ACUTE PANCREATITIS The term "acute pancreatitis", as it agreed by S.V. Lobachov, G.M. Mazhdrakov and some other authors, is in a certain sense a conditional concept, as not all morphological changes, which take place in the pancreas in case of acute pancreatitis, correspond to generally accepted manifestations of inflammatory process. In acute pancreatitis there not only* the symptoms of acute inflammation in the pancreas are present, but there are also the signs of hemorrhages and necrotic processes, which are stipulated by auto-digestion of the glandular tissue by pancreatic enzymes. Etiology The main factors causing the development of acute pancreatitis are: • bile and digestive-pancreatic reflux; • obstruction and hypertension of the biliary ducts; • blood supply disturbance of the pancreas; • allergic and infectious processes. Theory of bile reflux into the biliary duct (E. Opie, 1901). Regurgitation of bile into the system of the pancreatic ducts increases the intraductal pressure, which results in destruction of the glandular cells. Z. Dragstedt had approved, that the cells of impaired parenchyma of the gland, under the influence of the bile, secrete cytokynase, which has a destructive effect on the tissues of the pancreas. Theory of hypertension of the pancreatic duct (A. Rich, G. Duff, 1936). The authors had approved, that the increase of pressure in the ductal system of the pancreas results in rupture of its acinoses and small ducts and leads to the damage of cells. As a result, cytokynase is eliminated. Self-activation of enzymes and autodigestion of the glandular cells take place. Blood supply disturbance of the pancreas (I.G. Rufanov, 1925; V.M. Voskresensky, 1951). Arterial blood supply disturbance of the pancreas may provoke acute pancreatitis. It may be proved by the fact that edema and necrosis of the pancreas infrequently occurs in elderly and obese patients, who suffer from extensive atherosclerosis. Allergic theory. Role of allergy in development of acute edema and hemorrhagic necrosis of the pancreas is noted by many authors (R. Gregroire, R. Couvelaire, 1937; P.D. Solovov, 1940; O.S. Kochnev, 1958). Abrupt course of its symptoms, rapid development of edema and necrosis of the glandular tissue with subsequent development of shock phenomena and infrequently appeared eo-sinophilia testify possible allergic nature of acute pancreatitis. The allergic character of pathologic changes in acute pancreatitis is confirmed morphologically by hemorrhagic nature of inflammation and the presence of fibrin thrombus in the pancreatic vessels. Role of infection in development of acute pancreatitis is confirmed by the fact, that acute hemorrhagic pancreatitis may arise in acute inflammatory process in the gallbladder without impairment of bile passage through the bile ducts, in acute parotiditis, statuses typhosus and other infectious diseases. Infection penetrates the pancreas through the blood and lymph vessels.
Thus, the essence of acute pancreatitis consists in that fact, that intracellular activation of enzymes, which are produced by the pancreas with subsequent fermentative autolysis of acinar cells with formation of necrotic foci with aseptic (bacterial) inflammation around them. Infectious inflammation of the pancreas, as a rule, is a complication of pancreatonecrosis. It develops at the latest stages of the disease due to microbial infection of necrosis. Activation of enzymes inside the pancreas itself promotes: a) damage of acinar cells; b) hypersecretion of the pancreatic layer; c) impediment of the pancreatic juice outflow with development of acute hypertension inside the pancreatic ducts. Damage of acinar cells may result from: 1) abdominal and pancreatic injury; 2) pancreas surgical intervention; 3) blood flow disturbance in the glandular tissue (thrombosis, embolism, ligation, etc); 4) exogenous intoxication; 5) allergic reaction; 6) alimentary disorders. 