Acute respiratory distress syndrome pathophysiology: Difference between revisions

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Latest revision as of 03:53, 20 July 2016

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

Overview

ARDS is a syndrome of inflammation and increased permeability with the lung parenchyma that leads to loss of type I pneumocytes, impaired gas exchange, inappropriate cell proliferation within alveoli, and, in survivors, fibrosis.

Pathophysiology

ARDS typically develops within 24 to 48 hours of the provoking illness or injury and is classically divided into three phases:^[1]^[2]^[3]

Exudative phase (within 5 to 7 days): Systemic inflammation results in increased permeability of the alveolar-capillary barrier and leads to the formation of hyaline membranes along alveolar walls, accumulation of proteinaceous exudate within the alveolar air spaces (non-cardiogenic pulmonary edema), and extravasation of inflammatory cells (predominantly neutrophils) into the lung parenchyma, leading to extensive alveolar damage and, occasionally, diffuse alveolar hemorrhage
Proliferative phase (within 7 to 21 days): Fibroblast proliferation, collagen deposition, and early fibrotic changes are observed within the pulmonary interstitium as alveolar exudate and hyaline membranes begin to be absorbed
Fibrotic phase (within several weeks): Many patients with ARDS will develop some degree of pulmonary fibrosis, of which at least one-quarter will go on to develop clinically apparent fibrotic lung disease with a restrictive ventilatory defect on pulmonary function tests;^[4] the development and extent of pulmonary fibrosis in ARDS correlates with an increased mortality risk^[5]

Genetics

The role of genetics in the development of ARDS is an ongoing area of research. While studies have demonstrated associations between certain genetic factors (including single nucleotide polymorphisms and allelic variants of angiotensin-converting enzyme) and increased susceptibility to the development of ARDS, the nature and implications of these relationships remain uncertain.^[6]^[7]^[8]

Pathology

On gross pathology, the following are characteristic findings of ARDS:

Firm, boggy, and dusky lungs
Generally increased weight compared to healthy lungs due to edema

On microscopic histopathological analysis, the following are characteristic findings of ARDS:

Lung parenchyma demonstrates:
- Hyaline membranes lining the alveolar air spaces
- Edema fluid within alveoli and the interstitium
- Shedding of type I pneumocytes and proliferation of type II pneumocytes
- Infiltration of polymorphonuclear and other inflammatory cells into the interstitial and alveolar compartments,
- Thrombosis and obliteration of pulmonary capillaries
- Hemorrhage into alveoli
Features specific to the underlying disease process (e.g., pneumonia or aspiration pneumonitis)
With progression, alveolar infiltrates are reabsorbed and the inflammatory milieu is replaced by increased collagen deposition and proliferating fibroblasts, culminating in interstitial fibrosis

Hyaline membranes - very high magnification

References

↑ Katzenstein, A. L., C. M. Bloor, and A. A. Leibow. “Diffuse Alveolar Damage--the Role of Oxygen, Shock, and Related Factors. A Review.” The American Journal of Pathology 85, no. 1 (October 1976): 209–28.
↑ Tomashefski, J. F. “Pulmonary Pathology of Acute Respiratory Distress Syndrome.” Clinics in Chest Medicine 21, no. 3 (September 2000): 435–66.
↑ Thille, Arnaud W., Andrés Esteban, Pilar Fernández-Segoviano, José-María Rodriguez, José-Antonio Aramburu, Patricio Vargas-Errázuriz, Ana Martín-Pellicer, José A. Lorente, and Fernando Frutos-Vivar. “Chronology of Histological Lesions in Acute Respiratory Distress Syndrome with Diffuse Alveolar Damage: A Prospective Cohort Study of Clinical Autopsies.” The Lancet. Respiratory Medicine 1, no. 5 (July 2013): 395–401. doi:10.1016/S2213-2600(13)70053-5.
↑ Burnham EL, Janssen WJ, Riches DW, Moss M, Downey GP (2014). "The fibroproliferative response in acute respiratory distress syndrome: mechanisms and clinical significance". Eur Respir J. 43 (1): 276–85. doi:10.1183/09031936.00196412. PMC 4015132. PMID 23520315.
↑ Martin C, Papazian L, Payan MJ, Saux P, Gouin F (1995). "Pulmonary fibrosis correlates with outcome in adult respiratory distress syndrome. A study in mechanically ventilated patients". Chest. 107 (1): 196–200. PMID 7813276.
↑ Jerng JS, Yu CJ, Wang HC, Chen KY, Cheng SL, Yang PC (2006). "Polymorphism of the angiotensin-converting enzyme gene affects the outcome of acute respiratory distress syndrome". Crit Care Med. 34 (4): 1001–6. doi:10.1097/01.CCM.0000206107.92476.39. PMID 16484896.
↑ Cardinal-Fernández P, Ferruelo A, El-Assar M, Santiago C, Gómez-Gallego F, Martín-Pellicer A; et al. (2013). "Genetic predisposition to acute respiratory distress syndrome in patients with severe sepsis". Shock. 39 (3): 255–60. doi:10.1097/SHK.0b013e3182866ff9. PMID 23364437.
↑ Tejera P, Meyer NJ, Chen F, Feng R, Zhao Y, O'Mahony DS; et al. (2012). "Distinct and replicable genetic risk factors for acute respiratory distress syndrome of pulmonary or extrapulmonary origin". J Med Genet. 49 (11): 671–80. doi:10.1136/jmedgenet-2012-100972. PMC 3654537. PMID 23048207.

