Acute respiratory distress syndrome (ARDS) is an acute respiratory failure syndrome characterized by progressive respiratory distress and refractory hypoxemia due to severe intra- and extra-pulmonary diseases, based on diffuse pulmonary capillary damage and increased permeability, with pulmonary edema, hyaline membrane formation and pulmonary atelectasis as the main pathological changes. The disease starts rapidly, develops rapidly, and has a very poor prognosis, with a mortality rate of more than 50%.
A, the etiology of ARDS induced by the original or underlying disease or the initiating causative factors, many of them are summarized in the following aspects.
1, shock various types of shock, such as infectious, hemorrhagic cardiogenic and allergic, especially infectious shock due to gram-negative bacillary sepsis.
2, trauma, polytrauma, pulmonary contusion, craniocerebral trauma burns, electric shock, fat embolism, etc.
3.Infection, severe infection of lung or systemic bacteria, virus, fungal protozoa, etc.
4, inhalation of toxic gases, such as high concentrations of oxygen, ozone, ammonia fluorine, chlorine, nitrogen dioxide phosgene, aldehydes, smoke, etc.
5, accidental inhalation, gastric juice (especially pH <2.5 drowning water, amniotic fluid, etc.)
6, drug overdose, barbiturates, salicylic acid, hydrochlorothiazide colchicine, aconitine, heroin methadone, magnesium sulfate, terbutaline streptokinase, fluorescein, etc. ADRS due to poisoning by toxic and anesthetic drugs has been reported in China, it is worth noting
7, metabolic disorders, liver failure uremia, diabetic ketoacidosis. Acute pancreatitis 2% -18% complicating acute respiratory distress syndrome.
8, hematologic disorders, massive transfusion of stock blood and wrong blood type transfusion, DIC, etc.
9.Other, subacute pain or pre-eclampsia, pulmonary lymphatic duct cancer. Pulmonary hemorrhage a nephritis syndrome systemic lupus erythematosus, after cardiopulmonary resuscitation, radiation therapy organ transplantation, etc.
In summary, trauma, infection, and shock are the three major causative factors for the occurrence of ADRS accounting for 70%-85%, and multiple pathogenic factors either act directly on the lung or act on tissues far from the lung causing acute damage to the lung tissue and causing the same clinical manifestations. Directly acting on the lung pathogenic factors such as chest trauma, accidental aspiration, inhalation of toxic gases caused by various pathogenic microorganisms and serious lung infections and radiation lung injury; indirect factors include sepsis. Shock, extra-pulmonary trauma drug poisoning, blood transfusion, hemorrhagic necrotizing pancreatitis extracorporeal circulation, etc.
Second, the pathogenesis
The etiology of ARDS varies, but the pathophysiology and clinical course are basically not dependent on a specific etiology, and the common basis is acute injury to the alveoli-capillaries. Pulmonary injury can be direct, such as gastric acid or gas inhalation, chest trauma, etc., resulting in endothelial or epicellular physicochemical damage. More commonly, indirect lung injury is seen. Although the mechanism of lung injury has not been fully elucidated to date, it has been recognized as part of a systemic inflammatory response syndrome. The acute inflammatory response mediated by cells and humors at the alveolar capillary level involves two main processes namely migration and aggregation of inflammatory cells and release of inflammatory mediators, which complement each other and act on specific components of the alveolar capillary membrane, resulting in increased permeability.
