In d iv id u a l L a b T e s ts ¡'Pedíale Rev 2011 ;32:333; G astrdcnterology 2002:123:136/:
N Engl J Med 2000:342:1266)
* A s p a rt a t e a m in o tra n s fe ra s e ( A S T ) a n d a la n in e a m in o tra n s fe ra s e (A L T )
• To ge the r they are sensitive m arkers o f acute/ongoing hepacocyte in ju ry
• A S T alone is less specific; released fro m heart, skeletal muscle, kidney, brain, RBCs as w ell as liver; A LT m o re specific
• T in nonhepatic dz as w ell; h ypo /hyp erthyro id lsm , muscle dz, celiac dz
Jauhpice7-14
Hepatitis7-15
• Lactate dehydrogenase ( L D H ) : M u lti sources (heart, muscle, neoplasm, liver), n o t spec/sens,T in h epatocellular damage
• Alkaline phosphatase (AP)
• Released fro m liver, bone, and ¡ntestlnes; use GGT, 5NT, o r isozymes to distinguish
• If seen w ith increased d ire c t bilí, indicative o f b ilia ry o b s tru c tio n o r cholestasis
• Isolated elevation seen w ith infiltrative processes o f the liver o r bone (infection, tu m o r)
• Levels are decreased in h ypothyroidism and W ils o n disease
• Can see 2 x nm l adule levels in rapidly g ro w ln g adolescents 2/2 bone tu rn o v e r
• Gamma-glutamyltransferase (G G T ) and 5'-nucleotidase (5NT)
• G G T is fro m live r and bilia ry tra c t, 5 N T is fro m liver. muscle, heart, kidney
• N e ith e r are fro m bone so can be used co distinguish if AP fro m b o n e /n o t bone
• Albumin: M a rke r o f the llver's synthetlc fun ctio n assuming adequate nutrición
• A bn in hepatic dysfxn, malnut, p ro te in loss (n e ph ro tic, e nteropathy). and w / inflam
• Decrease ¡s seen only w ith ch ro nic States as V2 Ufe is 20 d; m arkers such as prealbum in (1/ i Ufe 2 d) o r tra n sfe rrin (V2 life 10 d) reflecc m o re acute change
• Prothrombin time (PT): M a rke r o f live r synchecic function, assess e xtrin sic pathway (Factors I, II.V.VII. X )
• Can be p ro longed w ith live r dysfunction. congenital o r acquired bleeding States, consum ptive coagulopathies. Coum adln, and vitam in K deficiency
• Liver produces all clo ttin g factors aslde fro m V III,so w ith severe hepatocellular dysfxn can see prolonged PT as w ell as a PTT
• B ilir u b in : From hem e catabollsm ¡n live r and spleen, m a rke r o f live r e x c re to ry fxn
• Elevatlons seen in cholestasis, b ilia ry o b s tru c tio n , and ¡mpaired conjugation
• N o t specific o r sensitive fo r live r disease P a tte rn s o f L iv e r In ju ry
A S T A LT Bili A P
H e p a to c ellu lar ++ + 4 + /- +
/-C holestatic + /- +/- ++ +
In filtra tive Nml Nml Nml ++
• H e p a t o c e llu la r : Elevated A ST and ALT w ith o r w ith o u t increased bili and AP
• <5x nml levels w / A LT > AST: C h ro nic viral hepatitis w / HCV. HBV. hereditary hem ochrom atosis, N ASH (nonalcoholic steatohepatitls),W ilson, chronic autoim m une hepatitis, cellac disease. some drugs
• <5x nml w / A ST > ALT; E tO H , cirrho sis, n on hepatlc (hemolysis, myopathy, drugs)
• >15x nml; acute viral hepatitis, d rug o r to x in mediated, ¡schemlc hepatitis, acute bile d u ct o b s tru c tio n , acute B ud d -C h ia rl
• C h o le stas is: Inc d ire ct (>20%TSB) and in d ire c t bilí a nd A P w / o r w /o IncA S T /A L T
• Biliary tra c t o b s tru c tio n (cholelithiasis, choledochollthiasis, etc.), PSC, meds (ce ftrla xon e, e ryth ro m ycin .T M P —SMX, carbamazepine, anabolic steroids, estrogen), T P N , m e tab o lic diseases (CF and A1 AT)
• Isolated elevation o f Ind ire ct b ilirub in ; co nsid e r hemolysis and see Jaundlce sectlon
• In filtra tiv e : Increased AP w ith near n orm al bill/A S T /A LT
• Lymphoma, o th e r neoplasm, sarcoidosis.TB, histoplasmosis
H E P A T I T IS
D e fin itio n (P e cialrR e v 2011 ;32:333)
• M ú ltip le etiologies w / live r Inflam m ation and hepatocyte death w / T serum AST/ALT
• Etiology, evaluation, and tre a tm e n t varíes p er age groups and risk factors/exposures E tio lo g y (Pediatr Rev 2311:32:333; Pediatr Rev 2001;22:219)
• Neonatal: Usually p /w cholestasis; DB >20%TSB (C lin Liver Dis 2006;10:27)
• 25% 2/2 b ilia ry atresia, 25% bile acid synthetic defect, Alagllle, etc.
