Chronic pancreatitis (2) etiology pathogenesis management.pptx

Chronic pancreatitis..etiology pathogenesis

1. Chronic pancreatitis Naveen 1

2. Anatomy of pancreas Physiology of pancreas ; exocrine and endocrine Definition Etiology Pathogenesis Clinical features Investigations Medical therapy Surgical therapy 2

3. It lies in the transpyloric plane(L1) Retroperitoneal organ Surgical anatomy 3

4. Anterior Relations: From right to left: Transverse colon Attachment of the transverse mesocolon Lesser sac Stomach 4

5. Posterior Relations From right to left Bile duct Portal and Splenic veins Inferior vena cava Aorta Origin of the superior mesenteric artery Left psoas muscle Left suprarenal gland Left kidney Hilum of the spleen 5

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7. Head of the pancreas and duodenum The head of the pancreas adheres to the duodenal loop. Osler offers a very poetic description of this junction: "The abdominal area of romance where the head of the pancreas lies folded in the arms of the duodenum." 7

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9. Body of pancreas Anterior surface double layer of peritoneum of omental bursa separating stomach from pancreas Posteriorly,it is related to aorta origin of superior mesentric artery left crus of diaphram left kidney & its vessels 9

10. Duct of Wirsung : The main pancreatic duct Arises :in the tail of the pancreas Terminates : at the papilla of Vater in the duodenum . It is usually only 2 to 3 mm in diameter and runs midway between the superior and inferior borders of the pancreas , usually closer to the posterior than to the anterior surface . 10

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12. Ampulla of Vater Vs papilla of vater There is confusion between definitions of the terms papilla and ampulla of Vater . The so-called papilla of Vater , which should be called the major duodenal papilla , is a nipplelike formation and projection of the duodenal mucosa through which the distal end of the ampulla of Vater passes into the duodenum. The ampulla of Vater ( hepatopancreatic ), with its several formations, is the union of the pancreaticobiliary ducts. 12

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14. Pressure inside the pancreatic duct is about twice that in the common bile duct, which is thought to prevent reflux of bile into the pancreatic duct. Duct of Santorini : The minor or accessory pancreatic duct, it is smaller than the main duct. It extends from the main duct to enter the duodenum at the lesser papilla which lies about 2 cm proximal and slightly anterior to the major papilla . 14

15. Variations in the relation of the common bile duct and main pancreatic duct at the main duodenal papilla. (a) common channel between the ducts, (b) partial common channel, (c) separation of the two channels. Gallstone pancreatitis is more likely with (a) and (b). 15

16. Sphincter of oddi The smooth muscle fibers around the ampulla form the sphincter of Oddi. It controls the flow of pancreatic and biliary secretions into the duodenum. Contraction and relaxation of the sphincter is regulated by complex neural and hormonal factors. 16

17. Sphincter of Boyden -- Sphincter of the common bile duct. Sphincter of Oddi -- Sphincter of the hepatopancreatic ampulla. Sphincter of Helly – Sphincter of the duct of santorini. 17

18. Blood supply to papilla Posterior superior pancreaticoduodenal artery crosses bile duct and gives rise to dorsal and ventral branches. These join to form arterial plexus of papillae. The incision for endoscpic papillotomy should be at 10 o'clock to 11 o'clock with an approximate length of 5 to 8 mm to avoid bleeding complications 18

19. Arterial supply "The most important pancreatic artery is the splenic artery“. The pancreas is supplied by branches arising from the celiac trunk and the superior mesenteric artery . Blood supply to the B cells and the rest of the parenchyma 19

20. The head of the pancreas and the concave surface of the duodenum are supplied by Two pancreatico duodenal arterial arcades. They are the chief obstacles to complete pancreatectomy without duodenectomy. 20

21. Venous Drainage In general, the veins of the pancreas parallel the arteries and lie superficial to them. The drainage is to the Portal vein, Splenic vein, Superior mesenteric vein, Inferior mesenteric vein. 21