III. Migration and aggregation of inflammatory cells
Almost all intrapulmonary cells are involved in the pathogenesis of ARDS to varying degrees, and one of the most important effector cells of acute inflammation in ARDS are polymorphonuclear leukocytes (PMNs). Only a small number of PMNs, about 1.6%, are isolated from humans and are present in the interstitium. In cases of trauma, sepsis, acute pancreatitis, physical and chemical stimulation or extracorporeal circulation, PMNs accumulate in large numbers in the pulmonary capillaries due to factors such as endotoxin lipopolysaccharide (LPS), C5a, interleukin-8 (IL-8), etc. They first flow attached to the wall and adhere to endothelial cells, then migrate to the interstitium via the transendothelium and then to the alveolar lumen by alveolar epithelial debridement. The respiratory burst of PMNs and the release of their products are important aspects of lung injury. In addition to being phagocytes and antigen-presenting cells for immune responses, alveolar macrophages (Ams) are also important effector cells for inflammatory responses and are involved in the pathogenesis of ARDS. The release of IL-1, tumor necrosis factor-α (TNF-α), and IL-87 from stimulated AMS drives the chemotaxis and aggregation of PMNs in the lung and is likely to be the initiating factor for ALI. Platelet aggregation and microembolism are presumed to be common pathological changes in ARDS, and platelets and their products are also presumed to play an important role in the mechanism of ARDS as disease. In recent years, it was found that structural cells such as pulmonary capillaries and alveolar epithelial cells are not only target cells but also can participate in the inflammatory immune response, which has special significance in ARDS in the secondary inflammatory response.
IV. Release of inflammatory mediators
Inflammatory cell activation and release of mediators are inextricably linked to the inflammatory response and are discussed separately here for narrative convenience only. Take bacterial LPS stimulation as an example, it binds to macrophage surface receptors, causing cell shedding and release of numerous mediators from cellular organelles, including.
1. lipid mediators such as arachidonic acid metabolites and platelet-activating factor (PAF).
2, reactive oxygen metabolites such as superoxide anion (O2-), hydrogen peroxide (H2O2), hydroxyl radical (OH?) and monomeric oxygen (IO2), except for H2O2, symmetric oxygen itself vapour qua.
3, peptides such as PMNs/Ams proteases, complement substrates, various components involved in coagulation and fibrinolytic processes, cytokines, and even integrins belonging to the muka group of adhesion molecules have been listed as such mediators.
The first two types of mediators have been much studied in the past years, but in recent years more attention has been paid to peptide mediators, especially pre-inflammatory cytokines and adhesion molecules, which may be important mediators of the initiation and promotion of the ARDS “inflammatory waterfall”, cell chemotaxis, transmigration and aggregation, inflammatory response and secondary mediator release.
V. Alveolar capillary damage and increased permeability
Components that maintain and regulate capillary structural integrity and permeability include the extracellular matrix, intercellular junctions, cytoskeleton, and the interaction of cytosolic transport with cellular substrates. direct and indirect injury from ARDS can have an effect on each of these components. Oxygen self-substrates, proteases, cytokines, arachidonic acid metabolites, and highly charged products (e.g., neutrophil major cationic proteins) can alter membrane barrier permeability through the following pathways.
1. cleavage of basement membrane proteins and/or cell adhesion factors.
2. altering the structure of the fibrous matrix network of the extracellular lineage
3, affecting the fibril system of the cytoskeleton, leading to cell deformation and tearing of connections.
VI. Pathophysiology
1.Basic pathophysiology
It is important to note that it is generally accepted that ARDS injury and its pathological changes are diffuse, whereas recent studies from imaging and application of inert gases to measure gas exchange have shown that lung injury is not as diffuse and homogeneous as previously understood, and therefore a “two-compartment model” is proposed: a near-normal lung with no pressure or ventilatory response to the pressure applied to it. The second chamber is the diseased lung, which is dilated and ventilated, but receives a disproportionate amount of blood flow. In the early stages, many of the open lung units in both chambers can be interchanged with increasing pressure or changes in position, so that the apparent pressure-cellar curve is significantly lagged and biphasic. Early pulmonary edema reduces alveolar volume, in the sense that it is only a reduction in filling air volume, not a reduction in lung volume per se. Total lung and thoracic volumes are in the normal range in the functional residual air position, and specific lung compliance, i.e., compliance/lung volume, is also normal.
