Renal Transport Mechanisms Flashcards
What is primarily resorbed in the PCT
Water, Na, K, Cl, HCO3, Ca, Pi
What should be completely resorbed in the PCT
Glucose and AA
What is TF:P?
The ultrafiltrate concentration ratios for various solutes as a function of proximal tube length
TF:P ratios greater than 1 are? Less than 1?
Secreted; reabsorbed
What fraction of filtered water is reabsorbed by the proximal tubule
2/3
Why doesn’t the Na TF:P ratio change
Na is being reabsorbed at the same rate as water
Why do we see Urea and Cl increase in TF:P diagrams
They are being reasborbed as quickly as water is
Is PAH being reabsorbed?
No, it is secreted into the tubule
What are the Na symporters in the early proximal tubule
- glucose
- amino acids
- Pi
- HCO3
What are the antiporters for Na in the early proximal tubule
- H
- organic solutes
What drives reabsorption
Na-K ATPase
What causes water to cross from the tubule to the capillary
There is an osmolality gradient that pulls water into the capillaries
What causes Cl to be reabsorbed
- Water flow concentrates Cl
- Causes increase in tubular [Cl]
- Generates negative transepithelial potential difference
- Drives transepithetlial paracellular reabsorption of Na and Cl
What is the driving force for paracellular reabsorption
Concentration gradient between lumen and interstitium
What does paracellular Cl reabsorption depend on
Passive process but depends on Na and water reabsorption
How is the late proximal tubule kept neutral when moving charged substances
They exchange things that are charged similarly
What does Na exchange with in the lumen to come into cells
Na comes in; H goes out
What is Cl exchanged for in the late proximal tubule
Cl in; base out
What bases are used in the late proximal tubule to move Cl
Formate, oxalate, bicarbonate
What in the late proximal tubule moves Na into the interstitium from cells
NaK ATPase pump
What moves Cl in the late proximal tubule from the cells to the interstitium
Cl crosses basolateral membrane via Cl channels
What pushes water from the interstitium into capillaries
π_c since proteins never left the capillaries and P_i pushes it back in
What moves glucose from the lumen to the cell
SGLT
Sodium glucose transporter (brings gluc and Na in)
What is glucose into the cell dependent on
NaK ATPase b/c SGLT relies on there being a decent gradient set up
If the _______________ exceeds the saturation (of GLUT) then you will get _________________
Filtered load; glucosuria
Does the filtered load affect the transporter’s saturation
No
Where is secretion most active in the nephron
Proximal tubule
What all is secreted in the proximal tubule
- organic anions
- organic cations
- PAH
- creatinine
- weak acids and bases
On the basolateral membrane organic anions are exchanged for what
OA go in; α-ketoglutarate goes out
What moves organic anions from the capillaries to the cell
OAT1-3
What moves α-ketoglutarate into the cells from the capillaries
NaDC3
Na goes in; α-ketoglutarate goes out
What moves organic anions into the tubules
- MRP2/4
- BCRP (ATP dependent)
- OAT4 (in exchange for α-ketoglutarate)
What moves organic cations from the caps to the cells
OCT2
What moves organic cations out of the cells and into the tubules
- MDR1 (ATP dependent)
- MATE (H+ in and OC out)
PAH is moved into the urine where
Mostly secreted in tubules but some is filtered
What is the issue with PAH secretion
It can be saturated giving inaccurate measurements of RPF
What is creatinine
Organic cation
How is creatinine secreted into the tubules
Organic cation and anion transporters
Increased luminal pH causes what to be preferential reabsorbed? Secreted?
Reabs of bases
Excretion of acids
What would you do to increase secretion of aspirin
Increase luminal pH so acids (salicylic acid) is excreted
Low luminal pH causes what to be reabsorbed preferentially? Excreted?
Favors reabsorption of acids
Favors excretion of bases
What causes increased intracellular K
- insulin
- aldosterone
- β-adrenergic stim
- alkalosis
What causes decreased intracellular K
- diabetes mellitus
- aldosterone deficiency (addisons)
- β-adrenergic blockade
- acidosis
- cell-lysis
- strenuous exercise
- increased extracellular fluid osmolality
What does low K do to skeletal muscle
Hyperpolarizes it, makes it more difficult to fire
What does high K cause in skeletal muscle
Hypopolarizes it; causes it to be easier to fire
What happens in cardiomyocytes with high K
- High T waves
- eventually v-fib
- “too much repolarization” which is why we see high T
What happens in cardiomyoctes with low K
- low T wave
- high U wave
- “too little repolarization” which is why we see the low T wave
Where is K secreted or reabsorbed
Late DT (distal tubule) and cortical CD (collecting duct)
What types of cells secrete K
Prinicipal cells and β-intercalated cells
What stimulates secretion of K
- Increased ECF [K]
- Aldosterone
- Increased tubular flow rate
What drives K secretion in principal cells
Na
What drives K secretion in β intercalated cells
H and HCO3
What moves K out of the principal cells
BK and ROMK
What is reabsorbed by principal cells
Na and H2O
What is secreted by principal cells
K
What is reabsorbed by α intercalated cells
K and HCO3
What is secreted by α intercalated cells
H
What is reabsorbed by β intercalated cells
H and Cl
What is secreted by β intercalated cells
K and HCO3
What is normal serum K
4.2 mEq/L
Increased tubular flow rate causes increased secretion of what
K
What does increased aldosterone do for K secretion
Increased aldosterone increases K secretion
What causes hypokalemia with acute alkalosis
Increased activity of NaK ATPase —> increased [K]i —> passive diffusion of K into lumen —> increased K channels —> increased K secretion
This causes hypokalemia
What does acute alkalosis do for K
Causes hypokalemia
What does acute acidosis do for K
Causes hyperkalemia
How does acute acidosis cause hyperkalemia
Decreased activity of NaK ATPase —> decreased [K]i —> decreased passive diffusion of K into lumen —> decreased K channels —> decreased K secretion —> hyperkalemia
How does chronic acidosis differ from acute
Chronic acidosis stimulates K+ secretion
How does chronic acidosis stimulate K secretion
Chronic acidosis decreases reabs of water and solutes which inhibits the NaK ATPase
Increase tubular flow to DT and CD which increase K secretion
RAAS is stimulated which causes K secretion
During acidosis what favors K secretion? What opposes it?
