2. Physiology I Flashcards
1
Q
The Bile
• Bitter-tasting, dark green to ____ brown fluid, produced by the liver.
• Stored in the gallbladder and upon eating is discharged into the duodenum.
- Physical properties;
- Hepatic bile: pH ____, golden yellow.
- Bladder bile: pH ____, green to dark yellow.
- Volume of bile produced: up to 1 liter/day (depending on body size)
• Functions:
1. Enhancement of intestinal absorption:
• ____, calcium, iron.
- Route of excretion of solutes poorly filtered by the kidney:
• Lipid-soluble compounds: ____, bilirubin, ____, plant sterols.
• ____-bound trace minerals.
• Antigen-antibody complexes.
• ____. - Secretion of ____- to neutralize any excess stomach acid before it enters the ileum.
- ____ action of bile salts on microbes ingested during meals.• When bile leaves hepatos > composition and acidity of the liver is around pH 7.4 (within psyiologic range of pH)
• Bile that leaves the gallbladder > changes color (change in composition) and in pH
• Most of recycled bile is ____ fluid (in terms of solutes)
• Hydrophobic/lipid soluble molecules can cross the membranes of cell easily > difficult to excrete through the ____ (immediately reabsorbed)
○ Bili eliminated via bile instead of kidney
• May contain high cxn of HCO3-
○ Physiology of GI tract > stomach makes food/fluids that’s high in acidity
○ Secretory of pancreas > bicarbonate; another source is also provided by the bile
A
yellowish
- 4
- 8
lipids cholesterol xenobiotics protein IgA HCO3 bactericidal
recycled
kidney
2
Q
Biliary Tract: Liver Histology
Liver lobule is the basic functional unit of the liver:
• Hepatocytes:
• synthesis of ____ components.
- Endothelial cells:
- Lack a ____.
- Facilitate exchanges between the ____ and the sinusoid.
- Kupffer cells:
- Monocyte/____ lineage: reticuloendothelial system.
- Line the hepatic ____.• Hepatocytes are organized into hepato plates
○ ____ cells
§ One side is in contact with the space of Disse that is separated with endo cells from ciruclation
§ On the other side > domain forms a secretory duct
○ Hepatos can obtain from portal circulation > absorb and recycle > secrete substances into the bile canaliculus > bile excreted
A
bile basal lamina space of disse macrophage sinusoids
polarized
3
Q
Biliary Tract: Liver Histology
Bile is secreted in two stages:
1. Secretion by the hepatocytes into ____ located between rows of hepatocyte cells
(____).
2. The bile flows toward the ____, hepatic
duct and common bile duct.
• Important for recirculation of bile acid and salts
A
bile canaliculi
hepatic plates
bile ductules
4
Q
Biliary Tract: Hepatic Duct and Gallbladder
From the hepatic duct and common bile duct the bile either:
• Empties directly into the ____ at the sphincter of Oddi, or…
• Is diverted through the cystic duct into the
____: modification and concentration.
• Bile leaves liver through the bile duct > common hepatic duct > bile is directly excreted into the duo thorugh sphincter of Oddi, or stored in the gallbladder
A
duodenum
gallbladder
5
Q
The biliary tract has 4 components
• Canaliculus ○ At level of hepatos > formation of bile > excreting bile into \_\_\_\_ (basal domain of hepato) • Ductules & ducts ○ Passage thorugh the ducts > primary bile will be modified at the level of \_\_\_\_ ○ Composition of bile reaching and leaving is \_\_\_\_ ○ Secretion of \_\_\_\_ takes place • Gallbladder ○ Ion exchanges and absorption of water > \_\_\_\_ bile ○ \_\_\_\_ delivery of the bile when its required for digestion ○ During \_\_\_\_: stored in the gallbladder, and contracted and bile excreted through the sphincter of Oddi reaches the duodenum • Sphincter of oddi ○ Highly \_\_\_\_ in terms of opening/closing > prevents \_\_\_\_ of material from duo into the gallbladder
A
canaliculus
ion balance
different
bicarb
secondary controlled fasting regulated reflux
6
Q
Bile composition
• Don't memorize • Composition of hepato bile and gallbladder bile is different ○ Hepatic bile § \_\_\_\_ cxn of solutes ○ Gallbladder bile § Relative cxn of solutes has \_\_\_\_ § High rate of water absorption in bile during the storage time • Out of the solutes > mix of molecules ○ Majority (2/3) is \_\_\_\_ > synthesized by the hepatos ○ \_\_\_\_ ○ \_\_\_\_ ○ \_\_\_\_ ○ \_\_\_\_ products (bilirubin) • Composition of solutes is constant in both, but the biles are different ○ Gallbladder is more \_\_\_\_
A
lower increased bile acid cholesterol lipid electrolytes waste
cxn
7
Q
Bile Acids and Bile Salts
- Bile acids:
- Synthesized by hepatocytes from ____.
