multisystem organ failure
Introduction
Introduction to multiple system organ failure Multiple systemic organ failure (MSOF), also known as mul-tipleorganfailure (MOF), occurs two or more simultaneously or sequentially after severe infection, trauma, major surgery, pathological obstetrics, etc. The clinical syndrome of organ failure. The concept of MSOF began in the late 1960s and early 1970s, when it was a new clinical syndrome, so it was also called the "70s syndrome." It is also a hot topic in medical research at home and abroad. Although domestic and foreign scholars have made a lot of efforts for this purpose for more than 20 years, the incidence and mortality of MSOF have not really decreased. One of the main reasons is the lack of MSOF concept. Unified understanding and early clinical diagnosis methods. Too much emphasis on the end point of MSOF, it is difficult to guide the early diagnosis and clinical prevention of MSOF. basic knowledge The proportion of sickness: 0.01% Susceptible population: people with serious infections, trauma, major surgery Mode of infection: non-infectious Complications: metabolic acidosis, hepatic encephalopathy, coma
Cause
Causes of multiple system organ failure
Non-infectious severe lesions (20%):
Such as acute pancreatitis, extensive tissue damage and so on. Especially when the immune function of the body and the function of the mononuclear phagocytic system are weakened, or when the treatment is improper or delayed, if the tissue hypoperfusion and acid-base balance disorder are not corrected in time, excessively fast infusion, massive blood transfusion or excessive application of sedatives In the case of anesthesia, etc., it is more likely to cause MOF.
Severe infection (50%):
70% to 80% of MOF occurs on the basis of severe infection. In the shock, long-term low perfusion and sympathetic hyperresponsiveness are organized.
Pathogenesis
The pathogenesis of MSOF is very complex and is not fully elucidated. In essence, MSOF is an uncontrolled systemic self-destructive inflammatory response. MSOF is not directly derived from exogenous pathogenic factors (such as bacteria, endotoxins, trauma, etc.). ), because it usually occurs after exogenous pathogenic factors for a certain period of time (days), and the organ of MSOF is often away from the site of the pathogenic factors, most patients have no evidence of infection; even if there is infection, active treatment of suppuration Sexual infections may not necessarily improve the survival rate of MSOF. These phenomena suggest that MSOF is caused by endogenous factors, and the endogenous factors causing MSOF are mainly related to the following links:
1. Overproduction of cytokines: Under the direct or indirect effects of pathogenic factors, macrophages in vivo can be over-stimulated to produce a large number of cytokines (also known as cytokines) and other mediators, resulting in a series of fluid and cell-effect systems. Cascade reactions, exerting harmful local and systemic effects, such as excessive cytokines can lead to local tissue destruction, microvascular damage, hypermetabolism, hemodynamic insufficiency and ultimately lead to refractory shock, macrophage activation Produces the same systemic response as in severe infections, where the effects of cytokines are complex, a cytokine secretes a second or additional cytokine (cytokine cascade); a cytokine regulates other cells on the same cell The role of factors; many cytokines can inhibit each other, add, symbiotic or form new effects; the physiological state of cytokine-producing cells can determine the release of cytokines, and the order in which target cells are exposed to cytokines can affect their response; The response of cytokines is related to the size of the dose. There are dozens of cytokines discovered so far. Cytokines involved in the development of MSOF include tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-6 (IL-6), etc. These cytokines have a certain pro-inflammatory effect, under normal circumstances, The inflammatory response is self-limiting in both time and space, and has no obvious damage to normal cells and distant organs. If excessive pro-inflammatory cytokines are produced, systemic multi-organ cells can be extensively damaged. Among the factors, TNF is in the first place, because after the pathogenic factors, the circulating blood TNF rises fastest and reaches the peak; TNF can stimulate the formation of other pro-inflammatory cell peptides, such as IL-1, IL-6. , IL-8, etc.; injection of very large doses of TNF can cause typical systemic inflammatory response syndrome (SIRS) and lead to MSOF; in the septic shock model, early application of TNF monoclonal antibody or soluble TNF receptor can not only eliminate blood The TNF is elevated, and it can inhibit the increase of IL-1 and IL-6, and prevent the production of MSOF and improve the survival rate.
The factors that make TNF- occupy such an important position in the pathogenesis of MSOF have the following four aspects:
1TNF- activates neutrophils, which expresses the leukocyte differentiation antigen CD11/CD18 complex on the surface, and simultaneously activates vascular endothelial cells to express intercellular adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion molecules on the surface. 1 (ELAM-1), which leads to leukocyte-endothelial cell interaction, through which, in addition to promoting the entry of neutrophils into the interstitial space, it is more important to promote the release of large amounts of reactive oxygen species and elastase to the blood vessels. Endothelial cells and organ cytoplasmic cells produce damaging effects. Once the cell membrane is damaged, intracellular Ca2 overload is produced, which inhibits mitochondrial respiratory function and activates intracellular phospholipase, endonuclease and protease, thereby causing the cell itself. damage.
