ACUTE PANCREATITIS

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ACUTE PANCREATITIS :ACUTE PANCREATITIS Dr. Gangadhar

History :History The pancreas was one of the last organs in the abdomen to receive the critical attention of anatomists, physiologists, physicians, and surgeons It was first referred to as the “finger of the liver” in the Talmud, written between 200 bc and 200 ad Galen named it “pancreas” The description of acute pancreatitis by Fitz in 1889 Pan – All , Kreas - Flesh

Anatomy :Anatomy

embryology :embryology During 4th week of gestation the hepatic diverticulum gives a dorsal pancreaticbud and a ventral pancreatic bud. The dorsal pancreatic bud that forms the body and tail of pancreas. The ventral pancreatic bud developes in to uncinate process and head of pancreas The ventral pancreatic bud rotates clockwise around the duodenum and lies in the medial side of duodenum On 37th day of gestationthe 2 pancreatic buds fuse.

Congenital anamolies :Congenital anamolies Pancreas divisum: failure of dorsal and ventral duct systems during embryogenisis results in this condition Ectopic and Accessory pancreas:most of them are functional common sites arewalls of stomach , duodenum and ileum Mostly ectopic pancreatic tissue is submucosal Annular pancreas: presence of normal pancreatic tissue that completely or partially surrounding the duodenum(2nd part) and extends in to head of pancreas

histology :histology

Slide 7:Histology & Physiology :- Pancreas  Exocrine Endocrine 85% 2%   500-800 ml of Islets of Langherans Alkaline / isosomatic  (Acinar and duct cell secretion) Cell types :-    glucagon Amylase / lipase / protease and enzymes   insulin   Somatostatin pp  Pancreatic polypeptide

Enzyme Secretion :Enzyme Secretion The acinar cell (Latin term meaning “berry in a cluster”) - zymogen granules, lysosomes, or other cell compartments Amylolytic enzymes - such as amylase The lipolytic enzymes include lipase, phospholipase A, and cholesterol esterase Proteolytic enzymes include endopeptidases (trypsin, chymotrypsin), which act on internal peptide bonds of proteins and polypeptides exopeptidases (carboxypeptidases, aminopeptidases), which act on the free carboxyl- and amino-terminal ends of peptides, respectively; and elastase

Slide 9:Ribonucleases (deoxyribonucleases, ribonuclease) Enterokinase, an enzyme found in the duodenal mucosa, cleaves the lysine-isoleucine bond of trypsinogen to form trypsin Trypsin then activates the other proteolytic zymogens in a cascade phenomenon

Autoprotection of the Pancreas :Autoprotection of the Pancreas Autodigestion of the pancreas is prevented by the packaging of proteases in precursor form protease inhibitors – pancreatic secretory trypsin inhibitor (PSTI) serine protease inhibitor - kazal type 1 (SPINK1) These protease inhibitors are found in the acinar cell, the pancreatic secretions, and the α1 and α2 globulin fractions of plasma In addition, low calcium concentrations within the pancreas decrease trypsin activity Loss of any of these protective mechanisms leads to zymogen activation, autodigestion, and acute pancreatitis

General Considerations :General Considerations Pancreatic inflammatory disease may be classified as (1) acute pancreatitis (2) chronic pancreatitis The incidence of pancreatitis varies in different countries and depends on cause The estimated incidence in England is 5.4/100,000 per year in the United States it is 79.8/100,000 per year resulting in >200,000 new cases of acute pancreatitis annually

DEFINITION: :DEFINITION: 1. “Acute pancreatitis is an acute inflammatory process of the pancreas with varying involvement of other regional tissues or remote organ systems” (BRADLEY) 2.Acute pancreatitis is an acute condition with a abdominal pain and is usully asociatted with raised raised pancreatic enzyme levels in the blood or urine as a result of pancreatic inflammation.( BAILEY & LOVE’S)

