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bile and stones

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									                                                                                                                                                                               bile	
  and	
  stones

       	
  	
  	
  	
  	
  	
  biliary	
  anatomy                                                                                                                                              	
  	
  	
  	
  	
  	
  	
  	
  gallstone	
  disorders
                                                                                                                                                                                               types:	
  80%	
  cholesterol=	
  10-­‐15%	
  with	
  enough	
  calcium	
  to	
  radio-­‐opaque	
  [opp.	
  to	
  kidney	
  stones-­‐	
  85%	
  radio	
  opaque]
                                                                                                                                                                                                   ::	
  cholesterol.	
   most	
  common	
  in	
  Us.	
  >50%	
  cholesterol
                                                                                                                                                                                                   ::	
  black.	
  pure	
  calcium	
  bilirubinate	
  or	
  calcium	
  complexes	
  w/	
  Cu	
  and	
  mucin.	
  common	
  in	
  cirrhosis	
  and	
  hemoly;c	
  states
                                                                                                                                                                                                   ::	
  brown.	
  calcium	
  salts	
  of	
  unconjugated	
  bilirubin	
  and	
  cholesterol.	
  assoc.	
  w/	
  infec;on.
                                                                                                                                                                                               pathogenesis.	
  precipita;on	
  of	
  cholesterol	
  from	
  the	
  bile	
  leads	
  to	
  stone	
  forma;on.
                                                                                                                                                                                                   +	
  concentra-on	
   of	
  cholesterol[supersatura;on]	
  favors	
  gallstone	
  forma;on.
                                                                                                                                                                                                   +	
  mo-lity	
  of	
  gallbladder.	
  stasis	
  favors	
  gallstone	
  forma;on.
                                                                                                                                                                                                   +	
  at	
  least	
  2/3	
  factors	
  required.	
  supersat	
  cholesterol	
  levels	
  in	
  bile,	
  slowed	
  gallbladder	
  mo;lity,	
  nuclea;on	
  factors
                                                                                                                                                                                                          promote	
  precipita;on	
  of	
  cholesterol	
  into	
  crystals-­‐	
  act	
  as	
  nidus	
  for	
  stone	
  forma;on	
  [mucin	
  may	
  be	
  such	
  factor]
                                                                                                                                                                                               RF’s	
  [‘fat,	
  forty,	
  female’]
                                                                                                                                                                                                   +	
  age.	
  r are	
  in	
  kids.	
  age	
  >40	
  assoc.	
  w/	
  higher	
  risk	
  of	
  stone	
  development
                                                                                                                                                                                                   +	
  gender.	
  women	
  >	
  men	
  if	
  <55	
  y.o.	
  [may	
  be	
  due	
  to	
  estrogen	
  induced	
  cholesterol	
  secre;on	
  by	
  liver]
                                                                                                                                                                                                   +	
  preg.	
   higher	
  during	
  preg	
  and	
  w/	
  more	
  preg.	
  [related	
  to	
  estrogen,	
  altered	
  bile	
  acid	
  syn.,	
  more	
  gallbladder	
  stasis]
                                                                                                                                                                                                   +	
  other.	
   oral	
  contracep;ves/HRT,	
  	
  family	
  hx,	
  obesity,	
  rapid	
  wt	
  loss	
  [high	
  cholesterol	
  secre;on	
  +	
  decreased	
  gb
                                                                                                                                                                                                          mo;lity	
  w/	
  low-­‐fat	
  +	
  calorie	
  diet].	
  cephtriaxone,	
  clofibrate	
  and	
  octreo;de.
                                                                                                                                                                                               natural	
  hx.	
  60-­‐80%	
  asx!!	
  	
  aker	
  20	
  yr	
  follow	
  up:	
  50%	
  remain	
  asx,	
  30%	
  biliary	
  colic,	
  20%	
  have	
  complica;ons.	
  stones
                                                                                                                                                                                                   w/	
  no	
  sx=	
  NO	
  SURGERY.
                                                                                                                                                                                               clinical	
  presenta-on.
                                                                                                                                                                                                   ::	
  biliary	
  colic.	
  most	
  common	
  presenta;on	
  for	
  sx	
  gallstones	
  [~70%].	
  localized	
  to	
  epigastric	
  area/RUQ.	
  has
                                                                                                                                                                                                          crescendo-­‐plateau-­‐decrescendo	
  panern	
  las;ng	
  30	
  min	
  to	
  3	
  hours.	
  oken	
  at	
  night.	
  N/V	
  oken.
                                                                                                                                                                                                   ::	
  acute	
  cholecys--s.	
  	
  	
  stone	
  stuck	
  in	
  cys;c	
  duct=	
  gb	
  inflamma;on	
  and	
  infxn.	
  75%	
  preceded	
  by	
  biliary	
  colic.
                                                                                                                                                                                                          severe	
  RUQ	
  and	
  epigastric	
  pain,	
  may	
  radiate	
  to	
  chest	
  or	
  shoulder.	
  N/V	
  common,	
  fevers.	
  minimal	
  eleva;on
                                                                                                                                                                                                          of	
  bili/	
  LFT’s	
  in	
  <20%	
  in	
  pa;ents.	
  TX:	
  cholecystectomy.	
  if	
  not	
  surg.	
  candidate=	
  percutaneous	
  	
  tube	
  placement.
	
