Pancreatic Disorders Past Paper HY 2025-01 PDF

Exocrine pancreatic Disorders Gonzalez MD START  Content: Acute and chronic pancreatitis & Pancreatic adenocarcinoma Anatomy - Histology Management 01...

Exocrine pancreatic Disorders Gonzalez MD START  Content: Acute and chronic pancreatitis & Pancreatic adenocarcinoma Anatomy - Histology Management 01 05 Main concepts Prognosis 02 06 03 Histology 04 Patophysiology The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc  Objectives: Acute and chronic pancreatitis & adenocarcinoma 1. Enumerate the multifactorial etiology of pancreatic pathologies (acute and chronic pancreatitis and adenocarcinoma. 2. Elucidate the intricate pathophysiology underlying prevalent pancreatic disorders. 3. Examine the clinical significance of intricate genetic and environmental risk factors in pancreatic neoplasms. 4. Formulate a di erential diagnosis. 5. Appraise the e icacy of curated current therapeutic approaches for pancreatic disorders. Resources (Exam focus) Pathophysiology - Histopathology Clinical setting Main Focus : Exocrine pancreas In ammation: Neoplasia: acute & chronic adenocarcinoma Pancreas: Macroscopic view Lobular architecture. Adjacent adipose tissue and lymph nodes are surrounding the pancreas in the retroperitoneum. The lesser omental sac is posterior to the pancreas. WELLL-DEFINED OUTER BORDERS The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc Anatomy (micro): The Exocrine pancreas The exocrine pancreas accounts for about 85% of the pancreatic mass 10% extracellular matrix 4% blood vessels and the major ducts 2% endocrine tissue The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc  The pancreas: Histology The functional unit of the exocrine pancreas is the acinus (digestive enzimes) The pancreas is composed of ʻberry-likeʼ clusters of acinar cells, connected by intercalated ducts (merge to form interlobular and the main pancreatic duct) About 40 acinar cells are arranged into a spherical acinus. The acinar cells are triangular in shape with the apex opening into a duct. The pancreatic duct delivers exocrine secretions into the duodenum One of the most important role of the ducts is bicarbonate secretion The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc  Pancreatic juice Exocrine pancreas produce 2~3 L/day of juice, which is alkaline (pH 8.0-8.3) and isotonic The large amounts of NaHCO3 (90 mmol/L at rest, 140 mmol/L a er a meal) are secreted by the centroacinar cells (exchanging chloride for bicarbonate via the CFTR chloride channel). Rich in enzymes (amylase, lipase, trypsin, elastase, nucleases) and proenzymes millimoles per litre. The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc Pancreatic exocrine secretion: Stimulants Vago-pancreatic reflex and acetylcholine are the primary mechanism by which exocrine secretion occurs ****Note: CCK is released from specialized enteroendocrine cells (I cells) in the upper small intestine depending on protein concentration The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc  C12 and C18 fatty acids Palmitic acid Estearic acid Caproic acid The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc Pancreatic exocrine secretion: inhibitors The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc Pancreatic exocrine secretion: Stimulators vs inhibitors The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc Acute pancreatitis  Acute pancreatitis A complex, progressive and destructive inflammatory disease of the pancreas (systemic-remote organs) with a high risk of morbidity and mortality. The third most common indication for hospital admission among GI diseases. 20% of patients with a first episode of AP develop recurrent acute pancreatitis, and 3–35% of patients will progress to chronic pancreatitis. 30% develops a severe form with multiple organs dysfunction and necessity of intensive care unit admission. First 24-48 hours: Cytokine storm & multiorgan dysfunction Recognizing patients with severe acute pancreatitis as soon as possible is critical for achieving optimal outcomes. The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc  Acute pancreatitis: Diagnostic criteria (Atlanta Classi cation) Diagnostic criteria requires two of the following three diagnostic criteria to be fulfilled: (I) Persistent and severe abdominal pain, o en radiating to the back (II) A threefold increase in serum lipase and/or amylase above the upper limit of the normal value (III) Typical imaging manifestations of AP (CT scan) *** Abdominal pain of the epigastrium, of the "belt" type that radiates also posteriorly The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc  Acute pancreatitis: Diagnostic criteria (Atlanta Classi cation) A 69 year-old woman, was stung in the right hand by a scorpion, which had been brought by the patient and been identified as a Tityus stigmurus, one of the most prevalent in Brazil. The time elapsed until emergency admission was about five hours a er the sting and she reported severe epigastric pain 10/10 radiating to the back, one episode of emesis and sweating. Upon admission, the patient presented a compromised general condition, lowered consciousness level. Laboratory findings: The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc Etiology:  Etiology The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc Etiopathogenesis: Biliary pancreatitis These events include increased intraductal pressure, ductal cell exposure to bile acids and intraductal acidification. Bile acids decrease the aquaporins amount within the ductal cells (intraductal fluid stasis) The mechanoreceptor PIEZO1 in the acinar cells triggers the pathological calcium signalling. Examples of ductal hypertension include: Papillary oedema, acidic contrast injection into the pancreatic duct during ERCP and gallstone obstruction of the duct. The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc  Alcoholic pancreatitis Alcohol inhibits apical secretion and instead promotes basolateral secretion, lipase is freely released into the interstitium. The alcohol metabolism in acinar cells converts alcohol to fatty acid ethyl ester, acetaldehyde and ROS that can destabilise lysosome and ZG membranes. Fatty acid ethyl esters cause loss of ATP synthesis in acinar cells A high drinker was defined as one who has drunk at least 40 g/d (20 g/d for female) for over 5 