Pancreas.pdf pathology’s and diseases dysfunction

Pancreas disorders pathology

1. Pancreas –I
Exocrine pancreas
DrA Rapsang

2. •The pancreas has
–Endocrine functions
–Exocrine function -major source of potent enzymes that
are essential for digestion.
•Retroperitoneal location of the pancreas -allow
many pancreatic diseases to progress undiagnosed
for a long time
•The pancreas is a transversely oriented
retroperitoneal organ extending from the duodenum
to the hilum of the spleen.
–Head
–Body
–Tail.

3. •The pancreas gets its name from the Greek pankreas,
meaning “all flesh,”
•It is a lobulated organ with endocrine and exocrine
elements.
Endocrine portion
•1% to 2% of the pancreas
•Composed of about 1 million islets of Langerhans
•Secrete insulin, glucagon, and somatostatin.
•Causes
–Diabetes mellitus
–Neoplasms

4. Exocrine pancreas •Composed of
–Acinarcells -produce the digestive enzymes
–Ductulesand ducts -convey them to the
duodenum.
–The epithelial cells lining the ducts -active
participants in pancreatic secretion
–The cuboidal cells lining the smaller ductules -
secrete bicarbonate-rich fluid
–The columnar cells lining the larger ducts -
produce mucin.

5. CONGENITAL ANOMALIES
Agenesis
•Pancreas is totally absent –very rare
•Associated with additional severe malformations tha t
are incompatible with life.
Pancreas Divisum
•Most common
•Occurs when the duct systems of the fetal pancreas
fail to fuse.
•Main pancreatic duct drains only a small portion of
the head of the gland
•Has elevated intraductalpressures
•Increased risk for chronic pancreatitis.

6. •Annular Pancreas
•Pancreatic fusion in which a ring of pancreatic tis sue
completely encircles the duodenum.
•Present as duodenal obstruction -gastric distention
and vomiting
Ectopic Pancreas
•Pancreas present in stomach, duodenum, jejunum,
Meckel diverticulum, and ileum.
•They are composed of normal pancreatic aciniwith
occasional islets.
•Usually asymptomatic
•Can cause pain from localized inflammation, or caus e
mucosal bleeding.

7. Congenital Cysts
•Congenital cysts result from anomalous development
of the pancreatic ducts.
•Generally are and range from microscopic to 5 cm in
diameter.
•They are lined by either uniform cuboidal or
flattened epithelium and are enclosed in a thin,
fibrous capsule.
•These cysts contain clear serous fluid

8. PANCREATITIS
•Inflammatory disorders of the pancreas range in
severity from mild, self-limited disease to life-
threatening
•Acute pancreatitis -function can return to normal i f
the underlying cause of inflammation is removed.
•Chronic pancreatitis –irreversible destruction of
exocrine pancreatic parenchyma.

9. Acute Pancreatitis
•Can range from focal edema and fat necrosis to
widespread hemorrhagic parenchymal necrosis.
•Acute pancreatitis is relatively common
•Approximately 80% of cases are attributable to eith er
–Biliary tract disease
–Alcoholism

11. Morphology
•Microvascular leakage
causing edema
•Necrosis of fat by
lipases
•Acute inflammatory
reaction
•Proteolytic destruction
of pancreatic
parenchyma
•Destruction of blood
vessels leading to
interstitial hemorrhage.

12. M/E
•Interstitial edema
•Focal areas of fat
necrosis in the
pancreatic substance
•and peripancreaticfat
Can affect acinarand
ductal tissues as well as
the islets of Langerhans
•Vascular damage causes
hemorrhage into the
parenchyma of the
pancreas.

