Chronic pancreatitis

• Chronic pancreatitis is a chronic

inflammatory disease characterized by fibrosis
and destruction of exocrine pancreatic tissue.

• Diabetes mellitus occurs in advanced cases

because the islets of Langerhans are involved
Y EPIDEMIOLOGY
• Incidence with Chronic pancreatitis in Europe and the US
is 4-8 cases per 100 000 population per year;
• Chronic pancreatitis occurs 4 times more often in men than
women;
• In developed countries Chronic pancreatitis is noticeably
"younger“:
• - the average age of patients decreased from 50 to 39 years;
• - the proportion of alcoholic pancreatitis increased from
40% to 75%.
Causes of chronic pancreatitis

Toxic–metabolic Genetic
• Alcohol • Hereditary
• Tobacco pancreatitis
• Hypercalcaemia (cationic trypsinogen
mutation)
• Chronic kidney disease
Idiopathic
• SPINK-1 mutation
• Tropical • Early-/late- • Cystic fibrosis
onset types
Causes of chronic pancreatitis (cont.)
Autoimmune
• In isolation or as part of multi-organ problem
Recurrent and severe acute pancreatitis
Obstructive
• Ductal adenocarcinoma
• Intraductal papillary mucinous neoplasia
• Pancreas divisum
• Sphincter of Oddi stenosis
CLASSIFICATION
ON ETIOLOGY AND PATHOGENESIS
Secondary forms
Primary forms
• - biliary-dependent;
• - alcoholic; • - associated with pathological
• - hereditary; processes in the duodenum;
• - drug; • - infectious;
• - ischemic;
• - autoimmune;
• - traumatic;
• - metabolic;
• - metabolic;
• - idiopathic. • - radiation.
Pathophysiology
• Around 80% of cases in Western countries result
from alcohol misuse.
• In southern India, severe chronic calcific
pancreatitis occurs in non-alcoholics, possibly as a
result of malnutrition, deficiency of trace
elements and micronutrients, and cassava
consumption.
Pathophysiology
• Alcohol and other risk factors may trigger acute pancreatitis
through multiple mechanisms. The first (or ‘sentinel’)
episode of acute pancreatitis initiates an inflammatory
response involving T-helper (Th) cells.
• Ongoing exposure to alcohol drives further inflammation but
this is modified by regulatory T cells (Treg)with subsequent
fibrosis, via activation of pancreatic stellate cells.
• A cycle of inflammation and fibrosis ensues, with
development of chronic pancreatitis.
• Alcohol is the most relevant risk factor.
• In рathogenesis, activation of own enzymes
(trypsinogen, chymotrypsinogen, proelastase, and
phospholipase A) of the pancreas followed by the defeat
of its tissue.
• This leads to the development of edema, coagulative
necrosis and fibrosis of the pancreatic tissue.
• The process of fibrosis with consecutive loss of
pancreatic parenchyma leads to exocrine insufficiency
and maldigestia and, in advanced stages of the disease,
to diabetes mellitus.
• Ectatic ducts,
fibrosis and
dystrophic
calcifications of
the pancreatic
parenchyma
 Clinical features
• Chronic pancreatitis predominantly affects middle-
aged alcoholic men.
• Almost all present with abdominal pain.
• Pain is due to a combination of increased pressure
within the pancreatic ducts and direct involvement of
peripancreatic nerves by the inflammatory process
Pain syndrome
• pain localized in epigastrium, left or right
hypochondrium, around the navel;
• Pain can irradiates to the back, lumbar region;
• pain can be constant or intermittent, dull or acute;
• pain intensifies after taking fatty, spicy food,
drinking alcohol, lying on the back;
Features
• pain is typically worse 15 to 30 minutes following a
meal
• steatorrhoea: symptoms of pancreatic insufficiency
usually develop between 5 and 25 years after the
onset of pain
• diabetes mellitus develops in the majority of
patients. It typically occurs more than 20 years after
symptom begin
Dyspeptic syndrome:
• nausea;
• vomiting, not bringing relief;
• loss of appetite;
• flatulence.
Symptoms of maldigestia and malabsorption:
• a copious stool (polyphecal), mushy with an unpleasant odor;
• the stool is poorly washed with water and leaves traces on the
toilet;
• Pancreatic insufficiency: diarrhea (steatorrhea) and weight
loss caused by malabsorption, the frequency of defecations
can vary up to 4-6 times a day or more;
Pancreatic insufficiency is a common cause of
malabsorption.
a. Pancreatic enzymes, such as trypsin,
