Block 2 - Epithelium 1-3 Flashcards
A layer of epithelial cells often forms…
a barrier between two compartments
There are two main ways to get across a cell barrier. What are they, and describe them.
paracellular route: between cells, depends on the properties of cell-cell junctions
transcellular route: through cells, materials need to cross the membrane, depends on properties of transporters/channels/lipid solubility
What properties of an epithelia can be changed?
solute selectivity, rates of transport, barrier resistance
Tight junctions are —– —— ——- that enable…
complex protein structures
enable the paracellular route to be selective
What component of a tight junction impacts its selectivity? How?
claudins
negative amino acids repel anions (selective for cations)
positive amino acids repel cations (selective for anions)
What ion is necessary for tight junctions to form?
Ca++
Epithelia are tight or leaky based on…
their ability to prevent water and solute movement
Where are examples tight and leaky epithelia located in the body?
tight - distal convoluted tubule, collecting duct of the nephron, bile duct, blood brain barrier
leaky - renal proximal tubule, jejunum, gallbladder
Trans epithelial ion transport results in electrical properties like…
trans epithelial electrical voltage
trans epithelial electric current
What is the trans-epithelial electrical resistance (TEER)?
indicator of the tightness of the epithelium (leaky have a TEER less than 1,000 omega-cm)
It is important that epithelia allow the movement of…
water
The lipid bilayer reduces the free diffusive flux of H2O by about —- fold
10,000 fold
Water crosses the cell membrane (faster/slower) than the lipid bilayer
faster (10-100 times faster)
Researchers revealed that —— ——- enable movement of water through the membrane.
specialized proteins (called water pores, or aquaporins)
Describe the process of discovering aquaporins
- isolated from RBCs, molecular weight was 28 kDa, and it was extremely abundant (200,000 copies per RBC)
- when the protein was expressed in an toad oocyte it increased rate of swelling when the cell was placed in a hypo osmotic solution
Cell polarity refers to…
the intrinsic asymmetry of a cell’s shape, structure, or subcellular organization
Epithelial cells typically have – regions:
2 regions, the apical and basolateral which are structurally and functionally different
Describe the basolateral surface
includes the plasma membrane which is in contact with the basal lamina, and the lateral membrane between neighboring cells (the boundary is the tight junction)
Describe the apical surface
on the other side of the tight junction, the surface of the epithelium, the side that faces the lumen in tubes like the intestine
Which surface has mechanisms of transcellular pathways for solute movement?
both - apical and basolateral
Describe glucose absorption mechanisms at the apical surface
- Na Glucose cotransporters (SGLTs) move glucose across the apical membrane and into the cell
- uphill against its concentration gradient by using the Na+ concentration gradient across the plasma membrane
Describe glucose absorption mechanisms at the basolateral surface
- Na+ gradient is established by Na,K ATPase located on the basolateral membrane
- glucose exits the cell by facilitated diffusion across the basolateral surface using GLUT
- this process of entering the ECF is a passive process, since glucose is flowing down its concentration gradient
What is the rate-limiting step of intestinal secretion?
movement of Cl- ions across the apical plasma membrane
Describe the mechanism of chloride secretion
Cl- is transported into the epithelial cell by the Na/K/2Cl cotransporter on the basolateral membrane
the cotransporter uses the Na+ gradient and transports 1 K+ and 2 Cl- ions along with each Na+ ion and raises the concentration of intracellular Cl-
Cl- ions exit through CFTR Cl- channels in the apical surface, moving down their concentration gradient
How is Cl- secretion regulated?
opening and closing of the CFTR Cl- channel is regulated by phosphorylation
cell signaling by cAMP and other pathways controls CFTR function
What can harmfully affect the regulation of Cl- secretion?
cholera (a bacterial toxin) blocks signaling from turning off, so intestinal secretion is unregulated causing osmotic water movement across the epithelium and leading to watery diarrhea
True or False: the transport mechanisms are the same on the apical and basolateral surfaces
False - they are different, and get there via vesicles
The basolateral membrane is specialized to have proteins that…
interact with extracellular proteins of the basal lamina
this is important for cell attachment and adhesion
interactions with the extracellular matrix proteins influences cell growth and differentiation
The apical membrane may have…that are composed of….
microvilli, composed of actin
What is the specialized epithelium in the intestinal tract called, and what does it do?
the brush border - an array of actin-supported membrane protrusions known as microvilli that increases surface area and therefore the functional capacity of the epithelium for absorption
What is the structure of microvilli and how are they formed?
cells use their actin cytoskeleton and bundle 30-40 actin filaments
microvilli are 0.1 um in diameter and 1 um in length
a cell can have as many as 1,000 microvilli
What do integrins do? What is the end result of their actions?
attach the cells cytoskeleton to the extracellular matrix, which causes epithelial cells to polarize
Transcellular solute and water transport requires coordination of…
transporters and channels on the apical and basolateral surfaces
True or False: the arrangement of channels and transporters does not affect the function
False - the arrangement of the channels and transporters results in differences in function
Describe the basics of zymogen release
VIP and Secretin bind, through a pathway causing vesicles to fuse and release their contents
CCK and ACh bind, through a pathway causing vesicles to fuse and release their contents
but ALSO
cause the ER to release Ca++
(V- SNAREs bind to T-SNAREs cuasing fusion and release of contents)
Ca++ causes vesicles to fuse and release their contents
Ca++ binds synaptotagmin which interacts with SNAREs and pulls the vesicle to the membrane where they fuse and release their contents
The mechanism for zymogen release involves a set of processes called… that involve…
stimulus secretion coupling:
synaptic transmission, insulin release from pancreatic beta cells, zymogen release from pancreatic acinar cells
What are the “secretagogues” for zymogens
VIP and Secretin (PKA pathway)
CCK and ACh (PKC pathway)
How do the charges of the blood and the lumen of the acinar cells compare to eachother? What does this cause?
the lumen of acinar cells is negatively charged, so water and salt move into the lumen through aquaporins
How is Cl- moved into the lumen of the acinus?
