This document provides an overview of chronic pancreatitis, including its definition, epidemiology, pathology, etiology, clinical features, complications, diagnosis, and treatment. Key points include: chronic pancreatitis results from permanent pancreatic damage and inflammation; common causes include alcohol abuse and genetic factors; complications involve pain, diabetes, maldigestion; diagnosis utilizes tests of pancreatic structure and function; treatment focuses on pain management, enzyme supplementation, and addressing underlying causes such as alcohol cessation.

1. CHRONIC
PANCREATITIS

2.  DEFINITION
 EPIDEMIOLOGY
 PATHOLOGY
 PATHOPHYSIOLOGY
 ETIOLOGY
 CLINICAL FEATURES
 COMPLICATIONS
 PHYSICAL EXAMINATION
 DIAGNOSIS
 TREATMENT

3.  DEFINITION :
Permanent & irreversible damage to pancreas with inflammation ,
fibrosis & gland destruction
 Acute & Chronic pancreatitis
two ends of same spectrum
 Histological evidence
without c/fs

6. EPIDEMIOLOGY –
 Alcohol abuse – 2/3rd of cases
 Geographic variation
 Mortality Rate – 3.6
 Continued alcohol use – increased mortality risk by 60%
 Cause of death – conditions
associated with smoking , alcoholism , pancreatic cancer

7. PATHOLOGY –
 Interlobular fibrosis
 Infiltration of lymphocytes , plasma cells & macrophages
 Ducts – Eosinophilic plugs , dialation & strictures
 Islets – involved very late in the course of disease
 Calcified protein plugs – cause duct obstruction

8.  Obstructive Chronic Pancreatitis –gland upstream of obstruction
 Autoimmune Chronic Pancreatitis -
Positive for IgG4 staining
Obstructive phlebitis of major
and minor veins
Whirling fibrosis
Diffuse or segmental irregularity
& narrowing of pancreatic duct

9.  PATHOPHYSIOLOGY –
 Cellular necrosis & apoptosis
 Fibrogenesis by stellate cells
 PP OF ALCOHOLIC C.P. –
 10% Of. heavy alcohol users
 Alcohol Acetaldehyde in liver
Fatty Acid Ethanol Esters ( FAEE) in Pancreas
increase in IC Ca+ & Cell injury

10.  Alcohol Increases sensitivity to CCK
 Alcohol & metabolites Stimulate Stellate cell
 STELLATE CELL –
Quiscent cells - Vitamin A & lipid
Activated Stellate cell - Myofibroblastic
Secrete ECM
Proliferation
Migration
Phagocytosis
 alcohol use protein rich & low volume & HCO3-

11.  Genetic Background in C.P. –
PRSS1 mutations
SPINK1/PTSI Idiopathic &Heriditary & Tropical pancreatitis
CFTR
 SAPE hypothesis –
- Sentinel Acute Pancreatitis Event theory
- Alcohol & other stimuli
Activation of MMPs Destruction of normal collagen &
Pro inflammatory cytokines release
Activation of PSCs & remodeling

12.  TIGAR –O CLASSIFICATION SYSTEM FOR ETIOLOGY OF CHRONIC PANCREATITIS –
- Toxic – Metabolic
Alcohol
Tobacco Smoking
Hypercalcemia
Hyperlipidemia
- Idiopathic
Early onset
Late onset
Tropical
- Genetic
PRSS1 , CFTR , CASR, CTRC, SPINK1 gene mutations

13. - Autoimmune
Type 1
Type 2
- Recurrent , Severe Acute Pancreatitis
Post necrotic
Vascular diseases
Radiation
- Obstructive
Pancreas Divisum
Duct Obstruction
Duodenal wall cysts
duct scars

14. ETIOLOGY –
1. ALCOHOL –
 5 years of intake of >150gm/day
 Cofactors - Smoking ,
Genetic polymorphisms ,
Protein & fat rich diet
trace element deficiency
 Recurrent acute pancreatitis for 5-6years
 Prognosis - poor
2. TOBACCO –
 Independent risk factor & increases r/o pancreatic cancer