22. Four pancreaticoduodenal veins form venous arcades draining the head of the pancreas and the duodenum. The ASPD vein joins the right gastroepiploic vein. The PSPD vein enters the portal vein above the superior margin of the pancreas. 22

23. Surgical applications The veins of the pancreatic parenchyma are located between the ducts above and the arteries below . The superior and inferior pancreaticoduodenal arteries should not be ligated until the neck of the pancreas can be elevated from the underlying vessels. Premature ligation could cause necrosis of the head of the pancreas and duodenum. 23

24. Injury may occur to the ASPD artery during the Puestow side-to-side pancreatojejunostomy . Pancreatic veins enter the lateral side of the portal vein or SMV. There are usually no branches on the anterior surface of the portal vein. 24

25. Nerve supply to pancreas Innervation of the pancreas occurs by : the sympathetic division of the autonomic nervous system through the splanchnic nerves and by the parasympathetic division through the vagus nerve. The nerves generally follow blood vessels to their destinations. 25

26. Nerve supply Both the sympathetic and parasympathetic divisions provide efferent (motor) fibers to: the wall of the blood vessels, the pancreatic duct, and pancreatic acini . Further, both contain visceral afferent (pain) fibers. 26

27. definition Hallmark persistent and progressive fibrosis of pancreas resulting in loss of both exocrine and endocrine activity with pancreatic atrophy of parenchyma 27

28. 28 Etiology Gallstones Pancreatic stones Hereditary tropical Autoimmune Genetic causes Congenital Cystic fibrosis Hyperlipidemia Hyperparathyroidsm 60% <20%

29. Multiple hit theory Multiple episodes of the acute pancreatitis cause progressively more organized inflammatory changes that ultimately result in chronic inflammation and scarring. 29

30. 30 Newer classification TIGAR-O

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32. pathogenesis of chronic pancreatitis Oxidative stress theory Stone and duct obstruction theory SAPE hypothesis 32

33. Alcohol  inc.total protein conc . in pancreatic juice causes synthesis and secretion of lithostathine by acinar cells Protein precipitation occursprotein plugs are formedfinally stones in the pancreatic duct autodigestion 33

34. 34 How alcohol increases lithogenecity? Hyper secretion of enzymes & Proteins Decreases bicarbonate & water secretion Decreases citrate concentration Decreases synthesis of PSP ( Lithostatin )

35. 35 Oxidative Stress theory Over activity of hepatic Mixed function oxidases Generates reactive byproducts Oxidative Damage to Pancreas Via Systemic circulation or Bile reflux Substrates like fats inducers like alcohol

36. Stone and duct obstruction theory Pancreatic stone formation Pa ncreatic stones are composed largely of : calcium carbonate crystals trapped in a matrix of fibrillar and other material Pancreatic stone protien / lithostathine 36

37. Pancreatic stone protein / lithostathine Potent inhibitor of calcium carbonate crystal formation at conc. Of 0.1micromol/l In pancreatic juice  20-25micromol/lit In alcoholics  lithostathine expression and secretion are dramatically inhibited In addition ,precipitated lithostathine is elevated 37

38. 38 The SAPE Hypothesis Normal Recovery Chronic pancreatitis SAPE SAPE = Sentinel acute Pancreatitis event Massive inflammatory response Release Cytokines TGF- B 1 Profibrotic cells Fibrosis

39. Hyperparathyroidism Hypercalcemia  pancreatic hypersecretion chronic hypercalcemia  chronic calcific pancreatitis. Hypercalcemia is also a stimulant for pancreatic calcium secretion  calculus formation and obstructive pancreatopathy 39

40. Hyperlipedemias what type Hyperlipidemia and Hypertriglyceridemia when they receive estrogen replacement therapy. Fasting triglyceride levels less than <300 mg/dl Mechanism of action unknown Aggressive therapy of hyperlipidemia is therefore important in peri - or postmenopausal patients who are candidates for estrogen therapy. 40

41. CLASSIFICATION BY SINGER AND CHARI 41

42. Tropical (nutritional) pancreatitis Seen in developing countries Classic triad abdominal pain,steatorrhea,diabetes Pancreatic duct stones wil be hallmark Pts will be malnourished,extreme emaciation,cyanotic colouration of lips 42