[1] Katzenstein, A. L., C. M. Bloor, and A. A. Leibow. “Diffuse Alveolar Damage--the Role of Oxygen, Shock, and Related Factors. A Review.” The American Journal of Pathology 85, no. 1 (October 1976): 209–28.

[2] Tomashefski, J. F. “Pulmonary Pathology of Acute Respiratory Distress Syndrome.” Clinics in Chest Medicine 21, no. 3 (September 2000): 435–66.

[3] Thille, Arnaud W., Andrés Esteban, Pilar Fernández-Segoviano, José-María Rodriguez, José-Antonio Aramburu, Patricio Vargas-Errázuriz, Ana Martín-Pellicer, José A. Lorente, and Fernando Frutos-Vivar. “Chronology of Histological Lesions in Acute Respiratory Distress Syndrome with Diffuse Alveolar Damage: A Prospective Cohort Study of Clinical Autopsies.” The Lancet. Respiratory Medicine 1, no. 5 (July 2013): 395–401. doi:10.1016/S2213-2600(13)70053-5.

[pmid23520315-4] Burnham EL, Janssen WJ, Riches DW, Moss M, Downey GP (2014). "The fibroproliferative response in acute respiratory distress syndrome: mechanisms and clinical significance". Eur Respir J. 43 (1): 276–85. doi:10.1183/09031936.00196412. PMC 4015132. PMID 23520315.

[pmid7813276-5] Martin C, Papazian L, Payan MJ, Saux P, Gouin F (1995). "Pulmonary fibrosis correlates with outcome in adult respiratory distress syndrome. A study in mechanically ventilated patients". Chest. 107 (1): 196–200. PMID 7813276.

[pmid16484896-6] Jerng JS, Yu CJ, Wang HC, Chen KY, Cheng SL, Yang PC (2006). "Polymorphism of the angiotensin-converting enzyme gene affects the outcome of acute respiratory distress syndrome". Crit Care Med. 34 (4): 1001–6. doi:10.1097/01.CCM.0000206107.92476.39. PMID 16484896.

[pmid23364437-7] Cardinal-Fernández P, Ferruelo A, El-Assar M, Santiago C, Gómez-Gallego F, Martín-Pellicer A; et al. (2013). "Genetic predisposition to acute respiratory distress syndrome in patients with severe sepsis". Shock. 39 (3): 255–60. doi:10.1097/SHK.0b013e3182866ff9. PMID 23364437.

[pmid23048207-8] Tejera P, Meyer NJ, Chen F, Feng R, Zhao Y, O'Mahony DS; et al. (2012). "Distinct and replicable genetic risk factors for acute respiratory distress syndrome of pulmonary or extrapulmonary origin". J Med Genet. 49 (11): 671–80. doi:10.1136/jmedgenet-2012-100972. PMC 3654537. PMID 23048207.