15. 3. TROPICAL PANCREATITIS –
 Mean age – 24years
 Classical – pain abdomen , severe malnutrition , endocrine & exocrine insufficiency
 endocrine insufficiency - inevitable
 Steatorrhea – rare
 Mutations in SPINK1 & Chymotrypsinogen gene
 environmental triggers
Cyanogenic glycosides in cassava
Trace element deficiency
Oxidative stress
PEM
4. GENETIC –
 PRSS1/Cationic Trypsinogen Gene
 Rest - cofactors or modifier genes

16. 5. AUTOIMMUNE PANCREATITIS –
 Characteristic feature – lymphoplasmacytic cells with IgG4 expression
 IgG4 antibodies - UBR2, H.pylori protein
 Rapid response to Glucocorticoid therapy
 MC in men & in middle age
 MC presentation – painless obstructive jaundice
 USG – Diffusely enlarged pancreas
 CT – Sausage shaped pancreas with delayed & prolonged enhancement
 Lab – Raised Sr. Igs esp Sr. IgG4 > 280 mg/dL

17.  Salivary glands , Kidneys, Retroperitoneum, Bile ducts
 Mayo clinic HISORt criteria for autoimmune pancreatitis –
- Histology
- Imaging
- Serology
- Other organ involvement
- Response to glucocorticoid therapy

18. 6. OBSTRUCTIVE CHRONIC PANCREATTITS –
 Tumors , Scars , Stones, Strictures
 Pancreas divisum
7. RECURRENT OR SEVERE ACUTE PANCREATITIS –
 Pancreatic necrosis or Surgical debridement
 Hypertriglyceridemia >1000mg/dL
8. ASYMPTOMATIC PANCREATIC FIBROSIS –
 Elderly,
 Chronic renal failure ,
 hemodialysis

19. 9. IDIOPATHIC CHRONIC PANCREATITIS –
 Two types – Early onset & Late onset
EARLY ONSET ICP LATE ONSET ICP
Mean Age – 20 years 56 years
Gender Distribution – Equal Equal
Predominant c/f – Pain Exocrine & endocrine insufficiency

20. CLINICAL FEATURES OF CHRONIC PANCREATITIS –
 Abdominal Pain
 Steatorrhea
 DM

21. ABDOMINAL PAIN –
 Epigastric,
 deep boring & penetrating
 worsened after a meal ,
 relieved by sitting or leaning forward ,assuming knee chest position on one side & clasping knees onto
chest
 Causes of pain –
1. tissue ischemia
2. Altered peripheral & central nociception
3. Complications
4. Hyperstimulation by CCK

22. STEATORRHEA –
 lipase secretion is reduced to <10% of maximal output
 Bulky foul smelling stools or passage of frank oil droplets
 Vs small bowel diarrhea – No Watery diarrhea & abdominal cramps
 Fat maldigestion earlier & severe compared to protein & carbohydrate maldigestion
R – 1. Lipase secretion decreases earlier
2. Lipase more sensitive to acid destruction & pancreatic proteases
3. Bile salt precipitation
 Median time for development of exocrine insufficiency – 13 – 26 years
 Weight loss – less common

23.  Weight loss can occur with
1. painful flares
2. Small bowel bacterial overgrowth
3. Pancreatic or extrapancreatic malignancy
 Fat soluble vitamin deficiencies – esp. Vit D def

24.  DIABETES MELLITUS –
 MC after pancreatic resection & tropical pancreatitis
 Vs Type 1 or Type 2 DM –
1. Loss of hepatocyte insulin receptor Decreased hepatic
glucose output d/t IAPP
2. Decrease in stimulated glucagon secretion due to coexistent alpha cell injury
prolonged & severe hypoglycemia with insulin Rx
 Mean time to development of DM - 19 – 26 years

25.  COMPLICATIONS OF CHRONIC PANCREATITIS –
- Chronic Abdominal Pain
- DM / IGT
- Gastroparesis
- Malabsorption
- GI bleeding
- Cholestatic Jaundice
- Biliary stricture / Biliary Cirrhosis
- Metabolic bone disease
- Pancreatic Fistulas
- Pancreatic Cancer

