PANCREAS

PANCREAS

1. Exocrine 80-85%

   • Endocrine
     • Langerhans islets (1-2%): insulin, glucagon, somatostatin, pancreatic polypeptide
       • alpha 20%: glucagon
       • beta 70%: insulin
       • delta 5%: somatostatin
       • F cells 5%: pancreatic polypeptide
   • acinar cells
     • Zymogen granules (proenzymes): chymotrypsinogen, trypsinogen, procarboxypeptidase, proelastase, kallikreinogen, prophospholipase A and B

2. CONGENITAL MALFORMATIONS

   • Divided pancreas (+ frequent)
     • 3-10%
     • Predisposing factor for chronic pancreatitis
     • There's no fusion of ventral and dorsal pancreatic primordiums
       • No Wirsung conduct (principal)
   • Anular pancreas
     • doudenal obstruction
   • Ectopic pancreas
     • stomach and duodenum (+ frequent)
     • Jejunum, Meckel's diverticulum and ileum
     • can cause pain and hemorrhage

3. PANCREATITIS

   • Self-digestion by own enzymes
   • Mechanisms of protection against self-digestion
     • Proenzyme production
     • Proenzyme activation is due to trypsin which is activated by enterokinases (small intestine)
     • Acinar and ductal cells secrete trypsin inhibitors
   • Acute pancreatitis
     • reversible injury
     • Etiologic factors: metabolic, genetic, mechanical, vascular, infectious
       • Hereditary pancreatitis
         • PRSS1 (+ frequent) = increases trypsin activity
         • SPINK1 = there's no inhibition for trypsin
         • CFTR = decreases HCO3 secretion, it causes obstruction by protein caps
     • Pathogenesis
       • inflammatory reaction due to parenchyma injury by inadequate enzyme release and activation
         • Pancreatic duct obstruction
           • Caused by: gallstones, periampullary neoplasms, parasites, choledococele, divided pancreas
           • enzyme rich liquid accumulation
             • lipase causes fat necrosis
             • necrosis produces inflammatory reaction
               • edema
                 • ischemia
                   • acinar cell injury
         • acinar cells injury
           • endogenic, exogenic or iatrogenic injury
             • oxidative stress=free radicals
               • lipid membrane oxidation, transcription factor activation
                 • chemokin expression
                   • mononuclear cells attraction
                     • inflammation
                       • acinar cell injury
           • intracellular Ca++
             • low = trypsin inactivation
             • high = trypsin activation
         • defective intracellular transport
           • proenzymes and hydrolases transported by the same route
             • proenzyme activation (intracellular)
               • acinar cell injury
     • clinic manifestations
       • abdominal pain, radiates to the back
         • anorexia, nausea, vomiting
       • acute florida pancreatitis / severe
         • medical emergency
         • acute abdomen, leukocytosis, edema, SDRA, disseminated intravascular coagulation (DIC)
   • Chronic pancreatitis
     • long term inflammation
     • IRREVERSIBLE destruction of exocrine and endocrine parenchyma
     • Caused by: ALCOHOL, chronic obstruction, autoimmune injury, hereditary pancreatitis
       • Alcohol: duct dilation,intraluminal protein caps, calcifications
       • Auntoimmune: Ig4
     • Pathogenesis
       • different acute pancreatitis episodes
         • chronic pancreatic injuries induce profibrinigenic cytokines production
           • fibrosis and acinar cell lost

4. NON-NEOPLASTIC CYST

   • Congenital
     • cubic epithelium
     • can be associated to renal polycyst
   • Pseudocyst 75%
     • no epithelium
     • necrotic and bleeding material, enzyme rich
     • appears after acute pancreatitis episode or truma

5. NEOPLASIAS

   • Cyst neoplasia
     • serous 25% (+ frequent)
       • multicyst, pancreas tale
       • cubic epithelium (glycogen rich)
       • VHL gen supressor inactivation
       • women
       • benign
     • mucinous
       • cilindric epithelium, ovaric epithelium like stroma, pancreas tail
       • mutated genes: KRAS,TP53, RNF43
       • women
       • can become malign (infiltrative)
     • NMPI
       • pancreas head
       • larger caliber pancreatic ducts
       • men
       • No ovaric stroma
       • can become malign
       • mutated genes: GNAS , KRAS, TP53, SMAD4, RNF43
     • solid pseudopapillar
       • malign
       • young women
       • mutated gen: CTNNB1

6. PANCREATIC CARCINOMAS

   • Ductal adenocarcinoma/ pancreas cancer
     • intraepithelial pancreatic neoplasia (PanIN)
       • precursor to invasive carcinoma
       • mutated genes
         • KRAS (+ frequent): transmission of growth factor signals. It activates MAPK and PI3K/AKT
           • 12p chromosome
         • CDKN2A (+ frequent) inactivated): negative regulator of cellular cycle. It activates p16/INK4a and ARF
           • 9p chromosome
         • SMAD4: TGF-B pathway
           • 18q chromosome
         • TP53: DNA injury response
           • 17p chromosome
     • age range: 60 - 80
     • smoking
     • head pancreas 60%, bile duct obstruction = jaundice
     • INFILTRATIVE, DESMOPLASTIC RESPONSE (fibrosis)
     • clinic manifestations
       • they appear when it's already incurable
       • PAIN, obstructive jaundice, weight loss, anorexia, asthenia and adinamia
         • Trousseau syndrome 10% (migratory thrombophlebitis)
   • Acinar cells carcinoma
     • metastatic fat necrosis syndrome
   • Pancreatoblastoma
     • flaky islets with acinar cells

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