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@@ Line 1: / Line 1: @@
+__NOTOC__
 {{Acute respiratory distress syndrome}}
-{{CMG}}
+{{CMG}}; {{AE}} {{BShaller}}
 ==Overview==
-Acute respiratory distress syndrome primarily results from the diffuse inflammation of lung parenchyma. Loss of aeration can cause fundamental changes in inflammation amplification and progression.
+ARDS is a syndrome of [[inflammation]] and increased [[permeability]] with the lung parenchyma that leads to loss of [[pneumocyte|type I pneumocytes]], impaired [[gas exchange]], inappropriate [[cell proliferation]] within [[alveolus|alveoli]], and, in survivors, [[fibrosis]].
 ==Pathophysiology==
-[[Image:ARDS.jpg|thumb|A pathohistological image of ARDS.]]
+ARDS typically develops within 24 to 48 hours of the provoking illness or injury and is classically divided into three phases:<ref>Katzenstein, A. L., C. M. Bloor, and A. A. Leibow. “Diffuse Alveolar Damage--the Role of Oxygen, Shock, and Related Factors. A Review.” The American Journal of Pathology 85, no. 1 (October 1976): 209–28.</ref><ref>Tomashefski, J. F. “Pulmonary Pathology of Acute Respiratory Distress Syndrome.” Clinics in Chest Medicine 21, no. 3 (September 2000): 435–66.</ref><ref>Thille, Arnaud W., Andrés Esteban, Pilar Fernández-Segoviano, José-María Rodriguez, José-Antonio Aramburu, Patricio Vargas-Errázuriz, Ana Martín-Pellicer, José A. Lorente, and Fernando Frutos-Vivar. “Chronology of Histological Lesions in Acute Respiratory Distress Syndrome with Diffuse Alveolar Damage: A Prospective Cohort Study of Clinical Autopsies.” The Lancet. Respiratory Medicine 1, no. 5 (July 2013): 395–401. doi:10.1016/S2213-2600(13)70053-5.</ref>
-* ARDS is characterized by a diffuse inflammation of lung parenchyma.
+*'''Exudative phase (''within 5 to 7 days'')''': Systemic inflammation results in increased permeability of the [[alveolar-capillary barrier]] and leads to the formation of hyaline membranes along alveolar walls, accumulation of proteinaceous [[exudate]] within the [[Pulmonary alveolus|alveolar air spaces]] (''non-cardiogenic [[pulmonary edema]]''), and extravasation of inflammatory cells (predominantly [[neutrophils|neutrophils]]) into the lung parenchyma, leading to extensive alveolar damage and, occasionally, diffuse alveolar hemorrhage
-* The triggering insult to the parenchyma usually results in an initial release of [[cytokines]] and other inflammatory mediators, secreted by local [[epithelium|epithelial]] and [[endothelium|endothelial]] [[cell (biology)|cell]]s.
+*'''Proliferative phase (''within 7 to 21 days'')''': [[Fibroblast]] proliferation, [[collagen]] deposition, and early [[fibrosis|fibrotic changes]] are observed within the pulmonary [[interstitium]] as alveolar exudate and hyaline membranes begin to be absorbed
-* [[Neutrophils]] and some T-[[lymphocytes]] quickly migrate into the inflamed lung parynchema and contribute in the amplification of the phenomenon.
+*'''Fibrotic phase (''within several weeks'')''': Many patients with ARDS will develop some degree of pulmonary [[fibrosis]], of which at least one-quarter will go on to develop clinically apparent [[interstitial lung disease|fibrotic lung disease]] with a [[spirometry#restrictive lung patterns|restrictive ventilatory defect]] on [[pulmonary function tests]];<ref name="pmid23520315">{{cite journal| author=Burnham EL, Janssen WJ, Riches DW, Moss M, Downey GP| title=The fibroproliferative response in acute respiratory distress syndrome: mechanisms and clinical significance. | journal=Eur Respir J | year= 2014 | volume= 43 | issue= 1 | pages= 276-85 | pmid=23520315 | doi=10.1183/09031936.00196412 | pmc=4015132 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23520315  }} </ref> the development and extent of pulmonary fibrosis in ARDS correlates with an increased mortality risk<ref name="pmid7813276">{{cite journal| author=Martin C, Papazian L, Payan MJ, Saux P, Gouin F| title=Pulmonary fibrosis correlates with outcome in adult respiratory distress syndrome. A study in mechanically ventilated patients. | journal=Chest | year= 1995 | volume= 107 | issue= 1 | pages= 196-200 | pmid=7813276 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7813276  }} </ref>
-* Typical histological presentation involves diffuse [[Pulmonary alveolus|alveolar]] damage and [[hyaline]] membrane formation in alveolar walls.
-* Although the triggering mechanisms are not completely understood, recent research has examined the role of inflammation and mechanical stress.
-===Inflammation===
+===Genetics===
-* Inflammation alone, as in sepsis, causes:
+The role of [[genetics]] in the development of ARDS is an ongoing area of research. While studies have demonstrated associations between certain genetic factors (including [[single nucleotide polymorphism]]s and [[allele|allelic variants]] of [[angiotensin-converting enzyme|angiotensin-converting enzyme]]) and increased susceptibility to the development of ARDS, the nature and implications of these relationships remain uncertain.<ref name="pmid16484896">{{cite journal| author=Jerng JS, Yu CJ, Wang HC, Chen KY, Cheng SL, Yang PC| title=Polymorphism of the angiotensin-converting enzyme gene affects the outcome of acute respiratory distress syndrome. | journal=Crit Care Med | year= 2006 | volume= 34 | issue= 4 | pages= 1001-6 | pmid=16484896 | doi=10.1097/01.CCM.0000206107.92476.39 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16484896  }} </ref><ref name="pmid23364437">{{cite journal| author=Cardinal-Fernández P, Ferruelo A, El-Assar M, Santiago C, Gómez-Gallego F, Martín-Pellicer A et al.| title=Genetic predisposition to acute respiratory distress syndrome in patients with severe sepsis. | journal=Shock | year= 2013 | volume= 39 | issue= 3 | pages= 255-60 | pmid=23364437 | doi=10.1097/SHK.0b013e3182866ff9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23364437  }} </ref><ref name="pmid23048207">{{cite journal| author=Tejera P, Meyer NJ, Chen F, Feng R, Zhao Y, O'Mahony DS et al.| title=Distinct and replicable genetic risk factors for acute respiratory distress syndrome of pulmonary or extrapulmonary origin. | journal=J Med Genet | year= 2012 | volume= 49 | issue= 11 | pages= 671-80 | pmid=23048207 | doi=10.1136/jmedgenet-2012-100972 | pmc=3654537 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23048207  }} </ref>
-:* Endothelial dysfunction
-:* Fluid extravasation from the [[capillary|capillaries]]
+===Pathology===
-:* Impaired drainage of fluid from the lungs
+On gross pathology, the following are characteristic findings of ARDS:
-* Dysfunction of type II pulmonary epithelial cells may also be present, with a concomitant reduction in surfactant production.
+*Firm, boggy, and dusky lungs
-* Elevated inspired oxygen concentration often becomes necessary at this stage, and they may facilitate a '[[respiratory burst]]' in immune cells.
+*Generally increased weight compared to healthy lungs due to [[edema]]
-* In a secondary phase, endothelial dysfunction causes cells and inflammatory exudate to enter the alveoli
-* This [[pulmonary edema]] increases the thickness of the alveolo-capillary space, increasing the distance the [[oxygen]] must diffuse to reach [[blood]].
+On microscopic histopathological analysis, the following are characteristic findings of ARDS:
-* This impairs gas exchange leading to hypoxia, increases the work of breathing, eventually induces [[fibrosis]] of the airspace.
+*Lung parenchyma demonstrates:
-* Rdema and decreased surfactant production by type II pneumocytes may cause whole [[Pulmonary alveolus|alveoli]] to collapse, or to completely flood. This ''loss of aeration'' contributes further to the right-to-left [[shunt]] in ARDS.
+**Hyaline membranes lining the alveolar air spaces
-* As the alveoli contain progressively less gas, more blood flows through them without being oxygenated resulting in massive intrapulmonary shunting.
+**Edema fluid within alveoli and the interstitium
-* Collapsed alveoli (and small [[bronchi]]) do not allow gas exchange. It is not uncommon to see patients with a PaO<sub>2</sub> of 60 mmHg (8.0 kPa) despite mechanical ventilation with 100% inspired oxygen.
+**Shedding of [[pneumocyte|type I pneumocytes]] and proliferation of [[pneumocyte|type II pneumocytes]]
-* The loss of aeration may follow different patterns according to the nature of the underlying disease, and other factors. In pneumonia-induced ARDS, for example, large, more commonly causes relatively compact areas of alveolar infiltrates.
+**Infiltration of [[neutrophil|polymorphonuclear]] and other [[white blood cells|inflammatory cells]] into the interstitial and alveolar compartments,
-* Usually distributed to the lower [[lobe]]s, in their posterior segments, and they roughly correspond to the initial infected area.
+**[[Thrombosis]] and obliteration of pulmonary [[capillaries]]
-* In [[sepsis]] or trauma-induced ARDS, infiltrates are usually more patchy and diffuse. The posterior and basal segments are always more affected, but the distribution is even less homogeneous.
+**[[Hemorrhage]] into alveoli
-* Loss of aeration also causes important changes in lung mechanical properties. These alterations are fundamental in the process of inflammation amplification and progression to ARDS in mechanically ventilated patients.
+*Features specific to the underlying disease process (e.g., [[pneumonia]] or [[aspiration pneumonia|aspiration pneumonitis]])
+*With progression, alveolar infiltrates are reabsorbed and the inflammatory milieu is replaced by increased [[collagen]] deposition and proliferating [[fibroblast]]s, culminating in [[interstitial fibrosis]]
+[[File:Hyaline membranes - very high mag.jpg|thumb|left|Hyaline membranes - very high magnification]]
+<br><br><br><br><br><br><br><br><br><br><br>
 ==References==
-{{Reflist|2}}
+{{reflist|2}}
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