Function of Renal Tubules I and II Flashcards
In which of the following nephron segments do you find the epithelium with the highest electrical resistance?
a. Proximal tubule
b. Descending limb of loop of Henle
c. Ascending thick limb of loop of Henle
d. Distal convoluted tubule
e. Cortical collecting duct
E - cortical collecting duct
The collecting duct has the highest resistance (e.g., ‘tightest’) epithelium
An 84 year old woman developed recurrent “heartburn” that she self-medicated with an over-the- counter medication (cimetidine). One week later, her serum creatinine level of 2.7 mg/dl (increased from 1.8 mg/dl). Her physician is very concerned about rapid progression of her underlying renal disease, but is also suspicious that the serum creatinine elevation may have been caused by cimetidine. Why does the physician suspect cimetidine?
a. cimetidine is a kidney toxic agent and may cause acute renal failure
b. cimetidine blocks tubular secretion of creatinine by the thick ascending limb of the loop of Henle
c. cimetidine blocks tubular secretion of creatinine by the proximal tubule
d. cimetidine is excreted in the urine and is falsely measured as creatinine by automated chemistry
e. cimetidine blocks tubular secretion of creatinine by the thick ascending limb of the loop of Henle
c. cimetidine blocks tubular secretion of creatinine by the proximal tubule
This occurs through block of organic cation transporters
Which of the following statements is NOT true about the proximal tubule?
a. 90% of filtered bicarbonate is reclaimed
b. approximately 65-70% of total filtered sodium is reabsorbed
c. glucose reabsorption is near complete under all conditions
d. organic anion secretion can be blocked by probenecid
e. the apical membrane contains numerous microvilli
c. glucose reabsorption is near complete under all conditions
This is not true in situation where plasma glucose is very high and filtered glucose
exceeds the capacity (transport maximum) of the proximal tubule
Carbonic anhydrase inhibitors will evoke which of the following changes in proximal tubular solute reabsorption?
a. Diminished Na+ reabsorption by the Na-proton exchanger
b. Elevation in Na-bicarbonate efflux from the cell on the interstitial side
c. Diminished reclaimation of bicarbonate
d. Increased generation of cytosolic carbonic acid
e. Decreased generation of tubular fluid carbonic acid
c. Diminished reclaimation of bicarbonate
This is the main effect of carbonic anhydrase inhibitors
How thick are the cells which line the tubular segments?
monolayers with tight junctions
The apical segment of the tubular endothelium faces: lumen or interstitium
lumen
the basolateral segment of the tubular endothelial cell faces the: lumen or interstitium?
interstitium
Tight junctions are composed of what two protein types?
zona occludens and zonula adherens
The movement of fluid and solutes sequentially across the apical and basolateral cell membranes (or vice versa) mediated by transporters, channels and pumps is called…
cellular transport
movement of fluid and solutes through the narrow passageway between cells is called …
paracellular transport
When and how does paracellular occur?
when tight junctions are “Leaky”
Leaky epithelium has: low or high resistance
low
tight epithelium has: low or high resistance
high
The proximal tubule is an example of a : low or high resistance segment
low resistance due to leakiness
The collecting duct is representative of: low or high resistance
high resistance due to tight junctions
Which of the following are reabsorbed by up to 60% in the proximal tubule?
water sodium glucose/aa bicarbonate peptides
water and sodium
Which of the following are reabsorbed by up to 100% in the proximal tubule?
water sodium glucose/aa bicarbonate peptides
glucose/aa
Which of the following are reclaimed by up to 90% in the proximal tubule?
water sodium glucose/aa bicarbonate peptides
bicarbonate
Which of the following are endocytosed and degraded in the proximal tubule?
water sodium glucose/aa bicarbonate peptides
peptides (i.e. insulin etc)
Reabsorption of what ion in the proximal tubule is the driving force for solute transport?
sodium
Is the proximal tubule an example of iso osmotic reabsorption? what does this mean?
yes, the fluid leaving the tubule has an osmolality similar to plasma
How is H+ trapped in the lumen of the proximal tubule?
via metabolism of glutamine into ammonia
HOw many parts does the PT epithelium have?
3 - s1, S2, S3
What is the S1 segment of the PT epithelium?
The S1 segment is highly convoluted and is the earliest part of the PT.