14. Clinical Features
•Abdominal pain –mild to severe
–Constant and intense
–Often referred to the upper back
•Abdominal guarding
•Absence of bowel sounds
•Diagnosed by the presence of elevated plasma levels
of
–Amylase
–Lipase
–Exclusion of other causes of abdominal pain.
•Self limiting - 80% of cases acute pancreatitis
•Severe disease develop -20%

15. •The manifestations of severe acute pancreatitis are
attributable to
–Systemic release of digestive enzymes
–Explosive activation of the inflammatory response.
•Patients may develop
–Disseminated intravascular coagulation
–Acute respiratory distress syndrome (due to alveola r
capillary injury)
–Diffuse fat necrosis.
–Peripheral vascular collapse (shock) –due to increa sed
microvascular permeability and hypovolemiawith
endotoxemia(from breakdown of the barriers
between gastrointestinal flora and the bloodstream) ,
–Renal failure -due to acute tubular necrosis

16. Laboratory findings •Markedly elevated serum amylase
•Rising serum lipase levels.
•Hypocalcemia -precipitation of calcium in areas of fat
necrosis
•CT/MRI –Enlarged inflamed pancreas
Treatment
•Supportive
–Maintaining blood pressure
–Alleviating pain
–“resting” the pancreas by total restriction of food and
fluids.
Complications
•Sterile or infected pancreatic “abscesses”
•Pancreatic pseudocysts.

17. Pancreatic Pseudocysts
•A common sequelaof acute pancreatitis
•Liquefied areas of necrotic pancreatic tissue becom e
walled off by fibrous tissue to form a cystic space ,
lacking an epithelial lining
•The cyst contents are rich in pancreatic enzymes
•Laboratory assessment of the cyst aspirate can be
diagnostic.
•Pseudocystscan
–Resolve spontaneously
–Become secondarily infected
–Compress/perforate into adjacent structures.

18. Pseudocysts •Usually solitary
•Commonly attached to the
surface of the gland
•Involve peripancreatic
tissues
–Lesser omentalsac
–Retroperitoneumbetween
the between the stomach,
transverse colon or liver
•Can range in diameter
from 2 cm to 30 cm.

19. •M/E •Typically are composed
of necrotic debris
encased by fibrous walls
of granulation tissue
•They lack an epithelial
lining

20. Chronic Pancreatitis
•Long-standing inflammation, fibrosis, and
destruction of the pancreas
•Irreversible impairment in pancreatic function
•The most common cause of chronic pancreatitis is
long-term alcohol abuse
•Other causes are
–Long-standing pancreatic duct obstruction -pseudocysts,
calculi, neoplasms, or pancreas divisum
–Genetic -Tropical pancreatitis
–Hereditary pancreatitis -mutations in the pancreatic
trypsinogengene

21. Morphology •Parenchymal fibrosis
•Reduced number and
size of acini
•Variable dilation of the
pancreatic ducts
•Sparing of the islets of
Langerhans
•Chronic inflammatory
cells -eosinophilic
concretions

22. PATHOGENESIS
•Ductal obstruction by concretions.
•Toxic-metabolic.
Toxins/alcohol exert a direct toxic effect on acina rcells
↓
Lipid accumulation
Acinarcell loss
↓
Parenchymal fibrosis.
•Oxidative stress - generate free radicals in acinarc ells,
leading to membrane damage, acinarcell necrosis,
inflammation, and fibrosis.
•Cytokines- induce the activation and proliferation o f
periacinarmyofibroblastswhich deposit collagen

23. Clinical Features
•Repeated bouts of jaundice
•Vague indigestion
•Persistent or recurrent abdominal and back pain
•Weight loss
•Hypoalbuminemicedema
Attacks can be precipitated by
•Alcohol abuse
•Overeating
•Opiates or other drugs that increase the muscle ton e
of the sphincter of Oddi.

24. Diagnosis
•Clinical suspicion.
•Mild/ no enzyme elevations
•CT/ USG -visualization of calcifications within the
pancreas
Complications
•Chronic malabsorption
•Severe chronic pain
•Pancreatic pseudocysts
•Pancreatic cancer.

25. Cystic Neoplasms
•Only 5% to 15% of all pancreatic cysts are neoplast ic
•Usually benign
•Some can be malignant.
Serous Cystadenomas
•Account for 25% of all pancreatic cystic neoplasms
•Composed of glycogen-rich cuboidal cells surroundin g
small cysts
•Cysts contain clear, straw -colored fluid
•Patients present with abdominal pain
•Female-to male ratio is 2 : 1.
•Benign
•Surgical resection is curative

26. •Serous cystadenoma.
•Only a thin rim of
normal pancreatic
parenchyma remains.
•The cysts are relatively
small and contain clear,
straw-colored fluid.

