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What is the hepatic lobule?
The functional unit of the liver (hexagonal units)
centered around a central vein
the central vein drains into the hepatic vein
List the major structures associated with the hepatic lobule:
Interlobular vein (to hepatic vein)
Central vein
Plates of hepatocytes (liver cells)
Sinusoids (sinusoidal capillaries - very leaky)
Hepatic portal vein
Hepatic artery
Portal triad
Bile duct
What structures make up the portal triad?
At each of the 6 outer corners of a lobule are portal triads made up of branches of the:
bile duct
hepatic portal vein
hepatic portal artery
What are hepatocytes?
They are liver cells and about 70% of their surface faces the sinusoids
The liver has many metabolic and regulatory roles but its digestive function is to produce what?
Bile
What are the two cell types that are responsible for the production and release of the components of bile?
the hepatocytes (liver cells)
the epithelial cells lining the bile ducts
What is the major function of epithelial cells lining the bile ducts?
They release HCO3-
Where does the blood in the central vein eventually end up?
Into the hepatic vein
What are sinusoids?
They are large spaces lined with endothelium, through which blood passes
very leaky capillaries
big plasma proteins into blood
Which 2 blood sources supply the sinusoids?
The hepatic portal vein and the hepatic portal artery
What are bile canaliculi?
They are small channels into which bile is secreted
List the functions of the liver:
Carbohydrate metabolism
important in maintaining normal blood glucose level
Lipid metabolism
some triglyceride storage
cholesterol synthesis
Protein metabolism
synthesis of most plasma proteins: (alpha and beta globulins, albumin, and fibrinogen)
Detoxification
removal of drugs and hormones
Excretion of bilirubin and cholesterol
Synthesis of bile salts
Storage (glycogen, vitamins and minerals such as iron and copper)
Phagocytosis (Kupffer cells) “gobble up”
Activation of vitamin D
Synthesis of plasma proteins (albumin, fibrinogen)
In terms of digestion, what is the most important contribution of the liver?
The production/synthesis and secretion of bile
Which hepatic cells produce bile?
Hepatocytes
Is bile acidic, neutral or basic (alkaline)?
Basic (7.6-8.6)
Where is bile stored and concentrated?
By the gallbladder
Name the 4 major components of bile:
Bile salts (made from steroid bile acids combined with amino acids) conjugation!
Bile pigments
Cholesterol
HCO3-
Which of the major components of bile are produced by hepatocytes?
Bile salts
Bile pigments
Cholesterol
Which of the major components of bile are produced by the bile duct epithelial cells?
HCO3-
What are two major functions of bile salts?
Emulsification: the breakdown of large lipid globules into smaller droplets
the tiny lipid droplets present a very large surface area for the action of the pancreatic lipase (the major lipid digesting enzyme)
Lipid absorption: following their digestion
via formation of micelles
Name one prominent bile pigment:
Bilirubin
a build up of bilirubin causes jaundice
What role does bicarbonate play?
It neutralizes acid in the duodenum
What is some information about the cholesterol?
Excreted in feces
bile is the major vehicle for cholesterol excretion from the body
too much cholesterol or too few bile salts can lead to cholesterol crystallization (gallstones or biliary calculi)
What are the most important digestive components of bile?
The bile salts
What is the flow of bile?
Left & Right Hepatic Ducts → Common Hepatic Duct →
either Cystic Duct ↔ Gallbladder (for storage)
or → Common Bile Duct + Main Pancreatic Duct →
Hepatopancreatic Ampulla → Duodenum
When is bile secretion the greatest?
During a meal, but the liver is always producing and secreting some bile (ductile bile rich in bicarboante)
In between meals, is the sphincter closed or open? Explain.
It is closed and bile gets diverted to the gallbladder where it becomes concentrated
it moves up via the cystic duct
concentration: NaCl & H2O get absorbed into blood
Where is the sphincter of Oddi located?
It is located where the common bile duct and pancreatic duct open into the duodenum
When is the sphincter of Oddi open?
