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GB & Bile duct disorders

1. º´Å»ý¸®

1) Bile secretion & composition

* bileÀÇ Áֿ䱸¼º¼ººÐ : water(82%), bile acid(12%), lecithin & other phospholipid(4%)

unesterified cholesterol(2.7%), ±âŸ...

BileÀº °£¿¡¼­ ÇÏ·ç 500-600 mlºÐºñµÇ´Âµ¥ ÀÌ·¸°Ô °£¼¼Æ÷¿¡¼­ ºÐºñµÇ±âÀü

conjugation°úÁ¤À» °ÅÄ£´Ù

ÀÌ·¯ÇÑ bile flow¸¦ Á¶ÀýÇϴµ¥ Áß¿äÇÑ 3°¡Áö ±âÀüÀÌ ÀÖ´Ù.

i) hepatocyte -> bile canaliculi·Î active transport

ii) other organic anionÀÇ active transport

iii) cholangiocellular secretion : secretin-mediated, c-AMP-dependent Mx¿¡ ÀÇÇØ

sodium- & bicarbonate-rich fluid°¡ bile duct·Î secretion.

2) Bile acids

¨ç Á¾·ù

i) primary bile acids(°£): cholic acid, CDCA

cholesterol¿¡¼­ ÇÕ¼ºµÇ¾î glycine or taurine°ú conjugationµÇ¾î bile·Î excretion

ii) secondary bile acids(colon): deoxycholate, lithocholate

colon¿¡¼­ ¼¼±ÕÀÇ ´ë»ç¿¡ ÀÇÇØ Çü¼º

iii) tertiary bile acid: UDCA(CDCAÀÇ stereoisomer)

¨è ´ãÁóÀÇ ±â´É

i) Bilirubinµî°ú °°Àº ³»Àμº ³ëÆó¹° ¹× ¾à¹°°ú ¿©·¯ °¡Áö µ¶¼º¹°Áú ¹èÃâ

ii) Àå¿¡¼­ Á¤»óÀû Áö¹æ Èí¼ö

iii) ½Åü cholesterol ÆòÇüÀ¯Áö¿¡ ÁßÃßÀû ¿ªÇÒ

iv) ÀåÀ¸·Î IgA ¿î¹Ý¿¡ Áß¿äÇÑ ¿ªÇÒ

¨é CSI(Cholesterol saturation index)

Cholesterol Lecithin

Bile salt

¨ê Enterohepatic circulation

unconjugated : ÀüÀå°üÀ» ÅëÇØ passive diffuseÇÏ°Ô Èí¼ö

conjugated : distal ileum¿¡¼­ active transport·Î Èí¼ö, ¾çÀûÀ¸·Î ´õ Áß¿äÇÔ.

Á¤»ó bile acid pool size´Â ´ë·« 2-4g Á¤µµ µÇ´Âµ¥ ½Ä»ç¸¦ Çϸé bile acid poolÀº Àû¾îµµ

ÇѹøÀÌ»ó enterohepatic cycleÀ» µ·´Ù. Á¤»óÀûÀ¸·Î bile acid poolÀº ¸ÅÀÏ 5-10¹ø ¼øÈ¯

ÇÑ´Ù.

Àå³» Èí¼ö´Â ¾à 95% Á¤µµµÇ¸ç µû¶ó¼­ fecal loss´Â ÇÏ·ç 0.3-0.6 gÁ¤µµÀÌ´Ù.

fecal loss´Â °£¿¡¼­ÀÇ ÇÕ¼ºÀ¸·Î º¸ÃæµÇ¾î bild acid pool size°¡ À¯ÁöµÈ´Ù.

°£À¸·Î µ¹¾Æ¿Â bile acid´Â rate-limiting enzymeÀÎ cholesterol 7¥á-hydroxylase¸¦ ¾ïÁ¦ÇÔ

À¸·Î½á cholesterol·ÎºÎÅÍ primary bile acid°¡ ÇÕ¼ºµÇ´Â °ÍÀ» ¾ïÁ¦ÇÑ´Ù.

3) GB & sphincter function

°øº¹½Ã Sphincter of Oddi´Â high-pressure zoneÀ¸·Î ÀÖ´Ù.

ÀÌ·¯ÇÑ tonic contractionÀº

i) duodenum¿¡¼­ pancreas³ª bile duct·ÎÀÇ reflux¸¦ ¹æÁöÇϰí

ii) GB·Î bile fillingÀ» ÃËÁøÇϵµ·Ï ÇÑ´Ù.

GB evacuationÀ» Á¶ÀýÇÏ´Â Áß¿äÇÑ È£¸£¸óÀº CCKÀÌ´Ù.

