LIVER

THE PANCREAS

General Features


.arising from foregut, transverse retro- peritoneal organ extending from “C” loop of duodenum to hilum of spleen .20 cm long, 90 gm in men, & 85 gm in women .divided into head, body, & tail .duct of Wirsung most commonly drains into duodenum at papilla of Vater.duct of Santorini drains into duodenum by separate minor papilla.main pancreatic duct merges with the common bile duct>ampulla of Vater

Pancreatic ductal anatomy

.pancreas has 2 components -exocrine, (85% of the gland), produces 2-2.5 L of bicarbonate-rich fluid  -endocrine, (up to 2% of the gland), consists of 1 million clusters of islets of Langerhans, secrete insulin, glucagon, & somatostatin

Pancreatic acini (exocrine pancreas)

Congenital Anomalies



AGENESIS .very rare associated with wide-spread malformations, incompatible with lifePANCREATIC DIVISUM .failure of fetal duct systems of dorsal & ventral pancreatic primordia to fuse> chronic pancreatitis

ANNULAR PANCREAS.band-like ring of pancreatic tissue encircling second part of duodenum> duodenal obstruction early in life ECTOPIC PANCREAS .sites (stomach, duodenum, jejunum, Meckel diverticulum, ileum) .forms a sessile mass (inflammation, bleeding) .complicated in 2% by islet cell tumors

CYSTIC FIBROSIS.an autosomal recessive disorder of ion transport in epithelial cells that affects fluid secretion (abnormally viscous> obstruction) in exocrine glands and epithelial lining of respiratory, alimentary, & reproductive systems.incidence is 1/2500 live births

.the primary defect is abnormal function of epithelial chloride channel protein .heterozygous person has higher incidence of respiratory and pancreatic diseases than normal person.mild cases, accumulation of mucus in  ducts>dilation of exocrine glands.severe cases, squamous metaplasia of  ducts lining epithelium, atrophy of  exocrine glands, & fibrosis

Pancreas, cystic fibrosis

.clinical features -meconium ileus -exocrine pancreatic insufficiency> malabsorption syndrome -idiopathic chronic pancreatitis -endocrine pancreatic insufficiency -cardiorespiratory complications (recurrent sinonasal polyps, pneumonia, COPD, corpulmonale) -biliary cirrhosis -male infertility

Inflammation

ACUTE PANCREATITIS.reversible process .etiologic factors -metabolic (alcohol, hypercalcemia, drugs, hyperlipoproteinemia)  -genetic  -mechanical (gall stone, trauma, iatrogenic)  -vascular (shock, atheroembolism, vasculitis) -infection (mumps)

Hereditary Pancreatitis .about 10%-20% of idiopathic acute pancreatitis have genetic basis.characterized by recurrent attacks of severe pancreatitis usually beginning in childhood.mostly due to mutation in trypsinogen gene>trypsin formation .less commonly due to gene mutation encoding trypsin inhibitor .both mutations>pancreatic enzymes activation



.pathogenesis -autodigestion of the pancreatic by inappropriately activated pancreatic enzymes secondary to inappropriate activation of trypsinogen

Pathogenesis of acute pancreatitis

.morphology  -mild (inflammation, edema)  -severe (parenchymal necrosis, hemorrhage)

Acute pancreatitis, hemorrhage & fat necrosis

Acute pancreatitis, fat & parenchymal necrosis

.clinical features  -abdominal pain -DIC -respiratory distress syndrome -diffuse fat necrosis -shock, acute renal tubular necrosis.diagnosis  -laboratory findings .elevated serum amylase in 24 hrs .rise of serum lipase in 72-96 hrs .glycosuria, hypocalcemia -radiology

.management  -resting the pancreas plus supportive therapy.complications  -sterile pancreatic abscess -pancreatic pseudocyst -infected abscess

CHRONIC PANCREATITIS.irreversible process with inflammation & destruction of pancreas>fibrosis.etiology  -chronic alcohol abuse (most common) -obstruction of pancreatic duct  -tropical pancreatitis -hereditary pancreatic enzymes abnormalities -cystic fibrosis -idiopathic (40%)

.pathogenesis  -ductal obstruction by concretions -direct toxic effects on acini (alcohol) -oxidative stress (free radicals-alcohol)

.morphology  -parenchymal fibrosis -atrophy of acini -loss of the islets of Langerhans -variable dilation of pancreatic ducts


Chronic pancreatitis, interstitial fibrosis with glandular atrophy

Chronic pancreatitis, dilated duct with inspissated eosinophilic concretions

.clinical features -silent until pancreatic insufficiency & diabetes mellitus develop -repeated attacks of abdominal pain -recurrent attacks of jaundice or vague attacks of indigestion.diagnosis -high degree of suspicion -visualization of calcifications within the pancreas by CT scan & U/S .prognosis -long-term outlook is poor

Lymphoplasmacytic Sclerosing Pancreatitis .autoimmune chronic pancreatitis characterized by -duct-centric inflammation -venulitis -IgG4-producing plasma cells -clinically mimic pancreatic cancer -responds to steroid therapy

Non-Neoplastic Cysts

CONGENITAL CYSTS.solitary, sporadic.coexist with cysts in kidney & liver in -polycystic kidney disease -von-Hippel-Lindau disease .cysts or neoplasms in liver & kidney .vascular neoplasms in retina & brain

PSEUDO-CYSTS.account for 75% of pancreatic cysts, secondary to acute or chronic pancreatitis, or abdominal injury.usually solitary, embedded in peri- pancreatic tissue.resolve, secondarily infected or perforate into adjacent structures

Pancreatic pseudocyst

Pancreatic pseudocyst, lined by granulation tissue

Neoplasms

CYSTIC NEOPLASMS Serous Cyst Adenomas .female to male ratio is 2:1 .account for 25% of all cystic neoplasms of pancreas .present at 7th decade as -abdominal pain, or -abdominal mass

Pancreatic serous cystadenoma

Pancreatic serous cystadenoma


Mucinous Cyst Neoplasms .almost always arise in women.present as painless, masses in body & tail of pancreas.1/3 of surgically resected neoplasms harbor invasive adenocarcinoma

Pancreatic mucinous cystadenoma

Pancreatic mucinous cystadenoma


PANCREATIC CARCINOMA.has one of highest mortality rates of all cancers, 5-year survival of less than 5%.progression from non-neoplastic epithelium>noninvasive lesions in small ducts & ductules>invasive carcinoma (pancreatic intraepithelial neoplasias- PanINs), through multiple mutations


Progression model for development of pancreatic cancer


.epidemiology & pathogenesis  -a disease of elderly -contributing factors .cigarette smoking (strongest influence) .diet rich in fat .chronic pancreatitis (cause or effect) .diabetes mellitus (cause or effect) .genetic

.morphology  -60% in head, 15% in body, & 5% in tail; in 20% diffusely involving gland  -two characteristic features  .highly invasive  .presence of desmoplastic reaction  -gross, hard, stellate, gray-white,  illdefined mass  -histology, ductal adenocarcinomas

Pancreatic carcinoma, normal pancreas on left side, carcinoma on right side

Pancreatic carcinoma, poorly formed glands


.clinical features  -silent until local extension -obstructive jaundice -non-specific -migratory thrombophlebitis (Trousseau sign).diagnosis -imaging techniques (endoscopic ultrasonography, CT) -percutaneous needle biopsy -serum markers for follow up (CEA, CA19-9)