Increased distal flow; decreased [K]i
What part of volume expansino favors K secretion? Opposes it?
Increased distal flow; decreased aldosterone
What part of high water intake favors K secretion? What opposes it?
Increased aldosterone; decreased distal flow
What competes for binding sites on plasma albumin
H and Ca
What does hypoalbuminemia cause
Increased plasma Ca
What does hyperalbuminemia cause
Decreased plasma Ca
What does hyperalbuminemia cause
Decreases plasma Ca
In acidosis there is more/less free calcium in circulation
More
In alkalosis there is more/less calcium in circulation
Less
It is bound to plasma proteins
What does alkalosis predispose you to
Hypocalcemic tetany
What can induce symptoms that look like hypocalcemia
Acute alkalosis
Why can’t 100% of plasma calcium be filtered
The remainder is bound to proteins in the plasma
A decrease in calcium causes what to change
- increased intestinal Ca absorption through vitamin D
- increased PTH which increases renal Ca reabsorption
- increased Ca release from the bones
Where is the majority of calcium reabsorbed
Proximal tubule
What drives calcium reabsorption at the proximal tubule
Passive transport following water and Na
How is calcium absorbed in the thick ascending limb
Paracellularly due to lumen positive voltage pushing Ca away
What is the major site of regulation for Ca reabsorption
Distal tubule
How is Ca reabsorbed in the distal tubule
Active transport through TRPV5 which is regulated by Vit D3
What increases Ca reabsorption at the proximal tubule
Volume contraction
What is Ca reabsorption at the thick ascending loop related to
Na
As Ca abs goes up so does Na and vice versa
What stimulates Ca reabsorption at the thick ascending loop
ADH
Loop diuretics inhibit Na reabsorption in TAL. What effect does this have on Ca
Reduces magnitude of lumen transepithelial voltage thuse reduces Ca uptake and increases excretion
Loop diuretics can be used to treat what Ca issue
Hyercalcemia
How does Ca in the distal tubule cells get from the cell to the interstitium?
NCE
Sodium calcium exchanger
What is the diuretic that inhibits Na reabsorption in the DT? How does this affect Ca
Thiazide diuretics
Stimulates reabsorption of Ca which reduces excretion and can be used to treat Ca containing stones
What stimulates reabsorption of Ca in the distal tubule
- PTH
- Vit D
- Calcitriol
- Thiazide diuretics
Acidemia increases Ca excretion in the distal tubule by what means
Inhibits TRPV5
Alkalemia stimulates TRPV5
Where is most Pi reabsorbed
Proximal tubule
What does FGF 23 do?
Fibroblast growth factor 23 is released by bone to increase phosphate excretion
What causes FGF23 to be released
Secreted by bones in response to PTH, calcitriol, and hyperphosphatemia
What transporter reabsorbs Pi from the lumen
NaPi-IIa/c
They both pull sodium across with it
What causes Pi to cross the basolateral membrane
An unknown transporter
PTH inhibits what transporters
NaPi and NaH antiporter in apical membrane of proximal tubule
Vitamin D3 does what to Pi
Increases serum Pi by increasing intestinal absorption
What does insulin do to Pi
Lowers serum levels by shifting Pi into cells
Chronic acidosis and alkalosis do what to Pi
CAc- increases Pi excretion
CAl - decreases Pi excretion
Where is the majority of Mg reabsorbed
thick ascending loop
What 2 ions in the TAL depend on the lumen-positive voltage
Mg Ca
How is Mg reabsorbed in the proximal tubule
Paracellular and follows Na and water
What does TAL reuptake of Mg depend on
Uptake of NaK via NKCC2
What is the site of fine tuning for Mg
DCT
What is the primary driver of Mg in the DCT
Electrical potential since [Mg]i ~ [Mg]e
How does Mg cross the border in the DCT
TRPM6
How does Mg get to the interstitium
Unknown mechanism
What is the main regulator for Mg reabsorption for us
Mg depletion since most Americans don’t meet dietary requirements
What increases Mg reabsorption
- Mg depletion
- Ca depletion
- Elevated PTH
- Decreased ECV
- Alkalosis
What is the main factor leading to decreased Mg reabsorption
Diuretics
When is TF:P less than 1? Greater?
Reabsorbed more quickly than water; reabsorbed more slowly than water
What channel do prostaglandins act on? What is the end effect of this
K channels in the TAL
Increased intracellular Cl, which hinders NKCC channels, and thus reduces NaCl reasborption
What does FGF23 do
Increase Pi excretion