It opens during a meal (especially a fatty meal)
the sphincter relaxes (opens)
the gallbladder contracts
What role does CCK (released by duodenum) play in regulating the sphincter of Oddi?
It triggers dilation of the sphincter and contraction of the gallbladder
This ejects bile into the duodenum through the duodenal ampulla
What are bile acids?
Amphipathic end products of cholesterol metabolism
amphipathic means they both have a hydrophilic & hydrophobic regions and can form micelles
How does cholesterol form bile acids?
In the liver through 7α-hydroxylase enzymes
Where can primary bile acids get converted to secondary bile acids?
In the intestines
intestinal bacteria can do this conversion
What does primary bile acids consist of?
cholic acid
chenodeoxycholic acid
What does secondary bile acids consist of?
deoxycholic acid
lithocholic acid
All bile acids are secreted by the hepatocytes in what form?
Conjugated form
What are bile salts?
Conjugated bile acids
the amino acids glycine & taurine are used
this increases water solubility
What is the advantage of conjugating bile acids into bile salts prior to secreting them into the bile canaliculi?
They are charged and therefore, cannot cross cell membranes via passive means (they need active transporters)
It increases their water solubility, making them more effective at emulsifying fats, functioning in the intestinal environment, and aiding lipid absorption
What does the enterohepatic circulation refer to?
This refers to bile salt recycling between the small intestinal lumen and the liver
Normally about 95% of bile salts are reabsorbed by the terminal ileum
bile salts that make it into the colon, can be converted back to bile acids by the bacteria there
the bile salts can be returned to the liver via the hepatic portal vein
In which specific portion of the small intestine are bile salts reabsorbed?
The terminal ileum
Each hepatocyte is in contact with blood from what two sources?
The hepatic artery and hepatic portal system
What is the function of the hepatic artery?
It provides oxygenated blood to the liver
What is the function of the hepatic portal system?
It contains deoxygenated blood containing newly absorbed nutrients, drugs, microbes, and toxins
The vascular connection between the digestive tract and liver
What is the order of the blood vessels in relation to the liver?
Hepatic artery & Hepatic portal vein → Liver sinusoids → Hepatic vein → Inferior vena cava
What is important about the hepatic portal vein?
They are rich in absorbed nutrients from GI tract
What is important about the Liver sinusoids?
Leaky capillaries
receives blood from both the hepatic artery and the hepatic portal vein
What is important about the hepatic vein?
The blood leaves the liver via the hepatic vein which dumps its low oxygen blood into the inferior vena cava
Which blood vessel carries oxygenated blood to the liver sinusoids?
The hepatic artery
Which blood vessel brings low oxygen but high absorbed nutrient blood to the liver?
The hepatic portal system
Which blood vessel drains the liver sinusoids?
The central vein
Which vessels are part of the hepatic portal system?
Hepatic portal vein
Liver sinusoids
Hepatic vein
What role does the gallbladder play in our bile story?
It stores and concentrates bile
The gallbladder is not essential to what?
Normal digestion & absorption of a meal
What are the major functions of the gall bladder?
Storing and concentrating bile
Musculature: contractions of the gallbladder release bile into the cystic duct!
has receptors for the:
vagus nerve (PNS)
Ach
CCK
Name the 3 major functions of the gallbladder that play a role in bile release from the gallbladder:
parasympathetic stimulation
increases bile secretion via vagus nerve (Ach as the neurotransmitter)
CCK
stimulates bile secretion by causing contractions of the wall of the gallbladder
secretin
stimulates the secretion of bicarbonate (bile rich in bicarbonate) by epithelial cells lining the bile ducts
What 3 factors play a role in relaxing the sphincter of Oddi?
CCK
opens the valve by decreasing sphincter tone (relaxing)
VIP
locally relaxes the sphincter
Nitric Oxide
locally relaxes the sphincter
What is the importance of this relaxation of the sphincter of Oddi?
Normally, the relaxation of this sphincter is coordinated with gallbladder contraction