LMP299Y1 Lecture Notes - Lecture 16: Bile Canaliculus, Hepatic Portal System, Bile Duct

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Lecture'16'–'liver'disease'
Objectives'
" Understand!the!anatomy,!physiology!and!pathophysiology!of!the!liver!
" Understand!how!tests!are!used!to!assess!liver!function!
" Recognize!types!of!liver!injury/disease!present!from!patterns!of!test!results!
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Case'study'
Presentation!
" 52!YO!male!admitted!to!the!ED!with!a!1!day!history!of!abdominal!pain!and!vomiting!!
" Pain!was!severe!and!sharp!–!localized!to!the!centre!of!the!abdomen!–!did!not!radiate!
" Vomiting!was!profuse!and!water!–!barely!keep!fluids!down!
" This!case!and!symptoms!are!pretty!vague!–!could!be!anything!(stomach!flu,!pancreatitis,!pregnancy)!!
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Liver:'gross'anatomy'
" Located!at!the!upper!right!quadrant!of!the!abdomen!
" Has!small!left!lobe!and!large!right!lobe!
" Supplied!by!two!vasculature!–!!
o The!hepatic!artery!that!brings!fresh!blood!from!the!
systemic!circulation!into!the!liver!(fresh!nutrients!and!
oxygen!to!generate!the!hepatocytes)!!
o Also!have!blood!brought!in!from!the!portal!vein!–!the!
portal!vein!feeds!from!the!gut!–!brings!a!lot!of!nutrients!
and!etc.!from!GI!tract!through!liver!
o Exiting!liver!is!the!hepatic!vein!–!once!blood!enters!
through!the!hepatic!artery!or!portal!vein,!filters!through!
the!liver!and!exits!through!the!hepatic!vein!–!then!enter!to!
superior!vena!cava!and!into!heart!
" Exiting!liver!(green)!is!bile!tract!–!bile!eliminated!from!liver!(waste!product)!then!
eventually!into!bile!duct!and!into!intestinal!tract!
" Hepatic!portal!–!a!vasculature!system!–!all!the!vasculature!that!feeds!out!of!the!GI!tract!and!
into!liver!!liver!is!primary!source!of!contact!from!outside!world!apart!from!GI!tract!once!
things!are!absorbed,!they’re!re"ingested…!then!enters!the!liver!
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Liver'blood'supply'
" 1300!ml!of!blood!flow!into!the!liver!every!minutes!–!about!¼!of!the!cardiac!output!
o Portal!vein!(from!intestine)!–!high!flow,!supply!for!nutrients!from!intestine,!
constitutes!75%!of!blood!supplied!to!liver!
o Hepatic!artery!(systemic!circulation)!–!low!flow,!high!oxygen,!constitutes!25%!of!
blood!supplied!
" Biliary!tract!(bile!duct)!–!drains!bile!from!liver!to!intestine!with!storage!in!gall!bladder!
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" Left!hand!corner!–!
microscopic!slide!of!
liver!tissue!–!has!honeycomb/hexagonal!shape!to!it!
(lobules)!
" In!the!centre,!you!have!central!vein!and!in!the!
points!of!hexagon,!there’s!the!hepatic!artery,!portal!
vein!and!bile!duct!
" As!blood!enters!portal!vein!and!hepatic!
artery,!they!flow!through!the!sinusoid!veins!which!are!
lined!by!hepatocytes!!
" Flows!from!points!to!the!centre!!
" Things!can!be!secreted!into!the!sinusoids!
space!such!a!lipoprotein!or!coagulation!factors!etc.!!
LIVER: GROSS ANATOMY
LIVER: Blood Supply
-1300 ml of blood flow into the liver every
minute; about 1/4 of the cardiac output.
- Portal vein (from intestine) - high
flow, supply for nutrients from
intestine, constitutes 75% of blood
supplied to liver.
- Hepatic artery (Systemic
Circulation); low flow, high oxygen,
constitutes 25% of blood supplied.
