Chronic pancreatitis

Ermias D (MD)
Definition
Irreversible damage to the pancreas with
histologic evidence of inflammation,
fibrosis, and destruction of exocrine
(acinar) and endocrine (islets of
Langerhans) tissue
Etiologic classification clinically useful
Histologic accessibiliy of tissue
Imaging late morphologic changes

prevalence
Autopsy reports 0.04-5% - overestimates
Retrospective studies 3-9/100,000
Prospective data
among alcoholics 8.2/yr/100,000;
overall prevalence - 27.4/100,000
Japan overall prevalence 28.5/100,000;
M:F =3.5:1
Alcohol abuse 2/3 of causes
Mortality 3.6X age matched control
Advanced age, alcoholism and smoking are
poor prognostic conditions

pathophysiology
Incompletely understood

Why 10% heavy alcoholics develop
chronic pancreatitis and the rest not, or
limited to asymptomatic pancreatic fibrosis

Alcohol is the most studied
Ductal obstruction hypothesis
Chronic alcohol use
acinar and ductal cell
protein rich pancreatic juice, low in volume and HCO3
formation of protein precipitates plug
calcification of ppt ductal stone formation
ductule obstruction
parenchymal damage

Pancreatic ductal stone are seen in alcoholic, tropical, hereditary,
idiopathic
Histologic changes of CP may be seen with out ductal obstruction

Toxic metabolic hypothesis
(alcohol) Direct injurious effect on acinar and ductal
cells
Increased membrane lipid peroxidation (oxidative
stress), free radical production
Increase acinar cell sensitivity to pathogenic
stimuli
Stimulate CCK production (duodenal I cells)
activation of proinflammatory transcription factors
Activation of pancreatic stellate cells (alcohol,
cytokines) produce proteins of extracellular matrix
Necrosis fibrosis hypothesis
Repeated episodes of acute pancreatitis with
cellular necrosis or apoptosis, healing replaces
necrotic tissue with fibrosis
Evidence from natural history studies - more severe
and frequent attacks
More evidence from hereditary pancreatitis and
animal models


But some have evidence of chronic pancreatitis
at time of first clinical acute attack
CFTR cystic fibrosis trans-membrane conductance regulator
Cystic fibrosis is ass. with abnormalities of HCO3
secretion, ductal dilatation, ppt formation, pancreatic
atrophy
Seen in 50% of idiopathic CP, not common in
alcoholic CP
PRSS1 cationic trypsinogen gene
Once trypsinogen is activated to trypsin, becomes
resistant to inactivation and activate other
proenzymes leading to episodes of acute pancreatitis
like necrosis fibrosis theory
SPINK1 - serine protease inhibitor Kazal type 1
Seen in pediatric ICP, hereditary P, TP; but not in chronic
alcoholic pancreatitis
Trypsin inhibitor, mimic trypsinogen gene

Genetic forms
Disease modifying genes
Polymorphisms that modulate immune
response
Cytokines
transforming growth factors , , interleukin-
10, interferon gamma
Etiologic factors ass. With CP: TIGAR-O
TROPICAL PANCREATITIS
Africa, India, Brazil; with in 30 latitude
A disease of early childhood and youth
> 90% before age of 40yrs
Prevalence in endemic areas: 1 in 500-800
Abdominal pain, malnutrition, exocrine and
endocrine insufficiency
Pancreatic caliculi 90%
Fibrocalculous pancreatic diabetes, tropical
calcific pancreatitis
50% SPINK1 gene mutation (N34S)
Unclear environmental trigger PEM, Cassava

