Shock from cellular metabolic disease
It is basically represented by the effects of the damage to the cell and its mechanisms biochemical determined directly from microorganisms (bacteria, viruses, fungi) and their products: to initial subcellular alterations, if the process evolves, following involvement of organs and tissues also furthest from the inflammatory focus, with the initial purpose of compensation, but which may evolve (such as for the other form of shock) in a framework of multiple organ failure. Is also defined "Shock high flow" for the important and constant changes that cardioemodinamiche play a crucial role and a special feature in the evolution of the disease.
Definition of infection, sepsis and related syndromes
Preliminarily appears important to clarify the terminology commonly used in the context of this pathology. To do this, and aware of the difficulty of the many definitions applied to the patient septic, in 1991 two American scientific societies (the American College of Chest Physicians and the Society of Critical Care Medicine) have promoted a meeting of world experts to define the various clinical situations observed in septic patients and standardize terminology. Have been so established the following definitions:
It is the phenomenon characterized by the invasion, by any type of microorganism, tissue sterile organism: the majority of infections causes a response local inflammatory, many remain subclinical and only a "few" microorganisms that "infect"
- bacteraemia. It is given by the presence of viable bacteria in the blood. Similar terminology shall be valid for the presence in the blood of viruses, fungi, parasites (respectively: viremia, fungemia, parasitaemia).
-SIRS: Systemic Inflammatory Response Syndrome. It is the systemic inflammatory response to a variety of clinical insults of a certain severity including trauma and surgical stress. It is characterized by two or more of the following conditions:
-temperature> 38 ° C or <36 ° C;
-heart rate> 90 beats / min .;
-respiratory rate> 2 acts / min.o PaCO2 <32 mmHg;
- WBC> 12,000 per mm3, <4000 per mm3 or more than 10% immature forms.
- Sepsis. Represents the systemic response to infection. It is manifested by two or more medical conditions (such as SIRS) as a result of an infectious insult:
- temperature> 38 ° C or <36 ° C;
- heart rate> 90 beats / min .;
- respiratory rate> 2 breaths / min. or PaCO2 <32 mmHg;
- WBC> 12,000 per mm3, <4000 per mm3 or more than 10% immature forms.
- septicemia. This term should not be used anymore, least commonly.
- Sepsis syndrome. Sepsis + a shortage of organ: even this definition is no longer recommended in clinical practice.
-severe sepsis. Sepsis associated with organ dysfunction, hypoperfusion or hypotension.
Hypoperfusion or hypotension may include lactic acidosis, oliguria, or acute changes in the mental state.
-Hypotension caused by sepsis. A systolic blood pressure <90 mmHg or reduction in pressure> 40 mmHg from baseline value, in the absence of other causes of hypotension.
- Septic shock. Sepsis in the "moment" in which the hemodynamic compensation is overwhelmed and then appears hypotension, vasoconstriction, often hypothermia, despite adequate fluid replacement.
Signs of hypotension may include lactic acidosis, oliguria, acute altered state mental. If doses of inotropes or vasopressors such signs of hypoperfusion can occur without there being hypotension. These changes may occur in any stage of the septic process, and are more frequent in the late stages when there is greater impaired cellular and organic, and obviously worsen the prognosis.
- MODS: Multiple organ dysfunction syndrome. Implies the presence of abnormalities function of various organs in a critically ill patient where it is not possible to maintain homeostasis no therapeutic interventions.
Whatever septic focus of origin (among others not always easily identifiable), can be check on the level of symptoms and pathophysiological organismic responses correlated with the presence of the outbreak, with the presence of circulating microorganisms (bacteremia, septicemia) and / or their toxic products (endotoxemia), and finally with the effects of the many humoral mediators freed and the resulting immune mechanisms activated defensive purposes: this is the framework morbid define sepsis or septic state. But often, despite clinical evidence of a septic state, it is difficult to identify the source of infection and to document the presence of microorganisms in the circulation (blood cultures negative). In any case, whether there is evidence of the outbreak and the germs responsible for whether this is actually subsequently, there is more or less important modifications of the organism due to the damage induced cell microorganisms. Recent studies together with the finding of the vastness, complexity and importance on the floor diagnostic, prognostic and therapeutic of the pathophysiological response, confirm that sepsis can be considered an acquired disease of intermediary metabolism induced by microorganisms or produced by them and by the same immunological response to the invasion of infectious agents. There nature and extent of that response are not specific and do not depend on the type of infection (bacterial, viral, fungal) or from the office of the microorganisms. The pathophysiological involvement of the organism is, as already said, global and represents the response to cell damage (alterations of oxidative metabolism) determined directly from microorganisms, by their toxic products and the products of tissue degradation. Faced with such insult, in fact, the body operates an intense response biohumoral, immune and metabolic, together adaptation cardio-emo-dynamic and respiratory exposed later in detail, has the purpose of facilitating:
- action of direct defense against microorganisms and their toxic products;
- a limitation and repairing damage caused by microorganisms;
- enrichment with O2 to tissues (showing clear signs of failure oxidative).
