PANCREATITIS

DR ISAAC ERSKINE
DEPT OF PATHOLOGY, KBTH
OUTLINE
• Anatomy of pancreas
• Acute pancreatitis
• Chronic pancreatitis
Anatomy
• The adult pancreas is a transversely oriented retroperitoneal organ
extending from the C-loop of the duodenum to the hilum of the
spleen
• In adults the pancreas usually measures 15 to 20 cm in length and
weighs 85 to 120 g. It is slightly larger in men than in women
• The four anatomic regions of the pancreas (the head, neck, body, and
tail) are grossly indistinct
• A complex lobulated organ with distinct exocrine and endocrine
components.
Anatomy
Anatomy
• The exocrine pancreas constitutes 80% to 85% of the organ and is
composed of acinar cells that secrete enzymes needed for digestion.
• Acinar cells are pyramidally shaped epithelial cells containing
membrane-bound granules rich in proenzymes (zymogens),
including trypsinogen, chymotrypsinogen, procarboxypeptidase,
proelastase, kallikreinogen, and prophospholipase A and B.
• Upon secretion, these proenzymes and enzymes are carried by a
series of ductules and ducts to the duodenum, where they are
activated by proteolytic cleavage in the gastrointestinal tract
Anatomy
• The endocrine pancreas constitute only 1% to 2% of the organ.
• It is composed of about 1 million clusters of cells, the islets of
Langerhans, scattered throughout the gland.
• The islet cells secrete insulin, glucagon, and somatostatin
Anatomy
Anatomy
Pancreatitis
• Basically inflammation of pancreas
• 2 forms
• Acute
• Chronic
• Pancreatitis occurs when the protective mechanisms in pancreas are
deranged or overwhelmed
Pancreatitis
• Protective mechanisms
• Most digestive enzymes are synthesized as inactive proenzymes
(zymogens), which are packaged within secretory granules.
• Most proenzymes are activated by trypsin, which itself is activated
by duodenal enteropeptidase (enterokinase) in the small bowel;
thus, intrapancreatic activation of proenzymes is normally
minimal.
• Acinar and ductal cells secrete trypsin inhibitors, including serine
protease inhibitor Kazal type l (SPINK1), which further limit
intrapancreatic trypsin activity.
Acute pancreatitis
• Acute pancreatitis is characterized by reversible pancreatic
parenchymal injury associated with inflammation and has diverse
aetiologies
• toxic exposures (e.g., alcohol)
• pancreatic duct obstruction (e.g., biliary calculi)
• inherited genetic defects,
• vascular injury
• infections
• Acute pancreatitis results from inappropriate release and activation of
pancreatic enzymes, which destroy pancreatic tissue and elicit an
acute inflammation
Acute pancreatitis
• Inappropriate activation of pancreatic enzymes occurs in
1. Pancreatic duct obstruction. Obstruction is most commonly
caused by
gallstones and biliary sludge,
periampullary neoplasms (e.g., pancreatic cancer),
choledochocoeles (congenital cystic dilatation of the common
bile duct),
parasites (particularly Ascaris lumbricoides and Clonorchis
sinensis).
Obstruction raises intrapancreatic ductal pressure and leads to
the accumulation of enzyme-rich fluid in the interstitium
Acute pancreatitis
• Inappropriate activation of pancreatic enzymes cont’d
2. Primary acinar cell injury, leading to release of digestive enzymes,
inflammation, and autodigestion of pancreatic tissues. Acinar cells
can be damaged by a variety of endogenous, exogenous, and
iatrogenic insults that produce free radicals. Influx of calcium also
activates trypsin which in turn activates other proenzymes

