Pathophysiology of acute respiratory distress syndrome

Pathophysiology of acute respiratory distress syndrome
Pathophysiology of acute respiratory distress syndrome
	Micrograph of diffuse alveolar damage, the histologic correlate of ARDS. H&E stain.
Biological system	respiratory system

Last updated November 09, 2023

The pathophysiology of acute respiratory distress syndrome involves fluid accumulation in the lungs not explained by heart failure (noncardiogenic pulmonary edema). 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.^[1] 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.

Neutrophils and some T-lymphocytes quickly migrate into the inflamed lung tissue and contribute in the amplification of the phenomenon. Typical histological presentation involves diffuse 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

Inflammation, such as that caused by sepsis, causes endothelial cell dysfunction, fluid leakage from capillaries and impairs drainage of fluid from the lungs. Elevated inspired oxygen concentration often becomes necessary at this stage, and may facilitate a 'respiratory burst' in immune cells. In a secondary phase, endothelial cell dysfunction causes cells and inflammatory exudate to enter the alveoli. This pulmonary edema increases the thickness of the layer separating the blood in the capillary from the space in the air sacs, which increases the distance the oxygen must diffuse to reach the blood. This impairs gas exchange and leads to hypoxia, increased work of breathing, and eventually induces scarring of the air sacs of the lungs.^{[ citation needed ]}

Fluid accumulation in the lungs and decreased surfactant production by type II pneumocytes may cause whole air sacs to collapse or to completely fill with fluid. This loss of aeration contributes further to the right-to-left shunt in ARDS. A traditional right-to-left shunt refers to blood passing from the right side of the heart to the left side without traveling to the capillaries of the lung for more oxygen (e.g., as seen in a patent foramen ovale). In ARDS, a lung right-to-left shunting occurs within the lungs since some blood from the right side of the heart will enter capillaries which cannot exchange gas with damaged air sacs that are full of fluid and debris from ARDS. As the alveoli contain progressively less gas, the blood flowing through the alveolar capillaries is progressively less oxygenated, resulting in massive shunting within the lung. The collapse of the air sacs and small airways interferes with the process of normal gas exchange. It is common to see patients with a PaO^₂ of 60 mmHg (8.0 kPa) despite mechanical ventilation with 100% inspired oxygen.^{[ citation needed ]}

The loss of aeration may follow different patterns depending upon the nature of the underlying disease and other factors. These are usually distributed to the lower lobes of the lungs, in their posterior segments, and they roughly correspond to the initial infected area. 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. Loss of aeration also causes important changes^{[ vague ]} in lung mechanical properties that are fundamental in the process of inflammation amplification and progression to ARDS in mechanically ventilated patients.

Mechanical stress

As the loss of aeration and the underlying disease progress, the end tidal volume grows to a level incompatible with life. Thus, mechanical ventilation is initiated to relieve muscles responsible for supporting breathing (respiratory muscles) of their work and to protect the affected person's airway. However, mechanical ventilation may constitute a risk factor for the development—or the worsening—of ARDS.^[2] Aside from the infectious complications arising from invasive ventilation with endotracheal intubation, positive-pressure ventilation directly alters lung mechanics during ARDS. When these techniques are used the result is higher mortality through barotrauma.^[2]

In 1998, Amato et al. published a paper showing substantial improvement in the outcome of patients ventilated with lower tidal volumes (V_t) (6 mL·kg⁻¹).^[2]^[3] This result was confirmed in a 2000 study sponsored by the NIH.^[4] Both studies were widely criticized for several reasons, and the authors were not the first to experiment with lower-volume ventilation, but they increased the understanding of the relationship between mechanical ventilation and ARDS.^{[ citation needed ]}

This form of stress is thought to be applied by the transpulmonary pressure (gradient) (P_l) generated by the ventilator or, better, its cyclical variations. The better outcome obtained in individuals ventilated with a lower V_t may be interpreted as a beneficial effect of the lower P_l.

The way P_l is applied on the alveolar surface determines the shear stress to which alveoli are exposed. ARDS is characterized by a usually heterogeneous reduction of the airspace, and thus by a tendency towards higher P_l at the same V_t, and towards higher stress on less diseased units. The heterogeneity of alveoli at different stages of disease is further increased by the gravitational gradient to which they are exposed and the different perfusion pressures at which blood flows through them.

