Diarrheal syndrome in the clinic of infectious diseases. Pathogenesis and clinical features. Principles of treatment of dehydration shock.
http://www.medicinenet.com/cholera/article.htm
Cholera is an acute anthroponosic infectious disease with fecal-oral mechanism of transmission. Cholera is characterized by dehydration due to loss of the fluid with watery diarrhoea and vomiting. Cholera is concerned to the group of the diseases, which are submitted to “international medical-sanitary roles”.
Etiology
There are two forms of the vibrio cholera: classical biotype, which was discovered by Koch in 1883 and El Tor biotype.
The vibrion is short. It is gram-negative and curved organism which, from its shape, is often called the comma bacillus. Typically it is small, comma-shaped rod. It frequently occurs in S-shapes, owing to the attachment of a pair of organisms at their ends, and especially in the old and virulent cultures long treads showing a somewhat spiral appearance may be seen. The vibrio cholera is strictly aerobic and grows readily upon ordinary culture media. There are no spores and capsules.
Vibrio cholera has two antigens flagellar (H) antigen and somatic (O) antigen.
The somatic (O) antigens do distinguish V. cholera Ogawa, Inaba and Hikojima, which are responsible for epidemics.
V. cholera produce 3 fractions of toxin. Cholerogen-exotoxin plays the most important role in the development of dehydration. Cholerogen consists of two types of toxin: cholerogen A and cholerogen B. Cholerogen A consists of peptide A1 and peptide A2. Peptide A1 penetrates through the cells membrane. Then it manifests the specific toxication. Peptide A2 connects peptide A1 with peptide B. Peptide B is untoxic, it connects the whole molecule of toxin with cell receptors. V. cholera survives in low temperature. The boiling kills V. cholera during one minute. It survives in sea water (till 60 days).
Vibrio cholera is present in the intestine and in the rice water-like stool during acute stage of infection.
Epidemiology
http://www.cdc.gov/cholera/epi.html
Cholera is anthroponosic intestinal disease with tendency to pandemic spread. Reservoir and source of infection is infected man. Discharge of vibrions is realized with excrement.
The sources of infection may be sick man with typical or obliterated form of cholera, reconvalescent after cholera and clinically healthy vibrio-carriers.
The patients with clinical picture of cholera are the most intensive source of agents. They discharge till 10-20 liters of detachments during first 4-5 days of the disease with great content of vibrions (106-109 vibrions in 1 mL).
The source of infection may be reconvalescents-vibriocarriers. They discharge vibrions into environment in average during 2-4 weeks.Healthy (transitory) carriers can discharge the agent periodically during some month.
The mechanism of transmission of the infection is fecal-oral. It is realized by water, alimentary and contact ways. The leading way of the transmission of the agents of cholera is water. This way may lead to epidemic distribution of cholera. Infection may happen due to use of infected water and also after use this water for wash of vegetables, fruits or bathing.
Food has also been implicated in some epidemics. The cases of cholera were described due to infected milk use, boiled rice and other food-stuffs.
It is established that inhabitants of different water reservoirs (fish, crayfishes, mollusks, frogs and other hydrobionts) are able to accumulate and preserve vibrio El-Tor for a long time. They are temporary reservoir of infection and may be factors of transmission of the agents.
The susceptibility to cholera is general and high. In endemic areas morbidity is observed more frequently in children and elderly persons.
Pathogenesis
http://www.uptodate.com/contents/pathogenesis-of-vibrio-cholerae-infection
Cholera is cyclic infection with essential fermental systems damage of the enterocytes. Vibrions cholera enter the organism through the mouth with water or food. Some part of vibrions perishes under influence of acid medium of the stomach. Another part of vibrions enters small intestine. Intestine reproduction and destruction of vibrions is accompanied with discharge of large amount of endo- and exotoxic substances. There is no inflammatory reactions.
Cholera is characterized by dehydration due to loss of fluid and salts with watery stool and vomiting. Hypersecretory processes play the leading role in the mechanism of the diarrhea origin. These processes are promoted by activation of ferment adenylcyclase in the epithelial cells of the intestine under action of exotoxin-cholerogen and accumulation of cyclic-3-5-adenosinemonophosphates, leading to increase of secretion of electrolytes and water.