• 30% m etabolic diseases o f w hich 10% are alpha-1-ancitrypsin deficiency
• H e re d ita ry hem ochrom atosis, galactosemia, tyrosinem ia, h ere d ita ry fru cto se in tolerance, m ito ch o n d ria l diseases
• 5% congenital infections (T O R C H infections)
• 15% id iopathic neonatal hepatitis
• O ld e r infants, children, and young adults (Pediatr Rev 2001:22:219)
• V iral hepatitis is m o st co m m o n; accounts o f 7 0-80% live r failure in children
• H epatitis A (H AV ), HBV, HCV, HDV, HEV, EBV, CMV. HSV.VZV
• B iliary trace o bstruction/disease (see lacer discussion)
• Cholelichiasis (sickle cell), cholecystids, selerosing cholangitis (IB D)
• M e tab o lic live r disease: A lp ha -1 -a ntitryp sin deficiency, W ils o n dz, CF
• A u to im m u n e live r disease: G enerally progresses to cirrho sis: types 1 and 2
• H e pa toto xin s: A cetam inophen and E tO H m o s t co m m o n b ut many o th e rs
• A ntie p ile ptics (carbamazepine, phenytoin, va lproic acid)
• A n tib io tic s (sulfonamides, IN H , azoles)
• O th e r drugs o f abuse (ecstasy, PCP, cocaine)
• O ver-che-counters and herbáis (N SA ID s, amanita m u shroom )
• Vascular disease: B u d d -C h ia ri syndrom e, ischemia, veno-occlusive disease
• Infiltrative disease: S teatohepatitis (N A S H ), sarcoidosis.TB S e le c te d C lin ic a l M a n ife s ta tio n s , E v a lu a tio n , a nd T r e a t m e n t
• Presentación can va ry fro m a sym ptom atic to fulm in an t hepatic failure
• Sx may include, abdom inal pain (p a rticularly R U Q ), hepatomegaly, nausea and vo m iting, fever, acholic stools, jaundice, encephalopathy, tre m o r (asterixis)
• H e p a t it is A : R N A virus, acute and se lf-lim ited in fection w / fever, jaundice, fatigue, N /V and diarrhea; at risk fo r fulm in an t hepatic failure if underlying live r disease
• M o st com m o n cause o f acute viral hepatitis
• S ym ptom atic in -30% <6 yo (rarely w / jaundice). 70% sym p tom atic in o ld e r pts
• Transmission is feca l-ora l, b lo o d -b o rn e , and ve rtica l transm isslon rare; travel hx
• C heck serology fo r IgM (lases 4 - 6 m o a fte r acute in fectio n) and IgG
• T re a tm en t is su pp ortive; 2 dose vaccination fo r p revention
• Pt yo and likely fu tu re exposure; give im m unoglobulin (Pediatrics 1996:98:1207)
• H e p a t it is B: D N A virus, acute o r chronic, o r ju st abn labs (C lin Liver Dis 2 006:10:133)
• A sym p to m a tic, anicceric seroconversion is the n orm if young, m o re sx if o ld e r
• V ertical transm ission patients usually w / nml A LT fo r yrs, m ild h istopath ¡Vs
• Risk o f ch ro nic HBV inverse to th e age o f in fectio n. 90% w / ve rtica l transm ission, 2 5-50% b tw ages 1 -5 , and o n ly 5 -1 0 % in o ld e r (C lin Liver Dis 2006; 10:133)
• 25% o f in fan ts/o ld er children w / H B V develop cirrho sis o r HBV-related H C C
• HBcAg+, H B eAB negative usually w / high H B V viral load, inc in fectivity
• Endemic regions (Asia, A frica , S. A m e rica ); ve rtical transm ission m o st com m on
• M o th e r HBsAg and H B e A g ', v e rtica l in f rate 70-90% ; HB eAg neg 5-20%