Causes of Acute Pancreatitis :Causes of Acute Pancreatitis Common Causes Gallstones (including microlithiasis) Alcohol (acute and chronic alcoholism) Hypertriglyceridemia Endoscopic retrograde cholangiopancreatography (ERCP), especially after biliary manometry Trauma (especially blunt abdominal trauma) Postoperative (abdominal and nonabdominal operations) Drugs (azathioprine, 6-mercaptopurine, sulfonamides, estrogens, tetracycline, valproic acid, anti-HIV medications) Sphincter of Oddi dysfunction

Slide 16:Uncommon Causes Vascular causes and vasculitis (ischemic-hypoperfusion states after cardiac surgery) Connective tissue disorders and thrombotic thrombocytopenic purpura (TTP) Cancer of the pancreas Hypercalcemia Periampullary diverticulum Pancreas divisum Hereditary pancreatitis Cystic fibrosis Renal failure

Slide 17:Rare Causes Infections (mumps, coxsackievirus, cytomegalovirus, echovirus, parasites) Autoimmune (e.g., Sjögren's syndrome)

Pathogenesis :Pathogenesis Autodigestion is one pathogenic theory, according to which pancreatitis results when proteolytic enzymes (e.g., trypsinogen, chymotrypsinogen, proelastase, and phospholipase A) are activated in the pancreas rather than in the intestinal lumen A number of factors (e.g., endotoxins, exotoxins, viral infections, ischemia, anoxia, and direct trauma) are believed to activate these proenzymes Activated proteolytic enzymes, especially trypsin, not only digest pancreatic and peripancreatic tissues but also can activate other enzymes, such as elastase and phospholipase

Activation of Pancreatic Enzymes :Activation of Pancreatic Enzymes Evolves in three phases Initial phase – intrapancreatic digestive enzyme activation and acinar cell injury Zymogen activation mediated by lysosomal hydrolases such as cathepsin B ( co localization hypothesis by van Acker GJ, Perides G, Steer ML) The second phase – activation, chemoattraction, and sequestration of neutrophils Neutrophil sequestration can activate trypsinogen Thus, intrapancreatic acinar cell activation of trypsinogen could be a two-step process, i.e., with a neutrophil-independent and a neutrophil-dependent phase

Slide 20:The third phase effects of activated proteolytic enzymes and cytokines, released by the inflamed pancreas, on distant organs Activated proteolytic enzymes, especially trypsin, not only digest pancreatic and peripancreatic tissues but also activate other enzymes such as elastase and phospholipase The active enzymes then digest cellular membranes and cause proteolysis, edema, interstitial hemorrhage, vascular damage, coagulation necrosis, fat necrosis, and parenchymal cell necrosis.

Slide 21:Cellular injury and death result in the liberation of bradykinin peptides, vasoactive substances, and histamine  vasodilation, increased vascular permeability, and edema with profound effects on many organs, most notably the lung The systemic inflammatory response syndrome (SIRS) and acute respiratory distress syndrome (ARDS) as well as multiorgan failure may occur as result of this cascade of local as well as distant effects (lecithinase)

Slide 22:The course of acute pancreatitis appears to be modified by genetic factors that can increase the susceptibility and/or modify the severity of pancreatic injury Four susceptibility genes have been identified 1) cationic trypsinogen mutations (PRSS1m, R122Hm, and N291) 2) pancreatic secretory trypsin inhibitor (SPINK1) 3) cystic fibrosis transmembrane conductance regulator (CFTR) 4) monocyte chemotactic protein (MCP-1)

PATHOLOGY :PATHOLOGY Most causes of acute pancreatitis (i.e., alcohol, gallstones, and drugs) involve initial injury to peripheral acinar cells, fat necrosis, and autodigestion In comparison, infectious agents are directly toxic to acinar cells and cause generalized acinar cell necrosis associated with an acute inflammatory infiltrate The earliest lesion produced by pancreatitis due to hypotension is ductal necrosis Pathologically, there are two main types of pancreatitis Interstitial pancreatitis (edematous pancreatitis) Necrotizing pancreatitis