  	
  	
  	
  	
  	
  	
  	
  	
  bile                                                                                                                                                           ::	
  choledocolithiasis.	
  interminent	
  obstruc;on	
  of	
  common	
  bile	
  duct.	
  may	
  be	
  asx	
  or	
  may	
  be	
  exactly	
  like	
  biliary
                                                                                                                                                                                                          colic.	
  biliary	
  obstruc;on	
  can	
  lead	
  to	
  cholangi;s	
  and	
  jaundice	
  w/	
  elevated	
  bili	
  usually	
  <	
  10	
  mg/dL.
	
  	
  basics                                                                                                                                                                                            TX:	
  ERCP	
  [	
  endoscopic	
  retrograde	
  cholangiopancreatography]	
  for	
  stone	
  removal.
          ::	
  small	
  propor-on	
  of	
  GI	
  secre-ons.	
  take	
  in	
  1.5L	
  a	
  day,	
  saliva=	
  0.5-­‐1L,	
  gastric	
  secre;ons=	
  1.3L,                                          ::	
  gall	
  stone	
  pancrea--s.	
  caused	
  by	
  obstruc;on	
  of	
  ampulla	
  by	
  a	
  stone.	
  mechanism	
  =	
  pancrea;;s	
  unclear.
          pancrea;c	
  secre;ons=	
  0.2-­‐0.8L,	
  bile=	
  0.5-­‐1L,	
  intes;ne=	
  9L...	
  	
  	
  	
  OUTPUT=	
  100	
  mL/day!!                                                                    may	
  be	
  due	
  to	
  reflux	
  of	
  bile	
  into	
  the	
  pancrea;c	
  duct.
          ::	
  components	
  of	
  bile.	
  mostly	
  water.	
  	
  but	
  solid	
  components	
  are:~60-­‐70%	
  bile	
  acids/salts.	
  ~20%	
  phospholipids                              DX
                 [mostly	
  lecithins].	
  ~5%	
  proteins	
  [glycopro	
  like	
  mucin,	
  albumin,	
  enzymes,	
  immunoglobulins].	
  ~4%	
  cholesterol                                       ::cholecys--s.	
  U/S	
  =	
  thick-­‐walled,	
  inflamed,	
  edematous,	
  shadow	
  going	
  down.	
  HAIDA	
  SCAN:	
  radioac;ve
                 	
   bile	
  serves	
  as	
  THE	
  method	
  of	
  liver	
  excre;on	
  of	
  excess	
  cholesterol	
  [not	
  water	
  soluble,	
  normally	
  solubilzed	
  within                    food-­‐	
  liver	
  takes	
  it	
  up-­‐	
  secretes	
  into	
  bile	
  should	
  see	
  GB	
  filling/secre;ng-­‐	
  if	
  you	
  don’t=problem
                 micelles.	
  <	
  1%	
  bilirubin-­‐	
  waste	
  product=	
  yellow	
  people.	
  drugs	
  also	
  excreted	
  through	
  bile                                                    ::	
  choledocolithiasis.	
  CT:	
  see	
  stones	
  and	
  dilated	
  common	
  bile	
  duct/mess	
  of	
  pancreas.
bile	
  acids                                                                                                                                                                                             MRI:	
  MRCP-­‐	
  can	
  see	
  bile	
  duct/bile	
  tree	
  w/	
  filling	
  defect=	
  stone.	
  ERCP:	
  scope	
  from	
  stomach	
  →	
  duodenum→
          ::	
  synthesis	
  of	
  bile	
  acids.	
  c holesterol-­‐	
  substrate.	
  cascade	
  of	
  enzymes	
  changes	
  cholesterol	
  into	
  one	
  of	
  two	
  primary                           up	
  into	
  sphincter	
  of	
  oddi.	
  can	
  use	
  as	
  scope	
  or	
  tool	
  [	
  hard	
  on	
  pancreas-­‐	
  use	
  if	
  preny	
  sure
                 bile	
  acids	
  first	
  enzyme	
  in	
  pathway=	
  CYP7A	
  or	
  7α	
  hydroxylase=	
  RLS.	
  bile	
  acids	
  then	
  must	
  be	
  conjugated                                      problem	
  exists]
                 w/	
  glycine	
  or	
  taurine	
  =	
  bile	
  salts	
  before	
  being	
  secreted	
  in	
  bile.	
  gallbladder	
  stores	
  and	
  concentrates	
  [via	
  water
                 and	
  electrolyte	
  absorp;on]	
  then	
  releases	
  w/	
  meals
          ::	
  rela-onship	
  to	
  cholesterol.	
  only	
  2	
  [natural	
  ]	
  ways	
  for	
  body	
  to	
  get	
  rid	
  of	
  cholesterol:	
  secre-on	
  as	
  cholesterol	
  into
                 bile	
  +	
  t ransforma-on	
   into	
  bile	
  acids.
          ::	
  species.
                 +	
  primary.	
  p roduced	
  by	
  hepatocytes	
  from	
  cholesterol:	
  chenodeoxycholic	
  +	
  cholic	
  acid
                 +	
  secondary.	
  produced	
  by	
  transforma;on	
  of	
  primary	
  bile	
  acids	
  by	
  gut	
  bacteria:	
  lithocholic	
  +	
  deoxycholic	
  acid
          ::	
  characteris-cs.	
  amphipathic=	
  detergent	
  capability/	
  can	
  solubilize	
  fat	
  in	
  aqueous	
  solu;ons.	
  bile	
  acids	
  form
                 micelles	
  around	
  lipid	
  droplets
          ::	
  enterohepa-c	
  recircula-on.
                 +	
  liver	
  as	
  pump.	
   bile	
  salts	
  synthesized	
  from	
  cholesterol→	
  secreted	
  into	
  intes;ne→	
  absorp;on	
  of	
  lipids	
  in
                         intes;ne→	
  some	
  bile	
  salts	
  recirc	
  .to	
  liver	
  through	
  specific	
  R-­‐mediated	
  absorp;on	
  	
