Pancreas Flashcards
Acinar cells
Small Ductules
Large Ducts
Islet of Langerhans
Acinar cells-secrete digestive enzymes and proenzyme(cuboidal)
Small Ductules-bicarbonate
Larger Ducts-mucin
Islet of Langerhans-insulin, glucagon, somatostatin, PP, VIP, and serotonin
What is self digestion of the pancreas prevented by?
- inactive proenzymes are synthesized
- enzymes are in membrane bound zymogen granules
- activation of proenzymes requires activation of trypsinogen to trypsin
- trypsin inhibitors are present
- trypsin can inactivate itself
- resistance of acinar cells
acute pancreatitis
AUTODIGESTION of pancreatic substance by inappropriately activated pancreatic enzymes
- acute inflammatory process of the pancreas
- usually associated with acinar injury
- usually nonprogressive
- range from mild self limited disease to life threatening acute inflammatory process
Clinical:
abdominal pain resulting from enzymatic necrosis and inflammation of the pancreas
**80% of cases associated with biliary tract disease or alcoholism
Female 3X biliary tract disease
Male 6X alcoholism
What things can cause acute pancreatitis ?
- obstruction of pancreatic ductal system
- gallstones
- periampullary neoplasms - Alcohol
- Drugs
- Trauma
- Hypermetabolic
- hypertriglyceridemia, hyperparathyroidism-hypercalcemia - vascular (ischemia)
- shock, emboli, vasculitis (PAN) - Infectious
- mumps - Genetic
- mutations in cationic trypsinogen and trypsin inhibitor gene
What is the clinical picture for acute pancreatitis?
abdominal pain
elevated plasma amylase and lipase
diffuse fat necrosis–>hypocalcemia (less calcium more severe)
-ARDS
-acute renal failure
-disseminated intravascular coagulation DIC
-fluid sequestration
Treatment: supportive -analgesia -IV -correct electrolyte abnormalities
What are sequelae of acute pancreatitis?
5% death
pancreatic abscess
pancreatic pseudocyst pancreatic necrosis surrounded by granulation tissue (not lined by epithelium tissue)
infected necrotic debris
What are predisposing factors to Chronic pancreatitis?
- long term alcohol abuse
- long standing obstruction
- biliary tract disease/calculi
- pancreatic divisum
- neoplasm, pseudocysts - tropical pancreatitis-Africa and Asia
- Hereditary Pancreatitis
- Cystic fibrosis transmembrane conductance regulator gene mutation
- idiopathic (up to 40%)
What are some proposed mechanisms for chronic pancreatitis?
- hypersecretion of protein; insufficient ductal bicarbonate
- plug–>calcification & stone formation, or scar–>further obstruction - direct toxic effect
- antioxidant imbalance-generation of free radicals in stressed acinar cells–> injury
- profibrogenic cytokines
What happens in Chronic pancreatitis
- fibrosis
- reduced number and size of acini (exocrine pancreas)
- obstruction and dilation of pancreatic ducts
- protein plugs - late stage loss of islets of langerhans (endocrine pancreas)
- pseudocyst formation
- calcified concretions
What are clinical signs of chronic pancreatitis?
- recurrent attacks of abdominal pain
-radiation of pain to back
Triggers: ETOH, overeating, opiates - recurrent attacks of jaundice or vague indigestion
- Exocrine pancreatic insufficiency
-steatorrhea - diabetes mellitus
- pancreatic calcification on imaging
Pancreatic psuedocyst
-localized collections of pancreatic secretions in pancreatic interstitium as a result of damaged ducts
Pancreatic carcinoma
ductal adenocarcinoma of the pancreas
4th most frequent cause of cancer death in US
Pathogenic factors:
- Pancreatic intraepithelial neoplasia (PanIN)
- precursor lesions - Smoking
- Familial clustering
- chronic pancreatitis
- diabetes mellitus-produce more insulin, insulin is a growth factor
What is the molecular carcinogenesis of PanIN?
Pan1 Pan1b -telomere shortening -mutation of KRAS Pan2 inactivation of p16 pan3 -inactivation of p53, SMAD4, BRCA2
–>invasive carcinoma
WHere is pancreatic carcinoma mostly found? What is the hsitology
head 60% diffuse (20%) body (15%) tail (5%) -gritty gray white solid firm masses
Histology Adenocarcinoma -poorly formed infiltrating glands -majority of ductal origin Dense stromal fibrosis -desmoplastic response
Where does pancreatic carcinoma invade locally? What about distant metastases?
Local:
adjacent nerves—>SEVERE BACK PAIN
spleen, adrenals, transverse colon, stomach, vertebral column
-lymph nodes: peripancreatic, gastic, mesenteric, omental, portahepatic
Distal metastases:
-liver, lungs, bone
How does pancreatic carcinoma present?
- remain clinically silent until tumor impinges on other structures
- obstructive jaundice
- pain is usually first symptom
- weight loss, anorexia, malaise, weakness—signs of advanced disease
Tumor makers: CA19-9 and CEA-monitoring tool
Less than 20% of tumors are resectable at time of diagnosis
What happens if the pancreatic carcinoma is in the head of the pancreas? Body and tail?
HEAD
- tumor obstruction ampullary region/ common bile duct
- obstruction prevents conjugated bile from entering duodenum, bile pressure increases in the biliary tract and conjugated bile enters the vascular space
- distention of biliary tree
Body and tail
- does not impinge on biliary tract
- silent for long time
- large locally invasive and disseminated at time of diagnosis
What is trousseau sing?
migrating thrombophlebitis
- spontaneously appearing and disappearing venous thrombosis
- 10% of patients
- attributed to elaboration of platelet aggregating factors and procoagulants from tumor
-mucin in blood vessel causes intravascular coagulation
What are 3 cystic neoplasms of the pancreas?
- serous cystadenoma
- mucinous cystic neoplasm
- Intraductal papillary mucinous neoplasms
Serous Cystadenoma
Behavior
Gross morphology
Histology Clinical
Benign Small cysts-clear, straw colored fluid lined with CUBOIDAL cells which are glycogen rich femaleX2 70s nonspecific symptoms
Mucinous cystic neoplasms
Behavior
Gross morphology
Histology Clinical
Mucinous cystadenoma=benign
Mucinous cystadenocarcinoma=malignant
Cysts filled with thick mucin-not connected to main pancreatic duct
- cysts lined by COLUMNAR epithelium
- cytologically benign to severely dysplastic
- MAJORITY FEMALE!
- body/tail pancreas
- painless slowly growing masses
Intraductal papillary mucinous neoplasms
benign to malignant
- arise in main pancreatic duct or major branch
- lined by COLUMNAR epithelium
- various degrees of dysplasia
- Men>women
- head of pancreas
What is an annular pancreas?
ring of pancreatic tissue encircles duodenum
What is pancreas divisum?
failure of fetal duct to fuse
- 3-10% of population
- increased pancreatic pressure
- possible chronic pancreatitis
Ectopic Pancreas
Pancreatic tissue in other tissue stomach and duodenum, jejunum, meckel's diverticulum, ileum -submucosa -asymptomatic or pain, mucosal bleeding 2% of islet cell neoplasms