The different mechanical properties of alveoli in ARDS may be interpreted as having varying time constants—the product of alveolar compliance × resistance. Slow alveoli are said to be "kept open" using PEEP, a feature of modern ventilators which maintains a positive airway pressure throughout the whole respiratory cycle. A higher mean pressure cycle-wide slows the collapse of diseased alveoli, but it has to be weighed against the corresponding elevation in P_l/plateau pressure. Newer ventilatory approaches attempt to maximize mean airway pressure for its ability to "recruit" collapsed alveoli while minimizing the shear stress caused by frequent openings and closings of aerated units.^{[ citation needed ]}

Stress Index

Mechanical ventilation can worsen the inflammatory response in people with ARDS by inducing hyperinflation of the alveoli and/or increased shear stress with frequent opening and closing of collapsible alveoli.^[5] The stress index is measured during constant-flow volume assist-control mechanical ventilation without changing the baseline ventilatory pattern. Identifying the steadiest portion of the inspiratory flow (F) waveform fit the corresponding portion of the airway pressure (Paw) waveform in the following power equation:^{[ citation needed ]}

Paw = a × t^b + c where the coefficient b—the Stress Index—describes the shape of the curve. The Stress Index depicts a constant compliance if the value is around 1, an increasing compliance during the inspiration if the value is below 1, and a decreasing compliance if the value is above 1. Ranieri, Grasso, et al. set a strategy guided by the stress index with the following rules:

Stress Index below 0.9, PEEP was increased
Stress Index between 0.9 and 1.1, no change was made
Stress Index above 1.1 PEEP was decreased.

Alveolar hyperinflation in patients with focal ARDS ventilated with the ARDSnet protocol is attenuated by a physiologic approach to PEEP setting based on the stress index measurement.^[6]

Progression

If the underlying disease or injurious factor is not removed, the quantity of inflammatory mediators released by the lungs in ARDS may result in a systemic inflammatory response syndrome (SIRS) or sepsis if there is lung infection.^[2] The evolution towards shock or multiple organ dysfunction syndrome follows paths analogous to the pathophysiology of sepsis. This leads to the impaired oxygenation, which is the central problem of ARDS, as well as to respiratory acidosis. Respiratory acidosis in ARDS is often caused by ventilation techniques such as permissive hypercapnia, which attempt to limit ventilator-induced lung injury in ARDS. The result is a critical illness in which the 'endothelial disease' of severe sepsis or SIRS is worsened by the lung dysfunction, which further impairs oxygen delivery to cells.^{[ citation needed ]}

Related Research Articles

The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of the heart. Their function in the respiratory system is to extract oxygen from the air and transfer it into the bloodstream, and to release carbon dioxide from the bloodstream into the atmosphere, in a process of gas exchange. The pleurae, which are thin, smooth, and moist, serve to reduce friction between the lungs and chest wall during breathing, allowing for easy and effortless movements of the lungs.

The respiratory system is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies greatly, depending on the size of the organism, the environment in which it lives and its evolutionary history. In land animals the respiratory surface is internalized as linings of the lungs. Gas exchange in the lungs occurs in millions of small air sacs; in mammals and reptiles these are called alveoli, and in birds they are known as atria. These microscopic air sacs have a very rich blood supply, thus bringing the air into close contact with the blood. These air sacs communicate with the external environment via a system of airways, or hollow tubes, of which the largest is the trachea, which branches in the middle of the chest into the two main bronchi. These enter the lungs where they branch into progressively narrower secondary and tertiary bronchi that branch into numerous smaller tubes, the bronchioles. In birds, the bronchioles are termed parabronchi. It is the bronchioles, or parabronchi that generally open into the microscopic alveoli in mammals and atria in birds. Air has to be pumped from the environment into the alveoli or atria by the process of breathing which involves the muscles of respiration.

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.

Mechanical ventilation, assisted ventilation or intermittent mandatory ventilation (IMV) is the medical term for using a machine called a ventilator to fully or partially provide artificial ventilation. Mechanical ventilation helps move air into and out of the lungs, with the main goal of helping the delivery of oxygen and removal of carbon dioxide. Mechanical ventilation is used for many reasons, including to protect the airway due to mechanical or neurologic cause, to ensure adequate oxygenation, or to remove excess carbon dioxide from the lungs. Various healthcare providers are involved with the use of mechanical ventilation and people who require ventilators are typically monitored in an intensive care unit.