• Transmission throu g h infected b od y fluids, percutaneous, o r permucosal
• If m om HBsAg+/unl<nown, give HBV vac and HB IG w /i 12 h r at d iff sites
• N o risk associated w / breast-feeding
• Check HBsAg, HBeAg, anti-H BsA b, anti-H B cA b. a nti-H B e A B , HBV viral load H B s A g a n ti-H B s A b H B e A g a n ti- H B e A b a n ti- H B c A b
V a c c in a te d +
-A c u te in fe c tio n + - + + (IgM then IgG)
(h ig h ¡n fe c tiv e )
A c u te in fe c tio n + + + (IgM then IgG)
(lo w ¡n fe c tiv e )
C h ro n ic + - + /- + /- + (IgG only, if
in fe c tio n IgM - fiare)
• Managem ent o f ch ro nic HBV in children (Pediatrics 2009;124:e1007)
• Prove c h ro n ic ity (H B sA g - >6 mo)
• In a dd ition to above obtain baseline ALT, C B C , AFP, live r U/S, and FHx o f live r dz
• H B e A g + ,A n ti-H B e -,A L T nml, H B V D N A >20,000 lU /m L = im m une to le ra n t
• F ollow A LT and AFP q 6 - 1 2 m o and H B e A g /A n ti-H B e q 1 2 m o ;ifA L T elevated (above nm l o r >40 IU /L) o r AFP >10 ng/mL - re fe r to h ep atologlst
• H B e A g -, A n ti-H Be + /-.A L T nml. H B V D N A <2,000 lU /m L = inactive c a rrie r
• F ollow A LT and AFP q 6 -1 2 m o and H B e A g /A n ti-H B e and H B V q12m o; if ALT-elevated o r AFP >10 ng/mL. o r if H B V >2,000 lU /m L - Refer
• A LT elevated,AFP >10 ng/mL, H B e A g - w ith HBV >2,000 lU /m L & .o r +FHx live r dz o r H C C then im m ediate re ferra l to hepatologist
• Immunize all household contacts, im m unize/check im mune status o f p t fo r HAV
• Im m unize fo r hepatitis A, check yearly AFP and live r U/S
• H epatology w ill fo llo w q 1 —2yr live r U/S. obtain live r bx and consider tre a tm e n t if patient >2 yo and A LT > 1 .5 -2 x nm l fo r >3 mo, active HBV replication (+HBeAg o r HBV D N A >4 log) w /o seroconversion and bx w / evidence ch ro nic hepaticis
• N o tre a tm e n t o f proven efficacy in the p ed ia tric p opulation
• INF-alpha w / se roconversion in 2 0-58 % (used in children fo r last 10 y r)
Hepatitis7-16
• Lam ivudine w / se roconversion ¡n 2 3-35 % (N Engl J Med 2002;346:1706)
• Requires 1 y r o f therapy and can deveiop resistance, w ell-toleraced
• Rx optio ns in la m ivu d in e -re fra cto ry pts include entecavir, a defovir
• C h ro n ic H B V infección as infant confers a 15-25 % chance early death 2/2 live r dz H e p a t it is C : R N A virus; acute disease m ild, insidious, o fte n asym ptom atic
• <20% w / jaundice b u t 50-60 % w / persisten t in fection (less than in adults)
• Transmission is p rim a rily fro m exposure to infected b lood
• N o w ve rtica l x fr » transfusión as risk; since 1992 (universal b lo o d screening)
• Vertical risk -5 -6 % ; inc w / H IV co infe ction (- 20%) (C lin Liver Dis 2006;10:133)
• N o inc ris k o f x fr w / breast-feeding unless w / bleeding o r cracked nipples.in which case advisable to hold breast-feeds (A d v Exp Med Biol 2004:554:211)
• Usually a sym ptom atic in 1st 20 yr, w / m ild inflam, necrosis, and fibrosis on bx
• Risk o f cirrho sis and H C C in adu ltho o d exists; b u t lo w (-5%)