43. hereditary tropical pancretitis Clinically, tropical pancreatitis presents much like hereditary pancreatitis Recently an association with mutations of the pancreatic secretory trypsin inhibitor (PSTI) or SPINK1 gene in patients with tropical pancreatitis has been reported. 43

44. The accelerated deterioration of endocrine and exocrine function, the chronic pain due to obstructive disease, and the recurrence of symptoms despite decompressive procedures characterize the course of disease 44

45. Hereditary pancreatitis 45

46. Autoimmune pancreatitis 46

47. Etiology of pain Three possible etiologies. Ductal hypertension , due to strictures or stones, that is initiated or aggrevated by eating Chronic pain without exacerbation may be related to parenchymal disease or retroperitoneal inflammation with persistent neural involvement. . 47

48. Acute exacerbations of pain in the setting of chronic pain may be due to acute increases in duct pressure, or recurrent episodes of acute inflammation in the setting of chronic parenchymal disease. 48

49. steady, boring type not colicky hrs or days exacerbated by drinking eating chronic alcoholics  typically flex their abdomen anorexia m/c associated 49

50. Progression of disease &pain “BURNED OUT PANCREAS” There is development of narcotic addiction, inability to work, sequele of chronic illness 50

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52. Malabsorption and weight loss When pancreatic exocrine capacity falls below 10% of normal, diarrhea and steatorrhea develop . Stool  bulky,foul smelling ,loose ,typically floats on toilet wter In severe steatorrhea , an orange, oily stool is often reported. As exocrine deficiency increases, symptoms of steatorrhea are often accompanied by weight loss. 52

53. Weight loss Lipase deficiency tends to manifest itself before trypsin deficiency, so the presence of steatorrhea may be the first functional sign of pancreatic insufficiency . As pancreatic exocrine function deteriorates further, the secretion of bicarbonate into the duodenum is reduced, which causes duodenal acidification and further impairs nutrient absorption . 53

54. Pancreatogenic (type III ) diabetes Frank diabetes is seen initially in about 20% of patients with chronic pancreatitis, and Impaired glucose metabolism can be detected in up to 70% of patients. 54

55. Brittle diabetes Apancreatic diabetes is more common after surgical resection Distal pancreatectomy and whipple’s procedure have higher incidence of diabetes Loss of functioining pancreatic tissue ,there is global defeiciency of all 3 glucoregulatory hormone : insulin,glucagon , pancreatic polypeptide pathognomic signs of apancreatic diabetes 55

56. Pancreatic polypeptide defeciency correletes with severity of chronic pancreatitis & impairments in hepatic action of insulin are reversed by administration of pancretic polypeptide 56

57. Measurement of pacreatic secretory products Measurement of pancreatic products in blood   A.    Enzymes   B.    Pancreatic polypeptide 57

58. Measurement of Exocrine secretion Measurement of pancreatic exocrine secretion   A.    Direct measurements   1.    Enzymes   2.    Bicarbonate   B.    Indirect measurement   1.    Bentiromide test   2.    Schilling test   3.    Fecal fat, chymotrypsin , or elastase concnentration   4.    [ 14 C]- olein absorption 58

59. Role of imaging in CP Imaging is helpful in : (1) diagnosis, (2) the evaluation of severity of disease, (3) detection of complications, and (4) assistance in determining treatment options. 59

60. Ultrasonography TAUS used as a screening method for pts with abdominal symptoms The extension of ultrasonic imaging to include endoscopic ultrasound (EUS) and laparoscopic ultrasound (LUS) have resulted in the highest-resolution images that are capable of detecting very small (<1 cm) abnormalities in the pancreas. 60

61. Cambridge classification of morphology in CP 61

62. cambridge classification morphology in cp classification ERCP FINDINGS CT & US FINDINGS NORMAL No abnormal SBDs Normal gland size ,shape ;homogenous parenchyma equivocal MPD normal <3 abnormal SBD ; MPD 2-4mm ; heterogenous parenchyma 62

