Diseases of pancreas - Chronic pancreatitis

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1 Corso di laurea in Medicina e Chirurgia Anno accademico V Anno di corso- Primo Semestre Corso Integrato : Patologia Sistemica C- Gastroenterologia Prof. Stefano Fiorucci Diseases of pancreas - Chronic pancreatitis Harrison s Principles of Internal Medicine 18 or 19 Chapters and 292

2 Chronic pancreatitis Chronic pancreatitis (CP) is a progressive inflammatory disease of the pancreas, characterized by irreversible morphologic changes and gradual fibrotic replacement of the gland. Loss of exocrine and endocrine function results from parenchymal fibrosis. The primary symptoms of CP are abdominal pain and maldigestion.

3 Chronic pancreatitis Epidemiology The incidence of CP ranges from 1.6 to 23 cases per 100,000 population per year worldwide.

4 Regulation of Pancreatic Secretion Regulation of Pancreatic Secretion Vagal afferent FFA, peptides, amino acids, releasing peptides I-cells CCK Vagal efferent Acid, FFA, releasing peptides S-cells Secretin

5 Pancreatic Innervation Pancreatic Innervation Nucleus tractus solitarius Nodose ganglion Vagal efferent + Ach Vagal afferent Ach + + Ach Postganglionic (enteric) neuron Islet Acinus

6 Endocrine and Exocrine Pancreatic Secretion Endocrine and Exocrine Pancreas Secretion

7 Regional Differences in Islet Hormones Regional Differences in Islet Hormones Insulin Insulin Glucagon Head Glucagon PP Tail PP Somatostatin Somatostatin

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9 Alcholic pancreatitis

10 Chronic pancreatitis Heavy and prolonged alcohol use is a common cause of CP. In contrast to other causes, alcohol-related CP is associated with more-severe pain, extensive calcification and ductal changes, and more rapid progression to endocrine and exocrine insufficiency. Most patients experience recurrent episodes of acute pancreatitis for several years before CP develops. Interestingly, only 3% of alcoholics develop CP, implying the presence of cofactors that amplify the effect of alcohol. A high-fat diet and smoking might also contribute to pancreatic disease in alcoholics. Smoking adversely affects pancreatic bicarbonate and water secretion, induces oxidative stress, and increases the rate of pancreatic calcification.

11 Chronic pancreatitis Toxic Metabolic Table 1. TIGAR-O Etiologic Classification of Chronic Pancreatitis Idiopathic Genetic Etiologic Risk Factors Alcoholic Tobacco smoking Hypercalcemia Hyperlipidemia Chronic renal failure Tropical Cause unknown; likely genetic Autosomal dominant Cationic trypsinogen Autosomal-recessive/modifier genes CFTR mutations SPINK1 mutations Alpha-1-antitrypsin deficiency

12 Chronic pancreatitis Etiologic Risk Factors Autoimmune Isolated autoimmune chronic pancreatitis Associated with the following: Primary sclerosing cholangitis Sjögren's syndrome Primary biliary disorder Type 1 diabetes mellitus Recurrent and severe acute pancreatitis Postnecrotic (severe acute pancreatitis) Vascular diseases/ischemia Postradiation exposure Obstructive Pancreas divisum (controversial) Sphincter of Oddi dysfunction (controversial) Duct obstruction (tumors, posttraumatic) Table 1. TIGAR-O Etiologic Classification of Chronic Pancreatitis

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15 Alcohol

16 Alcohol

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22 Chronic pancreatitis Test Sensitivity Invasiveness, Risk Cost Comments US Reasonable screen Almost 100% specificity CT Detects advanced disease MRI/MRCP Assesses ducts and parenchyma Operator dependence Secretin enhancement may improve sensitivity EUS Assesses ducts and parenchyma Limited availability ERCP Detects early ductal changes Hormonestimulated PFT Traditional methods not widely available Endoscopic methods in development

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26 Chronic pancreatitis In chronic pancreatitis we need a test that allow the diagnosis and that also assess the severity of disease ( i.e. the severity of pancreatic insufficency)

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28 Pancreatic calcifications are strong predictor of reduced pancreatic function

29 Pancreatic calcifications are strong predictor of reduced pancreatic function

30 Chronic pancreatitis: US Poor accuracy for staging

31 Chronic pancreatitis: CT

32 Chronic pancreatitis: CT

33 Chronic pancreatitis: MR

34 Variations in Ductal Anatomy ERCP

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40 Chronic pancreatitis: US

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42 Chronic pancreatitis Pancreatic enzymes are used for the treatment of maldigestion in CP. Exogenous pancreatic enzymes are safe, are well tolerated, and produce few side effects. Pancreatic enzyme preparations differ based on enzyme content, the use of microspheres versus microtablets, and the presence of a coating for delayed release. Lipase is the most important determinant of the effectiveness of individual preparations. A minimum of 30,000 U lipase per meal allows adequate intraluminal digestion of fat and protein in most patients. The dose might need to be titrated to as much as 80,000 U lipase per meal, because not all the lipase may reach the proximal small intestine in active form.

43 Chronic pancreatitis Dosing of enzymes is most physiologic if one half the amount is taken at the onset of the meal and the other half is taken approximately 15 minutes into the meal. Because uncoated preparations are more easily denatured by gastric acid, acid suppression with a proton pump inhibitor (e.g., omeprazole 20 mg once daily) or histamine-receptor antagonist (e.g., famotidine 20 mg twice daily) is required

44 Chronic pancreatitis

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47 Medical treatment of pain

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50 Pancreatic Proteases Modulate the Effect of Releasing Factors on the CCK Cell CCK Release FFA AA Monitor peptide CCK-RP protease CCK cell CCK protease CCK cell CCK

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54 Endoscopic management: stones

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56 ERCP stenting

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61 Autoimmune pancreatitis

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63 Autoimmune pancreatitis

64 Autoimmune pancreatitis IGG4-related disease is a newly recognized fibroinflammatory condition characterized by tumefactive lesions, a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis, and, often but not always, elevated serum IgG4 concentrations. The disease was not recognized as a systemic condition until 2003, when extrapancreatic manifestations were identified in patients with autoimmune pancreatitis.

65 Autoimmune pancreatitis

66 Autoimmune pancreatitis

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68 Autoimmune pancreatitis

69 Autoimmune pancreatitis

70 Autoimmune pancreatitis

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78 AIP- Steroid therapy

79 Autoimmune pancreatitis Before steroid Steroid

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