• C heck H C V R N A viral load and genotype if R N A is positive; best prognosis fo r genotypes 2 and 3 as bese response to therapy, though type 1 is m o s t com m o n
• Treatm ent: Few contraindicacions to INF, higher frequeney o f response, less relapse, s h o rte r d uratio n o f disease, b u t natural h is to ry o f disease unclear
• FDA approved r x in clude INF-alfa-2b w / ribavirin (age 3 -1 7 ) w / 49% SVR (H ep ato lo gy 2002:36:1280) & PEG-INF-alfa-2b w / ribavirin w / 48% SVR (H ep ato lo gy 2005:41:1013). N e w agents und er study (te la pre vir & b oce previr)
• C o n sid e r fo r genotypes 2 and 3. also if bx w / significant in ju ry o r fibrosis
• G en o typ e 1 w / m inim al inflam m ation o r fibrosis can be follow ed
• Vaccinate all patients against hepatitis A and hepatitis B
• N eed fo r surveillance AFP and screening U/S unkn ow n a t present
H e p a titis D : O nly can infect pts w / HBV,at inicial infection o r afterwards;usually w / acute illness and 5% risk o f fulm inant hepatitis; rx is supportive care
H e p a t it is E; A cu te illness, developing w o rld , severe in pregnant pts (10% m o rta lity ) E p s t e in - B a r r v ir u s ( E B V ) : A cu te hepatitis and jaundice in adolescents w / m ononucleosis; acute jaundice, pharyngitis, LAD, splenomegaly
C M V , V Z V , H S V , t o x o : Usually w / system ic p re sentation in im m un o com pro m ised A lp h a - 1 - a n t it r y p s in d is e a s e : (A D g en etics),A A T opposes p ro te o ly tic enzymes
• O n ly 20% o f P iZ Z hom ozygous patients present w ith live r disease
• In 1 st 20 yr, live r dz > re sp ira to ry (C OP D/em physem a); can present w / neonatal jaundice, o r la te r w / acute jaundice, ch ro nic hepatitis, o r cirrhosis
• Smoke expo sure is m a jo r d e te rm in a n t o f lung fxn; can be mistaken fo r asthma
• C h eck alph a -1 -a ntitryp sin level (dz if <11 u m o l/L ) and genotype study
• Rx fo r significant liver disease is transplant; curative as live r makes A 1 A T W i ls o n d is e a s e : (A R genetics), dysregulation o f co p p e r m etabolism w / excess accum ulation in liver, CNS, kidney, corneas (P ediatr Rev 2001:22:219)
• A cu te hepatitis o r fulm in an t liver dz (m od 1 AST/ALT, lo w /n m l AP, w / C o om bs neg h em olytic anemia, coagulopathy), to ch ro nic hepatitis and cirrho sis
• O ften w / marked neuropsychiatric sx, m o to r disturbance, depression, psychosis, if present w ill also have Kayser-Fleischer ring (gold discoloration fro m copper deposit in Descem et membrane o f cornea seen on slit lamp)
• Renal ¡nvolvem ent w / p ro xim a l tubule dysfunction, p ro te in uria .g lu cosu ria , RTA
• Diagnosis by 2 4 -h r u rin a ry co p p e r e xcre tio n >100 meg (H ep ato lo gy 1992:15:609)
• U riñ e co p p e r T in o th e r live r dz. check w / penicillam ine challenge test; 500 mg a t s ta rt and at 12 h r o f co lle ctio n . level >1,600 meg (p e r 24 colleccion) u rin a ry co p p e r diagnostic o fW ils o n (large validación study in children)
• C eruloplasm lo w in disease, and can be variable, p o o r p ositive pre dictive valué A u t o im m u n e h e p a titis : C h ro n ic ¡nflam m atory disease, u nknow n etiology, generally re sulting in cirrho sis; 2 types (C lin Liver Dis 2006:10:89)
