Kidney tubular function Flashcards
What is the primary site of reabsorption in the nephron?
proximal convoluted tubule
What portion of the filtrate is reabsorbed in the PCT?
2/3 (120L out of 180L/day)
What part of the kidney is the site of water reabsorption?
loop of Henle
What is the name of the mechanism in the loop of Henle that aids water reabsorption?
counter current multiplier mechanism
Function of the DCT
fine tuning - regulates fluid volume and electrolyte concentration
What other processes does sodium transport facilitate?
reabsorption of nutrients, water and ions
What percentage of Na+ is reabsorbed overall by the kidney?
98%
What percentage of the kidney’s energy consumption is spent on Na+ reabsorption?
80%
What percentage of Na+ is reabsorbed in the PCT?
65%
What percentage of Na+ is reabsorbed in the ascending loop of Henle?
25%
What percentage of Na+ is reabsorbed in the DCT?
Up to 8% depending on body requirements
How does the PCT maximise its SA for reabsorption?
its long and convoluted. Has microvilli on epithelium (brush border)
What components of the nephron are in the cortex / medulla?
cortex - renal corpuscle, PCT, DCT
medulla - loop of Henle, collecting duct
Why does the PCT stain more darkly than the DCT with masson trichrome stain?
PCT has a higher density of organelles (more metabolically active)
What is the name of the capillaries that are closely associated with all parts of the nephron?
peritubular capillaries (vasa recta)
What is the direction of movement of substances during reabsorption?
movement from filtrate in tubular lumen, across epithelial cells of PCT, across interstitial space to peritubular capillaries / vasa recta
When may substances move from the peritubular capillaries to the PCT?
if substances (e.g. excess H+) are actively secreted from peritubular capillaries into the filtrate
What substances are filtered by the renal corpuscle?
water, glucose, amino acids, urea, creatinine, electrolytes (Na+, Cl-, Ca2+, PO4 3-, K+, HCO3-)
Out of all the filtered substances, which is the only one that is not reabsorbed?
creatinine (50% of urea is passively reabsorbed) - therefore level of creatinine should be constant
Why does the PCT have a much higher concentration of solutes than peritubular capillaries?
Solutes have been filtered out of glomerular capillaries into the filtrate, therefore the PCT is rich in solutes while the vasa recta (comes from efferent arteriole) is solute deficient
Passive diffusion definition
Net movement of molecules from high to low concentration until equilibrium is reached
What percentage of the filtrate can be reabsorbed by passive diffusion in PCT?
50% (90 out of 180L/day of filtrate)
What structures are required for the movement of water?
aquaporins
What structures are required for the passive diffusion of ions?
ion channels
Apical specialisation of PCT epithelial cells
microvilli (brush border)
How do glucose and amino acids move across the apical surface of PCT epithelium?
via sodium cotransporter (carrier protein) by facilitated diffusion (passive). Na+ moves down its concentration gradient while glucose and amino acids associate with the carrier protein.
Why is creatinine not reabsorbed?
no transport protein for creatinine is present
Which structure allows the reabsorption of 2/3 of filtrate in the PCT (so reabsorption doesn’t stop at 50%/equilibrium)?
Na+/K+ pump
Location of Na+/K+ pump in PCT
Basolateral membrane of epithelial cells lining PCT
How many ions are moved by the Na+/K+ pump?
3 Na+ moved from epithelial cell to interstitial space while 2 K+ ions move in opposite direction (using 1 ATP)
Function of Na+/K+ pump
actively transports Na+ (uses ATP) against/up its concentration gradient (created by pump) to facilitate 2/3 filtrate reabsorption / up to 100% nutrient reabsorption in PCT
Why does water follow Na+?
Na+ lowers water potential therefore water moves by osmosis
Why do glucose and amino acids follow Na+?
the Na/K pump creates a low [Na+] in the tubule wall (epithelium) which drives facilitated diffusion of Na+ into the wall via the Na+ cotransporter (indirectly relies on ATP). Creates a nutrient gradient as glucose and amino acid concentration in the tubule wall increases.
Why do negative ions (e.g. Cl-) follow Na+?
Na+ is positively charged which creates an electrical gradient
Which disease prevents 100% nutrient reabsorption?
diabetes
Why can glucose be detected in the urine of diabetic patients?
high blood glucose concentration overwhelms Na+ cotransporters so not all the glucose can be reabsorbed leading to some being excreted
How is an osmotic gradient created for 2/3 water reabsorption in PCT?
Na/K pump in basolateral surface creates a perpetual osmotic gradient
What percentage of nutrient reabsorption in the PCT is enabled by Na+ active transport?
100% (glucose and amino acids)
What percentage of urea is reabsorbed in the PCT?
50% by passive diffusion (unaffected by Na+ active reabsorption)
What percentage of creatinine is reabsorbed in the PCT?
0%
What volume of filtrate per day proceeds to the loop of Henle?
60L (out of 180L/day)
Function of the loop of Henle?
Water reabsorption (which concentrates urine)
What are the 3 distinct sections of the loop of Henle?
thin descending, thin ascending and thick ascending limb
Which portion of the loop of Henle contains aquaporins?
thin descending limb (permeable to water)
Which portion of the loop of Henle is impermeable to water?
thin and thick ascending limbs (don’t contain aquaporins so water cannot follow Na+)
Function of thick ascending limb of the loop of Henle
active sodium reabsorption from the filtrate into IF of the medulla
Which membrane proteins are found in the thick ascending limb?
Na+/K+ pump on the basolateral membrane and NKCC2 on apical membrane
How does sodium reabsorption occur in the thick ascending limb?
The Na+/K+ pump moves Na+ up its concentration gradient which drives Na+ out of the filtrate via NKCC2 cotransporter.
