2 نام درس :بيمار يهاي پانكراس اهداف نام درس :بيمار يهاي پانكراس اهداف1-بيماري هاي پانكراس رابشناسد2-عوامل سبب زاي بيماري هاي پانكراس را بشناسد3- راه هاي پيشگيري بيماري هاي پانكراس را بداند.4- نحوه مراقبت بيماري هاي پانكراس را فراگيرد. (Surveillance)5-عوامل خطرزاي بيماري هاي پانكراس را بداند6- ويژگي هاي اپيدميولوژيك بيماري هاي پانكراس را بشناسد .7-روش هاي تشخیصی بيماري هاي پانكراس رابشناسد.8- روش هاي درمان را بداند.
3 Normal Anatomy & Physiology neutralize chymedigestive enzymeshormonesThe pancreas lies in the retroperitoneum nestled in the C-loop of the duodenum and posterior to the stomach.Physiologic function of the pancreas. Thehuman pancreas has three general functions:(1) neutralizing the acid chyme entering the duodenum from the stomach;(2) synthesis and secretion of digestive enzymes after a meal; and(3) systemic release of hormones that modulate metabolism of carbohydrates, proteins, and lipids.
4 Exocrine Function pancreatic enzymes common bile duct pancreatic duct BODYcommon bileductTAILHEADampullapancreatic ductTo understand pancreatitis, you need a basic understanding of pancreatic exocrine functionUNCINATEpancreatic enzymes
5 Enzyme Secretion acinus pancreatic duct microscopic view The pancreatic acinar cells are specialized cells which synthesize, store, and secrete digestive enzymesThese digestive enzymes are stored in zymogen granules (shown in blue) which serve as a compartment for inactive pro-enzymes thus preventing auto-activation.pancreatic ductmicroscopic viewof pancreatic aciniduodenum
6 Enzyme Secretion Neural Hormonal Secretin (hormonal) acetylcholine VIP GRPHormonalCCKgastrinEnzyme secretion is stimulated by neural pathways or by hormones with 2 most potent stimulators being CCK and secretin.The pancreatic fluid is rich in bicarbonate which makes it alkaline and the total daily volume is approx. 2.5 L.Secretin (hormonal)H2Obicarbonate
7 Digestive Enzymes in the Pancreatic Acinar Cell PROTEOLYTIC LIPOLYTIC ENZYMESENZYMES LipaseTrypsinogen Prophospholipase A2Chymotrypsinogen Carboxylesterase lipaseProelastaseProcarboxypeptidase A NUCLEASESProcarboxypeptidase B Deoxyribonuclease (DNAse)Ribonuclease (RNAse)AMYOLYTIC ENZYMESAmylase OTHERSProcolipaseTrypsin inhibitorThere are several different classes of digestive enzymes secreted by the pancreatic acinar cells. Most of these enzymes are proenzymes which are inactive with the exceptions of amylase and lipase.ProteinStarch and glycogenFatAmino acidsOther
8 Exocrine StimulationThe more proximal the nutrient infusion…the greater the pancreatic stimulation (dog studies)stomach – maximal stimulationduodenum – intermediate stimulationjejunum – minimal / negligible stimulationElemental formulas tend to cause less stimulation than standard intact formulasintact protein > oligopeptides > free amino acidsIntravenous nutrients (even lipids) do not appear to stimulate the pancreas
11 Clinical Case A man with acute onset abdominal pain h/o alcohol intake Or Gall stoneA 32-year-old man is admitted to the hospital with acute onset abdominal pain of presumed pancreatic origin.
