Physiology (And pharmacology) of Liver Flashcards
Where does arterial and venous blood mix?
liver sinusoids
What are sinusoids?
fenestrated capillaries
What shape are liver lobules in cross sections?
hexagonals
What do liver lobules have a branch of at their centre?
hepatic vein
What do liver lobules have at each 6 corners?
portal triad
How are cords of hepatocytes in the liver lobules arranged?
as hepatic plates
What direction does blood flow through sinusoids to the central vein?
inwardly
Where does bile secreted by hepatocytes flow?
outwardly through caniculi to the bile duct
How thick is the epithelium hepatocytes form and what does this separate?
1 cell thick, separates 2 fluid filled compartments
How are hepatocytes arranged?
in between sinusoids in plates 2 cells thick
What does the basolateral membrane face?
a pericellular space called the Space of Disse
What does the apical membrane form?
the caniculi
Which membrane is grooved?
apical
Which 3 cells do sinusoidal spaces contain?
endothelial cells, kuppfer cells and stellate cells
What structure do the endothelial cells form?
fenestrated
What do the endothelial cells in the sinusiodal spaces do?
allow for free movement of solutes but not cells
What do the Kuppfer cells do?
These are macrophages which remove particulate matter (eg bacteria) and senescent erythrocytes
Where are the Stellate cells and what do they do?
In space of Disse, store vitamin A and play role in fibrosis and cirrhosis
What may be used to dissolve non-calcified gall stones?
Ursodeoxycholic acid
What is bile involved in the digestion and absorption of?
fats
During a meal, what stimulates the gall bladder smooth muscle to contract?
chyme in duodenum via CCK and vagal impulses
What does the sphincter of Oddi contract via?
CCK
Via which ducts does bile spurt into the duodenum during a meal?
Cystic and common
Is bile from the liver mixed in with the bile spurted into the duodenum during a meal?
Yes
What soes primary juice secreated from hepatocytes into caniculi drain into?
biliary ductules
What does hepatic bile consist of?
primary bile acids (mainly cholic and chenoeoxycholic acids) water and electrolytes, lipids and phospolipids, cholesterol, IgA and bilirubin
What is bilirubin the breakdown product of?
breakdown product of the porphyrin component of haemoglobin
When do bile duct secretions have an ionic composition similar to plasma?
between meals
What happens to bile duct secretions during a meal?
During meals flow rate increases in response to secretin released from duodenal S cells
Where does HCO3-/Cl- exchange occur and when is it reduced?
across the duct cell apical membrane – reduced at high flow rate - therefore HCO3- content increases
What does the neutral/slightly alkaline pH of bile duct cell secretions contribute to?
micelle formation
neutralization of chyme
pH adjustment for digestive enzyme action
protection of the mucosa
How are bile salts synthesised?
from cholesterol in a series of 14 reactions, first mediated by cholesterol 7a-hydroxylase (CYP7a1) to form the primary bile salts
What is rate of synthesis of bile salts dependent on?
the hepatic portal blood concentration of the salts
- Low concentrate stimulates synthesis
- High concentration inhibits synthesis
Is secretion across the apical membrane by diffusion or active transport?
is by active transport (MRP2 and BSEP)
What causes aqueous alkaline bile secretion?
secretin
In what phase of digestion does vagal activity produce a mild secretory response?
cephalic
What are drug options for biliary colic?
For Analgesia
Morphine – but constricts the sphincter of Oddi; buprenorphine and pethidine are alternatives
For relief of biliary spasm
Atropine, or glyceryltrinitrate (GTN)
How are gall stones actually treated?
surgery or ursodeoxycholic acid
With what type of drugs do metabolites gain activity?
prodrugs
Does drug metabolism make a drug more or less polar?
more polar (Adds an endogenous compound)
Are some drugs excreted unchanged?
Yes
What is aspirin changed to in the 2 phases of drug metabolism?
Salicyclic acid (the derivative) and then Glucuronide (conjugate)