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64. EUS in chronic pancreatitis Endoscopic ultrasound (EUS) of chronic pancreatitis. The EUS appearance of the parenchyma is heterogenous , and dilated ducts are seen, indicating early obstructive pancreatopathy . 64

65. CT findings in CP CT can detect: Duct dilatation, calculous disease, cystic changes, inflammatory events, and Anomalies with a resolution of 3 to 4 mm CT scanning has a false-negative rate of less than 10% for chronic pancreatitis, but early or mild chronic disease may go undetected by CT imaging. The earliest changes are dilatation of secondary ducts and heterogeneous parenchymal changes, A dilated pancreatic duct is seen, with evidence of intraductal stones and parenchymal calcification 65

66. MRI in Chronic pancreatitis MRI, can disclose fluid-filled ducts and cystic lesions, have added greatly to the imaging options for chronic pancreatitis . The resolution of cross-sectional MRI scanning is now approaching that of CT scanning. A dilated pancreatic duct suggests obstructive pancreatopathy due to proximal scarring. 66

67. ERCP ERCP is considered to be the gold standard for the: diagnosis and staging of chronic pancreatitis. It also serves as a vehicle that enables other diagnostic and therapeutic maneuvers, such as biopsy or brushing for cytology, or the employment of stents to relieve obstruction or drain a pseudocyst Unfortunately, ERCP also carries a risk of procedure-induced pancreatitis that occurs in approximately 5% of patients. stent is placed in the proximal pancreatic duct to relieve obstruction and reduce symptoms of pain. Pancreatic duct stents are left in place for only a limited time to avoid further inflammation. 67

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69. Endoscopic stenting Pancreatic duct stenting is used for treatment of: proximal pancreatic duct stenosis , decompression of a pancreatic duct leak, and for drainage of pancreatic pseudocysts that can be catheterized through the main pancreatic duct Options for transpapillary placement include placement of the stent ( A ) beyond the point of duct disruption, ( B ) at the point of disruption, or ( C ) proximal to the point of duct disruption 69

70. Treatment of pain in Chronic pancreatitis what type of pancreatic enzymes are used for pain relief and what type uses for steatorrhea 70

71. Treatment of CP Medical therapy: Analgesics Enzyme therapy Anti- secretary agents Neurolytic therapy Endoscopic therapy Surgical therapy 71

72. Treatment of chronic pancreatitis The medical treatment of chronic or recurrent pain in chronic pancreatitis requires: the use of analgesics, a cessation of alcohol use, oral enzyme therapy, and the selective use of antisecretory therapy. Interventional procedures to block visceral afferent nerve conduction or to treat obstructions of the main pancreatic duct. 72

73. Enzyme therapy Pancreatic enzyme administration serves to reverse the effects of pancreatic exocrine insufficiency, and may reduce or alleviate the pain Enzyme preperations : Non enteric coated preperations Enteric coated preperations 73

74. Non enteric coated enzyme preps Mechanism of pain relief Conventional (non-enteric-coated) enzyme preparations are partially degraded by gastric acid, are available within the duodenal and jejunal regions to bind to cholecystokinin (CCK)-releasing peptide, and downregulate the release of CCK. This theoretically serves to reduce the enteric signal for pancreatic exocrine secretion, which reduces the pressure within a partially or completely obstructed pancreatic duct dose and cost 74

75. Anti secretary therapy Somatostatin administration has been shown to inhibit pancreatic exocrine secretion and CCK release Patients who had the best results were patients with chronic abdominal pain, suggestive of obstructive pancreatopathy it remains unclear what subgroups of patients, or what dose of octreotide , might be beneficial in the treatment of pain. Anecdotal 75

76. Neurolytic therapy A recent trial of EUS-guided celiac plexus blockade revealed successful pain relief in 55% of patients, but the benefit lasted beyond 6 months in only 10% of patients. The procedure therefore appears safe, but the effect is short lived in those patients who obtain pain relief 76