Approach to the Patient :Approach to the Patient Abdominal pain is the major symptom of acute pancreatitis Pain may vary from a mild and tolerable discomfort to severe, constant, and incapacitating distress Characteristically, the pain, which is steady and boring in character, is located in the epigastrium and periumbilical region and often radiates to the back as well as to the chest, flanks, and lower abdomen The pain is frequently more intense when the patient is supine, and patients often obtain relief by sitting with the trunk flexed and knees drawn up Nausea, vomiting, and abdominal distention due to gastric and intestinal hypomotility and chemical peritonitis are also frequent complaints

Slide 26:Physical examination frequently reveals a distressed and anxious patient Low-grade fever, tachycardia, and hypotension are fairly common Shock is not unusual and may result from 1) hypovolemia secondary to exudation of blood and plasma proteins into the retroperitoneal space (a "retroperitoneal burn") 2) increased formation and release of kinin peptides, which cause vasodilation and increased vascular permeability 3) systemic effects of proteolytic and lipolytic enzymes released into the circulation

Slide 27:Jaundice occurs infrequently - usually is due to edema of the head of the pancreas with compression of the intrapancreatic portion of the common bile duct Erythematous skin nodules due to subcutaneous fat necrosis In 10–20% - basilar rales, atelectasis, and pleural effusion, frequently left-sided

Slide 28:Abdominal tenderness and muscle rigidity are present to a variable degree Bowel sounds are usually diminished or absent An enlarged pancreas with organized necrosis or a pseudocyst may be palpable in the upper abdomen Cullen's sign, Turner's sign and Fox sign - indicate the presence of a severe necrotizing pancreatitis

Laboratory Data :Laboratory Data The diagnosis of acute pancreatitis is usually established by the detection of an increased level of serum amylase Values threefold or more above normal virtually clinch the diagnosis if overt salivary gland disease and gut perforation or infarction are excluded no definite correlation between the severity of pancreatitis and the degree of serum amylase elevation

Slide 30:The value rises within 6 to 12 hours of onset and is cleared fairly rapidly from the blood (half-life 10 hr) Probably less than 25% of serum amylase is removed by the kidneys The serum amylase value is usually increased on the first day of symptoms.

Slide 31:Serum lipase activity increases in parallel with amylase activity Serum lipase is always elevated on the first day of illness and remains elevated longer than serum amylase Measurement of both enzymes is important as serum amylase tends to be higher in gallstone pancreatitis and serum lipase higher in alcohol-associated pancreatitis A threefold elevated serum lipase value is usually diagnostic of acute pancreatitis - helpful in patients with nonpancreatic causes of hyperamylasemia Markedly increased levels of peritoneal or pleural fluid amylase (>5000 U/dL)

Slide 32:Leukocytosis (15,000–20,000 leukocytes per L) occurs frequently Patients with more severe disease may show hemoconcentration with hematocrit values >44% because of loss of plasma into the retroperitoneal space and peritoneal cavity Hyperglycemia is common and is due to multiple factors, including decreased insulin release, increased glucagon release, and an increased output of adrenal glucocorticoids and catecholamines Hypocalcemia occurs in ~25% of patients, and its pathogenesis is multifactorial and includes – hypoalbuminemia Hypomagnesemia calcium-soap formation hormonal imbalances (e.g., parathyroid hormone, calcitonin, and glucagon) binding of calcium by free fatty acid–albumin complexes intracellular translocation of calcium systemic exposure to endotoxin

Slide 33:Intraperitoneal saponification of calcium by fatty acids in areas of fat necrosis with large amounts (up to 6.0 g) dissolved or suspended in ascitic fluid - "soap formation" Hyperbilirubinemia [serum bilirubin >4.0 mg/dL] occurs in ~10% of patients jaundice is transient , return to normal in 4–7 days ALP & AST levels are also transiently elevated and parallel serum bilirubin