2TNF- stimulates the expression of tissue factor in vascular endothelial cells, which promotes the surface activation of microvessels and inhibits the expression of thrombin-modulating protein (TM), which weakens the anticoagulant activity of microvascular surface. At the same time, TNF- inhibits the expression of vascular endothelial cells. Tissue plasminogen activin (t-PA), but promotes the expression of plasminogen activin inhibitor-1 (PAI-1), resulting in decreased fibrinolytic activity, therefore, TNF- promotes microthrombus formation, especially On the basis of vascular endothelial damage, it is easier to do so. In addition, TNF- can also increase the activity of inducible NO synthase. A large amount of NO forms microcirculation, which also aggravates the development of microthrombus. In addition to directly threatening cell survival, blood/anoxic conditions can also cause the production of hypoxanthine, which produces a large number of oxygen free radicals under the action of xanthine oxidase. The resulting oxygen free radicals are also one of the important causes of cell destruction.
3TNF- increases glucocorticoid secretion through the hypothalamic-adenohypophyseal-adrenal axis, and increases catecholamine secretion through the sympathetic-adrenal medullary system. These hormones cause glycogen and lipid breakdown, and TNF- stimulates the liver. Synthetic acute phase reaction protein also causes protein breakdown of whole body muscle tissue, showing a negative nitrogen balance.
4 TNF- excess can promote apoptosis of vascular endothelial cells and organ primordial cells through direct and indirect pathways (such as reactive oxygen species), also known as programmed cell death (PCD), under physiological conditions, PCD is very important to ensure the normal differentiation and reproduction of cells. However, under pathological conditions, if PCD is caused by a large number of cells that should not be eliminated, it will inevitably lead to or aggravate the development of MSOF. It should be pointed out that cytokines are closely related to each other, and they often The network form plays a role. In the pathogenesis of MSOF, the effect of IL-1 is similar to that of TNF-, and there is a synergistic effect. Many clinical materials indicate that IL-6 content is directly proportional to the probability of MSOF, and the concentration of IL-6 in blood. The higher the patient's prognosis, the worse.
2. Microcirculatory disorders: Here are mainly the effects associated with tissue ischemia and vascular endothelial injury, including tissue and cellular oxygen supply deficiency, ischemia-reperfusion and tissue damage caused by endothelial-leukocyte interaction, regardless of the cause Tissue hypoxia is the conversion of ATP to adenosine via adenosine and inosine, and xanthine dehydrogenase to xanthine oxidase. During reperfusion, hypoxanthine is oxidized to xanthine under the action of xanthine oxidase. O2-, O2- is formed and then produces OH- and H2O2. The latter two substances are highly toxic to cells, causing damage to cells and tissues. Oxygen free radicals can destroy proteins, lipids and sugars. The biochemical properties of adenosine play a role in the phospholipids of cell membranes, destroying lysosomes, mitochondria and cell membranes. OH- and H2O2 can also decompose collagen and hyaluronic acid, causing cell swelling, destruction of epithelial basement membrane and vascular permeability. Increased sex, and finally caused vascular occlusion and microthrombus formation, in various tissues, the rate of transformation of xanthine dehydrogenase into xanthine oxidase is not the same, the small intestine is 10s, the myocardium is 8min, The spleen, kidney and lung are 30 min, indicating that various tissues and organs have different sensitivities to ischemia-reperfusion injury. In addition, activated leukocytes, mitochondria, prostaglandin synthetase, catecholamine self-oxidation, etc. are all oxygen free radicals. The resulting biological source, but with xanthine oxidase and activation of white blood cells is the most important.
Together with circulating neutrophils, endothelial cells promote tissue ischemia and damage, leading to the development of MSOF through bacteria, endotoxin, TNF, IL-1 and other cytokines that alter the endothelial phenotype from non-inflammatory. To pro-inflammatory, procoagulant manifestations, which cause these endothelial cells to lose anticoagulant properties, have the ability to bind to VII factors, activate exogenous coagulation pathways, and, in addition, express these proinflammatory endothelial cell surface receptors (ELAM-1, ICAM-1) It promotes leukocyte adhesion and secretion of leukocyte activating factors such as IL-1, PAF, IL-8, mitotic control protein-1, GM-CSF and G-CSF, and this endothelial cell phenotype changes cause lesions Microthrombus and leukocyte-mediated endothelial cell damage, if extensively impaired, eventually progress to tissue ischemia and MSOF, and neutrophil adhesion to endothelial cells is largely bound by CD11/CD18 to ELAM-1 and ICAM-1 is mediated, so this hypothesis can be tested with anti-CD18, anti-ICAM-1 or anti-ELAM-1 antibodies.
