Transcript Chronic pancreatitis - Selam Higher Clinic

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
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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
Genetic forms
• 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
Disease modifying genes
• Polymorphisms that modulate immune
response
• Cytokines –
– transforming growth factors α, β, interleukin10, 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
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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
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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
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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
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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,
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duct irregularity,
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cavity < 10mm,
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parenchymal heterogenity,
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increased echo of duct wall,
» irregular head and body,
» focal parenchymal necrosis
• Severe - + cavity >10mm,
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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