In cholera the loss of fluid with stool and vomiting reaches such a great volume in a short period, practically not met during diarrhea of other etiology. The general volume may exceed in some cases up to 2 times the body’s mass of the patient. The loss of electrolytes plays essential role in pathophysiology of cholera. So, loss of potassium may reach one third its content in the organism. It is manifested by disorder of function of myocardium, damage of kidneys and also paresis of the intestine. In cholera dehydration is isotonic. Fluid contains 135 mmole/L Na, 18 mmole/L K, 48 mmole/L HCO3 and 100 mmole/L Cl (or 5g NaCl, 4g NaHCO3 and 1g KCl in 1 liter of defecation’s. An acute extracellular isotonic dehydration develops in the patients with cholera. It is accompanied with decreasing of the volume of circulated blood and hemoconcentration, leading to hemodynamic disorders and violation of tissue metabolism. Hypovolemia, metabolic acidosis, hypoxia, thrombo-hemorrhagic syndrome and acute renal failure develops.
Pathological anatomy
In cholera basic tragedy happens in a zone of the jejunal capillaries. Liquid get into the intestine from them through the epithelium cells. A venous return is diminished and as a result of that the heart’s return diminishes too. Blood pressure decreases. The organism reacts with a tachycardia on that (there is no cholera without tachycardia).
The other compulsory sigh is decreased diuresis. It is explained by increase of the water resorbtion by the renal canaliculi. If the loss continues venous flow diminishes acutely. Tachycardia caot compensate it already and blood pressure decreases.
The organism includes a pressory mechanisms to preserve functions of the vital important organs (heart, brain, kidneys). A capillary spasm begins. It improves for some time blood supply of the heart and brain. Blood pressure is equated but venous return decreases more. As a result of it oxygen transport to the organs and tissues and metabolic products transport are violated. PH balance of the organism changes to acidosis. The organism reacts on acidosis. It includes a new compensatory mechanism. It is dyspnea. Respiratory alkalosis develops, but it caot cause neutral PH balance due to violation of microcirculations.
A pressory mechanism is proper for kidneys too. The kidneys capillaries are spasmated. Tissue acidosis develops. Resorbtion of water and products of metabolism is alterated. That excludes the kidney as organ regulating homeostasis. Renal filtration stops entirely under the decrease of blood pressure less than
These changes are reversible in case of moderate hypoxia (a renovation period is not shorter than a week). But if the patient did not get from the hypovolemic shock a necrosis of the sinous canals comes (death from anuria – “shock kidney”). In case of prolonged loss of water all compensatory mechanisms become unable to keep blood pressure. An original decompensation comes. It coincides with the loss of the liquid equal to 8-12 % of the body’s weight. Then the unreversable changes become and therapy is uneffective. The volume of loss shouldn’t be more than 10 %.
In accordance with classification WHO the patients with cholera may be divided on three groups:
1. The first degree of dehydration. There are the patients which have loss of fluid volume equaled to 5 % of body weight.
2. The second degree of dehydration. There are the patients which have loss of fluid volume equal to 6-9 % of body weight.
3. The third degree of dehydration. The patients which have loss of fluid volume over 10 % of body weight. That dehydration is dangerous for life if the reanimation measures are not entertained.
According to classification of V. I. Pocrovsky patients can be divided in four groups:
1. The first degree of dehydration with loss of fluid 1-3 % of body weight.
2. The second degree of dehydration with loss of fluid 4-6 % of body weight.
3. The third degree of dehydration with loss of fluid 7-9 % of body weight.
4. The fourth degree of dehydration with loss of fluid more then 10 % of body weight.
It’s worth to underline that the clinical manifestation of the third degree of dehydration (by the WHO classification) or the fourth degree (by classification of V. I. Pocrovsky) is hypovolemic shock.
Clinical manifestations
http://www.mayoclinic.com/health/cholera/DS00579/DSECTION=symptoms
Clinical manifestations of cholera, caused by classic vibrion and vibrion El-Tor are similar.