What is the S2 segment of the PT epithelium?
A more distal portion of the convoluted part of the PT is called the S2 segment
What is the S3 segment of the PT epithelium?
the last part of the PT before its junction with the descending limb of the loop of Henle is called the S3 segment (a.k.a. proximal straight tubule or pars recta).
What part of the nephron is composed of microvilli/brush border on the apical side?
the PT - increases surface area for reabsorption
What transport mechanisms does the PT use?
endocytosis, cellular and paracellular
What drives paracellular movement of water and solutes in the PT?
occurs by diffusion and convection driven by the high oncotic pressure and low hydrostatic pressure within the peritubular capillaries.
How does sodium removal from the cell by the ATPase favor water reabsorption?
The removal of Na+ and other solutes from the tubular fluid creates small local osmotic gradients favoring water reabsorption through both the cellular pathway (through water channels) and the paracellular route.
Define glomerulotubular balance
Physiological adjustments in GFR mediated by changing efferent arteriolar tone cause proportional changes in tubular fluid reabsorption
For example, vasoconstriction of the efferent arteriole by angiotensin II will increase glomerular capillary hydrostatic pressure but lower pressure in the peritubular capillaries. At the same time, increased GFR and increased filtration fraction cause a rise in oncotic pressure near the end of the glomerular capillary. What is this an example of?
glomerulotubular balance
What effect does lowering hydrostatic pressure and increasing oncotic pressure by efferent arteriole vasoconstriction have on the driving force for liquid absorption in the peritubular capillaries?
increases it
What drives H+, aa, phosphate and glucose transport in the PT?
sodium coupling
What direction does the Na/H transporter move solutes in the PT?
H moves into lumen, Na into cell
What direction do Na/solute cotransporters OTHER than the Na/H antiporter move solute in the PT?
both Na and solute move into the cell
Other than the Na/K ATPase, how can sodium enter the interstitium in the PT?
Bicarb/Na symporter and paracellularly
How is Cl reabsorbed in the PT?
cellular (Cl/formate exchange) and paracellular
How is Cl cellular transport achieved in the PT?
from lumen to cell: Cl/formate exchanger
cell to interstitium: Cl/K symporter
How are formate ions exchanged for Cl in the PT?
Formate/formic acid recycling:
formate ions inside the cell form by equilibration of formic acid, then excreted into the lumen in exchange for Cl. In the lumen, formate ion equilibrates to formic acid, which can diffuse through the membrane down it’s concentration gradient
Which form of formic acid can diffuse freely from lumen to cell: formic acid or formate ion?
formic acid
How does water reabsorption occur in the PT?
cellular (AQP 1) and paracellular
Where are aquaporins located in the PT?
apically and basolaterally
What provides the driving force for water reabsorption in the PT?
osmotic gradients created by sodium reabsorption move water into the higher osmolality intercellular space
What drives the paracellular reabsorption of water in the PT?
oncotic pressure is high in the peritubular capillaries
What enzyme is important for the bicarbonate reclamation of the PT?
carbonic anhydrase in the microvilli and cytoplasm
Where is bicarb titrated in the nephron? what transporter is important for this?
lumen, forms carbonic acid by addition of proton (provided by Na/H antiporter)
Where does carbonic acid dissociate into water and CO2 in the PT?
in the microvilli, by action of CA
In what form can bicarbonate diffuse passively across the membrane in the PT?
as water and CO2
Once diffused into the cell as water and CO2, what happens to bicarb?
it is turned into carbonic acid by CA again, then immediately dissociates into bicarbonate
How does bicarb exit the PT cell on the basolateral side?
via the Na/bicarb co transporter
What is the stoichiometry for movement of Bicarb and sodium on the basolateral side of the PT cell?
3 to 1 bicarb to sodium
If filtration of bicarb exceeds the renal bicarbonate threshold, what happens in the PT?
bicarb will be secreted because the bicarb/Na co transporter will be saturated
What effect do CA inhibitors have on bicarb reclamation?
they block it, leading to metabolic acidosis
In the PT, what is true of glucose plasma and tubular fluid concentrations?
they are equal because glucose is freely filtered
What mediates glucose uptake in the PT cells?
Na/glucose co transporters (SGLT2)
What mediates glucose transport into the interstitium at the PT?
GLUT transporter