PANCREATITIS
AGENESIS
totally absent
incompatible with life
Pancreatic duodenal homeobox 1 (PDX1) : transcription factor critical
for pancreatic development
PANCREATIC DIVISUM
In most individuals, main pancreatic duct (duct of Wirsung) joins
common bile duct just proximal to papilla of Vater
accessory pancreatic duct (duct of Santorini) drains into duodenum
through a separate minor papilla.
• failure of fusion of fetal duct systems of dorsal and ventral pancreatic
primordia
• bulk of pancreas (formed by dorsal pancreatic primordium) drains into
duodenum through small-caliber minor papilla
ANNULAR PANCREAS
ring of pancreatic tissue encircles duodenum.
duodenal obstruction such as gastric distention and vomiting.
ECTOPIC PANCREAS
stomach, duodenum, jejunum, Meckel diverticulum, ileum.
located in submucosa
normal pancreatic acini with islets
can be inflamed, leading to pain or mucosal bleeding
CONGENITAL CYSTS
unilocular and range from microscopic to 5 cm in diameter
lined by uniform cuboidal or flattened epithelium
enclosed in a thin, fibrous capsule
contain clear serous fluid (an important point of distinction from
pancreatic cystic neoplasms, which often are mucinous )
PANCREATITIS
Inflammation of pancreas
1. Acute (function return to normal if underlying cause is removed)
2. Chronic (irreversible destruction of exocrine pancreas)
ACUTE PANCREATITIS
reversible inflammatory disorder
ETIOLOGY
1. gallstones in common bile duct, impeding flow of pancreatic enzymes
through ampulla of Vater (gallstone pancreatitis)
2. excessive alcohol intake
3. Non–gallstone-related obstruction of pancreatic ducts ( pancreatic cancer,
pancreas divisum, biliary “sludge,” or parasites particularly Ascaris
lumbricoides & Clonorchis sinensis)
4. Medications: anti-convulsants, chemotherapeutic agents, thiazide diuretics,
estrogens
5. Infections: mumps virus or coxsackievirus
6. Metabolic disorders: hypertriglyceridemia, hyperparathyroidism, other
hypercalcemic states
7. Ischemia due to vascular thrombosis, embolism, vasculitis, or shock
8. Trauma during surgery or endoscopy
9. Germline mutations in genes encoding pancreatic enzymes or their
inhibitors.
HEREDITARY PANCREATITIS:
rare , autosomal dominant
recurrent attacks of severe pancreatitis, beginning in childhood
mutations
in PRSS1
gene which alter site pancreas
through which abrogating an Hyperact is prone
encodes ivation
important to
trypsinogen trypsin cleaves negative of autodiges
(proenzyme and inactivates feedback tion and
trypsin
of itself, injury
pancreatic
trypsin)
IDIOPATHIC PANCREATITIS
10% to 20% of cases of acute pancreatitis
subset : underlying germ line mutations of CFTR gene
PANCREATIC DUCT OBSTRUCTION
periacinar
myofibroblasts, and Edema
Blocks ductal flow, leukocytes release compromises
increasing intraductal cytokines that blood flow,
pressure, accumulation promote local
of enzyme rich inflammation and causing
interstitial fluid interstitial edema ischemic
through a leaky injury
microvasculature
PRIMARY ACINAR CELL INJURY
Ischemia
Viral infections (e.g., mumps)
Drugs
direct trauma to pancreas
WITHIN ACINAR CELLS
In normal acinar cells, digestive enzymes intended for zymogen
granules and hydrolytic enzymes destined for lysosomes are
transported in discrete pathways
1. Proenzyme
activation
pancreatic
proenzymes
2. Lysosomal
and lysosomal rupture (action of
Metabolic injury hydrolases phopholipases)
become
packaged
3. Release of
together activated enzymes
ALCOHOL & ACUTE PANCREATITIS
Increases pancreatic exocrine secretion
Contraction of sphincter of Oddi muscle regulating flow of pancreatic
juice
Direct toxic effects on acinar cells( oxidative stress )
chronic alcohol ingestion: secretion of protein-rich pancreatic fluid,
which leads to deposition of protein plugs
PATHOGENESIS
1. Autodigestion of pancreas by activated pancreatic enzymes. activated
trypsin converts zymogen forms of other pancreatic enzymes to active forms
2. Premature activation of trypsin unleash these proenzymes (e.g.,
phospholipases and elastases), leading to tissue injury and inflammation
3. Trypsin converts prekallikrein to activate form, thus sparking kinin system
4. activation of factor XII activates clotting and complement systems
MORPHOLOGY
microvascular leakage causing edema
necrosis of fat by lipases
proteolytic destruction of pancreatic parenchyma
destruction of blood vessels leading to interstitial hemorrhage.
MORPHOLOGY
MILD FORMS:
interstitial edema and focal areas of fat necrosis
released fatty acids combine with calcium to form insoluble salts that
precipitate
MORPHOLOGY
SEVERE FORM:
Acute necrotizing pancreatitis, damage involves acinar and ductal
cells, islets of Langerhans and blood vessels
Macroscopically, red-black hemorrhagic areas interspersed with foci of
yellow-white, chalky fat necrosis
CLINICAL FEATURES
Abdominal pain is cardinal manifestation : constant, intense and
referred to upper back
sudden onset of an “acute abdomen” with pain, guarding, and the
ominous absence of bowel sounds.
elevated plasma levels of amylase and lipase
Full-blown acute pancreatitis is a medical emergency.
