Downloaded 323 times
More Related Content
Exocrine pancreas
- 1.
- 4. Anatomy Pancreas –“all flesh” Transversely oriented retroperitoneal organ Extending from “C”loop of duodenum to the hilum of spleen Measures 20 cm in length Weighs 90gms in men,85gms in women.
- 5. 3 parts Head Body Tail
- 6. Pancreatic duct system Highly variable. Main pancreatic duct –duct of Wirsung- papilla of Vater. Accessory pancreatic duct –duct of Santorini- minor papilla MPD merges with CBD to form ampulla of Vater.
- 7. Embryology From fusionof dorsal & ventral outpouchings of foregut. Dorsal primordium- body,tail superior aspect of head & accessory duct. Ventral primordium- inferior part of head, major duct.
- 8. Functional Anatomy Complexlobulated organ Distinct exocrine & endocrine components Exocrine -80 to 85% of pancreas. Endocrine- 1 to 2% Exocrine-acinar cells & a series of ductules & ducts Endocrine- about 1million clusters of cells- islets of Langerhans
- 9. Histology Acinar cells-pyramidally shaped epithelial cells radially oriented around a central lumen. Basal portion-deeply basophilic-abundant ER. Supranuclear golgi complex Membrane bound zymogen granules-granular eosinophilic appearance to the apices. Smaller ductules-lined by cuboidal cells-secrete fluid rich in bicarbonate. Larger ducts-columnar cells –mucin-express cystic fibrosis trans membrane conductance regulator
- 11. Physiology Secretes 2to 2.5 liters of bicarbonate rich fluid-digestive enzymes & proenzymes Neural stimulation- vagus nerve Humoral factors-secretin & cholecystokinin. Secretin-water & bicarbonate Cholecystokinin-digestive proenzymes
- 12. Proenzymes Trypsinogen Chymotrypsinogen Procarboxypeptidase Proelastase Kallikreinogen Prophospholipase A & B Enteropeptidase –cleaves trypsinogen to trypsin
- 13.
- 14. Prevention of selfdigestion Inactive proenzymes Sequestered in zymogen granules Activation requires duodenal enteropeptidase Trypsin inhibitors –SPINK 1- present in acinar cells Trypsin –critical self recognition site-allows trypsin to inactivate itseif. Lysosomal hydrolases-degrade zymogen granules when secretion is blocked Acinar cells –resistant to trypsin, chymotrypsin & phospholipase A 20.
- 15. Pathology –exocrine pancreas Congenital anomalies Acute pancreatitis Chronic pancreatitis Neoplasms
- 16. Congenital anomalies Agenesis veryrare associated with severe malformations incompatible with life Germline mutations in homeodomain transcription factor –IPF 1 gene on chromosome 13q 12.1
- 17. Pancreas divisum Mostcommon clinically significant anomaly. Incidence- 3 to 10% Failure of fusion of fetal duct system of dorsal & ventral primordia. Bulk of the pancreas -dorsal duct & diminuitive minor papilla. Main duct is very short Relative stenosis- predisposes to chronic pancreatitis
- 18. Annular pancreas Relativelyuncommon condition Associated with other anomalies Band like ring of normal pancreatic tissue completely encircling 2nd portion of duodenum May present early in life or in adults Signs & symptoms of duodenal obstruction.
- 19.
- 20. Ectopic pancreas Presentin 2% of careful routine autopsies Favoured sites- stomach,duodenum jejunum,Meckel diverticula & ileum. Few mms to cms in size & situated in the submucosa. Composed of normal appearing pancreatic acini & glands ; occasionally islet cells. Usually incidental sessile mass cause pain from local inflammation may incite mucosal bleeding islet cell tumor -2%
- 21. Acute pancreatitis Agroup of reversible lesions Characterised by inflammation of the pancreas. Ranging in severity from edema & fat necrosis to parenchymal necrosis with severe hemorrhage.
- 22. Acute pancreatitis Relativelycommon Incidence – 10 to 20 cases per 100,000 people annually. 80% cases are associated with either biliary tract disease or alcoholism. M :F is 1:3 in biliary tract diseases & 6:1 in alcoholism.
- 23. Etiologic factors Metabolic alcoholism hyperlipoprotinemia hypercalcemia drugs genetic Mechanical trauma gall stones periampullary tumors,pancreas divisum,choledochoceles,parasites – Ascaris lumbricoides,Clonorchis sinensis iatrogenic injury-perioperative injury,endoscopic procedures(ERCP)
- 24. Etiologic factors Vascular shock athroembolism PAN,SLE,HSP Infectious Mumps Coxsackie Mycoplasma pneumoniae
- 26. Drugs Thiazide diuretics Azathioprine Estrogens Sulphonamides Furosemide Methyl dopa Pentamidine procainamide
- 27. Idiopathic 10 to20% Genetic basis
- 28. Hereditary pancreatitis Autosomaldominant Recurrent attacks of severe pancreatitis beginning in childhood Caused by germline mutations in the cationic trypsin gene-PRSS 1 Affects a site on the cationic trypsinogen molecule essential for the inactivation of trypsin by trypsin itself. Trypsinogen & trypsin become resistant to inactivation &abnormally active trypsin activates other digestive proenzymes –development of pancreatitis
- 29. Hereditory pancreatitis Inheritedhomozygous inactivating mutations in the SPINK1 gene(serine protease inhibior,Kazal type1) SPINK1 gene codes for a pancreatic secretory trypsin inhibitor which helps to prevent autodigestion of pancreas by activated trypsin.