Slide 34:Markedly elevated serum LDH levels (>500 U/dL) suggest a poor prognosis Serum albumin is decreased to 3.0 g/dL in ~10% of patients Hypertriglyceridemia occurs in 15 to 20% of patients, and serum amylase and lipase levels in these individuals are often spuriously normal Approximately 25% of patients have hypoxemia (arterial PO2 60 mmHg), which may herald the onset of ARDS

Slide 35:electrocardiogram is occasionally abnormal in acute pancreatitis with ST-segment and T-wave abnormalities simulating myocardial ischemia Plain radiography sentinel loop and colon cutoff sign In addition, an abdominal plain film helps exclude other causes of abdominal pain, such as obstruction and bowel perforation And may give clues to etiology or severity, including calcified gallstones (gallstone pancreatitis), pancreatic stones or calcification (chronic pancreatitis with a bout) Sonography is useful to evaluate the gallbladder

Slide 36:A CT scan, especially a dynamic contrast-enhanced CT (CECT) scan, provides valuable information on the severity and prognosis of acute pancreatitis In particular, a CECT scan allows estimation of the presence and extent of pancreatic necrosis Necrosis is present in 12–20% of patients with acute pancreatitis A CT scan can confirm the clinical impression of acute pancreatitis even in the face of normal serum amylase levels

Computed Tomography (CT) Grading System of Balthazar and CT Severity Index Scoring System (CTSI) :Computed Tomography (CT) Grading System of Balthazar and CT Severity Index Scoring System (CTSI) Balthazar Grades Grade A Normal pancreas consistent with mild pancreatitis Grade B Focal or diffuse enlargement of the gland, including contour irregularities and inhomogeneous attenuation but without peripancreatic inflammation Grade C Grade B plus peripancreatic inflammation Grade D Grade C plus associated single fluid collection Grade E Grade C plus two or more peripancreatic fluid collections or gas in the pancreas or retroperitoneum

Slide 38:CTSI = Balthazar Grade Score Plus Necrosis Score Balthazar grade score:   A = 0 B = 1 C = 2 D = 3 E = 4 Necrosis score: Absence of necrosis = 0 Necrosis of up to ⅓ of pancreas = 2 Necrosis of 50% = 4 Necrosis of >50% = 6 * Highest attainable score = 10 (Balthazar grade E + necrosis >50%)

Slide 39:The likelihood of prolonged pancreatitis or a serious complication is negligible when the CT severity index is 1 or 2 and low with scores of 3–6 However, patients with scores of 7–10 had a 92% morbidity rate and a 17% mortality rate

Diagnosis :Diagnosis The diagnosis is usually entertained when a patient with a possible predisposition to pancreatitis presents with severe and constant abdominal pain, nausea, emesis, fever, tachycardia, and abnormal findings on abdominal examination Laboratory studies frequently reveal leukocytosis, hypocalcemia, and hyperglycemia. The diagnosis is usually confirmed by the finding of a threefold or greater elevated level of serum amylase and/or lipase Strong indicators include hemoconcentration (hematocrit > 44%) and signs of organ failure

Slide 42:Differentiation between alcoholic and gallstone pancreatitis is important Alcoholic pancreatitis occurs more frequently in men approximately 40 years old Biliary pancreatitis is more common in women, after age 40 years A serum ALT(alanine amino transferase) concentration above 150 IU/L is 96% specific for gallstone pancreatitis, the sensitivity is only 48% The aspartate aminotransferase (AST) concentration is nearly as useful as the ALT There are differing reports as to whether a high serum lipase-to-amylase ratio can differentiate alcoholic pancreatitis from pancreatitis of other causes Abdominal ultrasonography should be performed in every patient with a first attack of acute pancreatitis to search for gallstones in the gallbladder, common duct stones, and signs of extrahepatic biliary tract obstruction