Incubation period is from some hours till 5 days (in average 48 hours). Cholera may be present in typical and untypical forms. In typical course the next forms of the disease are differented in accordance with the degree of dehydration: light, moderate and severe form. In untipical course obliterated, fulminant forms may be present.
The onset of the disease is an acute, as rule. In light course of cholera the gradual development occurs in the part of the patients. The prodromal period may be 1-1.5 days. The patients mark weariness, ailing, headache, sometimes subfebrile temperature, heartbeating, sweet.
A diarrhoea is the first clinical manifestation of cholera. It appears suddenly, without the pain, often at night or in the morning. Diarrhoea is accompanied by gurgation in the stomach. After 1-2 defecation stool has typical shape. It is cloudy, white, fluid, without smell and “rice-water”.
In mild course (dehydration of the first degree). The loss of fluid is till 3 % of body weight. In majority patients stool may be till 10 times in a day, scanty. In one-third of the patients vomiting may occur 1-2 times. Thirst, light dizziness, weakness trouble the patients. Their state is satisfactory. Skin is humid, usual color. The mucous of the mouth is dry. There is no hypothermia. Subfebrile temperature may be in the part of the patients. There are no changes of the pulse and arterial pressure. An insignificant painfulment occurs due to palpation of the stomach. The changes of the blood are not typical. There is no blood’s condensation, change it’s pH and electrolytes.
After corresponding therapy a vomiting, dizziness, weakness disappear at the first day. The stool become normal on the 2-3 day of the treatment.
In moderate course (dehydration of the second degree) the loss of fluid is 4-6 %. There is considerable weakness, dizziness, and thirst in patients. A quantity of the defecation is from 10 till 20 times in a day. The stool is liquid, plentiful. Dehydration appears already after 3-5 defecation at the half of the patients. A vomiting is annexed early, and it is rice-water-like. The skin is pale. The moderate cyanosis of lips and extremities may be in the part of the patients. There is harsh voice. Turgor of the skin decreases. The feature of this degree of dehydration is appearance of the cramps without tonic tension. The pulse is frequent up to 100 per minute. The arterial pressure is decreases till
There are no changes of the red blood. Erythrocyte sedimentation rate (ESR) is lightly accelerated. Leukocytosis, neutrophylosis with the shift of the formula to the left, lymphopenia, monocytopenia and uneosinophilia occur in the part of the patients. Hematocrit is 51-54 %. The relative density of the plasma is 1026-1029. The change of electrolytes is insignificant. Hypokalemia and hypochlorinemia are more expressed. Hypotension disappears usually through 20-30 minutes from the onset of rehydration. Turgor is restored through 3-4 hours. The skin becomes pink. A vomiting continues till a day. Rarely a vomiting is observed on the second day. The stool becomes facesic through 1-3 days, and it becomes normal to 4-5 day. The general loss of the fluid is 5-
Severe course (dehydration of the third degree) occurs more rarely, approximately in 10 % of the patients. The loss of fluid is 7-9 % of body weight. The detachment this degree of dehydration is connected with necessity of prevention of development extremly severe course. There are no secondary changes of the important system of the organism due to this degree of dehydration. Because, it may be possible rapid compensation of dehydration and restoration of electrolytes. The third degree is characterized by more intensive clinical manifestations of dehydration and unfirm compensation.
The disease develops impetuously. The stool is watery, abundant from the first hours of the disease. Sometimes the patient cannot count a quantity of defecations. In patients sharp weakness, adynamia, severe thirst, cramps of the muscles are observed. The state of the patients is serious and very serious.
A cyanosis of lips and extremities is observed. The skin is cold and shriveled. The turgor decreases. The face is pinched, eyes are deeply sunken in the orbits. In a third of the patients a symptom of “black eyeglasses” is observed. The mucous of the mouth cavity is dry. The lips are dry too. Tongue is dry and covered. A voice becomes hoarse. The cramps are often of long duration, with tonic character. Cramps are accompanied with pain. The cramps of the trunk muscles and diaphragm are not observed. The temperature is 35.7-35.5 ºC. The pulse is 120-
Extremly severe course (dehydration of the forth degree) or decompensated dehydration. It occurs more rarely than the other clinical variants. The loss of fluid is 10 % of body weight and more.