The respiratory tract is the subdivision of the respiratory system involved with the process of respiration in mammals. The respiratory tract is lined with respiratory epithelium as respiratory mucosa.

Gas exchange is the physical process by which gases move passively by diffusion across a surface. For example, this surface might be the air/water interface of a water body, the surface of a gas bubble in a liquid, a gas-permeable membrane, or a biological membrane that forms the boundary between an organism and its extracellular environment.

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

Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms include shortness of breath (dyspnea), rapid breathing (tachypnea), and bluish skin coloration (cyanosis). For those who survive, a decreased quality of life is common.

Hypoxemia is an abnormally low level of oxygen in the blood. More specifically, it is oxygen deficiency in arterial blood. Hypoxemia has many causes, and often causes hypoxia as the blood is not supplying enough oxygen to the tissues of the body.

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

Positive end-expiratory pressure (PEEP) is the pressure in the lungs above atmospheric pressure that exists at the end of expiration. The two types of PEEP are extrinsic PEEP and intrinsic PEEP. Pressure that is applied or increased during an inspiration is termed pressure support.PEEP is a therapeutic parameter set in the ventilator, or a complication of mechanical ventilation with air trapping (auto-PEEP).

High-frequency ventilation is a type of mechanical ventilation which utilizes a respiratory rate greater than four times the normal value. and very small tidal volumes. High frequency ventilation is thought to reduce ventilator-associated lung injury (VALI), especially in the context of ARDS and acute lung injury. This is commonly referred to as lung protective ventilation. There are different types of high-frequency ventilation. Each type has its own unique advantages and disadvantages. The types of HFV are characterized by the delivery system and the type of exhalation phase.

In respiratory physiology, the ventilation/perfusion ratio is a ratio used to assess the efficiency and adequacy of the matching of two variables:

A pulmonary shunt is the passage of deoxygenated blood from the right side of the heart to the left without participation in gas exchange in the pulmonary capillaries. It is a pathological condition that results when the alveoli of parts of the lungs are perfused with blood as normal, but ventilation fails to supply the perfused region. In other words, the ventilation/perfusion ratio of those areas is zero.

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.

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.

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). It is important to note that DAD can be seen in situations other than ARDS (such as acute interstitial pneumonia) and that ARDS can occur without DAD.

Modes of mechanical ventilation are one of the most important aspects of the usage of mechanical ventilation. The mode refers to the method of inspiratory support. In general, mode selection is based on clinician familiarity and institutional preferences, since there is a paucity of evidence indicating that the mode affects clinical outcome. The most frequently used forms of volume-limited mechanical ventilation are intermittent mandatory ventilation (IMV) and continuous mandatory ventilation (CMV). There have been substantial changes in the nomenclature of mechanical ventilation over the years, but more recently it has become standardized by many respirology and pulmonology groups. Writing a mode is most proper in all capital letters with a dash between the control variable and the strategy.

Prone ventilation, sometimes called prone positioning or proning, refers to mechanical ventilation with the patient lying face-down (prone). It improves oxygenation in most patients with acute respiratory distress syndrome (ARDS) and reduces mortality. The earliest trial investigating the benefits of prone ventilation occurred in 1976. Since that time, many meta-analyses and one randomized control trial, the PROSEVA trial, have shown an increase in patients' survival with the more severe versions of ARDS. There are many proposed mechanisms, but they are not fully delineated. The proposed utility of prone ventilation is that this position will improve lung mechanics, improve oxygenation, and increase survival. Although improved oxygenation has been shown in multiple studies, this position change's survival benefit is not as clear. Similar to the slow adoption of low tidal volume ventilation utilized in ARDS, many believe that the investigation into the benefits of prone ventilation will likely be ongoing in the future.

Proning or prone positioning is the placement of patients into a prone position so that they are lying on their front. This is used in the treatment of patients in intensive care with acute respiratory distress syndrome (ARDS). It has been especially tried and studied for patients on ventilators but, during the COVID-19 pandemic, it is being used for patients with oxygen masks and CPAP as an alternative to ventilation.

