Basic Epithelial Transport Mechanisms Flashcards
Reabsorption and secretion involves crossing which 2 barriers?
- tubule epithelium
- endothelial cells lining the peritubular capillaries
How are the following handled in the tubules?
Sodium
Phosphate
PAH
Potassium
Sodium - filtration + reabsorption
Phosphate - filtration + reabsorption
PAH - filtration + secretion
Potassium - reabsorption + secretion
How can the filtrate be modified?
- reabsorption
- secretion
- combinations of the two
What are the 2 possible routes of crossing the epithelial barrier?
- paracellular route
- transcellular route
Paracellular route
- single step
- substance goes around cells through the matrix of the tight junctions
Transcellular route
- two steps
- step 1: across apical membrane facing lumen
- step 2: across basolateral membrane
How do substances move across membranes and cells? (4)
- diffusion
- transporters
- channels
- active transport
What are the driving forces for movement by diffusion?
- chemical gradient
- electrical gradient (potential)
Diffusion applies to what type of movement?
- across capillary walls (endothelial barrier)
- paracellular route (some transcellular)
Characteristics of transporters
- binds substance more strongly (specificity)
- carrier proteins undergo more elaborate conformational change
Name 3 types of transporters
- uniporters
- symporters or antiporters
- primary active transport
Characteristics of uniporters
- facilitated diffusion
- follows electrochemical gradient
- transporter protein facilitates movement
- permit movement of a single solute
Characteristics of symporters and antiporters
- move 2 (or more) substances across membranes
- at least one of the solutes moves down its electrochemical gradient
- provides energy to move 1 or more solutes up its electrochemical barrier
What type of transporter is sodium glucose linked transporter (SGLT)?
symporter - moves 1 glucose and 1 or 2 sodium molecules into cells
What type of transporter is sodium hydrogen exchange transporter (NHE)?
antiporter - moves Na+ into cells and H+ out of cells
Characteristics of channels
- small pores allowing passage by diffusion with movement down electrochemical gradient
- usually specific for water or substance (examples: sodium channel, potassium channel, aquaporins)
Characteristics of secondary active transport
- ATP not hydrolyzed
- energy from transport of another solute, often sodium
- energetics of Na+ distribution always favors entrance into the cell
Characteristics of primary active transport
- moves 1 or more solutes up electrochemical gradient using energy from hydrolysis of ATP
- example: sodium pump (Na/K-ATPase)
How can proteins be moved across membranes?
- receptor-mediated endocytosis
- receptor-mediated transcytosis
C. Right hand column will increase
What is osmolality?
ability of solutes to lower water concentration
(ability: proteins > sugars > small ions)
Which one of the following provides the energy required for glucose reabsorption in the proximal tubules?
A. Solute drag associated with water flux
B. The Na-K ATPase pump in the basolateral membrane
C. The Na-glucose symporter in the apical cell membrane
D. The glucose uniporter in the basolateral cell membrane
B. The Na-K ATPase pump in the basolateral membrane
What is the main transport mechanism in the kidneys?
- reabsorption
- most reabsorption occurs in the proximal tubules
- most movement is essentialy iso-osmotic
What is mostly reabsorbed in the proximal tubules?
- sodium
- anions to maintain elecroneutrality (Cl and bicarbonate)
(PT cells highly permeable to water, water follows the solute)
How might overzealous administration of 0.9% (normal) saline impact PT reabsorption of filtrate in a well hydrated dog with normal kidneys?
A. Decrease reabsorption by increasing hydraulic pressure in peritubular capillaries
B. Increase reabsorption by increasing interstitial hydraulic pressure
C. Decrease reabsorption by diluting oncotic pressure in the peritubular capillaries
D. Increase reabsorption by increasing GFR
C. Decrease reabsorption by diluting oncotic pressure in the peritubular capillaries
(explanation: if you overload the capillaries with fluid, you will dilute oncotic pressure)
What is edema?
fluid in interstitial spaces
excess fluid administration that overwhelms ability to move through the system
What are the effects of renal interstitial edema?
- reduced RBF
- increased interstitial pressure
- reduced GFR
- uremia
- salt and water retention
Steps of transcellular epithelial transport with sodium
Step 1 - Na/K-ATPase pumps sodium out of cell
Step 2 - sodium from lumen moves down concentration gradient into cell to replace lost sodium
Step 3 - water follows sodium out of cell from basolateral membrane
Step 4 - sodium, anions, and water move into peritubular capillary
What type of transports can be involved with passive reabsorption? (3)
- simple diffusion
- paracellular transport
- non-ionic transport
Characteristics of passive reabsorption
- occurs by simple diffusion
- determined by concentration gradient and permability of tight junctions
- example: urea
Characteristics of paracellular transport
- need a chemical gradient across tight junctions
- tight junctions must be permeable to substance
- voltage gradients also play a role (early PT lumen slightly -, late PT lumen slightly +)
- facilitates paracellular transport of anions in early proximal tubules
Is glucose reabsorbed by paracellular transport?
No, tight junctions are impermeable to glucose
Characteristics of non-ionic diffusion
- passive process by which impermeant ions derived from dissociation of weak acids or bases can cross cell membranes
- only uncharged species can diffuse across cell membrane
Are transport systems quantitatively limited in their ability to move substances across membranes?
yes
What are the two limits to transport mechanisms?
- tubular maximum-limited system (Tm)
- gradient-limited system
Explain tubular maximum-limited transport
- in tubule, symporter transports glucose into cells with sodium
- if the plasma [glucose] > Tm, the transporter is saturated
- increased plasma [glucose] will not increase the rate of absorption
Explain gradient-limited transport
- epithelium has a finite passive permeability
- limit is reached when transcellular and paracellular transport are equal
- the leakier the tight junctions, the lower the gradient limit
