Case 3- Water and ion Reabsorbtion Flashcards
Starling forces in the proximal tubule
The efferent arteries and peritubular capillaries have a higher oncotic pressure as the proteins remain in the blood after ultrafiltration. The PCT and interstitium have a lower oncotic pressure as they don’t contain any proteins. Water moves down the oncotic gradient from the interstitium to the peritubular capillaries. Ions can be taken up via solvent drag. The fluid moves by osmosis
Glomerulus starling forces
The hydrostatic pressure is less then in the Bowmans capsule so fluid is pushed in
Peritubular capillaries starling forces
The interstitium has a high hydrostatic pressure driven by reabsorption of fluid and electrolytes via active transport. The peritubular capillaries have a low hydrostatic pressure due to the small amount of fluid in the efferent arteriole. Fluid is reabsorbed into the peritubular capillaries from the interstitium down the hydrostatic gradient
Water reabsorption in the proximal tubule
1) The microvilli in the apical surface move ions from the tubular lumen into the interstitium and then the capillaries down their concentration gradient.
2) The microvilli also increase the surface area.
3) Water follows the solutes through aqua porins, this is obligatory water reabsorbtion.
4) The epithelium is leaky so water absorption can be passive and transcelular.
5) It goes from the tubular lumen through the apical surface into the brush border cells and then through the basolateral surface and into the interstitium
Mechanisms in which Na+ is absorbed in the proximal tubule
1) Na/solute cotransport
2) Na/HCO3 transport
3) Passive Na/Cl absorption
Proximal tubule- Na/solute cotransport
Uses the the movement of Na down its concentration to move solutes like glucose against their concentration gradient. They move in cotransporters via secondary active transport. Glucose and sodium move from the tubular lumen to the brush border cells via an Na+/ glucose cotransporter. Glucose then diffuses into the interstitium via GLUT1 and Glut2 and passively diffuses into the peritubular capillary. The N+/K+ removes Na+ from the brush border cells into the interstitium and then passively absorbs into the capillary
Proximal tubule- paracellular transport of sodium
A leaky tight junction allows the paracellular transport of sodium from the tubular lumen to the interstitium. Moves due to difference in hydrostatic gradient, the water carries the Na+ on solvent drag. It then diffuses into the peritubular capillary. It’s negative in the early PT due to chloride. So, the NA+ gets attracted back into the tubular lumen by paracellular backflow
Early Proximal tubule- Na/HCO3 transport
In the tubular lumen HCO3 reacts with the H+ brought in by the Na/H+ exchanger on the apical membrane of the tubular lumen: HCO3 + H+ ↔ H2CO3 ↔CO2 + H2O. The reaction is catalysed by carbonic anhydrase. H2CO3 crosses into the renal proximal tubule cells inside the reverse reaction occurs and HCO3 and H+ are produced. The gain of Na from Na/H exchange results in the net movement of Na and HCO3 (bicarbonate) from the tubular lumen to the proximal tubular cell interior. HCO3 exits the cell via NA/HCO3 transporter on basolateral membrane into the peritubular capillary, Na is pumped out by Na/K-ATPase.
Proximal tubule- Na+/ HCO3 with Glutamine
The Na/HCO3 cotransporter is also used by Glutamine. It gets broken down into ammonium (NH4) and HCO3-. The ammonium is moved into the tubular lumen for excretion. And the Na+/HCO3- cotransporter moves sodium and bicarbonate into the peritubular capillary.
Late Proximal tubule- passive NaCl absorbtion
As water gets reabsorbed the concentration of chlorine in the proximal tubule increases. Cl moves from the lumen of the tubule down its electrochemical gradient passively and paracellularly back into the bloodstream. This results in net Cl reabsorption. As Cl carries a negative charge, movement of Cl from the lumen generates a positive charge in the lumen. Generation of a +ve transepithelial potential creates a transepithelial driving force for the passive paracellular reabsorption of Na+ as it moves down its concentration gradient away from the lumen.
Sodium reabsorption in the thin limb of the loop of Henle
Sodium movies passively into the interstitium through shallow tight junctions, down the concentration gradient. A type of paracellular transport through the squamous epithelia cells. Ascending limb of the loop of Henle
Sodium reabsorption in the thick limb of the loop of Henle
In the ascending limb of the loop of Henle. On the apical surface we have a Na/K/2Cl cotransporter which move potassium and sodium into the cuboid cells surrounding the tubular lumen. This is a form of secondary active transport, so when the sodium moves down its concentration gradient it provides the energy to move the chlorine and Potassium. The Na+/K+ ATPase then moves 3 sodium into the interstitium and pumps two Potassium ions out of it and into the cuboidal cells.