12 Acute Pancreatitis Definition Acute inflammatory process involving the pancreasUsually painful and self-limitedIsolated event or a recurring illnessPancreatic function and morphology return to normal after (or between) attacksHere are the details…
17 Hereditary Pancreatitis Autosomal dominant with 80% phenotypic penetranceRecurrent acute pancreatitis, chronic pancreatitis, and 50-fold increased risk of pancreatic cancer
18 Pancreatitis Background Potentially fatalMortality – 10-15%Necrosis determines the prognosisAcute pancreatitis is a potentially fatal disease, with reported mortality rates ranging from zero to almost 25%, depending on severity. Severity itself depends greatly on whether or not pancreatic necrosis is present. Since majority of the patients with mild acute pancreatitis recover without any short term complications or long term sequelae. So majority of the studies have focussed on management of acute necrotizing pancreatitis. I would also
19 Background Mild AP (no necrosis) – 0% Sterile necrosis – 10% Infected necrosis – 25%Overall mortality: %Since majority of the patients with mild acute pancreatitis recover without any short term complications or long term sequelae. So majority of the studies have focussed on management of acute necrotizing pancreatitis. I would also
20 What do you think? Amylase or lipase Ultrasound or CT scan If yes, When?ICU or medical wardEnteral nutrition or TPNAntibioticsERCPSurgery
21 Epidemiology of acute pancreatitis There appears to be an increase in the incidence of acute pancreatitis.This rise attributed to increased alcohol consumptionNo seasonal or weeklyMen are affected much more than womenMain age group affected is 40–60 year olds.
22 Acute Pancreatitis Pathogenesis acinar cellinjuryfailed protective mechanismspremature enzyme activationtalk about failure of compartmentalization, premature activation, and overwhelming or absence of inhibitors
24 Acute Pancreatitis Pathogenesis premature enzyme activationautodigestion of pancreatic tissuelocalvascularinsufficiencyactivationof whiteblood cellsrelease of enzymes intothe circulationlocal complicationsdistant organ failure
25 Acute Pancreatitis Pathogenesis SEVERITYMildSevereSTAGE 1: Pancreatic InjuryEdemaInflammationSTAGE 2: Local EffectsRetroperitoneal edemaIleusSTAGE 3: Systemic ComplicationsHypotension/shockMetabolic disturbancesSepsis/organ failureThree stages of pathophysiology of acute pancreatitisThe pathophysiology ofacute pancreatitis can be considered as involving three stages. The first stageis pancreatic injury with edema, inflammation, necrosis of pancreatic fat, andvariable degrees of necrosis of pancreatic secretory cells. The second stage isspread of the inflammatory process to surrounding tissues, with development ofretroperitoneal edema, peripancreatic fat necrosis, and an ileus, with ;thirdspacing; of fluid and electrolytes in the gastrointestinal tract resulting inhemoconcentration (increased hematocrit). The third stage involves systemiccomplications, such as hypotension/shock, multiorgan system failure (eg,respiratory, renal), metabolic disturbances, such as hypoalbuminemia andhypocalcemia, and sepsis.
27 Pancreatitis Clinical Presentation Pain: Steady & severe in nature; located in the epigastric or umbilical region; may radiate to the back. Worsened by lying supine; may be lessened by flexed knee, curved-back position.Vomiting: Varies in severity, but is usually protracted, worsened by ingestion of food or fluid. Does not relieve the pain. Usually accompanied by nausea.
28 Pancreatitis con’t…… Fever: Rarely exceeds 39 C. Abdominal Finding: Rigidity, tenderness, guarding, distended Abd, decreased or absent peristalsis and paralytic ileus.Fatty stools-(steatorrhea)Laboratory Finding: Elevation of WBC count ,000. lipase and amylase(5 to 40 times); elevated(glucose, bilirubin, alkaline phosphatase.,Urine amylase).Abnormal low serum CA, Na & Mg.-due to dehydration. Binding of Ca in areas of fat necrosis.
41 Abdominal Exam Skin Exam Abdominal tenderness and rigidity Bowel sounds decreasedPalpable upper abdominal mass Acute fluid collections and pseudocystsSkin ExamErythematous skin Nodule (Subcutaneous Fat Necrosis)Cullen's Sign (periumbilical discoloration)Turner's Sign (flank discoloration) * due to exudation of blood-stained fluid into the subcutaneous tissue, usually 72 h into the illness.
