Pathogenesis of Salmonellosis
Salmonella, having overcome the factors of nonspecific protection of the oral cavity and stomach, enter the lumen of the small intestine, where they attach to the membranes of enterocytes and secrete thermostable and / or thermolabile exotoxins. With the help of permeability factors (hyaluronidase), pathogens penetrate into the enterocytes through the brush border. The interaction of bacteria with epithelial cells leads to degenerative changes in microvilli. Intervention of pathogens in the submucosal layer of the intestinal wall is counteracted by phagocytes, which is accompanied by the development of an inflammatory reaction.
When the bacteria are destroyed, the lipolysaccharide complex (endotoxin) is released, which plays a major role in the development of intoxication syndrome. The lipopolysaccharide complex activates the arachidonic cascade through the lipoxygenase and cyclooxygenase pathways. The lipooxygenase pathway leads to the formation of leukotrienes, stimulating chemotaxis and degranulation, enhancing vascular permeability, and, indirectly, reducing cardiac output. The cyclooxygenase pathway leads to the formation of prostanoids (thromboxanes, prostaglandin E, PGF2aa, etc.). The enhanced synthesis of prostanoids induces platelet aggregation, leading to thrombosis in small capillaries. The DIC-syndrome with disturbances of microcirculation develops. The latter cause changes in metabolism with the accumulation of acidic products in organs and tissues (metabolic acidosis). Prostaglandins stimulate the secretion of electrolytes and fluid in the lumen of the intestine, reduce smooth muscle and increase peristalsis, which ultimately leads to the development of diarrhea and dehydration of the body. Moreover, the action of bacterial enterotoxins, which activate the adenylate cyclase system and the production of cyclic nucleotides, promotes dehydration. The consequence of dehydration and intoxication is a violation of the cardiovascular system due to extracardiac mechanisms, which is manifested by tachycardia and a tendency to lower blood pressure. With the maximum severity of exsicosis, the development of cellular hyperhydration is possible due to the difference in osmotic potentials between cells and the intercellular space. Clinically, the condition is manifested by acute swelling and edema of the brain. Disturbances of microcirculation and dehydration lead to dystrophic processes in the tubules of the kidneys. Develops acute renal failure, the first clinical sign of which is oliguria with the further accumulation of nitrogenous slag in the blood.
Usually (95-99% of cases), salmonella does not spread beyond the sub-mucosal layer of the intestine, causing the development of the gastrointestinal form of the disease. Only in some cases penetration of pathogens into the blood is possible, while a generalized form of salmonella with a typhoid-like or septic course is observed. The infection is facilitated by the inadequacy of cellular and humoral immune responses.
At a microscopic examination, the intestinal walls reveal changes in the vessels in the form of hemorrhages in the mucous and submucous layers of the intestinal wall. In the submucosal layer, in addition to microcirculatory disorders, leukocyte reaction and edema develop.
Clinical Picture of Salmonellosis
The following forms and variants of the current are distinguished:
1. Gastrointestinal (localized) form:
- gastritis variant,
- a gastroenteric variant,
- gastroenterocolitis variant.
2. Generalized form:
- typhoid-like variant,
- septic variant.
3. Bacteriovenous:
- sharp,
- chronic,
- transient.
With all forms and variants of the disease, the incubation period ranges from a few hours to 2 days.
The gastroenteric variant is the most common form; develops acutely, a few hours after infection. It is manifested by intoxication and disorders of water-electrolyte balance. In the first hours of the disease, signs of intoxication predominate: fever, headache, chills, body aches. In the future there are pains in the abdomen (usually spastic), localized in the epigastric and umbilical areas, nausea, multiple vomiting. Diarrhea quickly joins. Stools are initially stained, but quickly become watery, frothy, offensive, sometimes with a greenish tinge. The frequency of vomiting and defecation may be different, however, in order to assess the degree of dehydration, it is not the frequency but the amount of the released fluid that is more important. Defecation is not accompanied by tenesmus.
Despite the high body temperature, when examined, the pallor of the skin is noted, in more severe cases, cyanosis develops. The tongue is dry, coated. The abdomen is swollen, with his palpation, you can notice a slight diffuse soreness and rumbling of the intestine. Tones of the heart are muffled, they mark tachycardia, a tendency to lower blood pressure, a pulse of soft filling. The excretion of urine decreases. In more severe cases, the development of clonic seizures, more often in the muscles of the lower limbs.
Gastroenterocolitis variant. The onset of the disease resembles a gastroenteric variant, but already on the 2-3rd day of the disease the volume of feces decreases. Slime appears in them, sometimes blood. When palpating the abdomen, spasm and soreness of the colon are noted. The act of defecation can be accompanied by tenesmus. Thus, the clinical manifestations of this variant have many similar features with the same-named variant of acute dysentery.
The gastric variant. Observe much less often. Characterized by acute onset, repeated vomiting and pain in the epigastric region. As a rule, the intoxication syndrome is poorly expressed, and there is no diarrhea at all. The course of the disease is short-term, favorable.