Na+ reabsorption in the early distal convoluted tubule
Sodium moves down its concentration gradient into the tubular cells using secondary active transport with a Na/Cl cotransporter. As sodium moves down its concentration gradient it provides the energy to move chlorine across. Sodium moves out of the tubular cells into the interstitium using an Na+/K+ ATPase pump. In the early DCT Na+ reabsorptions is load depended meaning that when there is more Na more can be reabsorbed.
Na+ reabsorption in the late DCT and collecting
Na moves down its concentration into the principal cells (surrounds tubular lumen in late DCT and collecting duct) through an ENaC (epithelial Na channel). This is controlled by Aldosterone which promotes the excretion of sodium. The Na+/K+ ATPase pump moves sodium out of the principal cells and into the interstitium
Permeability of loop of Henle
In the descending loop of Henle, it is water permeable and has a low permeability for ions, water passively move by osmosis through the aquaporins into the interstitium. In the ascending limb it is impermeable to water as there are no aquaporins but its permeable to ions
How water is reabsorbed in the loop of Henle
The filtrate in the nephron increases in osmolarity as you go down the loop of Henle. This is known as the cortico-papillary Hyperosmotic gradient. The further down the fluid goes in the loop of Henle the more water leaves into the interstitium. The same thing happens in the collecting duct. The hyperosmolar environment is due to the build up of NaCl and urea in the medulla due to selective transport of water and salt in different nephron segments.
The osmolarity of the loop of Henle compared to the interstitium
The descending loop of Henle is hyposmotic compared to the interstitium, it increases in osmolarity and becomes more hypersmotic as water leaves. The bottom of the loop of Henle is isosmotic with the interstitium. As it does up the ascending limb the fluid in the loop of Henle is more hyperosmotic then the interstitium so ions move down the concentration gradient into the interstitium. The filtrate starts to dilute in thick ascending limb until it is isosmotic with the interstitium. In order to make the interstitium saltier sodium is actively pumped out. The filtrate at the end of the PCT is Hyposmotic compared to the filtrate at the start and the interstitium.
How is the corticopapillary gradient establishes (small)
It is established through Counter current multiplication (bringing electrolytes into the interstitium) and urea recycling (bringing urea to the interstitium). It is maintained by the counter current exchanger mechanism of the Vasa Recta. Aims to create a difference of 200mOsm/L between the fluid that enters and the fluid that leaves.
Steps in maintaining the corticopapillary gradient (first half)
- Step 1- Assume the loop of Henle is filled with a 300mOsm/L concentration
- Step 2- The solutes in the ascending limb are pumped out, the osmolarity in the tubule fluid will decrease.
- Step 3- H2O will leave the descending limb to equilibrate the osmolarity, till the descending limb is isosmotic to the interstitium. The osmolarity of the interstitium does not change due to the removal of water in the Vasa recta.
Steps in maintaining the corticopapillary gradient (second half)
- Step 4- Additional fluid flows from the PCT into the loop of Henle, the hyperosmotic fluid previously produced in the descending limb will flow into the ascending limb.
- Step 5- additional ions are pumped into the interstitium from the ascending limb till a gradient of 200mOsm/L is established.
- Step 6- again the fluid in the descending limb come to equilibrium with the hyperosmotic interstitial medullary fluid. As the hyperosmotic tubular fluid is pushed into the ascending limb from the descending limb the more solutes are drained out.
- Step 7- these steps are repeated over and over producing a gradient of osmolarity down the tubule and increasing the osmolarity at the bottom to 1200 mOsm/L.
How does the corticocapillary gradient allow for dilute and concentrated urine
The filtrate is now very dilute at 375mOsm/L allowing for dilute urine but the interstitium is very concentrated so if the collecting duct becomes permeable the urine can become concentrated as water moves out.
Counter current Exchanger- Vasa Recta
Maintaince the cortical pupillary hyperosmotic gradient. The Vasa Recta loops around the loop of Henley. As the vasa recta goes down the ascending loop of Henle water is secreted, and solutes are re-absorbed down their concentration gradient. The osmolarity of the Vasa recta at the bottom of the loop of Henle is equal to the interstitium. As it goes up the descending limb water is reabsorbed, and solutes are secreted down their concentration gradient. The gradient is maintained and is not washed away by the blood supply as both water and solutes are secreted and absorbed at the same rate. Only a small amount of solutes are lost to the blood and this is dependent on blood flow.
Counter current exchanger- urea recycling in loop of Henle
There is more urea at the bottom of the loop of Henle then at the top. As the fluid goes down the descending limb of the loop of Henle urea moves down its concentration gradient into the loop of Henle and is reabsorbed. Increasing the concentration of the urea in the filtrate. The rest of the nephron is impermeable to urea so it cant leave.