Autoimmune pancreatitis
Confusing and evolving nomenclature
5% of CP, more in males, middle age
12 50% ass. With other autoimmune diseases
abdominal pain, weight loss, jaundice
Imaging studies show focal or diffuse (sausage
shaped) enlargement
Pancreatogram diffuse narrowing (thread like)
or alternating pattern
Dx clinical, imaging, Ig, autoAb
Tx glucocorticoids 1-2m and tappering in 3-4m
Diabetes mellitus
1% of DM from CP
In DM - pancreas is smaller,
abnormal duct in 40-50% ,
abnormal pancreatic fn in 40-50%
Insulin is a trophic factor for exocrine fn of the pancreas
Insulin def + microangiopathy of DM lead to pancreatic
damage
DM and CP cause effect r/n is not clear
Increased risk of hypoglycemia due to glucagon
deficiency when insulin therapy is initiated
Glucagon like peptide infusion increases endogenous
insulin
Glucocorticoid tx for autoimmune cp reverses ass. DM
Idiopathic CP
10-30% of acute pancreatitis
Early onset 20yr mean age, m=f
96% pain
Calcification, exocrine or endocine insufficiency
develop slowly over time 25, 26 -27.5 yrs
CFTR, SPINK1 genes
Late onset
Pain is less frequent 54%-75%
Age of onset 56yrs, m=f
Exocrine and endocrine insuf. Upto 46 and 41%,
in 16.9 and 11.9yrs; 90% calcification
Clinical features
Abdominal pain
Acute pancreatic inflammation
Increased intrapancreatic pressure
Alterations in pancreatic nerves
Steatorrhea lipase secretion <10%
DM
diagnosis
No single test is adequate
Tests for function
Tests for structure
Both are more accurate in advanced
disease
Indicate large reserve functionally, late
structural changes
Big duct vs small duct disease
Tests of function hormone stimulation
Secretin/ secretin CCK test
Fecal elastase
Fecal chymotrypsin
Serum trypsinogen (trypsin)
Fecal fat
Blood glucose

Tests of structure
Endoscopic US
ERCP
MRI/MRCP
CT
Abdominal US
Plain abdominal film
Routine lab. tests
Serum amylase and lipase
May be elevated in acute exacerbations
Also found increased in pseudocyst, ductal
stricture, internal pancreatic fistula

Other chemistry and electrolytes depend
on associated conditions

Classics of Chronic pancreatitis
Pancreatic calcification
Steatorrhea
Diabetes mellitus
Found in less than a third of pts with CP

abnormal secretin stimulations test when
>60 % affected
Serum trypsinogen < 20ng/ml, fecal
elastase < 100mcg/mg stool - severe
exocrine insuf.
US or CT grading system
Normal no abnormality on good quality study
Equivocal mild parenchymal duct dilatation (2-4mm)
gland enlargement <2 fold
Mild moderate - + duct dilatation >4mm,
duct irregularity,
cavity < 10mm,
parenchymal heterogenity,
increased echo of duct wall,
irregular head and body,
focal parenchymal necrosis
Severe - + cavity >10mm,
intraductal filling defects,
caliculi/ pancreatic calcification,
ductal obstruction/stricture,
severe ductal dilatation or irregularity,
contiguous organ invasion
complications
Cobalamin malabsorption
Excess binding by cobalamin binding proteins other
than intrinsic factor which were degraded by
pancreatic enzymes
DM but end organ damages of DM and DKA are rare
Non DM retinopathy (peripheral) due to Vit A and Zn
defc.
Pleural, peritoneal and pericardial effusions with high
amylase
GI bleeding PUD, gastritis, pseudocyst, varies (SV
thrombosis)
Cholestasis, icterus, cholangitis, biliary cirrhosis
Fistula internal or external
Subcutaneous fat necrosis tender red nodules on the
shins
Pseudocyst, obstruction
Pancreatic carcinoma 4% life time risk
Narcotic addiction
treatment
Aim - Pain control and mx of maldigestion
Pain
Avoid alcohol
Low fat meals
Antipain narcotics (addiction)
Surgical pain control
Resection (local - - - - 95%) pancreatic insufficiency
Splanchinectomy, celiac ganglionectomy, nerve block
Endoscopic tx
Sphinctorotomy, dilatation of strictures, caliculi removal, duct
stenting
Cpx acute pancreatitis, abscess, ductal damage, death
Pancreatic enzymes
Abdominal pain
R/o ddx US (no mass)
secretin test (decreased HCO3 and volume)
3-4wk pancreatic enzyme
(4-8tablets at meals and at bed time)
minimal change CP pt get relief of pain
if not, ERCP/EUS
pseudocyst, obstruction, dilated duct
surgery, octreotide
If No response
subtotal pancreatic resection
Tx of maldigestion
Pancreatic enzyme replacement
2-3 enteric coated or 8 conventional tablets with meals
adjuvants with conventional tablets H2 blockers, PPI,
Na bicarbonate,
Ca carbonate and Mg OH may even ppt steatorrhea
Steatorrhea can be abolished if 10 % of normal
lipase amount can be delivered to the duodenum
at the right time
Limitations
Lipase is inactivated by gastric acid,
food and enzyme emptying from the stomach is
different,
variable enzymatic activity of the preparation,
high potency prep. And colonic stricture reports