• 40% type I (mean age 10 yr) and 80% o f type II (6.5 yo) d x ’d before age 18 y r
• Usually presents as acute hepatitis w / F > M; usually evidence o f ch ro n ic dz already present a t dx; sp ide r nevi, ascites, palm ar erythem a, splenomegaly
• A ST/A LT inc, usually w / hypergam maglobulinemia
• Type I: + anci-sm ooth muscle A b and A N A ? ; o th e r sx IBD, vasculitis, a rth ritis , i pies, G N , h em olytic anemia, fib ro sing alveolitis
• Type II: M o re rapidly progressive, la n ti-live r-kid n e y m icrosom e A b and o r ra n ti-live r- cytosol A b; DM , th yro id itis, vitÍligo, alopecia, A l enteropathy
• Rx w / im m unosuppression; generally prednisone and then Imuran co m p lete / sustained response in 95% patients
H e p a to to x in s : A cetam inophen O D is 1c cause o f acute hepatic failure in ch ildhood
• T re a tm en t (e xce pt f o r acetam inophen O D ; see ED chapter) is su pp ortive usually w /
¡m provem ent a fte r w ith d ra w a l o f h e p ato toxin . (Pediatrics 2004; 113:1097)
• A ST/A LT 8 - 2 0 + x n m kA cetam inophen, ASA, halothane, IN H .V P A
• A S T/A L T >3x n m h A ugm entin, 6MP, carbamazepine, ketoconazole, m inocycline, phenobarbital, PTU, sulfonamides
• A ST/A LT <3x nml: C yclo sp orine , e ryth ro m ycin , estrogens
B u d d - C h ia r i: A ny blockage o f b lo o d o u tflo w fro m live r resulting in congestión
• A cu te . subacute, ch ro nic, o r fulm inant: dx w / U/S + D oppler, CT, MRA, venogram Rx may involve meds (anticoag. chrom bolysls). IR (stent, angioplasty.TIPS), o r surgery (shunts, transplant).
B I L I A R Y TR AC T D IS EA S E
D e f in itio n
• Impaired bile sec by the liver w / subseq t serum to ta l and d ire c t bili; o fte n w / jaundice
• B iliary hepatic congestión -> ch ro nic hepatic inflam m ation -> fibrosis and cirrhosis E tio lo g y (Pediatr Rev 2004:55:388; P e d a lr Rev 2007;28:83)
• Neonatal o bstru ctive cholestasis: Biliary atresia, choledochal cysts, bile duct paucity (Alagille syndrom e as w ell as nonsyndrom ic), neonatal selerosing cholangitis. inspissated bile syndrom e, cholecystitis, bile sludging, CF
• C h ild and young adult: C holedochal cyst, cholecystitis, tum or, p rim a ry b iliary cirrhosis, p rim a ry selerosing cholangitis, missed neonatal diagnosis (Alagille, nonsyndrom ic bile ducc paucity, C a ro li disease)
S e le c te d C lin ic a l M a n ife s ta tio n s , E v a lu a tio n , a n d T r e a tm e n t
• Presentation varíes based on age, etiology, severity, and d ura tio n o f illness
• B ilia r y a tr e s ia : M o st com m on cause o f extra-hepatic cholestasis in 1 st m o o f life (33%)
• C o m p le te blockage o f bile o u tflo w 2/2 co m p lete o r partial d e stru ctio n o r absence o f extrah e pa tic bile ducts. (C lin L iver Dis 2006;10:73; Pediatr Rev 2006:27:243)
• Results in - 50% o f all p ed ia tric live r transplants; m o st freq hepatic cause o f death
• P /w jaundice at 3 -6 w k o f life, o th e rw ise healthy; rare e m b ryon ic fo rm a t b irth