In this case the organism cannot compensate the indigence of water-electrolytes balance and function of the significant organs. It leads to hypovolemic shock. The relapsing vomiting is observed. Decompensated dehydration may develop through 6-8 hours and even at the first 2-3 hours. The state of the patients is serious and very serious. In the last hours diarrhoea and vomiting may be absent. It is connected with paresis of the stomach and intestine muscles, with hypokalemia and metabolic acidosis. At the same time there are expressive symptoms of dehydration: cold clammy skin, intensive total cyanosis.
The color of the hand’s clusters, nouse, aural areas, lips and eyelids is violet or black. The face is pinched, eyes deeply sunken in orbits. There is impression of the suffering and entreaty about help on the face (facies cholerica).
The skin is shriveled. The turgor of the skin is decreased (“washwoman’s hands”). A voice becomes hoarse. The temperature is 34.5 ºC. The generalized tonic muscles cramp are observed, including muscles of the abdomen and back. The agonizing hiccup may be due to clonic spasm of diaphragm. There is no pulse. The arterial pressure is not determined. The breathing is frequent and superficial. There is anuria. The condensation of the blood is observed. In peripheral blood the concentration of hemoglobin increases. Expressive leucocytosis, neutrophylosis, lymphopenia, uneosinophilia occur. Hematocrit is higher than 66 %. The relative density of the plasma is 1036 and more. The alterations of electrolytes are very expressive: hypokalemia, hypochlorinemia. Hyponatremia is expressed in a smaller degree. Dehydration has isotonic character. The deficit bicarbonium (more than 10mmol/l) leads to decompensated metabolic acidosis and respiratory alkalosis.
Untreated patients die. The cause of the death is an acute heart’s failure (at the first three days of the disease) or renal failure (up to 14-16 day).
Complications
The next complications may develop in patient with cholera: pneumonia, sometimes abscesses, phlegmon. The row of complications are connected with intensive therapy: pyrogenic reactions, phlebitis, thrombophlebitis, hyperkalemia and other.
Diagnosis
The bacteriological research of material from sick man or corpse is the principal method of laboratory diagnostics. The purpose of bacteriological method is detachment of cholera¢s agent and it¢s identification.
The correct taking of the material has a great meaning for bacteriological research as the delivery of material to the laboratory. A quantity of the material is 0.1-
The serological methods may be also used for diagnostics of cholera. There are methods of discovering antibodies to vibrio cholera in blood, the methods of detaching antigens of vibrio cholera at stool and other materials. At the last years luminescent-serological method is used. The result may be received through 1.5-2 hours.
Differential diagnosis
Differential diagnostics of cholera is performed with toxical food-borne infections, esherichiosis, rotaviral gastroenteritis. In some untypical cases of cholera, especially in obliterated course of the disease it is necessary to perform differentiation of gastrointestinal form of salmonellosis, gastroenterocolitic variant of acute shigellosis, poisoning with mashrooms, organic and inorganic chemical remedies.
Treatment
http://sprojects.mmi.mcgill.ca/tropmed/disease/chol/treatment.htm
Patients needs immediate hospitalization in choleric department. They require emergency treatment which should be started at the pre-admission stage. It’s necessary to put them on special bed (Fig.7) and indicate pathogenetic preparations with the purpose of compensation of liquid and electrolytes loss, and corrections of metabolic changes. Isotonic polyionic solutions – Trisol, Acesolum, Lactasol, Quartasol, Hlosol are indicated. Quartasol is more effective.
Quantity of liquid, which should be infused for initial rehydratation (during 1-2 hours), should correspond to stage of the organism dehydratation. At III and IV stages of dehydratation it makes accordingly 7-9-10 % of body weight and more. Polyionic solutions infuse in vein initially-stream introduction, then volumetric rate 70-120 mL/minutes. To infuse liquid with such rate, it is necessary to use simultaneously two and more systems for transfusion. Stream introduction of liquid is replaced by dropwise infusion after normalization of pulse, restoration the arterial blood pressure and normalization of body temperature, hemoconcentration and acidosis.
