4.3. Concentration and dilution in the kidney. The function of the urinary bladder and the regulation of the urination Flashcards
I. Urine production
1. General summary of urine production?
- The kidney generates the osmotic gradient by creating hyperosmotic (↑[electrolytes]) interstitial fluid in the medulla
=> That drives water out of the renal tubule - Fluid in the renal tubule can finally equilibrate with the hyperosmotic medullary interstitium at the water-permeable medullary collecting duct, making the urine even more concentrated, before being excreted
I. Urine production
2. What are the 3 mechanism in urine generation?
- Countercurrent multiplication:
- to reabsorb water from the filtrate (concentration of urine) - Countercurrent exchange:
- to maintain osmotic gradient in the medulla - Urea recycling:
- to maintain osmotic gradient in the medulla
II. Countercurrent multiplication
1. What is the definition of Countercurrent multiplication?
The process of using energy to generate an osmotic gradient (by pumping solutes out of the renal tubule) that enables the kidneys to reabsorb water from the filtrate and produce concentrated urine
II. Countercurrent multiplication
2. How are the parts of kidney participating in Countercurrent multiplication?
- To understand this mechanism, let us look at the function of the loop of Henle:
1) Descending limb: water permeable, solute impermeable
2) Ascending limb: solute permeable, water impermeable
=> Vasa recta and loop of Henle work together to really concentrate the urine
(LOOK AT PICTURE WHILE READING THIS MECHANISM!)
II. Countercurrent multiplication
3. What is the 6 step process of countercurrent multiplication?
Countercurrent multiplication builds up a gradient of osmolarity in the interstitium through the single effect and the flow of tubular fluid.
1) Single effect: in TAL, NaCl is reabsorbed via Na+K+2Cl- cotransporter, but it is impermeable to water that water is not reabsorbed along with NaCl and the tubular fluid is diluted (200). The NaCl from TAL enters into interstitial fluid, increasing the osmolarity in interstitial fluid (400). In DL, it is permeable to water and small solutes that water flows into interstitial fluid until it equilibrates with the osmolarity of intersititial fluid (both 400). As a result, osmolarity of TAL decreases and the osmolarities of interstitial fluid and the descending limb increase.
2) Flow of tubular fluid: the new fluid enters DT which is 300 mOsm/L and at the same time, the high osmolarity fluid in DL (400) is pushed down towards the bend of the loop of Henle as an equal volume of fluid needs to be displaced also in TAL. (fluid shift).
These steps repeats until the full corticopapillary gradient is established. (1200 mOsm/L at inner medulla and 300 mOsm/L in the outer cortex)
- The renal fluid entering the descending limb is initially 300mOsm
- The same amount of Na+ and water were reabsorbed in the proximal tubule, so the filtrate remains isotonic with the blood plasma - The TAL actively transports solutes via the Na+/K+/2Cl—cotransporter into the interstitium
- Increases osmotic activity of interstitium (tubular fluid = hypoosmotic, since solutes move out) - Since there is an osmotic dragging force in the medullary interstitium, water will move out from the TDL and into the interstitium – where it equilibrates its osmolarity with that of the interstitium = single-effect
- As fluid flows (due to the constant filtration of the glomerulus), the high osmolarity tubular fluid coming from the TDL, flows into the TAL
- As solutes and water undergo the mentioned procedures, TAL will have fluid with increased osmolarity flowing into its pathway - The single-effect takes place again and again, pumping solutes from the TAL into the interstitium and equilibrating the TDL with the interstitium
- As solutes are reabsorbed every time in the TAL, the next segment (distal convoluted tubule and connecting duct) becomes hypoosmotic (less solutes in tubular lumen) - This whole process continues until the normal osmotic gradient levels are reached
- Renal fluid entering TDL is initially 300mOsm
- Filtrate gets increasingly concentrated – 1200mOsm at bottom of the loop
- As solutes leave the filtrate through TAL, the osmolarity falls to ≈ 200mOsm
II. Countercurrent multiplication
4. Why is the high osmotic activity necessary in the medulla?
- The hyperosmotic medullary interstitium ‘’sucks’’ out water from the collecting duct, making the tubular fluid more concentrated
II. Countercurrent multiplication
5. How does Volume reduction in the cortex contribute to making the urine more concentrated?
- The connecting and cortical collecting duct become water- permeable in the cortex (in the cortex we have a huge blood Flow, 90% of blood flows to the peritubular capillaries)
- With the water being washed away, the tubular fluid goes from being hypoosmotic to isosmotic (if water is removed = volume loss in tubular fluid)
- Smaller amount of volume will be concentrated
- More water removal will result in hyperosmotic tubular fluid = concentrated urine