Sepsis is a condition very common in surgical patients and trauma: is favored by underlying disease, conditions that cause immunosuppression (malnutrition, therapies immunosuppressive), from the frequent and indispensable diagnostic and therapeutic procedures (use of catheters, surgical interventions) that interrupt the anatomical barriers of protection from the elements pathogens.
Mortality, despite therapeutic advances, is still high: ranging from 20 to 50%, and is even more high in the advanced stages. The term "septic shock" should be reserved for the "moment" more or less enduring, where the compensation hemodynamic no longer adequate despite adequate fluid therapy and then appear hypotension (systolic blood pressure <90 mmHg), vasoconstriction, often hypothermia (icy shock): these changes may occur at any stage of the septic process, but are more frequent in the late stages when there is more impaired cellular and organic, and of course worsen the prognosis. Patients receiving inotropic and vasopressor may not present hypotension despite obvious signs of hypoperfusion. The onset of sepsis therefore involves a set of neurohormonal changes, immunological and metabolic disorders that alter the body's defense mechanisms. alteration primitive is at the cellular level and disrupts the metabolism: the difficulty of using oxygen from a part and the implementation of other defense mechanisms involve a restructuring biological-humoral which is the basis of further alterations multisystem (cardio-hemodynamic, respiratory, kidney, liver, brain), which combine to produce the typical picture of sepsis clinic. The harmfulness produced directly by microorganisms or their toxic products at the cellular level, the response biohumoral (damaging effects of mediators) and the effects of the mechanisms adaptation can derive conditions organic failure (heart failure, circulatory, respiratory, kidney, liver, brain), very often responsible for lethal outcome.
- Based on the pathophysiological changes can recognize different phases in the evolution of septic process:
- preclinical stage;
- phase compensation;
- phase failure;
- stage renal pluriorganica.
Sepsis: clinical stages and fees pathophysiological preclinical phase The majority of septic conditions of surgical interest follows a "traumatic event" acute that is configured mostly as a destruction of tissue with disruption of the natural barrier that exists between microorganisms and organismoospite; this event ("injury" of the Anglo-Saxon authors or "Trauma" in the broad sense) can be determined from a real accidental trauma, by a anestesiologicochirurgico trauma or often by a pathological event acute (hemorrhage gastrointestinal massive, acute pancreatitis, perforation of a hollow viscus). In the period between the "trauma" and the eventual development of a clinically apparent sepsis (fever, leukocytosis, positive blood culture, the presence of purulent material) takes the comparison between microorganism and host: between size and quality of the bacterial invasion and adequacy activation of specific and non-specific defenses of the organism. Until a short time ago this phase was mainly qualified in terms neuroendocrine, as a matter of "Stress response" (sympathetic activation / parasympathetic with overproduction of corticosteroids, catecholamines, glucagon, insulin) research of recent years have shown next these phenomena there is a more complex immune biological activation that involves the immune system, the complement system, the reticuloendothelial system and a series of mediators, mostly cytokines released mainly by activated macrophages, monocytes, and other cells, favoring the initial defense mechanisms to the invading microorganism. in the early stages subsequent actions of these mediators and cytokines in particular contribute to automantenere, sepsis and even more in the MOF, the characteristics pathophysiological changes. Interleukin-1 (IL-1) was among the first cytokines studied and appears to be responsible, together with the activation of all other mediators, of many biological processes already detectable in this initial phase of sepsis:
- stimulation of hepatic gluconeogenesis and hepatic synthesis of "phase proteins Acute ";
- induction and maintenance of muscle proteolysis (through a product of cleavage, the PIF or Proteolysis Inducing Factor);
- increase in body temperature, perhaps by direct action at diencephalic;
- stimulus, in the bone marrow, production and commissioning of the circle polymorphonuclear.
