Plasma osmolarity normally stays around 280-300 mosm/kg. Your kidneys dilute or concentrate urine to keep plasma osmolarity within this range. Urine osmolarity can vary widely, from about 50 to 1200 mosm/kg.
Maintenance of cortico-medullary osmotic gradient: The osmolarity of the renal interstitial fluid progressively increases from the cortex to the medulla, and it is highest at the renal papilla. Two mechanisms help establish the corticomedullary osmotic gradient: the countercurrent multiplier and urea recycling.
Two processes drive countercurrent multiplication: the single effect and the flow of tubular fluid in the loop of Henle.
The single effect is produced by the thick segment of the ascending limb of the loop of Henle. This segment is impermeable to water and contains the Na+K+2Cl- transporter, which reabsorbs NaCl. Because electrolytes are absorbed while water is not, the tubular fluid becomes diluted. The absorbed NaCl enters the interstitial fluid, increasing its osmolarity. Water then moves out of the descending limb into the interstitium (which now has a higher osmolarity). The end result is:
This pattern is called the single effect. The single effect, and therefore the corticomedullary osmotic gradient, is enhanced by ADH.
The ultrafiltrate in the PCT is isotonic to plasma. As this fluid enters the descending limb, it pushes the higher-osmolarity fluid already in the descending limb toward the bend of the loop of Henle. This movement is called the flow of tubular fluid. The single effect and the flow of tubular fluid repeat in a cycle until the full corticomedullary gradient is established. The size of the gradient depends on the length of the loop of Henle. In humans, the maximum osmolarity of the interstitial fluid near the bend of the loop of Henle is about 1200 mosm/kg.
Urea recycling occurs in the inner (not outer) medullary collecting ducts. Only the inner medullary collecting ducts are permeable to urea, through the urea transporter UT1, which is induced by ADH. Urea diffuses down its concentration gradient into the interstitium. Note that urine flows from the inner medullary segments toward the outer medullary segments. The cortical and outer medullary collecting ducts are not permeable to urea. This creates a urea gradient between the inner and outer medullary ducts, leading (under the effect of ADH) to increased urea concentration in the tubular fluid in the outer and cortical ducts.
Vasa recta are capillaries in the medulla and renal papilla that run alongside the loop of Henle. Blood flows slowly through the vasa recta. They perform countercurrent exchange, which maintains the corticomedullary gradient that has already been established by the countercurrent multiplier system of the loop of Henle and medullary collecting ducts.
The descending limb of the vasa recta starts at an osmolarity of about 300 mosm/kg. Because these capillaries are permeable to water and electrolytes and are surrounded by an interstitium with progressively higher osmolarity (due to the corticomedullary gradient), electrolytes (Na+, Cl-, urea, etc.) diffuse into the descending vasa recta while water diffuses out. As a result, osmolarity in the vasa recta increases, reaching a maximum of about 1200 mosm/kg at the bend.
As the vasa recta ascends, it encounters interstitium with lower osmolarity. Water diffuses into the vasa recta, lowering its osmolarity from about 1200 to about 325 mosm/kg (depending on the body’s water status). The end result is that blood exiting the vasa recta has a higher osmolarity than blood entering the vasa recta.
| Dehydration | Drinking excess water | |
| PCT | Isotonic | Isotonic |
| Thick ascending limb* | Hypotonic* | Hypotonic# |
| Early distal tubule | More hypotonic* | Hypotonic |
| Late distal tubule | Isotonic** | Hypotonic## |
| Collecting ducts | Hypertonic*** | Hypotonic## |
Tubular fluid becomes more hypertonic in the straight part of the PCT and in the descending limb of the loop of Henle.
*electrolytes are absorbed while water remains in the tubule
**late distal tubule is in the cortex where the interstitium has an osmolarity about 300 mosm/kg
***Collecting ducts start at the cortex and end in the medulla where the osmolarity is high.
#Lack of ADH so no activation of Na+K+2Cl- transporter, electrolytes absorbed less
##Lack of ADH, no aquaporin channels to absorb water
Free water clearance: Free water means solute-free water. The thick ascending limb and early distal tubule are the free-water-generating segments of the kidney.
Free water clearance measures the kidney’s capacity to concentrate or dilute urine.
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