Renal Transport Mechanisms Flashcards
Na+ and H2O percentage reabsorption in:
- proximal convoluted tubule
- proximal straight tubule
- thick ascending limb
- distal convoluted tubule
- collecting duct
- bladder
PCT: 70% h20 , 60-70% Na PST: none Thick LOH: 25% Na, no H20 DCT: 5% Na, H2O variable Collecting Duct- 3% Na, H20 variable Bladder- 1% Na, H20 variable
PCT reabsorption for:
- glucose
- amino acid
- urea
- H2O, Na, Cl, K
What is main transporter?
What is special feature of PCT?
Glucose: 100%
Amino acids: 100%
Urea: 50%
others: 67%
Na/K ATPase in basolateral membrane
*Freely permeable to water
Transcellular vs paracellular diffusion and pathway
Transcellular- through the cell membrane
Through luminal membrane-> cytosol-> basolateral membrane of tubule cell-> interstitial fluid -> endothelium of peritubular capillaries
Paracellular- between cells
- between tubule cells
- tight junctions, but can be leaky and ions can get through (Ca, Mg, K)
- into PCT
Four ways to transport
1) ATPase
- only in basolateral membrane
- Na/K (Na out, K in)
2) Cotransporter
- ions move in same direction
3) Countertransporter
- ions move in opposite direction
4) Channel
- water channel, sodium channel, potassium channel
Sodium Reabsorption (4)
- most abundant cation in filtrate
- 80% of energy used for active transport for reabsorption
- active via transcellular route
- can occur sodium ion leak channels
Transport Na (3 steps)
1) Na+ diffuses across luminal membrane (apical) via Na/K ATPase pump
2) Na+ diffuse across basolateral membrane
3) Na H20 reabsorved from interstitial fluid into peritubular capillaries by ultrafiltration (passive)
Na+/H+ Exchange
- effects
- significance
-important for reabsorption for Na, Cl, and HCo3
- sodium reabsorption
- bicarbonate reclamation
Issues with Na+/H+ exchange (2)
5 step process of H+ ad HCO3
- H+ outside=acidic
- presence of carbonic anhydrase
1) Lumen: H+ + HCO3=> H2CO3
2) H2CO3 converted into CO2 + H2O via carbonic anhydrase
3) CO2 diffused into tubule cell cytosol (transcellular) + H2O => H2CO3 via carbonic anhydrase (splits into H and HCO3)
4) HCO3 into interstitial fluid then into blood
5) H+ recycles and helps process over again in lumen
Chloride Reabsorption
- mechanism
- PCT: H2O> Cl- reabsorbed more
- more Cl- in in tubule
- Drives Chloride movement passively=> paracellular pathway (down conc gradient)
- chloride reclamation
Paracellular Route (H2O) - examples
- depends on presence/absence of tight junction
- thin descending limb : not a lot of tight junction => paracellular water movement occur freely
- Thick ascending limb and Collecting duct : lots of tight junction => no paracellular water movement
Transcellular Route (H20)
Aquaporins 1- Proximal Tubule, endothelia
Aquaporin 2- collecting duct , under control of ADH
Water Reabsorption in:
- Proximal Tubule
- Loop of Henle
- Distal Tubule
- Late distal tubule and CD
state %, mechanism, and hormones
PT: 67% , passive, no hormones
LoH: 15%, DESCENDING LIMB ONLY, passive, no hormone
Distal Tubule: no water reabsorption, no hormone
-Late distal tubule and CD: 8-17, passive, AVP, ANP, BNP
Glucose Transport
- location
- percentage
Proximal Convoluted Tubule
2 Sodium coupled Glucose Transporter
1) SGLT2- 90% of reabsorption
- high capacity
- low affinity
- S1, S2
2) SGLT1- 10% of reabsorption
- low capacity
- high affinity
- S3
Diabetes effect with SGLT2 inhibition
with SGLT 2 inhibition
- reduced blood glucose levels=> less glucose resorption
Transport Maximum for Glucose
Tm= 375 mg/min (typically 200mg/dl)
Descending Loop of Henle reabsorption
- what can get filtered
H2O permeable (25%) NaCl IMPERMEABLE
increase solute= increase tubular fluid concentration => osmolarity increase( hyperosmolar)
-passive
Thin and thick ascending loop reabsorption
WATER IMPERMEABLE
- 75% of particles that enter are reabsorbed
Na K 2Cl cotransporter
ALL INTO loop of henle
1 NA
1 K
2 Cl
Countercurrent Multiplier (7 steps)
1) Fluid enter tubule
- Active transport Na, Cl, K into medullar interstitial fluid increases osmolarity
2) water moves out of descending limb by osmosis
3) iso-osmotic state in descending limb ; osmotic difference in descending and ascending limb
4) more fluid enter tubule, push fluid through bulk fow
- active transport of Na, Cl, K into medullary interstitial fluid increases osmolarity
5) water moves out of descending limb by osmosis
6) iso-osmotic state in descending; osmotic difference btw ascending and descending limbs
7) continuous process=> osmotic gradient
Distal tubule Reabsorption
- normally reabsorbs
- water
- at DCT what is % of originally components
Water IMPERMEABLE
5-8% of filtered sodium chloride
at DCT
about 10% of NaCl and 25% of water originally remains
Collecting Ducts
- hormones
- if no ADH, what happens
- Aldosterone for NA
- ADH for water
- PTH for Ca2+
- no ADH= water IMPERMEABLE
- no Na leave body in urine
Aldosterone goal
-location
- on thick segment of LOH, DCT, CD (cortical)
- retain NaCl and water
- urine volume reduced
- elevated K concentration
-increase Na+ reabsorption and K+ secretion
Salt Reabsorption in:
- Proximal Tubule
- Loop of Henle
- Distal Tubule
- Late distal tubule and CD
state %, mechanism, and hormones
PT: 67, Na/H antiporter, SGLT2, angiotensin II, NE, EPI, Dopamine
LOH: 25, N/k 1cl symporter, na/h antiporter, aldosterone, angiotensin II
Distal:5, NaCL symporter, aldosterone, angiotensin II
Late distal tubule and collecting duct: 3, Na channel, aldosterone, anp, bnp, angiotensin II
Inhibiting Transporters (3) mechanism of action effect
1) Thiazide Diuretics
Mode of Action: Inhibits the reabsorption of Na+ & Cl in the cortical diluting segment of DCT.
-increase Ca2+ reabsorption in the distal tubule. - Natriuresis and decrease blood volume and pressure.
2) Loop Diuretics (Furosemide)
Mechanism of Action: Inhibits Na-K-2Cl co-transporter in thick ascending limb of loop of Henle.
-decrease reabsorption of Na+ , K+ & Cl-
- Diuresis— increased urine output
3) K + Sparing Spironolactone
Mechanism of Action: Aldosterone-dependent potassium sparing
diuretics.
Inhibits Na+ /K+ exchange in distal tubule and collecting duct.
-Promotes K+ retention and Na+ and water loss. -Hypotensive effect
Water Deficit on Urine Concentration
ADH secretion->increase h2o permeability in tubule-> increase osmolarity in medullary
- gradient higher osmolarity in lower medulla
(100 at distal and collecting tubule) - small volume of concentrated urine
- reabsorbed h20 pick up by peritubular capillaried and conserved for body
Water Excess on urine concentration
no ADH secretion=> water IMPERMEABLE-> fluid entering distal tubule hypotonic
Net result= large volume of diluted urine, get rid of excess h20
- no h2o reabsorbed in distal portion of nephron