2) Hypersecretion of the pancreas may be caused by: 1) alcohol abuse; 2) abundant, especially fatty food. Difficulty in pancreatic blood outflow may be provoked by pathological processes, localized in the area of excretory duct of pancreas, occlusion of ampula of the major duodenal papilla with a gallstone, and edema of the duodenal mucous membrane in the area of the major duodenal papilla. Pathogenesis The initial point of pathogenesis of acute pancreatitis is the process of activation of proteolytic enzymes as a result of their interaction with cytokynase. In pathogenesis of acute pancreatitis two stages are distinguished. I. Tripsin stage. • Cytokynase activates tripsinogen, transforming it in trip-sin. Tripsin activates tripsinogen and chemotrypsinogen owing to cytokynase of digested tissues. • Tripsin and tripsinogen affect the interstitial tissue and vessels of the pancreas, which result in edema, stasis and hemorrhage. In such conditions there is cell death and death of the glandular tissue and, accordingly, inflow of cytokynase continue. II. Lipase stage. • Salts of fatty acids activate lipase, which initiates the development of fat necrosis. • The presence of edema, hemorrhage and fat necrosis result in destruction of the pancreatic tissue, extension of edema to surrounding tissues, to transudation of fluid into the abdominal and pleural cavities, and sometimes into the peri-cardial cavity and into the retroperitoneal space. Abdominal organs (peritonitis), organs of the retroperitoneal space (paranephritis) and thoracic organs (pleurisy and pericarditis) are involved in the pathologic process. The so-called pleuro-visceral syndrome develops. In the foci of fat necrosis binding of calcium by salts of fatty acids takes place, and by the end of the 2-nd of 3-rd day hypocal-cemia may develop, which may be followed by tetany.
Progressive peritonitis with enteroparesis results in disturbance of waterelectrolytic and protein metabolism. On the background of lipase stage of pancreatitis the conditions for development of purulent pancreatitis are produced. Thus, in acute pancreatitis the following "local" pathomorphologic changes are noted: 1. Edema of the pancreas and surrounding tissues. 2. Fat necrosis. 3. Formation of hemorrhagic foci. 4. Necrosis of the pancreatic parenchyma. 5. Suppurative inflammation. Pathomorphologic changes, which develop in the pancreas in case of acute pancreatitis, underlay the classification of acute pancreatitis. In 1978 the V-th AllRussian Congress of Surgeons suggested the following classification of acute pancreatitis: • Edematous pancreatitis. • Fatty pancreatitis. • Hemorrhagic pancreatitis. • Purulent pancreatitis. However, recently classification of acute pancreatitis adopted in 1992 in Atlanta is introduced. According to this classification, acute pancreatitis is subdivided into the following forms: edematic-interstitial, necrotic, pseudocyst of the pancreas, and abscess of the pancreas. The following classification of acute pancreatitis, which underlay the form of pathologic process at the period of progress of the disease, is proposed for estimation of a general state of a patient: I. Clinico-anatomical forms: • Edematous pancreatitis. • Fatty pancreatitis. • Hemorrhagic pancreatitis. • Mixed pancreatitis. II. Periods of the disease: • The period of hemodynamic disturbances and pancreato-genic shock. • The period of functional insufficiency of parenchymatous organs. • The period of degenerative suppurative complications. III. Complications: A. Toxic: pleural effusion (pancreatic lung), massive hepatic and kidney necrosis; erosive-hemorrhagic gastritis; delirium; coma. B. Necrotic and pancreatic: parapancreatic infiltration, abscess of the pancreas, phlegmonous or apostematous pancreatitis, phlegmon of the retroperitoneal fat, pseudocyst of the pancreas. C. Visceral: External and internal fistula (pancreatic, biliary, gastric, intestinal, pancreatobronchial, and pleural). D. Arrosive hemorrhages.
