Phys: Gallbladder and Bile Flashcards
hepatic blood supply
1 a. Hepatic artery (25%): Arterial blood which provides the liver’s O2 supply and metabolites for hepatic processing
b. Hepatic portal vein (75%): venous blood draining the stomach, digestive tract, pancreas, and spleen for processing and storage of newly absorbed nutrients
2. Hepatic vein: Blood leaves the liver via hepatic vein
Functions of liver
- Metabolism of major nutrients: carbs, lipids, proteins
- synthesis of plasma proteins, albumins, glucose, chol, FA’s
- Storage of glycogen, fats, iron, vitamins
- *Detox: steroids, hormones, drugs, toxins
- Inactivation: removes foreign particulate matter by Kuppfer macrophage cells: bacteria, endotoxins, parasites, agin RBC’s
- Activation: convert hormones and vitamins into more active form hydroxylation of vitamin D
- Bile production
Bile
- “gall”
- green-yellow from bilirubin
- bitter, neutral or slightly alkaline fluid synthesized by the liver
- consists of salts, proteins, cholesterol, hormones, enzymes and bilirubin
Bilirubin
- breakdown product of heme from Hgb
- excreted by liver in bile
bile secretion
hepatocytes –> bile canaliculus –> bile duct (periphery of lobule) –> common bile duct –> duodenum
hepatocyte lobule
- functional units of liver, hexagonal arrangements surrounding a central vein.
- At each of the 6 corners of the lobule there are 3 vessels (hepatic artery, hepatic portal vein, bile duct)
sinusoid
: expanded capillary spaces between rows of hepatocytes
- hepatic artery & portal vein flows blood from sinusoids to central veins to hepatic veins
bile canaliculus
- bile carrying channels runs between sinusoids and within each hepatic plate
- Each hepatocyte is in contact with a sinusoid on one side and bile cannaliculus on other side
cells of liver:
parenchyma composed of hepatocytes (95%) - sinusoidal space contains: 2% Kuppfer (phagocytic cells) 1% Stellate (Ito) cells: fibroblasts 2% endothelial cells
Stellate cells
= Ito cells
- when inflammation occurs: Ito cells turn into myofibroblasts, produce collagen, liver becomes fibrotic, constricts blood flow and this blood supply results in necrosis –> cirrhosis
Space of Disse
- space between sinusoid and hepatocyte
- stellate cells present here
- Kuppffer cells cleanse blood of bacteria, toxins, parasites, aging RBC’s as it passes through
- albumin is secreted here
Portal acinus
lobular arrangement purposed around the supply of oxygenated blood to hepatocytes
sphincter of Oddi
- regulates flow out of common bile duct and pancreatic duct
- prevents bile from entering the duodenum
- after meal, this relaxes and bile enters the duodenum due to CCK and ACh
Bile flow?
Bile produced in hepatocytessecreted
into canaliculbile ductulescommon
ductgall bladderbile duct
small intestine
2 components to bile secretion:
- Hepatocyte cells: secrete bile acids, cholesterol.
- Secretory eptihelial cells: located in ducts and ductules: secrete watery solution of sodium and bicarb in response to secretin
secretin
- stimulates cholangiocytes of ductules and ducts to secrete bicarb. into ducts and initial bile
- secretin, glucagon, VIP are all stimulatory to bile secretion
flow of bile?
hepatic cells - minute bile canaliculi -
interlobular septa – terminal bile ducts –
larger ducts – hepatic and common bile duct –
duodenum or via cystic duct into gallbladder.
3 steps of bile formation
- canalicular bile is active and isotonic
1. Hepatocytes actively secrete bile into the bile canaliculi: The hepatocytes conjugate most of primary bile acids to small molecules such as glycine and taurine before secreting them into the bile.
2. Intrahepatic and extrahepatic bile ducts not only transport this bile but also secrete into it a watery, HCO3−-rich fluid
These first two steps may produce ∼1000 mL/day of so-called hepatic bile.
- Half the hepatic bile-(500 mL/day) is diverted to the gallbladder, which stores the bile and iso-osomotically removes salts and water
bile compensation
67% bile acid 22% phospholipids 4% cholesterol .3% bilirubin 4.7% protein (includes bicarb.)
Bile salts
Bile Salts (cholates, chenodeoxycholate, deoxycholate): produced by hepatic metabolism of cholesterol and excreted into bile. - Bile salts in bile act as detergents to dissolve dietary fat for absorption
Disruption of bile excretion disrupts fat absorption & causes malabsorption:
- Patients develop diarrhea because of the resultant steatorrhea and then develop associated deficiencies of fat-soluble vitamins (A, D, E, & K)
Cholesterol and Phospholipids
- hepatic secretion of cholesterol and its metabolites (bile salts) into bile is the body’s major route of cholesterol elimination.
- Bile phospholipids enhance cholesterol solubilizing properties of bile salts
- Inefficient excretion cholesterol can cause an increased serum cholesterol
Bilirubin
Comprises only 0.3% bile; responsible for bile’s green-black color.
- Obstruction of bile flow leads to jaundice.
functions of bile
- Fat digestion and absorption: After eating, gallbladder contracts & releases bile acids into intestines. Digests/absorbs lipids by emulsifying and assisting through intestinal mucosa.
- Waste product excretion: bilirubin, cholesterol, liphophilic drugs, trace minerals
Bile salts actions in intestinal tract
- Detergent action or Emulsification on fat particles.
- decreases the S/A
- increase agitation in intestinal tract to break fat globules - Absorption of:
- Fatty acids, monoglycerides, cholesterol and other lipids by formation of small complexes called micelles (semi-soluble in chyme)
somatostain
- inhibits bile flow by lowering [cAMP]i, an effect opposite that of secretin.