27. PHYSICAL EXAMINATION IN CHRONIC PANCREATITIS –
 Abdominal tenderness
 Weight loss
 Jaundice
 Palpable spleen
 Coexistent autoimmune features

28. DIAGNOSIS OF CHRONIC PANCREATITIS –
 Two categories
1. Tests for pancreatic function
2. Tests for pancreatic structure
 All diagnostic tests more accurate in far advanced disease

29.  Functional abnormalities – Reduced maximal secretory capacity
Exocrine insufficiency
Endocrine insufficiency
 Structural abnormalities - Main pancreatic duct
Side branches
Parenchyma
 Classified as
Small duct disease Big duct disease
Normal / Equivocal on Imaging Abnormalities in duct on imaging
Functional abnormalities less common More common
MC Idiopathic MC d/t Alcohol abuse
Rx – Medical therapy Duct Decompression

30. TESTS FOR PANCREATIC FUNCTION –
 Two types – Direct
 Indirect
DIRECT TESTS –
 Direct Hormonal stimulation – most sensitive
 Mean peak bicarbonate conc. - > 80 mEq/L - N
 Hormonal stimulation is more sensitive & specific than ERCP
 Limitations - Not well standardized
Limited availability
Oroduodenal tube for an hour or more

31. INDIRECT TESTS –
 Include Sr. Trypsinogen
Pancreatic enzymes in stool
Fecal fat excretion
 Serum trypsinogen < 20 ng/mL in advanced chronic pancreatitis
 False positive in Other malabsorptions , diarrheal diseases , severe malnutrition
 Fecal Elastase < 200 microgm/ gm of stool
 Fecal fat is measured over a 7 hr stool collection
 N < 7% of ingested fat in stool
 > 6 fat globules per hpf is abnormal

32. TESTS FOR PANCREATIC STRUCTURE –
1. Plain abdominal radiography –
 Diffuse pancreatic calcification is specific
 MC in alcoholic , late onset idiopathic , hereditary , tropical pancreatitis
2. Abdominal USG –
 Difficult to distinguish age related variability form chronic pancreatitis
3. CT –
 Grading can be done on CT / USG into Normal, Equivocal , Mild-moderate & Severe

33.  Findings in chronic pancreatitis – Duct dilatation
Duct obstruction
Parenchymal heterogenity
Irregular contour
Calcification
4. MRI –
 Duct Visualisation improved by secertin administration
5. ERCP –
 Diagnostic as well as therapeutic
 Risk - 5%
 Diagnosis based on abnormalities in main pancreatic duct & side branches

35.  CHAIN OF LAKES Appearance
 Changes similar can also be seen with normal ageing
 CAMBRIDGE GRADING OF CHRONIC PANCREATITIS ON ERCP
GRADE MAIN PANCREATIC DUCT SIDE BRANCHES
NORMAL Normal Normal
EQUIVOCAL Normal <3 Abnormal
MILD Normal >/= 3 Abnormal
MODERATE Abnormal “
SEVERE Abnormal with
Large cavity >10mm)
Obstruction
Filling defects
Severe dilatation /
irregularity
“

36. 6. ENDOSCOPIC USG –
 Presence of >/= 3 features is positive
 Rosemont criteria -
 Score >5 highly specific
 Score of 3 or 4 is indeterminate
 EUS abnormalities in chronic pancreatitis -
PARENCHYMAL ABNORMALITIES DUCTAL ABNORMALITIES
Hyperechoic foci Main duct dilatation & irregularity
Hyperechoic strands Hyperechoic ductal walls
Lobularity of contour Visible side branches
Cysts Calcification

38. DIAGNOSTIC STRATEGY IN CHRONIC PANCREATITIS –
 In patients with pain as primary complaint & suspected chronic pancreatitis
High quality multidetector CT / MRI With MRCP is best initial diagnostic test
If nondiagnostic , Hormal stimulation direct pancreatic testing , If unavailable , EUS
 If exocrine or endocrine insufficiency is suspected
Fecal Elastase / Serum Trypsinogen / USG / CT