E. Occlusive vascular impairments. In case of acute destructive pancreatitis it is very important to make a prompt estimation of the variants of pathomorphologic transformation of necrotic areas in the pancreas and in the retro-peritoneal space, which, as clinical practice shows, is closely related with the terms of the disease progress: Pathomorphologic transformation of acute pancreatitis
Clinical Picture Clinical picture of acute pancreatitis depends on form of the pathologic process and stage of the disease. Complaints of the patients with acute pancreatitis are reduced to description of pain syndrome, clinical picture of dynamic intestinal obstruction, respiratory and cardiac insufficiency. At late stages of the disease they are characterized by impaired function of basic systems of the internal organs (pleurovisceral syndrome). Pain in acute pancreatitis may be moderate in edematous form of pancreatitis and unbearable in pancreonecrosis. It occurs most often after inaccuracy in diet. In most cases pain appears suddenly, localizes in the epigastric area and along the projection of the pancreas. In case, when pathologic process impairs the head of the pancreas, pain is usually localized in the pit of the stomach or to the right of the median line of the abdomen. If body of the pancreas is involved, pain is localized in epigastric area, and if the tail of pancreas is impaired, it is felt in the left upper abdomen. In case of total impairment of the pancreas pain is felt through the upper abdomen, infrequently it is girdle (Voskresensky-Lobachev's symptom). Pain in acute pancreatitis may radiate to the lumbar area (Mayo-Robson's symptom), to the right scapula (Mussy's symptom), to the left part of the chest.
The cause of pain in acute pancreatitis is compression of nerve plexuses, which are located around the pancreas; they may occur in enlarged pancreas and in case when edema extends on the parapancreatic fat. Vomiting is a characteristic symptom of acute pancreatitis. It appears simultaneously with pain or accompanies it, may be recurrent and persistent, and sometimes becomes uncontrollable. Emesis contain mucous, food debris, and sometimes blood. Some patients with acute pancreatitis note distention of abdomen and gas retention. On examination of patients with acute pancreatitis patient's position in bed should be taken into consideration. In mild and moderate clinical course the patients are active and quiet in bed. In severe forms of pancreatitis during the attack of pain some patients are exited, toss in bed, cry with pain, and others lie motionless with bending knees. Body temperature in patients with acute pancreatitis either within normal limits, or subfebrile one. In case of suppurative inflammation it may attain 38°C and higher. When examining the skin integuments of patients with acute pancreatitis the following may be revealed: • Mondor's symptom — violet spots on the body and face alternating with the sites of the pale skin; • Halsted's symptom — cyanosis of skin of the abdomen; • Turner's symptom — cyanosis of the lateral surfaces of the abdomen and the lumbar region; • Grunwald's symptom — petechial skin rash in the navel area. Change in color of skin integuments is the result of dystonia of the skin vessels caused by pain symptom, general hypoxia of tissues, raised number of histamine I blood. The abdomen of the patient with acute pancreatitis may be distended. Intestinal peristalsis may be either increased, or sluggish. On percussion of the abdomen there may be revealed the presence of fluid in the abdomen and clear percussion sound over the surface of the intestine. Muscular tension is not defined on palpation. Even in peritonitis the degree of muscular tension is insignificant. At the same time, its considerable regional tension in the epigastric area and along the projection of pancreas (Korte's symptom) is pronounced on the background of moderate general protective muscular tension. This symptom should be estimated as visceromotor or axon-reflex. On palpation of the abdomen in patients with acute pancreatitis there is pronounced skin hyperesthesia, which area of location is associated with location of pathologic process in one or another portion of the pancreas. Deep palpation of the abdomen in the area of the pancreas reveals the absence of pulsation of the abdominal aorta (Voskresensky's symptom). On palpation in the area of the left costover-tebral angle it is possible to establish the presence of rigidity or tenderness (Mayo-Robson's symptom). Laboratory diagnostics. Blood investigation is of great importance for diagnosis of acute pancreatitis. In destructive forms of acute pancreatitis in some patients