: Áö¹æÀ̳ª ¾Æ¹Ì³ë»êÀ» ¼·ÃëÇÏ¸é ½ÊÀÌÁöÀå Á¡¸·¿¡¼­ ºÐºñµÇ¾î ´ÙÀ½°ú °°Àº ±â´ÉÀ» ¼öÇà

ÇÑ´Ù.

i) GBÀÇ powerful contraction

ii) sphincter of Oddi resistance¡é

iii) bilary content¸¦ duodenumÀ¸·Î flow¡è

cf. normal GB capacity : 30-50 mL

2. GB diseases

1) Gallstones

(1) º´ÀÎ

¹Ì±¹¿¡¼­ 40¼¼ ÀÌ»ó ºÎ°Ë¿¹¿¡¼­ ¿©ÀÚÀÇ 20%, ³²ÀÚÀÇ 8%¿¡¼­ ´ã¼®ÀÌ ¹ß°ßµÇ¾ú°í

¹Ì±¹¿¡¼­ ¸Å³â ¹é¸¸¸íÀÇ È¯ÀÚ°¡ ¹ß»ýÇÑ´Ù.

* 3 types

mixed & cholesterol stone : cholesterol monohydrate(50%ÀÌ»ó ÇÔÀ¯)

+ Ca salt, bile pigment, protein, fatty acid

pigment stones: ÁÖ·Î Ca bilirubinate(cholesterolÇÔÀ¯·®Àº 20%¹Ì¸¸)

(2) Cholesterol & Mixed stones & Bilary sludge

* Fig 302-1. Gallstone formation pathogenesis

cholesterol : bile acid + lecithin ratioÀÇ Áõ°¡ = gallstone formation¡è

* Gallstone formation¿¡ °ü¿©ÇÏ´Â Áß¿äÇÑ Mx(Áß¿äÇÑ ¼ø¼­´ë·Î)

i) cholesterolÀÇ biliary secretion¡è(°¡ÀåÁß¿ä)

ii) cholesterol monohydrate crystalÀÇ nucleation

iii) GB hypomotility

¨ç Biliary cholesterol secretion¡è ( most important )

ÀÌ¿Í °ü·ÃµÈ »óȲ

: obesity, high-caloric diet, cholesterol-rich diet, drug(clofibrate),

HMG-CoA reductase activity¡è

- lithogenic bileÀº ileal resectionÀ̳ª prolonged parenteral alimentation°°ÀÌ bile acidÀÇ

enterohepatic circulation¿¡ Àå¾Ö°¡ »ý±â´Â »óȲ¿¡¼­µµ »ý±ä´Ù.

- GallstoneȯÀÚ ´ëºÎºÐÀº hepatic cholesterol 7¥á-hydroxylase activity¡é

- Biliary cholesterolÀÇ °ú´Ù´Â ÀÏÂ÷ÀûÀ¸·Î´Â cholesterol hypersecretion¿¡ ÀÇÇÏÁö¸¸

bile acids hyposecretionµµ ±â¿©ÇÑ´Ù.

- ÀÌ·¯ÇÑ bile acid metabolism¿¡ ±â¿©ÇÏ´Â µÎ°¡Áö Àå¾Ö·Î ÀÎÇÏ¿© bileÀÇ supersaturation

ÀÌ ÀϾ´Ù.

i) bile acid pool¡é

¼ÒÀå¿¡¼­ ´ëÀåÀ¸·ÎÀÇ ºü¸¥ primary bile acid loss

ii) cholic acid -> deoxycholic acid·ÎÀÇ ÀüȯÀÌ

cholic acid pool -> expanded deoxycholic acid pool·ÎÀÇ Àüȯ ÃËÁø

: cholic acid dehydroxylation¡è, deoxycholic aicd Èí¼ö¡è

Áõ°¡µÈ deoxycholate secretionÀº cholesterol hypersecretion°ú °ü·Ã.

¨è Nucleation of cholesterol monohydrate(2nd important)

i) prenucleating factors excess

: mucin & certain non-mucin glycoprotein, heat-labile proteins

ii) antinucleating factors

: apolipoprotein AI & AII, other glycoprotein

¨é GB hypomotility ( 3rd important )

¨ê Biliary sludge - thick mucous material

±¸¼º¼ººÐ : lecithin-cholesterol crystals

cholesterol monohydrate crystals

calcium bilirubinate

mucin thread, muous gels

dependent portion¿¡ crescent-like layerÇü¼º

gallstone diseaseÀÇ precursorÀÌ´Ù.

ÇÑ ¿¬±¸¿¡¼­ biliary sludge¸¦ °üÂûÇÏ¿´À» ¶§

18% : ¼Ò½ÇÈÄ Àç¹ß¡¿

60% : ¼Ò½ÇÈÄ Àç¹ß

14% : GB stone¹ß»ý(8%-¹«Áõ»ó, 6%-Áõ»ó)

6% : severe biliary pain

* cholesterol stone or biliary sludgeÇü¼º°ú °ü·ÃÇÑ 2 conditions

: pregnancy, very low calorie diet

i) pregnancy -> bile acid pool±¸¼º°ú cholesterol-carrying capacityÀÇ º¯È­¸¦ ÀÏÀ¸Å´

-> cholesterol saturation¡è(3rd trimester)

ÀӽŶ§ GB sludge 20-30%, gallstones 5-12%

biliary sludege°¡ common findingÀ̳ª ´ëºÎºÐ ¹«Áõ»óÀ̸ç Ãâ»êÈÄ ÀÚ¿¬¼Ò½ÇµÈ´Ù.

gallstoneÀº ÈçÄ¡ ¾ÊÀ¸³ª biliary colic°ú °ü·ÃÀÖÀ¸¸ç ºÐ¸¸ÈÄ ¼Ò½ÇµÈ´Ù.