III. Urea recycling
1. What is the role and summary of urea cycling?
Contributes to the concentration gradient development
- This events start at a state when water-reabsorption is simultaneously increased by ADH in the proximity, which established the concentration gradient in urea between the collecting duct and the medullary interstitium
III. Urea recycling
2. What is the 4-step process of urea cycling?
- ADH binds on V2-receptors (Gs-coupled) at basolateral side (AC -> cAMP↑ -> PKA -> Aq2)
- ADH increases (cortical / outer medullary collecting duct) water-permeability - Urea permeability is not increased, so its tubular fluid concentration increases
- In the inner medullary collecting duct, ADH increases tubular urea permeability
- PKA phosphorylates proteins that cause translocation of intracellular vesicles containing urea transporters A1 (UT-A1) and the fusion of these with the apical membrane - Urea now diffuses from its high tubular concentration into the interstitium, increasing the osmolarity
- Contributes to urine concentration at the loop of Henle
IV. Countercurrent exchange
1. What is Countercurrent exchange?
- A process occurring between the vasa recta and interstitium which differs from countercurrent multiplication in that it is passive and only maintains the gradient,
rather than creating it - An exchange of solutes and water between limbs of vasa recta flowing in opposite direction to each other
IV. Countercurrent exchange
2. What is the 5-step process of Countercurrent exchange in the kidney?
- A passive process occurring between vasa recta and interstitium which helps maintain the gradient.
- In DL, water diffuses out of blood and solutes diffuses into the blood.
- In TAL, solutes diffuses out of blood and water diffuses into blood.
- At the end of TAL, the blood leaving the vasa recta has an osmolarirty of 325 mOsm/L, which is slightly higher than the original.
- Some of the solute from the corticopapillary osmotic gradient was picked up and will be carried back to the systemic circulation.
V. Concentration in the kidney
1. Summary of concentration in the kidney
When water needs to be conserved, higher levels of ADH are released and the kidney produces hyperosmotic urine.
-> The driving force of concentration (and dilution) of urine is Na+-reabsorption in TAL and the concentration gradient (via Na+/K+/2Cl—cotransporter)
V. Concentration in the kidney
2. What is the 9-step process of concentration in kidney?
1) NaCl is reabsorbed from TAL (NaK2Cl cotransporter)
=> Tubular fluid becomes hypoosmotic and interstitium of medulla becomes hyperosmotic
2) Water moves out from the TDL
=> Tubular fluid becomes hyperosmotic, and volume decreases
3) NaCl is reabsorbed from distal convoluted tubule by NaCl cotransporter
=> Tubular fluid becomes more hyposomotic
4) NaCl is reabsorbed from connecting duct and cortical collecting tubule
=> ENaC, regulated by aldosterone
5) In response to ADH, water is reabsorbed in cortical regionofcollectinganet
=> Tubular fluid becomes isosmotic, and volume decreases further
6) Same in outer and inner medulla
=> Tubular fluid becomes hyperosmotic, and volume decreases further
7) In response to vasopressin, UT1 transporters increases in inner medullary collecting duct
=> Urea is reabsorbed
8) Urea recirculates into thin ascending limb
9) Na+ is reabsorbed from thin ascending limb, because intratubular
VI. Dilution (hypoosmotic urine production)
1. What are the characteristics of Hypoosmotic urine?
Hypoosmotic urine has an osmolarity lower than blood osmolarity, and it is produced when there are low circulating levels of ADH. (e.g., water drinking, central diabetes insipidus) or ADH is ineffective (nephrogenic diabetes insipidus).
VI. Dilution (hypoosmotic urine production)
2. How does dilution happen?
When water must be excreted (due to low body fluid osmolarity), ADH secretion decreases and this affects the mentioned water-reabsorption in the tubular system
- NaCl is always reabsorbed isosmotically in the PT, where ADH has no effect, so tubular fluid here is always isosmotic (300mOsm)
- Processes are all the same as usual in the descending limb (concentration), thick/thin ascending limbs + early DCT (dilution)
- In the late DCT and collecting ducts, the lack of ADH leads to Aq2-removal from the membrane, so water remains in the tubular fluid and no osmotic equilibrium occurs between the tubule and interstitium
=> The interstitial osmolarity becomes greater than the osmolarity of the tubular
- The interstitial osmolarity in the inner medulla is also lower in the diluting kidney (600mOsm VS 1200mOsm)
- This is due to lack of ADH-induced urea reabsorption from the distal collecting duct
- Urea usually accounts for half of the osmolarity of the inner medullary interstitium, but since urea cannot be reabsorbed, NaCl provides the osmotic activity of the interstitium