chymotrypsin, amylase, and lipase are required for
intraluminal digestive functions.
b. Pancreatic acinar damage in chronic pancreatitis
and cystic fibrosis leads to malabsorption of fats
and proteins.
Clinical features (cont.)
• Weight loss is results from a combination of
anorexia, avoidance of food because of
post-prandial pain, malabsorption and/or
diabetes.
• Steatorrhoea occurs when more than 90% of
the exocrine tissue has been destroyed;
• protein malabsorption develops only in the
most advanced cases.
• Physical examination reveals a thin, malnourished
patient with epigastric tenderness.
• Many patients have features of other alcohol- and
smoking-related diseases.
Complications of chronic pancreatitis
• Pseudocysts and pancreatic ascites
• Obstructive jaundice due to benign stricture of the
common bile duct as it passes through the diseased pancreas
• Duodenal stenosis
• Portal or splenic vein thrombosis leading to segmental
portal hypertension and gastric varices
• Peptic ulcer
LABORATORY EXAMINATION
• CBC – increased ESR, leukocytosis with a shift to the left at
an exacerbation.
• Urinalysis for a-amylase,
• Fecal pancreatic elastase.
Biochemical tests
- Elevated serum amylase, serum lipase, LFT,
- transaminases,
- alkaline phosphatase,
- fibrin,
- glucose.
Scatology investigation
Reveals:
- greasy consistency,
- undigested fibers,
- kreatoreya,
- steatorrhea,
- amylorrhea in severe exocrine insufficiency.
Tests to establish the diagnosis
• Ultrasound
• Computed tomography (may show atrophy, calcification or
ductal dilatation)
• Abdominal X-ray (may show calcification)
• Magnetic resonance cholangiopancreatography
• Endoscopic ultrasound
Management
• Common activities: refusal from alcohol, smoking
• In severe chronic pancreatitis with severe pain and dyspeptic
syndromes, hunger is recommended for 1-3 days;
• During the exacerbation, fat intake is reduced to 70-80 grams
per day, sometimes up to 50 grams;
• Food intake up to 5-6 times a day in small portions.
• pancreatic enzyme supplements
• analgesia
Drug therapy is aimed at arresting pain, dyspeptic syndromes.
Relief of pain:
Myotropic spasmodics:
• - drotaverin 2% - 2-4 ml intramuscularly or intravenously;
• - mebeverine 200 mg x 2 times a day;
• - papaverine 2% - 2 ml intramuscularly 2 times a day;
• - no-spa 2% - 2 ml intramuscularly;
• - buscopan 1ml cubcutaneous 2-3 times per day.
• When the sphincter of Oddi is deficient, Motilium is used 0.01
grams 3-4 times a day.
Pain relief
• A range of analgesic drugs, particularly
NSAIDs, are valuable but the severe and
unremitting nature of the pain often leads to
opiate use with the risk of addiction.
• Analgesics, such as pregabalin and tricyclic
antidepressants at a low dose, may be effective.
• PPI and H2 blockers suppressing the synthesis
of hydrochloric acid, reduce the secretion
production and exocrine activity of the
pancreas. This has a pronounced analgesic
effect.
• PPI: omeprazole, lansoprazole, pantoprazole,
rabeprazole.
• H2 receptor blockers – ranitidine, famotidine.
Antacids, neutralizing hydrochloric acid - reduce of
secretin production. This leads to a decrease in the
exocrine function of the pancreas.
• (Maalox, remagel, almagel – 10-15 ml in 15 min before
meal or 1 - 1.5 hours after meals and at night).
Sandostatin (octreotide) is a synthetic analogue of
somatostatin, inhibits the formation of secretin and
pancreosimin in the duodenum, increases the release of
endogenous morphines with an analgesic effect.
• Assign 100 mcg subcutaneously 3 times a day, 5-10
days.
Oral pancreatic enzyme supplements suppress
pancreatic secretion.
• - Panzinorm 1 - 2 tablets 3-4 times a day with
meals;
• - Festal 2 tablets 3 times a day with meals;
• - Creon 1 capsule 3 times with meal;
• - Mezim forte 1 tablet 3 times with meal.
In case of the development of purulent complications of
chronic pancreatitis: parapancreatitis, cholangitis, abscess,
prescribe high doses of antibiotics intravenously.
These
include cyclosporins 3 to 4 generations, fluoroquinolones:
• ciprofloxacin 200 mg 2 times per day,
• ofloxacin 200 mg 2 times per day,
• cefotaxime 1-2 gr 2 times per day.
• To correct the water-electrolyte balance, intravenously
injected saline solutions, reopolyglucin, Ringer's solution,
glucose.
 CHOLELITHIASIS