- Secreted as conjugates of ____ or glycine.
• Classification: • Primary: • Synthesized by the \_\_\_\_. • Examples: \_\_\_\_ acid and \_\_\_\_ acid.
• Secondary:
• ____ of bile acids by GI bacteria.
• Examples: Cholic acid is converted to
____ acid and chenodeoxycholic acid to ____ acid.
A
cholesterol
taurine
hepatocyte
cholic
chenodeoxycholic
dehydroxylation
deoxycholic
lithocholic
8
Q
Bile acids and bile salts
• BA derive from cholesterol ○ Complicated and long pathways ○ Hepatos synthesize primary BA from cholesterol • BA are divided into primary and secondary BA ○ Primary > directly synth by the hepatos (chenodeoxycholic and cholic acid) § When reach the colon > the bacterial flora will use some of the primary BA to modify them and produce > secondary bile acids (deoxycholic and lithocholic acid) § Since the BA are continually recycled bt the GI and liver, eventually the bile that's stored in the gallbladder are \_\_\_\_ and \_\_\_\_ § Usually the primary BA produced by the liver are further modified to be secreted as conjugates □ Cholic acid has carboxy acid group; hepatos add taurine or glycine (AA) > glycocholic acid (conjugated) ® Either conjugated or nonconjugated > still haevt eh \_\_\_\_ group at the end; most common species that you find in bile is the \_\_\_\_ form of acid that's balanced out by a + ion > most common presented as \_\_\_\_ (sodium glycolate, instead of glcyocholic acid) ® The bile salts (ionized) are more \_\_\_\_ than free BA > much lower \_\_\_\_ across membranes then the case for the nonionized BA ® When the bile salts reach the intestine > will not be efficient as crossing PM of enterocyte; the SI absorbs bile salts \_\_\_\_ than BA ® Since bile salts have detergent function > to produce small globules of fat > and SI poor at absorbing BS > the lipids that are composing those droplets of fat + BS > the lipids are absorbed \_\_\_\_ ® The droplets of fat get smaller > the lipids are more \_\_\_\_ at being absorbed than the bile salt molecules ® Only once all lipid absorbed > then \_\_\_\_ can cross the membrane (mostly do not cross by diffusion bc they're electrical, but there's a \_\_\_\_ located in the ileum)
A
primary
secondary
carboxyl
ionized
bile salt
polar
diffusion
slower
first
BS
transporter
9
Q
Bile Acids and Bile Salts
• Neutral pH: bile acids ionized to ____ (e.g. sodium cholate).
• Conjugated bile acids ____ more readily than the unconjugated bile acids (e.g., sodium glycocholate).
• Bile salts more polar than bile acids: lower ____
across cell membranes → Small intestine absorbs bile
salts much ____ than bile acids:
• Role in the intestinal absorption of lipid: smal intestine
absorb bile salts only after all of the ____ has been absorbed.
A
bile salts ionize diffusion poorly lipid
10
Q
Bile Acids and Bile Salts
• Detergent action:
• Emulsification of lipid particles in the food which
decreases the ____ of the particles.
- Formation of micelles:
- ____ particles, 3-6 nm in diameter, 20-40 molecules of bile salt.
- Transporters of monoglycerides and free fatty acids to the ____ of the enterocytes.
- Hydrophilic sides positively charged due to ____ and other phospholipids → prevent bile salt-coated lipid droplets from aggregating into ____ particles: increased ____ for pancreatic lipase in lipid digestion.• BA/BS > detergent function
○ Ability of the molecules of BS to emulsify the globules of fat that is released during the digestion of the lipid-rich diet > convert into much smaller emulsified droplets
○ Where the fat globules cannot be referred to as dissolved in chyle, but emulsified molecules are essentially dissolved > more easily ____ to receptors and absorbed
○ Bc of their composition and of the fat > control the maximum size of mycelles
§ Two spheres > the smaller one has a higher ratio of ____
§ Since th elipids that form the spheres need to be degraded by panc lipase > needs a lot of surface > more efficient at digesting a ____ droplet than something like a fat globule
□ Bigger ball, surface:volume ratio is smaller
A
surface tension colloidal brush borders lecithin larger surface area
attached
surface:volume
small
11
Q
Bile Formation: Canalicular Bile
• ____-dependent transporters.
• Bile salt secretion→ osmotic gradient→ water flow ____ the canaliculus.
• Ion exchanger: passage of ____- and ____- ions.
• Process of formation of the bile • Hepatic bile > canalicular bile > primary bile by the hepatos • Liver cell plates > substance being secreted • Most of the substances secreted in the canaliculus > \_\_\_\_ org moleules (BA, phospho, glutathiamine) > secreted by transporters that are \_\_\_\_ (against their cxn gradient, and require ATP) ○ Solution into canaliculus is becoming more \_\_\_\_ ○ When have the situation where the compartment is getting higher and higher > \_\_\_\_ of water into the canal bc of the inc of org substances ○ At level of liver cell > secretion of bicarb in exchange for Cl- § To balance the cxn of ions, since the \_\_\_\_+ ion is also being secreted by following the water
A
ATP
into
HCO3
Cl
large
active
cxn
influx
Na
12
Q
Bile Flow
Canalicular bile flow: sum of two components:
- Bile acid–independent flow: “____” component ____ of bile acid secretion.
