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