(spontaneous dissolution)

ii) rapid weight reduction + very low calorie dietÇÏ´Â »ç¶÷ÀÇ 10-20%¿¡¼­

gallstone»ý¼ºµÈ´Ù.

* UDCA(600 mg/d)´Â gallstone formation¿¹¹æ¿¡ ¾ÆÁÖ È¿°úÀûÀÓÀÌ Áõ¸íµÇ¾î ÀÖ´Ù.

( º¹¿ëȯÀÚ stone¹ß»ý 3% : placebo 28% )

¿ä¾àÇϸé cholesterol gallstone disease´Â ´ÙÀ½°ú °°Àº defect·Î »ý±ä´Ù.

i) bile supersaturation with cholesterol

ii) nucleation of cholesterol monohydrate with subsequent crystal retention & stone

growth

iii) abnormal GB motor fx with delayed emptying & stasis

(3) Pigment stones

- ÁÖ·Î calcium bilirubinate·Î ±¸¼ºµÇ¸ç ¼­±¸º¸´Ù´Â ±Øµ¿¿¡¼­ ´õ ÈçÇÏ´Ù.

- unconjugated insoluble bilirubinÀÌ Áõ°¡ÇÏ¿© °á±¹bilirubinÀÌ Ä§ÂøÇÏ°Ô µÇ¾î pigment

stoneÀÌ Çü¼ºµÈ´Ù.

- ±×·¯³ª ¼­±¸¿¡¼­´Â chronic hemolytic states or alcoholic liver disease°¡ pigment

stone°ú °ü·ÃÀÖ´Ù.

- soluble bilirubin mono- & diglucuronideÀÇ °ú´ÙÇÑ deconjugationÀº

endogenous ¥â-glucurondase¿¡ ÀÇÇØ¼­µµ ¸Å°³µÇÁö¸¸ spontaneous alkaline hydrolysis

¿¡ ÀÇÇØ¼­µµ ÀϾ´Ù. ¶§·Î´Â ´ãÁóÀÌ ¼¼±Õ¿¡ ÀÇÇØ ¸¸¼ºÀûÀ¸·Î °¨¿°µÇ¾î ÀÖÀ»¶§µµ

¥â-glucuronidase°¡ »ý¼ºµÈ´Ù.

(4) Áø´Ü

¨ç simple abdomen

cholesterol, mixed stone : 10-15%

pigment stone : 50%

* simple abdomenÀ¸·Î Áø´ÜÀÌ °¡´ÉÇÑ conditions

: emphysematous cholecystitis, porcelain GB, limey bile, gallstone ileus

¨è USG : Áø´Ü¿¡ °¡Àå Á¤È®, 2mm Á¤µµ·Î ÀÛÀº°Íµµ ¹ß°ß°¡´É

¨é OCG : lithotripsy or bile acid dissolution tx´ë»óȯÀÚ¿¡¼­ gallstone Å©±â, °¹¼ö¸¦

ÆÄ¾ÇÇϴµ¥ À¯¿ë

¨ê DISIDA scan µî

(5) Gallstone diseaseÀÇ Áõ»ó

CBD or cystic duct obstruction -> intraluminal pr¡è -> visceral pain(biliary colic)

s-Bil¡è, and/or ALP¡èÀÏ °æ¿ì CBD stoneÀÌ ÀÖÀ» °¡´É¼ºÀ» ½Ã»çÇÔ.

fever or chill(rigors) - complicationÀǹÌ(cholecystitis, pancreatitis or cholangitis)

vague sx(epi fullness, dyspepsia..)À» biliary colic°ú È¥µ¿ÇÏ¿©¼­´Â ¾ÈµÈ´Ù.

(6) Natural Hx

'silent' or aymptomatic gallstonesÀÌ Áõ»óÀ» ¾ß±âÇÒ È®·ü

10%(5³â), 15%(10³â), 18%(15³â)

15³â ÀÌÈÄ¿£ ´õ Áõ°¡ÇÏÁö ¾Ê´Â´Ù.

(7) Ä¡·á

¨ç ¼ö¼ú

asymptomatic stone : Áõ»óÀ¯¹ß È®·ü = 1-2%/yr

* op Ix

i) Hx of acute cholecystitis, pancreatitis, gallstone fistula

ii) Cx risk³ôÀº °æ¿ì(calcified or porcelain GB)

iii) very large stone(>2cm)

iv) congenitally anomalous GB

¨è medical Tx

i) Dissolution - UDCA

radiolucent stone( <10mm ) - 50%°¡ complete resolution, 6°³¿ù-2³â Ä¡·á

8-10 mg/kg/d

5mm¡é, floating radiolucent stone - 70%ÀÌ»ó ¼º°ø·ü

ii) ESWL

radiolucent solitary(<2cm) in well-contracting GB

5³â³» 30%¿¡¼­ Àç¹ß