Slide 43:The differential diagnosis should include the following disorders: (1) perforated viscus, especially peptic ulcer (2) acute cholecystitis and biliary colic (3) acute intestinal obstruction (4) mesenteric vascular occlusion (5) renal colic (6) myocardial infarction (7) dissecting aortic aneurysm (8) connective tissue disorders with vasculitis (SLE&PAN) (9) pneumonia (10) diabetic ketoacidosis

Ranson’s 11 Prognostic Criteria for Pancreatitis :Ranson’s 11 Prognostic Criteria for Pancreatitis

Slide 45:APACHE II scores on admission and within 48 hours help distinguish mild from severe pancreatitis and to predict death Most patients whose APACHE II scores are 9 or less during the first 48 hours survive However, patients with APACHE II scores of 13 or more have a high likelihood of dying

Complications of Acute Pancreatitis :Complications of Acute Pancreatitis Acute fluid collections These commonly occur early in the course of acute pancreatitis. They are primarily detected by imaging studies and not physical examination. Because they lack a defined wall and usually regress spontaneously, most acute fluid collections require no specific therapy. Pseudocyst This is a collection of pancreatic fluid enclosed by a wall of granulation tissue and requires 4 or more weeks to develop. .

Intra-abdominal infections: :Intra-abdominal infections: Within the first 1-3 weeks, fluid collections or pancreatic necrosis can become infected and jeopardize clinical outcome Intestinal florae are the predominant source of bacteria causing the infection. The usual suspects areEscherichia coli (26%), Pseudomonas species (16%), Staphylococcus species (15%), Klebsiellaspecies (10%), Proteus species (10%), Streptococcus species (4%), Enterobacter species (3%), and anaerobic organisms (16%).

Pancreatic necrosis :Pancreatic necrosis This is a nonviable area of pancreatic parenchyma that is often associated with peripancreatic fat necrosis and is principally diagnosed with the aid of dynamic spiral CT scans. Sterile pancreatic necrosis is usually treated with aggressive medical management, whereas almost all patients with infected pancreatic necrosis require surgical debridement or percutaneous drainage if they are to survive

Slide 49:Pancreatic ascites     Disruption of main pancreatic duct     Leaking pseudocyst   Involvement of contiguous organs by necrotizing pancreatitis     Massive intraperitoneal hemorrhage     Thrombosis of blood vessels (splenic vein, portal vein)     Bowel infarction   Obstructive jaundice

Slide 51:Systemic Pulmonary   Pleural effusion   Atelectasis   Mediastinal abscess   Pneumonitis   Adult respiratory distress syndrome Cardiovascular   Hypotension   Hypovolemia   Sudden death   Nonspecific ST-T changes in electrocardiogram simulating myocardial infarction Pericardial effusion

Slide 52:Hematologic   Disseminated intravascular coagulation Gastrointestinal hemorrhage   Peptic ulcer disease   Erosive gastritis   Hemorrhagic pancreatic necrosis with erosion into major blood vessels   Portal vein thrombosis, variceal hemorrhage Renal   Oliguria   Azotemia   Renal artery and/or renal vein thrombosis   Acute tubular necrosis

Slide 53:Metabolic   Hyperglycemia   Hypertriglyceridemia   Hypocalcemia   Encephalopathy

Slide 54:Sudden blindness (Purtscher's retinopathy) this ischemic injury to the retina appears to be caused by activation of complement and agglutination of blood cells within retinal vessels. It may cause temporary or permanent blindness. Central nervous system   Psychosis   Fat emboli Fat necrosis   Subcutaneous tissues (erythematous nodules)   Bone   Miscellaneous (mediastinum, pleura, nervous system)

Slide 55:Pancreatitis in Patients with AIDS The incidence of acute pancreatitis is increased in patients with AIDS for two reasons: The high incidence of infections involving the pancreas, such as infections with cytomegalovirus, Cryptosporidium, and the Mycobacterium avium complex The frequent use by patients with AIDS of medications such as didanosine, pentamidine, trimethoprim-sulfamethoxazole, and protease inhibitors