• Subclinically, B A pts w / T / D bili T on D O L 1-2 (Pediatrics 2 01 1; 128:e 1428)
• Rapidly progressive process w / co ntinuing inflam m ation and fib ro sis/d e stru ctio n
• Prenatal fo rm (less co m m o n) assoc w / polysplenia, m alro, C D H in 10—15%
• E tiology u nkn ow n. proposed viral association; reovirus, CMV, HPV, rotavirus C
• Evaluation: Can screen generally w / s to o l c o lo r cards (Pediatrics 2 0 1 1;128:e1209)
• M o s t p /w elevated d ire c t b ilirub in and evaluated fo r o th e r causes (above)
• A bd U/S: R/o o th e r stru ctu ra l disease. looking fo r the absence o f gall bladder though nonspecific finding, pathognom onic finding is triangular cord sign
• H ID A sean: If tra c e r to intestines. argües against dx. b u t may need to repeat as b ilia ry atresia is a progressive disease; m o s t people use phenobarb x5 d p rio r
• MRI cholangiography and live r bx also good b u t sensitivities to o lo w to exelude b ilia ry atresia if strongly suspected
• Intra o pe ra tive cholangiogram (o r ERCP w h ere available) necessary to ru le o u t if above equivocal; if present, surgical c o rre c tio n a t tim e o f study
• Rx w / Kasai hepatic p o rto je ju n o s to m y (anastomosis o f p o rta hepatis to R oux en Y), wh ich allows fo r small p atent bile ducts to drain re storing bile flo w
• Success related to p t age a t c o rre c tio n w / 80% <2 m o b u t o nly 20% >3 m o
• Kasai is essentially palliative and these patients eventually go on to transplant
• C h o le lith ia s is : Rare in pediatrics (0.15-0.22% ) e xcept sickle cell, o th e r hem olytic dzs, CF, obesity, O C P use, c h ro n ic T P N . ileal resection. Has 4:1 predom inance, inc to 1 1-22 :1 in adolesccnce (C u rr O pin Pediatr 1997;9:276; Pediatr Rev 2009;30:368)
• Pigment stones (he m olytic dz.TP N , ¡leal resection), ch ole sterol stones in o thers
• Acalculous ch olecystitis a lm o st always post-o p o r assoc w / o th e r severe illness
• A sym p to m a tic generally b u t can develop c h o le c y s titis , c h o le d o c h o lith ia s is , o r p a n c r e a titis , w / jaundice, R U Q pain, v o m itin g + /- fever
• D o n o t always see elevated b ilirub in w ith uncom plicated cholecystitis; if present, co nsid e r cholangitis (pus und er pressure), choledocholithiasis (stone in C B D )
• Radiographs d em ón strate radiopaque stones in 3 6-47% (vs. 15% adults)
• A bd U/S check fo r + M urphy sign (te n d e r R U Q ), and thickened w all (4 -5 mm )
• Sens 84% and spec 95% in adults; likely higher in ch ildren given habitus
• H ID A sean: If d x suspected clinically b ut U/S equivocal; sens 97%, spec 90%
• Rx: IVFs.Abx (ce ftria xon e o r quin o lo ne + flagyl), surgery o r ERCP once p atient is stable and in fectio n/in fla m m a tio n has quieted on a ntib io tics
• P r im a r y s e le r o s in g c h o la n g itis : Progressive ch ro nic ínflam o f in tra & e xtra hepatic b ilia ry ducts (small o r large ducts). (C u rr G astro e n te ro l Rep 2010:12:195)
BiliaryTract
Pancreatitis7-19