39.  TREATMENT -
 1. ABDOMINAL PAIN
 associated conditions
- Pancreatic pseudo cyst
- Duodenal & bile duct compression
- Superimposed pancreatic cancer
- Gastroparesis
 Identify patients with big duct pancreatitis
 MEDICAL THERAPY –
1. Analgesics
2. Cessation of Alcohol & Tobacco
3. Antioxidants
4. Pancreatic enzyme therapy
5. Octreotide

40.  ANALGESIA –
 acetaminophen or aspirin
 narcotic analgesics
 Propoxyphene or Tramadol
 Coexistence depression lowers pain threshold
 TCAs
 SSRIs
 SNRIs
 Voltage gated N type Ca channel inhibitors.

41.  CESSATION OF ALCOHOL & TOBACCO
 ANTIOXIDANTS –
- Selenium , beta carotene , Vitamin C, Vitamin E & methionine

42.  PANCREATIC ENZYME THERAPY –
- deliver proteases to duodenum or very proximal jejunum
- Enteric coated preparations may not release majority of proteases until they reach the
more distal small bowel
- Non Enteric coated preparations
- Non enteric coated enzymes cinactivated by gastric acid , concomitant use of
acid suppressant
- Enzyme therapy is not successful in pain a/w big duct chronic pancreatitis

43.  OCTREOTIDE –
- Reduces pancreatic secretion & circulating CCK levels
- It also has some direct anti nociceptive effect
 ENDOSCOPIC THERAPY –
- Most appropriate in patient with dominant stricture & ductal stone
- Options include
Pancreatic duct Sphincterotomy
Stent Placement
Pancreatic duct stone removal
I

44.  SURGICAL THERAPY –
- Considered for intractable pain abdomen with failed medical therapy
- Other indications
Other organ involvement
Failure of endoscopic therapy for pseudo cysts
Internal pancreatic fistulas
Exclusion of malignancy
- For pain , Pancreatic duct drainage
Resection of all or part of pancreas
 NERVE BLOCK & NEUROLYSIS –
- Celiac plexus block with a glucocorticoid & LA Under
- Celiac plexus neurolysis with absolute alcohol EUS or CT guidance

45.  2. TREATMENT OF MALDIGESTION & STEATORRHEA –
- 30,000 IU / 90,000 USP of lipase with prandial & postprandial
portion of each meal
- Concomitant acid suppression with H2RA or PPI necessary with enteric coated tablets
- Clinical parameters to gauge the effectiveness of enzyme supplementation
Improvement in stool consistency
Loss of visible fat in stool
Gain in body weight
- periodically evaluate for fat soluble vitamin deficiencies especially Vitamin D
- BMD assessment for osteopenia is necessary
- Causes for failure of enzyme therapy
Inadequate dose d/t Patient Noncompliance ( MC cause ) Have patient
eat more frequent , small meals

46. - If. fail , search for an alternative cause for malabsorption
- If all measures fail , replace diet fat with medium chain TGs

47.  3. TREATMENT OF DIABETES MELLITUS –
- Therapy is directed at control of urinary losses of glucose
- Insulin requirement is lower than that with T1 DM patients
- Overvigorous BG control are a/w hypoglycemia
- Tight BG control are indicated in patients with hyperlipidemic
pancreatitis

48.  TREATMENT OF AUTOIMMUNE PANCREATITIS –
- Glucocorticoids have clinical , histolopathological & morphological efficacy
- Start with Prednisone at 40 mg/ day for 4 weeks
- Parameters to be followed include
Symptomatic relief
Serial changes in pancreas & bile ducts on imaging
Reduced serum gamma globulin & IgG4 levels
Improvement in liver tests
- Poor response to GCs in 2 to 4 weeks should raise the suspicion of pancreatic cancer or
other causes of Chronic pancreatitis
- For relapse , agents useful are
6- Mercaptapurine , Azathioprine , Rituximab, Cyclosporine & Cyclophosphamide

49.  REFERENCES –
- Sleisenger & Fordtran GI and Liver Disease , 9th Ed
- Harrison Principles of Internal Medicine 19th Ed

50. THANK YOU