Pancreas Flashcards
(23 cards)
Pancreas Anatomy
95% made up of ACINAR TISSUE –> makes DIGESTIVE ENZYMES (trypsin, chymotrypsin, lipase)
Ducts lined by flat, cuboidal epithelium carry these digestive enzymes
Acini + Ducts = EXOCRINE compartment
2% of the parenchyma is made of islet cells –> INSULIN and GLUCAGON = ENDOCRINE compartment
Pancreatic Agenesis
Absence of the pancreas via a germline mutation of PDX1, a transcription factor responsible for pancreas formation; not really compatible with life
Heterotopic or Ectopic pancreas
More common than agenesis; could be asymptomatic
Pancreatic tissue outside of where it should be, usually within the GI tract
Acini and glands may or may not have islets
Acinar cells are functional –> auto-digestion can occur –> pain or mucosal bleeding
Pancreas DIVISUM
Failure of FUSION OF THE DUCTAL SYSTEMS
In the adult the pancreas is a single structure –> during embryonic development there are TWO different buds (dorsal facing backward, ventral forward)
VENTRAL pancreatic bud rotates and joins dorsal bud, and the VENTRAL persists, becoming the main drainage of the whole organ
In PANCREAS DIVISUM, there are two systems draining into the duodenum –> NARROW DORSAL duct (normally not involved) now has to carry a lot of secretions –> narrow with lots of secretions = buildup/backup
Enzyme leakage occurs –> Pancreatic damage –> RECURRENT ACUTE INFLAMMATION (Pancreatitis)
ANNULAR PANCREAS
Constriction that occurs when the ROTATION OF THE VENTRAL PANCREAS IS INCOMPLETE
Constricts the SECOND part of the DUODENUM
Child will present with intestinal obstruction soon after birth because the constriction won’t allow food material to pass beyond the stomach
Main difference between acute and chronic pancreatitis?
ACUTE –> glands will usually return to normal if the underlying cause of inflammation is removed
Chronic –> IRREVERSIBLE destruction of the pancreatic parenchyma
Two most important causes of Pancreatitis?
ALCOHOL –> direct cytotoxicity in the US; also causes constriction of the ampulla of Vater, causing a function obstruction in the outflow tract
BILIARY TRACT DISEASE –> gallstones leave the gallbladder and can get impacted in the ampulla of Vater and thus prevent flow of the pancreatic enzymes –> back-leak of enzymes into the pancreas –> destruction!
Other causes –> pancreas divisum, parasites, meds, trauma to the ducts, infections (mumps, Coxsackie), genetics
Genetic Causes of Pancreatitis
Most common – Mutation tot he PROTEIN CATIONIC TRIPSINOGEN (PRSS1) gene
Children have recurrent attacks with this mutation; this gene normally breaks down proteins –> no breakdown of trypsin –> parenchymal damage; INCREASED risk of pancreatic cancer
Mutation of SPINK1 –> normally a trypsin inhibitor; loss of function mutation –> too much trypsin –> damage to the parenchyma; not as common as PRSS1
Mutation in CFTR gene –> same gene as CF; may or may not have other classic CF symptoms (can be solely pancreatic)
Two types of ACUTE pancreatitis?
Interstitial –> Inflammation that often responds well to conservative therapy (adequate HYDRATION)
Necrotic/Hemorrhagic –> MUCH more severe; surgical emergency; blood leaks through pancreatic tissue and settles outside of the abdominal muscles –> bruising in the LATERAL FLANK REGION
How do acute pancreatitis patients present?
SEVERE ABDOMINAL PAIN; dull and constant, gradually starts out and reaches a steady peak; RADIATION TO THE BACK in about half of cases; N/V
Complications of Pancreatitis?
SHOCK –> decreased BP with all the fluid leaking out of damaged vessels
DIC – activation of the coagulation cascade; particularly bad in END ORGANS
ARDS – from breakdown of surfactant in the lungs and collapse of the alveoli
RENAL FAILURE - either from microthrombi or from shock
PANCREATIC ABSCESS – infection; life threatening
PANCREATIC PSEUDOCYST – LATE complication, particularly in alcohol induced pancreatitis –> SYMPTOMATIC CYSTIC LESION –> pseudo b/c it is NOT lined by epithelium, but instead lined by FIBROUS GRANULATION TISSUE with ragged edges and enzyme rich fluid –> aspiration shows ridiculously high amounts of pancreatic enzymes –> the fear with these is that they can grow so large and compress other structures, or perforate and secrete all their contents
Chronic Pancreatitis
IRREVERSIBLE destruction of the pancreatic parenchyma!!!
