Pathophysiology of chronic pancreatitis

Although the most common causes of chronic pancreatitis have not changed, it has become clear that a host of modifying biochemical, inflammatory, neural, and genetic deviations allows the disease to progress. Alterations in biochemical composition allow calcific stone formation, whereas various toxins, cytokines, and neuropeptides contribute to the progression of fibrosis and pain production. The basic cellular structure contributing to fibrosis of the pancreas has been elucidated and factors responsible for its activation delineated. Of most importance is the recent recognition of a set of genetic mutations that results in several aberrations of normal pancreatic physiology, which, in conjunction with other inciting insults or by themselves, allow the disease to begin and progress.     

Pathophysiology and treatment of severe pancreatitis

The current study was designed to characterize toxic substances in hemorrhagic ascitic fluid by using in vivo dogs model and to examine the toxicity of hemorrhagic ascitic fluid by using an in vivo mice model injecting the fluid intraperitoneally. Our experiment showed that high levels of bradykinin, histamine and prostaglandin E were found in serum and in hemorrhagic ascitic fluid which reported as toxic substances during severe pancreatitis. A similar finding was also obtained clinically in four patients with severe acute pancreatitis. The mortality rate on 72 hours following the intraperitoneal injection of 2.0 and 3.0 ml of ascitic fluid were 66.0% and 89.7% respectively. Mice which died following the injection of ascitic fluid showed shock lung at autopsy. These results indicate that peritoneal lavage might be an effective method for the treatment of severe pancreatitis. We evaluated 25 patients with severe acute pancreatitis clinically. Laparotomy and drainage operations were performed in 16 patients of these patients. Twelve among 16 patient had good results. The cause of death were multiorgan failures.     

Pathophysiology of acute pancreatitis: Evaluation of the effect and mode of action of steroids in experimental pancreatitis in dogs

Three experiments were performed to evaluate the effects and hemodynamic changes brought about by steroids in experimental pancreatitis in dogs. The results show (1) a significant improval in survival in steroid-treated groups, (2) no difference in cardiac output or mean blood pressure between groups, (3) a decrease in relative pancreatic arterial blood flow in the untreated animals, and (4) an increase in arterial flow to the pancreas after steroid therapy. The experiments suggest that the reversal of reduced pancreatic flow may be important in improving the prognosis.     

Pathophysiology of acute pancreatitis: Evaluation of the effects and mode of action of indomethacin in experimental pancreatitis in dogs

Prostaglandins are known to affect vascular flow and the inflammatory response. Since acute pancreatitis involves both of these phenomena, we undertook studies using anesthetized mongrel dogs to investigate changes in blood pressure, cardiac output and pancreatic arterial flow for 6 hr in both normal animals (10 dogs) and following induction of acute pancreatitis (15 dogs). Indomethacin (5 mg/kg), which inhibits synthesis of prostaglandins, was then injected intravenously, and the animals were subsequently monitored for 2 hr. Results showed: (1) A significant fall in pancreatic arterial flow, relative to cardiac output, over the first 6 hr of the disease in the acute pancreatitis animals (P < 0.001). (2) A further significant decrease in relative pancreatic arterial flow following indomethacin in these animals (P < 0.001). A similar reduction in pancreatic arterial flow was observed following indomethacin administration in the control animals (P < 0.001). Conclusions: (1) Relative pancreatic arterial flow falls during experimental acute pancreatitis. (2) Indomethacin reduces both basal and compromised pancreatic arterial flow in the anesthetized dog; this suggests that prostaglandins may participate in the maintainance of basal acid-compromised pancreatic blood flow in the anesthetized dog.     

Pathophysiology of acute renal failure

Acute renal failure (ARF) is a common renal disease affecting up to 5% of all hospitalized patients, with a higher prevalence of 10-30% in patients in critical care units (1-3). Despite advances in the management of critically ill patients and technological advances in renal replacement therapy, the high mortality of patients with ARF has not changed over the last decades and remains above 50% (4-6). Moreover, as a consequence of more advanced medical therapy and more complicated surgical interventions in older and multimorbid patients, the number of patients with ARF is increasing (1, 4, 5). Moreover, ARF itself increases the risk to develop additional complications that can be deleterious. Recently, an independent association between ARF and mortality has been shown in patients following administration of radiocontrast media in an intensive care unit and in patients following cardiac surgery (6, 7). Following radiocontrast media the mortality of patients with ARF was increased five fold and following cardiac surgery sixteen-fold as compared to patients with the same underlying disease without ARF. The pathophysiology of ischemic ARF is reviewed with the emphasis on the following mechanisms: Increased fractional excretion of sodium, Activation of tubuloglomerular feedback, Cytoskeletal disruption, Tubular obstruction, Vascular mechanisms. The following mediators will also be discussed: Calcium, Cysteine proteases, Nitric oxide, Adhesion receptors and integrins.     