The next infusions of polyionic solutions is determined by rate of proceeding loss of water and salts. The compensatory rehydratation is provided during several days in severe cases. For definition of its volume it is necessary every 2 hours to determine quantity of excrements and vomitive masses to investigate clinical (a pulse rate, the arterial pressure, body temperature) and every 4 – 6 hours laboratory (relative density of blood plasma, haematocrite number, concentration of electrolytes in blood plasma and erythrocytes, PH, concentration of standard Sodii hydrogenii) parameters.
For prevention of side reactions of polyionic solutions preliminary warm up to 38 – 40 °С, at the first hours of treatment infuse Prednisolon 0,5 gr/kg per day. At infusion there is plenty of solution Trisol the metabolic alkalosis and hyperkalemia can be developed. In these cases infusion therapy is continued with solution Disol.
It cases of not compensated hypokalemia it is necessary to infuse preparations of potassium in addition. At a pernicious vomiting, cramps, anaphylactoid reaction there should be used Dimedrol or Suprastin with Promedol. As at patients with severe current of cholera the clotting develops, Cordiamin, coffein or epinephrin of hydrochlorid is contrindicated.
In case of I-II stages dehydration (liquid loss up to 6 % of body weight) and more severe dehydration is managed by intravenous injection of saline solutions, at absence of vomiting recommend to apply peroral indication of Glucosani in tablets or Rehydroni in packages 18,9 gr: the content of 1 package dissolve in
Water-salt therapy should be over after appearance of excrements of normal character and at prevalence of quantity of urine over quantity of excrements in the last 6-12 hours.
Panangin or Asparcam during 1 mounth are indicated during early reconvalescence.
Antibiotics are the additional remedies. They accelerate clinical convalescence and prevent the further allocation of choleric vibrions. A preparation of a choice is Ciprofloxacin: 0,25-
Complication of rehydration
It may be pyrogenic reaction to solutions, hypokalemia, hyperkalemia.
Hypokalemia is observed more than 25 % of the patients with III degree of dehydration. The clinical manifestations are: distention of the stomach, pain in the stomach (hypokalemitic ileus).
Hyperkalemia develops in 15 % of the patients. The clinical manifestations are: red face and upper part of the body, cardialgia, typical changes of ECG, bradycardia. In this case it is necessary to inject Phillips solution №2. Phillip’s solution № 1 is injected again after signs of hyperkalemia elimination.
Etiotropic therapy is performed with antibiotics. Antibiotics cause shortening of diarrhoea duration and give possibility to decrease a quantity of fluid for injection.
Doxicycline is prescribed in dose 0,1 mg through 12 hours at the first day, than 0,3-0,5 mg through 6 hours during 3 days. Tetracycline is used for treatment of the patients with cholera in dose 0,3-0,5 mg through 6 hours during 5 days. It is possible to use chloramphenicol in 0,5 mg dose through 6 hours during 5 days.
Prophylaxis
http://www.cdc.gov/cholera/prevention.html
The measures of prophylaxis depend on epidemic situation in the country. The information of world health organisation about cases of cholera in different countries has an important meaning.
The incidence of disease can be diminished by sanitary-hygienic measures, sanitary disposal of human feces, purification and protection of water supplies, pasteurization of milk and milk products, strict sanitary supervision of preparation and serring of flood exclusion of persons with diarrhea from handling food, organization of the work about diseases of gastrointestinal tract and their examination on cholera.
Specific prophylaxis of cholera is performed by corpuscular vaccine and cholerogen-anatoxin.
Parenterally inoculated killed complete cell vaccine has been available for years, this vaccine stimulates high titers of serum vibriocidal antibodies, but it does not induce antibodies to toxin. Protection by vaccine has been induced for approximately 1 year, with vaccine efficacy approximately 70 %. Local gastrointestinal tract immunity against the organism and against the toxin should provide a better, less reactogenic immunogen using recombinant DNA technology an “attenuated” V. cholerae organism that lacks the genes for production of the A and B subunits of toxin was created. A plasmid containing the subunit gene was then constructed and inserted. Thus a candidate live V. cholera vaccine containing all the cell-was antigens necessary for adherence and the capacity to produce only the subunit of toxin has been engineered.