The severity of the gastrointestinal form of salmonella determines the severity of intoxication and the magnitude of water-electrolyte losses. In assessing the degree of intoxication, first of all, take into account the level of the temperature reaction. Body temperature can be very high, in these cases, her ascent usually accompanies a feeling of chills, headache, weakness, body aches, anorexia. In cases of a more mild disease, the fever is mild, even subfebrile.
At the same time, one of the leading conditions determining the severity of the disease with different variants of salmonellosis is the severity of water-electrolyte losses.
During the generalization of the process, a typhoid-like variant of salmonellosis, similar in the clinical picture with typhoid paratyphoid diseases, or a septic variant, may develop. As a rule, the generalized form is preceded by gastrointestinal disorders.
Typhoid-like variant. It can begin with manifestations of gastroenteritis. In the future, on the background of stagnation or disappearance of nausea, vomiting and diarrhea, an increase in the temperature response, acquiring a constant or undulating character, is observed. Patients complain of headache, insomnia, severe weakness. On examination, the paleness of the patient’s skin is noted, in some cases separate rose-cell elements appear on the skin of the abdomen and lower chest. By the 3-5th day of the disease hepatolienal syndrome develops. & Arterial blood pressure is prone to decrease, relative bradycardia is expressed. In general, the clinical picture of the disease acquires features that closely resemble the course of typhoid fever, which complicates clinical differential diagnosis. A typhoid-like variant of salmonellosis is not excluded even in the absence of initial manifestations in the form of gastroenteritis.
Septic variant. In the initial period of the disease, it is also possible to observe manifestations of gastroenteritis, later replaced by a prolonged remittent fever with chills and severe sweating with its decrease, tachycardia, myalgia. As a rule, hepatosplenomegaly develops. The course of the disease is long, torpid, characterized by a tendency to form secondary purulent foci in the lungs (pleurisy, pneumonia), heart (endocarditis), in the subcutaneous tissue and muscles (abscesses, phlegmon), in the kidneys (pyelitis, cystitis). Irit and iridocyclitis may also develop.
After the transferred disease irrespective of the form of its course, some of the patients become bacterial invaders. In most cases, salmonella discharge ends within 1 month (acute bacterial release); if it lasts more than 3 months, after a clinical recovery, it is regarded as chronic. With transient bacterial isolation, single or double sowing of salmonella from feces is not accompanied by clinical manifestations of the disease and the formation of significant antibody titers.
Differential Diagnosis of Salmonellosis
Salmonellosis should be distinguished from many diseases accompanied by the development of diarrhea syndrome: shigellosis, escherichiosis, cholera, viral diarrheal infections, fungal poisoning, heavy metal salts, phosphorus-organic compounds, etc. In addition, in some cases, there is a need for urgent differential diagnosis of salmonellosis from myocardial infarction, acute appendicitis, gallstone attack, thrombosis of mesenteric vessels.
The gastroenteric variant of salmonellosis is characterized by the predominance of signs of intoxication in the first hours of the disease, then development of dyspeptic phenomena – nausea and vomiting, spastic abdominal pain, diarrhea with a watery, frothy stool stool. The gastroenterocolitis variant is distinguished by a decrease in the volume of feces from the 2-3rd day of the disease, the appearance of mucus in them and, possibly, blood, spasm and soreness of the colon, and sometimes tenesmus. Salmonella gastritis, as a rule, develops against the background of general toxic signs of varying severity. Typhoid-like and septic variants of the generalized form of salmonellosis are more easily suspected if they start with manifestations of gastroenteritis; in other cases, their differential diagnosis with typhoid and sepsis is extremely difficult.
Laboratory Diagnostics of Salmonellosis
The basis is the isolation of the causative agent by the cultivation of vomit and stool, and in the case of generalized form and blood. Material for bacteriological research can also serve as washing water of the stomach and intestines, urine, bile. With a septicopyemic variant of the disease, pus or exudate can be sown from inflammatory foci. For the epidemiological control of salmonellosis outbreaks, a bacteriological analysis of food remains suspected of contamination, as well as dishwashing. It is mandatory to use enrichment media (magnesium medium, selenite medium), several differential diagnostic environments (Endo, Ploskirev, bismuth-sulfite agar), a wide range of biochemical tests and a set of monovalent adsorbed O and H sera.
As serological diagnostic methods, RNGA is used with complex and group salmonellosis erythrocyte diagnosticums when the reaction is performed in paired sera with an interval of 5-7 days. The minimum diagnostic antibody titer in the RNGA is -1: 200. Unfortunately, serological methods in most cases are of value only for retrospective confirmation of the diagnosis.
More promising is the rapid detection of salmonella antigens in the RCA, RLA, ELISA, and RIA.
To determine the degree of dehydration and assessment of the severity of the patient’s condition, as well as to correct the ongoing rehydration therapy, hematocrit, blood viscosity, acid-base state and electrolyte composition are determined.