Enzyme production impaired –> patients usually on supplements; EXOCRINE (digestive) INSUFFICIENCY OCCURS EARLY
ENDOCRINE (insulin, glucagon) INSUFFICIENCY OCCURS LATER
Most common cause? CHRONIC ALCOHOL ABUSE
Others? Recurrent acute pancreatitis, pancreas divisor, hereditary pancreatitis
Not acutely life threatening, but 20 yr mortality is 50%
Five Features of CHRONIC pancreatitis?
Loss of ACINI
Fibrosis
Dilated DUCTS
Enlarged Islets (acini are gone, so they seem more apparent)
Chronic inflammation
Clinical Manifestations of Chronic Pancreatitis
Lose EXOCRINE long before ENDOCRINE, so there is less trypsin/lipase –> POOR BREAKDOWN/ABSORPTION OF FAT
Fat soluble ADEK vitamins are not absorbed either; deficiencies of these vitamins can have serious complications –> blindness, clotting problems, etc
Lack of PROTEIN ABSORPTION –> HYPOproteinemia and thus a loss of fluid into the pleural/abdominal cavity = PLEURAL EFFUSIONS, ASCITES
Stones/calcifications of the pancreas
PAIN –> Pancreas is very NERVE-RICH structure, and fibrosis can impinge on the nerves
SEVERE pain radiating to the BACK –> make sure to rule out PANCREATIC CANCER when this symptom presents
Most prevalent pancreatic tumors?
90% are DUCTAL ADENOCARCINOMAS
Ductal Adenocarcinoma
Gross - neoplastic area of pancreas is grayish-white with irregular borders
Histo - adenocarcinoma is trying to RECAPITULATE THE GLANDS; fibrosis and stromal rxn to the infiltrating glands; stromal DESMOPLASIA is a host response –> most of the removed tissue will be DESMOPLASIA rather than actual neoplastic tissue
Cancers of the pancreas can also include PERI/INTRANEURAL invasion –> glands sitting within the nerve –> this is the cause of the severe pain radiating to the BACK
Lymphatic invasion by glands can occur, and this is how it can metastasize
80% of patients are OLDER than 60
Strongest risk factor = SMOKING!!!!!!
Clinical Features of Ductal Adenocarcinoma
PAIN from the neural invasion (specifically back)
Obstructive JAUNDICE (tumors in the head of the pancreas will block the common bile duct)
Migratory thrombophlebitis (recurrent venous thrombosis because tumor makes hypercoaguable substances)
Unexplained WEIGHT LOSS
Gene associated with 90% of pancreatic cancers?
K-RAS - proto-oncogene
Pancreatic Intraepithelial neoplasias (PanINs)
Precursor lesions for pancreatic cancers
Range from innocuous low grade to HIGH grade that closely resemble neoplastic changes
Because it has NOT breached the BASEMENT MEMBRANE, the lesion is NOT neoplastic
High grade = Carcinoma in situ
Intraductal Papillary Mucinous Neoplasms
More commonly seen in the HEAD of the pancreas
Intraductal and papillary
Arise from the MAIN PANCREATIC DUCT or a branch duct
Neoplastic cells that make LOTS OF MUCIN
FInger-like papillae with clear mucin in the cells (histo)
More common in MEN
Can be benign (usually) but have the potential to become malignant
Mucinous Cystic Neoplasms
Far more common in WOMEN
Likely in the TAIL of the pancreas
NO CONNECTION with ducts
To diagnose, must demonstrate ovarian-type stromal tissue
Have malignant potential
Cystic Lesions of the Pancreas
Most common SYMPTOMATIC LESIONS of the pancreas are the NON-NEOPLASTIC PSEUDOCYST (associated with ALCOHOLIC PANCREATITIS)
Asymptomatic cysts –> usually diagnosed incidentally via radiography, usually are NEOPLASTIC (IPMN, MCN), incidentalomas, do NOT present with symptoms, can be resected if caught early –> remember these have malignancy potential so are worrisome
Pancreatic ENDOCRINE tumors
Rarest of the pancreatic tumors, make their own hormones that can be functional/non-functional
Sheets or ribbons of cells on histology (as opposed to diffuse stromal desmoplasia/fibrosis and scattered glands) –> classic feature is SALT AND PEPPER CHROMATIN APPEARANCE
INSULINOMAS –> most common ENDOCRINE tumors; arise from beta cells and secrete insulin; AMYLOID DEPOSITION and PANCREATIC CANCER = INSULINOMA until proven otherwise;
Whipple’s Triad –> HYPOGLYCEMIA, CNS MANIFESTATIONS, Symptoms RELIEVED by glucose administration –> 10% malignant, resection curative
GASTRINOMAS –> Zollinger Ellison syndrome –> Hypergastrinemia, multiple and intractable peptic ulcers, diarrhea –> 50% malignant
