Renal Tubular Function 1 L05 Flashcards
What percentage of the proximal tubule is convoluted?
60% convoluted *convoluted becomes straight for the other 40%
How is the surface area of the proximal tubule increased?
presence of microvilli brush border on apical membrane.
What is the difference between primary and secondary active transport?
primary - relies on ATP
secondary - relies on concentration gradient of another ion e.g. Na+
define transcellular and paracellular.
transcellular - across cells
paracellular - between cells
Give examples of secondary active transporters
ion channels, co-transporters, exchangers
give examples of primary active transporters
protein pumps
In which direction is the Na+ gradient in the PCT and what is this important for?
high concentration in filtrate»_space; low concentration in epithelial cells *strong electrochemical gradient
- secondary active transport of glucose, AA, etc.
- creates an osmotic gradient for the movement of water into cells (water follows movement of Na+)
How is a low concentration of Na+ maintained inside epithelial cells in PCT?
Na+/K+ ATPase on BASOLATERAL membrane moves Na+ out of cell and into the interstitial space
What percentage of water is reabsorbed from PCT?
70%
Through which routes is water reabsorbed from the PCT?
transcellular and paracellular routes
describe the transcellular route of water absorption in PT
water moves by osmosis through AQP1 water channels present on both apical and basolateral membrane of epithelial cell
What is solvent drag?
when the paracellular absorption of water (across tight junctions) by osmosis facilitates the absorption of other solutes e.g. K+, Mg2+, Ca2+. These solutes are carried across the membrane with the movement of water.
Is Inulin absorbed from the PT? How is its concentration at the end of the tubule compared to at the start?
- not absorbed (remember L03)
- concentration higher at the end of the tubule *due to LESS WATER
Is urea absorbed from the PT? How is its concentration at the end of the tubule compared to at the start?
- is absorbed weakly *at a slower rate than water
- concentration at the ends of tubule is HIGHER *due to LESS WATER
How quickly is Cl- reabsorbed from the PT in comparison to water? Is the concentration of Cl- higher or lower at the end of the tubule?
- absorbed weakly/at a slower rate than water
- therefore concentration is HIGHER at the end of the tubule *due to LESS WATER
How quickly is Na+ reabsorbed from the PT in comparison to water? Is the concentration of Na+ higher or lower at the end of the tubule?
- absorbed at the same rate as water *remember Na+ movement aids water movement
- concentration of Na+ is the same at the start and end of PT
How quickly is K+ reabsorbed from the PT in comparison to water? Is the concentration of K+ higher or lower at the end of the tubule?
- absorbed at the same rate as water
- concentration of K+ is the same at the start and end of PT
How quickly is HCO3- reabsorbed from the PT in comparison to water? Is the concentration of HCO3- higher or lower at the end of the tubule?
- absorbed at a faster rate than water
- concentration of HCO3- is LOWER at the end of PT *due to MORE WATER than ion
How quickly are amino acids reabsorbed from the PT in comparison to water? Is the concentration of amino acids higher or lower at the end of the tubule?
- absorbed more strongly than water
- concentration of amino acids much LOWER at end of PT
How quickly is glucose reabsorbed from the PT in comparison to water? Is the concentration of glucose higher or lower at the end of the tubule?
- absorbed more strongly than water
- concentration of amino acids much LOWER at end of PT
By what route is glucose reabsorbed from PT?
transcellularly
Describe how glucose is reabsorbed from PT.
- secondary active transport across apical membrane
- facilitated diffusion across basolateral membrane
early PT (90%):
- apical membrane: SGLT2 cotransporter transports glucose and Na+ in 1:1 ratio into cell
- basolateral membrane: GLUT2 channel transports glucose into cortical interstitial space
late PT (10%):
- concentration of glucose in filtrate diminishing, so more energy required to actively transport it into cell against electro-chemical gradient
- apical membrane: SGLT1 cotransporter transports glucose and Na+ in 1:2 ratio into cell
- basolateral membrane: GLUT1 channel transports glucose into cortical interstitial space
what is tubular maximum (Tm) transport and its value for glucose?
The maximum rate of reabsorption (for glucose) . After this limit is reached, rate of glucose excretion begins to rise as not all of the glucose can be reabsorbed > glucosuria. This occurs when plasma concentration/filtrate concentration of glucose is around 12mM.
2.1mmol/min or 380mg/min.
One of the symptoms of diabetes mellitus in glucosuria. Why does this occur?
Occurs as the glucose concentration in the filtrate exceeds Tm.
What drugs can be given for decreasing plasma glucose in diabetes mellitus and how do they work?
canagliflozin, dapagliflozin
SGLT2 inhibitors > inhibit reabsorption of glucose > increased glucosuria > decreased blood-glucose concentration
*side effects include UTIs
What is the normal plasma amino acid concentration?
2.5-3.5mM
How are amino acids reabsorbed from the PT?
- variety of cotransporters transporting different families of AA (e.g. different charges)
- similar to glucose transport - secondary AT
- use Na+ gradient to drive transport
- transport is Tm limited
Describe how HCO3- is reabsorbed from filtrate into interstitial space.
apical membrane:
- HCO3- reacts with excess H+ that has been transported back into the filtrate
- H+ moves out of cell through Na+/H+ exchanger (1:1)
- HCO3- + H+ –> H20 + CO2 *mediated by CARBONIC ANYHDRASE
- H20 and CO2 can readily diffuse across membrane into epithelial cell
- through CA (same reaction) –> HCO3- and H+
- H+ recycled through exchanger
basolateral membrane:
- HCO3- moves into interstital space through Na+/3HCO3- cotransporter
- HCO3- moves DOWN electro-chemical gradient while Na+ moves AGAINST electro-chemical gradient.
- few other transporters: Na+/K+ pump and K+ channels to mediate Na+ levels inside cell
How does acetazolamide affect HCO3- and water absorption?
inhibits CA
> HCO3- (and Na+) stay in filtrate (cannot be converted to CO2 and H20 - cannot cross membrane)
> decrease water potential of filtrate
> less water reabsorbed
Why is acetazolamide only classed as a weak diuretic?
although it decreases water reabsorption in PT, the body compensates for this in DT.
What is the drug acetazolamide used for?
mountain sickness, prophylaxis (preventing disease), glaucoma
How might acetazolamide affect pH? How might this help with mountain sickness?
decreases blood pH - metabolic acidosis
increases urine pH - alkaline urine
mountain sickness due to hypoxia at high altitudes > increase in respiratory rate > respiratory alkalosis (CO2 conc drops) > therefore provides metabolic acidosis > normal blood pH
Describe transcellular and paracellular movement of Cl- in the PT.
transcellular:
apical membrane:
- active transport of Cl- through antiporter for other anions (e.g. HCO3-, HCOO-)
basolateral membrane:
- Cl- channels - moves down electrochemical gradient
- at start of PT, Cl- absorbed weakly/slower rate than water
- therefore Cl- concentration increases in filtrate along tubule
- eventually becomes high enough to drive paracellular PASSIVE Cl- movement into the interstitial space.
Very little albumin enters the filtrate. How is albumin in the filtrate reabsorbed?
binds to tubule membrane > endocytosed > catabolised > AA > reabsorbed into the body
Describe the secretion pathway for PAH- in the PT.
basolateral membrane:
- organic ion transporter (OAT) exchanges PAH- with other anions such as alpha-ketoglutarate
- PAH- actively moved into cell from interstitial space
apical membrane:
- multidrug resistance-associated protein (MRP) exchanges PAH- with other anions such as Cl- or OH-
- PAH- actively secreted into filtrate.
*body uses secretion pathway to remove many different anions from the blood