years. Patients drinking small quantities of alcohol (1–20 g per day) run a higher risk of developing chronic pancreatitis. The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc  Diet and obesity Maximal pancreatic enzyme output: following a mixed meal of 20 kcal/kg body weight (no more than 15–30 grams of protein at each meal with a maximum of 100g/d) Those more than 40 grams (+ 20% total calories from proteins)— in one sitting may hyperstimulate the exocrine pancreas secretion (ER stress). The ketogenic dietary regimen mandates a limitation of carbohydrate intake to 5-10% and a fat composition of 70-75% along with 20-25% of protein intake Obesity may increase insulin resistance (hypersinulinemia) wich causes ER Exhaustion The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc  Smoking Risk of AP increases 2 fold with at least 20 pack years of cigarette smoking Smoking increases the risk of recurrent acute pancreatitis and CP Those with a history of >35 pack years of cigarette smoking are 4.6 fold more likely to develop CP It increases the risk of pancreatic cancer up to 6-fold depending on the duration and intensity of smoking Nicotine exposure, at low concentrations (100 µM) augments this CCK- induced amylase secretion (ER stress) The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc Drug-induced acute pancreatitis The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc Acute pancreatitis: Evolution The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc Acute pancreatitis: Evolution The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc Acute pancreatitis: Cytokine Storm - DAMPs + NF-KB pathway The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc  Acute pancreatitis: Evolution - SIRS The dysregulated AKI cytokine storm can + cause a massive ARDS inflammatory + cascade leading to Liver failure reversible or + irreversible end- Heart failure organ dysfunction + and even death Encephalitis The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc  Perpetuation of the disease Hypovolemia from vomiting, diarrhea, anorexia, substantial third space fluid loss occurs Ischemia of the intestine increases with increased rate of apoptosis of enterocytes and resultant bacterial translocation The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc Histopathology (macroscopy) Yellow-tan foci of fat necrosis. There is some edema. http://www.patologia.cm.umk.pl/atlas/endocrine/pancreas/acute/ Diagnostic approach Abdomen CT scan  Necrotizing pancreatitis Pancreas is necrotic and swollen with marked peripancreatic fat stranding, localized collection seen related to the pancreatic tail with air foci inside. Scoring Systems for prediction of severity The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc  Management Fluid resuscitation: (10 ml/kg bolus in case of hypovolemia, followed by 1.5 ml/kg/h) Pain management: multimodal approach (paracetamol, metamizole and simple opiates/epidural analgesia) Prophylactic antibiotics: Carbapemens Infected necrosis: Drainage  Management Nutrition (elemental diet): Energy requirements: +15-35 kcal/kg/day Glucose supply: 3 to 6 g/kg/day (associated with insulin in order to maintain blood concentrations < 10 mmol/l) Protein requirements: 1.2-1.5 g/kg/day and can reach 1.8 g/kg/day in cases with severe catabolism.  Chronic pancreatitis  Full recovery is observed in most patients with acute pancreatitis, whereas in chronic pancreatitis, the primary process is irreversible inflammation (monocyte and lymphocyte) that leads to fibrosis with calcification The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc  Etiopathogenesis AAlcohol and smoking together increase the risk of chronic pancreatitis as they o en coexist. Those who smoke less than one pack per day have a 2 fold risk of chronic pancreatitis those who smoke more than one pack per day have a 3 fold risk those with more than 35 smoking pack year history (which is equal to the number of packs per day times the years) have a 13 fold risk of chronic pancreatitis Continued smoking a er the development of chronic pancreatitis speeds up the progression of the disease Genetic mutations and cystic fibrosis can cause acute recurrent pancreatitis or may cause chronic pancreatitis The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc  Morphological triad The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc  Ductal adenocarcinoma  Ductal adenocarcinomas The most common cancer of the pancreas occurs in the exocrine portion (ductal adenocarcinoma) Fourth leading cause of cancer related deaths in the U.S. An invasive pancreatic epithelial neoplasm with glandular (ductal) di erentiation, Poor prognosis: It is one of the most lethal human cancers (a 5-year survival rate of less than 7%) , and a great proportion of patients die within 6 months a er diagnosis. Head of the pancreas: 60 - 70%; body: 5 - 15%; tail: 10 - 15% Head tumors: 50% have distention of biliary tree and progressive jaundice Metastases: Local lymph nodes (75%) Liver, lung, peritoneum, adrenal, bone, distal nodes KRAS mutation is the most frequent mutation (more than 90%). It is a member of the RAS gene family located at chromosome 12p12.1 which regulates cell proliferation, di erentiation, and apoptosis. The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc  Ductal adenocarcinomas Risk factors: 1. Smoking 2. Alcohol abuse 3. Obesity 4. High intake of dietary saturated fat 5. Chronic pancreatitis 6. Diabetes. 7. Peutz-Jeghers syndrome 8. Hereditary pancreatitis, 9. Familial atypical multiple mole melanom 10. Lynch syndrome 11. Familial breast cancer The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc  Ductal adenocarcinomas Clinical features: back pain, weight loss, malaise, jaundice, diabetes Trousseau sign: migratory thrombophlebitis in 10% due to tumor necrosis Coexisting pancreatitis in 10% Laboratory Serum tests: CA19-9 detection Radiology description: Double duct sign (dilation of both the biliary and pancreatic ducts) in pancreatic head mass Most (85%) tumors are not amenable to curative surgery Palliative treatment: bypass operations, chemotherapy and radiation therapy The World Society of Emergency Surgery (WSES) guidelines for the management of severe acute pancreatitis. 2019. Advances in acute pancreatitis. Co-critical Care Review. 2021 Wolters Kluwer Health, Inc [email protected]