27. M/E •The cysts are lined by
cuboidal epithelium
without atypia.

28. PANCREATIC NEOPLASMS
•Pancreatic neoplasms can be
–Cystic or solid.
–Benign or malignant
Mucinous Cystic Neoplasms
•Usually in the body or tail of the pancreas
•Manifest as painless, slow -growing masses.
•The cystic spaces are filled with thick mucin
•Cysts are lined by a columnar mucinous epithelium
•Up to one third of these cysts can be associated wi th
an invasive adenocarcinoma.
•Treatment -Distal pancreatectomyfor noninvasive
cysts

29. Mucinous cystic neoplasm
•Mucinous multi-loculatedcyst
•The cysts are large and filled with mucin.
M/E
•The cysts are lined by columnar mucinous epithelium
•They have a densely cellular “ovarian” stroma.

30. IntraductalPapillary Mucinous Neoplasms
•Mucin-producing intraductalneoplasms.
•More common in men
•More frequently involve the head of the pancreas.
•Various grades of dysplasia
•Associated with an invasive adenocarcinoma

31. Intraductalpapillary
mucinous neoplasm.
•Prominent papillary
neoplasm distending
the main pancreatic
duct.

32. M/E •The papillary mucinous
neoplasm involved the
main pancreatic duct
and is extending down
into the smaller ducts
and ductules

33. Pancreatic Carcinoma
•Infiltrating ductal adenocarcinoma
of the pancreas
(“pancreatic cancer”) carries one of the highest
mortality rates.
PATHOGENESIS
•Inherited and acquired mutations in cancer-
associated genes.
•There is a progressive accumulation of genetic
changes in pancreatic epithelium as it proceeds fro m
non-neoplastic, to noninvasive to invasive carcinom a
•The most common lesions of pancreatic cancer arise
in small ducts and ductules, and are called pancrea tic
intraepithelial neoplasias(PanINs).

34. •60% -head
•15% -body
•5% -tail
•Remaining 20% -diffuse
•It is highly invasive
•It elicits an intense non-neoplastic host reaction
composed of fibroblasts, lymphocytes, and
extracellular matrix (
desmoplastic response
).
•Obstruction of common bile usually occurs in
carcinoma head pancreas -jaundice.

35. •Often extend through the retroperitoneal space,
entrapping adjacent nerves -pain
•Also invade the spleen, adrenals, vertebral column,
transverse colon, and stomach.
•Adjacent LNs are involved
•Liver often is enlarged due to metastatic deposits.
•Distant metastases may occur
–Lungs
–Bones.

36. Carcinoma of the
pancreas
•Usually hard, graywhite
poorly defined masses

37. M/E •Moderately to poorly
differentiated
adenocarcinoma
•Form tubular structures
or cell clusters
•Exhibit aggressive,
deeply infiltrative
growth pattern
•Dense stromal fibrosis
•Perineuralinvasion
•Lymphatic invasion

38. Clinical Features
•Typically remain silent until their extension impin ges
on some other structure.
•Pain - first symptom
•Obstructive jaundice
•Weight loss, anorexia, and generalized malaise and
weakness
•Migratory thrombophlebitis (Trousseau syndrome)
occurs in about 10% of patients ( d/t platelet
aggregating factors and pro-coagulants from the
tumor or its necrotic products).

39. •The clinical course is rapidly progressive and brie f.
•Less than 20% of pancreatic cancers are resectablea t
the time of diagnosis.
•Early diagnosis is important -endoscopic USG, high-
resolution CT

40. Assignment
2 marks •Name the hormones secreted by the pancreas
•Enzyme disturbance in pancreatitis (
acute and chronic
)
Long answer
•What are the causes of acute pancreatitis? Describe the
pathogenesis, pathological features (
gross morphology,
cut section and M/E
), clinical features and lab findings of
Acute pancreatitis.
•What are the causes of chronic pancreatitis? Descri be
the pathogenesis, pathological features (
gross
morphology, cut section and M/E
), clinical features and
lab findings of chronic pancreatitis.
•Describe the pathogenesis, pathological features (
gross
morphology, cut section and M/E
), clinical features and
prognosis of pancreas carcinoma.