For every 1 Na+ transported, which other ions are co-transported by NKCC2 across the apical surface in the thick ascending limb?
K+, 2 Cl-
Why is the passive movement of Na+ across the apical surface in the PCT (by Na+ cotransporter) or thick ascending limb (NKCC2) referred to as secondary active transport?
process relies on / enhanced by ATP used by Na+/K+ pump
What is the difference in Na+ reabsorption in the PCT and thick ascending limb?
Na+ moves across apical surface via Na+ cotransporter (with glucose and amino acids) in PCT and via NKCC2 in thick ascending limb
What type of drug may target NKCC2?
diuretic drugs (e.g. furosemide)
Effect of furosemide
inhibits NKCC2 action so less Na+ is reabsorbed creating a lower solute concentration in the interstitial fluid of the medulla. Therefore, less water leaves the DCT/collecting duct so more is excreted.
What conditions are created in the medulla as Na+ is actively reabsorbed?
salty
What happens to the water in the filtrate as it enters the loop of Henle?
Water leaves the thin descending limb (contains aquaporin) by osmosis. Water is reabsorbed into vasa recta and carried away.
What happens to the concentration of the filtrate as it descends the thin ascending limb?
Filtrate concentration increases (300 to 1200 mosm/L) as water leaves and Na+ is trapped (no Na+ pumps)
What happens to the concentration of filtrate as it ascends the thick ascending limb?
Filtrate concentration decreases (1200 to 100 mosm/L) as Na+ pumped out and water cannot leave
What volume of the filtrate is reabsorbed in the loop of Henle / medulla?
45L (out of 180L/day which is 25%)
Why is the water reabsorption mechanism known as counter current multiplication?
Filtrate flows in opposite directions (at each level the descending limb as a higher filtrate concentration than the ascending limb to aid water reabsorption), and concentration increases deeper into the medulla
Where does water (and Na+) reabsorbed in the loop of Henle go?
returned to bloodstream via vasa recta
What is the advantage of the hairpin route the vasa recta takes?
slows blood flow which allows excess water and salt to be reabsorbed slowly to maintain osmotic gradient
Why is the concentration in the vasa recta higher when it leaves the medulla?
excess ions have been reabsorbed
What is the effect of sodium reabsorption from the thick ascending limb?
creates a high osmotic pressure in the medulla to drive water reabsorption from thin descending limb and DCT/collecting duct in presence of ADH
In which part of the nephron can fluid volume and electrolyte reabsorption be regulated by the body?
DCT (and collecting duct). The reabsorption in PCT and loop of Henle cannot be modified.
How is sodium and water reabsorption in the DCT regulated?
hormonally
Which 3 hormones regulate water and sodium reabsorption in the DCT?
Anti-diuretic hormone (ADH), Aldosterone, Atrial Natriuretic Hormone (ANH)
Effect of ADH
Increases water reabsorption
Effect of aldosterone
increases Na+ reabsorption
Effect of Atrial Natriuretic Hormone (ANH)
promotes Na+ secretion
What is the concentration of the filtrate as it leaves the loop of Henle?
approx 100 mosm/L (lower than (hypotonic) concentration of typical bodily fluids / cortex interstitium)
Why is it important that the tubule fluid entering the DCT is hypotonic with interstitium?
water can move down concentration gradient into the cortex interstitium for reabsorption in presence of hormone
Describe the urine produced in the absence of external hormonal regulation
large volume of hypotonic (dilute) urine is produced (no aquaporins are present so no water reabsorption)
What is another name for ADH?
Vasopressin
How does ADH increase water reabsorption?
epithelial cells of the DCT and collecting tubule insert aquaporins into apical membrane. Water leaves filtrate and is reabsorbed, restoring blood volume
How does ADH change urine composition?
smaller volume of concentrated urine is produced
Sequence that triggers ADH release
dehydration decreases blood volume which leads to a lower BP / serum osmolarity. This is detected by hypothalamus which sends APs to posterior pituitary glands to release ADH into circulation.
Which receptor detects ADH?
AVPR2 (vasopressin receptor 2)
Where is AVPR2 located?
Basolateral surface of DCT/collecting duct
How does ADH lead to insertion of aquaporins?
- ADH binds to AVPR2, activating signal transduction which enters nucleus
- activates transcription factor
- proteins required for aquaporins are synthesised and assembled
- aquaporins inserted into apical membrane
How does aldosterone increase Na+ reabsorption?
upregulates activity and insertion of Na+/K+ pumps and channels in DCT and collecting ducts
How can aldosterone also increase water reabsorption?
As Na+ leaves the filtrate and is reabsorbed into circulation, water follows
Effect of aldosterone on urine
Small volume of concentrated urine is produced
When may aldosterone be released?
reduced sodium, reduced blood volume (e.g. during exercise)
Which 2 hormones work together to increase water and salt reabsorption?
aldosterone and ADH
Why does aldosterone not require a cell-surface receptor to bind to?
Aldosterone is a steroid hormone therefore it can diffuse across the phospholipid bilayer and directly enter the nucleus
How does aldosterone cause increased Na+ reabsorption?
Aldosterone binds to and activates transcription factors in the nucleus which increases transcription and translation of Na+ channels (apical membrane) and Na+/K+ pump activity (basolateral membrane)
When is atrial natriuretic hormone released?
when an increased blood pressure causes stretched atria (must remove excess volume)
Action of atrial natriuretic hormone (ANH)
counteracts ADH and aldosterone by removing aquaporins, Na+ channels and Na+/K+ pumps from DCT and collecting duct. Salt and water retained in urine and excreted
Effect of atrial natriuretic hormone on urine
large volume dilute urine produced