44 Diagnosis: Biochemical Serum Amylase elevatedNonspecificReturns to normal in hoursNormal amylase does not exclude pancreatitisLevel of elevation does not predict disease severitySerum Lipase elevatedSpecific for pancreatic diseaseReturns to normal in 7-14 days
45 Diagnosis: Biochemical White Blood Cellsincreased to 15k-20kHypertriglyceridemia (15%)liver Function Tests(ALP) (AST) ,elevated(LDH) elevated (Poor prognosis)HyperglycemiaAlbumine(Poor prognosis)Serum ElectrolytesHypocalcemia (25%)
46 Acute Physiology And Chronic Health Evaluation Another criteria often used to assess the severity of pancreatitis is the (APACHE-II) .Acute Physiology And Chronic Health Evaluationage and vital signsSpecific laboratory parameters,Chronic health statusThe main advantage is the immediate assessment of the severity of pancreatitis.A score of eight or more at admission is usually considered indicative of severe disease
50 Glasgow Criteria Non-alcoholic Pancreatitis WBC > 15,000Glucose > 180BUN > 16Arterial PO2 < 60 mm HgCa < 8Albumin < 3.2LDH > 600 U/LAST or ALT > 200 U/L
51 Balthazar et al. Radiology 1990. CT Severity Indexappearancenormalenlargedinflamed1 fluid collection2 or more collectionsgradeABCDEscore1234necrosisnone< 33%33-50%> 50%score246So, even if we can’t identify severe cases sooner, the CT index appears to be the best way to judge severity.scoremorbiditymortality1-24%0%7-1092%17%Balthazar et al. Radiology 1990.
52 Useful markers of severe disease. Pleural effusionBMI (High body mass index)Necrosis on contrast-enhanced CT-SCANCRP level greater than 150 mg/L at 48 hInfection of the necrotic tissue after the first week of illness is the major determinant of later outcome.
54 CT-guided percutaneous fine-needle aspiration of the pancreatic tail
55 Immediate assessment Clinical assessment including great care to assess respiratory, cardiovascular and renal compromise.Organ failure ?BMI?. There is considerable risk (> 30 kg/m2) or much greater risk > 40 kg/m2Chest X-ray. Is there a pleural effusion present?CT.Scan Is there more than 30% of the volume of the pancreas malperfused?Scoring. Is it high score or low?
57 ResuscitationTransudation of fluid from the intravascular space to the peritoneum is the principle cause of hypovolemia in AP.Assessment of the patient’s volume status determined by heart rate, blood pressure, urine output and CVP line.
58 Treatment of Mild Pancreatitis Pancreatic restSupportive carefluid resuscitation – watch BP and urine outputpain controlNG tubes ,H2 blockers ,PPIs helpful??Refeeding (usually 3 to 7 days)bowel sounds presentpatient is hungrynearly pain-free (off IV narcotics)amylase & lipase not very useful heremild panc – support is all that’s neededhypotension probably predisposes to necrosis (poor microcirculation)
59 Treatment of Severe Pancreatitis Pancreatic rest & supportive carefluid resuscitation* – may require 5-10 liters/daycareful pulmonary & renal monitoring – ICUmaintain hematocrit of 26-30%pain control – PCA pumpcorrect electrolyte derangements (K+, Ca++, Mg++)Rule-out necrosiscontrasted CT scan at hoursprophylactic antibiotics if presentsurgical debridement if infectedNutritional supportmay be NPO for weeks, TPN*common serious error to underestimate volume needsmay need SG catheter – lookout for ARF or ARDSwe have impacted the early mortality by better support…late mortality still problem
60 AnalgesiaSevere pain should be treated with meperidine 50 to 100 mg IM q 3 to 4 h prn in patients with normal renal function (morphine causes the sphincter of Oddi to contract and should be avoided).