- Biliary Tract (Bile duct) - drains bile
from liver to intestine with storage in
gall bladder.
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" Bile!canaliculus!–!also!lined!by!hepatocytes!leads!from!bile!canaliculus!into!bile!duct!
o Bile!canaliculus!drains!into!the!opposire!direction!and!eventually!into!intestines!!
o Any!waste!products!(bilirubin)!will!be!discarded!into!canaliculus!and!drained!through!bile!duct!then!
eventually!intestines!
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Cells'of'the'liver'
" Hepatocytes!–!major!functioning!cells!in!liver,!site!of!metabolic!and!synthetic!functions!
" Kupffer!cells!–!phagocytic!cells!in!sinusoids!–!remove!foreign!antigens!(bacteria),!antigen"antibody!complexes!
o Plays!an!immune!response!role!–!take!up!bacteria/antigen!
o Makes!sense!because!things!are!coming!in!from!GI!tract!so!need!immunological!role!!
" Ito!(stellate)!cells!–!normally!store!fat,!can!be!transformed!to!produce!collagen!
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Liver'physiology'
1. Energy!metabolism/catabolism!
o Carbohydrate!metabolism!!example:!glycogenolysis!and!gluconeogenesis!
o Protein!metabolism!!example:!protein!catabolism!in!AAs!
o Lipid!metabolism!!example:!free!fatty!acid!metabolism!
2. Synthetic!functions!!produces!most!of!the!serum!proteins!
o The!liver!synthesizes!serum!proteins!!example:!albumin,!alpha"1"antitrypsin,!hormone!binding!proteins!!
! Most!serum!produced!by!liver!except!for!antibodies!!
! Serum!proteins!help!transport!and!bind!things!
! Help!maintain!colloid!osmotic!pressure!!edema!if!osmotic!pressure!drops!at!extremities!
o Produces!coagulation!factors!!example:!fibrinogen,!prothrombin,!clotting!factors!and!antithrombin!
o Synthesizes!lipids!!example:!cholesterol,!apolipoproteins,!triglycerides!
3. Excretory!and!secretory!functions!
o Secretion!of!bile!acids!
o Secretion!of!bilirubin!!important!in!assessing!liver!function!
o Clearance!of!hormones,!drugs,!activated!clotting!factors!from!portal!circulation!
4. Other!functions!
o Detoxification!–!the!liver!breaks!down!toxic!substances!and!most!medicinal!products!(drug!metabolism)!
o Storage!–!liver!stores!a!multitude!of!substances!–!glucose!(as!glycogen),!vitamin!A,!vitamin!D,!vitamin!B12,!
iron!and!copper!
o Immunological2role!–!the!reticuloendothelial!system!of!the!liver!contains!many!immunologically!active!
cells!that!help!to!remove!antigens!and!Ag"Ab!complex!(Kupffer!cells)!
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Formation'and'clearance'of'bilirubin'
" Bilirubin!=!breakdown!product!of!RBC!catabolism!–!major!component!is!hemoglobin!(protein!subunit!(α,!β)!with!
heme!group!on!it)!
" RBC!are!targeted!for!destruction!!goes!to!spleen!
" Hemoglobin!removed!from!RBC!once!targeted!for!destruction!then!globulin!and!heme!structure!is!removed!
" Protein!will!be!degraded!and!recycled!(as!with!most!protein)!
" Heme!has!iron!atom!at!the!centre!–!iron!is!toxic!to!the!body!so!won’t!be!much!free!iron!in!body!!
Formation and Clearance of Bilirubin
Globin structure is catabolized to
amino acids or recycled
Bilirubin
Biliverdin
Heme Oxygenase
Fe sequestered
+
Albumin
circulation
Bilirubin
Bilirubin Diglucoronide
UDP-glucoronyltransferase
Excreted into the
bile duct via the
canaliculis
Bilirubin
LIVER
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