Chronic_pancreatitis.ppt

7/23/2019 Chronic_pancreatitis.ppt

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Chronic pancreatitis

Ermias D (MD)


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Definition

Irreversible damage to the pancreas with

histologic evidence of inflammation,

fibrosis, and destruction of exocrine

(acinar) and endocrine (islets of

angerhans) tissue

Etiologic classification ! clinicall" useful

! #istologic ! accessibili" of tissue

! Imaging ! late morphologic changes


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prevalence

$utops" reports ! %&%'* overestimates

+etrospective studies ! -./%%,%%%

0rospective data

! among alcoholics ! 1&2."r./%%,%%%3

! overall prevalence 24&'./%%,%%%

5apan overall prevalence ! 21&./%%,%%%3

! M67 8&6/

$lcohol abuse ! 2. of causes Mortalit" &9: age matched control

$dvanced age, alcoholism and smo;ing are

poor prognostic conditions


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pathoph"siolog"

Incompletel" understood


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Ductal obstruction h"pothesis

Chronic alcohol use acinar and ductal cell

protein rich pancreatic =uice, low in volume and #C>

formation of protein precipitates ! plug

calcification of ppt ! ductal stone formation ductule obstruction

parench"mal damage

0ancreatic ductal stone are seen in alcoholic, tropical, hereditar",idiopathic

#istologic changes of C0 ma" be seen with out ductal obstruction


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?oxic metabolic h"pothesis

(alcohol)Direct in=urious effect on acinar and ductalcells

Increased membrane lipid peroxidation (oxidative

stress),free radical production Increase acinar cell sensitivit" to pathogenic

stimuli

@timulate CCA production (duodenal I cells)!

activation of proinflammator" transcription factors $ctivation of pancreatic stellate cells (alcohol,

c"to;ines)! produce proteins of extracellular matrix


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Becrosis fibrosis h"pothesis

+epeated episodes of acute pancreatitis withcellular necrosis or apoptosis, healing replacesnecrotic tissue with fibrosis

Evidence from natural histor" studies more severeand freuent attac;s

More evidence from hereditar" pancreatitis and

animal models

ut some have evidence of chronic pancreatitis

at time of first clinical acute attac;


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C7?+! c"stic fibrosis transmembrane conductance regulator

! C"stic fibrosis is ass& with abnormalities of #C>secretion, ductal dilatation, ppt formation, pancreaticatroph"

! @een in %* of idiopathic C0, not common in alcoholicC0

0+@@/! cationic tr"psinogen gene

! >nce tr"psinogen is activated to tr"psin, becomesresistant to inactivation and activate other proen"mes

leading to episodes of acute pancreatitis

! li;e necrosis fibrosis theor"

@0IBA/ serine protease inhibitor Aaal t"pe /! @een in pediatric IC0, hereditar" 0, ?03 but not in chronic

alcoholic pancreatitis

! ?r"psin inhibitor, mimic tr"psinogen gene

Fenetic forms


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Disease modif"ing genes

0ol"morphisms that modulate immune

response

C"to;ines !

! transforming growth factors G, H, interleu;in

/%, interferon gamma


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Etiologic factors ass&


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?+>0IC$ 0$BC+E$?I?I@

$frica, India, rail3 with in % latitude $ disease of earl" childhood and "outh

J -%* before age of '%"rs

0revalence in endemic areas6 / in %%1%%

$bdominal pain, malnutrition, exocrine andendocrine insufficienc"

0ancreatic caliculi ! -%*

7ibrocalculous pancreatic diabetes, tropicalcalcific pancreatitis

%* @0IBA/ gene mutation (B'@)

Knclear environmental trigger ! 0EM, Cassava


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$utoimmune pancreatitis

Confusing and evolving nomenclature

* of C0, more in males, middle age

/2 ! %* ass&


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Diabetes mellitus

/* of DM from C0

In DM pancreas is smaller,! abnormal duct in '%%* ,

! abnormal pancreatic fn in '%%*

Insulin is a trophic factor for exocrine fn of the pancreas

Insulin def L microangiopath" of DM lead to pancreaticdamage

DM and C0 cause effect r.n is not clear

Increased ris; of h"pogl"cemia due to glucagon

deficienc" when insulin therap" is initiated Flucagon li;e peptide infusion increases endogenous

insulin

Flucocorticoid tx for autoimmune cp reverses ass& DM


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Idiopathic C0 /%%* of acute pancreatitis