Pathophysiology of acute obstructive cholangitis

Because acute obstructive cholangitis is life-threatening, understanding of the pathophysiology of this disease is required to establish a medical treatment. Experimental results indicate that obstruction of the bile duct itself does not induce acute cholangitis, but infection of gut-derived bacteria such asEscherichia coli into the bile triggers fatal septicemia, which leads to liver injury and renal failure. In obstructive cholangitis, functional changes in sinusoidal lining cells are often seen. Mediators produced by Kupffer cells, endothelial cells, and stellate cells may modulate inflammatory reactions especially in the periportal area of bile duct ligated animals. In addition, proliferation of bile duct epithelial cells is induced by bile duct ligation. Recently, nitric oxide has been recognized as an important mediator of multiple organ failure. Actually, when bile duct ligated animals are treated with endotoxin, metabolites of nitric oxide in blood and plasma increase, indicating that nitric oxide may take part in the pathophysiology of acute obstructive cholangitis.     

Pathophysiology of ischaemic acute renal failure

This chapter summarizes the pathophysiology of ischaemic acute renal failure from both the experimental and clinical points of view. Traditionally, the abrupt fall in glomerular filtration rate (GFR) is thought to be due to an interplay of haemodynamic and tubular abnormalities. The intrarenal haemodynamic alterations include renal vasoconstriction, leukocyte-endothelium interactions and loss of blood flow and GFR autoregulation. During recent years it has become evident that pronounced outer medulary ischaemia makes an important contribution. In severe and prolonged ischaemia, the tubular epithelial cells can undergo either sublethal or lethal cell damage. Cell death occurs by necrosis and apoptosis. The different mechanisms of post-ischaemic cell damage are discussed. The post-ischaemic kidney also shows a dramatic capacity for recovery. During this recovery phase some of the damaged cells undergo de-differentiation--which is an important step in regeneration of the tubular epithelium. Recent evidence points to the possibility that infiltration of the kidney with bone-marrow-derived stem cells contributes to the repair process. The molecular mechanisms and the effect of growth factors are summarized.     

Sulindac-induced acute pancreatitis mimicking gallstone pancreatitis

Two patients with sulindac-induced acute pancreatitis presented clinically with abdominal pain, right upper-quadrant tenderness, markedly increased serum amylase values, and hyperbilirubinemia, findings initially suggestive of gallstone pancreatitis. Ultrasound examinations were negative for gallstones. One patient was inadvertently treated two years later with sulindac with recurrence of abdominal pain, marked hyperamylasemia, and jaundice. Clinical resolution was rapid with each episode following discontinuation of sulindac.     

Ascaris-induced acute pancreatitis

AIM OF THE STUDY: To indicate options in a surgical university team in Vietnam for treatment of ascaris-induced acute pancreatitis. PATIENTS AND METHODS: From January 1998 to April 2001, 33 patients (mean age 46 years) were admitted with a diagnosis of acute pancreatitis based on elevated serum amylase in 29 patients (88%), and elevated urinary amylase in all patients and a compatible clinical picture. The pancreatic ultrasonography was abnormal in 79% of cases. Biliary and pancreatic ultrasonography shown ascaris in 31 patients (94%). In other two patients ascaris was detected with duodenal endoscopy. RESULTS: In 24 patients, the worms from the duodenum and/or across the ampullary orifice was trapped and withdrawn during duodenoscopy and failed in three patients. Nine patients were operated on, three after failure of endoscopic treatment, five for lithiasis of the common bile duct associated to the ascariasis, and one for necrotic pancreatitis. Seven patients operated on underwent a choledocotomy with a T-tube drainage, two patients underwent a left pancreatectomy to withdraw the ascaris, and one patient a resection of pancreatic necrosis. All patients recovered without complications except the patient with a necrotic pancreatitis who developed a pancreatic fistula for 23 days. Mean discharge times were 5.6 days after endoscopic treatment and 12.2 days after surgery. Effective antihelminthic therapy was administered in all patients. CONCLUSION: Endoscopic treatment was effective in 24 out of 33 patients. Surgery was indicated for failures of endoscopic treatment, association of ascariasis and common bile duct stones, migration of ascaris in intra pancreatic duct, and pancreatic necrosis.