hypochromic anemia is re vealed, though in abrupt fluid loss erythrocytosis may be noted in the first two days. Leucocytosis is revealed in 60% of patients with acute pancreatitis. Deviation of the differential count to the left due to increase of immature forms, lymphopenia, aenosinophilia, and elevation of the erythrocyte sedimentation rate are characteristic. Examination of urinary amylase (diastase) is of great practical importance. Increase of its activity (over 128 units according to Volgemuth) is noted in 70% of patients. However, in case of necrosis of the glandular tissue urinary amylase (diastase) is low. In severe course of acute pancreatitis serum amylase, which count may be increased, should be determined. Estimation of serum potassium, sodium and especially calcium, blood sugar, total protein fractions of blood allow to determine degree of severity of a patient's general state. As a rule, in edematous form of acute pancreatitis and in fat necrosis hyperco-agulation is observed, but in hemorrhagic necrosis — hypocoagu-lation. Hyperfibrinogenemia and increased amount of C-reactive blood protein are noted nearly always. In pancreatonecrosis daily urine is decreased up to anuria. In urinalysis there revealed aproteinuria, microhematuria and cyl-indiria. Special methods of investigation. X-ray, CT, endoscopic examination (gastoduodenoscopy and laparoscopy) is applied for diagnostics of acute pancreatitis. X-ray examination does not give direct indications on affection of the pancreas, but only reveals indirect signs, which may be helpful in diagnostics of acute pancreatitis. Indirect X-ray signs of acute pancreatitis are the following: distension of the abdomen and the transverse colon, sometimes the presence of air-fluid levels (Kloiber's cups) in the intestine, high position of the left dome of the diaphragm and the absence of well defined outlines of the left psoas muscle. In isolated cases during the X-ray examination of the abdomen it is possible to reveal free fluid in it. Computer tomography is "a gold standard" in niveau (topical) diagnostics and the most sensing method of investigation in acute pancreatitis and its complications. It reveals the enlargement of the pancreas, which shadow has well defined outlines in edematous form of acute pancreatitis, but in hemorrhagic, necrotic 176 and suppurative pancreatitis the outlines of the pancreas become blurred. By means of CT it is possible to reveal pancreatogenic abscesses and fluid masses in the retroperitoneal space at early stage of the disease. Ultrasonic tomography at present is the most rapid, available to all and rather reliable special method of investigation, which allows to diagnose acute inflammatory process in the pancreas. Computer tomography and ultrasonic scanning of the pancreas allow distinguishing fluid mass from dense inflammatory-necrotic masses, but do not give the possibility to determine the level of infection of the revealed cavity
content. For differential diagnostics of sterile pancreatonecrosis against its septic complications percutaneous puncture of discovered fluid mass under the control of CT and US with subsequent immediate coloring of bio-substrate according to Gramm and bacteriologic investigation for determining the type of microbes and their sensitivity to antibiotics is applied. Gastroduodenoscopy reveals retrodisplacement of the pylorus and the posterior wall of the stomach, hyperemia, edema and the presence of erosions of the mucous coat of the stomach and the signs of gastroduodenitis and papillitis. Laparoscopy is of great importance for diagnostics of acute pancreatitis, as it allows diagnosing for sure the most severe form of the disease — pancreatonecrosis. Laparoscopic sign of pancreatonecrosis is the presence of plaques of the fat tissue necrosis foci, which may be located along the greater, and lesser omentum, gastrocolic ligament, on the peritoneum of the anterior abdominal wall, the round ligament of the liver, and the transverse mesocolon. In case of fat necrosis there may be revealed serous exudates in the abdominal wall; amount of it may be different. On investigation of this exudates hyperactivity of pancreatic enzymes may be found out. Frequent sign of pancreatonecrosis is the serous impregnation of fatty tissue, the so-called vitreous edema of fatty tissue. In contrast to pancreatonecrosis, edematous pancreatitis does not have characteristic laparoscopic signs, as pathologic process in this case