77. Surgical therapy 77

78. Surgical option surgery should be considered only when the medical therapy of symptoms has failed. The role of surgery in the treatment of chronic pancreatitis, and its timing, is now based on the elucidation of pancreatic ductal disease. the progression of chronic obstructive pancreatitis could be delayed or prevented by pancreatic duct decompression. 78

79. Indications of surgery Intractable pain Pancreatic ductal stenosis Biliary obstruction (Wadsworth syndrome) Duodenal obstruction Left sided portal hypertension from splenic vein thrombosis 79

80. Pseudocyst Pancreatic ascites Pancreatic fistula Pancreatic carcinoma 80

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82. Sphincteroplasty Transduodenal sphincteroplasty with incision of the septum between the pancreatic duct and common bile duct appears to offer significant relief for patients with obstruction and inflammation isolated to this region 82

83. Drianage procedures( puestow procedure) Main pancreatic duct dilation 6mm decompression of pancreatic duct Done secondarily to stones or strictures Described as chains of lakes 83

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89. Resection procedures Distal pancreatectomy Indicated in patients with focal inflammatory changes localised to body and tail and no significant duct dilation exists 89

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91. Whipple’s procedure Chronic pancreatitis complicated by Inflammatory mass in the pancreatic head Stenosis of CBD Multiple stenoses and dilatations of PMD Severe narrowing of peripapillary duodenum, causing gastric outlet syndrome advantages and disadvantages 91

92. Pancreas divisum , causing CP or recurrent acute pancreatitis Intraductal , papillary mucinous tumor in pancreatic head Mucinous cystic tumor in pancreatic head Large (>2 cm) endocrine neoplasia in pancreatic head 92

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94. Pylorus preserving pancreaticoduodenectomy 94

95. Hybrid procedures Duodenum preserving subtotal /total pancreatic head resection advantages and disadvantages 95

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100. Frey’s procedure local resection of the pancreatic head with longitudinal pancreaticojejunostomy (LR- LPJ)  which included excavation of the pancreatic head including the ductal structures in continuity with a long dichotomy of the dorsal duct 100

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102. Organ preserving pancreatic head resection Excavation of central portion of pancreatic head with lateral pancreaticojejunostomy without involving duct 102

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105. PPPD DPPHR PAIN RELIEF IS SAME FOR BOTH SHORTER HOSPITAL STAY , GREATER WEIGHT GAIN LESS POST-OP DIABETES LESS ENDOCRINE DYSFUNCTIO 105

106. PPPD LR-LPJ PAIN RELIEF IS SAME FOR BOTH LOW POST OPERATIVE COMPLICATION RATE , BETTER QUALITY OF LIFE 106

107. Islet cell transplantation Islet cell transplantation for the treatment of diabetes is an attractive adjunct to pancreatic surgery in the treatment of benign pancreatic disease Although 2 to 3 million islets are required for successful engraftment in an allogeneic recipient, the autotransplant recipient can usually achieve long-term, insulin-independent status occurs after engraftment of only 300,000 to 400,000 islets 107

108. Denervation procedures In patients : who have persistent and disabling pain, but who are poor candidates for resection or drainage procedures, a denervation procedure may provide symptomatic relief. neural ablation is a valid treatment strategy to block afferent sympathetic nociceptive pathways 108

109. True dennervation procedures include operative celiac splanchnicectomy , Transthoracic splanchicectomy with or without vagotomy Videoscopic transthoracic splanchnicectomy 109

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111. Treatment of CP Medical therapy: Analgesics Enzyme therapy Anti- secretary agents Neurolytic therapy Endoscopic therapy Surgical therapy 111

112. Treatment of chronic pancreatitis The medical treatment of chronic or recurrent pain in chronic pancreatitis requires: the use of analgesics, a cessation of alcohol use, oral enzyme therapy, and the selective use of antisecretory therapy. Interventional procedures to block visceral afferent nerve conduction or to treat obstructions of the main pancreatic duct. 112

113. Ch pancratitis is a progressive disease with remissions and exacerbations Self limiting when the whole of the pacreatic parenchyma atrophies and disappears 113