Mean age o f d x is 13 y r (2:1 M:F), 80% assoc w / IBD (U C in 85% cases) 2h pts w / sx at dx; in te rm itte n t abd pain (40%) & fatigue (25%) w / subseq anorexia &
w eight loss. 20% w / fever; o th e r signs - HSM, jaundice, and p ruritus. O th e r A l dz 5%
Labs w / elevated G G T /A P + / - AST/ALT, b u t 90% w / nm l b ilirub in , also w / + A N C A staining peripheral nudeus (>70%), + A N A (50%). and SMA (25%)
• See high serum and u riñ e co p p e r (2/2 bile flo w o bs),ce ru lo plasm high/nm l
• Diagnosis: Cholangiography o r ERCP can visualize large d u ct narrow ing /d ila tion b u t n o t w / small ducts. need live r b x to d x small d uct p re do m in a nt PSC
• MRCP e xcellen t o p tio n fo r noninvasive imaging o f in tra /e xtra h e p a tic ducts
• N o specific rx; u rso dio l fo r sx relief, no m o rta lity ben efit w / anti-inflam m atories, if c irrh o sis and liver failure then live r transplant; w /o x p lt mean lifespan 12 y r
• Increased incidence o f co lo re cta l C A and cholangiocarcinom a in lacer adu lt Ufe
ACUTE P A N C R E A T IT IS
E tio lo g ie s (J Pediatr Gastroenterol N u tr 2011:52:262)
• Idiopathic (1 3 -34 % )
• Trauma (1 0 -40 % ): B lunt abdom inal, postsurglcal, post-ERCP
• B iliary tra c t disease/structural dz (1 0 -30 % ): Divlsum , a nnular páncreas, choledochal cysts.du ct s trictu re .ch o le d o ch o lith la sis.d u p lica tio n cyst.sp h in cte r o f O d d i dysfunction
• M ultisystem disease (1 4 -33 % ): Sepsis, SLE, HSP, HUS, Crohn's, Kawasaki
• D rug s/to xln s (12-25% ); C o rtico stero id s.V P A , carbamazepine, sulfonamides, m e tronidazole, pentam idine, cetracydine, furosem ide, chlorothiazides, azathioprine, 6-MP, L-asparaginase, sco rp ion stings, ethanol
• Recent study w / 25.6% acute pancreatitis 2/2 drugs; m o st co m m o nly VPA and steroids, L-asp and 6-MP (J Pediatr G astro e n te ro l N u tr 2011 ;53:423)
• Infection (10%): Mumps, C oxsackie B, CMV, HAV.VZV, EBV, HBV, Flu A /B , mycoplasma.
le ptospirosis, ascariasis, malaria
• H e re d ita ry (5 -8 % ) - see C h ro n ic Pancreatitis fo r etiologies
• M etabolic (2%) -> D K A , hyperlipidem ia, hypercalcemia, organic acidemia, m alnut/refeed C lin ic a l P re s e n ta tio n (j Pediatr Gastroenterol N utr 2011:52:262)
• A bd pain (87%), classically e pigastric/LU Q radiating to back b u t <10% in children; w o rse a fte r eating, N /V (40-80% ), anorexia, and altered sensorium
• Exam: abd pain, + /- d isten tion , +/- guarding (2 9 -37 % )/re b ou nd , l BS, fever, T HR
• R e tro pe rito ne a l hem orrhage (C ullen - p erium bilical, G rey T u rn e r - flank)
• W id e sp ectru m o f presentation fro m norm al exam to hypotension and shock D ia g n o s tic S tu d ie s
• L a b o ra to ry testing (A m J G a stro e n te ro l 2002:97:1309)
• Amylase: Spec hlghest w hen >3x nm l lim it, rises w /i hrs, no co rre la tio n b tw rise and severity o f dz, 20% false neg, can fra ctio n a te pancreatic vs. salivary
• Upase; spec highest if >3x nm l, m o re spec than Amy, t up to 14 d, 8 5-95 % sens
• Imaging studies
• A b d U/S: W / pancr enlargem ent. 4- echogenicity. dilated ducts, pseudocyst. gallstones.