Treatment :Treatment In most patients (85–90%) with acute pancreatitis, the disease is self-limited and subsides spontaneously, usually within 3–7 days after treatment is instituted Conventional measures include analgesics for pain 50 to 100 mg of meperidine (Demerol) parenterally every 3 hours Morphine can also be used More severe pain requires hydromorphone (Dilaudid) IV fluids and colloids to maintain normal intravascular volume no oral alimentation nasogastric suction offers no clear-cut advantages in the treatment of mild to moderately severe acute pancreatitis

Endoscopic treatment :Endoscopic treatment THERAPUETIC ERCP SPHINCTEROTOMY STENTING

Slide 59:Role of Antibiotics The benefit of antibiotic prophylaxis in the treatment of necrotizing acute pancreatitis remains controversial Although the optimal drugs and duration of therapy remain incompletely defined, the current recommendation in patients with necrotizing acute pancreatitis is the use of a systemic antibiotic such as imipenem-cilastin, 500 mg thrice daily for 7 days fluoroquinolones (ciprofloxacin, ofloxacin, pefloxacin) metronidazole

Slide 60:Intraabdominal Candida infection was found to be associated with a mortality rate fourfold greater than that associated with intraabdominal bacterial infection alone suggest earlier use of fungicides

Slide 61:Several other drugs have been evaluated The list, by no means complete, includes Glucagon H2 blockers protease inhibitors -- aprotinin Glucocorticoids Calcitonin NSAIDs lexipafant, a platelet-activating factor inhibitor A reduced mortality rate but no change in complications with octreotide and somatostatin No effect on the mortality rate but reduced pancreatic damage with antiprotease gabexate mesylate pancreatic protease inhibitors and antibiotics can be better targeted to the affected regions in the pancreas with continuous regional arterial infusion (CRAI) into the celiac, splenic, inferior pancreaticoduodenal, and common hepatic arteries

Surgery :Surgery Pancreatic necrosis should be managed by a combination of radiologic and surgical means Peritoneal lavage through a percutaneous dialysis catheter does not influence the outcome of such attacks Aggressive surgical pancreatic debridement (necrosectomy) should be undertaken soon after confirmation of the presence of infected necrosis, and multiple operations may be required Since the mortality rate from sterile acute necrotizing pancreatitis is ~10%, laparotomy with adequate drainage and removal of necrotic tissue should be considered if conventional therapy does not halt the patient's deterioration

Slide 63:Symptomatic or enlarging pseudocysts can be treated by several methods Those in tail by distal pancreatectomy. Internal drainage is more advantageous than per cutaneous catheter( because of catheter induced infections) Internal drainage includes cystogastrostomy or cysto dudenostomy or Roux-en-Y cystojejunostomy

Slide 65:Pancreatic ascites initially managed my non operative methods includes decreasing pancreatic secretions by elemenation of enteral feeding,naso gastric drainage,anti secretory hormones like somatostatins are given. Persistent or recurrent ascites treated by pancreatic sphincterotomy Pancreatitis induced false aneurysms are treated by theraputic angiographic embolization

Specific Treatment :Specific Treatment Patients with severe gallstone-induced pancreatitis may improve dramatically if papillotomy is carried out within the first 36–72 h of the attack Finally, the treatment for patients with hypertriglyceridemia-associated pancreatitis includes (1) weight loss to ideal weight (2) a lipid-restricted diet (3) exercise (4) avoidance of alcohol and of drugs that can elevate serum triglycerides (i.e., estrogens, vitamin A, thiazides, and propanolol) (5) control of diabetes

bibilography :bibilography Gray’s Anatomy Guyton – text book of Medical Physiology Bailey & love’s – short practice of surgery , 24th & 25th edition Sabiston – Text book of surgery ,18th edition Schwartz – Principles of Surgery, 8th edition Current Surgical Therapy , 9th edition Sellisinger – text book of Gastroenterology Maingots – Abdominal Operations www.e-medicine . com

Thank you :Thank you Thank you