3. Defective intracellular transport of proenzymes within acinar cells

leading to mixing up of lysosomal hydrolases and proenzymes.
Acute pancreatitis
• Alcohol
• Alcohol consumption transiently increases contraction of the sphincter of
Oddi (the muscle at the Papilla of Vater)
• Chronic alcohol ingestion results in the secretion of protein-rich pancreatic
fluid that leads to the deposition of inspissated protein plugs and obstruction
of small pancreatic ducts
• Alcohol also has direct toxic effects on acinar cells. Alcohol-induced oxidative
stress may generate free radicals in acinar cells, leading to membrane lipid
oxidation and free radical production; has been linked to activation of the
proinflammatory transcription factors AP1 and NF-κB
• Oxidative stress also may promote the fusion of lysosomes and zymogen
granules and alter intracellular calcium levels, possibly through mitochondrial
damage, promoting the intraacinar activation of trypsin and other digestive
enzymes
Acute pancreatitis
• Metabolic disorders, such as hypertriglyceridaemia, and
hypercalcaemic states, such as hyperparathyroidism
• Medications including furosemide, azathioprine, 2′,3′-
dideoxyinosine, oestrogens etc. In most cases the
mechanism of drug-induced pancreatitis is unknown.
• Traumatic injury of acinar cells, either by blunt abdominal
trauma or by iatrogenic injury during surgery or endoscopic
retrograde cholangiopancreatography
Acute pancreatitis
• Genetic lesions. Hereditary factors are increasingly being recognized
as a significant cause of pancreatitis. The disorder is genetically
diverse, but the shared feature of most forms is a defect that
increases or sustains the activity of trypsin (gain of function mutation
in trypsinogen gene).
• Ischemic injury of acinar cells, caused by shock, vascular thrombosis,
embolism, and vasculitis
• Infections, including mumps, can lead to acute pancreatitis through
direct acinar cell injury
Morphology
• The morphology of acute pancreatitis ranges from mild inflammation
and oedema to severe extensive necrosis and haemorrhage.
• The basic alterations are
(1) microvascular leak and oedema,
(2) fat necrosis
(3) acute inflammation
(4) destruction of pancreatic parenchyma
(5) destruction of blood vessels and interstitial haemorrhage.
• The extent of each of these alterations depends on the duration and
severity of the process.
Acute pancreatitis
• In the milder form, acute interstitial pancreatitis, histologic alterations are
limited to mild inflammation, interstitial oedema, and focal areas of fat necrosis
in the pancreas and the peripancreatic fat
• In the more severe form, acute necrotizing pancreatitis, there is necrosis of acinar
and ductal tissues as well as the islet. Vascular injury can lead to haemorrhage
into the pancreatic parenchyma. Macroscopically, the pancreatic sub- stance is
red-black from haemorrhage and contains interspersed foci of yellow-white,
chalky fat necrosis.
• In most cases the peritoneal cavity contains a serous, slightly turbid, brown-tinged
fluid
• In its most severe form, haemorrhagic pancreatitis, extensive parenchymal necrosis
is accompanied by dramatic haemorrhage within the substance of the gland.
Acute pancreatitis
Clinical features
• Abdominal pain is the cardinal manifestation of acute pancreatitis. Its
severity varies from mild and uncomfortable to severe and
incapacitating.
• Anorexia, nausea, and vomiting frequently accompany the pain.
• Elevated plasma levels of amylase and lipase support the diagnosis of
acute pancreatitis
• Full-blown acute pancreatitis is a medical emergency
Acute pancreatitis
Clinical features cont’d
• Many of the systemic features of severe acute pancreatitis can be
attributed to release of toxic enzymes, cytokines, and other mediators
into the circulation
• Explosive activation of a systemic inflammatory response, resulting in
leucocytosis, disseminated intravascular coagulation, oedema, and
acute respiratory distress syndrome. Shock, due to the systemic
inflammatory response syndrome and acute renal tubular necrosis
may occur.
Acute pancreatitis
Clinical features cont’d
• Hypocalcaemia due to precipitates of soap in fat necrosis and traps
ca++ in the soap. Persistent hypocalcemia is a poor prognostic sign.
• X-ray shows a large pancreas shadow.
• Prognosis- 5% die from shock in first week.
• Complications: shock, ARDS, ARF, abscess, pseudocyst, duodenal
obstruction from inflammation of pancreas.
CHRONIC PANCREATITIS
• Chronic relapsing inflammation of pancreas leading to progressive
destruction of pancreas.
• There are repeated flare-ups of silent or mildly symptomatic
pancreatitis.
• Occurs in same type of patient likely to get acute pancreatitis.
• Age: middle age.
• Sex: male > female, alcoholic or with biliary disease
• Cause: alcoholism, biliary disease, hypercalcaemia, hyperlipidaemia,
non alcoholic tropical pancreatitis (familial/hereditary) occurs in
childhood and predisposes to pancreatic ca. 40% of chronic
pancreatitis is idiopathic.
• Autoimmune pancreatitis is a pathogenically distinct form of chronic
pancreatitis that is associated with the presence of IgG4-secreting
plasma cells in the pancreas. Autoimmune pancreatitis is one
manifestation of IgG- related disease
• Pathogenesis is varied:
1. ductal obstruction by concretions e.g. alcohol induced
abnormal secretion lead to formation of concretions or
opiates abuse
2. interstitial fat necrosis and haemorrhage lead to fibrosis,
duct distortion and altered pancreatic secretions and flow.
• Morphology
• Chronic pancreatitis is characterized by fibrosis, atrophy and dropout of acini,
and variable dilation of pancreatic ducts .
• Grossly, the gland is hard, sometimes with visibly dilated ducts containing
calcified concretions
• These changes are typically accompanied by a chronic inflamma-tory
infiltrate around lobules and ducts.
• The ductal epithelium may be atrophied or hyperplastic or may show
squamous metaplasia
• There is usually relative sparing of the islets of Langerhans, which become
embedded in the sclerotic tissue and may fuse and appear enla-rged
• alcohol abuse is characterized by ductal dilatation and
intraluminal protein plugs and calcifications
• Autoimmune pancreatitis is characterized by a ductcentric mixed
inflammatory cell infiltrate, venulitis, and increased numbers
of IgG4-secreting plasma cells.
Clinical features
• Chronic pancreatitis may present in many different ways. It may
follow repeated bouts of acute pancreatitis.
• There may be repeated attacks of mild to moderately severe
abdominal pain, or persistent abdominal and back pain.
• Attacks may be precipitated by alcohol or opiates abuse
• High index of suspicion is required
Complications
• Pancreatic exocrine insufficiency,
• chronic malabsorption
• diabetes mellitus can all lead to significant morbidity and contribute
to mortality.
• Severe chronic pain is a dominant problem
• Pancreatic pseudocysts develop in about 10% of patients.
• Patients with hereditary pancreatitis have a 40% lifetime risk of
developing pancreatic cancer