The presence of cholesterol, pigment, or mixed stones

(calculi) within the gallbladder
Synonym(s): gallstones

• Up to 24% of women and 12% of men may have

gallstones.
• Of these up to 30% may develop local infection and
cholecystitis.
EPIDEMIOLOGY
Incidence
• Increases with age ~1–3% per year; peaks at 7th decade
• 2% of the U.S. population develops gallstones annually.
Prevalence
• 8–10% of the U.S. population with gallstones
• 20% >65 years of age
• Female > male (2 to 3:1)
ETIOLOGY AND PATHOPHYSIOLOGY
Gallstone formation is a complex process mediated by genetic,
metabolic, immune, and environmental factors.
• Gallbladder sludge (a mixture of cholesterol crystals, calcium
bilirubinate granules, and mucin gel matrix) serves as the nidus
for gallstone formation.
Bile supersaturated with cholesterol (cholesterol stones)
precipitates as microcrystals that aggregate and expand.
• Stone formation is enhanced by biliary stasis or impaired
gallbladder motility.
ETIOLOGY AND PATHOPHYSIOLOGY
Bile supersaturated with cholesterol (cholesterol
stones) precipitates as microcrystals that aggregate
and expand.
• Stone formation is enhanced by biliary stasis or
impaired gallbladder motility.
RISK FACTORS
• Older age (>50 years)
• Obesity
• Pregnancy
• High-fat diet rich in cholesterol
• Prolonged total parenteral nutrition
• Rapid weight loss
• Diseases of the terminal ileum causing decreased
reabsorption of bile acids
RISK FACTORS
• Hereditary
• Hemolytic disorders (hereditary spherocytosis,
sickle cell anemia, etc.), cirrhosis (black/pigment
stones)
• Medications (estrogen replacement therapy at
high doses, and long-term corticosteroid or
cytostatic therapy)
• Viral hepatitis, biliary tract infection, and stricture
(promotes intraductal formation of pigment
stones)
Types of gallstones
• Distinguish 3 types of gallstones:
- Cholesterol stones (80-90%),
- Black pigmented stones (10-20%),
- Brown pigmented stones (10-20%).
Clinical features of gallstones
• Asymptomatic (80%)
• Biliary colic
• Acute cholecystitis
• Chronic cholecystitis
DIAGNOSIS
• Mostly asymptomatic (80%). In 15-20% of cases may appear clinical
symptoms.
• The classical symptoms are of colicky episodic right upper quadrant or epigastric
pain lasting >15 minutes and sometimes radiating to the back (biliary colic
—due to transient cystic duct obstruction).
• Pain is usually postprandial. Pain occurs after taking fatty, fried, spicy
foods, alcohol.
• Pain sometimes awakens patients from sleep.
• Bitterness in the mouth.
• Flatulence;
• Nausea;
• Heartburn.
DIAGNOSIS (cont.)
Other symptoms include
• nausea, vomiting,
• indigestion or bloating sensation, and
• fatty food intolerance.
PHYSICAL EXAM
• Epigastric and/or right upper quadrant tenderness
(Murphy sign) is a traditional physical finding
associated with acute cholecystitis.
• Charcot triad: fever, jaundice, right upper quadrant pain
historically associated with cholangitis
PHYSICAL EXAM(cont.)
Reynolds pentad:
• fever,
• jaundice,
• right upper quadrant pain,
• hemodynamic instability,
• mental status changes; also classically associated with
ascending cholangitis
DIFFERENTIAL DIAGNOSIS
• Peptic ulcer diseases and gastritis
• Pancreatitis
• Cholangitis
• Gallbladder cancer
• Gallbladder polyps
• Acalculous cholecystitis
• Biliary dyskinesia
• Choledocholithiasis
DIAGNOSTIC TESTS & INTERPRETATION
• Leukocytosis and elevated C-reactive protein level are
associated with acute calculus cholecystitis.
• LFT
• Ultrasound is the investigation of choice for diagnosing
gallstones.US detects gallstones in 97–98% of patients.
• CT, MRCP scan (magnetic resonance
cholangiopancreatography), has no advantage over US
except for detecting complications of gallstones (distal