- This inhibition may be caused by enhancing fluid reabsorption by bile ducts.
Secretin, Glucagon and Vasoactive Intestinal Peptide (VIP)
increases secretion via:
- Stimulates the cholangiocytes of ductules and ducts to secrete a watery, HCO−3-rich fluid
- raise [cAMP]i and thus stimulate apical Cl− channels and the Cl-HCO3 exchanger. (Cl- taken into cholangiocyte from lumen, and HCO3- excreted into lumen)
- A Ca2+-activated Cl− channel is also present in the apical membrane.
Mucus
- secretion by gallbladder epithelial cells protects the apical surface of the gallbladder epithelium from the potentially toxic effects of bile salts.
However, excessive mucin synthesis can be deleterious:
- -> Cholesterol cholelithiasis (i.e., formation of gallstones made of cholesterol), a marked
- increase in mucin release precedes crystal and stone formation.
CCK
- presence of fatty food in the duodenum results in release of CCK
- causes contraction of the gallbladder
- causes relaxation of the sphincter of Oddi
- increases bile flow into the duodenum
Ach
secreted from vagus and intestinal enteric NS
- stimulates gallbladder less strongly than CCK
Steps of Bile release:
- acidic/fatty chyme enters duodenum, results in release of CCK and secretin from duodenal wall enteroendocrine cells
- CCK and secretin enter blood stream
- bile salts and secretin stimulate liver to produce bild more rapidly
- vagal stimulation via ACh causes weak contraction of gallbladder
- CCK causes gallbladder to contract and sphincter of Oddi to relax
- bile salts reabsorbed into blood
enterohepatic circulation of bile acids
- recirculation of the bile salts
- liver makes small amount of total bile pool
- majority of bile is recycled via enterohepatic circulation from terminal ileum –> hepatic portal vein –> liver
- reabsorbed via diffusion and active transport in distal ileum –> portal vein.
- hepatocytes reabsorb and then resecrete the bile
Salmonella typhi
The gallbladder serves as “safe harbor” in the healthy carrier state for typhoid (enteric) fever.
Cholestasis: what are three things it causes
- suppression of bile secretion
- biliary constituents may be retained within the hepatocyte and regurgitated into the systemic circulation.
- causes three major groups of negative effects:
1. regurgitation of bile components (bile acids, bilirubin) into the systemic circulation gives rise to the symptoms of jaundice and pruritus (itching).
2. cholestasis damages hepatocytes, as evidenced by the release of liver enzymes (e.g. alkaline phosphatase) into the plasma.
3. because the bile acids do not arrive in the duodenum, lipid digestion and absorption may be impaired.
***Many acute and chronic liver diseases produce cholestasis by mechanically obstructing the extrahepatic bile ducts or by impairing bile flow at the level of the hepatocytes or intrahepatic bile ducts.
Cholelithiasis
formation of stones (calculi) within the gallbladder or biliary duct system
Cholecystitis
inflammation of gall bladder (often due to stones remaining in gall bladder for too long)
Cholangitis
inflammation of biliary ducts
Gallstones form due to…
- abnormal bile composition (too much absorption of water from bile, too much absorption of bile salts, too much cholesterol)
- biliary stasis
- inflammation of gallbladder
Places where cholelithiasis can occur:
- asymptomatic stone in gallbladder
2/3. stone lodged in cystic duct - causes intermittent biliary pain, can also cause cholecystitis - stone in cystic duct compressing into bile duct, causing Mirizzi’s syndrome
- stone in distal bile duct, causing jaundice, biliary-type pain, and risk of cholangitis/pancreatitis. obstructing ampulla of Vater.
- stone eroding through gallbladder into duodenum: causes cholecystoenteric fistula
- long-standing cholelithiasis resulting in gallbladder carcinoma
Risk for gallstones?
Female, Fat, Fair, old age
conditions for formation of cholesterol gall stones?
- supersaturation
- gallbladder hypomotility
- crystal nucleation
- accretion within mucous layer
cholecystectomy
removal of gallstones
- gallstones may be present for decades before symptoms develop
- larger the stone, the less likely it is to enter cystic or common ducts and obstruct - small “gravel” stones are more dangerous
Bile acids formation
- The major solutes driving the primary secretion of bile are the bile acids, which are amphipathic
molecules synthesized from cholesterol in the hepatocyte. - Bile acids can be modified by intestinal bacteria to yield compounds known as secondary bile acids. One of these, lithocholic acid, is relatively toxic, and so mechanisms exist to promote its elimination from the body.
Bile production summary: see slide.
- hepatocytes make bile acids from cholesterol. these acids are secreted into bile canaliculus in conjugated form. Bile includes glucose and calcium as well. Glucose is actively reabsorbed from bile as it passes to biliary ductules - which also add IgA and render bile alkaline via secretion of bicarb.
how does bile remain iso-osmolar during concentration?
Gallbladder storage of bile results in changes in its composition, such that bile acids become the
dominant anions.
Bile remains isotonic during this process as bile acid monomers are rapidly incorporated into mixed micelles.
Concentration of bile results from active transport processes taking place in the lining epithelial
cells.
Bile synthesis
The liver converts cholesterol to the primary bile acids—cholic acid and chenodeoxycholic.
Action of bacteria in terminal ileum and colon may dehydroxylate bile acids, yielding the secondary bile acids deoxycholic acid and lithocholic acid.
The hepatocytes conjugate most of primary bile acids to small molecules such as glycine and taurine before secreting them into the bile. The liver may also conjugate some primary and secondary bile acids to sulfate or glucuronate