Earl" onset! 2%"r mean age, m8f

-9* pain

Calcification, exocrine or endocine insufficienc"

develop slowl" over time ! 2, 29 24& "rs C7?+, @0IBA/ genes

ate onset

0ain is less freuent '*4* $ge of onset 9"rs, m8f

Exocrine and endocrine insuf& Kpto '9 and '/*,

in /9&- and //&-"rs3 -%* calcification


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Clinical features

$bdominal pain

!$cute pancreatic inflammation

! Increased intrapancreatic pressure

!$lterations in pancreatic nerves

@teatorrhea ! lipase secretion /%*

DM


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diagnosis

Bo single test is adeuate

?ests for function

?ests for structure oth are more accurate in advanced

disease

Indicate large reserve functionall", latestructural changes

ig duct vs small duct disease


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?ests of function! hormone stimulation! @ecretin. secretin CCA test

! 7ecal elastase! 7ecal ch"motr"psin! @erum tr"psinogen (tr"psin)! 7ecal fat

! lood glucose

?ests of structure! Endoscopic K@

! E+C0! M+I.M+C0

! C?!$bdominal K@

! 0lain abdominal film


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+outine lab& tests

@erum am"lase and lipase

! Ma" be elevated in acute exacerbations

!$lso found increased in pseudoc"st, ductal

stricture, internal pancreatic fistula

>ther chemistr" and electrol"tes depend

on associated conditions


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Classics of Chronic pancreatitis

0ancreatic calcification @teatorrhea

Diabetes mellitus

7ound in less than a third of pts with C0

abnormal secretin stimulations test when

J9% * affected @erum tr"psinogen 2%ng.ml, fecal

elastase /%%mcg.mg stool severe

exocrine insuf&


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K@ or C? grading s"stem

Bormal ! no abnormalit" on good ualit" stud"

Euivocal ! mild parench"mal duct dilatation (2'mm)! gland enlargement 2 fold

Mild !moderate Lduct dilatation J'mm,N duct irregularit",N cavit" /%mm,N parench"mal heterogenit",N increased echo of duct wall,N irregular head and bod",N focal parench"mal necrosis

@evere Lcavit" J/%mm,N intraductal filling defects,N caliculi. pancreatic calcification,N ductal obstruction.stricture,N severe ductal dilatation or irregularit",N contiguous organ invasion


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li ti


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complications Cobalamin malabsorption

! Excess binding b" cobalamin binding proteins other

than intrinsic factor which were degraded b"pancreatic en"mes DM! but end organ damages of DM and DA$ are rare Bon DM retinopath"(peripheral) due to Oit $ and Pn defc& 0leural, peritoneal and pericardial effusionswith high

am"lase FI bleeding! 0KD, gastritis, pseudoc"st, varies (@Othrombosis)

Cholestasis, icterus, cholangitis, biliar" cirrhosis 7istula! internal or external

@ubcutaneous fat necrosis! tender red nodules on theshins

0seudoc"st, obstruction 0ancreatic carcinoma ! '* life time ris; Barcotic addiction


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treatment $im 0ain control and mx of maldigestion

0ain

!$void alcohol

! ow fat meals

!$ntipain ! narcotics (addiction)! @urgical pain control +esection (local -*) ! pancreatic insufficienc"

@planchinectom", celiac ganglionectom", nerve bloc;

! Endoscopic tx

@phinctorotom", dilatation of strictures, caliculi removal, duct

stenting

! Cpx ! acute pancreatitis, abscess, ductal damage, death

! 0ancreatic en"mes


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$bdominal pain !

+.o ddx ! K@ (no mass)!

secretin test (decreased #C> and volume)! 'w; pancreatic en"me!

('1tablets at meals and at bed time)!

minimal change C0 pt get relief of pain ! if not, E+C0.EK@ !

pseudoc"st, obstruction, dilated duct !

surger", octreotide! If Bo response

subtotal pancreatic resection


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?x of maldigestion 0ancreatic en"me replacement

! 2 enteric coated or 1 conventional tablets with meals! ad=uvants with conventional tablets ! #2 bloc;ers, 00I,

Ba bicarbonate,! Ca carbonate and Mg ># ma" even ppt steatorrhea

@teatorrhea can be abolished if /% * of normallipase amount can be delivered to the duodenumat the right time

imitations! ipase is inactivated b" gastric acid,

! food and en"me empt"ing from the stomach isdifferent,

! variable en"matic activit" of the preparation,! high potenc" prep& $nd colonic stricture reports

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Chronic_pancreatitis.ppt