  in	
   ileum
                 +	
  consequences	
  of	
  impaired	
  enterohepa-c	
  circ.	
  available	
  bile	
  acid	
  pool	
  decreases=	
  can’t	
  solubilize	
  fat
                         =steatorrhea,	
  vit	
  KADE	
  malabsorp;on/deficiences.
                 +failure	
  to	
  reabsorb	
  bile	
  acids.	
  d ue	
  to	
  ileal	
  disease	
  or	
  absence	
  =	
  diarrhea	
  and	
  gallstone	
  forma;on

bilirubin.waste	
  product	
  of	
  heme	
  [	
  Fe+	
  holder]	
  heme	
  to	
  biliverdin→	
  unconjugated	
  bilirubin
    ::	
  forma-on
           +	
  outside	
  hepatocyte.	
  RBC’s	
  1/2	
  life=	
  90	
  days.	
  when	
  taken	
  up	
  -­‐much	
  is	
  recycled-­‐	
  HEME	
  IS	
  NOT	
  =	
  measured
                  in	
  blood	
  as	
  	
  indirect	
  bilirubin/insoluble.	
  t aken	
  up	
  by	
  hepatocytes
           +	
  inside	
  hepatocyte.	
  conjugated	
  	
  w/	
  glucuronic	
  acid=	
  direct	
  bilirubin/	
  soluble.	
   and	
  can	
  now	
  be	
  excreted	
  in	
  bile
                  in	
  the	
  colon-­‐	
  bilirubin	
  is	
  deconjugated	
  and	
  metabolized	
  by	
  bacteria	
  to	
  make	
  urobilinogens.	
  most	
  excreted	
  in
                  poo	
  as	
  waste	
  [but	
  remember	
  that	
  bile	
  acids	
  are	
  recycled	
  in	
  the	
  enterohepa;c	
  recirc]

cholestasis=	
  failure	
  of	
  bile	
  to	
  reach	
  duodenum.	
  due	
  to	
  obstruc;on
   ::	
  vs.	
  jaundice-­‐jaundice	
  =	
  elevated	
  bilirubin	
  in	
  blood	
  and	
  ;ssues.	
  can	
  occur	
  w/out	
  cholestasis.	
  but	
  cholestasis
          almost	
  always	
  assoc.	
  with	
  jaundice.	
  jaundice	
  caused	
  by	
  cholesta;s	
  or	
  hemolysis	
  [too	
  much	
  bili	
  to	
  excrete]
   ::	
  extrahepa-c	
  obstruc-on.	
  of	
  ducts	
  by	
  stone,	
  cancer,	
  stricture	
  [at	
  bile	
  ducts,	
  ampulla	
  of	
  vader	
  or	
  pancrea;c	
  head]
   ::	
  intrahepa-c	
  obstruc-on.	
  of	
  small	
  ducts	
  by	
  various	
  disease	
  process:	
  PBC,	
  PSC.	
  or	
  funxl	
  problem	
  in	
  hepatocyte
          produc;on	
  of	
  bile:	
  infec;on,	
  medica;on,	
  pregnancy	
  [estrogens]
   ::	
  clinical/lab	
  findings.	
  pruri;s,	
  jaundice,	
  acholic	
  stool,	
  choluria,elevated	
  D	
  bili/alk	
  phos	
  and	
  GGT

								
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