3. Intestinal bacteria and endotoxin translocation: Intestinal bacteria or endotoxin is a trigger that triggers, prolongs and strengthens the septic state, which can promote the occurrence of MSOF. According to a series of in vitro and in vivo studies, it shows the functional status of the intestinal barrier. There is an important clinical relationship between Puff cell function, ultra-high metabolic response and distant organ damage. Enterogenous endotoxin can regulate the activity of Kangpufu cells, releasing endogenous mediators that regulate hepatocyte function. The liver reticuloendothelial system plays an important role in the clearance of bacteria or endotoxins from the portal vein. Its damage will allow intestinal-derived bacteria or endotoxins to reach the systemic circulation and increase the systemic effects of intestinal barrier failure, which will aggravate septic Response, a large number of facts indicate that the strongest stimulator for the mononuclear-macrophage system to produce cellular peptides and complement activation alternative pathways is endotoxin. Experiments have shown that endotoxin-induced TNF expression is regulated by intracellular protein kinase C activation. In addition, endotoxin can also stimulate T cells to produce interferon r, which not only stimulates TNF production, but also has significant synergy with TNF. This synergistic effect is particularly prominent in causing apoptosis, due to the positive bacterial cell and endotoxin translocation peptide generation and complement activation has the effect of kill two birds with one stone, so it may be referred to MSOF accelerator.
4. Excessive activation of complement: The complement system is central to humoral immunity. Under various pathological conditions such as sepsis, endotoxemia, trauma, burn, etc., complement system activation is recognized, and complement activation products (C3a, C3b, C5a, etc. can stimulate macrophages and neutrophils. Macrophages release cell peptides (mainly TNF). Neutrophils produce MSOV by producing reactive oxygen species and releasing lysozyme. In addition, complement activation products are also associated with arachidonic acid metabolites (such as thromboxane A2, leukotrienes) and platelet activating factor production, and these activating substances can also cause an exacerbation of inflammatory reactions, therefore, under the above pathological conditions, If the treatment is not timely or the treatment is unreasonable, and the complement is continuously over-activated, it may develop into a self-destructive inflammatory reaction that is out of control, which is to cause the development of MSOF.
In summary, cytokine overproduction, microcirculatory disorders, intestinal bacterial and endotoxin translocation and complement overactivation are not isolated, many of which are repetitive or interrelated, in short, endotoxemia Inflammatory reaction, insufficient oxygen supply can destroy the normal internal environment stability, and then the intestinal mucosal barrier function is impaired, activation or release of body fluids and cellular mediators oxygen supply is insufficient, the latter two can in turn damage the intestinal mucosal barrier mechanism, directly or It indirectly causes insufficiency or failure of damaged organs and even distant organs. The role of cytokines and various mediators is very important. It can also be said that MSOF is the result of the sum of various cytokines and mediators.
Prevention
Multisystem organ failure prevention
Due to infection, persistent inflammatory state, oxygen supply and insufficient tissue perfusion are the most common and important crisis factors for MSOF. They should be controlled and treated first, such as correcting shock, timely treatment of primary disease and trauma, and removal of necrotic tissue. Drainage of abscesses, control of abdominal cavity contamination, etc., are important measures to properly handle critical vital tissue of large wounds and hidden intestinal wounds (including barrier disruption) to block persistent inflammatory responses, thereby reducing activation of the white blood cell system. Do not abuse broad-spectrum antibiotics, pay attention to maintaining the normal bacterial flora ecology in the intestinal lumen, strengthen the normal bactericidal effect of the stomach, reduce the entry of bacteria and their toxins into the body, provide sufficient energy and synthetic substrate, and support symbiotic anaerobic Bacteria, keep the bowel movements smooth, to reduce bacteria and their toxins in the colon.
Complication
Multiple system organ failure complications Complications, metabolic acidosis, hepatic encephalopathy, coma
It can be complicated by metabolic acidosis and hyperglycemia, and finally can be complicated by hepatic encephalopathy and coma.
Symptom
Symptoms of multiple system organ failure Common symptoms Respiratory alkalosis Metabolic acidosis Nitrogenemia sound traumatic jaundice coma
Because the pathogenesis of MODS and MOF is very complicated, the clinical manifestations are diverse. For the convenience of observation, the clinical manifestations can be generally divided into the following four phases, but the clinical process is not so clearly separated.
