Diseases Flashcards
Pancreas Divisum
congenital; results from failure of the fetal duct system of the dorsal and ventral pancreatic primordia fuse in utero
Predisposition to chronic pancreatitis due relative stenosis of the nearly the entire pancrea draining through the minor papilla
Annular pancreas
occurs in utero when one portion of the ventral pancreatic primordium becomes fixed , while the other portion is strung around the doudenum
causes signs and symptoms of DUODENAL OBSTRUCTION
ectopic pancreas
embryological rests in the submucosa (most commonly found in the stomach and duodenum)
MECKEL DIVERTICULA
Histo: unremarkable exocrine pancreas, sometimes with islets of langerhans
Acute Pancreatitis
- Reversible
- two top causes: ALCOHOL(more common in men) And GALLSTONES (more common in women)!!
- morphology of acute:
- -> micro vascular leakage causing edema
- -> necrosis of fat by lipolytic enzymes (“chalky white”)- within gland and parapancreatic adipose
- -> acute inflammation
- -> proteolytic destruction of pancreatic parenchyma
- -> destruction of blood vessels with resulting hemorrhage
Hereditary pancreatitis
AD disorder causes by mutation in trypsinogen gene (PRSS1), affects the site that essential for auto-inactivation (since now active inappopriately will continue to activate other enzymes)
-40% chance of developing pancreatic carcinoma
3 proposed mechanisms of pancreatitis
1) Duct obstruction
2) Acinar cell injury
3) defective intracellular transport
Chronic pancreatitis
- Irreversible
- long term alcohol abuse is most common cause
- whatever the process is the cause. the result is parenchymal fibrosis
- TFG and PDGF induces the activation and proliferation of myofibroblasts , leading to fibrosis
- calcifications and dilated ducts
Pathological characterization of chronic pancreatitis
Parenchymal fibrosis, loss of acini with sparing of islets of langherans, and variable dilation of pancreatic ducts
- protein rich secretions found in ducts
- eventually islets of langherans will dissappear
congenital cysts
- non-neoplastic
- anomalous development of pancreatic duct
- TRUE CYST lined by EPITHELIAL LAYER
Pseudocysts
-non-neoplastic
LACK EPITHELIAL LAYER–> therefore not True cyst
-majority of cysts in pancreas still (75%)
-associated with pancreatitis
-usually solitary; can be within substance of pancreas nut more commonly in the periphery of the gland extending into the adipose tissue
-created by walls of fibrous granulation tissue that have encased regions of hemorrhagic fate necrosis (result is necrotic and hemorrhagic material within non-epithelialized cavity)
-up to 30 cm in diameter
serous cystadenoma
- almost always benign neopasms
- 2x as common in women vs men.
- composed of GLYCOGEN RICH, low cuboidal cells surrounding small cysts that contain clear thin fluid
mucinous cystic neoplasm
- almost always arise in women
- benign, borderline, or malignant (dependent on the presence or absence of invasion)
- filled with THICK TENACIOUS MUCIN
- lined by columnar mucinous epithelium overlying dense OVARIAN like stroma
Intraductal papillary mucinous neoplasm
- produce cysts that contain mucin and can be benign, borderline, or malignant
- more common in men
- more often involve head of pancreas rather than tail
- Rise in the main pancreatic duct (note most mucinous cystic neoplasms do not connect with main ducts)
- lack dense stroma overlying epithelium
Pancreatic carcinoma
-infiltrating ductal carcinomal of the pancreas
-one of the highest mortality rates of cancer
-strongest environmental factor is smoking
-multiple genes altered in any given carcinoma
(oncogene KRAS or p16 tumor suppressor gene)
-inherited predisposition to pancreatic cancer: Hereditary breast and ovarian cancer, Peutz-Jeghers syndrome (highest risk at 120 fold), hereditary pancreatitis
pancreatic carcinoma distribution
60%-head 20% - diffuse gland 15%-body 5%-tail (note the more distant to the head, can remain clinically silent longer due to lack of involvement of common bile duct)
Pathologic features of pancreatic carcinoma
Gross: hard, stellate, grey-white, poorly defined masses
micro: forming primative glands, represented by a border of tubular structures, or cell clusters
moderate to poorly differentiated
-highly invasive and elicit an intense desmoplastin response consisting of fibroblasts, lymphocytes, and ECM
-local invasion can extend into adjacent organs and supporting tissue
-MIGRATORY THOMBOPHLEBITIS- characterized by spontaneous appearing and disappearing thrombosis (10% of patients with pancreatic adenocarcinoma)–> “trosseau sign” and caused by platelet aggregating factors and procoagulants
Familial Adenomatous polyposis (FAP)
hereditary and modifying factors (genes and diet)
the gatekeeper
NSAIDS and colon carcinogenesis
Autosommal dominant; 1000s of adenomas (small polyps)
deletion of chromosome 5q
mutant APC gene - center of an array of interactions that govern the epithelium of the GI tract (F-actin and microtubules and B catenin/TCF)
induce WNT signaling -activate B catenin to proliferate (never degrades)
ACCELERATED TUMOR INITIATION
HNPCC
decreased mismatch repair (MMR deficient)
genetic instability
increased mutation rate
apoptosis=safeguard
decreased apoptosis–> increased opportunity for mutants to survive
fewer larger polyps
ACCELERATED TUMOR PROGRESSION
what can scorpion venom induce?
acute pancreatitis
most common form of pancreatic cancer
adenocarcinomas
(ductal-75%)
most involve head
3 main signs of pancreatic cancer
weight loss, jaundice, pain
patterns of hepatic injury
degeneration and intracellular accumulation necrosis and apoptosis inflammation regeneration fibrosis
ballooning degeneration
swelling of hepatocytes due to toxic and hepatic insults ; irregular cytoplasmic organelles and large clear spaces
feathery degeneration
cholestasis-large, contains bile pigment
accumulation of bile pigment in parenchyma, hepatocytes can swell and look foamy (from hepatocyte dysfunction or intra/extrahepatic biliar obstruction)
HAVE YELLOW BROWN DISCOLOARTION caused by bile pigments
dubin-johnson syndrome
- abundant pigmented inclusion of cytoplasm of otherwise normal hepatocytes
- hereditary effect in excretion of conjugation bilirubin into caniculi
- pigmented material is epi metabolized within lysosomes
microsteatosis
small fat droplets that do not displace nuclei
seen in: acute fatty liver of pregnancy, and valproic acid toxicity
macrosteatosis
larger fat droplets that have displaced nuclei
seen diffusely in obesity and diabetes, and more limited extent hep C ; both macrosteatosis and microsteatosis can be present in alcoholic liver disease
Hep B histo (filled with hep b surface antigen in cytoplasm)
Ground glass hepatocytes
Hep C histo
lymphoid aggregates in portal tracts
autoimmune hepatitis
-more common in women
-absence of viral markers
-elevated serum IgG and gamma globulin
-Neg AMA
Positive ANA
-presence of plasma cells and lymphocytes
centrilobular necrosis associated with what drug
acetaminophen overdose
alcoholic hepatitis pathology
characterized by hepatocyte swelling and necrosis, mallory bodies, neutrophilic reaction accumulating around degenerative hepatocytes and fibrosis present around veins within sinusoids
NAFLD
resemble alcohol liver disease but involved in patients that are not heavy drinkers
- strong association with obesity , dyslipidemia, hyperinsulinemia, type 2 diabetes
- can be simple steasosis histologically
- most common cause of cryptogenic cirrhosis
hemochromatosis
-excessive accumulation of iron,