does not exceed the bounds of the omental bursa. Treatment Patients with acute pancreatitis have to be treated at the surgical unit only. Treatment mode depends on intensity of clinical picture, severity of the patient's state, and data of laboratory and instrumental investigation. Treatment of the seriously ill patients with pronounced toxemia is necessary to carry out at the intensive care unit. As it is very difficult to eliminate the etiologic factor during acute period of the disease, the main treatment of patients with acute peritonitis has to be directed on different aspects of pathogenesis and include both conservative and surgical methods of treatment. Conservative treatment of acute pancreatitis consists of complex of measures directed on: 1) elimination of pain; 2) decrease of exocrine function of the pancreas, and inactivation of enzymes; 3) infection prevention and fight against it. Different types of Novocain blocks, which also have positive neurotrophic action, are used for elimination of pain. Elimination of pain relieves the Oddi's sphincter spasm, which results in improvement of the pancreatic juice outflow. Besides that, the block promotes the decrease of enzyme activity of the pancreas. Choice of type of Novocain block depends on localization of pathologic process in the pancreas: The block of the round ligament of the liver is applied in cholecystopancreatitis, left vagosympathetic block — in sterile form of acute pancreatitis, bilateral paranephral block — in acute pancreatitis with marked signs of intestinal obstruction.
Intravenous injection of glucose-novocaine mixture (per 250 ml of 12% novocaine solution and 5% glucose solution) is a good anesthetic. To control the pain and to eliminate enteroparesis epidural anesthesia is widely used nowadays. To decrease the exocrine function of the pancreas a strict bed regimen, cold on the abdomen, starvation, evacuation of gastric contents by means of a nasogastric tube is indicated. The appliance of different preparations promotes the decrease of excretory function of the pancreas. Anticholinergic drugs, among which 1% atropine solution is used most frequently, are widespread. Atropine blocks the endings of the vagus in the pancreas and inhibits the pancreatic secretion. 178 Preparations, which decrease the pancreatic secretion, include methyl-thiouracil, pentoxyl, and azetazolamine. Recent years somatostatin and its synthetic analog ocreotid acetate (sand-ostatin), which are the strongest inhibitors of basal and stimulated secretion of the pancreas, stomach, and jejunum are used for decrease of pancreatic function. Inhibition of excretory function of the pancreatic cells may be attained by appliance of cytostatic drugs: 5-fluorouracil, cyclo-phosphan, and fluorofur. Action of these drugs is more effective on their introduction through celiac trunk following its catheter-ization according to Seldinger-Odman. It allows to taper a dose of the drug and to establish its high concentration in the glandular tissue. The appliance of cytostatic drugs is indicated in destructive pancreatitis. In case of total pancreatonecrosis and in suppurative complications of pancreatitis and hepatorenal insufficiency their administration is unpractical. Local hypothermia of the pancreas, which may be performed by continuous gastric lavage with cold water or by means of special cooling apparatus, has a suppressive influence on the excretory function of the pancreas. Antienzym drugs, such as trasilol, gordox, contrical, zimo-phren, calol, etc. are indicated to inactivate pancreatic enzymes. Antienzym action is achieved by intravenous injection of fresh frozen plasma (FFP) and albumin. Elimination of active pancreatic enzymes from the body may be realized by means of artificial (forced) diuresis, peritoneal dialysis and drainage of thoracic lymph duct. Complex of therapeutic procedures in edematous pancreatitis includes saline infusions and 5% glucose solution. Conservative treatment of pancreatonecrosis. At the intensive care unit it is necessary to exercise constant control of diuresis and cardio-vascular system parameters. It is also necessary to control the central venous pressure, Hb level, hematocrit and glycemia data, and also serum and urinary amylase. For treatment the patients with pancreatonecrosis it is important to determine the level of oxygen and acid-base balance in the blood.
The main aim of therapy of a patient with pancreatonecrosis is the treatment and prophylaxis of severe inflammation of the upper abdomen consequences. For that first of all it is necessary 179