2. Pathological dependence of oxygen consumption-oxygen supply and multi-organ failure
In recent years, some studies have found abnormal oxygen consumption-oxygen supply (Vo2Qo2) relationship in ARDS, and suggested that this is the common pathophysiological basis of ARDS and multi-organ failure. Oxygen supply can vary in healthy individuals, even if it decreases, while oxygen uptake and consumption of organs remain relatively stable, i.e., above a critical threshold organ oxygen consumption is not dependent on oxygen supply. It is due to local compensatory effects and increased perfusion of capillary interceptor species and increased oxygen uptake. In ARDS this compensatory mechanism is depleted and an absolute or pathological dependence of oxygen consumption on oxygen supply occurs at all levels of oxygen supply. This pathology manifests itself as a VA/Q ratio imbalance in the lungs and as impaired oxygen exchange between tissues and capillaries in extrapulmonary organs. abnormal Vo2/Qo2 relationships lead to impaired cellular oxygenation and metabolism, causing injury. The imbalance of oxygen supply and demand originates from the depletion of local compensatory mechanisms, which is explained by the redistribution of blood flow to low-drain organs such as skeletal muscle, causing insufficient oxygen supply to vital organs, or by capillary endothelial damage to vital organs, tissue edema, increased diffusion distances and reduced cross-sectional area of hair cells. The basic cause of the injury is the general activation of inflammatory cells and the release of mediators. The latter view is currently preferred, and it is believed that ARDS and multiorgan failure share a common pathogenesis, with the pulmonary capillary bed being particularly rich and often the first target organ for inflammatory injury. ARDS develops or evolves into multi-organ failure, and infection may be the most important trigger or driving factor.
3. Pathological changes
The pathological changes of ARDS due to various etiologies are basically the same and can be divided into three interrelated and partially overlapping phases: exudative, proliferative and fibrotic.
(1) Exudative phase
It is seen in the first week after the onset of the disease. The lungs show dark red or dark purple liver-like changes with visible edema and hemorrhage. Microscopic examination within 24 hours reveals pulmonary microvascular congestion, hemorrhage, microthrombi, and protein edema fluid and inflammatory cell infiltration in the interstitium and alveoli. In cases of sensible etiology, the alveolar lumen PMNs aggregation and infiltration are more pronounced. 72 hours later there is hyaline membrane formation from plasma protein clotting, cell fragmentation, and fibrin, and focal or large alveolar atrophy and atelectasis. In the acute exudative phase type I cells are damaged and necrotic.
(2) Proliferative phase
One to three weeks after injury, lung type II epithelial cells proliferate to cover the exfoliated basement membrane, fibrosis is seen in alveolar sacs and alveolar ducts, and fibroblastic intimal hyperplasia occurs in small muscular arteries, leading to a reduction in the luminal cross-sectional area of vessels.
(3) Fibrosis stage
Patients with ARDS surviving more than 3 to 4 weeks have extensive thickening of the alveolar septum and airspace walls, and diffuse irregular fibrosis due to proliferation of scattered segregated collagenous connective tissue. Extensive wall fibrous thickening of the pulmonary vascular bed occurs, with distorted arterial deformation and dilated pulmonary line vessels. Even in ARDS of non-infectious etiology, pulmonary infections are inevitably combined in the later stages, and tissue necrosis and microscopic abscesses are common.
VII. Clinical manifestations
In addition to the corresponding morbidity signs, the patient may have no respiratory symptoms within a few hours after the lung is first damaged. Subsequently, the respiratory rate increases and
1.X-ray chest film
The shortness of breath gradually worsens, and no abnormal lung signs are found, or small wet woven woven wool can be heard during inspiration. Arterial blood gas analysis showed that PaO2 and PaCO2 were low. As the disease progresses, the patient feels respiratory distress, tightness in the chest, inspiratory effort, cyanosis, often accompanied by irritability and anxiety, extensive interstitial infiltration in both lungs, which may be accompanied by odd vein dilatation, pleural reaction or a small amount of fluid accumulation. Respiratory alkalosis occurs due to marked hypoxemia causing hyperventilation and decreased PaCO2. Respiratory distress cannot be improved with the usual oxygen therapy. If these conditions continue to worsen, respiratory distress and cyanosis continue to worsen, and chest radiographs show large areas of pulmonary infiltrates that fuse and even develop into “white lung”. Respiratory muscle fatigue leads to hyperventilation, carbon dioxide retention, and mixed acidosis. Cardiac arrest. Some patients develop multi-organ failure.