61 Antibiotic prophylaxis Infectious complications are still regarded as the primary cause of mortality in severe pancreatitis.Thus, it is essential to identify the presence of pancreatic necrosis and take measures to prevent infection.The current recommendation is the use of a systemic antibiotic such as imipenem-cilastatin 500 mg three times a day for 2 weeks in patients with documented pancreatic necrosis.
62 Role of ERCP in pancreatitis 1-Gallstone pancreatitisCholangitisObstructive jaundice2-Recurrent acute pancreatitisStructural abnormalitiesNeoplasmBile sampling for microlithiasis3-Sphincterotomy in patients not suitable for cholecystectomy
63 Reduced Oral Intake in Acute Pancreatitis Abdominal pain with foodNausea and vomitingGastric atonyIleusPartial duodenal obstruction
64 Summary1-The overall mortality ranges from 2 to 10%. The incidence in males is usually 10–30% higher than in females.2-The commonest cause is gallstones with alcohol being the next most common cause.3-Patients with acute pancreatitis present with upper abdominal pain and/or different degrees of organ failure.4-The diagnosis is suspected by a typical clinical presentation and supported by raised serum amylase. Atypical presentations may require confirmation by CT imaging.5-Immediate management comprises analgesics, intravenous fluids and monitoring.
65 6-Acute pancreatitis, severity best defined by failure of one or more organ systems and/or the Acute Physiology and Chronic Health Evaluation, (APACHE II) score of 8 or more.7-Gallstone etiology is usually identified by early routine abdominal ultrasonography.8-The majority of patients have mild pancreatitis and recover without additional treatment.9-In 20%, the disease is severe and is associated with a mortality of about 20%.10-Patients with severe pancreatitis require management in a high dependency or intensive care setting; this may require transfer to a specialized unit.11-Clinical severity is paralleled by the degree of pancreatic and peripancreatic tissue necrosis as defined by dynamic CT.12-Antibiotic prophylaxis is advised in patients with greater than 30% necrosis and imipenem is recommended currently.
66 12- Enteral nutrition probably retains the integrity of the intestinal mucosal barrier and hence early mesenteric feeding is recommended. Parenteral nutrition is rarely indicated.13- In patients with severe gallstone pancreatitis, early endoscopic retrograde cholangiography is indicated and, where appropriate, a sphincterotomy and clearance of the bile duct.14--Where infection of pancreatic necrosis is proved by the presence of positive FNA or free gas in the area of necrosis, surgical intervention is indicated.15--In sterile necrosis, continued conservative management is justified.16--Patients with gallstone pancreatitis should either undergo cholecystectomy or endoscopic sphincterotomy and bile duct clearance prior to discharge.17--Acute fluid collections are a feature of severe acute pancreatitis and often resolve spontaneously.18--Pancreatic and peripancreatic abscesses, symptomatic pseudocysts and other ductal disruptions require interventional treatment.
67 Factors Differentiating Mild from Severe Pancreatitis ParameterMildPancreatitisSevereAdmissions80%20%Pancreatic necrosisNoYesOral diet within 5 days0%Morbidity8%38%Mortality3%27%
68 Total Enteral Nutrition in Severe Pancreatitis may start as early as possiblewhen emesis has resolvedileus is not presentnasojejunal route preferred over nasoduodenallikely decreases risk of infectious complications by reducing transmigration of colonic bacteria
69 Conclusions ( MOUSE CLICK) Acute pancreatitis is a self-limited diseaseMost cases are mild.Gallstones and alcohol are the leading causes of acute pancreatitis.In mild pancreatitis, nutritional support is usually not requiredIn severe pancreatitis, nutritional support will likely be required with the enteral route preferred over TPN because of both safety and cost.
70 Evidence A. Proven B. Possible/ Probable C. Consensus > 2 well designed trials, randomizedB. Possible/ Probable1 well designed study, randomizedC. Consensusagreed opinion with no supportive evidence