Urine concentration

Urine concentration and dilution

Plasma osmolarity varies from about 280-300 mosm/kg. Urine can be diluted or concentrated to maintain plasma osmolarity in the normal range. Urine osmolarity can vary from as low as 50 to as high as 1200 mosm/kg. Osmolarity equal to plasma is called isotonic, less than plasma is hypotonic and more than plasma is hypertonic to plasma.

1. Maintenance of cortico-medullary osmotic gradient: The osmolarity of the renal interstitial fluid progressively increases from the cortex to the medulla being highest at the renal papilla. Two mechanisms, the countercurrent multiplier and urea recycling help to establish the corticomedullary osmotic gradient.

   Single effect and flow of tubular fluid in the loop of Henle are the two processes involved in countercurrent multiplication. Single effect is a function of the thick segment of the ascending limb of the loop of Henle. The thick segment is impermeable to water. It has the Na+K+2Cl- transporter that absorbs NaCl. As electrolytes are absorbed while water is not, the tubular fluid becomes diluted. The absorbed NaCl enters the interstitial fluid, increasing its osmolarity. Water flows out of the descending limb into the interstitium which is at a higher osmolarity. End result is increased osmolarity in the descending limb and interstitium and decreased osmolarity in the thick segment of the ascending limb. This is called as single effect. The single effect and consequently the corticomedullary osmotic gradient is enhanced by ADH.

   The ultrafiltrate at the PCT is isotonic to plasma. As this fluid enters the descending limb, it pushes the higher osmolarity fluid in the descending limb towards the loop of Henle. This process is called the flow of tubular fluid. Single effect and flow of tubular fluid are repeated in a cyclical fashion until the full corticomedullary gradient is established. Size of the gradient depends on the length of the loop of Henle. In humans the maximum osmolarity of the interstitial fluid in the region of the bend of the loop of Henle is 1200 mosm/kg.

   Urea recycling is a function of the inner (not outer) medullary collecting ducts. That’s because only the inner medullary collecting ducts are permeable to urea through the urea transporter UT1, induced by ADH. Urea diffuses down its concentration gradient to enter the interstitium. Take note that urine is flowing from the inner medullary to the outer medullary segments. The cortical and outer medullary collecting ducts are not permeable to urea. This creates a urea gradient between the inner medullary and outer medullary ducts leading to increased urea concentration in the tubular fluid in the outer and cortical ducts, under the effect of ADH.

   Vasa recta are capillaries in the medulla and renal papilla. They follow the loop of Henle. Blood flows slowly through the vasa recta. They participate in 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 has a starting osmolarity of about 300 mosm/kg. As the capillaries are permeable to water and electrolytes and they are surrounded by an interstitium of higher osmolarity (owing to the corticomedullary gradient), electrolytes like Na+, Cl-, urea etc. enter the descending limb of the vasa recta while water flows out, to balance the osmolarities on each side. Following the same principle, the osmolarity in the vasa recta progressively increases to a maximum of 1200 mosm/kg at the bend of the vasa recta. As the vasa recta ascends, it is exposed to lower osmolarity than before, this leads to water diffusing into the vasa recta to reduce the osmolarity which will decrease from a maximum of 1200 to about 325 mosm/kg, depending on the water status in the body. End result is that the blood exiting the vasa recta is at a higher osmolarity that the blood entering the vasa recta.

Role of renal segments in concentration and dilution of urine

Tubular fluid becomes more hypertonic in the straight part of the PCT and 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

2. 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 is a measure of the capacity of the kidneys to concentrate or dilute the urine. It can theoretically be 0 when no free water is excreted, called isosthenuria as the urine osmolarity will be equal to the plasma osmolarity. It is seen with loop diuretics as no free water will be generated. Free water clearance will be positive when hypo-osmotic urine is excreted in the absence of ADH effect. Free water clearance will be negative when urine is hyper-osmotic as a result of increased ADH, which causes water absorption.