MONITOREO Y VERIFICACIÓN DE PROCESOS

Loop of Henle of juxtamedullary nephrons acts as a counter current multiplier. It maintains a conc. gradient btwn the two limbs by expenditure of energy (_A5).

The countercurrent flow amplifies:

the relatively small gradient at all points btwn the limbs (local gradient ≅ 200 mOsm/kgH2O) to a relatively large gradient along the loop (≅ 1000 mOsm/kgH2O).

The multiplied gradient is steeper when:

The loop is longer &

the one-step gradient is higher

Also, Multilplied gradient = 1 / (flow rate in the loop)²

(i.e it is inversely proportional to the square of flow rate in the loop) Countercurrent multiplier

 The hyperosmolarity of the medullary interstitial fluid is due to active reabsorption of Na+, Cl- & from ALLH into the medullary interstitium.

 The accumulated salt in the interstitium acts as an osmotic force which can be used to “draw”

& conserve water from the (DLLH).

 Due to conc. gradient, Na+ & Cl- ions diffuse from the interstitium into the DLLH & reach the ALLH again via hairpin bend.

 Thus Na & Cl ions are repeatedly recirculated btwn the DLLH & ALLH thru medullary interstitial fluid, leaving only a small portion to be excreted in urine (salt is saved to be used by the body).

 Besides, there is regular addition of more & more new Na+ & Cl- ions into the DLLH by constant filtration.

 So, continuous addition of NaCl (in DLLH) & reabsorption (in ALLH) increases or multiplies the osmolarity of medullary interstitial fluid & hence medullary gradient.

 Absorption of Na from the CD & recirculation of Urea btwn CD & ALLH are also responsible for the hyperosmolarity of medullary interstitial fluid.

Reabsorption of Water

Bowman’s capsule: The GFR is isotonic to plasma as it contains all the substances of plasma except proteins. Osmolarity of filtrate at Bowman’s capsule (300mOsm/L)

In the PCT: 65% of GFR is reabsorbed.

There is active reabsorption of Na+ & Cl–, followed by obligatory reabsorption of water.

Reabsorption of NaCl slightly dilutes the urine in the tubule, but H2O immediately follows this small osmotic gradient because the PCT is “leaky”.

So, the urine in PCT remains (virtually) isotonic.

Reabsorption of water in PCT can occur by:

paracellular route: thru leaky tight junctions or

transcellular route: thru water channels (aquaporin type 1 = AQP1) in the two cell membranes.

Oncotic pressure in the peritubular capillaries provides an additional driving force for water reabsorption.

The more water filtered at the glomerulus, the higher is the oncotic pressure.

Thus, the reabsorption of water at the PT is adjusted in accordance with the GFR (upto a certain extent) (glomerulotubular balance).

In the thick DLLH: It has aquaporins (AQP1) that make it permeable to water,

So water is reabsorbed into the hypertonic interstitium by osmosis & an osmotic balance is maintained btwn the urine & the interstitium.

The content of the interstitium becomes increasingly hypertonic as it approaches the papillae. So the urine becomes increasingly conc. as it flows in this direction (450 – 600mOsm/L) – slightly hypertonic to plasma.

In the thin DLLH: It is highly permeable to water, so more water is reabsorbed &

it is sparingly permeable to salt, this increases the conc. of Na+ & Cl– (1200mOsm/L).

Most water drawn into the interstitium is carried off by the vasa recta (_B).

ALLH is largely impermeable to water. So

In the thin ALLH: Na+ and Cl– passively diffuses into the interstitium.

In the thick ALLH: Na+ and C- are actively transported into the interstitium (_B).

Since water cannot escape, the urine leaving the loop of Henle is hypotonic.

Active reabsorption of Na+ and Cl– from the TAL creates a local gradient (ca. 200 mOsm/kg H2O) at the TAL on one side & the DLLH & medullary interstitium on the other (400mOsm).

Collecting Duct: Water is extracted (passively) from the CD due to the high osmolality of medullary interstitium.

Active NaCl transport is the ATP-consuming “motor” for the kidney’s urine-concentrating mechanism and is up-regulated by sustained stimulation of ADH secretion.

Along DCT & CD: they contain aquaporins & ADH receptors of type V2, the fluid in the tubule will again become isotonic (in osmotic balance with the isotonic interstice of the renal cortex) if ADH is present, i.e., when antidiuresis occurs.

Although Na+ and Cl– are still reabsorbed here, the osmolality does not change significantly because H2O is reabsorbed (ca. 5% of the GFR) into the interstitial space due to osmotic forces and urea increasingly determines the osmolality of the tubular fluid.

Collecting duct: Final adjustment of the excreted urine volume occurs in the presence of

ADH (which binds to basolateral V2 receptors). Aquaporins (AQP2) in the luminal membrane of principal cells are used to extract enough water from the urine passing through the

increasingly hypertonic renal medulla.

Thereby, the Uosm rises about 4 times higher than the Posm (Uosm/Posm = 4), corresponding to maximum antidiuresis.

The absence of ADH results in water diuresis, where Uosm/Posm can drop to < 0.3.

The Uosm can even fall below the osmolality at the end of TAL, since reabsorption of Na+ &

Cl– is continued in the DCT & CD, but water can hardly follow.

Urea also plays an important role in the formation of concentrated urine.

Protein-rich diet  ↑urea production  ↑urine-concentrating capacity of the kidney 50% of filtered urea  leaves PCT by diffusion (_C).

ALLH, DCT & CD (cortical & outer medullary sections): are only sparingly permeable to urea, so its conc. increases downstream in these parts of the nephron (_C).

Recirculation of urea

 ADH (via V2 receptors) can introduce urea carriers (urea transporter type 1, UT1) in the luminal membrane ^ making the inner medullary CD permeable to urea.

 Urea now diffuses back into the interstitium via UT1 (urea is responsible for ½ of the high osmolality of medullary interstitium).

 Urea is then transported by UT2 carriers back into the DLLH (_C).

The non-reabsorbed fraction of urea is excreted: FEurea ≅ 40%.

Urea excretion increases in water dieresis & decreases in antidiuresis, due to up-regulation of the UT2 carrier.

Urine concentration disorders primarily occur due to

(a) excessive medullary blood flow (washing out Na+, Cl– and urea);

(b) osmotic diuresis;

(c) loop diuretics

(d) deficient secretion or effectiveness of ADH, as seen in central or peripheral diabetes insipidus, respectively.