mark D; Siemieniuk, Reed (March 25, 2020). "Acute Respiratory Distress Syndrome: Supportive Care and Oxygenation in Adults". UpToDate. Archived from the original on 2014-11-08. Retrieved April 9, 2020.
  11. ↑ Bellani, Giacomo; Laffey, John G.; Pham, Tài; Fan, Eddy; Brochard, Laurent; Esteban, Andres; Gattinoni, Luciano; van Haren, Frank; Larsson, Anders; McAuley, Daniel F.; Ranieri, Marco (2016-02-23). "Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries". JAMA. 315 (8): 788–800. doi: 10.1001/jama.2016.0291 . hdl: 11573/859307 . ISSN   1538-3598. PMID   26903337.
  12. ↑ Kao, Kuo-Chin; Hu, Han-Chung; Chang, Chih-Hao; Hung, Chen-Yiu; Chiu, Li-Chung; Li, Shih-Hong; Lin, Shih-Wei; Chuang, Li-Pang; Wang, Chih-Wei; Li, Li-Fu; Chen, Ning-Hung (2015-05-15). "Diffuse alveolar damage associated mortality in selected acute respiratory distress syndrome patients with open lung biopsy". Critical Care. 19 (1): 228. doi: 10.1186/s13054-015-0949-y . ISSN   1466-609X. PMC   4449559 . PMID   25981598.
  13. ↑ Stapleton, Renee D.; Wang, Bennet M.; Hudson, Leonard D.; Rubenfeld, Gordon D.; Caldwell, Ellen S.; Steinberg, Kenneth P. (August 2005). "Causes and timing of death in patients with ARDS". Chest. 128 (2): 525–532. doi:10.1378/chest.128.2.525. ISSN   0012-3692. PMID   16100134.
  14. 1 2 Siegel, Mark D (March 2020). "Acute Respiratory Distress Syndrome: Prognosis and Outcomes in Adults". UpToDate. Archived from the original on 2020-07-30. Retrieved 2020-04-09.
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