Ventilation-perfusion coupling is the relationship between ventilation and perfusion processes, which take place in the respiratory and cardiovascular systems. Ventilation is the movement of gas during breathing, and perfusion is the process of pulmonary blood circulation, which delivers oxygen to body tissues. Anatomically, the lung structure, alveolar organization, and alveolar capillaries contribute to the physiological mechanism of ventilation and perfusion. Ventilation-perfusion coupling maintains a constant ratio near 0.8 on average, while the regional variation exists within the lungs due to gravity. When the ratio gets above or below 0.8, it is considered abnormal ventilation-perfusion coupling, also known as a ventilation-perfusion mismatch. Lung diseases, cardiac shunts, and smoking can cause a ventilation-perfusion mismatch that results in significant symptoms and diseases, which can be treated through treatments like bronchodilators and oxygen therapy.

References

↑ Boyle, AJ; Mac Sweeney, R; McAuley, DF (August 2013). "Pharmacological treatments in ARDS; a state-of-the-art update". BMC Med. 11: 166. doi: 10.1186/1741-7015-11-166 . PMC 3765621 . PMID 23957905.
1 2 3 4 Irwin RS, Rippe JM (2003). Irwin and Rippe's Intensive Care Medicine (5th ed.). Lippincott Williams & Wilkins. ISBN 0-7817-3548-3.
↑ Amato M, Barbas C, Medeiros D, Magaldi R, Schettino G, Lorenzi-Filho G, Kairalla R, Deheinzelin D, Munoz C, Oliveira R, Takagaki T, Carvalho C (1998). "Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome". N Engl J Med. 338 (6): 347–54. doi: 10.1056/NEJM199802053380602 . PMID 9449727.
↑ MacIntyre N (2000). "Mechanical ventilation strategies for lung protection". Semin Respir Crit Care Med. 21 (3): 215–22. doi:10.1055/s-2000-9850. PMID 16088734. S2CID 44550156.
↑ Slutsky AS (May 2005). "Ventilator-induced lung injury: from barotrauma to biotrauma" (PDF). Respir Care. 50 (5): 646–59. PMID 15912625.
↑ Grasso S, Stripoli T, De Michele M, et al. (October 2007). "ARDSnet ventilatory protocol and alveolar hyperinflation: role of positive end-expiratory pressure". Am. J. Respir. Crit. Care Med. 176 (8): 761–7. doi:10.1164/rccm.200702-193OC. PMID 17656676.

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[Boyle2013-1] Boyle, AJ; Mac Sweeney, R; McAuley, DF (August 2013). "Pharmacological treatments in ARDS; a state-of-the-art update". BMC Med. 11: 166. doi: 10.1186/1741-7015-11-166 . PMC 3765621 . PMID 23957905.

[Rippe-ARDS-2] 1 2 3 4 Irwin RS, Rippe JM (2003). Irwin and Rippe's Intensive Care Medicine (5th ed.). Lippincott Williams & Wilkins. ISBN 0-7817-3548-3.

[Amato_1998-3] Amato M, Barbas C, Medeiros D, Magaldi R, Schettino G, Lorenzi-Filho G, Kairalla R, Deheinzelin D, Munoz C, Oliveira R, Takagaki T, Carvalho C (1998). "Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome". N Engl J Med. 338 (6): 347–54. doi: 10.1056/NEJM199802053380602 . PMID 9449727.

[MacIntyre_2000-4] MacIntyre N (2000). "Mechanical ventilation strategies for lung protection". Semin Respir Crit Care Med. 21 (3): 215–22. doi:10.1055/s-2000-9850. PMID 16088734. S2CID 44550156.

[5] Slutsky AS (May 2005). "Ventilator-induced lung injury: from barotrauma to biotrauma" (PDF). Respir Care. 50 (5): 646–59. PMID 15912625.

[6] Grasso S, Stripoli T, De Michele M, et al. (October 2007). "ARDSnet ventilatory protocol and alveolar hyperinflation: role of positive end-expiratory pressure". Am. J. Respir. Crit. Care Med. 176 (8): 761–7. doi:10.1164/rccm.200702-193OC. PMID 17656676.

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