Can be used fo r gulded aspiration o f pseudocyst
• CT: W / diffuse enlarge, + /- hem orrhage, necrosis, pseudocyst. 20% w / nm l CT, rapid bolus b e tte r iden tify necrosis. Used w hen U/S n o t adeq to ¡dentify anatom y
• MRCP: Can define anatom y fo r the ra p eu tic in tervención b u t n o t the ra p eu tic - ERCP: Indicacions include re c u rre n t o r p ro longed pancreatitis, abn MRCP, traum a,
sp hincterotom y, gallstone e x tra ctlo n . G ro w in g p ed ia tric experience. M o st sensitive and specific te st fo r divisum and choledochal cyst, sp hin cter o f O d d i dysfunction In d ic a to rs o f S e v e rity (A m J G astroenterol 2002:97:1726)
• M ú ltip le scoring systems are used in adults (Ranson c rite ria , Glasgow,APACHE, CT-severity in dex) b u t none have been validated in children
• Some w idely agreed upon in dicato rs fo r severe disease include:
• Clinical: A lte re d sensorium , hypotension, renal failure, p ulm on a ry edema, shock
• Labs: i Ca, T gluc, hypoxem ia, T B U N and Cr, T W B C , alb, CRP 48 h r in to course
• Imaging: A m o u n t o f necrosis correlaces w / risk o f infection and se verity o f disease T r e a t m e n t (N FnglJ Med 2006:354:2142)
• Classic approach was initial flu id resuscitation, pain management, and bow el rest
• Enteral (N G T ) vs. parenteral nut: Recent adu lt data w / J. in infxn and dz se verity w / enteral feeding. (BMJ 2004:328:1407). PO should begin once pain im proved
• Pain mgmt: M e p eridine o ften used o ve r MSCh; n o studies sh ow advantage
• N G T decom p: O fte n used b u t lack o f published evidence (n o t in m ild disease)
• A n tib io tic : Use is co ntro ve rsia l (some studies show benefit, o th e rs do n o t)
• Hay be reserved fo r cases w ith severe n ecrotizin g disease
• ERCP papillotom y: Diagnostic and thcrap e utic, indications discusscd above
• Surgery: Indicated if ¡nfected necrosis (may be co nfirm ed by F N A ). traum a w / d u ct ru p tu re . Relative indications - s te rile necrosis w ith m o re than 50% involved C o m p lic a tio n s (N Ungí J Med 2006:354:2142)
• Systemic: Shock, metabolic derangement (hypoCa, hyperglycemia, hyperK, hyperlipidemia), Gl hem orrhage. ileus, stress ulcer, o bstru ctio n, colonic wall erosión, splenic hematoma, pericarditis, pleural e ffu sio n .A R D S .i MS, psychosis, coma, i plts, hemolysis, D IC
• Local:
■ Pseudocyst: expanding, organized flu id co lle ction ; diagnosed by abd U/S
• A sym p to m a tic cysts do n o t re q uire in te rve n tio n
• Some re q uire drainage (endoscopic, IR, surgical) need 4 - 6 w k fo r m a tu rity
• C o m p lica tion s include ru p tu re , h em orrhage, infection
• Necrosis: Diffuse o r focal, can develop early in course. Suspected w / fever, leukocy- tosis, and failure to im prove. D x by C T (rapid bolus technique)
• C o m p lica tion s: Infected necrosis/abscess (can dx by F N A ). Rx w / abx o r surgery
CHRONIC P A N C R E A T IT IS
E tio lo g ie s (G astroenterology 2001:120:682)
• T IG A R O classification
• T o xic/m e ta b o lic: E tO H , hypercalcemia, hyperlipidem ia, organic acidemias, CRF
• Idiop ath ic
• G en e tic (PMID: 22094894)
• PRSS 1 (24%) (serme protease 1 ):catio n ic trypsinogen; T trypsin a ct/block inactivation
• SPINK 1 (27%) (serme protease inhib Kazal type 1);AR, blocks tryp sin inhibition, early onset
• CFTR (48%); highest risk in co m pound heterozygotes
• H e re d ita ry pancreatitis; (A D genetics). o nse t age 1 0 -1 2 , stro ng risk fo r pancreatic Ca, m o st w / som e genetic m u tatio n (PRSS 1 m o s t co m m o n)
• A u to im m u n e : Isolated a utoim m une pancreatitis, Sjogren, IBD, PBC
• R e cu rre n t acute
• O b s tru c tiv e :W / pancreatic divisum, choledochal cysts, s tric tu re , traum a, id iopathic
• O b s tru c tiv e :W / pancreatic divisum, choledochal cysts, s tric tu re , traum a, id iopathic