- 30. Pathogenesis Auto digestionof pancreatic tissue by inappropriately activated pancreatic enzymes. Activation of trypsin is an important triggering event. 3 possible pathways
- 31. Pancreatic duct obstruction Cholelithiasis,ampullaryobstruction Accumulation of enzyme rich interstitial fluid Lipase-local fat necrosis Injured tissues – proinflammatory cytokines- IL-1B,IL-6, TNF, PAF, Sub-P Local inflammtion & interstitial edema- ischemic injury to acinar cells
- 32. Primary acinar cellinjury Viruses,drugs,alcohol,direct trauma Shock Release of intracellular proenzymes &lysosomal hydrolases Activation of enzymes-acinar cell injury.
- 33. Defective intracellular transport Metabolic injury,alcohol, duct obstruction Delivery of proenzymes to lysosomal compartment Intracellular activation of enzymes Acinar cell injury
- 34. Activated enzymes Lipase,phospholipase– fat necrosis Proteases – proteolysis Elastase - hemorrhage
- 35. Alcohol Direct toxiceffect on acinar cells Duct obstruction – protein rich secretion Sudden exacerbations of chronic pancreatitis
- 36. Morphology Basic alterations– microvascular leakage – edema fat necrosis acute inflammatory reaction proteolytic destruction of parenchyma destruction of blood vessels – interstitial hemorrhage
- 41. Acute interstitial pancreatitis Mild form Interstitial edema,focal areas of fat necrosis Released fatty acids + calcium – insoluble salts
- 42. Acute necrotising pancreatitis More severe form Necrosis of pancreatic tissue, hemorrhage Areas of red-black hemorrhage interspersed with foci of yellow-white,chalky fat necrosis Foci of fat necrosis in extrapancreatic fat depots Peritoneal cavity – serous ,slightly turbid brown tinged fluid with fat globules
- 43. Hemorrhagic pancreatitis Mostsevere form Extensive parenchymal necrosis Diffuse hemorrhage
- 44. Clinical features Abdominalpain – mild to severe Full blown Acute pancreatitis – medical emergency – “acute abdomen” – constant & intense pain. Systemic features – release of toxic enzymes,cytokines etc.
- 45. Lab findings Markedelevation of s.amylase during 24hrs Followed within 72 to 96 hours by a rising s.lipase level. Hypocalcemia – if persistent –poor prognostic sign.
- 46. Diagnosis Elevated s.amylase& lipase Direct visualisation of the enlarged inflammed panceas by radiographic means Exclusion of other causes of acute abdomen.
- 47. Complications Systemic organfailure Shock ARDS ARF DIC Pancreatic abscess P.pseudocyst Duodenal obstruction
- 48. Management “resting” thepancreas Supportive therapy
- 49. Chronic pancreatitis Inflammation Destruction of exocrine parenchyma Fibrosis Destruction of endocrine parenchyma – late stages.
- 50. Chronic vs acutepancreatitis Irreversible impairment of pancreatic function
- 51. Causes Long termalcohol abuse Long standing obstruction of pancreatic duct by calculi pseudocysts trauma neoplasms pancreas divisum Tropical pancreatitis
- 52. Causes Hereditary pancreatitis Idiopathic chronic pancreatitis – CFTR related 40%-no cause.
- 53. Pathogenesis Ductal obstructionby concretions-alcoholic pancreatitis Toxic-metabolic toxins,alcohol – direct toxic effect on acinar cells Oxidative stress – alcohol Necrosis – fibrosis in hereditary pancreatitis repeated attacks of acute pancreatitis – perilobular fibrosis,duct distortion &altered secretions – loss of parenchyma & fibrosis
- 54. Chemokines IL-8 MCP-1 TGF-b PDGF
- 55. Morphology Parenchymal fibrosis Reduced no & size of acini ,relative sparing of islets Variable dilatation of the ducts Chronic inflammatory infiltrate around lobules & ducts Interlobular & intralobular ducts – dilated,contain protein plugs Ductal epithelium – atrophied or hyperplastic Ductal concretions
- 57. Morphology Acinar cellloss – constant feature Islets of Langerhans embedded in sclerotic tissue & may fuse Eventually islets also disappear Gross – gland is hard with extremely dilated ducts &visible calcified concretions
- 59. Clinical features Differentpresentations repeated attacks of moderately severe abd.pain recurrent attacks of mild pain persistent abd &back pain Silent till pancreatic insufficiency & DM develop Recurrent attacks of jaundice or indigestion
- 60. Diagnosis Visualisation ofcalcifications by CT or USG
- 61. Complications Pseudocyst Malabsorption,steatorrhea Secondary DM Pancreatic carcinoma – 40% risk in hereditary pancreatitis
- 62.