- Bile acid–dependent flow: rising component that increases linearly with ____.• Measure flow of bile and relative composition > rate of excretion of BA vs the total flow of bile
• Looking at the canlaicular bile secretion; two flows:
○ BA independent
§ More or less constant independent of excretion of BA, whereas the flow that is depend on bile acid increases when the excretion rate of BA increase
○ BA dependent
§ When total excretion rate of BA increases (x-axis) > BA dependent flow is increasing, while the BA indepent is constant
A
constant
independent
bile acid secretion
13
Q
Bile formation: canalicular bile
• Two modes of hepatic bile secretion:
- Bile Acid-Dependent Bile Flow:
- [Na+] gradient created by the ____ (1)
- Na+-dependent reabsorption of free ____ (2: Na+/BA symporter) and ____ before secretion.
- Secretion: ____-dependent BA transporter(3).
- BAs stimulate secretion of other solutes by trapping them in the lumen: ____, organic anions, ____ and phospholipids.
- BA secretion → osmotic gradient → water flow ____ the canaliculus → bile flow.
- Bile Acid-Independent Bile Flow.• Initial disequilibrium in ions is driven by the Na/K ATPase (a pump) that excretes Na and imports K > disequilibrium in cxn of Na
• In the hepato > have the synthesis of BA (new) that may/may not be conjugated; since most of the BA are recirculated bt the liver and intestine, some of the recirculated BA come back through the portal circulation and are reabsorbed by the hepatocyte > two components:
○ Small comoponet (from new molecules)
○ Large component > recirucaltion of bile salts
• The bile salts are asborbed with hepato in combination with Na+ > ____ transport
○ ____
• This absorption of bile acid is being drived by the Na/K ATPase
• Now have a pool of recycled Bile acids and new bile acid > (3) the ____ xport of bile acids (slide 13) is moving the bile acid into the canaliculus
• Bile acids will not only stimulate secretion of other solutes (by trapping them in the lumen), but most important > secretion of BA > ____ gradient
○ Inc OG > inc flow of water into canaliculus > flow of bile increases
• Without the reabsorption of BA from portal circ and rexporting bile acid > the amount of water entering canal would be ____, and the amount of flow depends on the rate of ____ being reabsorbed and reexcreted
A
Na/K ATPase BAs re-conjugation ATP bilirubin cholesterol into
symport passive active osmotic lower BA
14
Q
Bile formation: canalicular bile
- Two modes of hepatic bile secretion:
- Bile Acid-Dependent Bile Flow.
- Bile Acid-Independent Bile Flow:
- Due to secretion of organic compounds, mainly ____.
- Secretion of inorganic ions: ____- (5).
- Energy provided by [Na+] gradient created by the ____ (1).
- ↑GSH → osmotic gradient → water flow ____ the canaliculus → solvent drag (↑____- ) → bile flow.• Na/K+ ATPase is present
• At the secretion of org molecules (glutathione) and bicarbonate
○ The energy that is provided depends on activity of Na/K+ ATPase
• For the secretion of bicarbonate > bc of the prod bicarb from Co2 and the ionization of carbonic acid into bicarb > ____ cahrge must be maintained, the protons derived from ionization are exported bc if you let the cxn of protons get high > low pH
○ Export of ____+ is balanced by absorption of Na+
○ Na+ follows cxn disequilibrium by the Na/K ATPase
• Org molecules will be secreted using ____ transport (____)
• Situation just like the dependent flow
○ The cell is secreting bicarb, and other org molecule
○ Inc cxn of solutes in canal > brings an inflow of water
§ The secretion of substances like GSH/bicarb is not at all dependent on the reciruclation/flow of ____
A
glutathione (GSH) HCO3 Na/K ATPase into HCO3
electrical
H
active
MOAT
BA
15
Q
Bile Modification in the Bile Duct
• Carried out by bile duct cells: ____.
• Similar to the secretion of ____- by pancreatic duct
cells.
• ↑HCO3- lumen → ↑____+ → osmotic gradient → water
flow.
• Result: ____ hepatic bile.
* Most impt modifcation of bile by epi cells that line the bile ductiles > cholangiocytes > is the secretion of bicarb in form of \_\_\_\_-bicarb * Bicarb is being secreted, electrical charge of bicarb (negative) must be balanced by the secretion of Na+ ions > creates a \_\_\_\_ cxn gradient > water flow * Most impt function of cells lining the bile duct is the secretion of \_\_\_\_
A
cholangiocytes HCO3 Na alkaline Na steeper bicarb