Na,K ATPase uses an ATP to pump 3 Na+ out and 2 K+ in, creating a gradient that pulls Cl- into the acinar cells and makes the interior of the cell negatively charged
ACh and CCK causes a release of Ca++ that activates protein kinases, which move Cl- into the lumen and K+ out of the cell
Cl- being taken from the extracellular space and K+ moving out makes the extracellular space positively charged in relation to the acinar cell and lumen
Why does water move into the lumen of the acinus?
As Cl- moves into the lumen and creates a negative charge, water and Na+ follow (because of electrical and osmotic flux) and move into the lumen
How does salt form in the lumen of the acinar cell?
Na+ and Cl- that move into the lumen combine to make salts
What is the main function of pancreatic duct cells?
secrete a HCO3- rich isotonic fluid which flushes the digestive enzymes from the acinar cells along the ductal tree into the duodenum and neutralizes acid chyme entering the duodenum from the stomach to create the correct luminal environment for the digestion of food
Where and how is HCO3- formed?
in the lumen of the pancreatic duct cells
overall, Na+ and HCO3- combine with water to form a NaHCO3 secretion
- Na,K ATPase establishes an Na+ and K+ gradient
- the inwardly directed Na+ gradient moves HCO3- into the cell with it
- Cl- from the lumen is exchanged with HCO3- (that Cl- can be recycled by being put back into the lumen again)
- electro diffusive flux of Na+ and osmotic flux of water move them into the lumen, where they form the secretion
Overall, the exocrine pancreas secretes 3 things - what are they and where do they come from?
zymogen (protein) secretion by acinar cells
NaCl (isotonic) fluid secretion by acinar cells
NaHCO3 and fluid secretion by duct cells
What is diffusion?
net movement of particles from a region of high electrochemical potential to a region of low electrochemical potential
(solutes move from high conc. to low conc.)
True or False: during osmosis or diffusion, solutes ONLY move from the area of high concentration to low concentration
False - solutes move in both directions, but the net flux is from high to low
Diffusion flux (Jnet) is proportional to…
the concentration gradient - difference in particle concentration divided by the distance over which the concentration difference occurs (delta C / delta x)
can also be multiplied by the diffusion coefficient D (the diffusability of each particular solute)
What is Fick’s First Law?
Jnet = D (delta C / delta x)
When looking at a Jnet vs. delta C graph…
what is the equation of the graph?
what determines the slope?
Jnet = P(delta C)
where P is the slope/permeability/slope and delta C is the concentration gradient
Rate of diffusion of a solute across a membrane depends on two things:
permeability and concentration gradient
What is the partition coefficient?
ratio of a solutes concentration in oil vs. water
Why is H2O an outlier on the permeability vs. partition coefficient graph?
because it is influences by aquaporins (water channels)
Does molecular size or the partition coefficient play a larger role in permeability?
partition coefficient
Rate of diffusion across a LIPID membrane is proportional to…
how lipophilic it is
Do uncharged or ionized molecules generally have greater permeability? What does this mean about acids and bases?
uncharged have a greater permeability
HA (opposed to A- and H+) and BH+ (opposed to B and H+) are more permeable
What happens if you add H+ to one side of a semipermeable membrane?
that side decreases pH, and it drives the equilibrium toward the HA form instead of the H+/A- form
HA is more permeable so it diffuses over to the other side, shifting that equilibrium toward H+/A- instead of HA
ions are not as permeable so they become trapped on that side of the membrane (ion trapping)
How does ion trapping effect things in the body?
molecules like drugs are more diffusable in an unionized form
if two compartments have different pH, weak acids will accumulate in the basic compartment and weak bases in the acidic compartment
What is osmosis?
the passive, net flow of water across a semipermeable membrane in response to a gradient in the chemical activity of water
What is the equation for osmotic pressure? What do we care about physiologically?
van’t Hoff relationship
pi = RTC
where pi is osmotic pressure, R is the gas constant, T is temp, and C is concentration of osmotically active solutes
R and T stay the same, so change in osmotic concentration causes change in osmotic pressure
What is so important about osmotic pressure?
represents a very large force, responsible for most of the movement of water between different tissue and organ compartments
small difference in solute concentration can lead to a huge difference in osmotic pressure
How do you calculate osmotic concentration of a solution?
Add the mM of each solute once for each ion piece
ex: 10 mM KCl = 20 mOsM, and 3 mM CaCl2 = 9 mOsM
Describe what happens to cells that are hypo/hyperosmotic and hypo/hypertonic
hyperosmotic/hypertonic - cell has lots of water and low solute, solution has lots of solute compared to water, so water exits the cell and it shrinks
hypoosmotic/hypotonic - cell has low water and lots of solute, solution has lots of water compared to solute, so water enters the cell and it swells
What is the difference between tonicity and osmolarity?
tonicity - how solute concentration affects volume
osmolarity - the solute concentration in a cell
When is a solution isotonic?
when it does not alter cell volume
What is the universal strategy for water flux?
move a solute, and water will follow
The “osmotic influence” of a solute is largely independent of…
chemical identity (they mostly have the same effect on the activity of water)