PERIPHERAL VASCULAR COLLAPSE (SHOCK)
Increased microvascular permeability and resultant hypovolemia
Endotoxemia breakdown of barriers between gastrointestinal flora and
bloodstream)
renal failure due to acute tubular necrosis
acute respiratory distress syndrome (due to diffuse alveolar damage) &
diffuse fat necrosis
DIFFERENTIAL DIAGNOSIS
1. Perforated peptic ulcer
2. Biliary colic
3. Acute cholecystitis with rupture
4. Occlusion of mesensteric vessels with infarction of bowel
LABORATORY FINDINGS
1. Blood CP: Elevated TLC
2. markedly elevated serum amylase : first 24 hours
3. rising serum lipase levels: within 72-96 hours
4. Inflammatory markers: CRP raised
5. Serum calcium levels: Hypocalcemia can result from precipitation of calcium in areas of fat
necrosis; (poor prognostic sign)
6. DIC screening: thrombocytopenia, prolonged PT &APTT, hypofibrinoginemia, raised D-dimers
7. Imaging: Enlarged inflamed pancreas can be visualized on CT or (MRI)
MANAGEMENT
Supportive therapy ( maintaining blood pressure and alleviating pain)
Intravenous fluids
Resting pancreas by total restriction of oral food and fluids
COMPLICATIONS:
1. Infection: necrotic debris becomes infected usually by gram negative
organisms
2. Acute respiratory distress syndrome and acute renal failure
3. Pancreatic pseudocysts
PANCREATIC PSEUDOCYSTS
(SEQUELAE OF ACUTE PANCREATITIS)
Liquefied areas of necrotic laboratory
pancreatic tissue become walled assessment of
cyst aspirate Resolve or
off by fibrous tissue forming cystic (contains infected
space, lacking an epithelial lining pancreatic
(designation pseudo) enzyjmes)
compress or
perforate adjacent
structures
CHRONIC PANCREATITIS
long-standing inflammation
irreversible destruction of exocrine pancreas leading to loss of islets of
Langerhans.
recurrent bouts of acute pancreatitis can evolve over time into chronic
pancreatitis
ETIOLOGY
Middle-aged men
1. Long-term alcohol abuse (most common cause)
2. Duct Obstruction. (pseudocysts, calculi, neoplasms, or pancreas
divisum)
3. Tropical pancreatitis(hereditary basis)
4. Hereditary pancreatitis due to mutations in pancreatic trypsinogen
gene (PRRS1), or SPINK1 gene encoding a trypsin inhibitor
idiopathic” cases : inherited mutations in genes, such as CFTR
polymorphisms in genes encoding exocrine pancreatic enzymes,
including carboxypeptidase A1 (CPA1) and lipase (CEL)
PATHOGENESIS
DUCTAL • increase protein concentration of pancreatic secretions
OBSTRUCTION BY forming ductal plugs.
CONCRETION
• direct toxic effect on acinar cells
ALCOHOL • oxidative stress generate free radicals
• promotes fusion of lysosomes and zymogen granules with
OXIDATIVE STRESS resulting acinar cell necrosis, inflammation & fibrosis.
MUTATION
• Inappropriate activation of pancreatic enzymes
FIBROSIS IN CHRONIC PANCREATITIS
Infiltrating activation and
immune cells such
as macrophages proliferation of Cells deposit
produce TGF-β, periacinar collagen and
connective tissue myofibroblasts give rise to
growth factor, and (“pancreatic fibrosis.
platelet derived
growth factor stellate cells”),
MORPHOLOGY
• gland is hard
GROSS • extremely dilated ducts
• visible calcified concretion
• parenchymal fibrosis
• reduced number & size of acini
• variable dilation of pancreatic ducts
MICROSCOPIC • ductal epithelium: atrophied or hyperplastic or
exhibit squamous metaplasia
• islets of Langerhans embedded in sclerotic
tissue
visualization of calcifications within pancreas by CT or USG
AUTOIMMUNE PANCREATITIS
distinct form of chronic pancreatitis
infiltration of pancreas by lymphocytes and plasma cell (positive for
IgG4)
“swirling” fibrosis and venulitis (lymphoplasmacytic sclerosing
pancreatitis).
CLINICAL FEATURES CHRONIC PANCREATITIS
Attacks can be precipitated by:
1. Alcohol abuse
2. Overeating (which increases demand on pancreatic secretions)
3. opiates or drugs that increase muscle tone of sphincter of Oddi
CLINICAL FEATURES
Jaundice, indigestion In end-stage, acinar Diabetes mellitus
destruction so
abdominal and back
advanced that enzyme
pain elevations are absent.
• Weight loss and
Gallstone-induced hypoalbuminemic
• modest elevations of edema from
serum amylase obstruction: jaundice
or raised serum ALP malabsorption
SEQUELAE OF CHRONIC PANCREATITIS
1. Malabsorption
2. Endocrine dysfunction (diabetes mellitus)
3. Severe chronic pain
4. Pancreatic pseudocysts
5. Pancreatic cancer
6. Hereditary pancreatitis secondary to PRSS1 mutations lifetime risk for
pancreatic cancer. undergo prophylactic pancreatectomy