common bile duct stone or gallbladder empyema).
• 10–30% of gallstones are radiopaque calcium or
pigment-containing gallstones (visible on plain x-
ray).
• A “porcelain gallbladder” is a calcified
gallbladder (also visible by x-ray) that is
associated with chronic cholecystitis and
gallbladder cancer.
GENERAL PREVENTION
• Ursodiol (Actigall) taken during rapid weight loss
prevents gallstone formation.
• Regular exercise and dietary modification may reduce
the incidence of gallstone formation.
• Lipid-lowering drugs (statins) may prevent cholesterol
stone formation by reducing bile cholesterol saturation.
Test Interpretation
• Pure cholesterol stones are white or slightly yellow.
• Pigment stones may be black or brown. Black stones
contain polymerized calcium bilirubinate, most often
secondary to cirrhosis or hemolysis; these almost always
form within the gallbladder.
• Brown stones are associated with biliary tract infection,
caused by bile stasis, and as such may form either in the
bile ducts or gallbladder.
COMPLICATIONS
• Acute cholecystitis (90–95% secondary to gallstones)
• Empyema of the gallbladder
• Choledocholithiasis
• Acute pancreatitis
• Fistulae from gallbladder to duodenum/colon
• Pressure on/inflammation of the common hepatic duct by a
gallstone in the cystic duct (Mirizzi’s syndrome)
• Gallstone ileus (Bouveret syndrome is a variant of gallstone ileus
where the gallstone lodges in the duodenum or pylorus causing a
gastric outlet obstruction)
• Gallbladder cancer
DIET
• A low-fat diet may help.
MEDICATION
First Line
• Analgesics for pain relief
• – Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-
choice treatment for pain
• control which is equivalent to opioid therapy.
• – Opioids are an option for patients who cannot tolerate or fail
to respond to NSAIDs.
• Antibiotics for patients with acute cholecystitis
SURGERY/OTHER PROCEDURES
• Asymptomatic gallstones which are located in the
gallbladder are common and do not require treatment.
• Surgery should be considered for patients who have
symptomatic cholelithiasis or gallstone related
complications (e.g., cholecystitis) or
• in asymptomatic patients with immune suppression,
calcified gallbladder, or family history of gallbladder
cancer.
• Symptomatic gallstones are best treated
surgically.
• Cholecystectomy: surgical technique
• Laparoscopic vs. open cholecystectomy
• Thus, surgery is currently considered the only
effective treatment in the management of
symptomatic gallstones.
• Medical treatment for gall bladder stone is
amenable for : stones less than 15 mm in size
• Can use oral dissolution therapy
(ursodeoxycholic acids)
• Extracorporeal shock wave lithotripsy is a
noninvasive therapeutic alternative for
symptomatic patients who are not candidates for
surgery. The lithotripsy was effective only in a
small proportion of patients
PATIENT EDUCATION
• Change in lifestyle (e.g., regular exercise) and
dietary modification (low-fat diet and reduction of
total caloric intake) reduce gallstone-related
hospitalizations.
 Chronic cholecystitis
Chronic cholecystitis: chronic inflammation and fibrosis of
the gallbladder
• Typically associated with cholelithiasis
• Can by seen with dyskinesia of the gallbladder
• Symptoms include biliary colic
Patients may
• recover spontaneously or following analgesia and
antibiotics.
• They are usually advised to undergo elective laparoscopic
cholecystectomy.
Best diagnosis of pancreatic disease:
a. Ultrasound
b. CT scan
c. ERCP
d. PTC
1. Davidson 23rd Edition
2. The 5 Minute Clinical Consult 2021 by Domino 29ed
2021
3. Johns_Hopkins_Internal_Medicine
4. 07.kasper notes 2020 gastroenterology
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