1. The first phase: the clinical manifestations of this patient are concealed, the appearance seems normal or the underlying disease is not aggravated, but there may be shortness of breath and respiratory alkalosis, a slight increase in blood flow and early changes in renal function, generally the first phase of patients Physical examination may be normal, but detailed examination found that their blood demand is slightly higher, renal function may be abnormal, and the function of all other organs may be abnormal, usually after shock and trauma, after resuscitation, breathing 25 to 30 times Above /min, oxygen deficiency occurs, which is an early manifestation of pulmonary insufficiency. At the beginning, abnormal changes are rarely observed on X-rays, no wet squeaks, rough voices, compensatory hyperventilation due to hypoxia Respiratory alkalosis, PaCO2 decreased.
2. The second phase: After the early resuscitation, the patient has stable circulation and normal renal function. After 12 hours or longer, the patient becomes ill, mild or basic disease aggravated after he enters the second phase. Hemodynamics Can be high-row and low-resistance type, shortness of breath, obvious hypoxia, respiratory alkalosis, azotemia, jaundice and platelet count decline, clinical observation of various organ systems shows that each system is mild The function is abnormal, these abnormalities can be detected more easily, respiratory distress occurs, the frequency is accelerated, PaO2 is obviously reduced, wet snoring sound appears at the bottom of the lung, and X-ray shows that the lung texture is aggravated. At this time, although oxygen inhalation is increased, PaO2 cannot be improved. The corresponding level.
3. The third period: After entering the third period, anyone can find the patient sick. Unfortunately, the treatment of many of the above patients started at this stage, and each organ system has obvious clinical abnormalities, which are obvious. MOF performance, critical illness, shock, decreased cardiac output, edema, severe hypoxia and azotemia, metabolic acidosis and hyperglycemia, abnormal blood coagulation in the blood system, difficulty in breathing, cyanosis, two The lung snoring increased, and the chest radiograph showed diffuse mass shadows of both lungs to the lung consolidation. Although high concentrations of O2 were inhaled, PaO2 could not rise due to increased intrapulmonary shunt, PaCO2 began to rise, and patients at this stage must Mechanical ventilation.
4. The fourth phase: The fourth phase of the patient is already in a state of sudden death, increased cardiac load, irregular breathing or even pause, oliguria, severe acidosis, increased oxygen consumption, hepatic encephalopathy and coma, accompanied by Multiple organ failure, circulatory failure, arrhythmia, and ultimately death from one or more of the failures that sustain the vital organ system.
Examine
Multi-system organ failure examination
Feasible blood gas analysis, three routine, liver and kidney function tests, CO2 binding test.
The electrocardiogram showed abnormal heart rhythm and normal chest electrical power.
Diagnosis
Diagnosis and identification of multiple system organ failure
1. The MODS diagnosis points must emphasize the following points:
(1) There are two basic conditions for the occurrence of MODS. One is that the body has been severely hit, and the other is the use of modern treatments since the 1970s, including resuscitation, life support and anti-infection. These positive measures have made many patients Suffering from severe trauma, early shock of shock or infection, it is often difficult to get rid of the complications that come with it, "uncontrolled systemic inflammatory response syndrome", and even impaired organ function, progressive MODS development MOF.
(2) It is closely related to severe trauma, shock and infection, and major surgery, but shock itself is not MODS.
(3) High catabolism and exogenous nutrition cannot prevent self-consumption.
(4) High-powered cycle, which is characterized by high row and low resistance.
(5) Pathological changes lack specificity, mainly a broad inflammatory response.
(6) Once cured, it does not leave traces of organ damage, nor does it turn chronic.
2. MOF diagnosis points MOF diagnosis points must emphasize the following points:
(1) The primary injury factor must be acute, usually severe trauma, shock, infection, extensive burns, major surgery, etc., and secondary injuries occur mostly in distant parts of the tissues and organs, which are fierce. The mortality rate is very high.
(2) There must be a certain interval (>24h) between the pathogenesis and the occurrence of MOF.
(3) Most organ function is good before the patient develops MOF.
(4) The damage of organ function is reversible. Once the pathophysiological mechanism is blocked, the organ function is expected to recover.
(5) MOF and some end-stage chronic diseases, liver and kidney syndrome, lung and brain syndrome, heart failure combined with liver, renal failure, late stage cancer and organ failure are completely different concepts.
(6) If it dies within 24 hours of the onset of illness, it is a failure of recovery and does not fall within the scope of MOF.