For overall effect of the mediators involved, then there is at this stage to an activation metabolisms protein hypercatabolism with one hand (muscle) and simultaneous stimulation protidosintesi the other (liver), in practice the muscle and peripheral tissues they sacrifice their structural proteins to ensure energy (gluconeogenetici amino acids - alanine, glutamine) and amino acids for the synthesis of proteins with greater meaning of "defense" (acute phase proteins). The magnitude of this catabolism is documented by the daily excretion of nitrogen (urea, creatinine, uric acid and 3-methyl-histidine) in the urine of 24 hours. The acute phase proteins seem to play an important role since the initial invasion of microorganisms: the actions and favoring opsonic phagocytosis, antioxidant, antiprotease, antienzimatica, give them a protective role of the host organism. There presence of these proteins since this first phase appears to be correlated with the ability organism to resist and control the septic insult, while other observations suggest that the hepatocellular failure and an inappropriate protein synthesis, along with a state of relative immunosuppression (reduced white blood cell function and the reticuloendothelial system, failure complement activation) can be critical factors for transition to subsequent stages of sepsis. Also in this phase, you may experience a relative neutropenia, some sign of failure leukocyte activation and therefore to reduced immunocompetence, in part, to phenomena of margining and diapedesis with accumulation of leukocytes in the outbreak of infection in the process of training. Among the mechanisms directly triggered by microorganisms, endotoxins and other bacterial products, among many still unknown and under study, we remember the activation of the phospholipase at the level of the cell membrane, which stimulates the release of leukotrienes, prostaglandins and thromboxanes. The cells that contain phospholipase A2 (eg. Neutrophils, monocytes, platelets) are stimulated to produce a platelet-activating factor (PAF: Platelet Activating Factor). These mediators have influence on vascular tone (reducing) on the permeability of the microcirculation, and aggregation of leukocytes and platelets configuring a "Endothelial damage" against all organs, even away from the primitive septic focus. For example thromboxane A2 and prostaglandin F2 produce marked pulmonary vasoconstriction, leukotriene C4 and D4 produce marked capillary permeability, leukotriene B4 and PAF promote platelet aggregation and activation of neutrophils. Microorganisms trigger, again, the way classical complement, and endotoxin activates the alternative pathway: both lead to production factors C3a and C5a complement with further effect on aggregation platelet and neutrophil and reduction of peripheral vascular tone. The activation of the complement, the synthesis of leukotrienes and the direct effect of endotoxin on neutrophils promote the accumulation of aggregates of these cells into the pulmonary, the release of their enzymes lysosomal, and the production of free radicals O2, that have proved toxic to the endothelium lung, beginning so early, the picture of acute respiratory failure. The activation of the coagulation system involves the synthesis of thrombin and the early formation of platelet thrombi in the microcirculation of many tissues. The interest of all these phenomena is that at this stage you decide the eventual evolution to the status of sepsis clinically evident.
It is the state of sepsis clinically evident where bacterial invasion prevail over host defenses and which is even more overt activation of the neuroendocrine system and immune (macrophages, interleukins, PIF, complement, and other factors not yet known). Also the effects of endotoxin - which in the past has been attributed great importance pathogenetic. Would actually mediated by the adrenergic system and various humoral mediators. We are witnessing a increased metabolic demands of all tissues, oxygen consumption and metabolism baseline, only partly related to the increase in body temperature, whereas in tissues peripheral there is an increased protein catabolism (mainly muscle protein) and a certain degree of insulin resistance (a phenomenon of nature postreceptor not fully clarified and tied according to some studies to a deficit of piruvicodeidrogenasi) that manifests as hyperglycemia, relative to the administration of glucose intolerance and need to administer insulin. To this is associated with a preferential use of other substrates (lipids, proteins) resulting in relative decrease in the carbon dioxide production (VCO2) than the consumption of oxygen (VO2) and then with reduced respiratory quotient (RQ: Respiratory Quotient). A the liver is marked synthesis and disposal of acute phase proteins, with increased uptake by the liver amino acid (available through the muscle catabolism) for the synthesis of protein and glucose. Recent studies have shown increased peripheral utilization and impairment of branched amino acids (used both peripherally and in the liver for energy purposes protido-synthetic) and normal or reduced use of aromatic amino acids. It follows one imbalance in plasma levels of branched chain amino acids (reduction) and aromatic (increase), framework similar to that observed in cirrhotic patients with encephalopathy and that could be the basis of mental changes observed in sepsis. The increased At muscle catabolism and the utilization of amino acids for the purposes gluconeogenetici justify the increased At ureogenesi with high urinary losses of urea nitrogen and 3-methylhistidine, with overall negative nitrogen balance.